PBW january issue by Pharma Bio World

January 2014 

Vol. 12

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Issue 6



Mumbai

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Price ` 150

www.pharmabioworld.com PHARMA BIO WORLD JANUARY 2014 VOL. 12 ISSUE 6 MUMBAI ` 150 B & R COVER PAGE .indd 1

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6 ď&#x201A;&#x192; January 2014

Contents.indd 6

Pharma Bio World

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EXPERT’S TAKE 10

The Essential Building Blocks of Effective Training – Ellen Leinfuss, UL EduNeering

INTERVIEW 16

“The rules for clinical trials in other countries are easy to comply with in comparison with India.” – Pawan Chaudhary, Venus Remedies

FEATURES 20

Shifting Paradigms in Clinical Translational Oncology – Dr Jean-Pierre Wery, Crown Bioscience Inc.

Unique Challenges of Transungual Drug Delivery to Treat Onychomycosis – Tage Ramakrishna, Valeant Pharmaceuticals North America, LLC

Understanding Nasal Drug Delivery – Stuart Wakefield, Malvern Instruments Ltd

36 20

Automated Formulation Tracking Ensures Accuracy, Saves Materials and Expense – Thomas Holzer, Mettler-Toledo AG

MARKET RESEARCH 38

Strategies for Indian Pharma in a Volatile World – Manish Panchal, Charu Kapoor & Mansi Mahajan, TATA Strategic Management Group

NEWS FEATURE 40

Quid Pro Quo – Ananya Sen

NEWS UPDATE 43

Pharma News

Biotech News

CORPORATE AFFAIRS 55

Product Trends

Events

BACKYARD 40

Bookshelf

AD Index Next Issue Focus: Health & Safety

8  January 2014

Contents.indd 8

Pharma Bio World

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expert's take

The Essential Building Blocks of Effective Training Ellen Leinfuss

Senior Vice President - Life Science UL EduNeering

The US Food and Drug Administration (FDA) has escalated its scrutiny of Indian pharmaceuticals and medical products. Beyond FDA, the same scrutiny is reflected in recent decisions by the Indian Supreme Court, regulations by agencies including the Central Drugs Standard Control Organisation, and heightened cooperation among international regulators regarding site inspections and compliance enforcement. 10 January 2014

The Essential Building Blocks of Effective Training.indd 10

he growing demand for India’s medical products has put significant stress on Indian companies to meet that demand while also complying with the quality standards of global regulators and customers. Recent experiences of well-known Indian companies illustrate the quality risks associated with rapidly expanding international markets, complex supply chains, global compliance requirements and often-limited corporate resources. Understanding and implementing programmes that address global compliance demands will enable companies to improve their reputations and avoid unnecessary costs. As the global market opportunity for Indian medical products increases, all companies large and small, generic and brand, domestic and global – will be held to strict standards of compliance and quality or face enforcement actions that have recently included Warning Letters, closed facilities, massive fines and product bans. Management Commitment Every company’s culture is defined at the top, by senior executives. Underlying that culture are the corporate philosophy, mission, expectations and standards that flow through middle managers to production employees, subcontractors and vendors. Yet, while “tone at the top” is essential, it is not enough to ensure compliance. Both inside and outside the Life Science industry,

companies have failed to follow through on the public statements of their senior executives, often with damaging results. Global regulation is clear on the subject of “management commitment.” It is a strict liability law and cannot be delegated. Unfortunately, middle managers may overlook quality problems because they are being pushed to increase production, no matter what. Documentation may be shortchanged because it “takes too much time” and provides no direct profit. When the message from the top is not supported with resources, reinforcement through training and consistent adherence throughout the organisation, quality always suffers. Walking the Talk Both ISO 9001 and ICH Q10 require executive management to provide evidence of its commitment to establishing and maintaining a company-wide culture of quality. This requires an ongoing training and communications programme that provides equal focus on the company’s financial (including product throughput) goals and quality topics. Leading topics identified in the UL annual 2013/2014 benchmarking study for “Critical to Quality” training and measurement are: CAPA, inspection and internal audit findings, adverse events, customer complaints and non-conforming products. Correlating this data, we have seen an increasing commitment to quality

The purpose of training is compliant behavior – not the number of hours or courses provided. Training should be based on the role and responsibilities of the learners. Pharma Bio World

22-01-2014 10:31:55

through the distribution of the UL-FDA library of courses on these topics. The most popular courses used in 2013 were “Handling an FDA Inspection,” Introduction to GMPs” and “Principles of Good Documentation.”

offers the added benefit of documenting distribution of required SOPs as well as the ability to incorporate testing on an individual or group of SOPs, providing defensible records for inspectors and regulatory agents.

Effective SOP Management

Risk versus Training Method Since SOPs form the basis of effective compliance; they also serve as the essential foundation for personnel performance and product quality. UL EduNeering’s SOP Management Suite is the most widely used feature available via our ComplianceWire ® Learning Management System, having recorded approximately 15 million training completions in 2013 alone. Best practices gleaned from this Suite include developing SOPs for each job task written in conjunction with users (and translated into native language); providing a documented distribution programme to ensure that only current SOPs are being employed; confirming employee comprehension on key SOPs via testing; risk ranking SOPs and aligning that risk to training approach, and maintaining a corrective and preventive action programme to identify, rectify and prevent quality failures. ComplianceWire 12 January 2014

The Essential Building Blocks of Effective Training.indd 12

Who is Qualified? Highly publicised quality issues have triggered public distrust and governmental anger, putting Life Science companies under the spotlight more than ever. A

High

PROBABILITY

The purpose of an SOP is straightforward: to ensure that essential job tasks are performed correctly, consistently and in conformance with internally approved procedures. Clearly, employees’ correct, consistent performance of essential job tasks is as much a business and quality issue as it is a regulatory requirement. Yet, regulators routinely cite Pharmaceutical and Medical Device companies because of inadequate Standard Operating Procedures (SOPs) management. Common observations during inspections include non-existent SOPs or those that are not understandable, regularly updated and easily accessible to employees and inspectors. In addition, a company with inadequate SOP management procedures at one facility is likely to face regulatory scrutiny for similar problems at its other facilities and those of its suppliers.

SOP Review with Assessments

SOP Review with Qualified Trainer Oversight

SOP Training with Read and Understand

SOP Review with Assessments

Low

SEVERITY

High

Figure 1: We recommend aligning training approach to match the risk and importance of each SOP

common complaint by FDA, for example, is a company’s failure to have “sufficient personnel with the necessary education, background, training and experience to assure that all activities are correctly performed.” Regulators from other countries make similar complaints, asking, “Are employees qualified to perform their assigned duties accurately, effectively and in compliance?” There are a number of factors that complicate a company’s ability to ensure appropriate qualifications of its employees. Among those factors are high turnover rates, rapid facility expansions, new production processes and reduced training budgets. Although each of these factors may complicate the employee qualification process, the single most common flaw is the lack of a cohesive programme that incorporates initial assessments of knowledge, targeted role-based training, testing to ensure comprehension, and automated delivery of remedial training when required test scores have not been achieved.

Training that Works The purpose of training is compliant behavior – not the number of hours or courses provided. Training should be based on the role and responsibilities of the learners. It should be relevant to their jobs and tailored by language, literacy, experience and culture. According to regulations, employees must be able to demonstrate their documented qualification to perform their specific job functions. “Qualification” could be represented by a collection of “rolebased” training items or tasks that must be completed to satisfy the defined expectations for that role. Those tasks could include prior education, a series of SOPS, demonstrated proficiency via on-the-job-training, attendance in instructor-led classes, and computerbased learning. As a role changes, so do the training requirements for that individual. Metrics and Technology FDA and its counterparts in other countries are adopting a risk-based approach to inspections and enforcement actions. As part of that approach, companies are encouraged to use metrics to improve their performance and quality. In fact, 67 per cent of respondents in our customer benchmarking study cited “collecting training data to support the organisation’s quality or compliance metrics” as a top priority. Although companies may agree about the value of “metrics,” there are key challenges in collecting relevant data and making effective use of the information. Critical records are often “lost” in a web of inefficient processes and conflicting technologies, forcing quality managers to grab vital information “on the fly.” Training metrics, including the status of each employee’s training completions, remedial requirements, distribution patterns and testing scores can enable managers to identify knowledge gaps before they result in serious quality issues. The reverse is also true. Pharma Bio World

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Figure 2: Training content should be aligned to each individual’s role to demonstrate qualification

Documentation about quality issues from specific facilities, production lines, product types, employees or departments can be used to target relevant training that reinforces the knowledge needed to perform well. Metrics for Visibility Companies that effectively use metrics to improve their training, compliance and operational performance typically turn to a technology-based management system that links data from across the entire organisation. By consolidating the data into a coherent system, managers are able to identify trends and respond quickly. There are key considerations in choosing a technology system capable of delivering the desired functions and results. Among those considerations: interoperability of the new system with established corporate infrastructure; presentation of data in real time; scalability to allow the seamless extension of existing programmes and systems to new facilities; flexibility to allow customisation for company-defined formats; data security and compliance with mandated documentation requirements; and robust capacity to handle additional company programmes and initiatives for the distribution of training, communications, competency testing, qualification certification, programme management and oversight. 14 January 2014

The Essential Building Blocks of Effective Training.indd 14

Document, Document, Document! There’s a saying in the compliance profession: “If it isn’t documented, it doesn’t exist.” Documentation has always been important; now, with the implementation of new laws including the US Food and Drug Administration Safety and Innovation Act (FDASIA), documentation has taken on even greater significance. Life Science companies face several issues in achieving effective documentation management. Many companies have several, often unconnected collections of documents. Conflicting policies among different facilities or even departments within the company increase the risk of inconsistency even further. In addition, some companies continue to rely on paper records that are easily lost, damaged or cannot be validated for accuracy. Increasingly, the consequence of poor documentation is a serious violation of Good Manufacturing Practices (GMPs), with the resulting enforcement actions by regulatory agencies and law enforcement groups. Documents Demonstrate Compliance Effective document management has several components. Documents must be properly designed and distributed; they must be approved, signed and dated

by the appropriate personnel; they must be regularly reviewed for accuracy and completeness; they must be stored in secure locations; and they must be available to regulators, investigators and compliance managers. Effective documentation procedures must ensure not only the quality of the recorded data but also the security of the records, and the validity of the signature (electronic records must comply with 21 CFR Part 11). Access should be limited to authorised personnel only and any corrections must be signed and dated. Recent FDA inspections have uncovered instances of falsified, nonexistent or destroyed records. For several companies, the cost of those “simple” documentation issues was a Warning Letter from FDA or a ban on the facility’s products. Conclusion The market for Indian Pharmaceuticals is expected to more than double in the next seven years. Along with that expanding market comes increased regulatory and consumer scrutiny, particularly regarding product quality and related quality training. Quality and compliance training is a challenge for companies at every sector of the Life Sciences industry. Even companies with well-established compliance programmes want to know why their training programmes aren’t working. Why are they still receiving complaints from regulators about inadequate knowledge and performance by employees – despite the company’s substantial investment in its compliance programme? For smaller companies or for those new to the emerging quality demands of global markets, the challenge of developing and implementing quality training programmes can seem overwhelming in complexity. Although companies may have different budgets, workforces, compliance requirements, product lines and facility locations, they can all benefit from these five building blocks of effective quality training, which have been gleaned over many years from our work supporting global companies and the US FDA’s training programme. Contact: ellen.leinfuss@ul.com Pharma Bio World

22-01-2014 10:37:33

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interview

PAWA N C H AUDH A RY

“The rules for clinical trials in other countries are easy to comply with in comparison with India.”

16 January 2014

final interview.indd 16

Venus Remedies has been exploring several international markets and recently made news on acquiring marketing approval for meropenem in Italy. Pawan Chaudhary, Chairman and Managing Director, Venus Remedies in an interview with Ananya Sen discusses more on this. How will the procurement of marketing authorisation for meropenem in Italy and Saudi Arabia add to your business? Meropenem has received marketing authorisation from Italy for its generic broad-spectrum antibiotic injectable, “meropenem”, via the de-centralised procedure (DCP) route. The company is planning to launch this product in Italy next year. The total meropenem sales in Italy stood at about Euro 50 million in 2012, and Venus Remedies is confident of bagging a 10 per cent share in this market. Being an important member state of the European Union (EU), Italy has immense potential for meropenem. This marketing authorisation offers a huge opportunity to Venus Remedies to expand its export base across the globe. With marketing approval from Saudi Arabia, Venus has become the first generic drug manufacturer in the world to get product registration for meropenem in the Gulf Cooperation Council (GCC). The USD 35 million market for meropenem in Saudi Arabia offers a huge opportunity to us, and we are aiming at capturing 25 per cent share in this market within the first year of the launch

itself. This marketing approval is a significant and prestigious achievement for the company as the Saudi Arabian market is known across the world for its stringent quality control. We are planning to launch this product in Saudi Arabia, considered one of the most lucrative pharmaceutical markets in the world, early next year. For how many other countries have you already acquired marketing authorisation for meropenem? At present, Venus is selling meropenem in various markets, including the European Union, and is in the process of extending its footprint and sales operations in regulated markets like Australia, Spain, Switzerland and South Africa. The company has already received marketing authorisation for meropenem from the UK (MHRA), France, Italy, Saudi Arabia, Austria, Denmark, Finland, Ireland, Germany, Netherlands, Poland, Slovenia, Slovakia, Sweden, Portugal, Czech Republic, Cyprus, New Zealand and Mexico. The product has also made its way to Balkan countries with marketing approvals from Bosnia & Herzegovina and Croatia. Pharma Bio World

22-01-2014 19:25:16

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Venus Remedies has acquired several marketing approvals as well as patents from different countries of the world. How challenging is it to comply with the regulatory requirements of different countries for obtaining their consent? The regulatory environments for pharma industry are challenging in nature across the globe and the year 2013 has presented new challenges to us. The regulations and guidelines for registration of drug product continue to be upgraded to ensure patient safety and better health. In order to comply with these regulations, we have to follow stringent quality standards that vary from country to country. Also, the lack of regulatory harmonisation throughout the world makes it more difficult for us to get the product registered. Moreover, the regulatory review process in many countries is very time-consuming. In many countries, we get approval in 2 -4 y e a rs . D ue t o t h is f a ct o r, a ve ry careful planning in terms of business perspective is required before entering such markets so that we do not lose out on major markets by the time the product gets approved. Which are the other countries you are targeting to enter? We are targeting to enter all major emerging markets, ie, Australia, Switzerland, South Africa, Canada, Singapore, Israel, Korea a n d U A E . We a r e a l s o t a r g e t i n g E U countries like Belgium, Estonia, Hungary Latvia, Lithuania, Luxembourg, Malta and Romania. H a v e y o u b e e n c onduc ti ng c l i ni c a l trials in other countries for some of your indigenously developed

products? How is the regulatory environment with respect to clinical trials in those nations? Yes, we have been conducting clinical trials in other regulated countries as well. The rules are defined and the process is pretty much simpler and easy to comply with in comparison with India. Brief us on your organisation’s indigenous R&D. What are the products under development in your company’s pipeline? We are a research-driven pharmaceutical company, which is into discovering and developing novel research injectables under the critical care and super-speciality segments. We are currently focusing on anti-infectives (antimicrobial resistance), o n c o l o g y, w o u n d & s k i n c a r e , p a i n management, over-the-counter (OTC) and neurology. We are one of the few companies which are into injectable drugs and manufacturing of complex molecules such as penems and oncology products. We manufacture around 30 oncology products under one roof and have a robust pipeline of 25 research products, of which 15 are already commercialised, which includes Elores, Potentox, Vancoplus, Tobracef, Achnil, Ezenus, Trois, Docetaxel and many more. As of now, we have around 10 research products in the pipeline, of which four research products are in the final stages of development. We are hopeful of introducing our cancer detection NCE (New Chemical Entity), VRP1620, by the end of 2014. This NCE is based on selective tumour targeting because tumour-infiltrating blood vessels deviate morphologically and biochemically from normal vessels. VRP1620 specifically increases tumour blood flow and this

Lack of regulatory harmonization throughout the world makes it difficult to get our products registered in different countries. 18 January 2014

final interview.indd 18

◆ Venus Remedies received marketing authorisation from Italy for its generic broad-spectrum antibiotic injectable ‘meropenem’. ◆ Venus targets to bag a 10 per cent share in this market. ◆ The company is planning to launch the product in Italy next year. property has been utilised to promote delivery of cancer detection contrast media to the site of tumors via blood stream. It is a target delivery of diagnostic agent which enhances image quality to several hundred times, thus making it clearly differentiated. As of now, there is no such technology for early detection of small-sized solid tumour available in the market across the globe. Secondly, VRP1620 will be of great help in staging of tumours as the technology omits false negatives. Apart from VRL1620, we have DETECTa Ty p h o i d D e t e c t i o n K i t , V R P 2 0 11 & DPPC in the oncology segment, which we are hopeful of launching in the next three-four years. With the emerging threat of antibiotic resistance, how are you planning to work so as to improve the conditions? With an almost dried up product pipeline for antibiotics, antimicrobial resistance (AMR) is emerging as the biggest global t h r e a t t o m a n k i n d . We h o w e v e r h a d foreseen the potential of antibiotics fading 10 years back and it is the result of our focused approach that today we have some superbug-tackling solutions under patent protection. We are constantly working in this regard to come up with breakthrough products that can offer effective solutions to this ever-growing menace. Our product Elores, which we had launched in January this year, is an answer to AMR. Elores has been adjudged as the No. 1 Innovation of 2013 under the DST-Lockheed Martin India Innovation Programme. Pharma Bio World

22-01-2014 19:27:33

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Shifting Paradigms in Clinical Translational Oncology The trend in translating oncology research into the clinic is undergoing a radical shift towards complementing patient treatment with the large-scale use of human surrogate mouse models for Pre-Clinical Phase II-like trials and Co-Clinical Trials in Mouse Clinical Trials Centers (MCTCs).

Dr Jean-Pierre Wery Chairman Crown Bioscience Inc 20 January 2014

Clinical Translational Oncology.indd 20

ranslational Sciences is nothing new. It’s been a common theme in drug discovery organisations over the last two decades. However, the delivery has often lagged behind the promise of “bench to bedside”. Oncology remains one of the greatest areas of unmet need in drug discovery today. The attrition rate of candidates entering the clinic and making it to market remains stubbornly high. Over 95 per cent of oncology candidates still fail to survive the rigors of the clinic 1 , and 50 per cent of all drug failures in the clinic are attributed to lack of efficacy 2 . Some might find this astounding since the plethora of technologies, information, knowledge and expertise available to drug researchers today continues to g r o w e x p o n e n t i a l l y. W h a t m a n y a r e beginning to surmise is that simply doing “the right thing” is not enough and doing “things right” may be a more appropriate paradigm. The principles of establishing a strong link and feedback loop between multidisciplinary teams in the clinic and drug discovery research, a deep understanding of the molecular mechanisms of disease and establishing patient-derived materials in the cycle of evaluating new drugs, are all becoming essential components in triaging novel

candidates both in the lead up to and during the clinical phases 3 . For years the “gold standard” models for oncology drug discovery were the immortalised cell lines. These cell lines still hold their place in the process o f c a n d i d a t e v a l i d a t i o n . H o w e v e r, cells that are selected based on their ability to grow on plastic rather than reflect a patient’s true disease are far from the reality of a patient in the c l i n i c 2. A s p r e c l i n i c a l s c i e n t i s t s w e need the toolkit that immortalised cell lines provide to study how candidate c o m p o u n d s e ff e c t c h a n g e s b a s e d o n particular genetic mutations, or turn on o r o ff p a r t i c u l a r p a t h w a y s . H o w e v e r, once you are seeking to reflect the complex multifactorial environment of a patient, their stage of disease, h e t e r o g e n e i t y o f t u m o u r , h i s t o r y, genetics, etc, the chances that just one element such as a single mutation will be the only controlling factor in disease progression are limited. We also have to recognise that a single model may not truly reflect the treatment history of a patient. Have they had previous c h e m o t h e r a p y, r a d i a t i o n t h e r a p y, surgery, etc, are they currently on a particular regimen?

Figure 1: Developing PDX (Patient-Derived Xenograft) Models. Crown’s system of quality control ensures models developed are robust and reproducible across a number of passages. Samples are retained at each passage in a tissue bank and a fully searchable database enables the rapid selection of models for efficacy testing based on genotypic, phenotypic and pharmacological response data.

Pharma Bio World

22-01-2014 10:55:04

The era of personalised cancer therapy came of age in the past ten years. As an option for high wealth individuals, the chance to have your regimen tailored to your specific needs may be an attractive option. For the majority of the millions of patients in need world-wide, this is still not an option today. The high failure rate of molecular targeted therapeutics, as well as the challenge of identifying mechanisms of action and validating molecular markers, identifying mechanistic feedback loops, molecular crosstalk and bypass mechanisms that can lead to unexpected effects on patient outcomes has significantly hampered the success of personalised medicine. Therefore the oncology research community today is seeking better ways to offer a wider cross section of society an improved quality of life and potential cures. There is a strong need to have tools available which can significantly improve the qualification of candidates at a much earlier stage in the drug discovery process, understanding the pathways and networks to target as well as the homeostatic loops induced by interventions with particular treatment regimens 4. Simply put, ensuring a significant improvement in the quality of those treatments we deliver into the clinic is an essential element in reducing the attrition rate in the clinic. Having the ability to improve the qualification process requires us to have models which far more closely reflect the patient’s disease stage and condition, and treatment status. The past few years have seen the rise in the use of PDX (Patient-Derived Xenograft) models (Figure 1). Maintaining a patient’s tumour in a mouse model provides a tumour environment that is far more closely aligned with a patient’s disease than an immortalised cell line. The fact that these tumours can be grown and passaged in multiple animals, means they have the potential to become a screening tool to test candidate compounds. Whilst not being the perfect model of human disease, PDX are significantly closer to the clinical situation. Amongst the significant advantages of 24 January 2014

Clinical Translational Oncology.indd 24

The challenge of identifying mechanisms of action and validating molecular markers, identifying mechanistic feedback loops, molecular crosstalk and bypass mechanisms that can lead to unexpected effects on patient outcomes has hampered the success of personalised medicine. using PDX as a screening tool is that they can be tested to ensure they consistently r e t a i n t h e r e l e v a n t o r i g i n a l p a t i e n t ’s tumour characteristics (mutational status, morphology, pharmacological response, etc) across multiple passages. Today, the paradigm in oncology drug discovery is changing. There is a greater use of PDX to investigate metabolism, bio-distribution and efficacy of candidate co mpounds . An additional s ignific ant advantage of PDX is that they can be used as human surrogates to provide a unique perspective on the likely outcome of a clinical trial before the first patient is ever recruited. Many such studies have already occurred and can clearly demonstrate de novo understanding of potential treatment regimens for patients and identify patients most likely to benefit from such treatments 5. The key to performing these human surrogate clinical trials (Figure 2) in preclinical mouse models are: 1) Having significant numbers of PDX for a particular cancer type to enable a trial team to select an appropriate population of models with the correct “signature”. 2) H a v i n g w e l l c h a r a c t e r i s e d , r o b u s t models and the data preferably in a searchable database to enable the easy selection of appropriate models. 3) H a v i n g a l a r g e n u m b e r o f m o d e l s “always on”. Reviving these models from frozen takes many months before they are ready to perform efficacy studies. Therefore there is a need to have a significantly large numbers of models constantly in passage, ready to use for screening.

So what are some of the advantages of using such pre-clinical human surrogate trials? 1) Speed. Even through patient recruitment to a clinical trial may be fairly quick, a comprehensive pre-clinical trial can be run in months rather than years, which means that you can gain a significant insight into your candidate’s efficacy well before you might move out into the clinic. 2) B i o m a r k e r D i s c o v e r y. S t r u g g l i n g to discover a predictive biomarker? Screening a significant population of PDX which are well characterised genetically and phenotypically may provide an insight into potential biomarkers which could be used in the clinic to identify responders and non-responders, or to develop companion diagnostics 5. 3) Knowledge. Screening human surrogate models provides a unique platform for greater understanding. It offers the opportunity to investigate mechanism of action, the ability to quantify MTD (Maximum Tolerated Dose), combination therapy – how you candidate will truly interact in combination with standard of cares, and adjusting a patient’s treatment regimen – timing is everything to successful combination therapy, where multiple interaction may be occurring. 4) Resistance. Patients today generally do not succumb to their primary tumour. Recurrence and metastasis are the issues of most need today. The fact that a patient may have already Pharma Bio World

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Figure 2: Human Surrogate Pre-Clinical Trials. Models are selected from a large population of PDX models, either randomly or based on a particular profile dependent on the trial design, and screened against the treatment regimen for responders and non-responders.

Maintaining a patient’s tumour in a mouse model provides a tumour environment that is far more closely aligned with a patient’s disease than an immortalised cell line. received primary and even secondary treatment before a further relapse requires mechanisms to overcome resistance to treatments which may have developed. PDX can be used to study these mechanisms of resistance and provide a screening platform prior to moving into first in man. 5) P r e p a r a t i o n a n d G u i d a n c e . T h e combination of all the above enables drug discovery teams to prepare a comprehensive tranche of information and knowledge about a potential candidate before it enters the clinic. This can help guide both the initial launch of early clinical phases and then also test hypotheses as the candidate advances through the clinic. The Rise of the Mouse Clinical Trial Centre and Co-Clinical Trials So what is the future for Oncology Drug D i s c o v e ry a n d t ra n sla t in g kn o w le d g e between preclinical research and the 26 January 2014

Clinical Translational Oncology.indd 26

clinic? Developing significantly large p o pulations of PDX, ready to s c reen is jus t part of the potential s olution. Creating environments which can mimic human clinical trial centres does help but use of human surrogate animal models is providing the next step forward. These MCTCs (Mouse Clinical Trial Centres) not only allow large scale screening of candidate compounds prior to entering first in man, but also enables human surrogate trials to be run in tandem with real clinical trials, forming a “Co-Clinical Trials”. In Co-Clinical Trials, the use of PDX and GEMMs (Genetically Engineered Mouse Models) running side-by-side with the human clinical trial are used to guide therapy in an ongoing human clinical trial. The elucidation of molecular mechanisms and therapeutic response using these model systems complements the approaches of molecular and clinical oncology, and represents the emergence of mouse models as significant tools in elucidating the complex nature of treating cancer in the clinic. Awareness across the spectrum of research and

clinical professionals, patients and advocacy groups about the potential use of human surrogate models in MCTCs will add momentum to the constant drive to improve cancer treatments for patients. References 1. Hutchinson, L, Kirk, R. (2011) High drug attrition rates-where are we going wrong? Nature Reviews Clinical Oncology 8, 189–190 2. Arrowsmith, J. (2011) Trial watch: Phase II failures: 2008–2010. Nature Reviews Drug Discovery 10, 328-329. 3. S a w y e r s , C . L . ( 2 0 0 8 ) T r a n s l a t i o n a l research: are we on the right track? J o u r n a l o f C l i n i c a l I n v e s t i g a t i o n 11 8 , 3798-3801. 4. G o n z a l e z - A n g u l o , A . M . , H e n n e s s y, B.T.J., & Mills, G.B. (2010). Future of Personalized Medicine in Oncology: A Systems Biology Approach Journal of Clinical Oncology vol. 28 no. 16, 27772783. 5. Zhang, L, Yang, J, et.al. (2013) A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab t h e r a p y. N a t u r e S c i e n t i f i c R e p o r t s 3 , Article number: 2992.

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Unique Challenges of Transungual Drug Delivery to Treat Onychomycosis This article discusses challenges treating a common nail disease, onychomycosis, by transungual antifungal delivery.

he only approved topical agent is a nail lacquer that has modest efficacy. Despite the unmet need, formulating antifungals to achieve optimal transungual delivery of active drug to the infection site has led to disappointing clinical results. Factors include both poor nail penetration and limited potency of the active drug. Given that systemic treatments are the most effective option, irrespective of disease severity, there remains an unmet need to develop efficient topical formulations. We discuss some of the important aspects to consider in such a development programme and critical success factors. New formulations are in development that may address these concerns. Human nails may be affected by a number of diseases. These range from relatively harmless conditions such as pigmentation in heavy smokers to more painful and devastating conditions, where the nail may be dystrophied, hypertrophied, inflamed or infected. This may result in emotional and psychological impact. The most common nail diseases are onychomycosis and nail psoriasis. Onychomycosis is a progressive fungal infection of the nail bed, matrix or plate that leads to destruction and deformity of the toenails, and less frequently fingernails. It represents up to 50 per cent of all nail disorders (studies suggest that 48 per cent of the population may be affected by age 70), is most commonly associated with tinea pedis, and has been reported as very distressing to patients. Nails

Tage Ramakrishna

Chief Medical Officer Valeant Pharmaceuticals North America, LLC 28 ď&#x201A;&#x192;January 2014

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infected with onychomycosis look ugly, discolored and thickened, often causing disability and pain, which in turn may affect a personâ&#x20AC;&#x2122;s well-being and self-esteem. Onychomycosis is difficult to treat because it is chronic, hard to eradicate and tends to relapse. Dermatophytes are the key organism associated with onychomycosis. They serve an important evolutionary role in breaking down keratin, hence their association with the toenail environment. The human nail plate is a sophisticated structure [Figure 1], despite its appearance. It protects the nail bed (the part directly under the nail plate filled with blood vessels), and it protects the nail matrix (the part at the proximal ventral surface of the nail responsible for the cellâ&#x20AC;&#x2122;s proliferation and nail growth). Although thin, the nail plate has 80-90 layers of dead, keratinised cells linked by desmosomal junctions and intercellular links. Tr a n s u n g u a l d e l i v e r y o f a n e ff e c t i v e antifungal would seem ideal for the successful treatment of onychomycosis. However, the applied active drug must first permeate through the nail plate and reach the nail bed and nail matrix in sufficient concentration to eradicate the infection. Although studies conducted on human skin have elucidated its structure, functions, and its permeability for some substances, much less is known about skin derivate, the nail, and the properties of nail keratin (which constitutes 90 per cent of total nail plate mass).

In controlled trials, the mycological cure rate reported with ciclopirox 8 per cent nail lacquer was reported as 29-36 per cent, suggesting other factors may be more important to obtain efficacy. Pharma Bio World

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Until recently, formulating antifungals to achieve optimal transungual delivery of active drug has led to disappointing clinical results in onychomycosis. Poor nail penetration is the main factor limiting their effectiveness. As a result, transungual drug delivery is usually reserved for the mildest disease, for use in combination with systemic therapy, for patients who cannot tolerate oral therapy (or where it is contraindicated), or for preventing relapse. There remains an unmet need to develop an efficient topical formulation to extend the utility of transungual delivery in the treatment of onychomycosis. Factors Influencing Transungual Drug Delivery Besides the characteristics of the nail plate (eg, thickness, presence of disease, level of nail plate hydration, presence of an intact dorsal layer), other factors influence transungual permeation [Table 1]. It is well recognised that penetration of a drug into the nail is affected by its physicochemical properties (eg, size, shape, charge, and hydrophobicity), formulation (nature of the vehicle and drug concentration), its contact time with the nail plate, presence of penetration enhancers, and interactions between the drug and the membrane. Presence of nail disease can alter the properties of nail plate. The thicker the nail is, the more difficult it will be for drugs to reach the nail bed. With increasing hydration rate an increase in drug Characteristics of the nail plate

Figure 1: The nail apparatus

permeability can be observed. The dorsal layer of the nail plate is the main barrier to drug permeation. Many techniques have been used to remove or damage the dorsal nail layer, not only to influence the main permeability barrier, but also to reduce the thickness of the nail plate. Molecular size of diffusing molecule has been shown to have an inverse relationship with permeation into the nail plate and the degree of ionization of a diffusing molecule plays an important role in permeation through the human nail plate. Nail permeability of an ionic drug is significantly lower than that of a nonionic drug suggesting that the decrease in permeability was caused by a decrease in diffusivity due to ion hydration. The formulation can influence drug delivery through the human nail plate through many aspects such as hydration of the nail plate, drug solubility, contact time between formulation and the nail plate, and ability to interact with nail constituents. Aqueous based formulations are suitable

Thickness Presence of disease Level of hydration

Presence of an intact dorsal layer Physicochemical properties (size, shape, charge, hydrophobicity) Contact time with nail plate Membrane interaction Characteristics of the formulation

Nature of vehicle and drug concentration Presence of penetration enhancers

Table 1: Factors influencing transungual drug delivery

30 ď&#x201A;&#x192;January 2014

for increasing the hydration rate of the nail plate, leading to higher permeability of the nail. Yet, in practice, aqueous based formulations are less suitable than lipophilic vehicles, due to their easy removal from the nail plate and short term contact with the nail surface. Lipophilic vehicles such as lacquers leave a hydrophobic film on the nail surface which limits transonychial water loss and at the same time, after the evaporation of the solvent, cause higher concentration of the drug in the film than from original applied formulations. Ciclopirox 8 per cent nail lacquer is the first topical product approved in the US to treat onychomycosis. It consists of ethyl acetate and isopropanol solvents which evaporate upon application and leave a thin film of the drug on the nail plate. The concentration of the drug in the film increases from 8 to 34.8 per cent. Thus the lacquer formulation improves the drug contact with the nail plate and the concentration gradient across the nail, which is important for passive diffusion of the drug. However, in controlled trials, the mycological cure rate reported with ciclopirox 8 per cent nail lacquer was reported as 29-36 per cent, suggesting other factors may be more important to obtain efficacy. Studies have shown that the concentration of ciclopirox was not such an important factor as the nature of the vehicle, and that antifungal drug delivery can be altered with formulation and delivery enhancers. Pharma Bio World

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Physical techniques

Filing or microporation of nails Acid surface etching Iontophoresis

Formulation characteristics

Chemical enhancers to destabilise keratin Penetration enhancers to improve permeation

Drug characteristics

Favorable physicochemical properties for nail matrix absorption Optimal keratin affinity (binding and release rate)

Table 2: Strategies to enhance transungual drug delivery

Strategies to Enhance Transungual Drug Delivery There are a number of physical techniques, often applied prior to applying drug, such as removal of the dorsal nail layer by filing or microporation (which leads to an improvement of the drug permeability coefficient), use of acid for surface etching of the nail, and application of electric current (iontophoresis). In addition, chemical enhancers can break the physical and chemical bonds responsible for the stability of nail keratin, and penetration enhancers can improve permeation [Table 2]. Drug partitioning into the healthy and infected toenail, drug-keratin binding, lateral diffusion, drug-epidermal binding and formulation components all may play a role in achieving optimum drug penetration and permeation through the nail. As mentioned previously, the two key factors that affect the accumulation and activity of drug in the nail following transungual delivery are: (1) the physicochemical properties of the drug need to be favorable for absorption through the nail matrix, and (2) the binding of drug to keratin reducing the availability of free active drug. A recent approach has been to reformulate approved drugs to increase the efficiency of drug delivery into the nail folds, the nail bed and nail plate. Antifungal drugs are known to possess a high binding affinity to

keratin that could have a deleterious effect on their efficacy by reducing the availability of free drug. For example, terbinafine, approved as a systemic treatment for onychomycosis, is 98.9 per cent keratin-bound and has shown limited success in treating onychomycosis when delivered transungually. The degree of drug-keratin binding is not necessarily a disadvantage as it can result in high drug concentrations and persistence in the nail, perhaps forming a drug â&#x20AC;&#x153;reservoirâ&#x20AC;? in the nail plate. However, the rate at which drug is subsequently released from the keratin and delivered into the nail bed must be sufficient to compensate for any loss due to binding, metabolism and clearance of drug from the nail bed. In addition, keratin binding may also decrease drug penetration to the deeper nail layers even with repeated application, because keratin-bound drug does not contribute to a concentration gradient that would otherwise increase drug penetration. Keratin binding and the rate of drug release are both important considerations in any formulation development programme.

the relevant pathogens. Onychomycosis is typically caused by dermatophyte fungi (mainly Trichophyton rubrum) in up to 90 per cent of cases, and can also be due to yeasts (mainly Candida albicans) or molds (mainly Scopulariopsis brevicaulis). With the growing emergence of nondermatophyte infections and mixed infections in onychomycosis, an antifungal with broad spectrum activity is becoming increasingly important. Valeant is among several companies in the process of developing new antifungal treatments for onychomycosis. Developing an Optimal Transungual Solution As this decade advances, the broad goal has been to develop stable non-lacquer formulations for antifungal drugs to provide optimal transungual delivery. As products from Valeant and other companies become available, it will soon become clear whether health care providers and patients prefer this approach. It is our hope that this approach will provide advancement over current treatments, and address a significant unmet need for patients. Contact: jason.olin@valeant.com

First Steps in Developing a Tr a n s u n g u a l S o l u t i o n : C h o o s e a n Effective Antifungal To stand a chance of eradicating the infection resulting in onychomycosis, the antifungal must have high potency against

Antifungal drugs are known to possess a high binding affinity to keratin that could have a deleterious effect on their efficacy by reducing the availability of free drug. 32 ď&#x201A;&#x192;January 2014

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Pharma Bio World

22-01-2014 11:08:01

Understanding Nasal Drug Delivery Nasal delivery additionally provides a method for achieving more rapid onset of action compared to oral delivery in case of nasal disorders. This article discusses the use of the Malvern Spraytec in characterising the output of nasal pump sprays and discusses the importance of ensuring that the conditions applied during testing mimic patient use as closely as possible.

he nasal route is commonly used for the delivery of drugs to alleviate a number of local disorders such as sinus congestion and allergic rhinitis. It is also being utilised as an alternative to oral or injection methods for the systemic delivery of a variety of drugs including vaccines, proteins and peptides. Here, the large surface area for absorption in the nose, coupled with the high density of blood vessels, enables efficient absorption into the blood stream. Nasal delivery additionally provides a method for achieving more rapid onset of action compared to oral delivery, as well as avoiding enzyme degradation of the drug within the GI tract and first pass hepatic metabolism. The ease of use for patients of this drug delivery system may also help improve compliance in comparison with other methods available.

Nasal Product Testing The US Food and Drug Administration’s (FDAs), Centre for Drug Evaluation and Research (CDER) has published a draft 'Guidance for Industry' document entitled Bioavailability (BA) and Bioequivalence (BE) Studies for Nasal Aerosols and Nasal Sprays for Local Action. This document outlines the testing which may be carried out in order to assess drug bioavailability/ bioequivalence during nasal product quality studies in support of New Drug Applications (NDAs) or Abbreviated New Drug Applications (ANDAs). Within the guidance there is a reliance on the use of comparative in vitro tests in order to determine bioequivalence. These tests may include measurements of the characteristics of the spray plume produced by a given device and formulation, as well as the variation in the delivered dose over the lifetime of the device. Droplet Size Characterisation

Figure 1: Malvern Spraytec system for the characterisation of nasal pump sprays.

Stuart Wakefield

Regional Manager Middle East & India Malvern Instruments Ltd Pharma Bio World

Understanding Nasal Drug Delivery.indd 33

A typical nasal spray formulation consists of the drug suspended or dissolved in an aqueous medium, which is filled into a bottle with a metered s pray pump. Pump actuation by the patient delivers drug-laden droplets into the nasal cavity. The pump is an integral part of the whole assembly and plays a crucial role in atomising and delivering an accurate drug dose.The properties of the emitted spray plume are thus considered important in assessing the performance of a given product.

One important consideration for nasal drug delivery is the droplet size produced by the spray pump. Most nasal spray pumps produce droplets in the range from 20μm to around 120μm. The droplet size should be such that the droplets deposit within the nasal passages. If the droplet size is too fine (< 10μm) there is a possibility that the particles will pass through the nasal passages and deposit in the lungs. This could lead to the deposition of drug particles and excipients that are not approved for pulmonary absorption. On the other hand, if the droplet size is too large, the spray may be trapped in the nostrils. It is therefore wise to ensure that the pump produces a spray that stated above during actuation by the patient. The FDA’s draft guidance recommends the use of laser diffraction to determine January 2014  33

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the droplet size produced for a given device and formulation. Laser diffraction systems, such as the Malvern Spraytec, measure the size of droplets by measuring the intensity of light scattered by particles as a function of angle. Key to the selection of the technique for the characterisation of nasal sprays is the ability to acquire this data very rapidly (one measurement can be made every 100Îźs). This allows the changes in droplet size during pump actuation to be followed in real-time, enabling the atomisation dynamics to be assessed. Results Figure 2 shows a typical measurement of a nasal pump spray produced using the Malvern Spraytec. The rapid data acquisition speed possible using the system allows each phase of spray formation to be detected. At the start of actuation the Formation Phase is observed where the pump produces large particles. This is due to the fact that the liquid flow rate through the spray nozzle is initially quite low. Beyond this the particle size reduces until the Fully Developed Phase is achieved, where the flow rate through the spray nozzle is optimal and the spray droplet size is most stable. Finally, towards the end of actuation, the Dissipation Phase is observed where, due to the emptying of

Figure 3: Average cumulative size distributions calculated for each phase of atomisation observed during nasal pump spray actuation.

the metering chamber within the device, the flow rate decreases causing the formation of large droplets. Complete actuation of a nasal spray is rapid and occurred in less than 130ms in this case. FDA guidelines recommend that, in order to characterise nasal spray delivery, the data collected during the fully developed phase should be analysed. Definition of the fully developed phase allows for a statistically valid comparison between Test and Reference products and is therefore an important part of data analysis. In the case of the example above, the formation phase is obvious within the profile, and can be defined within the Spraytec software on the basis of a time

Figure 2: Size history showing the changes in particle size observed during nasal pump spray actuation.

34 ď&#x201A;&#x192;January 2014

Understanding Nasal Drug Delivery.indd 34

window during which the reported Dv10, Dv50 and Dv90 is stable. Based on this time window, the average particle size for each phase can be calculated (Figure 3), and the reproducibility of delivery during the fully developed phase assessed. Realistic Measurements Accurate spray characterisation is obviously important for effective nasal spray testing, but equally critical is the need for representative spray pump actuation. During nasal spray pump testing using the Spraytec system, the variance associated with manual actuation pump can be eliminated by using automated actuation stations. These typically control either the force or velocity of actuation, ensuring that a specific, reproducible actuation profile is followed during all of the tests outlined by the FDA. Indeed, the FDA recommends that automated actuators be used in order to ensure that operator bias is eliminated, allowing variations between different pumps and formulations to be readily observed. However, care must be taken to ensure that the chosen actuation profile is representative of the manual actuation profile of the target patient group if the in vitro tests are to be a good mimic of in vivo performance. This requires some understanding of how the pump performs under different actuation conditions. An example of how automated actuation stations can be used to study the effect Pharma Bio World

22-01-2014 19:54:43

Figure 6: Comparison of manual and automation actuation results.

size irrespective of the patent if a large actuation force can be achieved. Figure 4: Change in droplet size as a function of actuation force for Pump A.

Modelling Manual Actuation Once the behaviour of the pump has been understood, the actuation parameters that best mimic patient use can be selected. This is shown in Figure 6, where the results obtained for manual actuation of pump B by an elderly patient are compared to those obtained using automated seen, the particle size observed in each case is comparable. However, the variance observed during the measurements made using the automated actuation station is significantly smaller. Conclusion

Figure 5: Change in droplet size as a function of actuation force for Pump B.

of actuation variance on droplet size is shown in Figures 4 and 5. Here the Dv10, Dv50 and Dv90 are shown for the same formulation delivered using two commercially available pump systems. For the actuator used in these experiments (NSP3000, InnovaSystems Inc) the applied force was varied and the droplet size delivered during the fully developed phase of the spray event recorded. The results indicate clearly that spray droplet size is a function of actuation force and also that this dependence is pump specific. With low actuation forces both pumps produce relatively large, broad droplet size distributions. However, the particle size observed for Pump B (Figure 5) is much coarser than for Pump A (Figure Pharma Bio World

Understanding Nasal Drug Delivery.indd 35

4), with a significant amount of material being present above 100 Îźm in size. This would suggest that Pump A may not be ideal for those patients who cannot older patients. As actuation force is increased, the droplet size decreases and the droplet size distribution width, as assessed from the difference between the Dv10 and Dv90, becomes narrower. For both pumps the dependency of droplet size on actuation force decreases markedly above 5 kg, but pump B is noticeably less sensitive to actuation force beyond thi s poi nt. This lack of sensitivity may be advantageous, as this pump will deliver a similar particle

Nasal pump sprays and aerosols are becoming increasingly popular as drug delivery systems because of the advantages associated with drug absorption within the nose. This is reflected in the publication of the FDAâ&#x20AC;&#x2122;s guidance document, which has set out the in vitro testing required in order to assess whether consistent g i v e n p r o d u c t . Te c h n i q u e s s u c h a s laser diffraction provide an extremely powerful tool for understanding how drug delivery is achieved. However, it is important that the target patient group is kept in mind during product testing if realistic results are to be obtained. This requires the use of the correct pump actuation conditions. (Article reprinted from Pharma Bio World Octomber 2012 - edition) January 2014 ď&#x201A;&#x201E; 35

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Automated Formulation Tracking Ensures Accuracy, Saves Materials and Expense Pharmaceutical formulation and manufacturing are complex processes, and complete adherence to government guidelines and accuracy in the pharmaceutical preparation is paramount to success. With every bad batch affecting a manufacturer’s bottom line, a systematic, automated way to document formulas and track raw materials can help reduce bad batches, rework, and disposal costs for significant time- and cost-savings.

n our modern world, most pharmaceutical companies still rely on manual processing, in whole or in part, for product manufacturing. Even when guided by highly detailed paper-based systems, these manual processes are subject to human error. Tracking raw materials in particular may be troublesome in these paper-based systems. Without warnings that critical (and often expensive) ingredients are going to expire, entire lots may need to be thrown out, creating not just costly materials loss but added disposal expense. In addition to occasional bad batches caused by human error, these high-volume errors further degrade a pharmaceutical manufacturer’s margins. H o w e v e r, a r o b u s t , d e t a i l e d , a n d configurable formulation and tracking software system that can either stand alone or be easily integrated into a manufacturer’s enterprise resource planning system can help achieve significant materials and cost-savings by providing complete inventory control, ensuring rare or costly raw materials are used within a particular timeframe to maintain maximum potency. It can also automatically prompt operators with detailed work instructions to further avoid bad batches, rework and disposal costs (and keep manufacturers from running afoul of regulatory bodies and the customers who rely on their products). Managing Recipe Creation & Dispensing

Thomas Holzer

Market Manager Chem/Pharma Business Unit Standard Industrial Mettler-Toledo AG 36 January 2014

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Appropriately designed formulation and dispensing software that help provides this kind of surety and traceability complements a pharmaceutical manufacturer’s current processes. Ideally, it works alongside current processes, providing an electronic repository and centralised database without compromising the flexibility that is so critical in today’s fast-paced and rapidly-changing pharmaceutical marketplace.

Formulations can be input and stored for easy recall. The software should also provide detailed, easy-to-understand work instructions on a computer interface. This ensures operators know their next steps — including which ingredients to use, how much of each one to dispense, and any additional processing that needs to occur in a particular processing sequence so that downstream results maintain required accuracy and potency. The automatic recall of stored information provides much-needed consistency in the heavily-regulated world of drug development and manufacturing. Audit trails, electronic signatures, and device identification within the confines of a userfriendly, password-protected workstation with an electronic formulation and inventory management system as its foundation goes a long way towards satisfying essential standards, such as the US Food and Drug Administration (FDA) 21 CFR, Part 11, as well. With a robust enough solution, workflows can be controlled in such a way so that operators know at a glance which orders have been completed, which are in process, and which await processing. This ability to accurately control workflows can enhance throughput and reduce time-to-market while still maintaining the kind of accuracy that is so crucial to manufacturing compliance and end-user safety. Maximising Inventory Management and Yield The bedrock of formulation potency is accurate inventory management. Softwaremanaged inventory control can help a manufacturer know exactly what is in its warehouse, when it arrived, and how long until it expires. Raw materials can be Pharma Bio World

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tracked from the moment they are received to the time they become a finished product heading to the clinic or marketplace. Current stock can be assessed immediately without having to consult multiple logs and personnel, making time-consuming collection and spreadsheet input of inventory reports a thing of the past. These changes dramatically improve information flow between a manufacturer’s warehouse and dispensing systems. With this improved flow of information, raw material use is maximised. Production yield also increases. Establishing guidelines in the software, such as First In, First Out (FIFO), and ensuring operators use the software for appropriate guidance when it comes to inventory management can help a manufacturer fully utilise its inventory and maximise yield from expensive and even sometimes rare or hard-tosynthesize materials. Additional hardware pieces, such as printers and barcode scanners enable this kind of robust tracking for optimum processing speed and inventory management accuracy. Making sure these hardware pieces are w i r e l e s s h e l p e n h a n c e p o r t a b i l i t y. I n essence, the ability to track and trace goes wherever the materials are, with data continuously communicated to the central repository so that an ingredient’s location is tagged and noted, offering what is perhaps the easiest materials tracking and tracing methodology available today. Passing Audits, Integrating Equipment Though formulations and processes differ from drug to drug and manufacturing company to manufacturing company, the need for validation to meet regulatory standards and pass audits is universal. The ability to track and trace enhances the ability to pass audit, ensuring a company can easily show when materials were received, that they were appropriately quarantined until requisite quality control checks could be made, and that they were only released into production after Pharma Bio World

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Though formulations and processes differ from drug to drug and manufacturing company to manufacturing company, the need for validation to meet regulatory standards and pass audits is universal. the quality review occurred. The ability to monitor, track, and control each phase of the production process validates every facet of the formulation process in real time. Being able to track and trace all these activities also necessitates the tracking and tracing of all weighing and calibration activities. Ensuring service records and calibration activities are also included in materials-management. Handling logs helps further show that manufacturing due diligence is occurring and formulations that the company is turning out are accurate, potent, and safe. One Company’s Implementation Experience How might the use of an electronic, softwarebased track and trace data repository look in a day-to-day pharmaceutical manufacturing environment? Are the benefits more than just word on a page? Do they justify the expense of purchasing and implementing such a system? One US-based pharmaceutical company that specialises in custom formulation development and analytical services to a worldwide group of pharmaceutical, biotech, academic and veterinary clients primarily for dosing in capsules and tablets decided that its legacy paperbased formulation-management system needed an upgrade. But because their work is primarily in custom formulation, manual processing would remain a critical component of their operations. Flexibility in their processes was key — but they also needed to eliminate transcription errors and spreadsheet entry slip-ups to improve their overall accuracy and consistency.

The company also wanted a system that would allow raw material, lot and batch numbers to be printed on a ticket with the time and date of intake, and one that would automatically provide operators with detailed work instructions and a complete understanding of current inventory at a glance. Of course, all new features would still have to provide 21 CFR, Part 11 c o m p l i a n t f u n c t i o n s t o f u l f i l l F D A requirements as well. Streamlined Processes and Reduced Costs By fully implementing an electronic inventory management and formulation software system, the company is now able to manage its inventory resourcefully and accurately. The system they chose ensures they can weigh raw materials, track them, and catalog finished products/packaged goods using integrated scales, barcode scanners, and printers. Automatic potency calculation and batch verification is also giving the manufacturer complete control over weighing activities on a daily basis, all but guaranteeing traceability. The addition of easy-clean touchscreen balances to their processes has allowed them to evaluate raw material batch information in production orders on the spot as well. Finally, because their tracking/tracing and formulation procedures are now electronic, the company has noted one additional cost-savings. They are buying less paper! All in all, the new software has allowed them to streamline formulation and inventory processes, continue compiling a record of safe, high-quality products, and really focus on what matters to them most: their clients. Contact: sm@molnarcommunications.com January 2014  37

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market research

Strategies for Indian Pharma in a Volatile World Fragmented Indian pharmaceutical market is facing high volatility and uncertainty. Increasing number of drugs in NLEM and price controls, changing FDI Policy, compulsory licensing, aggressive acquisition investments by MNCs, and declining global generic market opportunity is creating a new normal. Pharmaceutical companies need to re-visit their traditional growth strategies to succeed in a volatile world say Manish Panchal - Practice Head, Charu Kapoor - Principal and Mansi Mahajan - Associate Consultant of TATA Strategic Management Group.

ndian pharmaceutical industry was valued at USD 12 Bn in 2013. The market is primarily driven by exports to regulated as well as semi-regulated markets. Currently, India exports drugs to more than 200 countries and vaccines and bio-pharma products to about 151 countries. Globally, India ranks 3 rd in terms of volume and 14th in terms of value. Indian pharmaceutical industry is fairly fragmented with top 10 companies contributing to 41 per cent of total sales. The next ten companies contribute to 22 per cent of sales while the remaining companies contribute to 37 per cent of the total sales. Urban regions (Metros and Tier I cities) contribute to about 60 per cent of total sales while the remaining country contributes to the balance 40 per cent. Tier I cities are growing at ~10 per cent p.a. while rural areas are growing at ~14.5 per cent p.a. The growth has been driven by increased access to healthcare, improved infrastructure and greater penetration of pharmaceutical companies into Tier 1 cities and rural areas. Changing Market Dynamics The year 2013 has seen deceleration of industry growth rate from 16.6 per cent in 2012 to 9.8 per cent in 2013. During the year, the industry faced a different type of regulatory headwind; the patent office ruled against the intellectual property rights for several notable drugs, including Pfizer’s Sutent, Bayer’s Nexavar, etc. A still more daunting challenge for MNCs 38 January 2014

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operating in India has been compulsory licensing and uncertainty about patent validity. Domestic companies, on the other hand, have been equally impacted by the Drug Prices Control Order and the ensuing stalemate of stocks stuck at various levels in the distribution chain. The Parliamentary Standing Committee recommended multiple mandatory conditions for allowing FDI in brownfield projects while allowing 100 per cent FDI in Greenfield projects. Industry estimates show that generic drug user fee amendments in USA, compulsory licencing and national pharmaceutical pricing policy have increased the legal expenditures of the top 10 drug makers in India by ~50 per cent in the past three years. NPPP is expected to lead to value erosion to the tune of ` 1,600 Cr post implementation for the year 2013-14.

With the notification of the order, the NPPP 2012 comes into effect and 348 drugs under NLEM, which account for 60 percent of total domestic pharmaceutical market amounting to nearly ` 29,000 Cr, would come under price control. These factors, coupled with general elections in 2014 and a host of high-profile M&A deals and aggressive investments by MNCs in India clearly indicate that the industry is going through a period of significant volatility and uncertainty which has created a new normal for the companies. In such an uncertain playing field, it is imperative for companies to ask “How do we grow our business from here?” Companies will need to reinvent their business model or take on some disruptive new approach as traditional strategic approach would have limitation in this transient world.

National Pharmaceutical Pricing Policy -Price controls for drugs under NLEM -Ceiling price fixed on market based method -Short term topline impact

Changing Generic Market Space -ObamaCare opening up generic opportunity in USA -Reducing new generic opportunity at USD 3 Bn in 2013 vs USD 24 Bn in 2007

More Stringent Compliance Norms -Amendment in US FDA approval norms -Increased fee to sell products in USA -Additional cost for re-inspection of US FDA approved facilities & DMFs

VOLATILE & UNCERTAIN PLAYING FIELD

FDI Policy -100% FDI in Greenfield investments -Approvals for brownfield investments -Specific conditions on production levels of essential medicines, R&D expenses, technology transfers etc. Compulsory Licensing -Indiscriminate use would undermine both MNCs and domestic players -Balance needed between affordability of drugs and patent protection for life saving patented drugs

Figure 1: Key industry trends impacting Indian Pharmaceutical Market

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Strategies for Success in Uncertain and Volatile Environment TATA Strategic analysis suggests that companies which quickly adapt to the uncertain and volatile environment will be the possible winners in 2014 and beyond. Going forward, the companies will need to build their business using one or more of the following five levers. (Refer Figure 2) Review Product Portfolio The new pricing mechanism as specified in the NPPP 2012 would impact near term earnings of companies. The companies most affected will be the ones with

customer segments. For each customer segment in the value chain, be it channel partners, practicing physicians, or direct patients, companies need to look at building distinctive forms of customer connect through advanced mechanisms of sales force engagements, consolidation of field force, strengthen marketing channels with adoption of digital marketing, and organise patient education programmes. Companies should not just promote their products but see themselves as a disease prevention and management company.

co-marketing through use of common marketing channels and co-promotion to reduce advertisement & promotion costs by leveraging common distribution channels. It will also help companies to capitalise on licensing opportunities presented by international pharmaceutical players as they increasingly invest in emerging economies. Recent JV/M&A activities highlight the consolidation trend in the industry.

Strengthen Operational Capability

To successfully respond to uncertainty, companies will have to create a culture of agility and innovation. They will need to take a fresh look at their organisational structure, especially the number of layers in the organisation, the relationship between business units, and the mix of organisational boundaries. They will need to significantly redefine business processes to enable quick decisions and lower cycle times while also meeting increased compliance requirements. The leadership team and senior management will also have to be trained to accept the new normal as a â&#x20AC;&#x153;way of lifeâ&#x20AC;? and respond to change quickly.

Companies will need to revisit their operations to ensure that no complacency

Organisational Agility

Way Forward Figure 2: Levers for success

higher dependence on Indian market, premium pricing approach and having higher share of acute therapy segment. On the other hand, the impact of the new policy would not be substantial on companies that have sizeable share of earnings from regulated markets, especially US generics. Therefore, it will be vital for companies to re-look at its geographic spread and to re-new their portfolios by focusing on; therapeutic class synergies, increasing share of prescription, adding innovative and better margin products.

has set in. The legacy processes might be driving up costs due to outdated technologies or high e-factor1. Companies will need to focus on process innovations by adopting latest technologies such as micro reactors or critically evaluating and reducing the number of process steps. Furthermore, benchmarking of manufacturing processes and supply chain optimisation will help in establishing the extent of improvement required to be achieved by the company.

Build Customer Centricity

Companies need to look for inorganic value creation and speed to market opportunities. Alliances could help in deeper customer and market penetration with value creation happening in many forms such as co-production to reduce compliance costs,

To succeed in such a complex environment, companies will need to take a customer centric view to re-look at the value proposition for each major Pharma Bio World

MARKET RESEARCH.indd 39

Value Creation by JV/M&A

The regulatory environment in the pharmaceutical sector is more challenging now than ever before. To meet the new normal, companies will have to invest in re-establishing their competitive position. Optimisation of product portfolio to target high return products and building distinguishing capabilities to stay ahead of competition would be the key to success. Both domestic and multi-national players will need to look at inorganic growth opportunities including value creation through partial carve outs as it would play a key role in defining the long term sustainability of the companies. The winning companies will be the ones which analyse their competitive position and meet the rapid changes happening in the industry by evaluating and speedily implementing the five levers outlined above. Contact: manish.panchal@tsmg.com January 2014ď&#x201A;&#x201E; 39

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news features

Quid Pro Quo In a market that is emerged in aggressive competition, the easier way that has been chosen by most for decades now is indulging in unethical practices. But in the wake of tightening regulations and reforms, how long can these malpractices make way, questions Ananya Sen.

SK’s global s ales and mark eting polic y rec ently witnes s ed a dras tic rev is ion a ccording to whic h the c ompany w ill no longer mak e direc t pay ments t o healthc are profes s ionals for e n dors ing their produc ts and attending m e dic al c onferenc es . The new polic y a lso c laims to eliminate indiv idual t a rgets of s ales profes s ionals . The p e r formanc e of the s ales reps ins tead w ill now be bas ed on their tec hnic al kn owledge and other ev aluation p a r ameters . The c ompany plans to in itiate work ing on thes e reforms by 2 0 14 to hav e them in plac e by 2016.

based on International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Code.

C r acking the Codes

According to the Code laid by OPPI, pharma manufacturers are prohibited from extending any kind of financial benefit to healthcare professionals in the form of grants, scholarships, subsidies or support of any other kind for prescribing or recommending their drugs. The Code demands transparency of operations carried out by companies during the post marketing surveillance and discourages any kind of disguised promotions. It also forbids promotion of off label use of drugs without their required consent for marketing.

Th e pharmac eutic al c ompanies g lo bally hav e been prac tis ing an u n sav oury tradition of bribing h e althc are profes s ionals for p res c ribing c os tlier drugs in e xchange for ex pens iv e gifts and ca sh. The pric e of drugs ris es w it h the amount ex pended by m a nufac turers on s ops for phy s ic ians m a king all efforts for av ailing a ff ordable medic ation futile. MNCs in India are bound by O rganis ation o f Pharmac eutic al Produc ers of I n d ia (O PPI) Code of Pharmac eutic al M a r k eting Prac tic es whic h is c los ely

Although the Department of Pharmaceuticals (DoP) has its own set of Uniform Code of Pharmaceutical Marketing Practices for Indian drug makers, it is yet to be mandated. While the OPPI does not permit provision of travel facilities to a medical practitioner as a delegate in medical conferences or events, inside the country or outside limiting hospitality to refreshments and/or meals, the DoP’s code states “where appropriate and depending on the time, location and length of the meeting, support to healthcare professionals may

The price of drugs rises with the amount expended by manufacturers on freebies for physicians making all efforts for availing affordable medication futile. 40 January 2014

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Care Act, mandates manufacturers of drugs and medical devices in the US to report all monetary transactions with physicians that will be publicly available in a website. The physicians will have a chance to review the data updated by manufacturers and also rectify it within a given duration before it is made public.

Tapan Ray, former Director General, OPPI in his website questions, “Do these well-hyped ‘Codes’ really work on the ground or are merely expressions of good intent captured in attractive templates and released in the cyberspace for image building?” cover actual travel expenses, meals, refreshments, accommodation and registration fees.” Both the OPPI and DoP discourage distribution of cash or support in any other form to doctors. While drug companies have long used largesse as “brand reminders” for doctors, a prepaid cash card leaked by an industry whistleblower appears to be the first evidence to suggest doctors are also being offered cash cards that can be preloaded with up to ` 50000. A drug industry insider shared revealed an image of a prepaid gift card purportedly issued by HDFC Bank to a Mumbai-based drug company. The card mentions the company’s name, Macleods, and a drug it produces. The validity of the card had expired in March 2013. Courtesy: Prescribe and swipe, Doc. All prepaid : The Telegraph(Calcutta) dated Monday , December 23 , 2013.

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Tax It to Fix It The Medical Council of India (MCI) in December 2009 made an amendment to the Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations setting a code of conduct for medical professionals associated with pharmaceutical industry. This disallowed doctors from endorsing drugs and receiving gifts, travel facilities, hospitality and all sorts of pecuniary favours. Later in 2012, the Central Board of Direct Taxes announced that violating MCI’s code of ethics by way of acceptance of gifts or other favours on the part of medical professionals and distribution of the same by drug manufacturers will be made taxable depending on the value of those freebies.

Besides preventing drug makers and physicians from indulging in unethical practices this level of transparency is also intended to study and analyse the ongoing trend of treatments being chosen. This website containing the updated data is expected to be ready by September 2014. A model like this one adopted by the US, suggest experts is worth emulating. Walk the Talk Reacting to GSK’s bold decision Tapan Ray, former Director General, OPPI in his website questions, “Do these well-hyped ‘Codes’ really work on the ground or are merely expressions of good intent captured in attractive templates and released in the cyberspace for image building?” While the DoP’s codes for Indian manufacturers await implementation, a need to curb the menace has been strongly felt in the industry. References 1.OPPI Code of Pharmaceutical Practices 2012 2.Indian

Medical

Council

(Professional

Conduct, Etiquette and Ethics) (Amendment) Regulations, 2009 PartI 3.http://www.ama-assn.org/ (Sunshine Act: Physician financial transparency reports) 4.http://pharmaceuticals.gov.in/uniformcode. pdf

Let the 'Sunshine' The Physician Payments Sunshine Act (Sunshine Act), a part of the Affordable January 2014 41

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marketing initiative

B&R Expanding the Successful Power Panel HMI Family Terminal and controller with touch screen

designs

B&R is adding two new series to its successful Power Panel HMI family: Power Panel T-Series terminals and Power Panel C-Series controllers -both featuring touch screens. Equipped with an embedded browser, the Power Panel T30 terminal is fully web compatible and can even be used as a VNC client. The terminal series is being offered with four TFT display sizes ranging from 4.3” to 10.1” and comes with two Ethernet interfaces, two USB ports and an extensive array of configuration options. High-performance HMI with a wide range of connection options The Power Panel C70 controller is equipped with a 333 MHz Intel ® AtomTM CPU, 256 MB DDRAM, 16 kB FRAM and 2 GB onboard flash EEPROM memory. This controller provides a built-in touch screen and is being offered in three display sizes ranging from 5.7” to 10.1”. In addition to achieving cycle times as low as 1 ms, the Power Panel C70 also features POWERLINK and standard Ethernet, 2x USB 2.0 and X2X Link technology as well as optional RS232, RS485 and CAN connections to offer a wide range of possibilities for peripheral devices. Both of these device series have an extremely compact design, minimal installation depth and an intelligent cable outlet arrangement, making these panels easy-to-mount space savers. And because these two new 42 January 2014

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Two new HMI series from B&R – Power Panel T-Series terminals and Power Panel C-Series controllers – are available in a wide variety of display sizes.

series do not have hard disks, fans or batteries, they are completely maintenance-free. The panel front provides IP65 protection, which makes these systems extremely suitable for hygienic applications. About B&R B&R is a privately owned company with headquarters in Austria and offices all around the world. As a global leader in industrial automation, B&R combines state-of-the-art technology with advanced engineering to provide customers in virtually every industry with complete solutions for machine and process automation, motion control, HMI and integrated safety technology. With industrial fieldbus communication standards like POWERLINK and open SAFETY as well as the powerful Automation Studio

software development environment, B&R is constantly redefining the future of automation engineering. The innovative spirit that keeps B&R at the forefront of industrial automation is driven by a commitment to simplifying processes and exceeding customer expectations. For more information, visit www.br-automation.com

Pharma Bio World

22-01-2014 15:20:33

pharma news Centre to Revise D&C Rule

Aristo Wins Case Against Innova

During the National Regulatory Authority assessment conducted at Central Drugs Standard Control Organization (CDSCO), World Health Organization (WHO) expressed its concern that the vaccines which are manufactured by using different source of antigen have been labeled with the same manufacturing license number without having any unique identification number which otherwise does not provide the correct information in respect of the origin of the vaccine.

The Bombay High Court has ordered Innova Cap Tab and its sister companies to refrain from making and marketing any medicinal preparation or product by using the mark ‘MONTINAL’. On September 19 last year, Aristo Pharmaceuticals sued Innova Cap Tab in accuse of infringing its trademark.

In response to the WHO’s concern, The Union health ministry has proposed that Rule 96 of Drugs and Cosmetics (D&C) Rules for labeling of vaccines should be amended to include new drug approval number on the label of the vaccine granted by the Licensing Authority as defined under Rule 21(b) of the D&C Rules. As per Rule 122 E, all vaccines are considered as new drugs and any change in the source of antigen, the new drug approval is required to be obtained from the Licensing Authority. However, there is no specific provision under Rule 96 for labeling of the vaccine with specific reference to its origin.

Pharma Industry Wants Govt to Clarify Vague PET Ban As health ministry has been considering a ban on the use of plastic and PET containers for liquid formulations, Goa Pharmaceutical Manufacturer’s Association (GPMA) asked the government to take immediate steps to clarify its stand on the proposed ban. This demand comes in the wake of growing concern within the industry over the Drugs Technical Advisory Board (DTAB) recommendation to the DCGI on phasing out of the use of plastic and PET (Polyethylene Terephthalate) containers for liquid formulations from the market on a gradual base. GPMA pointed out that a lot of projects focused on expansion of oral liquid preparation have been stalled across the country due to the uncertainty and lack of clarity on the use of PET bottles. According to A K Burman, president, GPMA, globally PET is used as a well expected packaging material, even in the regulated markets like US, UK Japan etc. He stressed that industry finds it a little confusing on why India needs to suddenly ban the use of PET especially in the absence of any scientific evidence support the ban. In another move, the Federation of Pharma Entrepreneurs (FOPE), in a representation to the health ministry, said the ban recommendation had disturbed the industry. The pharma industry was earlier using glass bottles only as primary packaging material for pharmaceuticals. However, the industry switched to PET bottles primarily because they are easy to handle in the distribution and retailing process. Pharma Bio World

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According to the compliant, Aristo originally conceived and adopted the MONTINA trademark being, to be used for its products in December 2002. On December 31, 2002, it applied for and got the trademark MONTINA registered for medicinal and pharmaceutical preparations. Subsequently, it became a private limited company. The registration of the trademark was renewed on December 31, 2012, for 10 years by Aristo. The registration of the trademark is thus valid and subsisting. In June last year, Aristo started making a medical preparation in the form of syrup and tablets that was to be marketed under the trademark MONTINA. In August last, it started selling its products under the trademark MONTINA-L. Since then Aristo is selling the preparation. In September last year, Aristo came across the Innova’s preparation sold under the MONTINAL trademark.

Cadila, Novasaid to Develop Treatments in Inflammation and Pain Management NovaSAID AB and Cadila Pharmaceuticals Limited have entered into a strategic partnership to develop new treatments for inflammation and pain in conditions such as rheumatoid arthritis. NovaSAID is a company in Karolinska Development’s portfolio. The companies will collaborate around preclinical and clinical Dr Rajiv I Modi development of drug candidates that Chairman & MD Cadila have been developed by NovaSAID and the development will be conducted at Cadila Pharmaceuticals’ facility in Ahmedabad, India. According to the agreement, all revenue generated from the sale and marketing in India, Middle East and Africa of products covered by the agreement will be retained by Cadila and net sales in all other countries will be shared by the two companies. Cadila will bear all costs associated with the program through to Phase II. Speaking on this new initiative, Dr Rajiv I. Modi, Chairman and Managing Director, Cadila Pharmaceuticals said: “We have entered this partnership combining scientific expertise of NovaSAID and our drug development capabilities to work towards novel solutions in treatment of pain and inflammation, which is one of the largest therapy areas. This is in line with the vision of our Founder Chairman, I A Modi, who believed in nurturing innovations and bringing them to Indian patients at an affordable cost.” January 2014 43

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Mylan Appoints Rakesh Bamzai as GE Acquires Assets from Thermo Fisher President Scientific Mylan Inc announced that Rakesh Bamzai has joined the company and has been appointed president, India Commercial and Emerging Markets. Bamzai has more than 20 years of experience in the Indian and global biopharmaceutical industry. Prior to joining Mylan, he was president of Marketing at Biocon, where he played a key role in building the company’s global biopharmaceutical business. He had overall responsibility for active pharmaceutical ingredients (API) and branded formulations and managed a team of more than 2,000 people across functional areas and geographies. Through the years, he also spearheaded many strategic partnerships that enabled the organisation to gain wider global access and greater market penetration for its biopharmaceuticals business. Bamzai also led Biocon’s foray into branded formulations and built many successful brands across therapies in India and Gulf Cooperation Council states. Mylan President Rajiv Malik commented, “We were extremely pleased when Rakesh asked to join our company. Many of us at Mylan have had a firsthand opportunity to work with Rakesh over the course of our strategic partnership with Biocon and have observed his strong business and marketing acumen, his strategic insight and outstanding leadership skills. In this new role overseeing all of Mylan’s commercial operations in Indiaand emerging markets, we believe that Rakesh will add significant value to Mylan.” Bamzai said, “I have had the privilege of collaborating with Mylan during my time at Biocon, and I am excited about the significant opportunities I see for the company in India and other emerging markets. I believe Mylan’s commitment to quality and to setting new standards for innovation, reliability and service for patients and physicians in India will further distinguish Mylan from its peers. I look forward to supporting Mylan’s continued expansion and differentiation in these exciting growth markets.”

Allergan, Medytox Close Licensing Pact Allergan, Inc, and Medytox, Inc have closed the license agreement which was previously announced on September 25, 2013. Under the terms of the agreement, Allergan will pay Medytox an upfront cash payment of USD 65 million within seven business days of closing and Medytox has granted Allergan exclusive rights, worldwide outside of Korea, to develop and, if approved, commercialise certain neurotoxin product candidates currently in development, including a potential liquidinjectable product. Pursuant to the agreement, Allergan has also agreed to make additional contingent payments, including up to an aggregate of USD 116.5 million upon achieving certain development milestones, up to an aggregate of USD 180.5 million upon achieving certain commercialisation milestones, and royalties on product sales. 44 January 2014

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GE and Thermo Fisher Scientific have entered into an agreement for GE Healthcare to acquire Thermo Fisher ’s HyClone cell culture media and sera, and gene modulation and magnetic beads businesses for approximately USD 1.06 billion. The acquisition will allow GE to expand its offering of technologies for the discovery and manufacturing of innovative new medicines, vaccines and diagnostics in its growing Life Sciences business. The complementary product offerings and strong strategic fit of the acquired businesses will enable GE Healthcare to expand and accelerate the development of innovative “end-to-end” technologies for cell biology research, cell therapy and for the manufacture of innovative biological medicines and vaccines. The acquisition is consistent with GE’s strategy to invest in high-technology, innovative businesses that deliver strong top-line growth and expanded margins. GE’s acquisition of the businesses, which is subject to regulatory approvals, is anticipated to close in the first part of 2014. GE Healthcare’s century of leadership in medical diagnostic technology includes its USD 4 billion Life Sciences business, which delivers innovative products and services for the fast-growing

EarlySense 2.0 System Gets FDA Clearence EarlySense, the market leader in Proactive Patient Care Solutions, has received FDA Clearance for EarlySense 2.0 System, a newly designed Bedside Monitor for continuous measurement of respiration rate, heart rate and motion, in an automatic and contact-free manner. Dalia Argaman VP, Clinical and Regulatory Affairs EarlySense

“The newly designed Bedside Monitor is in line with EarlySense’s constant focus on innovation and patient care improvements.” said Dalia Argaman, VP of Clinical and Regulatory Affairs at EarlySense. “We provide the clinical team access to actionable information and empower them to identify potentially critical situations and respond in a proactive manner, in the hopes of preventing an adverse event from occurring as well as assisting the clinical team to become more efficient.” EarlySense is also enhancing its focus on Quality Assurance Tools and Benchmark Analysis Reports to provide sophisticated management tools that will allow hospital leaders to set quality goals, measure their results, drive staff behavior towards improvement and achieve their objectives. For example, providing the capabilities to measure staff response times to bed exit alerts, and then reviewing reports with staff has allowed several institutions to improve their response times, and thus reduce fall rates. Pharma Bio World

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Endo Sells Healthtronics Business to Altaris Endo Health Solutions has entered into a definitive agreement to sell its HealthTronics business to Altaris Capital Partners, LLC for an upfront cash payment of USD 85 million, subject to cash and other working capital adjustments. In addition, Endo will receive rights to additional cash payments of up to USD 45 million based on the future operating performance of HealthTronics for a total consideration of up to USD 130 million. The company previously divested two operating divisions of HealthTronics, its image guided radiation therapy (IGRT) and its anatomical pathology laboratory businesses, for total consideration of approximately USD 25 million. “The divestiture of HealthTronics enables us to focus more sharply on achieving our objective of building Endo into a leading productbased specialty healthcare company,” said Rajiv De Silva, president and CEO of Endo. “I am pleased that the agreement with Altaris will provide an opportunity for the employees of HealthTronics to join an organisation that will focus on growing this leading provider of products and services to US-based Urologists.” This transaction and the earlier announced sale of HealthTronics’ anatomical pathology business and IGRT business completes Endo’s full divestiture of all HealthTronics businesses. The transaction is expected to close in the first quarter of 2014, subject to customary conditions, including the expiration or termination of any applicable waiting periods under applicable competition laws.

and offers an important treatment option for these patients. In Europe, BOSULIF was granted conditional marketing authorisation for the treatment of adult patients with Ph+ CML previously treated with one or more TKIs and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.

A P Pharma Changes Name, Appoints New Directors A P Pharma Inc, a specialty pharmaceutical company, today announced that it has changed its name to Heron Therapeutics, Inc and affected a 1-for-20 reverse stock split, both effective January 13, 2014. The reverse split is being implemented to increase the Company’s stock price in support of the Company’s pending application to list on the NASDAQ Capital Market. Assuming satisfaction of listing standards, the Company expects to list on NASDAQ by the end of January. The Company is also expanding its board of directors and today announced the appointment of three new independent directors. Joining the Heron Therapeutics board of directors effective today are John Poyhonen, President and Chief Executive Officer of Senomyx, Inc, Kimberly Manhard, Senior Vice President of Regulatory Affairs and Development Operations at Ardea Biosciences, a subsidiary of AstraZeneca PLC, and Craig Johnson, a senior advisor and consultant in the biopharma industry.

Adamas Pharma Bags Milestone Payment Avillion, Pfizer to Co-develop BOSULIF from Forest Labs for MDX-8704 The Avillion Group (Avillion), a co-developer of late-stage clinical assets, has entered into an exclusive collaborative development agreement with Pfizer Inc to conduct a global Phase 3 clinical trial of Pfizer’s BOSULIF (bosutinib). The trial, which will be conducted across multiple sites in the United States, Asia and Europe, will evaluate BOSULIF, administered at a starting dose level of 400 mg daily, as a first-line treatment for patients with chronic phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML). Under the terms of the agreement, Avillion will provide the funding for and will conduct the trial to generate the clinical data necessary to potentially support a registration dossier for marketing authorisation of BOSULIF by regulatory authorities for an indication as first-line treatment of patients with chronic phase Ph+ CML. If approved for this indication, Avillion will be eligible to receive milestone payments from Pfizer upon regulatory approval of the drug. Pfizer will retain all rights to commercialise BOSULIF globally. BOSULIF is an oral, once-daily, TKI which inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases. BOSULIF is currently approved in the US for the treatment of adult patients with Ph+ CML with resistance or intolerance to prior therapy Pharma Bio World

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Adamas Pharmaceuticals has received USD 40 million in milestone payments from Forest Laboratories Holdings Limited for MDX-8704. MDX-8704 is a fixed dosed combination (FDC) of Namenda XR (memantine HCl extended release capsules) and donepezil HCl being developed as a once daily therapy for the treatment of moderate-tosevere dementia of the Alzheimer’s type in the United States. The milestone payments are for the successful completion of studies that support the planned New Drug Application (NDA) filing with the US Food and Drug Administration (FDA) for MDX-8704 by Forest in the first half of 2014. These studies are based on a development plan agreed to by Adamas and the FDA prior to its license agreement with Forest. Leveraging Adamas’ know-how and intellectual property, the companies are collaborating on the development of the FDC, for which Forest has exclusive US commercialisation rights. Forest is responsible for all regulatoryrelated activities. MDX-8704 is covered by multiple Adamas and Forest patents that extend to 2029. Pursuant to their license agreement for development and commercialisation of MDX-8704, Forest paid Adamas USD 65 million upfront in November 2012, and these USD 40 million payments are part of up to USD 95 million in subsequent development and regulatory approval milestones. January 2014 45

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arGEN-X Gets 2 Preclinical Milestone Payments Under Shire Collaboration arGEN-X, a clinical stage human therapeutic antibody company, announces the attainment of two important success milestones in its SIMPLE Antibody research and product development collaboration with Shire. The milestones, which trigger undisclosed payments from Shire, relate to demonstration of in vivo proof of concept for one of the ongoing antibody discovery programmes. Initiated in February 2012, the collaboration is focused on creating human therapeutic antibodies against complex targets implicated in severe, rare genetic diseases. Shire has an option to license the most promising antibody leads for further development and commercialisation worldwide, in return for fee, milestone and royalty payments. “Yet again the functional diversity of SIMPLE Antibodies has enabled our scientists to set a precedent in validating highly complex targets both in vitro and in vivo and identifying antibody leads with exciting therapeutic potential,” said Hans de Haard, PhD, Chief Scientific Officer of arGEN-X. “We value our collaboration with Shire very highly and continue to make excellent progress through the outstanding joint efforts of our teams.” arGEN-X also announced the initiation of a new pilot research agreement with Boehringer Ingelheim. No further details are being disclosed at this stage.

Regeneron, Geisinger Sign Human Genetics Research Collaboration Pact Regeneron Pharmaceuticals Inc and Geisinger Health System, one of the largest integrated health systems in the United States serving approximately 3 million residents, has announced major research collaboration focused on studying the genetic determinants of human disease.

associations between genes and human disease. “For Geisinger, this relationship is about the potential to improve individualised patient care,” commented David H Ledbetter, PhD, Executive Vice President and Chief Scientific Officer of Geisinger Health System. “We expect that many of our patients will directly benefit from their participation in this research because of Geisinger’s ability to validate and return clinically actionable results to them, and all of our patients will benefit from the knowledge we gain in how to help set the standard for genomically informed care. This collaboration has the potential to provide Geisinger with tools to transform our ability to foresee disease before the onset of symptoms, diagnose chronic and potentially fatal conditions before it’s too late to intervene, and determine how best to optimise the health and well-being for each of our patients.” The collaboration will benefit from Geisinger’s state of the art sample collection and storage capabilities, the MyCode biorepository, and extensive electronic medical records. Regeneron has built a team and an infrastructure to support sequencing and genotyping over the term of the collaboration. Regeneron intends to use its translational research and functional biology capabilities, including its VelociGene technology, to validate observed human genetic associations.

N o ven, Shio no gi t o Co - P r o mo t e Brisdelle Capsules Noven Pharmaceuticals Inc has entered into an agreement with Shionogi Inc to co-promote Brisdelle (paroxetine) capsules, 7.5 mg. The agreement will help extend physician awareness of the first and only FDA-approved, non-hormonal treatment for moderate to severe vasomotor symptoms (VMS) associated with menopause, commonly referred to as hot flashes. Brisdelle has been marketed and sold through Noven Women’s Health since November 2013.

David H Ledbetter Executive VP & Chief Scientific Officer Geisinger

Under the terms of the multi-year agreement, the Shionogi women’s health sales force will promote Brisdelle in the US to a range of health care providers not currently detailed by the Noven Women’s Health specialty sales force, including select primary care physicians who treat this condition, beginning in February 2014. Noven will retain all commercial rights to the product and will continue to be principally responsible for product marketing, promotion and overall commercial strategy. Financial terms of the agreement were not disclosed.

During the initial five-year collaboration term, Geisinger plans to collect samples from more than 100,000 consented patient volunteers, while Regeneron, through its wholly-owned subsidiary, Regeneron Genetics Center LLC, will perform sequencing and genotyping to generate de-identified genomic data. The size and scope of the study are meant to allow great precision in identifying and validating the

Brisdelle was specifically studied and FDA-approved to treat moderate to severe hot flashes associated with menopause. When used as directed, Brisdelle is clinically proven to reduce moderate to severe hot flashes so that they are less frequent and less intense. These moderate to severe hot flashes are sudden feelings of intense heat in the body that include sweating. At 7.5 mg, Brisdelle contains a lower dose of paroxetine than that used to treat a number of psychiatric disorders. The lower dose of paroxetine in Brisdelle has not been studied in any psychiatric conditions and Brisdelle is not approved for any psychiatric uses.

Beginning only ten years after the sequence of the first complete human genome was published, this new research collaboration will include one of the largest United States populations of participants for the analysis and sequencing of genetic material and comparison to long-term health outcomes.

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Prosensa, GSK End Collaboration on DMD Treatment Prosensa Holding NV and GlaxoSmithKline announced that Prosensa has regained all rights from GSK to drisapersen and will retain rights to all other programmes for the treatment of Duchenne Muscular Dystrophy (DMD). This transfer of rights represents the termination of the collaboration agreement between GSK and Prosensa executed in 2009. Prosensa will now have the full, unencumbered rights to continue the development of drisapersen as well as each of its DMD programmes. The parties have agreed that Prosensa is well suited to continue the development of all of the DMD programmes. Prosensa and GSK have also agreed to make certain data from the drisapersen studies available in due course to the scientific community for the purpose of furthering the general understanding of DMD. “We are fully committed to our mission of developing innovative, RNAbased therapeutics to address unmet medical needs for patients with rare genetic disorders,” said Hans Schikan, Prosensa’s Chief Executive Officer. “Prosensa is now in a favorable strategic position to advance the DMD portfolio, which includes drisapersen and five additional compounds, three of which are currently in clinical development. We will continue to work closely with patient groups, investigators, academia and regulators to ensure that we do everything we can to bring treatments to boys affected by DMD.”

Health Canada Okays Novartis Pharmaceuticals’ UltibroTM Breezhaler

Riad Sherif, President Novartis

Novartis Pharmaceuticals Canada Inc has received the Health Canada approval for the use of long-term once-daily dual bronchodilator Ultibro Breezhaler (indacaterol 110 mcg/glycopyrronium 50 mcg) as a maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

Health Canada approved Ultibro Breezhaler based on five studies from the IGNITE clinical programme (SHINE, ILLUMINATE, SPARK, BRIGHT and ENLIGHTEN studies). These studies showed that QVA149 provided rapid and sustained improvements in lung function, and significantly reduced shortness of breath. These improvements were maintained throughout the duration of the trials. The IGNITE clinical programme is one of the largest international phase III clinical trial programmes in COPD, with 11 trials in total and more than 10 000 patients involved.Ultibro Breezhaler is a fixed-dose combination (FDC) of two bronchodilators, Onbrez Breezhaler (indacaterol maleate), a long-acting beta2-adrenergic agonist Pharma Bio World

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(LABA) and Seebri Breezhaler (glycopyrronium bromide), a long-acting anticholinergic (LAAC).Both are currently used by healthcare professionals as individual therapies to treat COPD in Canada. “COPD is known to affect an estimated 210 million people worldwide and is projected to be the third leading cause of death by 2020. Several patients find COPD symptoms really tough to cope with – even if they’re already taking treatment,” said Dr Riad Sherif, president of Novartis.

EC Grants Orphan Drug Designation to NPS Pharmaceuticals’ Natpara NPS Pharmaceuticals Inc, a global biopharmaceutical company pioneering and delivering therapies that transform the lives of patients with rare diseases, has announced that the European Commission (EC) has granted orphan drug designation to Natpara (recombinant human parathyroid hormone (rhPTH[1-84]) for the treatment of hypoparathyroidism. Natpara is a bioengineered replacement for endogenous parathyroid hormone (PTH) that NPS has developed for the treatment of hypoparathyroidism, a rare endocrine disorder in which the body produces insufficient levels of parathyroid hormone, a principal regulatory of the body’s mineral homeostasis. Orphan drug designation in the European Union (EU) is given to products that are designed for the diagnosis, prevention or treatment of rare diseases that are life-threatening or chronically debilitating. A disease is defined as rare in the EU if it affects no more than five in 10,000 people. The company was also granted orphan drug status by the US Food and Drug Administration(FDA) in 2007. The company submitted its US Biologic License Application to FDA in October 2013.

Carmot Therapeutics, Amgen Ink Drug Discovery Deal Carmot Therapeutics has entered into a collaboration and license agreement with Amgen, Inc. During the collaboration Carmot will apply its proprietary Chemotype Evolution to discover novel drug leads for two targets selected by Amgen. Carmot and Amgen will work together to identify and optimise drug candidates, while Amgen will be solely responsible for their clinical development. Under the terms of the agreement, Carmot will receive an upfront payment, research funding, and pre-clinical and clinical milestone payments. In addition, a royalty will be paid on commercial sales of products emerging from the collaboration. “This collaboration with Amgen, one of the world’s largest and most successful biotech companies, is a significant milestone for Carmot and a recognition of the potential of Chemotype Evolution. We look forward to working with the excellent scientific team at Amgen to tackle two challenging therapeutic targets with significant market potential,” said Carmot CEO, Dr Stig K Hansen. January 2014 47

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Authorised Detrol Generic from Teva Teva Pharmaceutical Industries Ltd has announced the launch of the Authorised Generic of Detrol LA (tolterodine tartrate extendedrelease capsules) 2 mg and 4 mg in the US market. Detrol LA had annual sales of approximately USD 571.5 million in the US, according to IMS data as of September 30, 2013. Detrol is a registered trademark of Pfizer Enterprises Sarl. Te v a P h a r m a c e u t i c a l I n d u s t r i e s L t d i s a l e a d i n g g l o b a l pharmaceutical company, committed to increasing access to high-quality healthcare by developing, producing and marketing affordable generic drugs as well as innovative and specialty pharmaceuticals and active pharmaceutical ingredients. Headquartered in Israel, Teva is the world’s leading generic drug maker, with a global product portfolio of more than 1,000 molecules and a direct presence in about 60 countries. Teva’s branded businesses focus on CNS, oncology, pain, respiratory and women’s health therapeutic areas as well as biologics. Teva currently employs approximately 46,000 people around the world and reached USD 20.3 billion in net revenues in 2012.

Eisai Unveils Antiepileptic Drug Fycompa in US Eisai Co, Ltd has announced that on its US subsidiary Eisai Inc launched the AMPA receptor antagonist Fycompa (perampanel), a first-in-class antiepileptic drug (AED) discovered and developed inhouse, in the United States as an adjunctive therapy for partial-onset seizures with or without secondary generalised seizures in patients with epilepsy aged 12 and older. Fycompa is a highly selective, noncompetitive AMPA receptor antagonist discovered and developed by Eisai. With epileptic seizures being primarily mediated by the neurotransmitter glutamate, the agent works as a first-in-class AED that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at postsynaptic AMPA receptors. It is approved in more than 35 countries worldwide, mostly in Europe and North America, and has been already launched in Canada and in a number of European countries. In the United States, following approval by the US Food and Drug Administration (FDA) in October 2012, Fycompa was recommended to the US Drug Enforcement Administration (DEA) for scheduling classification under the country’s Controlled Substances Act and subsequently placed as a Schedule III drug. The number of patients with epilepsy in the United States is approximately 2.2 million people and approximately 150,000 people are estimated to be newly diagnosed with epilepsy in that country each year. Furthermore, some 60 per cent of patients diagnosed with epilepsy in the United States have partial seizures, of which approximately 25 to 30 per cent are unable to control their seizures with current treatment options. Fycompa, which has a mechanism of action different to that of other licensed AEDs, offers a new treatment option for epilepsy patients with partial-onset seizures. 48 January 2014

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ERT Reaches Milestone in Supporting Successful NDAs

Jeffrey Litwin, MD & CEO, ERT

ERT has reached a significant milestone in capturing important data to support the approval of new medical products. To date, global regulatory agencies have issued over 300 approvals to biopharmaceutical companies that relied on ERT’s cardiac safety, respiratory, or eCOA solutions to capture critical safety and/or efficacy data in their clinical programmes.

In order to receive regulatory approval of new medical treatments, biopharmaceutical companies must first demonstrate the product’s safety and efficacy through a series of controlled clinical trials. ERT’s suite of products and services for cardiac safety, respiratory, and eCOA – which include electronic patient reported outcomes (ePRO) – are repeatedly relied upon for capturing these important data. “It is extremely rewarding to realise that so many biopharmaceutical companies have brought new medical treatments to market using products and services delivered by ERT,” said Jeffrey Litwin, MD, CEO of ERT. “We are committed to delivering innovative and reliable solutions that meet the needs of our worldwide customers and supporting their efforts to bring life-enhancing and life-saving medical products to patients who need them.” ERT is sharing its knowledge of supporting regulatory approvals by offering a complimentary white paper entitled “ePRO Regulatory Inspections: Best Practices for Smooth and Successful Outcomes.”

TTP Labtech Acquires FLT Significant improvements in assay reagents and availability of High Throughput Screen (HTS)-compatible readers has propelled fluorescence lifetime (FLT) technology to the vanguard of costeffective screening technologies. TTP Labtech has consolidated its position in the field with today’s announcement of the purchase of assets from AssayMetrics Limited, Cardiff, UK a leading company in FLT.The acquisition enhances TTP Labtech’s new ameon system equipped with real-time decay curve analysis (RT-DCA), licensed from Fluorescence Innovations Inc (Minneapolis, US). The ameon represents the next generation of FLT reader technology providing a combination of speed, precision, and data quality that can be readily exploited in HTS workflows. “The development of the ameon reader introduces an exciting new dimension to FLT technology giving researchers a step-change in sample throughput and data quality,” said Dr Greg Gillispie, President of Fluorescence Innovations. “Reception to ameon has been very positive with early feedback from beta-partners reporting superior tolerance to compound interference compared to established methodologies,” commented Dr Wayne Bowen, Chief Scientific Officer of TTP Labtech. Pharma Bio World

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biotech news CTI’s Pixuvri Gets FAD from NICE National Institute for Health and Care Excellence (NICE), the independent body responsible for driving improvement and excellence in the health and social care system in the United Kingdom (UK), has issued its Final Appraisal Determination (FAD) for Cell Therapeutics Inc (CTI)’s PIXUVRI (pixantrone). The positive final James A Bianco draft guidance determines PIXUVRI cost President & CEO, CTI effective and recommends funding the treatment as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (aggressive B-cell NHL), which includes diffuse large B-cell lymphoma (DLBCL). CTI estimates that there are approximately 1,600 to 1,800 people in the UK diagnosed with multiply relapsed aggressive B-cell NHL per year. James A Bianco, MD, President and Chief Executive Officer of CTI stated, “The positive recommendation by NICE for the funding of PIXUVRI means that physicians in England and Wales now have access to the only approved therapy for their patients with aggressive B-cell NHL in the third- and fourth-line salvage setting.” The NICE Appraisal Committee reviewed CTI’s updated data analysis showing PIXUVRI’s cost effectiveness and recommended the treatment as an option for certain people with histologically confirmed aggressive B-cell NHLwho have previously received rituximab and are receiving PIXUVRI as a third- or fourth-line treatment.

Astellas, ClearPath Ally to Develop Vaccine for RSV Astellas Pharma Inc (Astellas) and ClearPath Development Company (ClearPath) have announced a strategic partnership to form a portfolio of development companies focused on vaccines targeting infectious diseases. The partnership was established to support Astellas’ goal of building a global vaccine franchise and launched its first company, RSV Corporation (RSVC), in December 2013. Astellas will fund RSVC’s development of a virosome vaccine technology, licensed from Mymetics Corporation, for respiratory syncytial virus (RSV) through completion of a Phase 2b human proof-of-concept study. Based on the strategic partnership, Astellas received exclusive rights to acquire RSVC as well as further develop and commercialise the vaccine product. RSV is a respiratory pathogen which infects patients of all ages. The infection can be especially severe in infants and older adults with chronic pulmonary or cardiovascular disease. Each year the virus infects 64 million people and is responsible for 160,000 deaths worldwide. Currently, there is no vaccine available for this virus. Pharma Bio World

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Dako, Merck to Develop Companion Diagnostics to Treat Cancer Dako, an Agilent Technologies company, has entered into a master framework agreement with Merck to develop companion diagnostic tests for oncology drugs currently in Merck’s development pipeline. The market for companion diagnostics is steadily growing, as personalised medicine may improve patient care and manage healthcare costs by targeting treatments to individuals more likely to benefit from specific therapies. Dako collaborates with many top-tier pharma companies to develop companion diagnostics, with a record of successful longterm partnerships with companies such as Bristol-Myers Squibb and Genentech, a member of the Roche Group. Dako continues to attract new partners, most recently Eli Lilly, Pfizer and now Merck. The financial terms of the master framework agreement were not disclosed.

Watson-Marlow Pumps Group Acquires Bio Pure Technology Limited Watson-Marlow Pumps Group (WMPG) strengthens its single-use biopharmaceutical offering through acquisition of Bio Pure Technology Limited (Bio Pure). Watson-Marlow, a world-leading positive displacement pump manufacturer, has acquired Bio Pure through its parent company Spirax-Sarco Engineering plc for 8.5 million Pund. Bio Pure, based in Portsmouth UK, specialises in the design and production of advanced single-use tubing connector systems for biopharmaceutical customers. Bio Pure is a natural extension of the Watson-Marlow peristaltic pump range, complementing its offering in the Biopharmaceutical sector, and joining a portfolio comprising Watson-Marlow Pumps, Watson-Marlow Tubing, Flexicon Filling Systems, Alitea OEM Pumps MasoSine Process Pumps and Bredel Hose Pumps. WMPG already has a positive commercial relationship with Bio Pure, jointly promoting Watson-Marlow pumps, tubing and Bio Pure connectors to shared customers, where both Bio Pure and Watson-Marlow products are integrated into customers’ equipment. There is clear synergy and a significant growth opportunity presented by bringing together Bio Pure’s product range and WMPG’s products to meet the needs of the rapidly growing single-use biopharmaceutical market. January 2014  51

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Marina, Mirna Amend Drug Cellceutix Seeks IRB Nod for Development Deal Prurisol Clinical Trial Marina Biotech Inc, a leading oligonucleotide-based drug discovery and development company, and Mirna Therapeutics Inc (Mirna), a privately-held biotechnology company pioneering microRNA (miRNA) replacement therapy for cancer have amended their license agreement regarding the development and commercialisation of microRNA-based therapeutics utilising Mirna’s proprietary microRNAs and Marina Biotech’s novel SMARTICLES liposomal delivery technology. Under terms of the amendment, Mirna paid certain pre-payments to Marina Biotech and now has additional rights to its lead programme, MRX34, currently in Phase 1 clinical development for patients with unresectable primary liver cancer or metastatic cancer with liver involvement. In addition, under the terms of the license agreement, Mirna has optioned exclusivity on several additional miRNA targets. Further terms of the Agreement were not disclosed. “Mirna and Marina Biotech have enjoyed a successful, durable collaboration by leveraging the systemic delivery of our proprietary, double-stranded, miRNA mimics with the SMARTICLES delivery technology,” said Paul Lammers, President and CEO of Mirna Therapeutics.

Leo Ehrlich, CEO Cellceutix

Cellceutix Corporation, a clinical stage biopharmaceutical company developing innovative therapies in oncology, dermatology, and antibiotic applications, has submitted the application to the Institutional Review Board (IRB) responsible for the planned clinical study of the Company’s psoriasis drug Prurisol.

The trial is a short crossover study being conducted at the request of the US Food and Drug Administration (FDA) with the purpose of demonstrating that Prurisol, an ester of abacavir, converts into abacavir in humans, just as it did in animal models. Once IRB approval is received, Cellceutix will immediately file an Investigational New Drug (IND) Application with the FDA. “We are excited to kick-off 2014 with Prurisol moving into human studies, our novel antibiotic Brilacidin commencing a Phase 2b trial in January, and Kevetrin, our flagship anti-cancer drug, reaching the latter stages of its Phase 1 trial. These trials represent our unwavering commitment to build shareholder value and bring new drugs to market spanning several areas of great unmet medical need,” commented Leo Ehrlich, Chief Executive Officer at Cellceutix.

Medlmmune, Immunocore to Jointly US Patent for Galectin’s Liver Fibrosis Develop Novel Cancer Therapies Combo Treatment MedImmune, AstraZeneca’s global biologics research and development arm, has entered into oncology research collaboration and licensing agreement with Immunocore Limited, a privatelyheld, UK-based biotechnology company. Both companies will research and develop novel cancer therapies using Immunocore’s Immune Mobilising Monoclonal T-Cell Receptor Against Cancer (ImmTAC) technology. This platform of biological medicines, or ImmTACs, exploits the power of the body’s own immune system to find and kill diseased cells. ImmTACs direct a patient’s T cells to specifically destroy only the cancerous cells, avoiding damage to healthy cells. Under the terms of the agreement, Immunocore and MedImmune will work together to generate ImmTACs against selected cancer targets. AstraZeneca and MedImmune will have the right to further develop and commercialise ImmTAC products to add to their immune-mediated cancer therapy portfolio. Immunocore will receive an upfront payment of USD 20 million per programme and the company is then eligible to receive up to USD 300 million in development and commercial milestone payments for each target programme and significant tiered royalties if the programmes are successful. 52  January 2014

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Galectin Therapeutics, the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, has received a notice of allowance from the US Patent and Trademark Office for patent application number 13/550,962 titled “Galactose-Pronged Polysaccharides in a Formulation for Anti-fibrotic Therapies.” The patent covers both composition claim for and uses of the Company’s carbohydrate-based galectin inhibitor compound GR-MD-02 for use in patients with liver fibrosis in combination with other potential therapeutic agents. The patent covers use of GR-MD-02 with agents directed at multiple targets, some of which are currently in clinical development for fibrotic disorders including monoclonal antibodies to connective tissue growth factor, integrins, and TGF-β1. Galectin Therapeutics is currently conducting a Phase 1 clinical trial to evaluate the safety, tolerability and exploratory biomarkers for efficacy for single and multiple doses of GR-MD-02 over four weekly doses of GR-MD-02 treatment in patients with fatty liver disease with advanced fibrosis. In March 2013, the US Food and Drug Administration (FDA) granted GR-MD-02 Fast Track designation for non-alcoholic steatohepatitis (NASH) with hepatic fibrosis, commonly known as fatty liver disease with advanced fibrosis. Pharma Bio World

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Aratana Buys Okapi Sciences Aratana Therapeutics, Inc, a biopharmaceutical company focused on the licensing, development and commercialisation of innovative medications for pets, has acquired Okapi Sciences NV, a Belgium-based company with a proprietary pet therapeutics antiviral platform and five clinical/development stage candidates for treating important viral diseases. The strategic acquisition of Okapi further enhances Aratana’s leadership position in pet therapeutics by bringing with it a unique combination of individuals, strong relationships with academic institutions, novel technologies and products, and favorable geographic location. Aratana plans to continue to advance the current Okapi pipeline of high value antiviral drugs, including its feline herpes and feline immunodeficiency virus franchises. Okapi’s lead antiviral product candidate is being developed as a treatment of ocular disease caused by feline herpes virus in cats and is poised to become the world’s first antiviral small molecule therapeutic developed specifically for veterinary use. If approved, Aratana plans to commercialise the product in certain territories under an existing development and commercialisation agreement with Novartis Animal Health. Okapi’s current pipeline also includes a product for the treatment of feline immunodeficiency virus as well as additional antiviral and oncology products for both cats and dogs.

Sutro, Memorial Sloan-Kettering Cancer Center Join Forces

Trevor Hallam, Chief Scientific Officer Sutro

Sutro Biopharma has entered into a collaboration agreement with Memorial Sloan-Kettering Cancer Center to use Sutro’s proprietary cell-free protein synthesis technology to produce bispecific antibodies that were discovered by Memorial Sloan-Kettering for the treatment of neuroblastoma in children.

“Neuroblastoma is the most common extra-cranial solid tumor in children, and long-term survival for children with advanced disease diagnosed after 18 months of age is unsatisfactory despite aggressive chemotherapy,” says Trevor Hallam, PhD, chief scientific officer of Sutro. “Sutro’s technology allows the generation, and importantly, the rapid screening of a large number of variations of bispecific antibodies. This will enable us to take bispecific antibodies with the desired characteristics faster into the clinic and potentially provide pediatric neuroblastoma patients with a much needed effective treatment option to combat this disease,” adds Sutro. Pharma Bio World

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Under the collaborative agreement Sutro will use its cell free protein synthesis technology to produce four different bispecific antibodies discovered by Memorial Sloan-Kettering. These antibodies will be directed against CD3 on T-cells and, as the second target, against the ganglioside GD2, which is expressed on the surface of human neuroblastoma cells, as well as in melanoma and osteosarcoma. Nai-Kong V Cheung, MD, PhD, head of Memorial Sloan-Kettering’s Neuroblastoma programme, will use preclinical models to test the bispecific antibodies manufactured by Sutro.

Ranbaxy Strikes Licensing Deal with EPIRUS Ranbaxy Laboratories Limited and EPIRUS Switzerland GmbH, a wholly-owned subsidiary of Boston-based Epirus Biopharmaceutical Inc has announced the signing of a licensing agreement for BOW015, a biosimilar version of Infliximab. The product will be introduced in India and other Emerging Markets. Currently, there is no biosimilar of Infliximab approved in India. Under the terms of the agreement, EPIRUS will develop and supply the product, and upon regulatory approval Ranbaxy will market the same in India and other emerging markets. Commenting on the partnership, Sanjeev I Dani, Executive Vice President & Head, Global Strategy, Ranbaxy said, “We are pleased to partner with EPIRUS for Biosimilar Infliximab. We will utilise our strong front-end capabilities in making this product available in India and other parts of the world.”

Exosome, Qiagen Extends Collaboration Exosome Diagnostics has announced an expansion of its strategic collaboration with Qiagen to develop non-invasive molecular diagnostics for use in detecting and monitoring actionable genetic mutations in lung cancer patients. In contrast with current molecular diagnostics requiring tissue biopsy, the focus will be to enable detection of well-understood cancer biomarkers in plasma, reducing both cost and patient risk. Financial terms of the collaboration were not disclosed. The programme will focus on detection of known mutations associated with non-small cell lung cancer (NSCLC) and other malignancies that have the potential to be paired with targeted therapies. Qiagen plans to submit the first diagnostic test developed under the collaboration to the Food and Drug Administration following clinical validation. Exosome Diagnostics’ proprietary technology is focused on rapid, robust isolation of clinically actionable genetic biomarkers from blood, urine and cerebrospinal fluid for diagnosis, monitoring and companion diagnostic applications. January 2014  53

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Biogen-Sangamo Pact to Develop Treatments for Haemoglobinopathies Biogen Idec and Sangamo BioSciences, Inc announced an exclusive worldwide collaboration and license agreement focused on the development of therapeutics for hemoglobinopathies, inherited conditions that result from the abnormal structure or underproduction of hemoglobin. The agreement will enable Biogen Idec to further enhance its expertise in non-malignant hematology by leveraging Sangamo’s proprietary genome-editing technology platform to develop treatments targeting sickle cell disease (SCD) and beta-thalassemia. Sangamo’s proprietary zinc finger nuclease (ZFN) genomeediting technology enables multiple pathways to treat SCD and beta-thalassemia. The technology can be used to precisely target and knock out key regulators of gene expression, or can be used to precisely insert a new corrective gene to replace the defective copy. Under the terms of the agreement, Sangamo is responsible for all research and development activities through the first clinical proof of concept trial in beta-thalassemia, and both companies will perform activities to enable submission of an Investigational New Drug (IND) application for SCD. Biogen Idec will be responsible for subsequent worldwide clinical development and commercialisation of products arising from the alliance. Sangamo retains an option to co-promote any licensed product to treat SCD and beta-thalassemia in the United States.

Bioblocks, Emerald Bio Tie-up to Boom Small Molecule Drugs Discovery

Johan Pontin Chairman & CEO Emerald Bio

BioBlocks, Inc, an emerging leader in fragment-based lead discovery, and Emerald Bio, a protein and structural biology service provider, are working together to streamline clients’ access to expertise that will accelerate lead discovery and generate high-quality, small-molecule drugs in a cost effective manner.

BioBlocks’ Leap-to-LeadTM platform joined with Emerald Bio’s biophysical screening and structural biology capabilities, which use co-crystallisation, nuclear magnetic resonance and other methodologies, provides clients with extensive, fully integrated, fragment-based, target-tolead generation services. “As the drug-discovery marketplace changes, our strategic alignment will enable more reliable external research because both companies are focused on streamlining processes based on our proprietary expertise, deep investments into orthogonal capabilities, and similar business cultures,” said Johan Pontin,

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Emerald Bio’s chairman and chief executive officer. “Together we look forward to offering our clients the ability to increase the probability of success for their drug discovery projects.” “Despite recent advances in drug discovery technologies, the identification of leads that are ultimately successful in clinical trials remains a challenge,” said Peter Pallai, PhD, BioBlock’s president and chief executive officer. “Our Leap-to-Lead platform addresses this problem using physical and virtual fragment-based approaches, which provide a dynamic lead-development pathway. Combined with Emerald Bio’s critical structural insights, we are well positioned to generate high quality leads for our clients, including against difficult targets.”

Five Prime Therapeutics, Adimab Ink Antibody Research Collaboration Deal Five Prime Therapeutics, Inc, a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, announced a sponsored research collaboration agreement with Adimab, LLC, a leader in discovery of monoclonal and bispecific antibodies. Five Prime will provide multiple targets to Adimab for the discovery and optimisation of therapeutic monoclonal antibodies initially focused in cancer immunotherapy. Under the terms of the collaboration agreement, Adimab will use its proprietary discovery and optimisation platform to identify fully-human antibodies for Five Prime. This agreement will grant Five Prime the right to develop and commercialise antibodies generated during the collaboration for potential use as therapeutic products. While financial terms were not disclosed, Adimab will be eligible to receive potential research funding, option payments, milestone payments and royalties.

Galena Partner with Dr Reddy’s for NeuVax in India Galena Biopharma and Dr Reddy’s Laboratories Ltd has announced a strategic development and commercialisation partnership on NeuVax (nelipepimut-S) in India. Galena Biopharma is a biopharmaceutical company commercialising and developing innovative, targeted oncology treatments that address major unmet medical needs to advance cancer care. Dr Reddy’s is an integrated global pharmaceutical company, committed to providing affordable and innovative medicines for healthier lives. Pharma Bio World

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Plough Shear Mixer Ribbon blender is a light duty blender mainly used for easy to mix powder components, which are preprocessed like dried granules, presieved powders, etc. It is a low shear mixer and mostly used for solid/solid mixing. Solid/liquid mixing can also be achieved when high shearing force is not desired. It occupies less head room space for large volume mixing unlike double cone V blenders, etc. The batch size is based on 7- per cent of blender volume. Crosscontamination is eliminated by mounting bearings on lanterns out of mixing zone. Plough shavels bolted on sockets are easily removable providing easy accessibility to all inside parts of the mixer. Feeding is through a charging port mounted on top of the mixer.It has inspection doors with safety interlocks. Choppers provision as an optional feature. Fully welded plough shovels can also be provided on request. They are available in size 100 to 10,000 litres.

Compact Dissolution Testing Instrument The PT-DT70 is fully compliant to all major pharmacopoeias, like USP <717>, EP <2.9.3> as well as the Japanese Pharmacopoeia. It is a lowhead dissolution tester, which provides low cost entry into tablet dissolution testing. It offers seven stirred positions as well as a pneumatically supported lift-off top for easy access to the dissolution vessels. The vessels are arranged in two rows (4 x 3) and are easily accessible to remove spent media and refill with solvent, simply by lifting up the pneumatically assisted drive housing. To insert and withdraw sample solutions, use the seven tube shafts which run through the top cover of the instrument. Simply place your tablets next to the holes and introduce them when ready to start. For easy sampling use the PT-MDS manual sampling system which includes a SS sampling tube, an in-line filter and a 10 ml disposable syringe. The PT-DT70 is already equipped with all necessary interfaces for easy integration into automated systems.

For more information, please contact:

Tapasya Engg Works Pvt Ltd A/212, Road No: 30 Wagle Indl Estate,Thane (W), Maharashtra 400 604 Tel: 022-25822287, Fax: 91-022-25825243 E-mail: sales@tapasyaindia.net

Pharma Test Instruments India Pvt Ltd No: 2 Sree Datri Niwas, Nagwara Circle, Outer Ring Road, Opp: Manyata Softech Park Bengaluru, Karnataka 560 045 E-mail: c.neelam@pharma-test.de

Dryer Batch fluid dryers are used for several reasons. Perhaps the most common reason is that upstream and downstream processes are already batch processed. In such cases running the fluid bed dryer in a batch mode simplifies material handling. Many customers like the ability to identify finished product with a specific batch number. This is particularly true for food and pharma but has application to the chemical, metallurgical, personal care and other industries as well. The excellent mixing in the batch fluid bed dryer assures uniformly of the final product within each batch. In a fluid bed dryer it is also possible to dry mixing followed by granulation and drying, etc. Fluidised bed technology has been widely used in the pharma industry for drying, granulating and coating. A fluid bed dryer significantly reduces drying time compared with a tray dryer or vacuum dryer. A fluid bed dryer exposes the entire product surface area to the high volume air stream and heat is transferred to the product surface by convection. However, if the inlet air velocity is not properly selected, consistent and uniform drying will not be obtained. For more information, please contact: FEDA Inc A2/51 Asmita Jyoti Chrkop Naka, Marve Road Malad (W), Mumbai 400 095 E-mail: info@fedainc.com

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Agitated Nutsche Filter cum Dryer

Hydro MPC Booster Systems

It consists of a cylindrical shell with a welded dished end at the top and a flat welded end at the bottom. The vessel is divided into two compartments by means of a perforated plate, provided with suitable filter cloth. The base plate is having arrangement of bolting bar to hold the filter cloth. Suitable support mesh is provided under filter cloth to facilitate the flow of filtrate.

Specially designed for the Grundfos booster systems, the MPC is easy to operate from installation to everyday surveillance. The main task of the MPC unit is to control the number of pumps in operation, as well as the speed of the individual pumps, in order to adjust the performance of the system to variations in demand. The MPC controller is capable of controlling up to six pumps connected in parallel.

An agitator has a unique design rigid and in S curved shaped provided inside the vessel to perform the movements of vertical and rotational directions simultaneously, with the help of pushbuttons/PLC based control. The system will take high torque generated during solid discharge and slurring operation.

The Hydro MPC control unit features an installation wizard, which guides the use through a series of dialogue boxes on the large graphic display. Via the Ethernet connection, the Grundfos Hydro MPC booster system can be operated from a remote computer where the operator will be able to view the control panel on the computer screen. Remote monitoring and data acquisition is also possible. Status on individual pump levels and system level, as well as operating conditions, settings, control mode, warnings and alarms can be read out from a remote computer.

Agitated Nutsche filter is extensively used in chemical, herbal, pharma, agrochemical and food industries. For more information, please contact:

For more information, please contact:

Saan Engineers Pvt Ltd Plot R-841 TTC Indl Area, MIDC, Rabale, Navi Mumbai 400 701 Tel: 022-27606242 Fax: 91-022-27606244 E-mail: saanengineers@saanengineers.com

Grundfos Pumps India Pvt Ltd 118 Rajiv Gandhi Salai Thoraipakkam Chennai 600 097 E-mail: salesindia@grundfos.com

Seal-less Drive Eccentric Disc Pumps Mouvex offers its SLS4 and SLS8 models of its seal-less drive eccentric pumps designed for use in a wide array of pumping applications in the food, cosmetic and pharma industries, all of which require extremely hygienic operations. The major technological advancement in the SLS4 and SLS8 pumps is the incorporation of double-wall bellows into the design, along with monitoring that is done by pressure switch. By mounting the pressure switch on the bellows flange, the bellows becomes an independent sub-assembly within the pump, making for safer and easier operation. This design has helped the pumps earn the ability to be used in hygienic applications from a number of regulating agencies, including EHEDG, 3A, FDA and the new European Commission (EC) Regulation No 1935/2004, which applies to all food-contact materials during production. Other improvements in the SLS4 and SLS8 pumps includes the ability to handle differential pressures up to 10 bar (145 psi) in the SLC4 and 6 bar (87 psi) in the SLC8, and high-quality machined parts for optimum surface finish, which are also compatible with SMS, DIN11851, DIN11864 and ASME-BPE clamp flanges. For more information, please contact: Dover India Pvt Ltd - PSG 40 Poonamallee By-pass Senneerkuppam, Chennai 600 056 Tel: 044-26271020 E-mail: sales.psgindia@psgdover.com

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Centrifugal Air Blower Vacunair Engg Co Pvt Ltd offers energy savings centrifugal air blower with fans utilising variable inlet vanes up to 75,000 m3/hr and pressure up to 1,500 mm WG. Features high pressure atomization/combustion air as per specific requirement to suit burners; efficiently designed impeller dynamically balanced in aluminium/MS riveted fitted with hub; minimum overhung and weight design for low starting inertia; different drive to directly coupled/ directly mounted on motor shaft/vee belt; etc. Optional accessories like inlet/outlet silencer, air filter, air control devices can be supplied. It finds application in cooling, conveying, air knives, fluidizing system, glass blowing, drying and various process system.

Multi Mill Multi Mill is a self-contained portable mill useful for high speed granulating, pulverizing, mixing, shredding and chopping, etc, of a wide range of wet and dry materials without special attachments. As compared to the four common principles of size reduction, ie, grinding, compression, impact and shearing, which often do not produce controlled size reduction, this machine utilizes the principle of variable force swing hammer blades having both knife and impact edges rotating with a carefully selected screen to control size reduction. Flow path of material in vertical rotor machine is streamlined. During comminution, material entering the chamber travels to the periphery and passes through the screen tangentially and radially, avoiding checking and temperature rise. It is used in the pharma, chemicals, cosmetics ceramics, food products, etc. It also finds application in pesticides, fertilizers, spices, detergents, insecticides, plastics and resins industries.

For more information, please contact:

Vacunair Engg Co Pvt Ltd Nr Gujarat Bottling, Rakhial Ahmedabad, Gujarat 380 023 Tel: 079-22910771, Fax: 91-079-22910770 E-mail: infoWvacunair.comy

Bombay Pharma Equipments Pvt Ltd Gala No: 02, P V K Compound, Laxminarayan Mandir Marg Kherani Road, Saki Naka,Andheri (E), Mumbai 400 072 Tel: 022-28594877, 28524608, Fax: 91-022-28521608 E-mail: bombaypharma@mtnl.net.in

Horizontal Pharma Peeler It is a batch type automatic/semi-automatic filtering centrifuge. The axis of rotation of the basket is horizontal. It is ideally suited for a clean room installation, through the wall using a flexible membrane as required in pharma applications. A filter media is fixed to the cylindrical surface of a perforated basket. The feed slurry is directed to the basket wall using a feed pipe. Feeding is carried out while the basket is rotating at an appropriate speed. After the required cake is built, feeding is stopped. The centrifuge is run for some time to partially de-water the solids. Feeding can be repeated if there is adequate space for further build up of cake. After feeding, washing is carried out by pumping wash liquid through the feed cum wash pipe. The basket is run at spinning speed to complete the de-watering process. The speed of the basket is reduced to scraping speed. A scraper knife cuts the solids, discharging them through the chute. Some material remains on the filter media after scraping and is called residual heel. This heel can be removed by using the heel removal system. Centrufuge can be cleaned using a CIP system. For more information, please contact: D Parikh Engg Works 115 Marol Co-op Indl Estate, Off M V Road, Nr Saki Naka Andheri (E), Mumbai 400 059 Tel: 022-28504787, Fax: 91-022-28505979 E-mail: sales@dparikh.com

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Automatic Tablet Inspection System E14 Technologies Private Limited of Mumbai in technical collaboration with Techno Sciences, USA, offers tab360 o automatic tablet inspection machine a multi-camera vision based complete inspection system checks for each tablet for imperfections in shape, size and colour. Features single process imspection of every tablet; no human intervention; compatible with wide range of size, shape and colour tablets; speed of 60,000 tablets/hour; ultra high speed and precision camera technology; inspection from top, bottom and side walls; real time textual and image logs and 21 CFR Part 11 complian. For more information, please contact: E14 Technologies Pvt Ltd 141-A Great Western Bldg Medows Street Extn, Fort, Mumbai 400 023 Fax: 91-022-22831652 E-mail: Pratik@e14tech.in

Fluid Bed Dryer Fluid bed drying is a commonly used process in pharma industry due to its highly efficient drying of granulated materials The drying is achieved through a combination of moisture diffusion from the solid material to the heated air stream and the removal of that moisture by forced air convention. The product to be dried is transformed into low expanding fluidized bed with the aid of drying air added from below by means of specialized inlet air distributor. In this condition, the particles are isolated from one another and kept in constant motion. The high specific surface of the fluidized product helps great amounts of heat transfer. For more information, please contact: Saan Engineers Pvt Ltd Plot R-841, TTC Indl Area, MIDC Rabale, Navi Mumbai 400 701 Tel: 022-27606242, Fax: 91-022-27606244 E-mail: saanengineers@saanengineerrs.com

Power Panel HMI B&R has added two new series to its successful Power Panel HMI family: Power Panel T-Series terminals and Power Panel C-Series controllers – both featuring touch screens. Equipped with an embedded browser, the Power Panel T30 terminal is fully web compatible and can even be used as a VNC client. The terminal series is being offered with four TFT display sizes ranging from 4.3” to 10.1” and comes with two Ethernet interfaces, two USB ports and an extensive array of configuration options. The Power Panel C70 controller is equipped with a 333 MHz Intel Atom CPU, 256 MB DDRAM, 16 kB FRAM and 2 GB onboard flash EEPROM memory. This controller provides a built-in touch screen and is being offered in three display sizes ranging from 5.7” to 10.1”. In addition to achieving cycle times as low as 1 ms, the Power Panel C70 also features POWERLINK and standard Ethernet, 2x USB 2.0 and X2X Link technology as well as optional RS232, RS485 and CAN connections to offer a wide range of possibilities for peripheral devices. Both of these device series have an extremely compact design, minimal installation depth and an intelligent cable outlet arrangement, making these panels easy-to-mount space savers. And because these two new series do not have hard disks, fans or batteries, they are completely maintenance-free. The panel front provides IP65 protection, which makes these systems extremely suitable for hygienic applications. For more information, please contact: B&R Industrial Automation Pvt Ltd 8 Tara Heights, Mumbai-Pune Road Wakdewadi, Pune, Maharashtra 411 003 Tel: 020-41478999, Fax: 91-020-41478998 E-mail: shyam.padwal@br-automation.com

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Zero Filter Press Brilliant Pharma Industries offers zero filter press - reverse flow zero hold up type . Here the direction of flow of liquid is exactly opposite to the flow in standard filter, ie, the impure liquid to be filtered enters the filter from the bottom into the center channel and goes to the top of each plate. The clear filtrate flow out from openings on side of plates to the shell and then to the outlet. This flow ensure almost 100 per cent filtration of the liquid. Features complete filtration of the batch without any hold up due to reverse flow of liquid, hence large savings in time and cost; back wash facility can be provided for continuous operations; no scavenger arrangement required; cake, filteraid and solids remain totally enclosed allowintg filtration of toxic, hazardous and explosive liquids; top dome structure ensures fast and easy removal of cartridge assembly and cleaning of cake; etc.

Aseptic Connectors Pure Fit SC fittings provide the ideal aseptic connector for your bioprocessing lines. Each connection features a triple redundant locking mechanism to help eliminate the chance of operator error. Caps on both barbed and aseptic connection ends protect the fitting from contaminants and damage prior to installation. To use, install the connector halves in tubing lines. Remove protective caps and line up locks on the inner and outer housings. Insert inner housing into outer housing; rotate inner housing to lock. Press down on the lock clip to allow the inner fitting to slide into the inner housing and rotate to lock. The connection is completely aseptic and fluid can flow through it. Choose from three sizes: ¼”, 3/8” or ½” tubing inner dia. All sizes are designed for a maximum operating pressure of 3.45 bar over a temperature range of 0 to 40 oC. Characterisation data is available. Choose from complete connections or connector halves. All parts are double bagged and non-sterile.

For more information, please contact:

Brilliant Pharma Machinery Unit No: 1, 2 & 14 Modern Indl Estate Waliv Phata, Vasai (E), Dist: Thane, Maharashtra 401 208 Tel: 0250-3293636, 2454015, Fax: 91-0250-2454015 E-mail: brilliantpharma@rediffmail.com

Cole-Parmer India Pvt Ltd 403-404 B-Wing, Delphi Hiranandani Business Park, Powai, Mumbai 400 076 Tel: 022-67162222, Fax: 91-022-67162211 E-mail: info@coleparmer.in

6 Station Dissolution Testing Instrument The new PTWS 100 is designed in compliance to the valid USP<711/724> and EP <2.9.3/4> Pharmacopoeia. It features a bench saving six vessel design, including automated lift and staggered start. Furthermore, it offers individual centering for all vessels. The PTWS 100 exists in two versions: the PTWS 100D is equipped with a single DC motor drive for all six stirring stations. The PTWS 100S includes individual stepper motors for each one of the six stirring stations. This makes it possible to run each station at a different stirring speed. Furthermore, both versions of the PTWS 100 are also available in a 2 litre format. For easy and fast maintenance, the pump and mains power are placed in a separate housing. The special design in which the blow moulded single piece water bath is held in the instruments chassis and the separated heating system, virtually eliminates any vibration transfer from both within the instrument and from external sources. Pump, heater, temperature, sensor and mains supply board are accessible without moving the bath. This saves the need to perform a USP Suitability Test using after instruments maintenance. For more information, please contact: Pharma Test Instruments India Pvt Ltd No: 2 Sree Datri Niwas Nagwara Circle, Outer Ring Road, Opp: Manyata Softech Park Bengaluru, Karnataka 560 045 E-mail: c.neelam@pharma-test.de

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events diary BANGALORE INDIA BIO

QbD in PHARMA Development

Dates: 10-12 February 2014 Venue: The Lalit Ashok, Bangalore

Dates: 24-25 th February 2014 Venue: Ramada Powai Hotel and Convention Centre, Mumbai

Bangalore INDIA BIO is an annual event organised by Department of IT, BT and S&T, Government of Karnataka, under the guidance of Vision Group on Biotechnology, an apex advisory body comprising of members from Government, Public and Private Sectors including Industry and Academia. Since 2001, Bangalore INDIA BIO has been instrumental in promoting the inherent strength of the Indian Biotech Industry to the outside world and is now acknowledged as the biggest and India’s National event on Life Sciences. The focal theme of Bangalore INDIA 2014 is “Biotech for a better tomorrow”.

The event is especially designed to discuss the implementation case studies, success stories and issues and challenges faced while implementing QbD principles at industry level.

Contact: Event Secretariat MM ACTIV Sci-Tech Communications 9, UNI Building, Thimmaiah Road Millers Tank Bund, Vasanthnagar Bengaluru 560 052 Tel +91-80-41131912/13 Email: enquiry@bangaloreindiabio.in

BioAsia 2014 Dates: 17-19 th February 2014 Venue: Hyderabad International Convention Centre (HICC), Hyderabad Research and surveys unveil that future NEXT is BIO, showcasing immense opportunities for Bio-business. The global economy, tomorrow, revolves around Bio-innovations & hence the 11 th edition of BioAsia shall unveil promising Lifescience-innovations and offer excellent opportunity for new business ideas. Be a part of BioAsia 2014, the future-driving bio-business platform to Discover & Deliver Tomorrow, Today. Contact: BioAsia Secretariat 204, B-Block, Imperial Apartment Greenlands circle, Ameerpet, Hyderabad -500016 Tel: +91 40 66446477/6577 Email: info@bioasia.in 60 January 2014

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It will offer definitive benefits to the scientists from academia and industry working in the domains of Product Development, Process R&D, Scale-up, Manufacturing, Quality Assurance, Global Regulatory Affairs, API, Excipients, Pharmaceutical Analysis and Technology Transfer. The speakers will articulate on all the pertinent areas of QbD Implementation including API, Analytical Development, Excipients and Formulation. Contact: Select Biosciences India Pvt Ltd SCO 28, 29,30 Sector 9 D Chandigarh 160009 Tel: +91-9814412082/9041725050 Email: india@selectbio.com

4th Annual Vaccine World Summit 2014 Dates: 4-6th March 2014 Venue: Hyderabad

The Vaccine World Summit is the most sought after vaccine conference for India and rest of the developing country manufacturers. The Summit will be the definitive meeting place for vaccine industry players to come together to establish and renew partnerships to help develop new products, acquire new technologies, and establish new relationships. Contact: Chamindika Konara Tel: +65 6493 2097 Email: chamindika.konara@imapac.com Pharma Bio World

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bookshelf Drug Discovery and Development: Technology in Transition, 2 nd Edition [Paperback] Author: Raymond G Hill Price: USD 62.58 No of Pages: 368 pages About the Book:This book provides an introduction to the way the industry goes about the discovery and development of new drugs. The first part gives a brief historical account from its origins in the mediaeval apothecariesâ&#x20AC;&#x2122; trade, and discusses the changing understanding of what we mean by disease, and what therapy aims to achieve, as well as summarising case histories of the discovery and development of some important drugs. The second part focuses on the science and technology involved in the discovery process. The third section of the book deals with drug development: the work that has to be undertaken to turn the drug candidate that emerges from the discovery process into a product on the market.

Guide to Drug Development: A Comprehensive Review & Assessment [Hardcover] Author: Bert Spilker Price: USD 212.60 No of Pages: 1232 pages About the Book: Guide to Drug Development is a comprehensive review of the principles and activities involved in developing new drugs, devices, and other medical products. The book covers many topics not discussed in any other textbook and includes timely discussions on electronic clinical trials, registries of clinical trials, data mining, computer simulations and modeling, and changing regulatory standards. Each chapter includes practical tips, lessons, guides, firsthand stories, quotes from experts, and three to six questions for group discussion. The last three chapters present twelve case studies each on clinical trials, regulatory affairs, and management of drug development.

Drug Design: Structure- and Ligand-Based Approaches [Hardcover] Authors: Kenneth M Merz (Editor), Dagmar Ringe (Editor), Charles H Reynolds (Editor) Price: USD 136.90 No of Pages: 286 pages About the Book: This book provides a complete snapshot of the field of computer-aided drug design and associated experimental approaches. Topics covered include X-ray crystallography, NMR, fragment-based drug design, free energy methods, docking and scoring, linear-scaling quantum calculations, QSAR, pharmacophore methods, computational ADME-Tox, and drug discovery case studies. A variety of authors from academic and commercial institutions all over the world have contributed to this book, which is illustrated with more than 200 images. This is the only book to cover the subject of structure and ligand-based drug design, and it provides the most up-to-date information on a wide range of topics for the practicing computational chemist, medicinal chemist, or structural biologist.

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