Pharma Bio World - October 2014 by Pharma Bio World

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PHARMA BIO WORLD R.N.I. No.: MAHENG/2002/8502 Chairman

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Pharma Bio World

FEATURES 12

Quality Control, Quality Assurance Certification for Phytopharmaceuticals – M N V Prasad

Protection of Traditional Knowledge – Sindhu Vijayakrishnan, Lakshmi Rajagopal, Meenakshi Chotia

Herbal Research in India @ Crossroads – Dr Gopakumar G Nair

Ebola Outbreak 2014: An Overview of the Experimental Therapeutics – Shailendra K Saxena, Santosh Dahal

Technology Transfer: Significance and Bottleneck in Pharmaceutical Industry – Dr Vivek Dave, Deepika Shukla, Dr Sachdev Yadav

Drug Abuse Liability Study: A Category Analysis – Siddhartha Shaurabh

Diabetes Care: New technologies in the Fight Against a Global Pandemic – Dr Johannes Rauschnabel

Regaining FDA’s Confidence in India’s Generic Drug Exports – C Gowri Shankar

The Irish Cluster is Delivering – Barry Heavy

NEWS UPDATE 55

Press Release

56 57

Pharma News

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CORPORATE AFFAIRS Product Trends Events Diary

BACKYARD Book Shelf Ad Index Next Issue Focus: Pharmaceutical Excipients

8  October 2014

Pharma Bio World

Quality Control, Quality Assurance Certification for Phytopharmaceuticals If phytopharmaceuticals are to be regarded as rational drugs, they need to be standardised and pharmaceutical quality has to be approved. This article will shed light upon the criteria of quality assurance and quality control of phytomedicines.

M N V Prasad

Department of Plant Sciences University of Hyderabad 12 October 2014

ndia has a very rich diversity of medicinal and aromatic plants (MAP). However, due to undesirable contaminants, export is negatively affected. The transfer of trace elements by MAPs could be beneficially used in bio-fortification programmes to increase human uptake of essential micronutrients such as Se, Fe and Zn. India has 15 agro climatic zones and about 18,000 species of flowering plants of which nearly 7,000 are believed to have healing properties and are used in Indian System of Medicine viz., folk medicine, ayurveda, siddha, unani and homoeopathy including modern medicine. There are about 7000 ﬁrms manufacturing traditional medicines with or without standardisation (Dubey et al 2004). In the recent past there has been considerable interest in drugs obtained from plants than at any time in history. About 960 species of medicinal plants are estimated to be in trade both nationally and internationally of which 178 species have annual consumption level exceeding 100 tons per year. It is being observed that there is a global resurgence in traditional and alternative health care systems resulting in growing world herbal trade which stands currently at USD 120 billion and is expected to reach USD 7 trillion by 2050.

view – the standards are based on WHO standards. The compliance checking will be done by independent, third party agencies conforming to international standards. Any producer/collector or group of producers/collectors can obtain certification from the designated certification body (CB). The notified CB will undertake surveillance and monitor the herbal materials and products. In the recent past there has been interest in the development of new commercial drugs from herbal materials and to reestablish traditions of yesterday as drugs of tomorrow (Gurib-Fakim 2006). The two commonly used terms related to herbal products quality are: Quality Assurance [QA], it is a wideranging concept that covers all matters that individually or collectively influences the quality of a drug. It is the total of the organised arrangements made with the objective of ensuring that drugs are of the quality required for their intended use. Quality Assurance therefore incorporates Good Manufacturing Practices, along with associated factors.

In order to attract international and national market they must have “good quality tag”.

Quality Control (QC) is the part of Good Manufacturing Practices [GMP] that is concerned with sampling, specifications, testing, documentation and release procedures. This approach ensures that materials are not released for use, and that drugs (are not) released for sale or supply, until their quality has been deemed satisfactory.

To implement this Government of India very recently launched the quality control and assurance jointly by the National Medicinal Plants Board (NMPB) and the Quality Council of India (QCI). According to QCI, the scheme has been designed keeping best international practices in

Good Manufacturing Practices (GMP) are the part of Quality Assurance that ensures that drugs are consistently produced and controlled in such a way as to meet the quality standards appropriate to their intended use, as required by the marketing authorisation. Pharma Bio World

However, there is a vast gap between demand and supply due to plan material availability becoming rare. Since agrotechnology is not known for many of the important plants, I vitro methods are to be established. Several of these plants are to be collected from nature. Some of the Existing Framework for QC/QA The World Health Organisation (WHO): The WHO recognises that the traditional use of herbal medicines with long historical use and that these may be accepted by national authorities WHO plays a greater role in reducing the undesirable side effects and morbidity especially among impoverished populations. A generalaised MAPs supply chain. Procurement of herbal raw materials for development and production of quality and safe phytomedicines. Several of products are is short supply for indigenous requirements and also due to fluctuating market price.

Owing to the great variability in plant chemical composition that results from factors to which plants are exposed during their growth, storage and different stages of manipulation, characterisation and/or standardisation of phytopharmaceuticals are necessary. Standardisation of herbal preparations should allow the knowledge of their composition and prevent, or at least make less likely, the consumption of drugs of questionable quality. The latest pharmacopoeias, attempts at standardisation, prescribe methods, usually chromatographic, for the analysis and quality control of medicinal products of plant origin (Prasad 2008). Microbiological contamination and foreign materials are important quality criteria in the testing of medicinal plants. As with any product from agricultural or wild sources, medicinal plants can be contaminated by organic or inorganic substances of natural or synthetic origin, such as insects, microorganisms, eg, fungi and their mycotoxins heavy metals (Chizzola and Franz 1996; Figura et al., 14 ď&#x201A;&#x192;October 2014

1998, Prasad 2008, Sathiyamoorthy et al., 1997; Wong and Koh 1986; Wong et al., 1993; radioactive materials (Karavaeva and Molchanova, 1998). Glocal demand (global +local = glocal) for plant raw materials (medicinal value) is increasing : Safety (undisclosed t o x i c c o n t a m i n a n t s ) , e f f i c a c y, affordability, availability of bioactive molecules and nutraceuticals as per consumer choice, promising plant products for the treatments for major diseases HIV/Malaria/TB/Cancer/ Diabetes etc. is gaining momentum. Several of the bioactive molecules and nutraceuticals act as: Adaptogen, Anticancer, Antidiabetic, Antidiarrhoeal, Bioavailability enhancers. Brain tonics, Antiasthmatic, Antihypertensive, Antiulcer, Antiurolithiatic, Hepatoprotective, Carminative stomachic and Purgative.

European Union (EU): The EU directives 2001/83/EC on the Community code relating to medicinal products for human use lays down a general framework for pharmaceutical products requiring pre-marketing approval before gaining access to the market and laying down the requirements for the documentation of quality, safety and efficacy. This framework has effectively been in operation and additionally the European Agency for the Evaluation of Medicinal Plant Products acts as a central agency for European medicines. However, individual Member States (UK, Germany, France, Italy etc.) have taken different approaches in reviewing herbal medicines. The United States (US): In the US, the Food and Drug Adminsitration (FDA) has responsibility for food and dru g pro duc ts . Drug s are regarded as products that claim to treat, cure,

Standardisation of herbal preparations should allow the knowledge of their composition and prevent, or at least make less likely, the consumption of drugs of questionable quality. Pharma Bio World

GAP = Good Agricultural Practice GCTP = Good Clinical Trial Practice GHP = Good Harvesting Practices GLP = Good Laboratory Practice GMO = Good Manufacturing Practice GSP = Good Sourcing Practice SOP = Standard operating procedures

Factors influencing the Quality, Safety and Efficacy of herbal products

mitigate or prevent a disease. Herbal medicines follow the same procedures as those for a chemical drug. Otherwise natural products are regulated as foods under a requirement for ingredients to be generally recognised as safe (GRAS). Natural products generally have GRAS status, provided that this is supported by expert concensus. Hence dietary supplements and herbs are considered to be foods provided that they are generally regarded as safe and do not make medicinal claims. Furthermore, the ingredients and the plants or parts of the plants must be quantiﬁed and where, ingredients are listed with a pharmacopeial reference, they must meet the standard laid down in the pharmacopeia. There are also speciﬁc requirements for food additives that do need a pre-market approval by the authority. Unless certified by the national and international standards marketing of phytoproducts in international market will not be possible under the current regulations. 16 October 2014

References 1) Chan, K. (2003) Some aspects of toxic contaminants in herbal medicines, Chemosphere 52: 1361–1371. 2)Chizzola, R., and Franz, C. (1996). Metallic trace elements in medicinal and aromatic plants from Austria. J. Appl. Bot.Angew. Bot. 70, 52-56. 3)Dubey NK, Kumar R, Tripathi P (2004). Global promotion of herbal medicine: India’s opportunity. Current Science; 86(1):37–41. 4)Ernst, E., (2004). Risks of herbal medicinal products. Pharmacoepidemiology and Drug Safety 13, 767–771. 5)Figura, B., Pluta, J., and Lorenz, K. (1998). Assessment of the level of certain heavy metals in Polish galenic preparations. Pharmazie 53, 458-462. 6)Gurib-Fakim, A., (2006). Medicinal plants: traditions of yesterday and drugs of tomorrow. Molecular Aspects of Medicine 27, 1–93. 7) Karavaeva, E. N., and Molchanova, I. V. (1998). Accumulation of radionuclides

by medicinal plants in the zone of impact from the Beloyarskaya nuclear power plant. Russ. J. Ecol. 29, 357359. 8)Prasad M.N.V. (2008) Trace elements in traditional healing plants - remedies o r r i s k s , I n . M . N . V. P r a s a d ( e d ) Tr a c e e l e m e n t s a s c o n t a m i n a n t s and nutrients: consequences in ecosystems and human health. John Wiley and Sons Inc. New York. pp. 137-160 9)Sathiyamoorthy P, Vandamme P, Oven M, Gologoldhirsh A. (1997) Heavy metals in medicinal and fodder plants of the Negev desert. J Environ Sci Health;32:2111-2123. 10)Wong, M. K., and Koh, L. L. (1986). M e r c u r y, l e a d a n d o t h e r h e a v y metals in Chinese medicines. B i o l . Tr a c e E l e m . R e s . 1 0 , 9 1 - 9 7 . 11)Wong, M. K., Tan, P., and Wee, Y. C. (1993). Heavy-metals insome Chinese herbal plants. Biol. Trace Elem. Res. 36,135-142. Contact: prasad.heavymetal@gmail.com Pharma Bio World

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Protection of Traditional Knowledge This article explores legal and policy developments in India regarding the protection of traditional ethnopharmaceutical knowledge.

Sindhu Vijayakrishnan Sr Associate K&S Partners, I P Attorneys

Lakshmi Rajagopal

Sr Associate K&S Partners, I P Attorneys

Meenakshi Chotia

Associate K&S Partners, I P Attorneys 18 October 2014

volution of ideas, of thoughts and knowledge for betterment of society has always had prominence, at times passed from one generation to another and taking the form of Traditional Knowledge; sometimes recorded and at times lost in translations. The knowledge however becomes part of national heritage, depicting within its intricacies age old ideologies requiring protection and safe keeping. Additionally, with the face of Traditional Knowledge constantly changing and its fragile nature demanding existence, it is imperative that measures be taken to safe-guard age-old concepts and ideas. This is also reinforced by the fact that monopoly is sought for such innovations which have been derived or developed by local/indigenous communities; and form part of their Traditional Knowledge and heritage. Therefore, the question then arises that on whom lies the responsibility of ensuring nonexploitation of such innovations. A part of the onus for protecting such knowledge lies with legal systems of a country, also bound by their Intellectual Property laws in the sectors of Patents, Trademarks and Geographical Indications etc. In the area of Patents, prior to grant of a Patent Application, there are various checkposts in place to ensure that no invention relating to any form of Traditional Knowledge is monopolised. One of the most popular ways of screening is by conducting searches by Patent Officials and issuance of search/ examination reports citing any documents relevant to the Patent Application. Such reports often cite any relevant literature, like Patent/Non-Patent documents which include information on Traditional Knowledge as well. In this regard, to maintain uniform prosecution across the four Indian Patent Offices and to bring further transparency to the public, Office of the Controller General of Patents, Designs and Trademarks, has published guidelines for processing of Patent Applications relating to Traditional Knowledge and Biological Material. These guidelines

also elucidate six ‘Guiding Principles’, which provide clarity and helpful illustrations to showcase the parameters to be employed during examination of Patent Applications relating to Traditional Knowledge. Another jurisdiction specific mechanism employed in most countries is inclusion of explicit sections in their Intellectual Property Laws, which capture in essence their approach towards Traditional Knowledge. As an exemplification, India replete with flora and fauna has a rich reserve of traditions owing to the presence of various local communities. Hence, the Indian Patent laws have been drafted keeping this aspect in mind. Particularly, Section 3 of the Indian Patents Act, 1970, includes inventions which cannot be patented in India. Sections 3(p) and 3(e) are of special significance with respect to the area of Traditional Knowledge and provide Patent Officials with instruments to reject any Patent Applications relating to Traditional Knowledge. These sections hence safe-guard and prevent misuse of Traditional Knowledge by ensuring that innovators are unable to seek monopoly for such inventions in India. Often it has been observed that abundance of flora and fauna, and developments of tradition have mutually inclusive relation with each other. Hence, in order to cover this area as well, yet another provision under the Indian Patents Act, 1970, and the Biological Diversity Act, 2002, is the requirement of informing and/or seeking permission from the National Biodiversity Authority for using any biological material from India, contravention of which could attract penalty and/or imprisonment. The crux of these provisions is to firstly cinch that efficient tools are in place for combating bio-piracy as well as misuse of biological resource stemming from India is prevented. Secondly, these provisions also ensure that local/indigenous communities primarily responsible for use and safe-guarding of the biological resource are duly compensated. Pharma Bio World

The Indian Patent laws also provide for mechanisms of Revocations and Pre/Post Grant Oppositions. These mechanisms ensure that if any relevant documentary evidence or literature has been missed out by Patent Office during scrutiny process, then the public has opportunity to bring such documents to notice of the legal system. It is important to note here that such documentary evidence or literature can also include Traditional Knowledge related documents. Similarly, other jurisdictions also include their own check-posts and mechanisms to ensure that Traditional Knowledge is not misused or exploited in the process of seeking monopoly for an invention. For instance, European Patent laws have provision for filing Third Party Observations which bring to the notice of the Patent Office any documentary evidence previously not cited by the Examiner, but which may be used at his discretion. Hence, apart from the legal systems of various jurisdictions, the onus also lies with general public to protect and safe-guard Traditional Knowledge from being exploited. It is pertinent to note that entire Patent System broadly revolves around the triad of novelty, non-obviousness and industrial applicability of an invention. The parameters of novelty and non-obviousness depend solely on presence of any prior published document, including Traditional Knowledge related documents. However, in the past, not all such documents were readily available for scrutiny. This could be due to the fact that some of the documentary evidence on Traditional Knowledge dates back to centuries and form part of ancient texts not easily accessible. Further, most of these documents were scripted in local/ancient languages as well. Keeping this in mind, the ‘Traditional Knowledge Digital Library’ was initiated in the year 2001, as collaborative project between Council of Scientific and Industrial Research (CSIR); Ministry of Science and Technology and Department of AYUSH; and Ministry of Health and Family Welfare. Traditional Knowledge Digital Library [TKDL] is an Indian Database which contains 20 October 2014

documented literature relating to Ayurveda, Unani, Siddha and Yoga. It is a digitalised resource which provides single dynamic platform for all such traditionally known and/or used documented information. In order to make the platform user friendly and accessible to International Community, the Library is available in different languages such as English, German, French, Japanese and Spanish. Further, the Library has been classified into Traditional Knowledge Resource Classification (TKRC) system, which divides resources into Ayurveda, Unani, Siddha and Yoga sections. The TKDL has been designed in a format such that customised searches can be conducted within the Library to identify relevant documents. Hence, the TKDL revolves around providing single-point passage to the user in accessing ancient documented data, whose existence otherwise might have been unknown. Having said the above, it is surprising to observe that only fraction of the entire information uploaded on TKDL is available for viewing on their website. Even though plethora of documents has been uploaded and translated into various languages, they are not readily accessible to anyone who browses the website. Hence, without complete access to TKDL, it becomes difficult to classify if any ongoing research falls under the purview of Traditional Knowledge or is being derived from it. Without such information at hand, the larger question of whether the outcome of such research can be monopolised or simply commercialised remains ambiguous. On the contrary, if all the documents uploaded on TKDL were readily accessible, then a researcher could take an informed decision on whether to invest further in the research or even improve upon existing knowledge. For instance, in the current pharmaceutical world governed by erratic movements of an everdemanding society, objective of research is not to replicate existing information but to improvise on the same based on modern practices. Therefore, use of only Traditional Knowledge to cater to varying requirements of society is not a viable option. However, it would be interesting to determine over time

as to what would be the thin differentiating line that exists between the aspects of bio-piracy and true innovation without any motivation. Hence, to avoid stagnation of technological advancements, it is imperative that suitable steps be taken to develop a process to ensure that all documents are made accessible. However, to also avoid any misuse of information, the process developed could include aspects such as execution of non-disclosure/confidentiality agreements, dissemination of information on ‘need to know’ basis, monetary compensations etc. However, it is important to mention here that access to all documents of TKDL has been provided to selective Patent Offices across the world, such as Indian Patent Office, European Patent Office, United States Patent and Trademark Office, Japanese Patent Office, Australian Patent Office etc. by way of access agreements. This enables the Patent Offices to conduct holistic search and prevent misuse of Indian Traditional Knowledge as well. It is noteworthy to mention here that during prosecution, some of the International Jurisdictions, such as Australia, Europe etc. frequently cite documents obtained from TKDL for raising objections against patentability of Patent Applications. This reaffirms the fact that TKDL has become an integral part of the search conducted during prosecution of a Patent Application. In fact various jurisdictions have either established or are contemplating initiation of similar platforms for compiling documents and literatures relating to their Traditional Knowledge and practices. Hence, the unmitigated contribution of TKDL in preservation and protection of an ebbing knowledge reservoir has had an unprecedented impact in the area of Traditional Knowledge. Although various provisions have been included, true capitalisation of Traditional Knowledge would occur only when optimal balance is achieved between prevention of exploitation and advancement of innovations employing such resources. Contact: avishek@knspartners.com Pharma Bio World

Herbal Research in India @ Crossroads This article is a brief review of the herbal research in India and the regulatory guidelines in relation to research applications and commercialisation of biological resources.

he Convention on Biological Diversity signed by more than 150 governments at 1992 Rio Earth Summit is dedicated to promoting sustainable development. It has been acknowledged that biodiversity is more than plants, animals and micro-organisms and their ecosystems-it is about people and our need for food security, medicines, fresh air and water, shelter, and a clean and healthy environment in which to live. 1

On 17 February, 2014 South Sudan became the 194th member country to the global treaty on biodiversity and sustainable development. United Nations has also announced a “Decade on Biodiversity, living in harmony with nature.” Strategic goals of 20 ambitious yet achievable targets, collectively known as the “Aichi Targets” have been identified to be achieved by 2020. The main goals are as follows: GOAL A: A d d r e s s t h e u n d e r l y i n g causes of biodiversity loss by mainstreaming biodiversity across government and society. GOAL B: Reduce the direct pressure on biodiversity and promote sustainable use. GOAL C: I m p r o v e t h e s t a t u s o f biodiversity safeguarding ecosystems, species and genetic diversity. GOAL D: Enhance the benefits to all from biodiversity and ecosystem services. GOAL E: E n h a n c e i m p l e m e n t a t i o n s through participatory planning, knowledge management and capacity building. 2

Dr Gopakumar G Nair CEO Gopakumar Nair Associates 22 October 2014

India was one of the first Countries to implement the Bio-Diversity Act. India’s ‘The Biological Diversity Act, 2002’ was enacted on 5 th February, 2003. In the preamble to the Act conservation

of biodiversity, sustainable use, fair and equitable sharing of benefits were highlighted as the objectives in line with the United Nations Declaration. 3 “Biological resources” has been defined under section 2(c) of the Act. The 2(c) reads as follows-“biological resources” means plants, animals and microorganisms or parts thereof, their genetic material and by-products (excluding value added products) with actual or potential use or value, but does not include human genetic material. Further, “sustainable use” is defined under section 2(o) as follows-it means the use of components of biological diversity in such manner and at such rate that does not lead to the decline of the biological diversity thereby maintaining its potential to meet the needs and aspirations of present and future generations. Section 2(p) defines “value added products” as follows- it means products which may contain portions or extracts of plants and animals in unrecognisable and physical inseparable form. However, the sections of the Bio Diversity Act and the rules, thereof (Bio Diversity Rules, 2004) leaves much to be desired in promoting sustainable development and benefit sharing. The Bio Diversity Authority (BDA) has recently celebrated its 10 th Anniversary. In the preamble the BDA states as follow; “The Act covers conservation, use of biological resources and associated knowledge occurring in India for commercial or research purposes or for the purposes of bio-survey and bio-utilisation. It provides a framework for access to biological resources and sharing the benefits arising out of such access and use. The Act also includes Pharma Bio World

december ads.indd 15

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in its ambit the transfer of research results and application for intellectual property rights (IPRs) relating to Indian biological resources. The Act covers foreigners, non-resident Indians, body corporate, association or organisation that is either not incorporated in India or incorporated in India with non-Indian participation in its share capital or management. These individuals or entities require the approval of the National Biodiversity Authority when they use biological resources and associated knowledge occurring in India for commercial or research purposes or for the purposes of bio-survey or bioutilisation. Indians and Indian institutions do not require the approval of the National Biodiversity Authority when they engage in the above mentioned activities. However they would need to inform the State Biodiversity Boards prior to undertaking such activities. However, any commercial application related to use of biological resources should be approved by the Authority. The Act excludes Indian biological resources that are normally traded as commodities. Such exemption holds only so far the biological resources are used as commodities and for no other purpose. The Act also excludes traditional uses of Indian biological resources and associated knowledge and when they are used in collaborative research projects between Indian and foreign institutions with the approval of the central government.” However, the definition on the website of the Biological Diversity Act differs substantially from the definition in the Act itself. Unfortunately while the BDA emphasises on prevention and regulation of use of biological resources, there appears to be no effort for encouraging sustainable development or for benefitsharing. The entire emphasis of Biological Diversity Act as interpreted and implemented by the BDA appears to 24 October 2014

be directed towards preventing access to Indian Researchers and use of national biological resources for Research and Protection of research funding. This leads to prevention of research and bioutilisation including commercialisation or licensing thereof, in a sustainable manner, which alone can generate results both tangible and intangible, intellectual or financial, for benefit-sharing. While there is no dispute with regard to the need of biodiversity preservation, the emphasis should shift from excessive policing to encouragement of sustainable development and benefit generation for sharing. The Nagoya Protocol on Access and Benefit-Sharing The initiative on Convention of BioDiversity has received a boost on 2014 through the Nagoya Protocol on Access and Benefit-Sharing. The Nagoya Protocol come into effect on October 12, 2014. The Honourable Cabinet Minister of India on Environment, Prakash Javadekar had announced this development in the Indian Parliament. It is earnestly hoped that the Indian Bio Diversity Acts and Rules as well as the procedures and approaches for the implementation of the same will be reviewed under the context of Nagoya Protocol of 2014 for better capacity-building and awareness-raising. It is further hoped that Indian researchers will get opportunities for research in biological resources including herbals and in protecting their research findings for improved benefit-sharing with the Indian communities in a fair and equitable basis. The need for reviewing the current working of the BDA and the procedures adopted to interpret the Acts and the Rules will become clear on an audit of the performance of BDA as available from the statistics of the benefit generated and shared till date, from the records of BDA itself.

The Patents Act, 1970 & Biodiversity Act The footnote in Form 1 under Patents Act, 1970 for filing of Patent Applications, states as follows with reference to declarations. “The invention as disclosed in the specification uses the biological material from India and the necessary permission from the competent authority shall be submitted by me/us before the grant of patent to me/us”. The Patent Controller should exercise his discretion for evaluation of applicability of Biodiversity Act for cases not involving exportation of Natural or biological resources. Section 3 (p) and TKDL Section 3 (p) of the Patents Act, 1970 states as follows: (Inventions not patentable/ What are not inventions) “an invention which, in effect, is traditional knowledge or which is an aggregation or duplication of known properties of traditionally known component or components”. Inventions which are not traditional knowledge and which have novelty and inventive step of their own, should be eligible for grant of Patents. Patent should not be denied to otherwise patentable subject matter, only because there is mention of the item in TKDL. References 1) www.cbd.int/convention/ 2)www.cbd.int/sp/targets/ 3)www.nbaindia.org/text/12/1 TheBiologicalDiversity Act2002.html Contact: gopanair@gnaipr.net Pharma Bio World

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Ebola Outbreak 2014: An Overview of the Experimental Therapeutics 2014 outbreak of Ebola associated viral hemorrhagic fever has fatality rate of 55-60 per cent. The incubation period of Ebola is below 21 days. Once there is appearance of symptoms the person will be infective. Lack of specific vaccine, antiviral or drugs for treating Ebola is causing large number of deaths. Most of the recent outbreaks occurred in remote areas of West Africa. Poverty, lack of awareness, access to health centers, human habitats taking account in spreading the disease in large scale. Certain therapeutic molecules such as antibody, nucleoside analog, and siRNA have shown a promising role in treating Ebola.

urrently various countries in Africa, including Liberia, Sierra Leone, Guinea, Nigeria, are facing disaster due to Ebola virus disease (EVD) with at least 7,493 suspected cases and 3,439 deaths (including laboratory confirmed 4,108 cases and 2,078 deaths; see Figure. 1 on the next page), and more recently the cases have been reported in Senegal, the United States and Spain [1,2,3] . Ebola virus disease (EVD), Ebola hemorrhagic fever (EHF) or simply Ebola is a serious fatal illness caused by the Ebola virus. The virus causes the disease in the human and other primates. The first evidence of the Ebola was dated in 1976, in two places simultaneously, one in Nzara, Sudan, and the other in Yambuku, Democratic Republic of Congo. The latter one occurred in the village near the Ebola River, thus the name given to the virus. Since then there are the reported cases of the chronological outbreaks of the Ebola in the various African countries (CDC). Recent outbreak in 2014 is supposed to be the largest outbreak considering the highest number of cases and deaths compared to all previous outbreaks. There is no data for the natural reservoir of the virus; however it is believed to be animal-borne zoonotic infection [4] .

Transmission: A Matter of Concern

Shailendra K Saxena

CSIR-Centre for Cellular and Molecular Biology (CCMB)

Santosh Dahal

CSIR-Centre for Cellular and Molecular Biology (CCMB) 26 ď&#x201A;&#x192;October 2014

The current Ebola outbreak is generally due to the human to human contact transmission of the virus. Transmission occurs via blood or bodily fluids from the infected person or by the contact with the objects contaminated by the virus, particularly needles and syringes [1,2,3] . The virus can enter into the body through nose, mouth, eyes, or open wounds, cuts and abrasions. As the contact with the fluids from the

dead person can also transmit disease, there are many reported cases for the transmission to the mourners during the burial ceremony of the dead infected patient. Health care personnel may also get the disease during the treatment of the infected individual [1] . Clinical Features The incubation period ranges between 2 to 21 days for the Ebola virus [1,2] . Human are non-infectious until they develop the clinical symptoms for the EVD [1] . The initial phase of the Ebola disease includes the flu like symptoms such as fatigue, fever, headaches, joint, muscle, and abdominal pain [5]. The initial phase is followed by the bleeding phase, which begins at 5-7 days after the first symptoms, which is characterised by internal and subcutaneous bleeding in the form of reddened eyes and hematemesis (blood vomiting), followed by heavy bleeding of the gastrointestinal tract etc. People infected with the Ebola generally shows symptoms related to the circulatory system and this includes the impair blood clotting. Diagnosis As there are no initial typical clinical symptoms for the EVD, thus it is difficult to distinguish the disease from the other infectious disease such as malaria, typhoid fever and meningitis. Isolating the virus (by cell culture), detecting its RNA or proteins (by PCR and ELISA), or detecting antibodies specific for viral antigens in a personâ&#x20AC;&#x2122;s blood are some of the methods applied to diagnose the disease. These techniques works best early and in those who have died from the disease, whereas detecting the antibodies work late in the disease and those who recovered from the disease. Pharma Bio World

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proteins and provide passive immunity. During the experiment on the rhesus monkey the drug efficiently protected the animal when injected with the live Ebola virus [12] . Research in the nonhuman Primates (NHPâ&#x20AC;&#x2122;s) showed that the Zmapp provides protection against EVOD even after the 5 days post infection [12] . However, it is too soon to say whether ZMapp is effective, since it is undergoing an experimental stage.

Figure 1: Actual case and deaths (in log scale) during Ebola outbreak of 2014 in West Africa [Source: 1,2]

Sequencing method can be used for the efficient identification of the virus and differential diagnosis [6] . The EBV biomarkers such as miRNA and IgG (specific for the Ebola virus) may be efficiently used as a method for the molecular diagnosis and prognosis of the EBV infection [7,8] . Treatment and Vaccines: Challenge to Mankind No vaccine/specific treatment for the EVD are approved by the Food and Drug Administration (FDA, USA) t i l l n o w. Tr e a t m e n t o f t h e E b o l a i s symptomatic and early supportive care with rehydration may increase the survival rate [9] . Several treatment measures such as clotting factors, blood products, inhibitors of fibrinolysis and regulators of coagulation have been tried to counteract hemorrhage. In contrast anticoagulants like heparin were administered in some patients to prevent disseminated intravascular coagulation and thrombosis [9] . However, there is no evidence that these methods are significant for the treatment. 28 ď&#x201A;&#x192;October 2014

Recombinant vaccines have evoked good levels of immunity in case of knock-out mouse but also the antibody response in interferon knock-out mouse was similar to vaccinated wild-type mice [10] . A wide variety of investigational drugs (See figure 2 on the next page) are being tested for the treatment against the Ebola [11] , but all of them are yet in the level of clinical trial in animals or further. A brief overview of the few experimental treatments is given below. Zmapp: Zmapp is a therapeutic combination of monoclonal antibodies for EVD. Treatment with Zmapp includes three monoclonal antibodies, which includes ZMab (consisting of murine mAbs m1H3, m2G4 and m4G7), c2G4 and c4G7, which attack proteins on the surface of the virus. Zmapp contains the neutralising antibodies which directly and specifically reacts with the viral

ZMapp is manufactured in the Nicotiana benthamiana (tobacco plant), due to its capability of expressing foreign (non-tobacco) proteins using indoor cultivation under tightly controlled conditions. Monoclonal antibodies (mAbs) were first developed in mice by treating them with antigens from Ebola virus, harvesting their spleens, and hybridoma cell line is created by fusion of the B-cell specific for the viral antigens and the cancer cell lines. After the best antibody was selected, the gene encoding the antibody was extracted, and tagged with the gene portions encoding human protein, the process called humanisation. After the extraction of the gene, the gene is transferred to the tobacco plant using the viral vectors. Finally the antibody is extracted from the tobacco plant. The process of the production of the antibody takes nearly a month after the extraction of the gene encoding the antibody. The resultant antibody is tested for purity and potency before being formulated into the drug. TKM-Ebola: TKM-Ebola is another experimental drug targeted to the genetic material of the virus (RNA). It is a RNA interference drug constructed in Stable Nucleic Acid-Lipid Particles (SNALPs) and developed by Tekmira

Transmission of Ebola occurs via blood or bodily fluids from the infected person or by the contact with the objects contaminated by the virus, particularly needles and syringes. Pharma Bio World

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Pharmaceuticals, and works by shutting off the genes of the virus. The drug is a combination of small interfering RNAs (siRNA) which targets three of the seven proteins in Ebola virus such as Zaire Ebola membrane-associated protein (VP24), Zaire Ebola L polymerase, and Zaire Ebola polymerase complex protein (VP35). The SNALP constructs were actively taken up by the cell targets of the EBOV such as reticulo-endothelial cell population [13] . Two (66 per cent) out of three rhesus monkey which were given four doses of the pooled antiZEBOV siRNAs post exposure were protected from the lethal dose of the ZEBOV (Zaire Ebola virus) whereas all the macaques which were given seven doses were protected [13] . Flavipiravir: Flavipiravir is a drug used to treat influenza, but the drug also appears to be useful in treating t h e E b o l a i n f e c t e d m o u s e . T- 7 0 5 (pyrazinecarboxamide derivative) has been found to suppress the replication of Zaire EBOV in cell culture by 4 log units constituting an IC90 of 110ÎźM [14] . Administrations of the drug after 6 days

of the infection with Zaire Ebola virus (EBOV) induced rapid virus clearance, decrease in biochemical parameters of disease severity, and prevented a fatal outcome in 100 per cent of the animals [14]. Immune deficient mice were protected from the 14 days of twice daily dosing, post-infection of aerosol Ebola virus E718 infection [15] . BCX4430: BCX4430 is an adenosine nucleoside analog, broad spectrum antiviral drug manufactured by BioCryst Pharmaceuticals. The drug is a viral RNA dependent-RNA polymerase inhibitor. The drug causes premature termination of the replication process by binding with the polymerase active site and gets incorporated in the growing chain. BCX4430 can be administered by oral route, Intravenous or Intramuscular injection. BCX4430 could stop post exposure Ebola and related Marburg infections from taking hold in rodents with the intramuscular administration [16] Brincidofovir: Brincidofovir is another oral drug, which is a nucleoside analog and a prodrug of Cidofovir, has shown

Figure 2: Investigational/experimental drugs for the treatment of Ebola virus disease.

30 ď&#x201A;&#x192;October 2014

Ebola_PBW Feature_Saxena.indd 30

broad spectrum antiviral activity in vitro against five families of the DNA virus including herpes virus family and adenovirus. Brincidofovir is formulated by the conjugation of the Cidofovir with the lipid, and is designed to liberate Cidofovir intracellularly. It has subsequently been used to treat the first patient diagnosed with Ebola in the USA, after he had recently returned from Liberia. Recently (Oct 6, 2014), FDA authorised Chimerix for emergency investigational new drug applications of Brincidofovir for the treatment of Ebola virus disease [17] . Future Perspectives: Can Humans Outrun Nature? Since the first evidence of Ebola in 1976, various research works has been conducted to prevent and cure the threat of Ebola. But there is no any specific vaccine or the therapeutic drugs against the Ebola virus yet. The outbreak of the 2014 has proposed great risk, since it has been described as the largest outbreak till date. After more than 30 years of the first Ebola outbreak, humans are still fighting to tackle with the virus. This directs towards the need of the specific therapeutic strategies to constrain the recent Ebola outbreak and minimise the fatality. The contact tracing should be efficiently monitored to prevent the spread of the Ebola from infected person, which is the only means of preventing the spread of outbreak. Prime focus must be given on the vaccine development. Health education must be provided in the areas having the outbreak to prevent further spreading of the virus. If optimum precautions are not taken then this outbreak might result into another historic epidemic in the history of mankind. This feature can be concluded from the epidemic potential and the fatality rate of the disease. In a nutshell there is an acute necessity of the development of the rapid and reliable diagnostic tools, vaccine and therapeutic drugs specific for Ebola. Pharma Bio World

17-10-2014 19:51:33

References 1. Global Alert and Response (GAR), Pandemic and Epidemic Diseases, Ebola virus disease. World Health Organization. http://www.who.int/csr/ disease/ebola/en/ (Accessed 8 Oct. 2014) 2. Ebola (Ebola Virus Disease). Centre for Disease Control, USA. http:// www.cdc.gov/vhf/ebola/index.html (Accessed 8 Oct. 2014) 3. Swamy MLA, Nair MP, Saxena SK. Current scenario of therapeutics for Ebola virus disease. Am J Infect Dis. 2014; 10: 100-104. doi: 10.3844/ ajidsp.2014. 4. Vogel G. Infectious disease. Are bats spreading Ebola across subSaharan Africa? Science. 2014; 3 4 4 ( 6 1 8 0 ) : 1 4 0 . d o i : 1 0 . 11 2 6 / science.344.6180.140. 5. Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keïta S, De Clerck H, Tiffany A, Dominguez G, Loua M, Traoré A, Kolié M, Malano ER, Heleze E, Bocquin A, Mély S, Raoul H, Caro V, Cadar D, Gabriel M, Pahlmann M, Tappe D, SchmidtChanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Günther S. Emergence of Zaire Ebola Virus Disease in Guinea. N Engl J Med. 2014; 371(15): 1418-1425. 6. Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara F K , Tu c k e r V, K o n u w a E , S a ff a S, Sellu J, Jalloh AA, Kovoma A, Koninga J, Mustapha I, Kargbo K, Foday M, Yillah M, Kanneh F, Robert W, Massally JL, Chapman SB, Bochicchio J, Murphy C, Nusbaum C, Young S, Birren BW, Grant DS, Pharma Bio World

Ebola_PBW Feature_Saxena.indd 31

Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut A, Garry RF, Khan SH, Sabeti PC. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014; 345(6202): 1369-1372. doi: 10.1126/science.1259657. 7. McElroy AK, Erickson BR, Flietstra TD, Rollin PE, Nichol ST, Towner JS, Spiropoulou CF. Biomarker correlates of survival in pediatric patients with Ebola virus disease. Emerg Infect Dis. 2014; 20(10): 1683-1690. doi: 10.3201/eid2010.140430. 8. Liang H, Zhou Z, Zhang S, Zen K, Chen X, Zhang C. Identification of Ebola virus microRNAs and their putative pathological function. Sci China Life Sci. 2014 Sep 29. doi: 10.1007/s11427-014-4759-2. 9. Clark DV, Jahrling PB, Lawler JV. Clinical management of filovirusinfected patients. Viruses. 2012; 4(9): 1668-1686. doi: 10.3390/ v4091668. Symptoms and diagnosis 10. O’Brien LM, Stokes MG, Lonsdale SG, Maslowski DR, Smither SJ, Lever MS, Laws TR, Perkins SD. Va c c i n a t i o n w i t h r e c o m b i n a n t adenoviruses expressing Ebola virus glycoprotein elicits protection in the interferon alpha/beta receptor knock-out mouse. Virology. 2014; 452-453: 324-333. doi: 10.1016/j. virol.2013.03.028. 11. Choi JH, Croyle MA. Emerging targets and novel approaches to Ebola virus prophylaxis and treatment. BioDrugs. 2013; 27(6): 565-583. doi: 10.1007/ s40259-013-0046-1. 12. Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, FaustherBovendo H, Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.

Nature. 2014; 514(7520): 47-53. doi: 10.1038/nature13777. 13. Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN, Sood V, Johnson JC, de Jong S, Tavakoli I, Judge A, Hensley LE, Maclachlan I. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proofo f - c o n c e p t s t u d y. L a n c e t . 2 0 1 0 ; 375(9729):1896-905. doi: 10.1016/ S0140-6736(10)60357-1. 14. Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S. Successful treatment of advanced Ebola virus infection with T-705 (Favipiravir) in a small animal model. Antiviral Res. 2014; 105: 17-21. doi: 10.1016/j.antiviral.2014.02.014. 15. Smither SJ, Eastaugh LS, Steward J A , N e l s o n M , L e n k R P, L e v e r MS. Post-exposure efficacy of o r a l T- 7 0 5 ( F a v i p i r a v i r ) a g a i n s t inhalational Ebola virus infection in a mouse model. Antiviral Res. 2014; 104: 153-155. doi: 10.1016/j. antiviral.2014.01.012. 16. Warren TK, Wells J, Panchal RG, S t u t h m a n K S , G a r z a N L , Va n Tongeren SA, Dong L, Retterer CJ, E a t o n B P, P e g o r a r o G , H o n n o l d S , B a n t i a S , K o t i a n P, C h e n X , Taubenheim BR, Welch LS, Minning DM, Babu YS, Sheridan WP, Bavari S. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature. 2014 Apr 17;508(7496):4025. doi: 10.1038/nature13027. 17. C h i m e r i x a n n o u n c e s e m e r g e n c y investigational new drug applications for Brincidofovir authorized by FDA for patients with Ebola virus disease. http://ir.chimerix.com/releasedetail. cfm?ReleaseID=874647; http:// w w w. c h i m e r i x . c o m / c / d i s c o v e r y clinical-trials/brincidofovir-ebola.php (Accessed 8 Oct. 2014). Contact: shailen@ccmb.res.in October 2014 31

17-10-2014 19:51:39

Technology Transfer: Significance and Bottleneck in Pharmaceutical Industry This article mainly focuses on the study of technology transfer: significance and problem relates with technology transfer (bottleneck) in pharmaceutical industry. Bottleneck is the mainly cause blocking and starving on the part system in production line and also increases the no value added time, that impede productivity and affect the quality and safety of product.

Dr Vivek Dave

Assistant Professor Department of Pharmacy

Deepika Shukla

Research Scholar Department of Pharmacy

Dr Sachdev Yadav

Assistant Professor Department of Pharmacy 32 ď&#x201A;&#x192;October 2014

Bottleneck.indd 32

echnology transfer is the practice of transferring scientific findings from one organisation to another for further development, So that new products such as medicines, educational tool, electronic devices, safety equipment and health services can become available to the public. Technology transfer is the intersection between business, science, engineering, law and government [1-2] . Technology transfer is both integral and critical to the drug discovery and development process for new medicinal product. This process is important for to elucidate necessary information for technology transfer from R&D (Research &Development) to PDL (product development laboratory) and for development of existing products to the production for commercialisation. Te c h n o l o g y Tr a n s f e r i s h e l p f u l t o develop dosage forms in various ways like it provides efficiency in process, helps to maintain quality of product, helps to achieve standardised process, which in turn facilitates timely & cost e f f e c t i v e p r o d u c t i o n [ 3 - 4 ] Te c h n o l o g y transfer is the practice of transferring scientific findings from one organisation to another for further development, So that new products such as medicines, educational tool, electronic devices, safety equipment and health services can become available to the public. Technology transfer is the intersection between business, science, engineering, law and government. Technology transfer is both integral and critical to the drug discovery and development process for new medicinal product. This process is important for to elucidate necessary information for technology transfer from R&D (Research & Development) to PDL (process development laboratory) and for development of existing products to the production for commercialisation.

Te c h n o l o g y Tr a n s f e r i s h e l p f u l t o develop dosage forms in various w a y s l i k e i t p r o v i d e s e ff i c i e n c y i n process, helps to maintain quality of product, helps to achieve standardised process, which in turn facilitates timely & cost effective production. [5-6] Technology Transfer is not a single way process and it was showed in figure 1 (on the next page). Technology transfer usually involves some source of technology that possess specialised technical skills, which transfers the technology to a target group that do not possess those specialised technical skills, and who therefore cannot create the tool themselves. Te c h n o l o g y t r a n s f e r o f t e n i n v o l v e s the licensing of intellectual property rights and extending property rights and technical expertise to developing firms. [7] In the pharmaceutical industry, â&#x20AC;&#x153;technology transferâ&#x20AC;? refers to the processes of successful progress from drug discovery to product development, clinical trials and ultimately full-scale commercialisation. It is the process by which an original innovator of technology makes its technology available to commercial partner that will exploit the technology. So, there are three standards in the definition of technology. Technology transfer is a complex and challenging process which needs deep and all out study. In case of overlooking of different aspects of the technology transfer; it may lead to weaknesses of the national technology. Technology t r a n s f e r i n d i ff e r e n t c o u n t r i e s a n d organisations with various levels of technical knowledge covers limitations and problems for the less developed recipient. Pharma Bio World

17-10-2014 20:40:35

implications on the success or failure of the change innovation adoption decisions are influenced by both rational and irrational factor, technology transfer takes time, change happens in a social context: factors like social structure, culture, and norms can facilitate or impede that change, social systems are complex and difficult to control and change, Important Issues Associated with the Transfer of Technology Bottleneck

Figure 1: Definitions of technology

Te c h n o l o g y i s d e f i n e d d i f f e r e n t l y. Sociologists, Economists, Management Scientists, and other faculties, have their own definitions of technology. Significance of Technology Transfer in Pharmaceutical Industry Te c h n o l o g y t r a n s f e r i s a l s o called , transfer of technology or commercialisation of technology, the process of skill transferring, knowledge, technologies, methods of manufacturing, samples of manufacturing and facilities among governments or universities and other institutions to ensure that scientific and technological developments are accessible to a wider range of users who can then further develop and exploit the technology into new products, processes, applications, materials or services. It is closely related to (and may arguably be considered a subset of) knowledge transfer. The goals technology transfer: Clearly define objective, quantified goals (measures-of-success) from the very start reduce time to market by some per cent, Reduce cost by some percent, increase quality by some percent, Make sure that the goals are attainable. The goals should be accompanied by a business case justification. Pharma Bio World

Bottleneck.indd 33

Choose the appropriate technology: Survey the available technologies, Assess the choices in light of the defined goal(s), choose the most appropriate technology, Notice that the goal(s) should drive the technology choice, not the other way around. Pursue technology transfer project plan : Pursue the established plan, but be willing to make adjustments, As you learn more about the technology and its impact, As the organisational goals change, As surprises and delays are encountered For the duration of the “Tech Transfer” project, Be honest in interpreting your observations, Be honest in reporting the status, including surprises and delays, Communicate during the entire “Tech Transfer” project, The benefits and costs of the technology, The impact of the technology on those concerned, The current status of the project and the current plan for the project listening to the experts, but also listen to those problem affected by the technology transfer project. Adaptation and change in technology transfer: People differ in their ability to adapt to change. the perceived attributes of an innovation have strong,

In many cases, the developing countries obtain foreign technology at unreasonably high prices. In a number of cases of foreign direct investment associated with technology transfer, the net outflow of capital by way of dividends, interest, royalties and technical fees are much higher than the corresponding inflow. The appropriateness of the foreign technology to the physical, economic and social conditions of the developing countries is an important aspect c o n s i d e r e d i n t e c h n o l o g y t r a n s f e r. There is a large no. of cases where the foreign technology transferred has been irrelevant or inappropriate to the recipient country’s social economic p r i o r i t i e s a n d c o n d i t i o n s . F u r t h e r, heavy reliance on foreign technology may lead to technological dependence. The import of modern sophisticated technology has tended to displace the traditional indigenous technology that has improved under a different set of policies. The steady stream of new products and processes introduced by multinationals into developing countries has been unfavorable to the promotion of domestic technological capacities and has discouraged local scientists and technicians from devoting themselves to practical development problems. It creates an attitude of subservient dependence, which may October 2014 33

17-10-2014 20:41:07

inhibit the capacity to do even relatively minor adaptive research or to adopt processes, which can develop locally. It has identified that there is a tendency to transfer outdated technology to the developing countries. Thus, they would not enjoy the advantages of the latest technology and would still technologically lag behind. It is unfortunate that the owners of modern technology view the developing countries as a means to salvage technology that is obsolescent in the advanced countries, even when they possess technology that is more advanced. The following are some of areas where the general disputes will arise. Disputes arise because of differentiation in interpretation of different clauses of the agreement. At least one party must unable to operate the some part of the agreement due to any reason. Deliberately come out of the agreement by one party (sometimes it is happen when the license company is taken over by another company, those are not interested and or their philosophy is different otherwise it is rarely happen), a) Disputes relating payment of royalty and fees, b) Delay in completion of the projects, c) Passing of unapproved technology, d) Te c h n o l o g y u p g r a d a t i o n a n d incomplete data and drawings, e) Licensor is competing with licensee with the latest models in India, After sales service and backup, Intellectual Property Rights (IPR) issues like of trade mark quality and cost of production, Delay and supply of inferior raw materials and components. Bottlenecks are defined as a restrictions or obstacle that limits throughput or the utilisation of capacity resulting in the limited performance of the entire system. In the procurement cycle, bottlenecks often appear as delays, which vary in length, depending on the 34 October 2014

Bottleneck.indd 34

Figure 2: Bottleneck in pharmaceutical industry

step in the procurement cycle where the bottleneck occurs [8] . Different types of procurements vary in complexity and length. For example, we would expect a low value local procurement to be completed in a shorter time than a high value international competitive bid. Therefore, when diagnosing bottlenecks, it is essential to distinguish between a perceived bottleneck and an actual bottleneck. In some cases, there may be no bottleneck, just an unrealistic expectation of turnaround time. A bottleneck is a phenomenon where the performance or capacity of an entire system is limited by a single or limited number of components or resources. The term bottleneck is taken from the ‘assets are water’ metaphor. As water is poured out of a bottle, the rate of outflow is limited by the width of the conduit of exit that is, bottleneck. By increasing the width of the bottleneck one can increase the rate at which the water flows out of the neck at different frequencies. Such limiting components of a system are sometimes referred to as bottleneck points. An activity which delays the performance of a system and reduces overall efficiency of the process is known as bottleneck. As for example a

manufacturing company has different line of Production; each of them are connected to each other ie, the work produced from one unit is the input for other nit and so on. In this case if one line is broken or halted due to some reason than the other lines of production is directly affected causing lower level of output as a result of bottleneck. Table 1 showed lists of common procurement bottlenecks and where they occur in the procurement. Figure 2 shows the inflow rate and out flow rate. In flow was higher than the outflow rate, it may be due to several reasons from design of the equipment to assemble and operation of the process, which helps to reduce the overall efficiency of the systems. All these restriction of the system are known as bottleneck. Thus a bottleneck is an obstacle in the process of manufacturing which restricts the production. It can vary according to time and changes in production process. A bottleneck in project management is one process in a chain of processes, such that its limited capacity reduces the capacity of the whole chain. Related concepts in project management are; a) Critical path method b) Theory of restrictions Genetic drift can cause big losses of genetic variation for small population bottleneck occur when a population’s size is reduced for at least one generation. Because genetic drift acts more quickly to reduce genetic variation in small populations, undergoing a can reduce bottleneck a population’s genetic variation by a lot, even if the bottleneck doesn’t last for very many generations. This is illustrated by the bags of marbles was showed below, where, in generation B, an unusual small draw can creates a bottleneck showed in figure 3. Reduced genetic variation means that the population may Pharma Bio World

17-10-2014 20:41:08

Steps

Function

Bottleneck

SUPPLY FUNCTION

Define supply requirement

C o m p l e t e b u d g e t i n g a n d c o m p l e t e Budget cycle timing does not match the process funding cycle

Submit procurement requisition and Requisitions not submitted on time Inadequate specification or missing specifications Specification changes made after purchasing procedures are initiated

Release funds to procuring units

Inaccurate and omitted

Timing does not match resupply needs Mid-term budget cuts; programmed funds withheld

PURCHASE ACTIVITY

P l a n t h e p u r c h a s i n g w o r k : A s s e s s Slow contract planning by procurement unit p r o c u r e m e n t o p t i o n s ; p l a n c o n t r a c t Slow work on procurement schedule Delayed groupings and schedule purchasing work input and approval of line supervisor above procurement unit Uncertainty over dates and amount of funds available

P r e p a r e b i d d i n g d o c u m e n t s , o b t a i n Slow or flawed preparation of draft by approvals procurement unit Slow or flawed decision making at levels above procurement unit Slow processing by funder or monitor

Invite offers: Advertise opportunity; provide bidding documents; hold prebid meeting; respond to questions by potential

Problems with advertising Bidding document revision required Bid deadline extended to accommodate amendment of bidding documents

Select suppliers and obtain approvals: Open bids; prepare preliminary examination worksheet; bid evaluation committee deliberates and makes decisions; submit decisions for required approval

Slow preparation of examination worksheet Disagreements with the final results of the evaluation process Slow approval process Rejection by monitor based on unsupported decision or flawed process

Aw a r d c o n t r a c t s : N o t i f y s u c c e s s f u l Protests by losing bidders Cancellation of bid b i d d e r ; p u b l i s h r e s u l t s ; n e g o t i a t e Irregularity in performance security minor points; process acceptance and signatures; obtain performance security

Protests by losing bidders Cancellation Protests by losing bidders Cancellation of bid of bid Irregularity in performance security Irregularity in performance security

Arrange payment guarantee: Make down Delay in requesting letter of credit or down payment, issue letter of credit payment Delay in processing by finance unit or Ministry of Finance Funds not available to collateralize letter of credit, or make down payment

CONTACT PERFORMANCE

Process order and manufacture goods

Perform pre-shipment inspection/testing Failed or disputed results

Deliver to port of entry

Shipping problems

Clear goods through customs

Slow processing of documents No access to funds for port fees Irregularities in goods or documents Pharmaceutical registration issues

Perform post-shipment inspection/testing Delayed or failed post-shipment inspection and testing Slow reporting and/or release

Raw materials shortage Overbooked manufacturing schedule Distributor issues

Table 1: Procurement, functions, bottleneck in pharmaceutical industry

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not be able to adapt to new selection pressures, such as climatic change or a shift in available resources, because the genetic variation that selection would act on may have already drifted out of the population. System and throughout the prevailing political system for example, the procurement environment play a large part in bottlenecks. In the supply process, bottlenecks frequently appear far from the origination point. The procurement bottleneck trends were identified around several themes; including access to funds, cumbersome processes, and quality concerns. Although corruption and quality assurance issues were not the most prominent bottleneck theme, these issues were significant threads throughout the article. The procurement environment in which the bottlenecks occurred found that most bottlenecks occurred outside the core procurement functions of technical capacity, staffing, and management. An activity which delays the performance of a system and reduces overall efficiency of the process is known as bottleneck. As for example a manufacturing company has different line of production; each of them are connected to each other i.e. the work produced from one unit is the input for other unit and so on. In this case if one line is broken or halted due to some reason than the other lines of production is directly affected causing lower level of output as a result of bottleneck. Types and Approaches of Bottleneck in Manufacturing Process in Pharmaceutical Industry There can be many different types of bottleneck in manufacturing industry as for example labor, time, material or machine etc. The bottleneck in manufacturing process in pharmaceutical industry was showed in figure 4. In October 2014ď&#x201A;&#x201E; 35

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general different forms of bottleneck can be described as below; People restrictions: People are one of the most important factors of the production and difficult to manage in an effective way. In any manufacturing unit there are different people working together with different experience, background and educational qualification. Each people have their own way of motive towards work. So in manufacturing unit different restrictions of bottleneck can be due to union problem, illness, unexpected vacancy, hiring and training problems etc. Material restrictions: Production capacity is highly affected by the poor management of inventory, inadequate f o r e c a s t , i n e ff i c i e n t s u p p l i e r, p o o r production planning, in adequate finance, changing product mix etc. one or all of these factors may cause improper flow of materials resulting reduction in overall production capacity and increasing lead time [9] . Equipment restrictions: Equipment for manufacturing should meet the current demand. The machines and equipment should be flexible to expand in order to meet future demand, but sometimes due to inappropriate planning, breakdown of machine, unavailability of spare parts, improper maintenance, low level of infrastructure machines and equipments becomes a restriction of manufacturing. Process restrictions : Process restrictions in manufacturing unit can be due to quality problems, in sufficient resources, poor plant layout and inflexible process (not able to change according to time and market demand). The restrictions can occur anywhere in the process, supply chain, customer, supplier etc. Hence any kinds of problems affecting entire output of the system are known as process restrictions [10] . 36 ď&#x201A;&#x192;October 2014

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Figure 3: Different bottleneck in different generations

M a n a g e m e n t r e s t r i c t i o n s : E ff i c i e n t management means better performance resulting in higher output and profit. Overall management of a manufacturing unit should comply with aim and objective of the company. Sometimes the management is not be able to meet the needs of the system and becomes a restriction causing different problems like demotivation of employee, ineffective flow of material and information etc. Policy restrictions: Policy of a manufacturing unit should meet the goal of company, it should be clearly defined what actions are to be taken at what conditions. Generally (not always) the management is not able to define all the issue in specific this way may leads to a restriction in manufacturing. It is the most common form of restrictions [11] Environmental restrictions: Operating environment of any business includes competitors activities, rules and regulations formulated by government, l a b o r l a w, u n i o n l a w, c u s t o m e r demands & expectation, economical situation, technological improvement, development in infrastructure etc. at the same time the firm should bear the social responsibilities. These all factors affecting the activities of business is called environmental restrictions [12]

Bottleneck is the main reason for slowdown of the production in a manufacturing unit. It has to be identified, analysed and needs to be resolved on the basis of facts. Once the bottleneck is identified correctly and efficiently; It helps to reduce production cost increasing overall efficiency of the system. There can be long term or short term restrictions in the system. The range of bottlenecks to expanding medicine production in the region as: A weak policy environment and limited governmental support to encourage domestic investment in the pharmaceutical industry; high tariffs on imported inputs, high interests rates on credit, ageing and unreliable energy, water and transport infrastructure; shortfalls in capital and skills, including in scientists and industrial pharmacists and in laboratories; limited international linkages and mechanisms for and intellectual property restrictions in technology transfer and in the sourcing of active pharmaceutical ingredients; gaps in the regulatory framework and in enforcement capacities to ensure quality assured, safe and efficacious medicines; small markets within individual countries, and weak or non-existent capacities for research and development. Failure mode and effect analysis is a methodology for Pharma Bio World

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in the system. A process of correlating different activities (process, product, service etc.) of a firm with similar others in order to find best possible options in order to improve or solving a problem of specified task or operation is known as Benchmarking. It helps to know where the improvement is necessary and how other industries are doing. Thus helping to improve own performance.

Figure 4: Manufacturing bottleneck diagram

Figure 5: Restrictions to local manufacturing of pharmaceutical industry

analysing potential problems early in the development or improvement process, by identifying relationship between process and product anticipating the potential for unacceptable outputs and their effects, enabling teams to take action to reduce risk and increase r e l i a b i l i t y. F a i l u r e m o d e a n d e ff e c t analysis helps to know all different ways for occurrence of failure and estimate its effect and seriousness, in the same time it also helps to find the possible ways of correction. Theory of restrictions guides for regular improvements on Pharma Bio World

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the system [13] . Any system is consists of a series of independent sub system working together in a defined way in order to meet fixed target. In the same way there can be a number of weak places working as restrictions in the system. Theory of restrictions focuses on those weak places where improvement is necessary. Theory of restrictions follows following five steps: Identify the restrictions, Exploit the restrictions, Elevate the restrictions and, Repeat the cycle Thus, it is effective method to find the bottleneck

Financial restrictions have an impact on the requisite infrastructure, technology and skills for establishing local production. The availability of infrastructure attracts investment in and use of technology. The availability of human resources both affects the capacity to use resources and is affected by the availability of resources to train, attract and retain skilled personnel (pharmacists, scientists, engineers, technicians). Figure 5 was describing the different restrictions and factors which can effects the final products of pharmaceutical industry. The review found a number of bottlenecks to local production and over reliance on imports of medicines from developed countries. They barriers to expanding medicine production in the region are identified as: A weak policy environment and limited governmental support to encourage domestic investment in the pharmaceutical industry; high tariffs on imported inputs, high interest rates on credit, ageing and unreliable energy, water and transport infrastructure etc. Gaps in the regulatory framework and in enforcement capacities to ensure quality assured, safe and efficacious medicines. Investment in skills and capacities for regulatory functions, technical, business and management aspects of manufacturing, and for strategic policy leadership, including investments in training industrial pharmacists, incentives to attract and retain skills and negotiating partnerships with international firms October 2014ď&#x201A;&#x201E; 39

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and governments; Setting laws and strengthening enforcement capacities with in national medicines regulatory authorities, including investing in quality management systems, laboratories, enforcement personnel and technical capacities in laboratories and that pharmaceutical development goes hand-in-hand with regulation in local R&D infrastructure. There are number of documents identify challenges to local pharmaceutical manufacturing production from shortages of skilled professional personnel and point to infrastructure and skills as major determinants for t e c h n o l o g y t r a n s f e r [14-16] T h e s a m e publications note the willingness of the pharmaceutical industry to transfer its know-how and techniques is not sufficient for successful transfer of technology. Governance issues are a challenge to local manufacturing production of pharmaceuticals. Local production that is supported by foreign aid to local public sector producers can distort the market by protecting a specific local producer against another more efficient and competent producer, due to government’s ability to direct aid to specific producers. Regulatory frameworks and stronger governance policies make fundamental, successful development and establishment of local pharmaceutical manufacturing production. [17-19]. Conclusion The paper focus on a large number of approaches, procurement, functions, issues bottlenecks in production networks have been discussed and analyzed in the pharmaceutical manufacturing industries to produce a good quality product. The article was showed that the degree of removing bottleneck is directly proportional 40 October 2014

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to the amount of production, means once the bottleneck is identified a n d r e m o v e d , i t s d i r e c t e ff e c t c a n be seen as increase in production capability and also removes the financial expenses. Reference 1. Domb E, Using TRIZ to Accelerate Te c h n o l o g y T r a n s f e r i n t h e Pharmaceutical Industry, PQR Group and The TRIZ Journal 3-5, 2004. 2. Notes on technology transfer, Cited October 07, 2009. 3. R e a m e r A , I c e r m a n L a n d J Youtie ,Technology Transfer and Commercialization: Their Role in Economic Development, (2003), 4. P a t e l D S , A n o v e r v i e w f o r p h a r m a c e u t i c a l i n d u s t r y, I n t B i o pharm Association publication 1, 2010. 5. P a t e l D S , A n o v e r v i e w o f pharmaceutical industry. IBAP, 1-10, 2010. 6. Council of Supply Chain Management Terms and Glossary. : Supply Chain Vision. 7. h t t p : / / w w w. a d b . o r g / D o c u m e n t s / Information/Knowledge-Solutions/ The-Five-Why Technique.pdf Asian Development Bank, 2012 Available ( Accessed 26 august 2014) 8. WHO, ‘Pharmaceutical production and related technology transfer’. 9. B a t e R , ‘ L o c a l p h a r m a c e u t i c a l production in developing countries: How economic protectionism undermines access to quality medicines’, Campaign for fighting diseases discussion paper 1: London.2008 10. WTO, Doha Declaration on TRIPs and Public Health, WTO decision in relation to TRIPS, WTO, Geneva, 2001. 11. Agnam A, ‘South south co-operation: Intellectual property and AIDS medicines’ 2011.

12. C o u n c i l o n H e a l t h R e s e a r c h f o r Development (COHRED) and New Partnership for Africa’s Development ( N E PA D ) , S t r e n g t h e n i n g pharmaceutical innovation in Africa: Designing strategies for national pharmaceutical innovation: Choices for decision makers and c o u n t r i e s ’ N E PA D s t r e n g t h e n i n g pharmaceutical innovation Africa, 2009. 13. http://oeas.ucf.edu/proces analysis/ what is pa.html, University of Florida, 2012. (Accessed: 28 august 2014) 14. U N C T A D , ‘ I n v e s t m e n t i n pharmaceutical production in the least developed countries: A guide for policy makers and investment promotion agencies’, UN: Geneva, 2011. 15. L o e w e n s o n R , ‘ O p t i o n s f o r sustainable access to medicines in Africa: Moving beyond TRIPs flexibility toward local production 2011 16. U N C TA D , A s i a n f o r e i g n d i r e c t i n v e s t m e n t i n A f r i c a : To w a r d s a new era of co-operation among developing countries’, 2007. 17. A f r i c a n U n i o n , P h a r m a c e u t i c a l manufacturing plan for Africa’, CAMH/MIN/7(III), AU: Addis Ababa, 2007. 18. C h a u d h u r i S , ‘ I n d i a n g e n e r i c companies, affordability of drugs and local production in Africa with special reference to Tanzania IKD, Working paper No. 37, Open University Research Centre on Innovation Knowledge and Development, 2008. 19. B a t e R , ‘ L o c a l p h a r m a c e u t i c a l production in developing countries: How economic protectionism undermines access to quality medicines’, Campaign for fighting diseases discussion paper 1: London, 2008. Contact: vivekdave1984@gmail.com

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Drug Abuse Liability Study: A Category Analysis The Drug Abuse Liability (DAL) testing market is largely driven by global central nervous system (CNS) therapeutics market which represents around 17 per cent of drugs in clinical trials in 2013. Considering drug abuse a major health concern, DAL, which was earlier confined to clinical phase, has been incorporated in preclinical stage by the regulatory bodies. The category managers at pharma companies employ a combination of CROs and academia at different stages of drug development to optimise spend on DAL testing. Also, DAL data, both at preclinical and clinical stages, would immensely help regulatory bodies in product labelling and drug scheduling recommendation with the hope of reducing its misuse and dependence.

rescription drugs hold the chance to be misused or used for nonmedical reasons and can lead to physical dependence and withdrawal symptoms. The symptoms thus results are generally noticed in the drugs that affect the central nervous system. Such drugs are found to have abuse potential or abuse liability. Drug abuse liability study has surfaced on the safety pharmacology space in recent years as a result of numerous safety guidelines and discussion documents from regulatory bodies in the US and Europe. Increasing incidents about prescription drug abuse and the withdrawal prospective of many common drugs have necessitated development of evaluation procedures (both non-clinical & clinical) like abuse liability testing. In the last decade, Asia, Europe, and Australia indicated major trouble with opiate dependence, South America primarily was affected by cocaine addiction, and Africans were treated most often for the addiction to cannabis. Only in North America was drug habit disseminated relatively uniformly between the use of opiates, cannabis, cocaine, amphetamines, and other narcotics. What Types of Prescription Drugs are Abused?

Siddhartha Shaurabh Lead Analyst Beroe Inc

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Three types of drugs are most often abused: 1) Opioids: generally prescribed for pain relief 2) CNS depressants: barbiturates and benzodiazepines prescribed for anxiety or sleep problems (often referred to as sedatives or tranquilizers) 3)Stimulants: prescribed for attentiondeficit hyperactivity disorder (ADHD), t h e s l e e p d i s o r d e r n a r c o l e p s y, or obesity.

Market Overview Drug abuse liability study has its significance across Pharma, bio-pharma, agrochemicals, medical devices and cosmetics industry. Recently, higher incidents of drug abuse have led regulatory body to solicit assessment of the safety profile of NCEs particularly for all new CNS-active medicinal products (parents + metabolites) that can cross the blood brain barrier (BBB), interact with central targets and precipitate an abuse liability potential. The estimated global market size for drug abuse liability study is around USD 1.5 billion growing steadily at ~3 per cent. This market has a close impact with the CNS therapeutic area as all drug substance entering the CNS drug R&D space has to undergo abuse liability test. There are three main types of studies that are typically employed to address abuse liability: Drug Discrimination: This model is used to determine the properties of novel compounds with that of a known class of drugs or to determine if the novel compound can be distinguished. It is hence, used to identify the extent of similarity of the subjective effects of the new chemical entity to those of the known drugs of abuse, such as CNS stimulants or depressants. Drug Self - administration: is a nonclinical model adopted to ascertain whether animals will work to get access to the direct injection of drugs. Administering the drug which induces the rewarding effect is the direct assessment of drugâ&#x20AC;&#x2122;s abuse liability. Amphetamine, morphine & cocaine are strongly positive in this test. Hence, it is used to directly measure the positive-reinforcing properties of the new chemical entity. October 2014ď&#x201A;&#x201E; 41

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Does the compound enter CNS? Yes

CNS binding panel x Including known abuserelated targets x Test major metabolites

Evaluate cellular functional activity

Hold

Low affinity or functionally dissim ilar

Binding IC50 < 1 μM or < 10x Primary Target or functionally similar to abused substance

Preliminary In-Vivo/Ex Vivo Characterization Inactive

Pre-Clinical

Phase 1-2

Clinical Findings x Spontaneous reports of euphoria, craving or withdrawal x Acute performance or cognitive effects x Taking more study drug than instructed x Requests to remain on study drug after trial

Active

Animal Abuse-related behaviors: x Discriminative x Reinforcing x Dependence x Performance Inactive in anim al tests

Summarize for FDA at EOP2 meeting

Active

Phase 3 Human Abuse Liability Study

Drug Abuse Testing Exhibit

Drug Dependence: produces continued drug use in order to avoid negative feelings—physical or emotional—that occur when drug administration is stopped. Continued administration of a drug that produces dependence may be associated with the development of tolerance to the pharmacological effect of the drug. A positive signal in 42 October 2014

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isolation doesn’t necessarily indicate abuse potential. However, together with positive effects in the other assays, could contribute to the potential for abuse. Current Service Provision Scenario in the Market Services in the drug abuse liability are

provided by both academia and CROs. Service provision in the drug abuse liability testing could be 20-30 per cent cheaper (could be even lesser depending on the particular area of interest) when done through academia but CROs are preferred due to two main reasons: a) Speeds of Completion: The work with the CROs are mainly business driven Pharma Bio World

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and customised as well. Hence, the focus is on the business outcome and timelines of client. b) G L P C o m p l i a n c e : M o s t o f t h e academia is non-GLP compliant and during the FDA reviews GLP compliance is mandatory. Hence, CROs are proactively chosen. Though, academia and CROs are two separate entities but there can be subcontracting from CROs to academia due to 1) Greater scientific understanding on the subject by academia. 2) Better choice with protocol compliance & writing. 3) Interpretation of potential mechanisms of abuse. However, CROs are mostly preferred for drug abuse liability studies due to the technology & expertise availability, regulatory compliance and capacity readiness. These CROs are also one stop shops for a battery of experiments required in abuse liability studies. As per pharma companies, it is more cost effective to rely on outside providers that can manage projects complexity and have an understanding of regulatory compliances. Drug Abuse Liability Study: Compliance Scenario The drug abuse liability testing is generally done as per GLP & nonGLP standard in the supply market greatly affecting the cost incurred & regulatory compliance requirement sought. However the quality of studies s h o u l d b e e q u i v a l e n t . Ta k i n g i n t o account a series of activities to evaluate the novel molecule with abuse potential, a two-tiered assessment is suggested by the regulatory body generally considered as Non-GLP (Tier 1) or pharmacology & GLP (Tier 2) or specific behavioral pharmacology studies. Pharma Bio World

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Non-GLP Compliance • Non-GLP studies are generally termed as tier1 study by regulatory body (EMA) and take in to account the testing of the novel molecule with abuse potential on account of chemical structure, PK/PD characteristics, pharmaceutical characteristics, etc. • Studies such as receptor-binding (in vitro), confirmation of binding & functional properties (in vivo) referred to under the first tier by European Medicines Agency as outlined under ICH S7A - largely need not meet the requirements of GLP. GLP Compliance • Studies for safety pharmacology are generally done with the GLP compliance which is largely considered as tier 2 studies as per regulatory body (EMA). • Specific behavioral pharmacology studies are done when the active substance has a novel mechanism of action & this is done on the basis of biochemical, pharmacological and clinical information already available through tier1 (non-GLP) test. Market Practices Vendor Option: The service for drug abuse study is a very niche area and provided in the market by very few CROs and research oriented universities. Several independent consultants are also available in the market functioning in this space; however they again collaborate with same set of CROs for the service delivery. • CROs: These are the commercial services providers, having a greater understanding of the client’s requirement, regulatory practices & conformity (Good manufacturing practices (GMP) compliance) and proven expertise & experience.

• Academia/University: These are the research centers with expertise of world leading disease scientists, technology experts, novel models etc. In abuse liability space, most of the academia is non-GMP compliant. • Consulting Firms: These are the group of Pharma consultants offering functional & regulatory affairs expertise and support services on the basis of their extensive experience & network of service providers. Consulting firms are generally chosen for the abuse liability studies when a pharma company is planning to start these studies for very first time in order to understand the developing guidelines & standard operating procedure (SOP) and regulatory compliance. At the later stage they are not preferred because of their redundant use & added cost. References 1) http://www.fda.gov/downloads/ Drugs/ GuidanceCompliance Regulatory Information/ Guidances/UCM198650. pdf 2 ) h t t p : / / w w w. f d a . g o v / d o w n l o a d s / AdvisoryCommittees/ Committees MeetingMaterials/ Drugs/ DrugSafetyand RiskManagement AdvisoryCommittee/ UCM337158.pdf 3 ) h t t p : / / w w w. h c - s c . g c . c a / d h p - m p s / prodpharma/ applic-demande/guideld/ abus/abuse_liability_ abusif_ usage_clin-eng.php 4 ) h t t p : / / w w w. f d a . g o v / d o w n l o a d s / AboutFDA/CentersOffices/ CDER/ UCM180770.pdf 5 ) h t t p : / / w w w. f d a . g o v / d o w n l o a d s / AboutFDA/CentersOffices/ CDER/ UCM180785.pdf 6)http://www.toxicology.org/isot/rc/nesot/ docs/07Alper.pdf 7 ) h t t p : / / w w w. n c b i . n l m . n i h . g o v / pubmed/10519736 8 ) h t t p : / / w w w. n c b i . n l m . n i h . g o v / pubmed/ Contact:sarabjeet.singh@beroe-inc.com October 2014 43

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Diabetes Care: New technologies in the Fight Against a Global Pandemic The number of people suffering from diabetes is increasing rapidly worldwide. In parallel, the global market for insulin therapies is growing at a much higher rate than total sales of prescription drugs. For people with diabetes who are dependent on insulin, pen systems that can be equipped with insulin cartridges and injection needles have long since surpassed all other injection systems. For the safe filling of insulin cartridges, manufacturers offer new technologies that ensure high output, low product loss, and optimal patient protection.

iabetes mellitus is the first noninfectious disease that has taken on the magnitude of a pandemic. The growing number of young people with diabetes is especially worrisome, as it increases the burden on health systems through diabetes-related long-term effects. Nevertheless, diabetes research has made great progress in recent years. The once deadly disease has become one that is chronic. Thanks to new, targeted therapies and application technologies for insulin administration, people who are suffering from diabetes today have the same life expectancy as their peers. The current figures are frightening, however: 382 million people worldwide suffer from diabetes. It is estimated that the number will increase to 592 million by 2035. Most people with diabetes – about 80 percent – live in countries with medium to low income, with an increasing percentage in the so-called emerging economies. Forms of Diabetes

Dr Johannes Rauschnabel Chief Pharma Expert Bosch Packaging Technology 44 October 2014

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In type 1 diabetes, the body’s own immune cells are directed against the insulinproducing beta cells of the islets of Langerhans in the pancreas. This happens very often already in childhood. What triggers this misguided immune response is still not scientifically clarified to its full extend. Due to the resulting insulin deficiency, insulin therapy is always necessary for treatment of type 1 diabetes. In contrast, experts now agree that the modern lifestyle is the main cause of type 2 diabetes. This type accounts for about 90 percent of all present cases. Obesity and lack of exercise lead to a resistance to the insulin hormone, preventing it from working properly on the cell membranes and from transporting glucose into the cells. The result is increased blood glucose concentration, which often goes unrecognised for many years.

All approaches to diabetes therapy have always been aimed at controlling blood sugar levels and preventing large fluctuations down (hypoglycemia) or up (hyperglycemia). In the 1920s, researchers Frederick Banting and Charles Best were able to extract insulin and successfully treat a young patient with it for the first time. A disease that had been fatal up to that point suddenly became manageable. Today, insulin is obtained from bacteria using biotech methods and brought to the market as human insulin. Since 1996, modified insulins have also been approved. Referred to as insulin analogs, they work particularly quickly or uniformly. Changing Diabetes Therapies and Delivery Methods Technical innovations since the 1980s have made domestic self-monitoring of blood glucose possible – an important advance for the calculation of the insulin dose, giving back some flexibility in everyday life to patients. Insulin pens were developed for more ease of delivery. The pens are used as multiple application systems with pre-filled insulin cartridges. For diabetes patients the independent administration of insulin is now a lot easier. Due to their shape, the pens can not only be transported more conveniently, they can also be applied “en route” without attracting attention. Patients are able to better adapt the therapy to their own rhythm of life. Another milestone was the development of insulin pumps, which continuously and flexibly provide diabetes type I patients with short-acting insulin. While needle-free injection systems do not yet have great penetration in the market, several developments promise further improvements in the quality of life of diabetes patients. One such Pharma Bio World

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example is inhalative insulin. Although the first commercial trials from around 2006 initially failed, a comeback may be imminent: The US Food and Drug Administration (FDA) is presently reviewing the inhalation formulation of an American pharmaceutical manufacturer. Further studies are currently underway, including ones on the development of orally administered insulin. 5 Safety of the Product and Patient Due to the worldwide increase in the number of people suffering from diabetes and constant improvements in therapy and delivery methods, the global market for insulin is growing continuously, along with the market for pens and other injection aids. Currently pens are the most widely used system for insulin injection, mainly due to their ease of use and relatively inexpensive production. The insulin pens are loaded with cartridges. The cartridge is a glass cylinder which is closed on the front end by an aluminum cap with a puncture membrane. The rear end of the cartridge is closed with a rubber stopper. For diabetes patients, easy and safe handling of the pens is the most important criterion. Insulin manufacturers in turn must pay particular attention to sterile filling and to the integrity of the materials used. Product safety is the highest priority for pharmaceutical manufacturers. For this reason, the pharmaceutical industry looks to reduce manual intervention during the production process as much as possible.

Insulin pens make it easier for patients to administer the insulin and to adapt their treatment to their own rhythm of life

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Modern barrier technology completely seals off products, processes, equipment, and operators from each other. Restricted Access Barrier Systems (RABS) ensure effective separation in the sterile room. Insulin manufacturers also increasingly rely on the use of isolators, which ensure higher product quality at lower cost compared to conventional cleanrooms. Market Growth Requires High Output Cost pressure is omnipresent in the highly competitive insulin market. As it is not possible to establish a high price for insulin preparations, manufacturers can generate profits only through volume. Although insulin pumps are even easier to use compared to pens, their higher production costs made it impossible for them to prevail globally. In addition to the cost factor, the growing number of diabetes patients in the emerging economies has driven major insulin manufacturers to expand their production to more and more locations worldwide. That is why machines for the processing of cartridges for insulin pens are increasingly used particularly in the so-called “pharmerging” markets such as India, Brazil, and China. The criteria by which manufacturers choose their machines are high output, high availability, and reproducible precision in insulin production. Filling and closing machines for cartridges with a capacity of up to 600 units per minute are now considered state-of-theart and are already installed in the market in large numbers. Filling lines integrated in isolator systems run continuously for 21 days in some cases, thus ensuring maximum productivity. In terms of filling systems and processing of the packaging, the industry demands ever greater flexibility. That is why modern plants and lines are compatible with all current filling technologies and partly also equipped with combi filling stations for several packaging types, such as cartridges, vials, and injection bottles or syringes.

Insulin manufacturers increasingly rely on the use of isolators, which ensure higher product quality at lower cost compared to conventional cleanrooms

Focusing on Glass Integrity The process a cartridge runs through includes many steps: washing, siliconising, sterilising, filling and closing in the isolator device, inspection, and tray loading. The cartridge is e x p o s e d t o d i ff e r e n t t e m p e r a t u r e s , pressures, and movements during these processes, all of which it must withstand unscathed. The higher the speed of a filling and closing machine, the more the manufacturing process subjects the glass to physical stress. This can cause damage to the glass, such as cracks, chips, or fractures. The product loss caused by these defects results in higher costs for pharmaceutical producers, which machine manufacturers are counteracting with new solutions for gentle processing. The primary objective of these innovations is to minimise contact between glass containers. During loading of the cleaning machine, for instance, the cartridges are loaded onto the conveyor belt in just one row and then transported in rows. Stainless steel containers, referred to as “transport pucks”, ensure smooth transportation from the washing station through the sterilising tunnel by preventing glassto-glass contact. This is particularly important for the processing of dualchamber cartridges, as they may be even more fragile due to the internal bypass. October 2014 45

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Adjusting the Physical Stress

Precise Filling for Safe Dosing

During the sterilisation process, the glass is exposed to an enormous heat influence. The high temperature leads to expansion of the glass mass in the tunnel. This can be compensated by a conveyor belt with flexible lateral support, which widens immediately after the tunnel entrance. To protect the cartridges from damage from tipping over, they are transported to the inlet of the filling machine in bulk, where a star wheel separates them again. The angle of the star wheel must be designed precisely, facilitating seamless loading of the receiving pockets in the star wheel with cartridges. Robotic feeding and removal of cartridges can provide further reduction in physical stress.

The filling of insulin products into a cartridge must meet special requirements. On the one hand, insulin suspensions often require filling with a homogeneous level of active ingredients. On the other hand, full and bubble-free filling should be ensured without overfilling. This demands a two-step filling process, in which 80 per cent of the maximum quantity is dosed into the cartridge in the first step. In a second station, the remainder is filled to the full point by laser-scanning the cartridge neck. The laser sensor switches off the dosing when the fluid meniscus reaches the laser beam. Suspensions require constant homogenisation of the product template and often also require that mixing bodies (sterile glass balls) are added to the cartridge. This enables the patient to perform simple homogenisation of the suspension by shaking prior to application. The glass ball feeding is also monitored using sensors.

Cosmetic glass defects are evidence of damaged packaging, which may also break on the way to the patient or be contaminated with particles after the filling and closing process. Above all, however, exact and correct closure of the cartridges is essential for safe drug administration, where 100-percent inspection plays an important role. With the “Static Division” (SD) technology, light is projected through the liquid onto an optical sensor, which allows differentiation between moving particles and static objects. Automatic camerabased systems in turn detect both particles and cosmetic defects. While the containers are rotated by more than 360 degrees, cameras take high-resolution images. By comparing these images, the system is also able to identify particles adhering to the walls or defects in the cap crimping.

Research for a Better Quality of Life Even at an early developmental stage of insulin preparations, safe filling of cartridges is top priority for the subjects in clinical trials. Insulin producers, therefore, have a great need for manual and semi-automated test machines for product development. New, highly flexible laboratory modules are primarily used in early clinical phases. It is particularly important that these machines can be equipped with different filling technologies and allow the filling parameters to be easily transferred to production systems via scale-up at a later point. Inspection is equally

Due to the worldwide increase in the number of people suffering from diabetes and constant improvements in therapy and delivery methods, the global market for insulin is growing continuously, along with the market for pens and other injection aids. 46 October 2014

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Manual inspection systems, supported by cameras where required, quickly and accurately inspect empty and full glass containers for particles in the liquid or for cosmetic defects.

important during product development: manual inspection systems, supported by cameras where required, quickly and accurately inspect empty and full glass containers for particles in the liquid or for cosmetic defects. It is still uncertain when alternatives to injecting insulin will prevail. For the time being, insulin pens are set to maintain their status as the preferred application system. But the near future already promises the introduction of further insulin formulations and new, improved insulin pens. The artificial production of the insulin hormone – from the first extraction in the twenties until the introduction of the first long-acting insulin analog in 2000 – is a success story unparalleled in medicine. Although prevention and avoidance of long-term consequences must always be top priority, advances in treatment provide people affected by diabetes with the hope of further, significant improvement in their quality of life. Contact: johannes.rauschnabel@bosch.com Pharma Bio World

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Regaining FDA’s Confidence in India’s Generic Drug Exports Over the last couple of years the Indian Pharmaceutical industry has been plagued by a number of quality issues which has been brought to light as a result of the inspections conducted by the USFDA. Established organisations have been faced with a ban on supply of manufactured products citing quality complaints identified during FDA audits in their plants. We have had about 19 instances of Companies facing a Ban on export of formulations from different plants in the year 2013-14.

C Gowri Shankar Executive Director TAKE Solutions Pharma Bio World

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ndia has almost 500+ approved facilities with marketing authorisation from the USFDA. Almost 40 per cent of US Generics market is supported by Indian generic drug Manufacturers and the business has been growing steadily. The Generics US market is significant for the Pharma Industry in India. As of last year it is estimated that Pharmaceutical Exports from India to the US was nearly USD 4.23 billion and is expected to touch USD 6 billion by the end of 2015. Moving Forward Will the industry regain FDA‘s confidence? As a domain centric technology enabled IT business solution provider to the Indian Pharmaceutical Industry, we have observed some very encouraging changes in the approach of the Indian Pharma Industry, as listed below. 1) The Indian Pharma Industry has over the last couple of years been very receptive to adopting IT enabled quality systems and solutions which would help it implement quality processes and adherence across different manufacturing facilities. 2) We observe that the Chief Information officers (CIOs) and technology heads of the Pharma Industry in India have formed a knowledge sharing forum to identify the right solutions for the industry and share experiences on their success and challenges. 3) CIO s in the Pharma Industry today have been vested with large budgets to implement IT automation projects especially those that directly influence the quality processes. 4) The CXO community in the Pharma industry today is receptive to working with strategic partners who can conceive and implement transformational projects across the organisation.

5) There is a great deal of receptiveness for SaaS based IT solutions amongst the small medium players in the industry which helps them replace CAPEX with Opex. Constructive Approach of the Pharma industry - Dispassionate and Objective Having been in the food industry earlier I have witnessed instances where industry confederations and influential groups have raised issues of trade discrimination or vested interests when faced with similar situations. Thankfully, the Pharma industry has had a dispassionate and objective view of the problem, which is the first very important step to addressing the issues faced. The USFDA also has been very positive in its entire approach by investing/ strengthening its team of inspectors to 17 members across multiple cities, who can visit Pharma organisations, consult on issues and help them resolve and improve product quality – a motive that clearly indicates the Health authorities commitment to ensure India succeeds as large global generics player and supports affordable care policies of the Obama Health Care initiatives. Possible Approaches to Challenges Faced It is clear that India is under enhanced scrutiny given the size of the industry and our market share of the Generics in US. Indian Pharma industry is at a crucial juncture to assure the world at large that they have adequate systems and controls that are needed to establish and bring back the confidence. Most of the quality issues identified can be addressed by streamlined Records October 2014 47

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Indian Pharma industry is at a crucial juncture to assure the world at large that they have adequate systems and controls that are needed to establish and bring back the confidence. Management, Training Management to the Staff, and Tracking Enterprise Quality Compliance. There are multiple product solutions that are available to enhance compliance adherence like Document Management systems (For Records Management), Track wise / Master Control / Pilgrim (For Enterprise Compliance Management) etc., which can support adherence to all the regulatory needs and help enhance product quality. The Pharma Research and Manufacturing Association can jointly work with the Drug Controllerâ&#x20AC;&#x2122;s office in Government and the vendors of these IT tool organisations

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in promoting these tools at affordable prices. This will help in capturing the quality issues and resolving them early. This will go a long way in regaining confidence of the regulatory agencies. The tools can be hosted on private cloud and organisations can access them on SaaS basis to reduce total cost of ownership of the application and focus more on maintaining quality of manufactured product. THE USFDA also has been in partnership with UL â&#x20AC;&#x201C; certifying agency on conducting training programmes to various

organisations as part of Public-Private partnership to ensure that organisations understand the rigor of quality initiatives, and the need to address them to ensure compliance to regulations. A compliance programme that encapsulates the local as well as the global regulations guiding the operations and practices of the Pharmaceutical and LS industry is underway. This will make it easier for the industry to meet the requirements of all global agencies. These small steps and extensive training to the shop floor manufacturing personnel on quality systems will infuse a greater amount of confidence in India thus helping it retain and strengthen its position as a major generics exporter to the US. Contact: jananee.gangadhar@2020msl.com

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The Irish Cluster is Delivering In order to bring down healthcare costs, the EU market is slowly welcoming the generic drugs, a forte for Indian pharma companies. The European pharma sector is currently pegged at USD 48 billion out of which USD 16 billion is held by generic drugs alone. Biosimilars is another segment that the EU government has slowly begun to accept, which spells an untapped opportunity that can be leveraged. Given these facts, Ireland makes for an attractive destination for pharma companies to expand their operations or set up their EU base. Additionally, Ireland’s high level of expertise in the high-end nuance of the industry further makes it an ideal destination to establish and expand operations in the EU region.

Barry Heavy

Head of Life Sciences IDA Ireland Pharma Bio World

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ctober started on a very positive note for the City of Waterford in the South East of Ireland. Long known for its history in production of high quality crystal, the city is now establishing itself as a location of choice in the life sciences. On October 2 nd , the CEO of West Pharmaceuticals announced plans to build their largest integrated manufacturing facility on a 44 acre site with a planned investment of EUR 100 million and potential to employ up to 300 people. The new facility is expected to produce components for insulin injector cartridges and other high value packaging components, in order to meet growing demand from pharmaceutical a n d biotec h c us tomers . This is Wes t Pharmaceuticals second investment in Ireland, it has had a manufacturing and development centre in Dublin since 2005. That centre, which employs more than 230 people, also serves as European headquarters for the company’s The Tech Group subsidiary. The West investment is just the latest of a string of exciting investments in Waterford and across Ireland. In March 2014 the medical device company Nypro establish a 200 person manufacturing facility in Waterford, complementing their medical device R&D centre of excellence near Dublin. In February 2013, Sanofi announced plans to diversify activity at the Sanofi-Genzyme drug product site in Waterford, bringing in manufacturing of their blockbuster Lantus product, to complement the suite of Genzyme biologic drugs already fill finished at the site. Teva also have a significant presence in Waterford, where the site is a strategic centre for respiratory product development and manufacturing. A common theme between these investments is that they are all at the interface of bio-pharma and medical devices. Behind this pocket of investments in Waterford is a wider global trend – closer

interplay between the biopharma industry and the medical device industry. The pharma industry has become the biopharma industry as more and more of the world’s top drugs are biopharmaceuticals (drugs developed and manufactured using the tools of biotechnology, such as monoclonal antibodies). These biopharmaceuticals are complex, fragile and require injection, but their efficacy in treating disease has resulted in sales growth of 353 per cent to EUR 163 billion between 2001 and 2012. The global biotech R&D budget has jumped from USD 10.5 billion in 2001 to USD 103 billion in 2012 and the biotech pipeline swelled 155 per cent, up from 355 treatments in 2001 to 907 in 2012. Bio-pharmaceuticals now dominate the list of the world’s top blockbusters and account for over 70 per cent of the annual sales of the world’s top ten most successful drugs. A significant area of innovation in the biopharmaceutical space is in development of devices that can improve the storage and delivery of biopharmaceuticals. The materials and surfaces in the device that contact the drug must be designed to avoid impacting on the quality of the delic ate biopharmac e u tic a l. T h e design and features of the device can assist in patient compliance by making it easier to inject the drug. This trend in “drug device combinations” is also seen with more traditional small molecule pharmaceuticals, where for example, devices that enhance inhalation of small molecule drugs for diseases such as COPD have help to differentiate the drug and supported enormous growth in sales. Large generic companies (such as Mylan and Teva) are active in this area of drugdevice combinations as device innovation is an area they can invest in to differentiate their products from other generic players Waterford is not the only place in Ireland benefiting from this trend. Limerick is a October 2014 49

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NIBRT facility

University city on the River Shannon in the west of Ireland and has faced challenges in recent years with the closure of a major manufacturing facility by Dell. However in August 2013 biopharmaceutical company Regeneron announced that it would acquire the 400,000 ft 2 Dell facility and invest over EUR 240 million in retrofitting the facility to become a biopharmaceutical manufacturing facility. In April 2014, J&J subsidiary Ethicon bio surgery invested EUR 80 million and created 270 jobs in Limerick, in development & manufacturing of a highly innovative drug-device combination for wound healing. J&J already have significant investment in Ireland in development and manufacturing of biopharmaceuticals and medical devices and when announcing their decision to invest in Limerick in April 2014 Dan W i l d m a n t h e Wo r l d w i d e P r e s i d e n t o f Ethicon Biosurgery said “The decision to manufacture EVARREST Sealant Matrix in Ireland was due to the unique clustering of medical device manufacturing, automation and biomanufacturing skill sets across the Johnson & Johnson companies already operating in Ireland.” 50 October 2014

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O n O c t o b e r 1 s t 2 0 1 4 O p t e l Vi s i o n , a leading Canadian company specialising in Track&Trace and vision inspection solutions for the manufacturing industries, is to create 140 new jobs in Limerick as part of a new European expansion. Optel Vision develops and installs packaging line vision inspection and control systems for the pharmaceutical, medical devices and chemical industries. These sophisticated automated vision systems significantly reduce the health risks associated with mislabelled products, dosage errors and product mix-ups, while protecting genuine manufacturers against illegal counterfeiting. The presence of Regeneron, Ethicon and other companies in Limerick as well as the wider biopharmaceutical and medtech sectors in Ireland was a major driver for attracting Optel Vision to Limerick. Ireland has a long history in both the medical device and pharmaceutical industry. 25,000 people are employed in the medical device sector, with particular s t r e n g t h i n a r e a s s u c h a s v a s c u l a r, orthopaedic and ophthalmic devices. The Ireland pharmaceutical sector has also evolved into the Irish biopharmaceutical sector in recent years, with over EUR 7 billion in capital expenditure on new

biopharmaceutical manufacturing facilities announced i n the last 10 years from companies such as Pfizer, Lilly, J&J and Regeneron. These sectors are now coming closer together as the demand for “drug device combinations” gets stronger and Ireland is recognised as having the skills base to deliver in this convergent area. Recent investments include: • Forest labs: establishing manufacturing of respiratory drug delivery devices in Dublin. • Aerogen: Irish company developing next generation drug inhalation technology in Galway. • Mylan: EUR 400 million investment in development and manufacturing of inhaler technology in their Dublin site and injectable products in their site in Galway. • Contract research organisation PPD have established a GMP analytics lab in Athlone, offering specialised analytical services to companies producing respiratory drug device combinations and biopharmaceuticals. A key aspect of Ireland’s value proposition is the combined skill sets of medtech and biopharma. The critical mass of medical device and biopharma industry scientists, Pharma Bio World

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Biopharma Cluster in Ireland

engineers, quality professional and management provides a very strong talent pool that companies can tap into. Ireland has an exceptionally strong regulatory track record in both sectors which provides real comfort to companies as they seek to mitigate risk. Biopharmaceuticals are extremely complex, expensive to manufacture and subject to intense r e g u l a t o r y s c r u t i n y. W h i l e p a c k a g i n g these products in an innovative device has the potential to drive sales through improving adoption and compliance, it also adds further complexity to the product and the supply chain, thereby increasing risk. Irelandâ&#x20AC;&#x2122;s track record in regulatory excellence in both sectors serves to significantly mitigate this risk. Adding complex and innovative devices to an already expensive drug also drives up COGS, but again Irelandâ&#x20AC;&#x2122;s medical device space has a tremendous reputation Pharma Bio World

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in managing cost through continuous improvement and operational excellence, while still maintaining an intense focus on quality. In the last year, four Irish medical device manufacturing have won the prestigious international Shingo Gold award for operational excellence. The Irish Government is also actively supporting this trend of the interface of medical devices and biopharmaceuticals and both sectors have been prioritised as areas for research investment as part of a government review of overall state investment in research. In 2004 Ireland was predominantly a location for small molecule pharmaceutical manufacturing (drug substance and drug product). At that time there was only one site in active production of a biopharmaceuticals, employing about 400 people in Cork (Merck-legacy Schering facility). In 2013,

after EUR 7 billion of capital investment there are biopharmaceutical manufacturing sites spread across the country, including new sites in development from Alexion, Regeneron and Jazz Pharmaceuticals (see map below). Employment in these new sites has grown to over 5,000 people and looks set to expand further. In response to this growth in biopharma manufacturing, the Government invested EUR 57 million in the creation of the national Institute for Bioprocess Research and Training, a unique facility that was designed to mimic a state-of the art biotech Drug substance and drug product manufacturing facility with state of the art analytics/quality labs. This allows research to be conducted on biopharmaceutical manufacturing processes in a real world environment. It also provides an environment for practical training of staff in a realworld biopharmaceutical manufacturing environment with access to state-of-theart industry relevant equipment. In 2013 NIBRT provided practical training to over 2,000 people, providing a strong supply of talent into the growing industry. NIBRT has recently announced collaboration with the Irish Medical Device Association, who have a very active program in development of training programs for the medical device industry, working with the Government training agency Skillnets. Such initiatives have the potential to underpin further growth in this exciting interface area of medical devices and biopharmaceuticals as the supply of highly specialised talent is maintained through highly foc us ed and prac tic a l tr a in in g programme+s. Ireland is a small country but punches significantly above its weight in these sectors. The close proximity and strong working relationships between industry sectors, government agencies and research and training centres creates the basis for an exciting and vibrant cluster. Contact: vidhi.shah@text100.co.in October 2014ď&#x201A;&#x201E; 51

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marketing initiative

Ten Reasons to Choose Image Based ID Readers

mage-based code readers stand The latest generation of image-based ID readers has proven to poised to replace laser scanners in outperform lasers in the following areas: a wide range of industries including 1. Read rate performance 6. Barcode quality feedback food, beverage, consumer goods, 2. Image archiving 7. 2D code reading pharmaceutical and automotive, but when considering a transition from 3. Long-term reliability 8. Visualization and communication laser scanners to image-based barcode 4. Ease of setup and deployment 9. Multiple code reading and output capability readers, many think that the is cost too 5. Omnidirectional code reading 10. Future proof high. Today’s most advanced imagebased readers have overcome the destination or replaces the defective portions of the code, distortion, and technical and economic hurdles and barcode and resends package back other defects. now offer a more attractive alternative through the sorting system. This failed • Another advantage from a reliability to industrial laser scanners on the condition increases the labor material perspective is that image-based factory floor. costs and reduces the efficiency of readers have no moving parts. sorting equipment because packages • An image-based system can display Thanks to advances in microprocessors, are handled more than once. the scanner image on a monitor or imaging sensors and decoding algorithms, industrial display in real time. image-based ID readers have become To cope with these limitations, the • As the user sets the system up, not only more affordable, but also more logistics industry has designed special the display shows exactly what the powerful. The logistics barcode-scanning labels that maximize read rates and scanner sees, ensuring that the market breaks down into three segments. equipment specifically optimized to images will be in-focus and that At the entry level, a mix of conventional handle high numbers of reads. the image will include all codes area-array imagers and laser scanners on any package that comes down read codes on slow moving or stationary Image-based readers have several the conveyor. objects. At the high end of the scale, significant advantages to traditional laser • Area array image-based readers fixed line scan image, based systems scanner technology, such as: also offer better uptime because handle high-speed, multi-sided barcode • An image-based reader can find and laser scanners use motors and other tunnel applications. Situated between locate a barcode regardless of its mechanical mechanisms to `move’ these two extremes, is an entire range orientation. This can also provide a the laser spot across the code. of applications that currently rely on an major advantage for set up, record increasingly challenged generation of keeping, and diagnostic purposes. The logistics industry is also into the laser-based scanners. • Imagers can use advanced software, introduction of two-dimensional (2D) to read 1D barcodes with significantly codes like Data Matrix. The amount of Today’s most advanced image-based ID less contrast—which is critical for information that 2D codes can store readers have overcome the technical and p o o r l y p r i n t e d c o d e s o r f o r 1 D makes them very attractive for a wide economic hurdles and now offer a more barcodes not printed on a standard range of applications and image-based attractive alternative to industrial laser w h i t e l a b e l , f o r i n s t a n c e o n a scanners are required to read these scanners on the factory floor. A laser corrugated box for an example. symbologies. As large retailers and scanner reads a barcode by measuring • I m a g e r s p r o v i d e t h e a b i l i t y t o internet fulfillment centers, consider the size of the printed modules using o v e r c o m e t h e i s s u e s p r e s e n t e d capital equipment purchases to add light reflected from the code. One of the by damage or reflections in the capacity or increase throughput, raising method’s advantage is its simplicity as it c o d e s i n c e t h e i m a g e r s o f t w a r e barcode read rates by just one per cent is easy to set up, connect, aim and can can use just portions of the code to could significantly shorten payback read codes fast enough to accommodate ‘reconstruct’ the data. schedules and increase ROI. high speeds. • The ability to use the entire 1D - Didier Lacroix barcode for reading instead of An unread code requires diverting the Vice President, International just a single laser line enables package to a manual station where Sales & Marketing image-based readers to read a code Cognex Corporation despite low resolution, voids in an operator directs the package to its 52 October 2014

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marketing initiative

Modularity: The Lead Time Killer

irtually none. That’s how much safety solution.” This elevated degree time is spent on programming of modularization and standardization during the construction and allows Seidenader to produce and test commissioning of a CS-series inspection its machine modules in advance. machine from Seidenader. The secret is the exceptional modularity of both the A New Level of Functional Safety machine and its automation architecture. For Seidenader ’s customers in the The end user has plenty to gain from pharmaceutical industry, this means this new machine design as well. Since spending more time in productive the software has already undergone operation and less on qualification and maintenance. Did we mention the thorough testing on a fully operational machines are also more flexible? Behind machine and didn’t have to be tweaked all of these advancements, you’ll find a and adapted throughout construction uniquely integrated automation solution a n d c o m m i s s i o n i n g , i t p r o v i d e s a n from B&R that facilitates a modular u n p r e c e d e n t e d l e v e l o f f u n c t i o n a l machine design along every step of safety. When it comes time to add or replace modules down the road, the the way. comprehensive standardization makes “ U n t i l v e r y r e c e n t l y, w e f a c e d t h e this much faster and easier as well. same mountain of programming that many OEMs face when building and “If the requirements change and you commissioning a new machine,” says need to swap out the infeed/outfeed Herbert Grindinger, head of Seidenader’s unit, it’s no problem at all – you just PLC programming department. “With our enable or disable the respective software new series of CS inspection machines, modules and the rest of the code remains we’ve finally leveled this mountain.” For untouched,” explains Grindinger. “This Seidenader this means a drastic reduction greatly simplifies the task of system in lead times throughout production, qualification for the end user.” Machine commissioning and maintenance of its operators are supported at every step inspection machines for liquid and freeze- along the way by B&R’s commitment dried medication and nutrition provided in to completely integrated automation. the form of infusions or injections – known as “parenterals”. For the programmers, it means being able to focus on enhancing machine performance and adding new features. Switching to integrated automation from B&R was the first step toward these achievements. Seidenader now works with a single software project that covers the entire inspection machine, including every piece of optional equipment. “For us, this turns the creation of custom control software into a simple matter of configuration rather than tedious programming,” explains Seidenader’s controls expert. “And the best part is that, with B&R, this also includes the Pharma Bio World

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The new solution makes it easy for them to generate a complete list of components that can simply be checked off during qualification. Grindinger ’s team found B&R’s engineering environment very helpful when it came time to create the machine’s control software. “What we really like about Automation Studio is that it doesn’t place any restrictions on the user with regard to selecting a programming language,” explains PLC developer Michael Grampp. “We went with Structured Text, for which B&R offers comprehensive and powerful libraries. The added support for pointers helped us manage the large volumes of data that come with modularization.” Transparency and User-friendliness Thanks to PackML B&R’s support for PackML further added to the system’s transparency. “We’ve implemented PackML as an internal standard that everyone must adhere to,” says Grindinger. “It’s not something we impose superficially just for the HMI benefits – we’ve broken it down to the level of each individual machine module. This makes the software more transparent

Seidenader uses PackML as an internal standard applied universally by all programmers, which makes the software easier to understand, diagnose and operate.

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marketing initiative and easier to use and maintain. Beyond that, it also simplifies the tasks of line integration and communicating with higher-level systems.” Another significant advantage of B&R’s engineering environment is that it allows machine control and motion control to be handled on a single hardware platform. “The fact that we no longer need two separate platforms substantially simplifies programming,” adds Grindinger. A powerful industrial PC from B&R’s Automation PC 910 series handles the control aspects of the new CS machine. It is mounted in the main control cabinet on the central machine module along with up to five image processing PCs, which ensure that the CS is able to detect a wide array of contaminants and optical defects. The machine is suited for ampules, cartridges and vials up to 100 ml, covering a broad spectrum of product and container formats. To complement visual inspection, it is also possible to integrate modules for headspace gas analysis (HSA), nearinfrared spectroscopy (NIR), polarimetric inspection (GSI) and high-voltage leak detection (HVLD). Software Cam Switch for Added Triggering Flexibility “When you use cameras for visual inspection, the way that they are triggered has a direct impact on the quality of the

In developing its new CS series of inspection machines, Seidenader took advantage of B&R’s commitment to fully integrated automation to drastically reduce lead times for its custom-built machines through improved modularity.

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re-sults,” says Grindinger. In the past, the and effort installing, commissioning and company had to use a separate electronic servicing the modules.” cam sequencer, which only permitted position-based triggering. This also meant Integrated Diagnostics for Service that a new recipe had to be created in Technicians advance for each new profile, or the cam switch software had to be modified, Thanks to B&R’s integrated automation retested and requalified. solution, commissioning and maintenance were already pretty simple to begin with. “B&R offered a better solution,” explains “With the software for all of the automation Grindinger. “The X20DS4389 module components managed and distributed from from their X20 series provides digital the central control computer, installing outputs that use the AsMcDcs library to or replacing a drive is child’s play,” allow triggering based on timestamps. confirms Grampp. “With B&R, there’s Used in conjunction with a position-based no need to use a separate programming trigger, this makes it possible to maintain device or pre-install any software.” No consistent timing and achieve optimal extra equipment is needed to perform inspection results – regardless of how diagnostics on the automation system, fast the inspection carousel passes the either. The diagnostic functions B&R containers in front of the camera and provides, such as System Diagnostics rotates them with the aid of small servo Manager, can be called up directly on the motors.” Not only does the CS no longer HMI. Seidenader programmed all of the require a separate cam switch, it also other tools needed for analysis directly allows the same software to handle a into its HMI application. whole range of speeds simply by tuning recipe parameters – so there is also no Grindinger has big plans for the system’s yet untapped potential. “B&R’s solution need for requalification. gives us so much capacity for growth, I expect we’ll soon be able to push Operators set these parameter values the specified output for the new CS in the same way they interact with every series even higher than the current 400 standard and optional module in the containers per hour. We also designed the machine – using a custom Panel PC 820 machines and the automation architecture HMI with an 18.5” display in 16:9 format, in a way that allows us to easily scale which communicates with the Automation the solution across our entire range of PC 910 control computer via Ethernet. products, including our most powerful inspection machine. With B&R, we’re Standardized Electrical Interface confident that we have the right partner between Modules for the job.” Seidenader selected POWERLINK to T h e I P 6 5 r a t i n g o f d e c e n t r a l i z e d network the up to twenty ACOPOS drives A C O P O S r e m o t e d r i v e c o m p o n e n t s used in its new inspection machine. allows them to be mounted directly Between machine modules, a single on the machine without an additional standardized hybrid cable provides control cabinet. Power runs through the power supply for the decentralized a single hybrid cable carrying both ACOPOSremote drives as well as two lines the POWERLINK and STO signals in for the STO signal and POWERLINK. The addition to the 24 V supply. By using this corresponding remote connection boxes standardised technology as the electrical allow either a line or star topology. “The interface between the various modules hybrid cable lets us take modularization that make up its new CS-series inspection to a whole new level,” says Grindinger. machines, Seidenader has taken its “We now spend considerably less time modular solution to a whole new level. Pharma Bio World

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press release The Best in Industry Felicitated at Frost & Sullivan’s Awards 2014 Frost & Sullivan successfully hosted its 6th Annual India HealthcareExcellence Awards at Taj Lands End, Mumbai recognising distinguished achievers in the Indian healthcare industry. The banquet witnessed the presence of the who’s who in the healthcare sector, and deserving companies and individuals were felicitated for their innovative growth strategies and solutions. This year, 26 awards were presented to companies and individuals who demonstrated best practices in the Indian healthcare and life sciences industry. The awards program followed a rigorous methodology to recognise superior planning and execution of product launches, strategic alliances, distribution strategies, technological innovations, customer services, healthcare delivery services, and mergers and acquisitions. Other crucial factors used to evaluate the nominees included leadership qualities, strategy, growth, service, innovation, integration, marketing, and financial performance.

KSB Launches Etanorm SYT KSB has launched their Etanorm SYT pump series to the Indian market. KSB’s latest generation of single-stage volute casing pumps has been specially developed for applications in modern heat transfer systems and hot water circulation. Etanorm SYT pump sets handle hot water as well as mineral oil based thermal fluids and synthetic thermal oils at tempera¬tures of up to 350 degrees Celsius. They are particularly suited to the rough conditions experienced in heat transfer systems. The new pumps’ stable rib design and reinforced bearings make them resistant to external forces.

Cavatak Immunotherapy Combination Shows Superior Anti-cancer Activity Viralytics Limited announced at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid that preclinical studies have generated further evidence of improved Cavatak anti-cancer activity when used in combination with immune checkpoint inhibitors, a new class of cancer immunotherapies with blockbuster potential. Cavatak is a proprietary formulation of a common cold virus that has been shown to preferentially infect and attack cancer cells. The latest preclinical study assessed the activity of Cavatak given in combination with either the mouse homologue of the CTLA4 monoclonal antibody ipilimumab, or an anti-PD-1 monoclonal antibody. In both cases, the combination of the checkpoint inhibitor Pharma Bio World

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with Cavatak produced superior efficacy outcomes in a twophased mouse melanoma study, compared to the efficacy of either agent alone.

Apollo Hospitals Collaborate with Sanofi Apollo Hospitals and Sanofi announced their decision to collaborate on the expansion of Apollo Sugar Clinics, which provide integrated diabetes care programmes in India. Through this collaboration, Apollo and Sanofi plan to leverage their respective expertise in diabetes to provide patients with access to comprehensive educational resources, treatment and care programs that can help patients better manage their diabetes. The first wave of this collaboration will focus on the establishment of 50 Apollo Sugar Clinics.

Smart Injection Pen Design for Precise Tracking of Insulin Delivery Product development firm Cambridge Consultants has designed an injection pen for diabetes patients that aims to make daily management of the disease an easier, more accurate task. The KiCoPen device is designed to capture the exact dose delivered – and send the information to an associated smartphone app. And all without a battery – the action of removing the injector cap powers the device. There is currently no injector pen on the market that combines these capabilities.

Mucosis Presents Infectious Diseases Vaccines Pipeline Update Mucosis B V, a clinical stage biotechnology company developing novel vaccines for infectious diseases, presented updates on its research and development programme at the Biotech in Europe Forum in Basel. Mucosis, which has recently announced several strategic partnerships including one with the Netherlands Enterprise Agency, an agency of the Dutch Ministry of Economic Affairs, and another with China-based Changchun BCHT Biotechnology Co (BCHT), is advancing its lead product, SynGEM, as a vaccine candidate for Respiratory Syncytial Virus (RSV).

SCHOTT Glass India Wins VNM’s Environmental Excellence Award In its first-time participation in VNM TV’s prestigious Environmental Excellence Awards competition, Schott Glass India Pvt Ltd has won the Environmental Excellence Award 2014. This recognition identifies Schott’s Pharmaceutical Tubing plant as the best “Green Manufacturing Unit” in Gujarat. October 2014 55

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pharma news Sucampo Extents Collaboration Agreement with Takeda Sucampo Pharmaceuticals, Inc has signed an amendment to the existing collaboration and license agreement (Collaboration Agreement) covering the United States and Canada for Amitiza (lubiprostone) with Takeda Pharmaceutical Company Ltd. The amendment includes various modifications to the Collaboration Agreement including the extension of the current term, minimum commercial investment during the current term and various governance changes allowing Takeda additional flexibility in commercialising Amitiza. During the extended term, which will begin on January 1, 2021, Takeda will split with Sucampo the gross profits of branded AMITIZA for any dosage strength and form for the existing indications in the US and Canada. In addition, on April 1, 2015 Takeda will no longer reimburse Sucampo for the product details made by Sucampo sales representatives to healthcare professionals as well as other ancillary costs of the sales force.

Medpro Collaborate with Teva Medpro Pharmaceutical Ltd - a subsidiary company of Cipla Medpro, the third largest pharmaceutical company in South Africa, has entered into a collaboration with Teva Pharmaceuticals Ltd, an affiliate of Teva Pharmaceutical Industries Ltd - the largest generic pharmaceutical manufacturer in the world with a presence in about 60 countries and approximately 45,000 dedicated employees worldwide. The collaboration is restricted to the territory of South Africa. The collaboration is a sales and distribution arrangement whereby Cipla Medpro will exclusively market Teva’s broad pharmaceutical product portfolio in South Africa.

Under terms of the agreement, Sun Pharma will acquire worldwide rights to tildrakizumab for use in all human indications from Merck in exchange for an upfront payment of USD 80 million. Merck will continue all clinical development and regulatory activities, which will be funded by Sun Pharma. Upon product approval, Sun Pharma will be responsible for regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing and commercialisation of the approved product. Merck is eligible to receive undisclosed payments associated with regulatory (including product approval) and sales milestones, as well as tiered royalties ranging from mid-single digit through teen percentage rates on sales.

Isis Pharma Bags USD 18 Million Milestone Payment from GSK Isis Pharmaceuticals, Inc has earned USD 18 million milestone payment from GlaxoSmithKline (GSK) related to the advancement of the Phase 2/3 study of ISIS-TTR Rx in patients with familial amyloid polyneuropathy (FAP). ISIS-TTR Rx is an antisense drug in development with GSK for the treatment of transthyretin amyloidosis, a severe and rare genetic disease characterised by progressive dysfunction of peripheral nerve and/or heart tissues. Including this USD 18 million milestone payment, Isis has generated USD 45 million of the USD 70 million in upfront and milestone payments Isis is eligible to earn for advancing ISIS-TTR Rx in development. In addition, if GSK elects to exercise its option to exclusively license the ISIS-TTR Rx programme, Isis is eligible to receive a license fee, regulatory and sales milestone payments and double-digit royalties on sales of ISIS-TTR Rx .

MSD, Sun Pharma Ink Licensing Deal Mylan Introduces Generic Combivir Mylan Inc has announced the US launch of its Lamivudine and for Tildrakizumab Merck & Co, Inc, known as MSD outside the United States and Canada, and Sun Pharmaceutical Industries Ltd through their respective subsidiaries, has announced an exclusive worldwide licensing agreement for Merck’s investigational therapeutic antibody candidate, tildrakizumab, (MK-3222), which is currently being evaluated in Phase 3 registration trials for the treatment of chronic plaque psoriasis, a skin ailment. 56 October 2014

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Zidovudine Tablets USP, 150 mg/300 mg, which is the generic version of Viiv’s Combivir. Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated for the treatment of HIV-1 infection in combination with other antiretroviral (ARV) agents. Mylan has begun shipping this product, further strengthening the company’s growing ARV portfolio in the US market. Pharma Bio World

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biotech news US FDA Approves AbbVie’s HUMIRA AbbVie, a global research-based biopharmaceutical company, has announced that the US Food and Drug Administration (FDA) approved the extension of the HUMIRA indication for moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) to reducing signs and symptoms in patients ages 2 and older. HUMIRA was approved in the United States in 2008 for polyarticular juvenile idiopathic arthritis (JIA) in patients ages 4 and older.

immatics and BioNTech to Advance GAPVAC into Trials immatics biotechnologies GmbH and BioNTech AG are moving a novel concept of fully personalised therapeutic cancer vaccines, Glioma Actively Personalised VAccine Consortium (GAPVAC), into the clinic. The German national authority, the Paul-EhrlichInstitute (PEI), has approved the start of a phase 1/2 study, GAPVAC-101, which applies for the first time the concept of treating glioblastoma patients based on drugs designed and manufactured for each patient individually according to specific characteristics of their tumor and immune system. The screening of first patients for the trial has commenced at the University Hospital of Heidelberg, Germany, and the University Hospital of Tuebingen, Germany. The complex manufacturing of the personalised vaccines will be performed by the GMP unit of the University of Tuebingen in close cooperation with the “GMP and Core Services platform” of the German Cancer Consortium (DKTK).

CytRx Commences Operations at Freiburg Laboratory CytRx Corporation, a biopharmaceutical research and development company specialising in oncology, has commenced operations at its new discovery laboratory, located in Freiburg, Germany. The new laboratory will conduct discovery and translational research to create drug candidates that utilise novel linker technologies that couple chemotherapeutic agents and proteins either inside the body or externally, and then concentrate drug in tumors. Led by Felix Kratz, PhD, Vice President of Drug Discovery and inventor of aldoxorubicin, and Andre Warnecke, PhD, Senior Director of Drug Discovery, the discovery team will work to expand CytRx’s novel albumin-binding anti-cancer drug pipeline. Pharma Bio World

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Sanofi Pasteur Starts Phase III Trial of Investigational Rotavirus Vaccine Sanofi Pasteur, the vaccines division of Sanofi, has announced the start of a phase III clinical trial in India for its investigational rotavirus vaccine, developed and manufactured by its affiliate Shantha Biotechnics in Hyderabad, India. The trial is designed to show non-inferiority against a currently licensed vaccine with the use of three, ready-to-use liquid doses administered orally, starting from six-to-eight weeks of age, with the subsequent doses administered at 4 weeks intervals. Close to 1,200 volunteers are being sought at 12 clinical trial sites in India. Shantha’s investigational rotavirus vaccine includes antigens against serotypes G1, G2, G3 and G4.

Alexion Submits NDA in Japan for Asfotase Alfa Alexion Pharmaceuticals, Inc has submitted a New Drug Application (NDA) for asfotase alfa, an investigational, first-inclass targeted enzyme replacement therapy for the treatment of hypophosphatasia (HPP), to Japan’s Ministry of Health, Labour and Welfare (MHLW). HPP is a genetic, chronic and progressive ultra-rare metabolic disease that can lead to destruction and deformity of bones, profound muscle weakness, seizures, respiratory failure and premature death. The MHLW submission includes positive data from 71 patients with HPP (ranging from newborns to 66 years of age), including Japanese patients, enrolled in three pivotal prospective studies and their extensions, as well as a retrospective natural history study in infants.

Tobira Doses First Patient in CENTAUR Tobira Therapeutics, Inc, a clinical-stage biopharmaceutical company advancing cenicriviroc (CVC) in liver disease and HIV, has dosed the first patient in its CENTAUR study of patients with non-alcoholic steatohepatitis (NASH) and liver fibrosis, a disease affecting approximately 3-5 per cent of the US population. The initiation of the CENTAUR study follows the completion of a Phase 1 safety study in subjects with liver cirrhosis. To date, approximately 580 subjects have been dosed with CVC in Phase 1 and Phase 2b clinical studies, including 115 HIV-1 infected subjects on treatment for up to 48 weeks. October 2014 57

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Media Preparation System The USP reference standard tablets are used to perform a dissolution instrument suitability test after a successful physical parameter qualification (OQ). Duirng this suitability test, the quality of degassing has a significant effect upon the test results obtained as does vibration. Naturally, the mechanical fitness of the instrument has to be established and is usually achieved by performing the OQ prior to the USP suitability test. Low vibration levels, low wobble, correct tool centering and precise tool depth settings are just some of the factors which may affect a successful qualification – but media degassing is one of the most influential factors. The PT-DDS4 media preperation system has proven in many tests and in general operation, that its automated degassing and dosing procedure fulfils the requirements of both the FDA and USP and that the USP Prednisone qualification test (PVT) will successfully

Automatic Syrup Manufacturing Plant Sugar syrup is transferred to manufacturing vessel through online sugar syrup prefilter by vacuum. Entry of all propeller agitators is from bottom through a specially designed cartridge mechanical seal with TC/TC seal face. The advantage of the bottom propeller agitator over the conventional agitator is that there are no vibrations of shaft, no couplings in the drive assembly. Pipes, pipe fittings and valves are of SS-316, seamless, internally electropolished with TC unions and silicon gaskets. Manhole of all the vessels is equipped with davit fitting and the cover of the manhole slides instead of being lifted. Values like current, product temperature are displayed digitally on the electrical control panel. The mechanical seal is equipped with a water circulating system and has a water detection sensor which trips the motor, if the water circulation to the seal is interrupted.

For more information, please contact:

Pharma Test Instruments India Pvt Ltd 2, Sree Datri Niwas, 2 nd Floor Nagwara Circle, Outer Ring Road, Opp: Manyata Softech Park. Bengaluru, Karnataka 560 045 E-mail: c.neelam@pharma-test.de

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

mapp Technology & ACOPOS P3 3-axis Servo Drive mapp technology simplifies the development of new programs through the use of modular software blocks, freeing developers from having to program basic functions so they can instead concentrate on their main task: implementing the machine or system process itself in application software. In addition to reducing the development time for new machines and systems by an average of 67 per cent, mapp technology also results in savings for service and maintenance. The ACOPOS P3 represents a similarly impressive progression in automation technology. This threeaxis servo drive allows space savings of up to 69 per cent in the control cabinet. It also features a sampling time of 50 μs for the entire controller cascade, making it the fastest servo drive with safety functions on the market. For more information, please contact: B&R Industrial Automation Pvt Ltd 8 Tara heights, Pune-Mumbai Road, CTS 21 (19A) Wakdewadi Shivaji Nagar, Pune, Maharashtra 411 003 Tel: 020-41476999, Fax: 91-020-41478998 E-naukL ninad.deshpande@br-automation.com

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FRP Filters

Carton Box for Pharma Packaging EPP offer different types of filters for various applications in industries like pharma, dyes and intermediates, chemicals, and petrochemicals.

Nutsche filter is one of the simplest batch type filter. It is a dish end type of tank with filter plate fitted or bolted inside with flanges having cloth as filter media. Filter plate is perforated to pass the filtrate. The slurry fed into the filter vessel is separated into filtrate and the residue in the form of cake on the filter cloth which can be removed manually. The filter can be offered up to operating vacuum of 720 mm of Hg.

Locked4Kids is reclosable carton box designed for pharma packaging. It contain special blister trays with small hooks on the long sides. These hooks are placed diagonally to one another, so that the tray is locked securely when it is pushed right in. In order to remove the tray, both hooks have to be released simultaneously by pressing on the box firmly and evenly at the marked points with the thumb and forefinger. This is no problem for adults but impossible for children, whose hands are too small to span the width of the carton and push both hooks in at once. Furthermore, both sides of the box are coated with a tear resistant laminate to prevent children from simply ripping it apart.

For more information, please contact:

EPP Composites Pvt Ltd Plot No: 2624, Kranti Gate Main Road, GIDC Lodhika Indl Estate Kalawad Road, Metoda, Gujarat 360 021 Tel: 02827-287059, 287060, 287061, Fax: 91-02827-287063 E-mail: marketing@epp.co.in

Romaco Group Am Heegwald 11, 76227 Karlsruhe, Deutschland Tel: +49 (0)721 4804 0, Fax: +49 (0)721 4804 225 E-mail: susanne.silva@romaco.com

Circulating Pumps for Heat Transfer Systems KSB offers their Etanorm SYT Pump Series to the Indian market. KSB’s latest generation of single-stage volute casing pumps has been specially developed for applications in modern heat transfer systems and hot water circulation. Etanorm SYT pump sets handle hot water as well as mineral oil based thermal fluids and synthetic thermal oils at temperatures of up to 350 o C. They are particularly suited to the rough conditions experienced in heat transfer systems. The new pumps’ stable rib design and reinforced bearings make them resistant to external forces. Especially the increasing use of highly efficient synthetic oils has been calling for new developments in pump technology. Etanorm SYT incorporates significant technical innovations, such as a new vent design through which gases can be reliably removed during operation. For very critical fluids a variant with double mechanical seal has been introduced. Customers may choose between carbon (standard) or SiC plain bearings. KSB’s Etanorm SYT pumps are hydraulically optimised and highly energy-efficient. The pumps are supplied with an impeller dia individually matched to the duty point of the actual system. By selecting the best impeller dia and pump size from the large range on offer, an ideal combination can be found for the majority of duty points. For more information, please contact: KSB Pumps Ltd Mumbai-Pune Road, Pimpri, Pune, Maharashtra 411 018 Tel: 020-2710 1241 E-mail: bipin.kode@ksb.com

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events diary

BioPharma India Convention

UBM India Pharma Awards 2014

Date: 18 th – 19 th November 2014

Date: 1st December 2014

Venue: Hyatt Regency, Mumbai

Venue: The Westin, 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.

The UBM India Pharma Awards provides a platform to demonstrate organizational capabilities in the direction of Innovations in 10 different categories on this most leading industry platform. The event is attended by the who’s who from the Pharma industry, policy makers from the country as well as Asia and Europe.

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.

As the pharma industry is increasingly looking towards India for higher quality, low cost pharma solutions, the UBM India Pharma Awards is the perfect place for companies to engage with the movers and shakers in India’s pharma machinery, technology, ingredients, outsourcing and biopharma industry.

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

Kumudini Bodha Tel: +91-22-61727163 Board: +91-22-61727000 M: +91-9833326239 | Fax: +91-22-61727273 E-mail: kumudini.bodha@ubm.com

5 th Annual Pharmacovigilance Asia 2014

BioFIT 2014 Pharma and Biotech Event

Date: 25 th – 27 th November 2014

Date: 2 nd – 3 rd December 2014

Venue: Grand Copthorne Waterfront Hotel, Singapore

Venue: Lille Grand Palais, France

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.

A partnering event entirely dedicated to tech transfer and open innovation in the Life Sciences sector. BioFIT attracts over 800 attendees from 30 countries among which top leaders from the pharma and biotech industry, academics and practitioners in technology transfer, intellectual property and licensing.

It is this developing threat environment and the challenges facing pharmacovigilance professionals that the 5th Annual Pharmacovigilance Asia Summit will be addressing Contact: IQPC Worldwide 61 Robinson Road Robinson Center, #14-01, Singapore 068893 Tel: +65 6722 9388 | Fax: +65 67203804 Email: enquiry@iqpc.com.sg 60 October 2014

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Together, they will share best practices, know-how and will maximise qualified alliances thanks to a cutting-edge partnering system. Contact: MARION SIGIER +(33) 3 28 55 90 60

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bookshelf Phytopharmaceutical Technology (Hardcover) Authors: P H List, P C Schmidt Price: USD 756.72 No of Pages: 374 pages About the Book:Drugs from plants are a major contribution to world health. Their production involves machinery, workers, quality control, standards, and legislation. Phytopharmaceutical Technology is a practical reference volume that provides the basic information necessary to select and operate machinery and to process plant products through to the desired liquid, solid, or powdered drug form. As a result, much of the book is devoted to the production process. The book contains details regarding the dozens of types of machinery that can be used, as well as drawings, including cross-sections and schematics of the working action. Quality assurance, standardisation, and regulation is also discussed. Phytopharmaceutical Technology is a handy reference tool for engineers and industrial chemists in the plant drug processing industry, as well as excellent reading for university students.

Herbal Drugs as Therapeutic Agents (Hardcover) Authors: Amritpal Singh Price: USD 109.05 No of Pages: 232 pages About the Book: Phytochemicals are the mainstay of therapeutics of herbal or botanical medicine. Research on phytomolecules is conducted worldwide and several have been screened for clinical trials. This includes several promising anticancer phytomolectules, such as withaferin-a and camphothecin. This book provides a scientific understanding of the mode of action of these molecules. It targets only those phytohemicals and herbal extracts that are subjects of recent pharmacological investigations. Chapters such as industrial crops for steroid manufacturing and anticancer and cytotoxic potential of sesquiterpenoids add special flavour to the book, making readers eager to learn more about the commercial viability of phytochemical and herbal extracts.

Freshwater Phytopharmaceutical Compounds (Hardcover) Authors: Santhanam Ramesh, Rajabalaya Rajan, Ramasamy Santhanam Price: USD 134.21 No of Pages: 250 pages About the Book: In an effort to bring together the disciplines of biology and pharmacy for the identification and large-scale collection of pharmaceutically important organisms, Freshwater Phytopharmaceutical Compoundspresents key information on freshwater flora, including common names, classification, global distribution, habitats, and biologyâ&#x20AC;&#x201D;all organised according to the activities of their bioactive compounds. An important resource for progress in pharmaceutical freshwater plant research, this book provides a comprehensive volume on pharmaceutical compounds of freshwater flora, covering the biology and ecology of the plants and the structures and activities of the different classes of pharmaceutical compounds derived from them.

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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:- 64