September 2014 l
Vol.13
PHARMA BIO WORLD
www.pharmabioworld.com
l
Issue 2
l
Mumbai
l
Price ` 150
SEPTEMBER 2014 VOL. 13 ISSUE 2 MUMBAI ` 150
QVF® solutions for Customized Reaction Units Production Kilo-Lab Miniplant
• Multipurpose, high potent reactions for high value products. • Temperature range: -90°c to +200°c. • GMP design: No static hold up / dead space, FDA compliant materials in product contact, black particle free solvent reflux overhead systems • High vacuum distillation, Azeotropic distillation. • Mixing / Heat transfer – various types of stirrers, Optimix welded baffles • Explosion protection Zone1, ATEX. • Customized skid designs. • TA-LUFT compliant - leak proof joint. • Reactor capacity: 5L to 16000L.
DE DIETRICH PROCESS SYSTEMS ( I ) PVT LTD. Phone: +91 22 67424272, FAX: +91 22 28505731 Email: sales@dedietrich.co.in, Website:www.dedietrich.com
PHARMA BIO WORLD R.N.I. No.: MAHENG/2002/8502 Chairman
Jasu Shah
Publisher & Printer
Maulik Jasubhai Shah
Chief Executive Officer
Hemant Shetty
EDITORIAL Editor
Mittravinda Ranjan (mittra_ranjan@jasubhai.com)
Editorial Advisory Board
Ajit Singh, Jai Shankar, Dr Narges Mahaluxmivala, Dr Prabuddha Ganguly, Dr Satish Ravetkar, Utkarsh Palnitkar
Feature Writer
Mahesh Kallayil (mahesh_kallayil@jasubhai.com)
Design Team
Arun Parab, Umesh Chougule
Events Management Team
Abhijeet Mirashi
Marketing Co-ordinator
Brenda Fernandes
Subscription Team
Dilip Parab
Production Team
V Raj Misquitta (Head), Arun Madye
Vol. 13 | No. 2 | SEPTEMBER 2014 | MUMBAI | ` 150
PLACE OF PUBLICATION
Jasubhai Media Pvt Ltd
210, Taj Building, 3 rd Floor, Dr. D. N. Road, Fort, Mumbai 400 001, Tel: +91-22-4037 3636, Fax: +91-22-4037 3635
SALES General Manager, Sales : Amit Bhalerao (amit_bhalerao@jasubhai.com) Prashant Koshti (prashant_koshti@jasubhai.com) MARKETING TEAM & REGIONAL OFFICES Mumbai
Godfrey Lobo / V Ramdas 210, Taj Building, 3rd Floor, Dr. D. N. Road, Fort, Mumbai 400 001 Tel: +91-22-4037 3636 Fax: +91-22-4037 3635 E-mail: godfrey_lobo@jasubhai.com, v_ramdas@jasubhai.com
Ahmedabad
Vikas Kumar 64/A, Phase 1, GIDC Indl Estate, Vatva, Ahmedabad 382 445 Tel: +91-79-4900 3636 / Ext:627, Fax: +91-79-25831825 Mobile: +919712148258 E-mail: vikas_kumar@jasubhai.com
Vadodara
Pervindersingh Rawat 202 Concorde Bldg, Above Times of India Office, R C Dutt Road, Alkapuri, Baroda 390 007 Telefax: +91-265-2337189, Mobile: +919737114204 E-mail: pervinder_rawat@jasubhai.com
Bengaluru
Princebel M Mobile: +919444728035, +919481888718 E-mail: princebel_m@jasubhai.com
Chennai / Coimbatore
Princebel M / Yonack Pradeep 1-A, Jhaver Plaza, 1 st floor, Nungambakkam High Road, Chennai 600 034 Tel: +91-44-43123936 Mobile: +919444728035, +919176963737 E-mail: princebel_m@jasubhai.com, yonack_pradeep@jasubhai.com
Delhi
Priyaranjan Singh / Suman Kumar 803, Chiranjeev Tower, No 43, Nehru Place, New Delhi – 110 019 Tel: +91-11-2629 3174, +91-11-4674 5513 Fax: +91-11-2642 7404 E-mail: pr_singh@jasubhai.com, suman_kumar@jasubhai.com
Hyderabad
Princebel M / Sunil Kulkarni Mobile: +919444728035, +919823410712 E-mail: princebel_m@jasubhai.com, sunil_kulkarni@jasubhai.com
Kolkata
E-mail: industrialmags@jasubhai.com
Pune
Sunil Kulkarni Suite 201, White House, 1482, Sadashiv Peth, Tilak Road, Pune 411 030 Tel: +91-20-24494572, Telefax: +91-20-24482059 Mobile: +919823410712 E-mail: sunil_kulkarni@jasubhai.com
Single Copy Price: ` 150/-, Annual Subscription: ` 1530/-, Foreign: US$ 180
Jasubhai Media Pvt Ltd Registered Office: 26, Maker Chambers VI, 2 nd Floor, Nariman Point, Mumbai 400 021, INDIA. Tel.: +91-22-4037 3737 Fax: +91-22-2287 0502 E-mail: sales@jasubhai.com
Printed and published by Mr Maulik Jasubhai Shah on behalf of Jasubhai Media Private Limited, 26, Maker Chamber VI, Nariman Point, Mumbai 400 021 and printed at Varma Print, Pragati Industrial Estate, N M Joshi Marg, Lower Parel, Mumbai 400 011 and published from Mumbai. Editor: Ms Mittravinda Ranjan, 26, Maker Chamber VI, Nariman Point, Mumbai 400 021.
6 ď‚ƒ September 2014
Pharma Bio World
Verderflex Vantage 3000 Solving your aseptic dispensing problems: 10 Program dosing memory Zero contamination Tube changes in seconds Manual, analogue and even RS232 controls Stackable multiple head options
Verdere ax
Verder India Pumps PVT. LTD Plot No - 3b +3part 11, D-1 Block, MIDC Block Chinchwad, Pune - 411019, India sales@verder.co.in
www.verder.co.in
3.25 l/min : 2 bar
FEATURES 10
Biosimilars: Expanding Manufacturing and Regulatory Horizon for Creating High Value Market – Dr Madhusudan Dabhole
24
Reducing Cell Batch Losses by Improving Process Monitoring – Graham Lewis
10 30
3 Dimensional Cell Based Assays in Hollow Fiber Bioreactors –
46
William J Whitford, John J S Cadwell
GST: A Sweet Pill for Indian Pharma – Manish Panchal, Siddharth Paradkar
NEWS UPDATE
24 50
Press Release
56
Pharma News
59
Biotech News
CORPORATE AFFAIRS 61
Product Trends
64
Events Diary
30 BACKYARD 65
Book Shelf
66
Ad Index
46 Next Issue Focus: Phytopharmaceuticals
8 September 2014
Pharma Bio World
s low F n
o
W
re he
ti va o n
In
Pumps that Meet the
Speed-To-Market Challenge
Quattroflow™ positive displacement quaternary (fourpiston) diaphragm pumps offer high purity, containment and one of the highest turn up/down capabilities in biologics and pharmaceutical production applications. • Scale-up capability assures pump operation does not adversely affect results • Constant flow rates from 1 L/hr (0.0047 gpm) to 20,000 L/hr (88 gpm) • Gentle transfer of shear-sensitive biological products • Self-priming and risk-free dry running • Ensures product safety, efficiency and reliability • Available in Single-Use and Multi-Use head options
Dover India Pvt. Ltd. - PSG 40, Poonamallee By-pass, Senneerkuppam, Chennai - 600056, India O: +91-44-26271020/21/22/30 M: +91-9840802283/09840404879 sales.psgindia@psgdover.com www.psgdover.com Branch Offices at Mumbai, Delhi, Bangalore, Hyderabad & Coimbatore
14-PSGI-0035 PSG India in Pharma Bio World - Full Page (April) - Quattroflow.indd 1
3/28/14 4:05 PM
Biosimilars: Expanding Manufacturing and Regulatory Horizon for Creating High Value Market Biosimilar industry has been growing stupendously. In the last few years, India has seen a robust growth in its biosimilar portfolio. This article aims to identify and analyse biosimilar market in India.
B
iological research and biologics has perceived a quantum upsurge in all areas from thinking about making a molecule in laboratory to commercial aspect of marketing and response. The Biopharmaceutical industry has gained a lot of impetus and has shown a commendable progress. Starting from Recombinant Human Insulin which was the very first therapeutic biopharmaceutical product to be approved to Antisense technology used today as a drug discovery platform, biopharmaceutical has come a long way. With the expiration of patents of innovator biologics, biosimilars have created opportunities for this industry to mature. Due to their high degree of specificity, biologics are the drivers of growth in the pharmaceutical industry in the long term.
“The identification of double helix has been a landmark discovery in the history of science and I am very proud to be associated with it”, said Dr James D Watson, sitting outside the auditorium at Tata Institute of Fundamental Research (TIFR) Mumbai, after finishing his lecture on Genes and Politics on December 1 st 1997.
Dr Madhusudan P Dabhole
Group Manager- Bioprocess, Richcore Life Sciences Ltd. 10 September 2014
I wondered why Dr Watson had not acknowledged the contribution of Rosalind Franklin and posed the question to Dr Watson. He smiled and said,”I am not selfish”. When asked about the significance of sequencing the human genome and its benefits in understanding disorders, he added, “Now that the Human Genome is being sequenced, proteins will be the key molecular machines which will play an integral part in future”. I was searching something distinct on which I can take his autograph and found one small Lord
Ganesh greeting. I moved forward and took his autograph which he signed off. I decided to pursue my PhD in Stress protein application. Biosimilar is a biopharmaceutical drug designed to have active properties similar to one that has previously been licensed. The USFDA defines Biological products as a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biological can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. Regulatory Hurdles in Biologics The Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER) plays a leading role in the development of therapies that will become the standard of care in the 21 st Century, both in the United States and around the world. These emerging therapies include a wide variety of biologic products, such as those for gene replacement and tissue regeneration. In addition, novel strategies and approaches may be employed for developing new biological products. (6) CBER-regulated products pose four significant regulatory challenges that reflect both the rapid pace of biomedical research and the nature of the products the center regulates: 1] Complexity and diversity: Biologics are complex and diverse, and often incorporate new scientific knowledge. CBER reviewers must have an in-depth understanding of the technology used to prepare them, Pharma Bio World
december ads.indd 15
20-01-2014 17:50:45
The fragmentation of outsourcing can lead to deficits in documentation, unclear division of responsibilities between CROs and sponsors, and limited real-time assessment of the CRO function. and when feasible, knowledge of the mechanism of action. 2] Vulnerability to contamination: Biologic source materials used to manufacture products (eg, mammalian cell lines) and the source of the product itself (eg, blood from human donors) are particularly vulnerable to contamination with infectious agents. 3] Processing difficulties: Biologics cannot withstand common purification and decontamination methods, and thus require rigorous control of the source materials, manufacturing processes, and sensitive and specific safety, potency, and purity testing. 4] Long-term adverse effects of treatment: Some biological products, for example certain infused cells or integrating viral vectors, have the potential to persist long-term in the body. Some types of adverse events, which might include cancer, may take years to occur, and understanding how to monitor and clinically respond to such adverse events poses unique challenges. (6, 7) Biologics and Clinical Trials In the last decade, India was considered as one of the major players in the clinical trials field due to the relatively low costs of R&D in India. But in the recent past, it was observed that there is a need for a medical ethics committee which has been inducted to control the clinical trials under the lens minutely. A n o t h e r b a r r i e r i s t h e d i ff i c u l t y i n attracting patients to clinical trials of 12 September 2014
biosimilars. Patients may be reluctant to participate in the trials, especially for serious diseases, because only some of them will receive the biosimilar rather than being confident of receiving the branded biologic outside of a clinical trial. Because many companies may be attempting to develop the same biosimilar, it may be difficult to get enough volunteers because they are competing for the same limited population. Based on discussions with people in the pharmaceutical industry, some biosimilar companies have encountered difficulties in obtaining the reference product for the trials, and when they do, it is often quite expensive. (8) Rising cost in Clinical Trials involving the number of studies and subjects at different time intervals is another factor which needs attention. The pharma sponsors use multiple clinical research organisations (CROs) — a mix of full service and niche CROs. They also prefer to use functional CROs in outsourcing. This means that the whole clinical trial process may be shared by multiple CROs managing diverse functions — regulatory approval, protocol preparation, site management, monitoring, data management, statistics, and medical writing. This could mean multiple CROs using multiple standard operating procedures (SOPs) or the sponsor asking each one to follow the sponsor’s SOPs. The fragmentation of outsourcing can lead to deficits in documentation, unclear division of responsibilities between CROs and sponsors, and limited real-
time assessment of the CRO function. It will also be difficult to carry out a comprehensive root cause analysis and corrective actions. The FDA is concerned that many third parties involved in the clinical trials can impact data integrity and/or human subject protection. (9) Some common deficiencies that were observed and are being taken care during Quality of Clinical trial site inspections include: • Failure to follow the investigational plan and signed investigator statement/agreement. • Protocol deviations. • Inadequate record keeping. • Inadequate accountability for the investigational product. • I n a d e q u a t e s u b j e c t p r o t e c t i o n , including informed consent issues. • Adverse Event (AE) recording and reporting. Currently estimated at USD 500 million, India’s clinical research market was projected to more than double and cross USD one billion mark by 2016 driven by favorable factors like diverse and accessible population, availability of low cost and effective resources. (10) Challenges in Developing Biosimilars Many biochemical and biophysical studies of proteins depend on the availability of milligram quantities of highly purified p r o t e i n s o f i n t e r e s t (3). I n c r e a s i n g development costs and a demand for more compelling demonstrations of the value of new products from regulatory agencies has increased the challenges for biologics development. The scale-up of a cell culture process can be very difficult and time-consuming, taking as long as several months before researchers can obtain a product. The entire process of producing a biotech product from start to finish is often called a campaign and is usually Pharma Bio World
divided into two main parts: upstream and downstream. Upstream processes involve production of the protein product, most often by using cells (microbial, insect or mammalian) growing in culture. Downstream processes include the recovery, purification, formulation and packaging of the protein product. Variability is the killer. Whether running 150 m 3 industrial processes or starting off a PhD with a couple of ‘control’ runs. Until the variability in any process is understood the results and any conclusions drawn will be open to interpretation, scrutiny a n d w o r s t o f a l l , e r r o r. S o m e w h a t worryingly, variation not only applies to existing processes, but to experiments not even thought of! Hence, Use of statistical tools will enable interpretation of data and phrasing of conclusions. The statistical software widely used is Minitab. Sources of variability include, but are not limited to: raw materials, operator error, engineering/mechanical faults, documentation or calibration. C o n t r o l c h a r t s , P r o c e s s c a p a b i l i t y, Regression, correlation and Fractional factorial design are some of the measurable tools that can be used for identifying and controlling variation. (5) Microorganisms in nature are subject to both favorable and unfavorable influences due to varying chemical and physical environmental factors. Living cells like bacteria and yeasts, therefore, display a rapid molecular response when exposed to adverse environmental conditions. This is known as stress response and can be induced by various means such as exposure of cells to high temperature, low temperature, ethanol, hydrogen peroxide, sodium chloride, cadmium and mercury which induce stress proteins. To combat these metals, cells use numerous mechanisms such as solubilisation and metal uptake from the extracellular environment. Various types of bacteria, filamentous fungi and algae have been used 16 September 2014
for metal removal from aquatic systems. Furthermore, there is very little information available about the uptake of cadmium and mercury by Rhodotorula mucilaginosa. (2)
MT gene was cloned and fused with protein transduction domains (PTDs), such as HIV-1 Tat and undeca-arginine, in a bacterial expression vector to produce PTD–MT fusion proteins. (17)
In order for proteins to be used as pharmaceuticals, delivery technologies need to be developed to overcome biochemical and anatomical barriers to protein drug transport, to protect proteins from systemic degradation, and to target the drug action to specific sites. Protein transduction domains (PTDs) are used for the non-specific transduction of bio-active cargo, such as proteins, genes, and particles, through cellular membranes to overcome biological barriers.
Logistics Issues
Metallothionein (MT) is a low molecular weight intra-cellular protein that consists of 61 amino acids, including 20 cysteine residues, and is over-expressed under stressful conditions. Although MT has the potential to improve the viability of islet cells and cardiomyocytes by inhibiting diabetic-induced apoptosis and by removing reactive oxygen species (ROS), and thereby prevent or reduce diabetes and diabetic complications, all MT applications have been made for gene therapy or under induced overexpression of endogenous MT. To overcome the drawbacks of ineffective intra-cellular MT protein uptake, a human
Cold Chain Management refers to the chain of logistics that keeps an item refrigerated from the time it leaves the factory until its final destination. Temperature Monitoring with Validation at all stages during Shipping, distribution and warehousing are major issues impacting Cold Chain Management. The supply chain for biosimilars will be very different to the current range of generic drugs. Biopharmaceuticals are less stable than chemical based pharmaceuticals and thus require cold chain distribution and have a shorter shelf life. This increases the cost and complexity of distribution (1) . Biopharmaceuticals are highly temperature sensitive and are recommended to be stored and transported at temperatures ranging from 2°- 8°C. Any failures in the cold chain transportation of these drugs can lead to a significant loss of their efficacy and can even make them harmful for the patient. Regulatory agencies have stated that drugs that have been temperature mistreated are every bit as dangerous Pharma Bio World
suggests that, realistically, product pricing reductions will be 20 to 30 per cent, compared to the 80 per cent typical for small molecule drugs. These relatively low margins, combined with pressure from healthcare systems on end-user pricing, will require less costly manufacturing alternatives than the big tank approaches now widely in use.
The laser sensor switches off the dosing when the fluid meniscus reaches the laser beam, thus ensuring especially precise filling results
as those that are not authentic. The demand for cold chain logistic services is currently experiencing explosive growth. IMARC Group, one of the world’s leading research and advisory firms, finds that the total size of the healthcare cold chain logistic services market is expected to expand from its current figures of USD 7.3 billion to nearly USD11.4 billion by 2018. The Biopharma companies along with the Cold Chain Logistics services should address how to monitor and control temperatures with other associated risks to biopharma products from manufacturing across the whole supply chain to the end user. Enhancing Cost Efficiency in the Manufacturing of Biologics The inherent risk in establishing Biologics production (product, process, t i m e l i n e , c a p a c i t y, r e g u l a t o r y a n d location) can be significantly mitigated by using a modular and standardised approach. Utilising a combination of standardisation, modularisation and use of modern process solutions such as single use equipment offers significant advantages over traditional design and construction. (11) The cost and complexity of developing and manufacturing biosimilars also 18 ď‚ƒSeptember 2014
The need for multiproduct facilities, with increased flexibility, reduces the requirements for expensive critical utilities such as water for injection and clean steam, decrease requirements for equipment cleaning and cleaning validation, lower capital investments, and shorten facility construction times. All of these realities have caused biopharma manufacturers to incorporate disposable or single-use process technologies into their product manufacturing. These systems offer a smaller footprint, flexibility, scalability, and mobility without compromising product quality. (12) One key advantage of modular construction for biopharmaceutical facilities is the off-site construction of modules. The benefits of this approach include enhanced quality control, reduced waste, reduced impact on current operations, and simplified site logistics. Transferring labor hours away from the construction site also reduces risk and overall cost for a facility construction project. Building multiple modular elements in parallel without, for example, weather impact, can reduce the construction schedule for a facility project by 50 per cent. The ability to leverage factory acceptance testing (FAT) at a module construction facility will often significantly shorten the time for startup and commissioning of a new facility. Once modules are delivered to the
construction site, they are assembled into the complete facility so that final testing and qualification can be completed. (11) A n t i - S e n s e Te c h n o l o g y i n D r u g Discovery Antisense compounds are biological molecules consisting of small ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) segments which have enormous potential for the treatment of number of diseases. The first report of usage of this particular antisense oligodeoxynucleotides to inhibit Rous sarcoma virus gene expression, there has been tremendous progress in the understanding and application of antisense oligodeoxynucleotides. This antisense approach should allow the design of drugs that specifically intervene with the expression of any gene whose sequence is known by that it will be more convenient for the treatment for genetic disorders or infections Antisense drugs are being researched to treat a variety of diseases such as cancers including l u n g c a n c e r, c o l o r e c t a l c a r c i n o m a , pancreatic carcinoma, malignant glioma and malignant melanoma, diabetes, amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy and some other diseases such as asthma, arthritis and pouchitis. The concept behind antisense technology is quite straightforward: the use of a sequence, complementary by virtue of Watson-Crick base pairs hybridisation. This Oligonucleotide is modulated to a specific mRNA which can inhibit its expression and then induce a blockade in the transfer of genetic information from DNA to protein, but mechanism of induction of its biological effect is subtle and complex. The aims for optimal delivery of antisense compounds are therefore to enhance cellular uptake and improved to exit from subcellular compartments as correct targeting Pharma Bio World
SCAN TO LEARN MORE
SPX - HELPING TO MAKE YOUR PROCESS MORE PRECISE SPX’s complete line of sanitary products is the answer for today’s stringent pharmaceutical and biopharmaceutical facilities. For virtually any sanitary processing application, the SPX brands you have come to trust can fulfill your validation and safety requirements with confidence. Depend on us for superior innovation, technology and service. To learn more visit us at www.spx.com/in or email your enquiries to ft.india.information@spx.com.
(spatial and temporal) to a particular site of action. Liposomes are considered very promising delivery systems for antisense therapeutic approach, offering drug protection and facilitating oligonucleotide cell internalisation. (13) Comparison of the Experimental Set up (A) Measurement principle of the microtiter plate fermentation in the BioLector via back scattering of light from cells and fluorescence emission of molecules; (B) Measurement principle of the stirred tank fermentation with online measurement of OD and fluorescence in the bypass. (4) Kensy et al. Microbial Cell Factories 2009 8:68. New Forms of Drug Delivery The practice of drug delivery has changed dramatically in the last few decades and even greater changes are anticipated in the near future. Clinicians historically have attempted to direct their interventions to areas of disease or areas at risk for disease. Depending on the medication, the way it is delivered, and how our bodies respond, side effects sometimes occur. Microneedle arrays are one example of a new method to deliver medications through the skin. In these arrays, dozens of microscopic needles, each far thinner than a strand of hair, can be coated or filled with a medicine. The needles are so small that, although they penetrate the skin, they don’t reach nerves in the skin, thus delivering medications painlessly. Nanosponges created by NIBIB-funded researchers, are a promising vehicle in treating cancer. Comprising a scaffold of tiny, specialised polyester particles coated with disease-targeting compounds 20 ď‚ƒSeptember 2014
The primary objective of machine manufacturers is to minimise contact between glass containers
and filled with an anticancer drug, the nanosponges home in on tumors after being injected into the body. Once at their intended site, they safely and slowly degrade, releasing medication at the tumor site at a steady, controlled rate. Early studies have also shown the nanosponges can be used to treat glaucoma, the fourth leading cause of blindness. (15) Corporate alliance deals structured as licensing transactions, Co-development agreements, joint ventures, or sales and marketing alliances play an integral role in many growth strategies for biopharmaceutical companies. Strategic partnerships can involve research focused on discoveries characterised by unique mechanisms of action at the molecular level and within cellular processes that can be targeted as a way to develop best-in-class medicines. (14) The explosive growth of biologic medicine and the emergence of biosimilars as revolutionary tools to fight the most difficult of disease are to provide advanced health care to patients worldwide. The future of biological medicines will be bright if patients, physicians, biotechnology companies, and other stakeholders work together to ensure
patient safety which are the foremost priority of the biosimilar policy discussion. Then, the future of healthcare debate can move beyond parochial discussion over healthcare access and cost, to a discussion of the diseases that biological medicines can successfully conquer next. (16) References: 1. J o P i s a n i a n d Ya n n B o n d u e l l e , Pharmaceutical strategy consultants at PriceWaterhouseCooper LLP: Opportunities and barriers in the biosimilar market: Evolution or Revolution for Generics companies? 2. Madhusudan P Dabhole and Dr K N Joishy, Use of rapid indirect Elisa to detect cadmium bound to stress protein in Rhodotorula mucilaginosa, Ph.D Thesis, 2002. 3. Uwe Riek et al, An automated homebuilt low-cost fermenter suitable for large-scale bacterial expression of proteins in Escherichia col. BioTechniques, Vol. 45, No. 2, August 2008, pp. 187–189. 4. F r a n k K e n s y e t a l - S c a l e - u p from Microtiter plate to laboratory fermenter: evaluation by online monitoring techniques of growth and protein expression in Escherichia coli and Hansenula polymorpha fermentations Microbial cell factories: 2009, 8:68 Pharma Bio World
Ad Template 01.indd 17
23-11-2013 21:37:59
5. Brian Mc Neil and Linda M Harvey. Practical Fermentation Technology, John Wiley & Sons Ltd. 6. Karen Midthun, Centre for Biologics Evaluation and Research, Strategic plan for Regulatory Science and Research, Draft - 2012-2016. 7. Dawn Willow: The Regulation of Biologic Medicine: Innovator’s rights and access to Healthcare, Chicago-Kent Journal of Intellectual Property, 2006. 8. Erwin A. Blackstone and Joseph P F u h r, J r , T h e E c o n o m i c s o f Biosimilars, September/October 2013, Vol 6, No 8 - Business. 9. Arun bhatt, Quality of clinical trials: A moving target Perspect Clin Res. 2011 Oct-Dec; 2(4): 124–128.
22 September 2014
10. Priyesh Sharma, Vaish associates advocates, Future of clinical trials in India. Mondag, 28thJan 2013. 11. Jan Lilja et al, Modularization in Biologics manufacturing. Pharma Focus Asia. 12. Patricia Fitzpatrick Dimond, Flexibility in Biopharmaceutical Manufacturing Capacity. Single-use bioreactors are changing the biomolecular production landscape. Genetic Engineering and Biotechnology News, 2013. 13. L a v a k u m a r e t a l , A n t i s e n s e technology: Oligonucleotides and its delivery strategy. British Biomedical Journal. 2014. 14. Wendy Tsai et al, Early stage Biotech companies: strategies for survival and
growth. Biotechnology Healthcare. 3(3), 49-50, 52-53, 2006 15. N a t i o n a l I n s t i t u t e o f h e a l t h . U S department of Health. Drug Delivery Systems: Getting Drugs to their Targets in a controlled manner. 16. Richard O Dolinar et al, The future of biological therapy: a pathway forward for biosimilars, Generics and Biosimilars Initiative Journal (GaBI Journal). 2013; 2(1):36-40. 17. Yo n g h e e K i m , P r e p a r a t i o n a n d functional analysis of recombinant protein transduction domainmetallothionein fusion proteins, Biochimie, 92, 8,964-970, 2010. Contact: madhusudan.d@richcoreindia.com
Pharma Bio World
.more than engineering
Consulting, engineering, construction and validation for the pharma and biotech industries. In all phases of the product lifecycle we deliver fast, reliable and innovative solutions.
Offerings for all pharma/biotech segments Biopharmaceuticals
Pharmaceuticals
Vaccines
Biotech
Vaccines
Sterile & aseptic
Active pharmaceutical ingredients
Medical devices
Medical devices and drug delivery systems
Industrial biotech
Industrial biotech
Oral solid dosage
GMP compliance Sustainability & environment Containment & cleanroom Logistics and facility design Laboratories Manufacturing information systems Validation and documentation
NNE Pharmaplan is one of the world’s leading engineering and consulting companies focused entirely on the pharmaceutical and biotech industries. We employ close to more than 2000 people at more than 30 locations worldwide. GMP Compliance Audits Bio Processing Process Excellence Process Automation
Our brilliant minds offer engineering and consultancy expertise within the pharma and biotech industries
NNE Pharmaplan India Limited Contact Person - Mr. Sanjay Gupta, Mob- 9818900253, General Manager- Sales & Business Development Email: SGPT@nnepharmaplan.com
Registered OfďŹ ce : 141, Ansal Chamber II, 6 Bhikaji Cama Place , New Delhi-110066, India. Telephone : +91 11 26197251
Noida : B-15, Sector-2, Noida-201301, India Telephone : +91 120 4775100. Fax: +91 120 4775200 & 300 Bangalore : # 12, Achiah Shetty Layout, RMV Extension, Sadhashiv Nagar, Bangalore-560080, India Telephone : +91 80 49056300, +91 80 23617234. Fax: +91 80 49056303, +91 80 23617240 Email: contact.in@nnepharmaplan.com
nnepharmaplan.com
Reducing Cell Batch Losses by Improving Process Monitoring Laboratories that develop biosimilars can go through thousands of fermentations before they successfully reproduce their target molecule. The goal, however, is to shorten the development lifecycle, eliminating errors and inefficiencies that lead to lost time and material. This article examines how improved fermentation monitoring can play a role in reducing batch loss and accelerating biosimilars development.
T
he advent of biologic medicines has exponentially increased the complexity of drug development processes. Unlike traditional small molecule drugs produced by chemical p ro c es s es , biologic s are made us ing genetically engineered microorganisms that generate protein-based medicines through fermentation and other biological processes. The resulting medicines are much more complex than small molecule drugs, often containing more than one thousand times the total number of atoms.
several groups, and new DNA designed to produce a particular protein is inserted into each. Scientists then evaluate the output of each of the different cell lines to see which produces a product most similar to the target biologic. This line is then expanded and refined again, and the process repeats until an acceptable biosimilar is produced. The cell line that produced the biosimilar is then divided into batches and developed using various growth media. Once the most efficient growth medium is found, the process can begin to scale up to production.
Due to the inherent complexity of large molecule drugs, the production of generic biologics is difficult. Small molecule drugs are relatively simple to characterise, and with some effort scientists can almost always engineer a process that results in an identical molecule. Large biologic medicines, on the other hand, are made primarily of proteins that are much more difficult to characterise and nearly impossible to reproduce identically. The difficulty is compounded by the fact that labs attempting to reverse engineer biologics rarely (if ever) have access to the original cell line that produced the drug. For the above reasons, generic versions of biologic drugs are never exactly the same as their branded counterparts. To make that difference clear, the generic versions are referred to as “biosimilars” and are evaluated on how reliably they achieve the same effect as the original product. Structural similarity of the two products is also considered, but does not have to be identical.
The speed of this development process largely depends on the lab’s ability to manage the healthy development of multiple groups of cells simultaneously – more lines and batches means faster iteration, which in turn means arriving at a finished product more rapidly. To achieve this speed, labs must have a reliable system in place to monitor the development of multiple different groups simultaneously and ensure that they are healthy, errors are detected quickly and remedies are administered as soon as possible. In biosimilar research and development, the failure of a batch of cells can be slow down the process and increase costs significantly, so recognising errors before they do significant damage should be a top priority.
Developing Biosimilars
Graham Lewis
Technical Sales Consultant: Process Mass Spectrometers Environmental and Process Monitoring Thermo Fisher Scientific 24 September 2014
Successfully designing organisms that produce a biosimilar and creating an environment in which they can operate at maximum efficiency requires rapid prototyping over many iterations. Research and development scientists typically begin with a bacteria, yeast or other living cell that produces something close to the target product. The cells are then separated into
The Importance of Monitoring Instruments Instruments that monitor drug production in real time are becoming increasingly important as pharmaceutical companies incorporate biological systems into their drug development processes. The development of comparatively simple small molecule drugs, produced using chemical reactions alone, does not require monitoring techniques as comprehensive as those necessary for large molecule biologic development. The living cells that produce biologics and biosimilars are much more sensitive to environmental factors and process changes. For that reason, they are also more prone to failure and their condition must be monitored very closely. Pharma Bio World
In addition to pressure from the processes themselves, labs that develop biosimilars are also under pressure from regulators to ensure the quality of their processes using analytical technology. Over the past decade, regulatory agencies (including the US FDA) have introduced quality by design (QbD), process analytical technologies (PAT) and current good manufacturing practices (cGMP) regulations and initiatives that require drug development labs to monitor their processes more closely. This means that quality process monitoring is more than just a good business practice – in many cases, it is also necessary for regulatory compliance.
diagnostic data are critical for preventing the loss of valuable batches.
Mass Spectrometry for Cell Monitoring
Benefits of Magnetic Sector Technology
One of the most reliable technologies for monitoring the health of multiple cell groups developing simultaneously is gas analysis mass spectrometry. Familiar to almost all laboratory professionals, mass spectrometry is a very common analytical technique that determines the composition of a sample by analysing the mass-to-charge ratio and relative abundance of gaseous ions.
To ensure reliable real-time detection of effluent composition changes, biosimilar research laboratories must select monitoring technologies that produce as few false positives as possible. The analysers within some gas analysis mass spectrometers are prone to drift over time – without calibration, this drift will generate false positive readings in effluent composition. For this reason, lab professionals should select instruments that incorporate analysers with minimal tendency to drift.
Bench top mass spectrometers designed specifically to monitor fermentation processes work by analysing the effluent produced as cell batches develop. Mass spectrometers designed specifically for analysis of developing cell batches feature multi-point inlets that can monitor up to 15 bioreactor effluent streams simultaneously, allowing biosimilar development laboratories to drastically reduce cell batch losses, increase development speed and minimise costly rework. Very small changes in the concentration of CO 2, O 2 and other gases in the effluent of a developing batch provide valuable diagnostic information on the batch’s overall health. Because cells used in biosimilar development are subject to damage by a wide range of variables, these
In addition to batch health information, precise effluent monitoring allows scientists to review respiration metrics and determine how efficiently each batch is converting its growth medium into its expected output. This information can be used to optimise growth media and improve the overall efficiency of the process. More detailed the respiration data allows development teams to realise smaller and smaller efficiencies – and while some of these efficiencies may seem small in the development lab, they become huge when they’re applied production scale.
One of the least drift-prone mass spectrometry technologies is magnetic sector analysis. Unlike quadrupole gas analysis mass spectrometers, which control the trajectory of effluent ions using a combination of DC and AC electric fields, magnetic sector mass spectrometers use a variable magnetic field. This field influences the path of each ion as it passes through the magnetic sector analyser, influencing their trajectory and separating them by their mass-to-charge ratios. The separated ions then land on a single detector that analyses the whole effluent sample.
“Mass spectrometry is a very common analytical technique that determines the composition of a sample by analysing the massto-charge ratio and relative abundance of gaseous ions.” 28 September 2014
Figure 1: Analyser section-operating principles and peak profile.
The analyser’s output signal is a series of flat-topped peaks (figure 1) where each amplitude is proportional to the concentration of ions at each mass. Each peak represents a large target with consistent amplitude, meaning that the detector is not thrown off even by relatively large variations in the incoming ions’ mass position. This capability makes magnetic sector mass spectrometers intrinsically fault-tolerant and perfectly suited for continuous monitoring of bioreactor effluent. The quadrupole MS, on the other hand, produces a round-topped Gaussian peak which is much more susceptible to drift. Conclusion The monitoring capabilities provided by multi-inlet magnetic sector mass spectrometers, such as the Thermo Scientific Prima BT, can significantly reduce the loss rate of biosimilar development cell batches. In addition to saving time and preventing unnecessary rework, this monitoring data can also help developers of biosimilars simplify their regulatory compliance obligations by providing clear documentation of quality processes. Finally, the highly detailed respiration metrics collected by the spectrometer allow development scientists to optimise the cell batches’ growth media, reducing time to scale up and increasing the overall efficiency of the final process. Contact: gberkman@greenoughcom.com Pharma Bio World
3 Dimensional Cell Based Assays in Hollow Fiber Bioreactors Hollow fiber based animal cell culture was first developed by Richard Knazek at the NIH in 1972 (Knazek et al, 1972). Hollow fiber bioreactors (HFBR) offer a method by which cells can be cultured at tissuelike densities over long periods of time. Hollow fibers act as “artificial capillaries” and perform much as capillaries do in the human body. These bioreactors hit their peak of popularity in the late 1970’s to 1980’s where they were employed in the bio-manufacturing of monoclonal antibodies (Tharakan and Chau, 1986).
John J S Cadwell President and CEO FiberCell Systems Inc
William J Whitford Sr Manager HyClone Cell Culture GE Healthcare 30 September 2014
T
he biomimetic HFBR system is a high-density continuous perfusion culture system. It presents many unique distinctions from the commonly employed non-porous plastic surfaces of eg, flasks, microcarrier beads and discs or roller bottles. An HFBR includes a cartridge containing thousands of semi-permeable hollow fibers in a parallel array within a tubular housing fitted with inlet and outlet ports. These fiber bundles are potted at each end so that any liquid entering the ends of the cartridge will necessarily flow through the interior of the fibers. HFBRs present a 3-D environment similar to the conditions found in vivo, and support the continuous control of such parameters as oxygenation levels, medium composition, drug concentration and shear stress. HFBRs are an effective means for in vitro assays and the generation of a number of products, from secreted proteins or viruses to cells or conditioned medium The fact that in a HFBR the cells are bound to a porous support provides a number of distinct features. Cultures in this system can maintain viability and production-relevant metabolism in a postconfluent manner for extended periods of time– months or longer. Another advantage is that due to the extremely low shear generated with the cartridge when cells become necrotic they will not release significant cytoplasmic proteins or DNA into the culture medium. Through the selection of fiber porosity, desired products can be retained to significantly higher concentrations and the location/effects of cytokines can also be controlled. Recombinant proteins can be selectively retained and concentrated and cytokines and other factors that facilitate cell-to-cell interactions can be concentrated as well. Small molecule drugs can easily exchange across the fiber and rapidly reach equilibrium.
The small diameter of the fibers (in the order of 200 microns) generates an extremely high surface-area-to-cartridge volume ratio in the range of 100-200cm 2/ ml. Coupled with the high gross filtration rate of the more optimised polysulfone fibers, the rate of exchange of primary and secondary metabolites appears high enough to support any practical purpose. Productive cell densities of 1-2x108 or more have been reported approaching in vivo tissue-like densities (Pera 2014). Operation of a HFBR, in its most simplified form, begins by seeding a prepared cartridge with either suspension or harvested adherent cells. The reactor cartridge is connected to an external reservoir and the medium recirculated from the reservoir through the cartridge. Mass transfer of gasses can be accomplished in a variety of ways, with one being diffusive exchange through a loop of gas permeable silicone tubing prior to the medium entering the bioreactor itself. Medium recirculation rate and culture feeding can be linked to any number of culture parameters, and a number of control and automation options have been explored. During this renaissance of perfusion employment in general, and of HFBR in particular, several characteristics of hollow fiber cell culture have recently been identified: 1) Reduction in apoptosis (Weeraphan, et al, 2012) 2) Consistency of culture over long periods of time (Pavlakis, 2013) 3) More in-vivo like growth conditions resulting in improved cell function (Bennet et al, 2007) 4) Facilitation of the use of serum free, protein free and chemically defined media formulations (Whitford and Cadwell, 2011) Pharma Bio World
2
B Publications
B
by Jasubhai Media Pvt Ltd
Instant Subscription www.chemtech-online.com
VOL. 48 NO. 7 July 2013 US $ 10 ` 150
CHEMICAL ENGINEERING WORLD The Official Organ of CHEMTECH Foundation is India’s premier technology magazine for the chemical process industry professionals. This highly reputed monthly publication provides novel insights on the dynamics of Indian and global process industries.
FILTRATION AND SEPARATION
Chemical Engineering World – ` 1620/- (Yearly Subscription - 12 issues)
ChemTECH South 2013 10-12 October 2013, Chennai, India
The Journal of Materials & Equipment for the Process Industries www.cpfindia.com Vol. 32 No. 2 July 2013 Mumbai ` 100/Vol 32 No 2
CHEMICAL PRODUCTS FINDER
Chemical Products Finder
Chemical Products Finder (CPF) is one of India’s premier information sources for the chemical process industry. CPF has been an important source of information on innovative products being used by the chemical process industry as well as newly launched products for the past two decades.
JULY 2013 MUMBAI ` 100
Chemical Product Finder – ` 1080/- (Yearly Subscription - 12 issues)
Safety in Process Plants ChemTECH
ChemTECH South 2013
SOUTH 2013
July 2013 z
Vol.11
z
Issue 12
z
Mumbai
z
Price ` 150
www.pharmabioworld.com
11th ANNIVERSARY SPECIAL ISSUE
A publication that caters to the strategic information needs of professionals in the pharmaceutical and biotechnology industries, covering the best manufacturing and management practices, technological developments, new markets and cutting edge products & services.
Pharma Bio World – ` 1530/- (Yearly Subscription - 12 issues)
Pharma Bio South 2013 10-12 October 2013, Chennai, India
Your Radar to Shipping, Marine & Ports World
PHARMA BIO WORLD
Vol - 5 Issue - 6 • JUNE - JULY 2013 • MUMBAI • ` 150
10-12 February 2014, Mumbai, India
SHIPPING, MARINE & PORTS WORLD A publication that caters to the strategic information needs of professionals in the maritime sector, covering the best management practices, technological developments, new markets and cutting edge innovation in services.
Shipping Marine & Ports World – ` 810/- (Yearly Subscription - 6 issues)
Risk & Security Management
June - July 2013 Vol. 10 No. 4 ` 150
OFFSHORE WORLD Offshore World is an all-encompassing magazine for the hydrocarbon and allied industries. A bi-monthly magazine launched in December 2003, Offshore World disseminates authentic, critical and well-researched information on global hydrocarbon industry innovations. New Frontiers
Offshore World – ` 810/- (Yearly Subscription - 6 issues)
10-12 February 2014 Mumbai, India
COMBO PACKS AVAILABLE! Choose your combination for Subscription.
Jasubhai Media Pvt Ltd Taj Building, 3rd Floor, 210, Dr. D N Road, Fort, Mumbai – 400 001, INDIA. Tel : 022 - 4037 3620 (Direct), 022 - 4037 3636 (Board) • Fax : (022) 4037 3635
E-mail : Girish Kamble (Subscription Executive) - girish_kamble@jasubhai.com Subscription offer design layout.indd 8
8/5/2013 3:23:47 PM
and highly controlled conditions. There is very little variation in oxygen tension, pH, glucose levels etc. It has been recently observed “The 2D cell culture systems used so far have several drawbacks: the morphology, proliferation, metabolism and expression profiles of cells grown in 2D systems are very different to cells in living tissues” (3D Cell Culture 2012). The consistency of HFBR culture conditions has a direct effect on cell physiology and product generation.
Figure 1: HEK 293 cells expressing a heavily glycosylated protein in CDM HD protein-free medium. HPLC demonstrates no structural changes over 137 days of continuous culture.
HFBR provides many particular (and some unique) culture characteristics due to a number of physical and ambient chemical conditions provided by the system, including; 1) Perfused medium flow and porous support permits long-term culture 2) High cell density culture increases cell-to-cell contact 3) S e l e c t a b l e M W C O o f f i b e r s concentrates interactive cytokines 4) Selectable MWCO of fibers segregates cells, metabolites and products. 5) Directional flow establishes gentle interstitial gradients within the cell mass. 6) H y d r o d y n a m i c ( s h e a r ) f o r c e o n endothelial cells required for proper physiology. 7) Long-term high-density culture on porous support facilitates cell-to-cell interactions. P. C . L i a o e t . a l . h a v e i d e n t i f i e d a potential mechanism for the greatly reduced degradation of product during HFBRs highly extended culture duration
(Wu et al, 2009). They found a significant reduction in apoptosis of up to 90 per cent. This, and the absence of celldisruptive shear forces inside the HF cartridge, results in dramatically reduced post-secretion product alterations and cleaner harvests (Srisomsap et al, 2010). In a HFBR, the cells are bound to a porous support, cell division rate and generation number is reduced, and cultures do not require splitting. Passage number becomes irrelevant and cells grow in multiple layers in a “post-confluent” fashion as exemplified by Dr George Pavlakis (NCI, Frederick, Md). Here, 293 T cells were transformed to produce a very complex, problematic protein. While attempts at producing this protein in standard cultures modes were unsuccessful, HFBR provided properly dimerised product with complete and consistent post-translational modifications through over 140 days of production. In-vivo, most animal cells grow in 3-D at very high density under tightly defined
Operation of a HFBR, in its most simplified form, begins by seeding a prepared cartridge with either suspension or harvested adherent cells. 32 September 2014
The culture-contact surfaces of many systems are composed of single-use (SU) materials and provide a number of benefits in manufacturing and assays systems. HFBR culture characteristics, such as very high cell density, allow for a reduction in serum concentration and facilitate adaptation to commercially available serum free media. This has been taken one step further with the introduction of commercially available perfusion optimised serum replacement (Whitford and Cadwell). Applications for Cell Based Assays Cell based assays and in vitro testing methods are a useful, time and cost e f f e c t i v e t o o l f o r d r u g d i s c o v e r y. However, it is generally accepted that many of the available assays are not effective for examining the effects of both time and concentration, and do not closely mimic physiologic kinetics. More specifically, that they do not report pharmacodynamic actions (what a drug does to the body) and pharmacokinetic actions (what a body does to the drug). Static cell based assays in plates, flasks or other formats do not readily permit changes in drug concentration as would be seen in humans from administration, uptake, distribution, distal metabolism and elimination effects. Animal models generally do not provide the same drug kinetics as would be found in humans, many infections cannot be supported Pharma Bio World
,
Jury Panel
Award Categories Special Award Lifetime Achievement Award Healthcare Entrepreneur of the Year Medical Technologies Imaging Company of the Year In-vitro Diagnostics Company of the Year Home Health Respiratory Solutions Company of the Year Cardiac Implant Company of the Year Innovation in Medical Technologies Company of the Year Biopsy Solutions Company of the Year Vascular Access Solutions Company of the Year Most Successful Product Launch of the Year Operating Room Solution Company of the Year Healthcare Delivery IVF Service Provider Company of the Year* Hair Restoration Service Provider Company of the Year* Diagnostic Service Provider Company of the Year* Eye Care Service Provider Company of the Year* Dialysis Service Provider Company of the Year* Mother and Child Service Provider Company of the Year* Comprehensive Cardiac Service Provider Company of the Year Comprehensive Orthopedic Service Provider Company of the Year Innovative healthcare Service Delivery Model of the Year * Independent Chain of Centers Only Pharmaceuticals and Biotechnology Multi-National Pharmaceutical Company of the Year Patient Access Program Company of the Year Diabetes Therapeutic Company of the Year Oncology Company of the Year Cardiovascular Disease Therapeutic Company of the Year Most Successful Brand Launch of the Year
Dr. Ajit S. Golwilkar, Managing Director,Golwilkar Metropolis Health Services Pvt Ltd Dr. Amit Varma, Founding Managing Partner, Quadria Capital Investment Advisors Private Limited Ms. Anju Arora, Founder & Managing Director, ADI Media Private Limited Mr. Annaswamy Vaidheesh, Vice President - Corporate Government Affairs & Policies, Asia PaciďŹ c, Johnson & Johnson Dr. Bharati Kondwilkar, Professor & Head Anaesthesia and Critical Care, Grant Medical College & Sir J.J. Group Dr. Bhavin Jankharia, President, Indian Radiology & Imaging Association and President, SRL Diagnostics - Jankharia Imaging Dr. Huzaifa Khorakiwala, Trustee & CEO,Wockhardt Foundation Dr. Jairam Nandakumar, Chairman and Group Medical Director, Columbia Asia Hospitals, India Dr. Jamshed J. Dalal, Director, Centre for Cardiac Sciences, Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute Mr. Narayanan Suresh, Group Editor, BioSpectrum Dr. Nilesh Shah, Chairman and Managing Director, NM Medical Dr. P.V. Appaji, Director General, Pharmaceuticals Export Promotion Council of India Dr. Prashant Chhajed, Director, Lung Care and Sleep Centre and Institute of Pulmonology, Chief Pulmonologist, Fortis Hiranandani Hospital Dr. Preeti Devnani, Clinical Director, Comprehensive Sleep Disorder Clinic, Jaslok Hospital & Research Centre Mr. R. Basil, Executive Director & CEO, STS Holdings Limited, Dhaka Mr. Sudhir Mishra, Chairman and Managing Partner,Trust Legal Advocates and Consultants Dr. Sujit Chatterjee, CEO, Dr L H Hiranandani Hospital Dr.Tester F. Ashavaid, Director - Lab Research, Consultant Biochemist HOD, Lab Medicine, P.D. Hinduja National Hospital and Research Centre Dr.Tilak Suvarna, Head Department of Cardiology, Senior Interventional Cardiologist, Asian Heart Institute Dr.Venkatesh Krishnamoorthy, Chairman and Medical Director, NU Hospitals
Media Partners
A i d i n g s m a r t b u s i n e s s d e c i s i o n s
For more details: Log on to: www.frost.com/hcawards2014 or Email: indiahcawards@frost.com
with an animal model and many times the bacterial load is not high enough to reveal the emergence of resistance. HFBR cartridges have continuous medium circulation supporting dynamic control of drug concentration over time and resulting in the mimicking of naturally occur gradients in tissue drug concentration. A high surfacearea-to-volume ratio permits extremely rapid exchange of metabolites and pharmacoactive molecules between the central reservoir and cells growing in the relatively small ECS of the cartridge. The volume of this central reservoir can be easily adjusted to permit rapid and reproducible changes in drug concentration. Simulation of the kinetics of multiple drugs can also be accomplished so drug/drug interactions and combination therapies, as well as transport and efflux, can readily be modeled. The system is compact enough that multiple cartridges can be conveniently manipulated in a relatively small space, providing multiplexed or parallel and higher throughput type activities. Such systems can be configured for cell based assays employing either a single-cell type or multi-cell in co-cultivation. Examples of HF-Based Cell Assays HF based assays are inherently more complex and costly to design and set up than conventional cell-based assays. However, these assays can generate data that is not available in any other manner, and can bridge an important gap between animal studies and phase I clinical trials. Large numbers of cells can be assayed and over a period of time. Drug concentrations can be controlled in a dynamic fashion and both adsorption and elimination curves can be modeled. Multiple tests can be performed on the same cell population. Three dimensional cultures of multiple cell types can 34 ď‚ƒSeptember 2014
Pros
Cons
Hanging Drop
Simple, characterized materials Consistent spheroid size/composition Co-culturing supported HTS compatible Low cost / high efficiency Cell harvesting easy and efficient
Scaffold
Large variety of supports available Co-culturing supported Static and perfused implementations possible Low cost culture medium possible (with some scaffolds / cell types) Dynamic control in perfused implementations Scalability limited by unit design only Constitutively adherent culture supported
Gels
Large variety of matrix (gelling) materials Co-culturing supported Low cost / high efficiency Supports some HTS approaches
Hollow Fiber
Most in vivo like culture system Long term culture/multiple samplings Presents a defined 3-D defined matrix Supports many disparate co-cultures Dynamic control of metabolites/drugs possible Low cost culture medium possible Scalability limited by unit design only Tissue/organ dynamics modeling possible Unlimited cell mass/metabolites for assays Constitutively adherent culture supported Cell-to-cell interactions facilitated
No matrix interactions Spheroid size / culture scale limited Cell mass / metabolites for assays limited Tissue/organ dynamics modeling not possible Dynamic control of drug concentration not possible Dynamic control of primary metabolites not possible Some monitoring / probing approaches may be limited Constitutively adherent culture not possible Cell mass / metabolites for assays limited Variability in matrix physical structure Cell growth limited to sub-confluence Suspension cells only in static culture HTS applications limited Cell harvesting may be difficult / artifactual No dynamic control in static implementations Tissue/organ dynamics modeling not possible Limited cell mass for analysis
Initial structural variation plus changes over time Natural gels are undefined plus variability in CQA Microscopy and some monitoring may be limited Product and nutrient exchange limited by diffusion Dynamic control of metabolites/drugs not possible Culture unit dimensions and scalability limited Cell mass / metabolites for assays limited Tissue/organ dynamics modeling not possible Constitutively adherent culture not possible Cell harvesting may be difficult / artifactual Assays must be carefully planned Each culture expensive to set-up Sometimes technically challenging HTS applications can be limited Cell harvesting variable and cell type dependent
Table1: Cell based assay features and limitations for major 3-D cell culture systems.
model complex processes such as virus infections in tissues, hematopoiesis, cancer cell propagation, cancer cell metastasis, and the blood brain barrier (Mancuso et al, 1990).
Assays Using Only One Cell Type The simplest type of 3-dimensional cell based assays performed in hollow fiber bioreactors consist of only one cell Pharma Bio World
Attend DIA INDIA 2014!
Experts in healthcare, pharmaceutical industry members, academia, researchers, regulators, payers and patients will deliberate on the emerging topics.
PROGRAM NOW AVAILABLE REGISTER
BY
1 AUGUST 3 ! AND SAVE
DIA 2014
9th Annual India Conference
The Future of Indian Healthcare: Patients, Access and Innovation October 16-18 | Hotel Palladium | Mumbai, India
PROGRAM CO-CHAIRS Padmashree Prof. Ranjit Roy Chaudhury Chairman, Task Force for Research Apollo Hospitals Group Alexandra Pearce Senior Vice President and Head Global Regulatory Affairs Glenmark Pharmaceuticals
KEYNOTE SPEAKERS DAY 1 | OCTOBER 16 M K Bhan Former Secretary Department of Biotechnology Govt. of India DAY 2 | OCTOBER 17 G N Singh Drug Controller General of India (DCGI) DAY 3 | OCTOBER 18 Kiran Mazumdar Shaw Chairperson and Managing Director Biocon
GUEST SPEAKERS Y K Gupta Professor and Head Department of Pharmacology AIIMS Swati Piramal Vice Chairman Piramal Enterprise Ltd.
Devi Shetty Chairman Narayana Hrudayalaya Group of Hospitals
PROGRAM OVERVIEW Good health is a fundamental human right. But despite rapid improvements in the recent past, there are unprecedented healthcare challenges in India today that demand immediate attention and action. The most critical aspect among these is ensuring safety, efficacy, quality, affordability and accessibility of medicines and treatment to patients at all times. The key imperatives to overcome these continual challenges and catalyze the transformation include putting patients first, fostering innovation, and enhancing access. The DIA 2014 9th Annual India Conference will bring together leading local and global experts in healthcare, pharmaceutical industry members, academia, researchers, regulators, payers and patients under one roof to deliberate on the emerging trends, opportunities and challenges.
PROGRAM OBJECTIVES
WHO SHOULD ATTEND
• Focusing on ‘Patient First’ approach and various patient centric paradigms covering innovation and access of Indian healthcare • Hear the views of leading experts from the academia, government, industry, researchers, patient representatives and regulators on current local and global trends and best practices • Bringing all healthcare stakeholders together to discuss current issues/topics • Covering important issues/topics such as, patient health and safety, pharmacovigilance, clinical trial, quality and manufacturing, health economics, healthcare delivery, public-private partnership in innovation and healthcare access, case studies on Indian innovation and many more
• Drug development and clinical research managers and associates • Pharmaceutical physicians and medical directors • Drug safety and drug surveillance personnel • Professionals engaged in discovery research • Clinical pharmacology scientists • Pharmacologists • Regulatory affairs managers • Quality professionals • Academic scientists • Biostatisticians • Data managers • Medical writers • Outsourcing and marketing managers • IT professionals • Patient Engagement Stakeholders
CONTACT Manoj Trivedi Senior Manager Marketing and Program Development DIA (India) Private Limited cell: +91 98.1977.7493 Manoj.Trivedi@diaindia.org
For more information visit, diahome.org/India-9thAM
The 2D cell culture systems used so far have several drawbacks: the morphology, proliferation, metabolism and expression profiles of cells grown in 2D systems are very different to cells in living tissues. type, seeded in the ECS. HF bioreactor culture is the only cell culture method that can support cells at physiologic cell densities and provide for in vivo-like viral infection- and pharmaco-kinetics at these densities. Both adherent and suspension cells can be cultured in a HFBR. Adherent cells bound to a porous support do not require periodic splitting and can be maintained for extended periods of time. Suspension cells can also be supported for extended periods of time due to the same constant feeding and removal of metabolites. The ability to add medium with or without drugs is particularly important for dose fractionation pharmacodynamic studies where compounds are added to the system over a short period of time and then removed by dilution with drug free medium without disturbing the cells or their environment. Both absorption and elimination can be simulated. The small volume of the ECS contributes to the rapidity and economy with which this equilibrium takes place. Lastly, and perhaps most importantly because of their large size viruses and virus infected cells are retained in the small volume of the extra-capillary space. These infectious agents cannot cross the fibers into the medium. The system is completely closed to the external environment and provides an added biosafety component protecting laboratory personnel from exposure. Antiviral Pharmacodynamics HFBR support the establishment of a pharmacodynamic index (dose and schedule) of a particular entity for a particular virus: 36 September 2014
The high density culture within H F r e a c t o r s s u p p o r t s t h e e ff i c i e n t (biomimetic) cell-to-cell spread of virus is very for either matrixed or suspension cells. In either case, released virus and virus-infected cells accumulate in the ECS over time. Computer controlled pumps administer drug through a port in the central reservoir to model any schedule of ambient drug exposure. The concentration of antiviral drug in both the reservoir and the ECS itself can also be monitored by regular LC/MSn (or equivalent) assay of representative samples. The dosing regiment providing inhibition of viral replication and/or cellto-cell spread of virus can be determined by sequential analysis of cell and ambient media viral titer and drug concentration from identified points later validated by, eg, LC/MSn. (McSherry, et al 2011). HIV Recently, the nucleoside analogue, 2′, 3′-didehydro-3′deoxythymidine (d4T) was examined using hollow fiber infection models (HFIM) (Drusano et al, 2002). In separate experiments hollow fiber units infected with the same amount of virus and treated in the same way, but with d4T at half these doses failed to completely inhibit virus replication. The HFIM system predicted that the minimum effective dose of d4T to treat patients infected with HIV was approximately 0.5 mg/kg/day administered twice a day. This prediction was confirmed in a clinical study (Anderson et al, 1992). Protease inhibitors: A hollow fiber system was used to determine the
minimum concentration of the protease inhibitor A-77003 that would inhibits the replication of HIV in CEM cells (Preston et al, 2003). Vaccinia Virus For improved pharmacodynamic studies on the smallpox (varola) model virus, vaccinia, some researchers are employed hollow fiber-based models. One group looked at the effect of cidofovir on vaccinia virus replication in the HeLa-S3 cells monitored by FACS analysis of virus-infected cells and by the production of infectious virus using a plaque assay (McSharry et al, 2009a). Influenza Virus The current recommendation for treatment of influenza with oseltamivir is to take two 75 mg tablets twice a day. Recently researchers employed hollow fiber-based models to performed dose range and dose fractionation experiments in MDCK (McSharry et al, 2009b). The data showed that in the absence of drug the virus grew well in the HFIM system and that the pharmacodynamicallylinked index for oseltamivir for the R292 strain of influenza A virus is the AUC/ EC50/95 ratio. This means that the model indicates that at the appropriate dose, oseltamivir could be given once a day. The demonstration that adherent cells can be used to grow virus in the HFIM system opens this system up to the pharmacodynamic analysis of antiviral compounds for a wide variety of viruses (Brown et al, 2011). Anticancer Agents Another example of a 3-D cell based assay using only one cell type in the ECS of the hollow fiber cartridge is for the analysis and characterisation of anticancer agents. Anti-cancer agents also exhibit both time and concentration dependent efficacy. Pharma Bio World
Mark Kirstein reported on the use of the hollow fiber model for anticancer drug evaluations. In this case gemcitabine was examined in the anchorage dependent MDA-MB-231 breast cancer cell line (Kirstein et al, 2006). More accurate results are obtained for a few reasons. One, because the multi-layer, 3-dimensional organisation of these continually perfused cells more closely reflects the in vivo structure of the tumor, they have an increased relevance for assays of anti-cancer agents. Another is that the cell division rates in static cultures are commonly artificially high, and this can render them more sensitive to some chemotherapeutic agents then their natural counterpart (Kirstein et al, 2008).
Figure 2: Co-cultivation of a mixed cell population derived from collagenase digestion of a human placenta results in the formation of 3-dimensional structures capable of generating suspension cells with stem-like phenotypes. (reference fibercell poster)
Assays Using More Than One Cell Type Hollow Fiber and 3-D Co-cultivation for Cell Based Assays HFBR-based culture is one of the few in vitro techniques providing large numbers of cells in close enough proximity and sufficiently high density to observe a number of tissue-like behaviors. These behaviors include: 1) Signaling and direct interactions between different cell types 2) Coordinate (or synergistic) activity upon the ambient media 3) Coordinate (or synergistic) activity upon a compound or drug 4) Mixed cell type-specific effect (+/-) upon of viral infections HF cell culture permits the recapitulation of natural structures containing more than one cell type in a defined, controlled, and more biomimetic environment. Endothelial cells are the only cells that can be easily cultured on the insides of the fibers. There are two types of cell co-cultivations that can be performed in a hollow fiber bioreactor. They are, one or more cell types 40 ď‚ƒSeptember 2014
Figure 3: Photo of bone marrow stroma cells bound to the surface of the 5kd MWCO polysulfone fibers. These cells can interact with hematopoietic stem cells, leukemic lymphocytes or other cell types.
1) on both the inside and on the outside of the fibers (Davis, 2007) 2) on only one side of the fibers (typically on the ECS)(FCS Application, 2012) An example of the first type of cellular cocultivation is the use of HFBRs to culture endothelial cells on the insides of the fibers while culturing a different cell type on the outside to provide cell signaling (Redmond, Cahill, and Sitzman, 1995). The concept of “organ recapitulation� in hollow fiber was first applied by Jorg Gerlach using liver tissue (Gridelli et al, 2012). The system used was a complex HFBR with two different fiber types
and three separate bundles of fibers. Primary function in a mixed population of liver cells was maintained for 4 weeks. Bone Marrow Model Perhaps the most rigorous application of HF systems for single-compartment cell co-cultivation is in the area of stromal cell/suspension cell interactions. In demonstration of the second type of culture, Dr Mayasari Lim at University Hospital, Hong Kong has published an article on the co-cultivation of a human bone marrow stromal cell line with a leukemic T cell line (Usuludin, Cao and Pharma Bio World
Brilliant technology Italian quality Saurus939: Versatile and long life piston vacuum pump • Uncontaminated vacuum • Operational costs lower than other vacuum technology
Criox System: Patented rotary vacuum dryer with electric lump-breakers
• Simple and cheap maintenance • Environment friendly • ATEX zone 0
Planex System: New patented paddle vacuum dryer with eccentric agitator
Multispray Cabinet Dryer: Vacuum tray dryer with extractable shelves
Agent for vacuum pumps
Your vacuum drying specialist marketing@italvacuum.com italvacuum.com
EMJAY ENGINEERS, Mr. Jayant Joshi B/102, Shubh Sarita CHS, Near Shrikirshna Nagar, Appasaheb Sidhaye Marg, Borivali (East), Mumbai 400066 Tel. 02228975275 Mobile 9820047858 E-mail:electromech.engg.entp@gmail.com
longitudinal studies of the effects of flow and co-culture in a controlled and fully recyclable environment.
Figure 4: Endothelial cells attached to the inside of a PVDF hollow fiber without shear stress. Note the round shape of the cells.
Lim, 2012). When cultured in the HF cartridge the T cells underwent a 4000 fold expansion, in line with what occurs in vivo. Recently, the efficacy of such an HF platform was evaluated in comparison to standard cultures performed on tissue culture polystyrene (TCP). A human stromal cell line (HS-5) was employed as a co-cultured stromal support of lineage-cell depleted human cord blood cells (Xue et al, 2014). Results showed that the performance of the HFBR in supporting total cell and CD34+ progenitor cell expansion was comparable to that of cultures on TCP, while cells harvested from the HFBR had a higher clonogenic ability. The findings demonstrate the feasibility of utilising an HFBR for creating a complex cell matrix architecture, which may provide good in vitro mimicry of the bone marrow supporting large-scale expansion of HSCs. Asymmetric Co-Culture using Endothelial Cells 3-Dimensional cell based assays utilising co-culture of multiple cell types in hollow 44 September 2014
fiber bioreactors can recapitulate more complex structures than those with a single cell type. One type of cellular co-cultivation, as described above, is the use of hollow fiber bioreactors to culture endothelial cells on the insides of the fibers and a different cell type on the outside. In one study, altering the flow rate changed the shear stress, g-protein formation and endothelin receptor expression was directly modulated, even though there was no physical contact between the two cells types (Redmond, Cahill and Sitzman, 1995). Blood/Brain Barrier Model There are many in vitro approaches to the modeling BBB physical and biochemical behavior, but most fail to represent its natural three-dimensional nature, and do not support the associated exposure of endothelial cells to such complex influences as exist in vivo. To a n s w e r t h i s c h a l l e n g e , J a n i g r o developed a new, dynamic, in vitro BBB model (NDIV-BBB) designed to allow for extensive pharmacological, morphological and physiological studies (Stanness et al, 1999). His new dynamic HF-based model of the BBB allows for
In perhaps the ultimate embodiment of state of the art hollow fiber based cell assays, Dr Chris Pepper et al have developed a model for primary investigations and assaying for cancer metastasis (Walsby et al, 2014. A dynamic in vitro model was developed in which CLL cells experience shear forces equivalent to those in capillary beds and are made to flow through capillary-like hollow fibers lined with endothelial cells. CLL cells treated in this way increased their expression of CD62L, CXCR4, CD49d and CD5 and migrated through the endothelium into the ‘extravascular’ space’ (EVS). The degree of migration observed strongly correlated with CD49d expression and treatment with the CD49d blocking antibody. Taken together these data provide evidence for a novel, dynamic and reproducible in vitro model of lymphocyte migration and cancer metastasis. Summary Novel material features supporting a renaissance in the technology include fibers composed of new materials, new surface derivatisations and porosities providing improved binding, flux and flow rates. New and creative application development has kept pace with the availability of these new technologies expanding the scope of applicability of 3-D hollow fiber cell based assays. The result is a robust and flexible technology with diverse applications. Such applications range from protein biological production providing ultraclean harvest and simplified purification– to improved in vitro viral infection systems providing more accurate drug candidate PK/PD modeling. Contact: bill.whitford@thermofisher.com Pharma Bio World
GST: A Sweet Pill for Indian Pharma Goods and Service Tax (GST) is high on the agenda for the new government and its rollout is a priority. GST will benefit the Indian pharmaceutical manufacturers by rationalising the tax structure and optimising distribution. Even a 2 per cent reduction in production or distribution cost will add to the profits by over 20 per cent. It could be the single biggest shot in the arm for the Pharmaceutical industry and create competitive advantage for those who move early.
T
he Indian Pharmaceutical industry with a domestic turnover of over USD 15 billion is amongst the largest producers of pharmaceutical products in the world (by volume). While the sector has been witnessing high growth over the past decade it has been burdened with diminishing margins. The domestic industry is facing pressures of increasing span of price control on account of changing regulations, price erosion with more generics and increasing competition added by lack of R&D productivity and limited new molecules. Multistage taxation in the pharmaceuticals industry ie, Customs duty on imports, Central excise duty on manufacture, Central Sales Tax (CST)/Value Added Tax (VAT) on sale of goods, Service tax on provision of services and levies such as entry tax, octroi, cess by the State or municipalities; loss of credit of tax paid, adds to the inefficiencies and cost. GST will help in rationalising the tax structure and could be the single biggest shot in the arm for the Pharmaceutical sector. What is Goods and Services Tax (GST)?
Manish Panchal
(Practice Head – Chemicals, Lifescience & Supply Chain) TATA Strategic Management Group
GST is an evolution of the current tax regime, transforming the complex and cascading structure into a unified value added system of taxation. Under this, a value added tax would be levied at every point of the supply chain providing for credit for any/all taxes paid previously.Keeping in line with the governance structure of the country GST would be levied simultaneously by the Centre and State (CGST and SGST respectively). All essential characteristics in terms of its structure, design applicability, etc. would be common between CGST and SGST, across all states. GST is expected to replace most of the current applicable indirect taxes as listed in Exhibit 1.
Siddharth Paradkar
(Practice Head – Chemicals, Lifescience & Supply Chain) TATA Strategic Management Group 46 September 2014
Benefits to the Pharmaceutical Industry Implementation of GST will have significant impact and will change the manner in which
business is carried out in comparison with the existing ways.The application of a single tax rate across all goods and service will result in redistribution of taxes across all categories. This will lead to a reduction in taxes on manufactured goods and thereby impacting the pricing of the final product. The integration of tax on Goods and Services through GST would provide the additional benefit of providing credit for service tax paid by manufacturers. Both CENVAT & VAT, which are being levied at present, give tax credit to the manufacturer for the tax paid for raw materials (hence a tax is charged only on the value added by the manufacturer). More often than not, there are various services including logistics involved in getting the input material to its final customers. Service tax is paid on the cost of such services too. With the implementation of GST, cost of any service, including logistics, will be considered as value add, and the manufacturer will get tax credit for the service tax paid. The biggest advantage to the industry would be that of reduction in transaction cost, with an immediate impact coming from the discontinuance of CST. The multistage taxation along with the inability to take full benefit of the CENVAT credit /refund has been an issue for the industry. With central GST expected to be a single rate for goods and services, going forward credit accumulation may not be an area of concern. Furthermore, if the legislation provides for carrying forward of the unutilised credit this would be an additional boost to the industry. India a single common market: Under GST inter-state sales transactions between two dealers would be cost equivalent and comparable with stock transfers/branch transfers. Inter-state transactions would become tax neutral, making India one single common market no longer divided by state borders (Exhibit 2). This will result in lower cost which can add to margins or can be passed on to customers. Pharma Bio World
could be addressed by designing logistics efficient networks of mother and daughter warehouses to ensure optimisation of cost and superior availability of products. While the qualitative benefits arising out of GST are well established, there is a definite impact to economics of companies as well. Logistics cost accounts for nearly 13-14 per cent of our GDP. Of the total logistics cost transportation contributes ~35 per cent, warehousing & storage ~10 per cent, inventory holding cost ~25 per cent and other inefficiencies’ make up the balance 30 per cent. Implementation of GST and alignment of a firm’s supply chain to it will directly help in reducing cost on transportation, warehousing and inventory holding by 5-8 per cent, 10-12 per cent and upto 28 per cent respectively for each of the cost heads, leading to an overall savings in the range of 10-12 per cent of the total logistics cost.
Exhibit 1: Taxes subsumed under GST
Looking Forward
Exhibit 2: GST will enable manufacturers to realise higher margine
Opportunity to explore alternate distribution models: Organisations will be able to explore different distribution models such as setting up mother warehouses and regional distribution hubs and consider stepping away from traditional C&F and distributor based models currently adopted. This will lead to logistics and distribution to evolve as a competitive advantage through improved service levels, faster turnaround times and better fill rates at lower costs. Rationalisation of Warehouses and Transport network: GST would do away with the existing penalties on inter-state sales transactions and facilitate consolidation of vendors and suppliers, eliminating the need to have state wise warehouses to avoid CST and the associated paperwork. This will enable companies to consolidate warehouses, rationalise their networks and take advantage of economies of scale, improved efficiencies, better control 48 ď‚ƒSeptember 2014
and reduction in inventory (ie, working capital deployed in the business). For example: By setting up a large warehouse in a place like Zirakpur, a large logistics hub with good infrastructure, a company can serve markets across the states of J&K, Himachal, Punjab, Uttrakhand and Haryana as against having five different warehouses to serve these markets in the current scenario. Furthermore, the pharmaceutical sector currently enjoys various location based tax holidays on its manufacturing activities. Under the proposed structure of GST, such area based exemption will be done away with. However, taking into account past precedents suitable work around/ refund process would be constituted to ensure that any existing hubs do not get impacted and continue to get the agreed benefits. However, the challenges faced in distributing from these remote locations
The government has already begun the process of getting the necessary consensus from all the stake holders to pave the way for implementing this landmark tax reform. Though the exact details are still sketchy, the structure and deliverables have been clearly laid down for all to see. The government has set itself an ambitious target to roll it out by July 2015. As Indian pharmaceuticals companies look forward to revenue growth on one side and the need to reduce costs, GST offers a great opportunity to revisit their Supply Chain & distribution strategy to develop an agile, customised and cost-efficient supply chain. Companies need to act now to assess the impact of GST on their businesses and functions and develop an action plan and road map for the future. Those who move early are likely to gain an advantage on cost and service levels over their competitors and deliver a better value proposition to the customer. Contact: manish.panchal@tsmg.com Pharma Bio World
Pump in chemlin Technology to pump out more profits !
VERTICAL SUBMERGED PUMPS
HORIZONTAL CHEMICAL PROCESS PUMPS The Impeller & Casing design enable maximum energy conversion & the mechanical design allows minimum frictional losses. &DSDFLW\ 8S WR Pñ KU 7HPS Û & WR Û & Head : Up to 120 m. Size : 32 mm thro' 100 mm Working Pressure : 18 kg/cm². Material of Construction : Cl, CS, CF8M, CN7M, R-55 DIN 4136, CA6NM, Ca15, Hastalloy grades, Special Alloy Steels & Non-ferrous Materials, Pump Flanges according to DIN, ANSI, BS Stds.
To Handle corrosive, abrasive liquids & Slurries where leakage is intolerable Capacity : Up to 800 m³/hr. Total Head : Up to 120 m. Pump Setting: Up to 3 m. Size : 25 mm thro' 250 mm. Material of Construction: Cl, CS, Ca15 CF8, CF8M, DIN 4136,Ni-hard, Ni-resist, 28/2 CrMo steel, CN7M,R-55, Hastalloy grades & Special Stainless Steels Alloy. Pump flanges according to DIN, ANSI, BS Stds.
Authorised Distributors for India
&KHPOLQ 3XPSV 9DOYHV 3YW /WG OFFICE : F-5, 'Atharva Estate', 238/2,E,Tarabai Park, Kolhapur - 416 003 (Maharashtra) India. Phone : HO (0231) 2653123, 2651964 Fax : 0231 - 2655389, E- mail : sales@chemlinindia.com WORKS : 235/6,Pune - Banglore Road, KAGAL - 416 216,Dist. Kolhapur (Maharashtra) Phone : 02325- 244108, 245108, Email :- works@chemlinindia.com , Website : www.chemlinindia.com Reg. No. 9910000526
MUMBAI : mumbai@chemlinindia.com
N.DELHI : delhi@chemlinindia.com
ERNAKULAM : ernakulam@chemlinindia.com
BARODA : vadodara@chemlinindia.com
68% '($/(56+,3 (148,5,(6 )25 81 5(35(6(17(' $5($6 $5( :(/ &20(
ADVERTISE TO EXPAND YOUR REACH THROUGH
Peroxide Cured
C HEMICAL
ENGINEERING WORLD
Platinum Cured
Braided
Tri Clover
OffshoreWorld
Ring
Septa Septa
INSIGHT INTO UPSTREAM & DOWNSTREAM HYDROCARBON INDUSTRY
Washer
Cork
The Journal of Materials & Equipment for the Process Industries www.cpfndia.com Vol. 30 No. 3 August 2011 ISSN 0971-5274 ` 50/-
Chemical Products Finder
Chemicals, Petrochemicals
& Agrochemicals
Gripper August 2011 Vol.10 l Issue 1
l
Price `100
l
www.pharmabioworld.com
Flush Bottom www.smpworld.com
Butterfly
86 )'$ UHJXODWLRQV &)5 IRU FRQWDFW ZLWK IRRG
Vol - 3 Issue - 6 • JUNE - JULY 2011 • ` 100
South Special
Port Sector in South India
863 FODVV 9, UHTXLUHPHQWV (XURSHDQ 3KDUPDFRSRHLD
Interview of Y S Prasad, Kakinada Seaport
For Details Contact:
Jasubhai Media Pvt. Ltd. rd
Taj Building, 3 Floor, 210 Dr D N Road, Fort, Mumbai - 400 001 Tel: 022-4037 3636, Fax: 022-4037 3635 Email: industrialmags@jasubhai.com
Advertisment.indd 3
Profile
tices
Prac
) )
DMF No. 26710 Certified Cleanroom
$QLPDO GHULYDWLYH IUHH
M. K. Silicone Products Pvt. Ltd. 205 & 206 Hill View Industrial Premises, Amrut Nagar, Ghatkopar (W), Mumbai - 400 086, India. Tel.#:022-2500 4576 Fax #:022-2847 5722 E-mail :sales@mksilicone.com
Blue Heaven
Your Radar to Shipping, Marine & Ports World
ring
actu
anuf
M Good
18-09-2014 18:20:41
press release SRL Diagnostics Introduces Butterfly Cipla Awards Gas Piping Installation Needles Technology Contract to Excel Gas & Equipments In an endeavour to minimise the pain and psychological fear associated with a Blood Test, SRL Diagnostics has recently announced the use of high-end technology needles named, Butterfly Needles, making diagnosis Pain - Free.
Cipla, one of the largest pharmaceutical drugs manufacturing companies had awarded gas piping installation contract at their latest R&D Centre at Vikhroli, Mumbai to Excel Gas & Equipments, one of the leaders in Gas piping installations. .
It is said that Diagnosis is the first step in disease management; thereby SRL is taking steps to ease the first step of the illness cycle, Diagnosis, through introduction of pain – free Butterfly Needles for blood collections. This is SRL’s effort to curb syringe phobia amongst patients as well. The butterfly needles serve another purpose of safeguarding the phlebotomists (persons who collect your blood) from accidental needle stick injuries that are a crisis in the healthcare systems around the globe. Therefore, safer blood drawing devices like butterfly needles help mitigate the dangers of needle stick injuries during routine blood draws.
NitinGodse, Managing Director, Excel Gas & Equipments said “We are extremely happy to work with Cipla and our relationship with Cipla has been continuing for years now. This is one of the huge project for us. We have executed similar installations in R&D laboratories of other pharma companies like Dr Reddy’s, Pfizer, Novartis, Syngenta and many more. However, this is special because it’s a 7 storeyed building and the research and development has various laboratories. Since each Lab Incharge had their requirements to be independent, our team had to interact with all the different users. We had to design systems that would be independent to each lab, yet are monitored at a single point. This works out like different clients in one order! Post completion of this contract, Excel Gas & Equipments will have a continued AMC with Cipla to ensure trouble free working of our systems.”
The butterfly needle is a relatively pain free tool for collecting blood from patients – especially those who are hypersensitive to pain, have syringe phobia (entetophobia), children, newborn babies, have very fragile or small veins or have tremors. So, butterfly needles can be used for all age groups (0-70).
Free Webinar & Demo of Pharmacovigilance Indian Excipients Industry Joins Software PV247 Hands to Set Up IPEC India India’s leading names in pharmaceutical excipients join hands to set up its first ever excipients council. The founding members of IPEC India are Ajit Singh of ACG Worldwide and Mr. Subodh Priolkar of Colorcon Asia. Indchem International, Micro Labs, Dow Chemicals, Lubrizol India, BASF India, SPI Pharma, and Merck Group are the other founder-member companies. IPEC India is the 5th member of the IPEC Federation, the others being the Americas, Europe, Japan and China. Internationally, the IPEC Federation is the leading federation of the pharmaceutical excipients industry and has over 250 members across all affiliates. The IPEC Federation provides a unified voice which promotes the proper use of excipients in medicines as a means of improving patient treatment. IPEC India will work actively to promote excipients safety and harmonization of regulatory standards and pharmacopoeial monographs. It will be a source of advice and expertise on excipients and excipients-related regulations. The Council will focus its attention on the law, regulations, science and business landscape of the Indian pharmaceutical industry for excipient manufacturers and suppliers. It aims to be a proactive colleague of the Indian pharmaceutical industry associations and federations. 50 September 2014
Coimbatore-based global pharmacovigilance consulting & drug safety services company Oviya MedSafe and St Neots-based software development company Assured Information Systems joined hands in April 2014, to provide phenomenally cost-effective pharmacovigilance support to pharmaceutical companies. This strategic alliance aspires to promote the adoption of drug safety systems, especially among small & mid-sized innovators and generic drug marketers of any size throughout the world, by delivering comprehensive pharmacovigilance solutions in an economical and user-friendly manner. PV247, a product of Assured, is a human pharmacovigilance hosted software database that offers intuitive end-to-end pharmacovigilance support to the global pharmaceutical industry. PV247 is E2B and 21 CFR Part 11 compliant. It is capable of electronic reporting to all regulatory authorities across the globe, including EMA and USFDA. Oviya MedSafe represents Assured in India & the Asia Pacific region. Oviya MedSafe and Assured have jointly announced a free webinar & demo session on PV247 to share the advantages of this hosted application with its prospective users. This session has been exclusively designed to showcase the user-friendliness of PV247 and to educate the end-user of its capabilities. Pharma Bio World
Frislam
. . . . . . . . . .PUAWPS速
Engineered For Lasting Performance速
Driven by innovation: we want to make sure that Fristam pumps will always be the best choice for your company.
Fristam side channel centrifugal pumps FZ
Fristam centrifugal pumps FP
Fristam positive displacement pumps FKL
Fristam positive displacement pumps FUFL2/FL3
Fristam powder mixer series PM
Fristam positive displacement pumps FK
Flexibility is quite simple: we build each of our pumps considering your individual requirements.
Frllam
..._ _ _ _PUMPS
Fristam Pumps India Pvt.Ltd.
Tel +91 (0) 20 271 30 751
J 340 Bhosari MIDC
Email:- sales@fristam.in
411026 Pune
Website:- www.fristam.in
100% Subsidiary of FRISTAM Pumpen KG (GmbH & Co.),Hamburg, Germany
press release Sanofi’s Dengue Vaccine Completes Clinical Efficacy Study in Latin America Sanofi Pasteur, the vaccines division of Sanofi, has announced that the final landmark phase III efficacy study of its dengue vaccine candidate in Latin America successfully achieved its primary clinical endpoint. Results showed an overall significant reduction of 60.8 per cent of dengue disease cases in children and adolescents 9-16 years old after a three-dose vaccination schedule. Importantly, efficacy was observed against each of the four dengue serotypes. Additional observations of the results showed a clinically important reduction by 80.3 percent* in the risk of hospitalisation due to dengue during the study. The results also showed in the study population an efficacy against dengue haemorrhagic fever (DHF), the severe form of dengue1, which is consistent with the results released from Sanofi’s phase III dengue study in Asia. Lastly, the results suggest better protection in case of prior exposure to dengue. Safety analyses (solicited reactions, unsolicited events and Serious Adverse Events SAEs) during the study showed similar reporting rates between the vaccine and control groups and are consistent with the favorable safety profile documented in previous studies (phase I, II, III). “For the first time ever, after 20 years of research and industrial commitment, dengue is set to become a vaccine preventable disease,” said Olivier Charmeil, President and Chief Executive Officer, Sanofi Pasteur. “The data generated from our comprehensive research and clinical program involving 40,000 children, adolescents and adults from 15 countries, will be submitted to the health authorities in countries where dengue is a public health priority.” Each year, an estimated 500,000 people, including children, have severe dengue requiring hospitalisation, putting a huge strain on health care systems during outbreaks. Dengue has dramatically increased over the past 30 years with an acceleration over the last decade.
Breast Cancer Has Pharma’s Largest and Most Innovative Drug Pipeline The breast cancer therapeutics pipeline boasts a high degree of innovation in first-in-class molecules, with many new technologies holding the potential to transform the clinical and commercial treatment landscape over the coming decade, says business intelligence provider GBI Research. 54 September 2014
The company’s latest report states that breast cancer has the largest drug pipeline in the pharmaceutical industry, with 816 products in active development across all stages. Of these treatments, GBI Research has identified 245 first-inclass programs acting on 175 first-in-class molecular targets, accounting for 39 per cent of all products with a disclosed molecular target. Dominic Trewartha, Analyst for GBI Research, says: “The mechanisms of action in the breast cancer pipeline cover an extremely diverse range. Traditional chemotherapies and hormone therapies, for example, represent just 22 per cent of the total pipeline, while there is an increasing move towards developing therapies that directly target proliferative signaling pathways. These therapies account for 31 per cent of the pipeline.” According to GBI Research, the most widely studied, first-inclass targets in the breast cancer pipeline are signal transducer proteins. These are components of proliferative and survivalpromoting signaling pathways, such as Ras/MAPK and PI3K/Akt, which operate downstream of the receptor. It is now understood that these agents share a high degree of crosstalk with one another.
Superba Krill Oil Gets Regulatory Approval in India Aker BioMarine Antarctic AS, a customer-driven supplier of krillderived phospholipid omega-3 products, has received product approval for Superba Krill oil from Food Safety Standards Authorities of India (FSSAI). According to publically available information, Superba Krill oil is, as of today, the first and only krill oil that has obtained product approval by the FSSAI. “This new ingredient approval will enable Indian consumers to benefit from omega-3 fatty acids in phospholipid form. Omega-3 phospholipids are more efficiently incorporated into cell membranes and are therefore an excellent source of omega-3 fatty acids to support heart, brain and joint health,” said Atul Barman, Aker BioMarine Antarctic AS’s India representative in Mumbai. “This approval represents a key milestone for our entry into India,” said Tim de Haas, Vice President of Business Development, Aker BioMarine Antarctic AS, Oslo, Norway. “We feel confident that with our local presence we can successfully support our customers in India. Backed by our success, especially in the US and Australian markets, expanding into the Indian dietary supplement market presents great opportunities for Superba Krill oil.” Pharma Bio World
press release OPPI Organises HR Summit on ‘Attracting, AstraZeneca Opens Global Technology Developing & Retaining Talent’ Center in Chennai The Organisation of Pharmaceutical Producers of India (OPPI) has organised its annual HR Summit on “Attracting, Developing & Retaining Talent”. The event witnessed participation of business leaders, academia and HR professionals from the pharmaceutical and allied industry. The Indian pharmaceutical industry has been growing at a steady pace and now exports drugs to more than 200 countries across the globe. This growth has fueled employment opportunities across functions including research and development, sales and marketing, finance, project management and supply chain. However, identifying the right talent for every role, and retaining talent over the long term remains a significant challenge for the industry. At the event, distinguished speakers discussed the HR challenges of the pharmaceutical industry and drew upon experiences from other industries to provide likely solutions to these challenges. In his inaugural address Dr Shailesh Ayyangar, President, OPPI and Managing Director, India & Vice President, South Asia, Sanofi said, “Each business leader needs to be a good HR manager. It is important that the pharma industry is cognisant of the current HR challenges. Innovative talent development programmes along with competency and skill development workshops are the need of the hour to harness young talent.” Dr Ayyangar further stressed that the generation Y has to believe that this industry is indeed a great place to work in. This can happen only when they are empowered with independence along with accountability. While moderating a CEO’s panel discussion during the summit, Ajay Bhatt, Regional Human Resources Director, Abbott India, said, “It is only when the talent can see a clarity of role, a clear career path and more importantly feels valued that he/ she finds fewer reasons to leave. The onus is on business leaders and HR managers to provide this clarity and create a participative environment.” The panel concluded that the nuances of the pharma industry demand a quality workforce. This calls for significant investment in continuous skill upgradation and will go a long way in talent retention. Pharma Bio World
Press Release.indd 55
AstraZeneca has inaugurated a new state of the art Global Technology Center (GTC) in Chennai, to develop its world-class IT capability. The establishment of a GTC in Chennai will help improve the IT organization’s efficiency and responsiveness while reducing costs and support 51,500 AstraZeneca employees worldwide. AstraZeneca has significantly invested in this India based IT hub, both in terms of manpower and technology. The center will drive many of the IT tools, technologies and capabilities to that support delivery of AstraZeneca’s strategic ambitions. The company is also looking to develop additional technology centers with a second GTC planned for San Francisco in 2015.
DIA 9 th Annual India Conference to Kickstart on 16 th October in Mumbai Coimbatore-based global pharmacovigilance consulting & drug safety services company Oviya MedSafe and St Neots-based software development company Assured Information Systems joined hands in April 2014, to provide phenomenally cost-effective pharmacovigilance support to pharmaceutical companies. This strategic alliance aspires to promote the adoption of drug safety systems, especially among small & mid-sized innovators and generic drug marketers of any size throughout the world, by delivering comprehensive pharmacovigilance solutions in an economical and user-friendly manner. PV247, a product of Assured, is a human pharmacovigilance hosted software database that offers intuitive end-to-end pharmacovigilance support to the global pharmaceutical industry. PV247 is E2B and 21 CFR Part 11 compliant. It is capable of electronic reporting to all regulatory authorities across the globe, including EMA and USFDA. Oviya MedSafe represents Assured in India & the Asia Pacific region. Oviya MedSafe and Assured have jointly announced a free webinar & demo session on PV247 to share the advantages of this hosted application with its prospective users. This session has been exclusively designed to showcase the user-friendliness of PV247 and to educate the end-user of its capabilities. September 2014 55
19-09-2014 19:34:09
pharma news Gilead Ink Generic Licensing Deal A u x i l i u m A n n o u n c e s C o r p o r a t e Restructuring with Indian Pharma Companies Gilead Sciences, Inc has signed non-exclusive licensing agreements with seven India-based generic pharmaceutical manufacturers to expand access to its chronic hepatitis C medicines in developing countries. The agreements allow the companies – Cadila Healthcare Ltd, Cipla Ltd, Hetero Labs Ltd, Mylan Laboratories Ltd, Ranbaxy Laboratories Ltd, Sequent Scientific Ltd and Strides Arcolab Ltd – to manufacture sofosbuvir and the investigational single tablet regimen of ledipasvir/sofosbuvir for distribution in 91 developing countries. The countries within the agreement account for more than 100 million people living with hepatitis C, representing 54 per cent of the total global infected population. Under the licensing agreements, the Indian companies receive a complete technology transfer of the Gilead manufacturing process to enable them to scale up production as quickly as possible. The licensees also set their own prices for the generic product they produce, paying a royalty on sales to Gilead to support product registrations, medical education and training, safety monitoring and other essential business activities. The licenses also permit the manufacture of sofosbuvir or ledipasvir in combination with other chronic hepatitis C medicines. Meanwhile, Médecins Sans Frontières (MSF) expressed concern over these agreements. They argued that although Gilead agreements will allow some generic companies to market generic versions of both drugs in 91 countries regardless of the patent status in those countries, most of the countries expected to be included in the license agreements are low-income economies, many of which may not have had patent protection on these new drugs in the first place.
Mylan to Commercialise Arixtra in US Mylan Inc announced that its subsidiary Mylan Ireland Limited has entered into an agreement to acquire the US commercialisation, marketing and intellectual property rights relating to Arixtra (fondaparinux sodium) Injection and the authorised generic (AG) of Arixtra from Aspen Global Incorporated. Arixtra is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing hip fracture surgery, including extended prophylaxis, hip replacement surgery, knee replacement surgery or abdominal surgery who are at risk for thromboembolic complications. Mylan already is selling Arixtra in the US through an interim distribution arrangement with Aspen and Apotex is currently selling the AG of Arixtra, which will be transitioning to Mylan Institutional by year end. 56 September 2014
Auxilium Pharmaceuticals a specialty bio-pharmaceutical company, announced steps it is taking to reduce its costs and more fully support the company’s goal to drive earnings growth and build shareholder value. These steps are being launched after a comprehensive assessment of Auxilium’s broadened product portfolio and current cost structure and what management believes to be Auxilium’s growth assets, commercial strengths, opportunities and challenges and the company’s manufacturing needs and capabilities. The restructuring is designed to reduce annual operating expenses by at least USD 75 million and align cost structure with the company’s current product portfolio, stabilise cash flow and improve leverage ratio, realign the commercial organisation, & strategically consolidate the current three sales forces into two sales forces, strengthening the company’s urologist franchise offering while maintaining the momentum for the Xiaflex for Peyronie’s Disease and Stendra launches and supporting the growth potential of Testopel and edex. Maintain the targeted commercial resources dedicated to continuing the stable growth momentum of Xiaflex for Dupuytren’s contracture, focus R&D efforts on the efficient development of near-term value programmes cellulite and Frozen Shoulder Syndrome, Improve manufacturing efficiency and enhance inventory management.
Merck’s Keytruda Gets FDA Nod Merck, known as MSD outside the United States and Canada, has announced that the US Food and Drug Administration (FDA) has approved KEYTRUDA (pembrolizumab) at a dose of 2 mg/kg every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Keytruda is the first anti-PD-1 (programmed death receptor-1) therapy approved in the United States and received FDA’s Breakthrough Therapy designation for advanced melanoma, which was granted based on the significance of early study findings and the unmet medical need. Keytruda is a humanised monoclonal antibody that works by increasing the ability of the body’s immune system to fight advanced melanoma. Pharma Bio World
pharma news Astellas’ Xtandi Gets USFDA Approval Astellas Pharma, a pharmaceutical company dedicated to improving the health of people around the world through provision of innovative and reliable pharmaceuticals, and Medivation announced that the US Food and Drug Administration (US FDA) approved a new indication for the use of Xtandi (enzalutamide) capsules to treat patients with metastatic castration-resistant prostate cancer (CRPC). This new approved use follows a priority review of the supplemental New Drug Application (sNDA) that was based on results of the phase 3 PREVAIL trial. The FDA initially approved Xtandi, an oral, once-daily androgen receptor inhibitor, in August 2012 for use in patients with metastatic CRPC who previously received docetaxel (chemotherapy). The new indication approves Xtandi for use in men with metastatic CRPC who have not received chemotherapy. Metastatic CRPC is defined as a cancer that has spread beyond the prostate gland and has progressed despite treatment to lower testosterone (ie, with a gonadotropin-releasing hormone (GnRH) therapy or with removal of the testes). In the phase 3 PREVAIL trial, men receiving Xtandi and GnRH therapy exhibited a statistically significant improvement in both overall survival and delayed time to radiographic progression or death as compared to those on placebo and GnRH therapy. The safety profile for Xtandi was updated to reflect data from both the AFFIRM and PREVAIL phase 3 trials.
Neos Resolves Patent Litigation with Shire Neos Therapeutics, a specialty pharmaceutical company with a portfolio of novel and proprietary oral drug delivery technologies as well as a late-stage pipeline of innovative extended release (XR) products for Attention Deficit Hyperactivity Disorder (ADHD), has settled all pending litigation with Shire LLC (Shire) in connection with Neos’ amphetamine polistirex orally disintegrating tablet known as NT-0202 for the treatment of ADHD. NT-0202 is positioned to be the first-ever, extended release orally disintegrating tablet (XR-ODT) dosage form of amphetamine for the treatment of ADHD. The litigation involved a patent infringement lawsuit brought by Shire under the Hatch-Waxman Act framework stemming from Neos’s filing of its New Drug Application under section 505(b)(2) of the Federal Food, Drug, and Cosmetics Act for NT-0202 with the United States Food and Drug Administration (US FDA). On April 11, 2013, Shire filed suit against Neos asserting that Neos Pharma Bio World
infringed US Patent No. RE 42,096 and US Patent No. 41,148 (collectively, the “Patents”). The parties have entered into a Licence Agreement which provides Neos with a licence to the Patents and US Patent No. 6,913,768, to make, market and sell NT-0202. Neos will pay Shire a royalty from the sales of NT-0202 until the expiration of the patents. Vipin K Garg, PhD, president and chief executive officer, of Neos, stated, “We are very pleased to have reached this settlement with Shire. Neos will continue to pursue FDA approval of NT0202 without further risk of delay due to this litigation.”
NeuroVive Signs Global Outlicencing Pact with OnCore Biopharma NeuroVive Pharmaceutial AB, a leading mitochondrial medicine company, has signed an exclusive global outlicencing agreement with the US biotechnology company OnCore BioPharma, Inc. related to the development and commercialisation of NeuroVive’s drug candidate NVP018 for oral treatment of chronic Hepatitis B Virus (HBV) infection. The agreement can give NeuroVive in total USD 150 million in conditional milestone payments plus royalties on future drug sales. “After extensive discussions with a number of leading pharmaceutical companies, I am delighted to announce that we have signed this agreement with OnCore, a strong partner that provides optimal resources to develop NVP018 from a stage of a promising drug candidate to a complete treatment for a global medical challenge. This confirms the financial potential inherent in our pharmaceuticals portfolio, and the revenues will allow us to further intensify our work in prioritised areas of mitochondrial medicine. I would also like to take the opportunity to put the spotlight on our COO Jan Nilsson, whose work has been critical to get this agreement in place,” commented NeuroVive’s chief executive officer, Mikael Brönnegård. The licensing agreement provides OnCore with the exclusive global rights to develop oral formulations of NVP018 for the treatment of chronic Hepatitis B infection. The compensation to NeuroVive consists of an initial upfront payment plus a number of conditional payments based on pre-determined milestones and as well payments relating to sales targets. In addition, NeuroVive will receive incremental royalty payments based on gross revenue from future sales of NVP018. The total value of the agreement is USD 150 million excluding royalty payments. The exact terms of the agreement regarding payments and royalty figures are not disclosed. September2014 57
pharma news Par Pharma Resumes Shipment of Generic Precedex Par Pharmaceutical Companies, Inc has resumed shipping dexmedetomidine hydrochloride (HCl) injection, EQ 100 mcg base/mL, the generic version of Hospira’s Precedex Injection. Par immediately resumed shipping after a US District Court lifted a temporary restraining order that was issued in August at Hospira’s request. Last month, Par received final approval from the US Food and Drug Administration for its Abbreviated New Drug Application for dexmedetomidine HCl injection, which is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures. Par’s dexmedetomidine HCl injection is packaged in 200 mcg/2 mL single-use vials (preservative free). According to IMS Health data, annual US sales of Precedex Injection are approximately USD 156 million. Due to the known pharmacological effects of dexmedetomidine HCl, patients should be closely monitored while receiving dexmedetomidine HCl. Use of dexmedetomidine has been associated with serious adverse reactions such as hypotension, bradycardia, sinus arrest and transient hypertension. Safety and efficacy have not been established for Procedural Sedation in pediatric patients. Additional information describing clinical studies in a different indication in which efficacy was not demonstrated in pediatric patients is approved for Hospira’s dexmedetomidine injection. However, due to Hospira’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. The use of dexmedetomidine HCl for procedural sedation in pediatric patients has not been evaluated. Par Pharmaceutical Companies, Inc is a privately held, USbased specialty pharmaceutical company that develops, manufactures and markets high barrier-to-entry generic drugs and niche, innovative proprietary pharmaceuticals through its wholly-owned subsidiary’s two operating divisions, Par Pharmaceutical and Strativa Pharmaceuticals.
S&D Pharma, Cipla Collaborate to Enter Czech Republic and Slovakia Cipla, a Rs 9,800 crore plus fifth largest Mumbai based pharma major, has entered into a commercial collaboration with S&D Pharma in the Czech Republic and Slovakia. This collaboration will enable Cipla to focus on its core therapy areas, while S&D Pharma will be the key partner for generics. 58 September 2014
Under the collaboration, Cipla will be driving its respiratory product portfolio in both Czech Republic and Slovakia through a Cipla owned sales force team, managed by Cipla commercial head. S&D Pharma will physically distribute all products, including respiratory products, and this portfolio will increase over the next few years. Frank Pieters, head Cipla Europe said, “We are excited to partner with S&D Pharma and believe that this collaboration will enable us to drive access in the Czech Republic and Slovakia across therapy areas in the coming years.” Daniel Straus, CEO S&D Pharma said, “We are delighted to extend our cooperation with such an innovative company as Cipla and to have the opportunity to further develop the Cipla brand and portfolio in our markets. Through this collaboration we have secured a competitive and varied product pipeline for the future and very much look forward to contributing to the future success of Cipla’s respiratory range.” In the near future, once the necessary regulatory and reimbursement approvals are in place, the salmeterol-fluticasone fixed combination will be launched in both markets under the name Fullhale. With Fullhale we will offer in Czech Republic and Slovakia an alternative which is effective and efficient and therefore brings many advantages into a market which suffers from limited resources.
Venus, Mylan Sign Pact to Market Meropenem in 3 EU Countries Venus Pharma GmbH, Germany, a wholly owned subsidiary of Venus Remedies has entered into a distribution-cum-out-licencing agreement with Mylan to market its generic broad-spectrum antibiotic, Meropenem, in three European countries of Denmark, Sweden and Finland for a period of five years. Venus already has a non-exclusive marketing tie-up with Mylan for the same product in France, where the drug has been successfully launched and is contributing to the company’s top and bottom lines. Meropenem belongs to the carbapenem class of antibiotics and can be used effectively in both children and adults. The global annual generic sales drug is USD 1,879 million in 2012 and estimated to grow at a compounded annual growth rate of 7.5 per cent to reach around USD 2,100 million in 2014-15. The drug is a broad-spectrum antibiotic used in ICU infections as a last resort for the treatment of life-threatening infections. As per IMS Health, the market size for this product in Denmark, Sweden and Finland is approximately Euro 12.54 million. Pharma Bio World
biotech news MorphoSys Gets Research Grant from BMBF MorphoSys AG, a leading biotechnology company, announced the receipt of a grant of up to EUR 1 million from the German Federal Ministry of Education and Research (BMBF), comprising funding for two of its therapeutic antibody programmes. The funding will support the company in developing Ylanthia antibodies against two undisclosed G protein-coupled receptors (GPCRs). The grant will cover all necessary steps involved in the early drug development stages and will run for two years. The superfamily of G protein-coupled receptors is the single largest and most important family of drug targets. Receptors of this class play a central role in many biological processes and are linked to a wide range of diseases. However, due to immense technical difficulties in generating selective and potent antibodies against this target class, only one GPCRtargeted antibody drug has been approved so far. With the help of its advanced proprietary technologies, first and foremost its next-generation antibody platform Ylanthia, MorphoSys is able to exploit the full potential of therapeutic antibodies against GPCRs. “We are delighted to receive this valuable support from the German government. Our Ylanthia platform is the perfect fit for therapeutic antibody discovery, especially against technically challenging targets. By applying our antibody capabilities to the discovery of novel therapeutics against GPCRs, we are opening up a whole range of new product opportunities,” commented Dr Marlies Sproll, chief scientific officer of MorphoSys AG.
Tute Genomics Launches MyGene Portal for Genome-Guided Medicine Tute Genomics announced the launch of MyGene, a patient portal that puts genome sequencing results at the fingertips of the individual where it is most useful and actionable. The USD 1000 was announced earlier this year by Illumina, which is thought by many to be the tipping point towards widespread adoption of genome sequencing in research and clinical settings. With 6 billion letters and 4 million variants per human genome, data analysis has become the bottleneck. To enable genome-guided medicine, Tute Genomics has created a cloud-based platform that allows healthcare organisations and researchers to analyse entire human genomes to quickly Pharma Bio World
Biotech news.indd 59
go from DNA to diagnosis or discovery. The addition of MyGene opens a new door for patient-centric, personalised medicine. MyGene was unveiled at TEDMED, where Tute Genomics was selected from among hundreds of companies worldwide to participate in The Hive, an immersive social environment dedicated to exploring and showcasing transformative startups and the inspiring entrepreneurs who power them. TEDMED, an affiliate of the TED organization, is a global community dedicated to unlocking imagination in service of health and medicine, and features demonstrations of the best new ideas accelerating healthcare.
Taiwan Approves ThromboGenics’ Jetrea ThromboGenics NV, an integrated biopharmaceutical company focused on developing and commercialising innovative ophthalmic medicines, has announced that Jetrea (ocriplasmin) has been approved in Taiwan. The approval has been granted following priority review by the Taiwan health authority. Taiwan is the third country in Asia to grant Jetrea approval, following approvals in Singapore and Malaysia.ThromboGenics’ partner Alcon, which is commercialising Jetrea outside the US, will be responsible for the launch of the drug in Taiwan.
Ganeden Biotech Announces GanedenBC30 for HIV+ Population Ganeden Biotech announced that a new study has been published in the peer-reviewed publication, AIDS Research and Human Retroviruses. The study was a randomised, double blind and placebo controlled trial in HIV positive subjects who consumed either 2 billion CFU of GanedenBC30 daily or a matching placebo for 90 days. This study demonstrated that GanedenBC30 supports both digestive and immune health in HIV subjects. The study also provided additional evidence that even in an immunecompromised subject group, there is an absence of safety concerns when consuming GanedenBC30 on a daily basis. “This research further builds on the science supporting the benefits of GanedenBC30,” said David Keller, VP of Scientific Operations at Ganeden Biotech. “Now not only do we have data that GanedenBC30 is safe for individuals with a healthy immune system, but this study provides evidence which supports safety in an immune-compromised population.” September 2014 59
19-09-2014 19:45:53
biotech news CIRM Awards USD 16.6 mn Grant to ViaCyte to Expand Clinical Development of VC-01 Diabetes Therapy Candidate ViaCyte, Inc., a privately held regenerative medicine company developing a stem cell-derived islet replacement therapy for the treatment of diabetes, called VC-01, has been selected to receive a USD 16.6 million Accelerated Development Pathway Award from the California Institute for Regenerative Medicine (CIRM). According to CIRM, the Accelerated Development Awards were created to “provide selected applicants who are making rapid progress with additional resources and financial support to accelerate their stem cell-based therapy towards demonstrating evidence of an acceptable safety profile and clinical proof of concept.” ViaCyte’s innovative stem cell-based therapy, which is initially targeting type 1 diabetes, has been supported by several prior rounds of funding from CIRM. The financial and technical support from CIRM has played a crucial role in the development of VC-01, which was recently cleared by the US Food and Drug Administration (US FDA) to begin evaluation in human clinical trials. ViaCyte’s VC-01 combination product candidate consists of pancreatic progenitor cells, called PEC-01 cells, derived from a proprietary human stem cell line, encapsulated in ViaCyte’s proprietary Encaptra device. When implanted under the skin, the PEC-01 cells are designed to mature and further differentiate into insulin-producing beta and other endocrine cells that regulate blood glucose in a manner similar or identical to the islets that normally comprise the endocrine pancreas. “Once again we are expressing our gratitude to CIRM and the citizens of California for supporting the work we are doing to develop a new approach for the treatment of type 1 diabetes and concurrently demonstrate the potential of stem cell-derived therapy,” stated Dr. Paul Laikind, president and chief executive officer, of ViaCyte. “Today’s grant allows us to continue to accelerate our efforts as we move into the critically important stage of evaluating VC-01 in human clinical trials.” ViaCyte recently announced the acceptance of its Investigational New Drug (IND) Application by the FDA, which allows clinical testing of the VC-01 product candidate to commence. CIRM funding will help support the recently initiated phase 1/2 clinical trial in patients with type 1 diabetes, as well as additional clinical testing in the future. JDRF, the leading global organisation 60 September 2014
Biotech news.indd 60
focused on type 1 diabetes research, is also providing support for the VC-01 development programme. The phase 1/2 clinical study will evaluate the VC-01 product candidate directly in patients with type 1 diabetes who have minimal to no insulin-producing beta cell function. In addition to evaluating the safety of the product candidate in these patients, the study is designed to demonstrate the effectiveness of the VC-01 product candidate in replacing the lost endocrine function that is central to the disease. In an open-label, dose-escalating format, ViaCyte expects to enroll approximately 40 patients in the study at multiple clinical sites. Type 1 diabetes mellitus (previously called juvenile diabetes) is a life-threatening chronic condition in which the pancreas produces little or no insulin, a hormone needed to allow glucose to enter cells to produce energy. It is typically diagnosed during childhood or adolescence, though it can also arise in adults. Though less common than type 2 diabetes, which occurs when the body becomes resistant to insulin, type 1 diabetes affects several million Americans, according to JDRF. Currently, there is no cure for type 1 diabetes and the risk of long-term complications is high even with diligent treatment. Standard treatment involves multiple daily injections of insulin and rigorous management of diet and lifestyle.
Cellectis Sells Swedish Subsidiary to Takara Bio Cellectis, a leader in the development of adoptive immunotherapies based on engineered allogeneic CART cells (UCART), has closed the sale of its subsidiary Cellectis AB to Takara Bio Inc., an innovative biotechnology company based in Shiga, Japan. The financials terms have not been disclosed. The company now concentrates its activities in the field of oncology through the development of Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy products generated through its allogeneic CAR-T platform, both on its own as well as in partnership with Servier and Pfizer. Cellectis is a biopharmaceutical company focused on oncology. The company’s mission is to develop a novel generation of therapy based on engineered T-cells to treat cancer. As a world leader in biotechnology research and development, Takara Bio was the first company to market PCR technology in Japan and is also the developer of the RetroNectin reagent, which is a world-standard in gene therapy protocols. Pharma Bio World
19-09-2014 19:46:16
Bag Filter Housing
Air Driven Boiler Tube Cleaner
Bag filter system is designed for optimum filtration performance. Its range provides filtration solution for a broad variety of fluid applications in the process industry. They are particularly useful for filtering large volumes of high viscosity liquids. Bag filter is constructed of filter housing, filter bags, internal cage to support bags, positive sealing arrangement and choice of end connections. The internal support ensures bags will not burst as high differential pressures build up during operation. For more information, please contact: Filter Concept Pvt Ltd 302 Aalin, Ashram Road Ahmedabad, Gujarat 14 Tel: 079-27541602 E-mail: info@filter-concept.com
The tubes and piping of boiler heat exchangers and condensers must be kept clean in order to maintain 100 per cent production efficiency and to prevent damage to the boiler due to overheating. DBX Tools developed new pneumatic boiler and heat exchanger tube cleaner, which cleans tubes thoroughly by mechanical means. This air motor along with cutter or brush goes inside the tubes of vessels and cleans the tubes. This system consists of few moveable parts, easy to operate, faster, economical and versatile. It saves more manpower and time for handling tube cleaning job, gives polished inner surface, can clean straight and bent tubes (even U-bents) of any length from tube ID 25 up to 150 mm. Air pressure required is 6 kg. For more information, please contact: DH Boiler Exchangers Tools Pvt Ltd 3101 Bhandup Indl Estate, Pannalal Silk Mill Compound LBS Marg, Bhandup (W), Mumbai 400 078 Tel: 022-66711682, 25948419, 25948120, Fax: 91-022-25948419 E-mail: dh.boilertools@gmail.com / info@dbxtool.com
Modular Mechatronic Systems ACOPOSmotor sets new standards for decentralized motion control. With the ACOPOSmotor, B&R combines a servo motor and drive in one compact unit. Safety technology can also be integrated as an option. This gives developers more freedom when designing a machine and can save valuable space in the control cabinet. The ACOPOSmotor is connected to the drive network using a hybrid cable. This cable includes all necessary power and signal lines and establishes the connection to the POWERLINK network. ACOPOSmotor modules come in three sizes with torque ranging from 1.8 to 12 Nm. If needed, an optional fan assembly can provide a performance boost of up to 100%. In addition to the proven wired safety functions STO (Safe Torque Off) and SS1 (Safe Operational Stop 1), a network-based ACOPOSmotor module variant will also be available in the future. This will allow users to access the following functions (as with the ACOPOSmulti): STO, SOS, SS1, SS2, SLS, SMS, SLI and SDI. The ACOPOSmotor is fully compatible with the ACOPOSmulti drive system. This makes it possible for users to select the best-suited servo drive for each machine without having to do any additional engineering work. 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 Email: shyam.padwal@br-automation.com
Pharma Bio World
Product Final 2.indd 61
September 2014 ď‚„ 61
19-09-2014 19:48:49
Condenser Tube Cleaner
Auto Coater All the product contact parts are made from SS-316. Pan speed 1 to 15 RPM. The pan speed is variable and can be changed from the control panel. Perforated pan with more than 55 per cent opening for better quality finish. Pan speed control is via variable frequency AC drive. The coating pan along with the drive system, hot air plenum, exhaust plenum, pan washing sink, washing pipeline, etc, are housed in a SS cabinet. CIP system include high-pressure pumps and jet nozzles; Schnider make PLC-based control panel with coloured touch screen; HMI and 80 column printer. For more information, please contact: Brilliant Pharma Machinery Unit Nos: 1, 2 & 14, Modern Indl Estate Next to Paras Indl Estate, Opp: IPOL, Waliv Phta, Vasai (E), Dist: Thane Maharashtra 401 208 Tel: 0250-3293636, 2454015, Fax: 91-0250-2454015 E-mail: brilliantpharma@rediffmail.com / sales@brilliantpharmaa.com
To function efficiently, every tube of condenser must be kept clean in order to maintain production efficiency and to prevent permanent damage from overheating. DBX Tools developed new condenser tube cleaner consisting of a pneumatic or electric motor with water feeding attachment. The motor drive various cleaning tools by means of driven shafts and cutter brush. Water is supplied through the shafting by a feed attachment on the motor and is used to flush away the deposit removed by the tool. Best for removing extremely hard scale from straight tubes of condenser and heat exchangers from 9 to 28 mm ID. For more information, please contact: DH Boiler Exchangers Tools Pvt Ltd 3101 Bhandup Indl Estate, Pannalal Silk Mill Compound LBS Marg, Bhandup (W), Mumbai 400 078 Tel: 022-66711682, 25948419, 25948120 Fax: 91-022-25948419 E-mail: dh.boilertools@gmail.com / info@dbxtool.com
Titrator Hanna Instruments offers two new automatic titration systems utilizing 40,000 step dosing pump - the HI 903 Karl Fischer volumetric titrator and the HI 902C2 two channel potentiometric titrators. The HI 903 Karl Fischer volumetric titrator conducts moisture analysis, combining an ultra-precise titrant delivery system with a magnetic stirrer, sophisticated endpoint determination and background drift correction algorithm. The titrant delivery system is capable of dosing as little as 0.125 μL of titrant maintaining a minimal amount of drift rate. The HI 903 also features a unique anti-diffusion tip preventing unwanted diffusion of titrant into the solvent. These features allow for a 0.1% accuracy when measuring water content from 100 ppm to 100%. The HI 902 Potentiometric Titrator supports two analog inputs allowing sequential titrations to be performed with different sensors for the precise analysis of acid/base, ISE, Oxidation Reduction Potential (ORP), and complexometric reactions. Both titrators offer Hanna’s unique “Clip Lock” Exchangeable Burette system for quickly and easily swapping burettes with reagents used to perform different titrations. The other advantage of the Clip Lock Exchangeable Burette system is the ability to utilize burettes of different sizes (5, 10, and 25 mL) allowing for flexibility in the accuracy (0.1% full burette volume) and the minimum amount of titrant that is dosed. For more information, please contact: Hanna Equipments (India) Pvt Ltd Aum Sai Bldg, 3/4/5/6, 1 st Floor Plot No: 23-C, Sector 7, Kharghar, Navi Mumbai 410 210 Tel: 022-27746554, 27746555, 27746556 E-mail: marketing@hanna-india.com
62 September 2014
Product Final 2.indd 62
Pharma Bio World
19-09-2014 19:49:12
Polishing Filters
Habonim Line of Clean Ball Valves
Single or multibag polishing filters are basically used for postfiltration. Baskets are fitted with quick opening type arrangement. Filter bags used on polister, PP, PPS or special material depending on the process. It finds application in edible oil industries and chemical and pharma industries.
The 48 TuBore Series is the Habonium line of clean ball valves for the pharma and bioprocessing industries. These valves are designed for applications which require maximum flow capacity of minimum pressure drop, where sterility, cleanability and drainability are essential for faultless product quality. The 48 TuBore valve port matches tube ID dimensions, provides light shut-off and has exceptional performance in many servicc applications. A fully encapsulated body seal provides an improved seal under fluctuation temperatures and pressures.
For more information, please contact:
For more information, please contact:
SAP Filter Pvt Ltd Plot No: A-5, Sector 1, Vasai Taluka Indl Co-op Estate Ltd Goraipada, Vasai (E), Thane, Maharashtra 401 208 Tel: 0250-2458982, 2023040, 3208273, 2450366 Fax: 91-0250-2481095 E-mail: info@sapfilter.com / sales@sapfilter.com
Jasubhai Engineering 64/A, GIDC Indl Estate, Phase 1 Vatva, Ahmedabad, Gujarat 382 445 Tel: 079-25831042 Fax: 91-079-25831825 E-mail: Mumbai@jasubhai.com
Ergonomic Machine Operation B&R offer new line of swing arm systems in wide range of variants and feature IP65 protection, allowing them to be placed optimally on machines. Multi-touch widescreen panels are available in sizes ranging from 18.5” to 24” with either HD Ready or Full HD resolution. The larger displays and higher resolution make it possible to include even more information on each screen.
existing HMI applications in any way.
A 21.5” model in portrait format is also available. With optional side handles, it is easy to maneuver and operate these devices at the machine. Two system variants with analog resistive touch screens are also available in 4:3 format, allowing users to upgrade their operator hardware without having to modify their
These swing arm systems can be equipped with buttons, selector switches, key switches and an integrated E-stop button as needed. Thanks to an integrated RFID reader, individual access rights can be assigned to anyone from service engineers to system operators. Displays from the Automation Panel Series are available in 9 different swing arm models and can be equipped with additional switching elements as needed. 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 Email: shyam.padwal@br-automation.com
Pharma Bio World
Product Final 2.indd 63
September 2014 63
19-09-2014 19:49:12
events diary
Indian Pharma Expo 2014
BioPharma India Convention
Date: 11th – 12 th October 2014
Date: 18 th – 19 th November 2014
Venue: Pragati Maidan, New Delhi
Venue: Hyatt Regency, Mumbai
Indian Pharma Expo 2014 provides an opportunity for the participating companies to display their products & services to the gamut of visitors, globally from pharma and healthcare industries. The two day expo will bring together eminent personalities from various sectors of pharma, non-pharma and healthcare industries. IPE-2014 is one stop juncture to all those who are planning to expand their business through various channels of franchise and distribution; as well as wholesalers and hospital purchase personnels who seek to buy bulk products on concessional rates. Contact: Alok Sharma Tel : +91-22-66122646 | Mobile: +91-9819224222 Email: alok.sharma@cims.co.in
Bio Pharma India Convention 2014 Date: 10 th – 11th November 2014 Venue:Hyatt Regency, Mumbai
BioPharma India Convention is a perfect platform for pharma and medical professionals to understand the biopharmaceutical sector in depth. The conference will highlight the new opportunities available in Indian biopharmaceutical sector. The conference is scheduled at the Grand Hyatt, Mumbai. Topics of the conference will be drug discovery and clinical trails to manufacturing. Professionals will get an opportunity to meet more than 80 speakers, 800 decision makers and 500 products. Be a part of this conference to know the latest developments in pharmaceutical sector and build business rapport with associates. Contact: Rebecca Koh Terrapinn Pte Ltd, 1 Harbourfront Place #18-01 Harbourfront Tower 1, Singapore 098633 Tel: +65 6322 2725 | Fax: +65 6271 2035 Email: rebecca.koh@terrapinn.com
5 th Annual Pharmacovigilance Asia 2014
BioPharma India Convention is a perfect platform for pharma and medical professionals to understand the biopharmaceutical sector in depth. The conference will highlight the new opportunities available in Indian biopharmaceutical sector. The conference is scheduled at the Grand Hyatt, Mumbai. Topics of the conference will be drug discovery and clinical trails to manufacturing. Professionals will get an opportunity to meet more than 80 speakers, 800 decision makers and 500 products. Be a part of this conference to know the latest developments in pharmaceutical sector and build business rapport with associates.
Date: 25 th – 27 th November 2014
Contact:
Contact:
Terrapinn Pte Ltd 1 Harbourfront Place #18-01 Harbourfront Tower 1, Singapore 098633 Tel: +65 6222 8550 | Fax: +65 6226 3264 Email: enquiry.sg@terrapinn.com
IQPC Worldwide 61 Robinson Road Robinson Center, #14-01, Singapore 068893 Tel: +65 6722 9388 | Fax: +65 67203804 Email: enquiry@iqpc.com.sg
64 September 2014
Events.indd 64
Venue: Grand Copthorne Waterfront Hotel, Singapore Pharma/Biotech companies are faced with the challenge of finding solutions that can improve the quality and analysis of safety data, while managing the increase in the quantity of data and the need to satisfy regulatory requirements. It is this developing threat environment and the challenges facing pharmacovigilance professionals that the 5th Annual Pharmacovigilance Asia Summit will be addressing
Pharma Bio World
19-09-2014 19:49:51
bookshelf Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs (Paperback) Author: Rodney J Y Ho Price: USD 132.40 No of Pages: 744 pages About the Book: Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs, Second Editionaddresses the pivotal issues relating to translational science, including preclinical and clinical drug development, regulatory science, pharmacoeconomics and cost-effectiveness considerations. The new edition also provides an update on new proteins and genetic medicines, the translational and integrated sciences that continue to fuel the innovations in medicine, as well as the new areas of therapeutic development including cancer vaccines, stem cell therapeutics, and cell-based therapies.
Biopharmaceutical Supply Chains: Distribution, Regulatory, Systems and Structural Changes Ahead (Hardcover) Author: Robert Handfield Price: USD 72.85 No of Pages: 272 pages About the Book: A comprehensive exploration of the massive changes in the biopharmaceutical supply chain that have occurred during the past 10 years, and predicted future trends, Biopharmaceutical Supply Chains: Distribution, Regulatory, Systems and Structural Changes Ahead documents the specific impacts of these changes for key players in the supply chain.Based on interviews with industry professionals, the book presents an overview of the key challenges and discusses how leading biopharmaceutical companies handle these challenges.
Applied Biopharmaceutics & Pharmacokinetics, Sixth Edition (Hardcover) Authors: Leon Shargel, Andrew Yu, Susanna Wu-Pong Price: USD 60.75 No of Pages: 811 pages About the Book: Applied Biopharmaceutics & Pharmacokinetics, Sixth Edition provides you with a basic understanding of the principles of biopharmaceutics and pharmacokinetics and applies these principles to drug product development, drug product performance and drug therapy. The revised and updated sixth edition is unique in teaching basic concepts that relate to understanding the complex issues associated with safe and efficacious drug therapy.Practical problems and clinical examples with discussions are included in each chapter to help you apply these principles to patient care and drug consultation situations.
Pharma Bio World
Bookshelf.indd 65
September 2014 ď‚„ 65
19-09-2014 19:50:28
ad index Sr. No
Client’s Name
1
Ani Engineers
2
B & R Automation
Front Cover
3
Bhavya Polymers
47
4
Busch Vacuum India Pvt Ltd
11
5
Chemlin Pumps & Valves Pvt Ltd
49
6
ChemTECH World Expo 2015
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Citizen Industries De Dietrich Process Systems India Pvt Ltd DIA India 2014 Dover India Pvt Ltd Emjay Engineers Fristam Pumps India Pvt Ltd Frost & Sullivan Glatt (India) Pharma Engineering Pvt Ltd Inos Tech Kimberly-Clark Hygiene Products Pvt Ltd M K Silicone Products Pvt Ltd Mist Resonance Engg Pvt Ltd NNE Pharmplan (India) Pvt Ltd Pharma + Biotech World Expo 2015 Praj HiPurity Systems Ltd
22 23 24
SPX Flow Technology (India) Pvt Ltd SSP Pvt Ltd Verder India Pumps Pvt Ltd
19
25
West Pharmaceutical Services Pvt Ltd
25
26
Refining & Petrochemicals 2015
45
27
WaterEX World Expo 2015
67
66 September 2014
Ad Index.indd 66
Page No
43
Inside Cover II 21 5 35 9 43 51 33 17 29 13 49 47 23 Inside Cover I Back Cover 37 7
Pharma Bio World
19-09-2014 19:51:27
R.N.I. No.: MAHENG/2002/08502. Date of Publication: 26th of every month. Postal Registration No: MH/MR/SOUTH-284/2014-16 Posted at Patrika Channel Sorting Office, Mumbai 400001, on 26th & 27th of every month. Total Pages:- 68