Pharma Bio World August 2017

Vol 16 | Issue 01 | august 2017 | Mumbai | Total Pages 60 | Price ` 150

PHARMA BIO WORLD

www.pharmabioworld.com

Vol 16 Issue 01 AUGUST 2017

Outsourcing

MUMBAI total pages 60 ` 150 HYDERABAD - 2017

GUJARAT - 2018

13-15, December 2017 Venue: Hyderabad, India

23-25, January 2018 20-23, February 2019 Venue: Ahmedabad, Gujarat, India Venue: Mumbai, India

MUMBAI - 2019

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

Maulik Jasubhai Shah

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Mahesh Kallayil (mahesh_kallayil@jasubhai.com)

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INSIGHT INTO THE PHARMACEUTICAL AND BIOTECH INDUSTRIES

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4  August 2017

Pharma Bio World

INTERVIEW 08

“There is a huge opportunity for biosimilar manufacturers to capitalize on market opportunities and bring more affordable medicines to the market.”

- Graham Reynolds Vice President and General Manager - Global Biologics West Pharmaceutical Services, Inc. FEATURES

14

Pharmaceutical Contract Manufacturing - Shyam Sunder Singh

08 18

Technology Transfer during Outsourcing - Dr Gopakumar G Nair

21

QbD and Risk Based Approach for Efficient Design of Pharma Plants - Shailesh Dhume

24

Increasing the Access to Orphan Drugs and Specialty Medicines - Dr Piyush Gupta

27

14

GST: Initial Speed Bumps for the Pharmaceutical Industry - Kabir Bogra, Tushaar Talwar

30

Recent Advancement in Clinical Trials and Drug Development in Pharmaceutical Industry - Dr Vivek Dave, Dr Sachdev Yadav, Ms Smita Kumari

38

Serialization: Coding and Marking is Paramount to Readiness - Thierry Protas DOCTOR’S PERSPECTIVE

40

Prevention of Stroke in Atrial Fibrillation: One of the Major Roles of Oral Anticoagulants - Joanne van Ryn

18

46

NEWS UPDATE Press Release

48

Products

56

Events

CORPORATE AFFAIRS

BACKYARD

24

57

Book Shelf

58

Ad Index

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6  August 2017

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interview

“There is a huge opportunity for biosimilar manufacturers to capitalize on market opportunities and bring more affordable medicines to the market.”

Graham Reynolds, Vice President and General Manager - Global Biologics, West Pharmaceutical Services, Inc,

Graham Reynolds

i n a n e m a i l i n te r a c t i o n w i t h M a h e s h Kallayil, shares insights on trends in the biosimilar market and improving patient experiences through optimized biologic drug deliver y systems

Could you please tell us about West's journey so far?

What are the key thrust areas for West?

West Pharmaceutical Services, Inc. is a leading manufacturer of packaging components and delivery systems for injectable drugs and healthcare products. Founded in 1923, we have a long history of working side-by-side with the top pharmaceutical and biotechnology companies around the globe to meet th with more than 50 locations around the world, including a manufacturing facility in India's Sri City Special Economic Zone.

West offers proprietary packaging, containment and drug delivery products, including:

•• •• •• •• ••

Stoppers and seals for injectable packaging systems Syringe and cartridge components Self-injection systems Containment and delivery systems

Additionally, we provide contract manufacturing services, harnessing a powerful combination of innovation, technology infrastructure and expertise to serve customers in the pharmaceutical, medical and consumer industries. We offer quality, safety and reliability in injection molding, contract assembly and finished packaging.

8  August 2017

Our top priority is delivering quality products that meet the exact specifications and quality standards our customers require and expect. This focus includes excellence in manufacturing, scientific and technical expertise as well as management.

Please elucidate over the key difference between biosimilars and bio betters?

Biosimilars are a type of biological product that are licensed (approved) by regulatory agencies because they are highly similar to an already approved biological product, known as the biological reference product (reference product), and have been shown to have no clinically meaningful differences from the reference product."Bio-Betters"differ from biosimilars in that they are not identical to the original product and have been designed to have some clinical advantage. This term may not have an official designation, but is commonly used for those biosimilars that demonstrate benefits over and above those of the innovator and can, therefore, not be classed as biosimilars.

What are latest global trends in biosimilar drug delivery?

It's important to first talk about an overarching trend in the biopharmaceutical industry: a shift toward specialty care Pharma Bio World

interview and patient-centric, precision-based medicine.

With this as a driver, increased competition and the healthcare industry's focus on costs and qualitybased metrics are spurring drug companies to engineer better patient experiences into their treatments. This has particular implications for drug delivery for biosimilars and other biologics: biopharmaceutical manufacturers are focusing on the drug's delivery system earlier in the drug development process and working with delivery system manufacturers to create administration systems that are easy and convenient for patients to use, and can help differentiate drug products from other competitors.

What is the current status and future growth of biosimilar drug delivery in India?

Other notable trends include: •• A rise in the patient as the decision maker, rather than the provider, driven by better access to information, payer formulary, copay and benefit tiers •• Increasing access to continuous and integrated medical/patient data, driven by payers, physicians, hospitals and regulatory agencies •• Increased patient access in developing nations, driven by lower-cost medicines and biosimilars

Today and into the future, it is important for biosimilar manufacturers to pair their injectable drugs with delivery systems that patients want to use. This means incorporating design features that provide ease of use, versatility and adaptability to address emerging challenges in administration. This presents significant opportunity for packaging and delivery system manufacturers to design innovative, integrated delivery systems that not only function effectively, but are also designed to be easy and intuitive for patients to use.

Specifically, for biosimilars, drug makers will often aim to provide a delivery system that offers the same general mode of action, but they may have options to offer improved systems. As an example, if the innovator's product is delivered by subcutaneous injection by an autoinjector or other device, a biosimilar should use the same basic route of administration (subcutaneous injection), but the injection system for the biosimilar could be different from the innovator's injection system.

A prospective biosimilar applicant will not be able to obtain licensure under section 351(k) for its product when a design difference in the delivery device or container closure system results in any of the following: •• A clinically meaningful difference between the proposed product and the reference product in terms of safety, purity, and potency; •• A different route of administration or dosage form; or •• A condition of use (e.g., indication, dosing regimen) for which the reference product has not been previously approved; or otherwise does not meet the standard for biosimilarity.

In your opinion, which are the key processes that need to be in place for India to be globally competent in this space?

10  August 2017

The market for biologics is continuing to grow in India and around the world. As patents expire on marketed biologics, there is a huge opportunity for biosimilar manufacturers to capitalize on market opportunities and bring more affordable medicines to the market.

This means being ready to file first, and that requires having a plan to bring the biosimilar to the market, and to the patient, quickly and efficiently with innovative drug delivery systems that can help their products stand out.

Biosimilars, as the name suggests, are not exact copies of the drug itself, and must be proven to be as safe and effective as the innovator's product. This also means that manufacturing facilities and regulatory filings need to meet the requirements of the market that is being served. Many biologic drugs use delivery systems such as autoinjectors for self-injection, needle safety systems or reconstitution devices, and these systems, as well as the drug itself, also need to be recreated to ensure equivalency to the innovator. Selecting the appropriate container and delivery system can often be as important as the drug molecule in ensuring success.

Biosimilar manufacturers often lack the budget to create a custom-made delivery system for their drug, so their product must be delivered in ready-made systems. The good news for drug makers is that these offerings are being created based on previous designs and data

utilized for original biologics drugs. The challenge biosimilar manufacturers face is knowing which delivery system is best for their drug and how quickly their partner can assist them in getting the offering to market. This is where having a trusted partner in the drug delivery device manufacturer space to guide them as they choose the appropriate system to deliver their drug is incredibly helpful.

How supportive is the regulatory landscape for research and development of biosimilars in India?

There is a growing interest in biosimilars among biopharmaceutical companies in India, and according to the recent Quintiles IMS report, "Outlook for Global Medicines through 2021," pharmerging markets such as India will continue to be driven by non-original products over the next several years. At the same time, there is also a shift toward regulatory bodies in India and elsewhere across the Asia Pacific region placing increased focus on quality standards and lower particle burden for injectable drug products. Greater regulatory scrutiny and quality standards are placing added demands on drug manufacturers, suppliers and contract service providers. Driven by concerns for patient safety, regulatory agencies in India and around the world are asking drug and packaging manufacturers to build quality into their products from the start to ensure consistent quality throughout a drug product's lifecycle.

What are the best practices followed by West for improving patient outcomes through integrated containment and delivery systems?

More and more, drugs are coming to market as combination products, meaning the injectable drug is paired with a delivery system. As a result, pharmaceutical companies are paying closer attention to the design, function and efficacy of integrated delivery systems. This, coupled with a broader trend in the market toward patientcentric design and increased home-based administration, means that it is important for drug manufacturers to carefully consider the delivery system they select for their drug.

Drug manufacturers have often relied upon patient focus groups for insight into end user Pharma Bio World

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interview considerations for self-injection systems.

However, the narrow focus group setting doesn't provide a full picture of how patients use injection systems in multiple environments: at home, work and other settings. Integrated drug delivery system development must be considered in the context of how a patient interacts with the system differently at each stage of their journey and in the various environments they encounter each day.

A best practice employed by West is to utilize human factors analysis, usability testing and engineering to provide a detailed understanding of patient behaviors, motivations and needs. By applying human factors principles and conducting extensive usability testing early in the design process, drug manufacturers and their delivery system partners like West can maximize the likelihood that that the self-injection system user interface is safe and effective for use by the intended users, uses and environments.

What are West's innovative solutions for injectable drug administration?

West has several innovative drug delivery system and packaging component technologies, including: •• SmartDose platform - a wearable, subcutaneous injector with an integrated drug delivery system that incorporates human factors and usability testing to deliver a truly patient-centric approach to self-administration.

•• SelfDose patient-controlled injector an off-the-shelf delivery system that is ergonomically designed for optimal patient administration.

•• Administration systems - including devices for reconstitution, transfer and delivery.

•• NovaPure components - high-quality components for higher-volume pre-filled delivery systems designed using Quality by Design (QbD) principles to reduce particulate and ensure consistency of delivery.

•• Daikyo Crystal Zenith cyclic olefin polymer - a high-performance alternative to glass and an integrated lifecycle solution for containment and delivery systems designed to help maintain drug safety, purity and efficacy from development through to commercialization.

12  August 2017

How is West contributing to the biosimilars and generics market in India?

West works by the side of drug companies in India and around the world to improve the delivery of healthcare to patients. We know the complexity of these drugs and their need to be delivered through an integrated system that is safe, reliable and patient-centric.

We also know that generic and biosimilar manufacturers feel immense pressure to file first, and we have a comprehensive portfolio of offerings to help them to get their products to market quickly.

A key part of our approach is a focus on quality. Regulators and drug manufacturers alike place significant emphasis on quality standards. No longer just an innovative suggestion, Quality by Design has become a non-negotiable aspect of drug delivery technology development. Applying a datadriven, design control process and QbD approach to the design and development of packaging components and delivery systems can help ensure a delivery system that consistently functions as expected.

What are the challenges that we need to address to realize the vision 2020 to reach USD 200 billion industry?

Providing better healthcare to its citizens and being a nation that attracts the most talented scientists and scholars are key components as India moves toward Vision 2020, and a burgeoning biosimilars market is one way to progress toward achieving the vision. But before touching on challenges, I think it is important to note that India has significant potential to become a leader in the biosimilars market. As discussed above, with many biologics poised to come off patent over the next several years, there is opportunity for biosimilar manufacturers to capitalize on market opportunities and bring more affordable medicines to the market.

it will be important to choose drug delivery systems that are patient-centric. The therapy cannot be effective if the patient doesn't want to take the drug.

Which are the areas that West is currently working on? Could you update us on West's product pipeline?

West is continuing to focus on the trends we are seeing in the industry. One that we’ve talked about a lot here is quality, and that remains a top priority. Another is a move toward more self-administration. In India and around the world, care for many chronic conditions is moving out of the doctor's office and into the home environment.

Finally, an additional area of focus for West is on speed and flexibility in the supply chain. Once a medicine is manufactured, it's important to get it to market quickly without compromising quality or reliability. At West, we have the flexibility to respond quickly to customer needs. One example is our AccelTRATM Component Program that delivers packaging quality, speed and simplicity for generics customers, for whom it is so important to file quickly. The AccelTRA Program offers market-leading delvery times and a single next-generation formula for stoppers that help customers stay competitive.

How do you intend to steer the growth of West in the years to come?

To remain competitive, we plan to continue to grow our manufacturing capabilities for products. We will also keep collaborating with pharmaceutical companies in India as they bundle their products for regulatory approval. Last but certainly not least, we will make sure we continue to manufacture products that are innovative and designed with the patient in mind.

In India, where biologics continue to be one of the fastest growing segments, there are a few considerations to keep top of mind. First, it will be important to keep quality built into the drug itself as well as the delivery system. Second, Pharma Bio World

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Pharmaceutical Contract Manufacturing                                                  

C

ontract manufacturing is production of goods by one firm, under the label or brand of another firm. Contract manufacturers provide such service to several (even competing) firms based on their own or the customers' designs, formulas, andor specifications. Also called private label manufacturing.

The main reason a pharmaceutical company would be interested in pharmaceutical contract manufacturing through another company is efficiency. If a company that sells pharmaceuticals is unable to produce either medicines or their packaging in their own facilities, or if making their facilities capable of mass production would be expensive, then that company is likely to look into contract manufacturing.

Surplus labour costs, labour union problems have led to the re-structuring and downsizing of many organisations and prompting many companies to adapt contract manufacturing as a basic mechanism for labour adustment strategies in India and even developed economies. at to oo o  nan a Contact anact The only point a company should keep in mind while deciding a contract manufacturer is the basic infrastructure of the manufacturer to scale up  the capability to provide quality products on long term basis. Therefore at Septalyst we select the manufacturers after taking feedback from the market on the quality  punctuality of the manufacturer. After that we conduct thorough audit of the manufacturing plant on the quality  infrastructure setup.

a n n MD  CEO Septalyst ifesciences 14  August 2017

Once we are satisfied on the above mentioned criteria, then  then only we finalise the manufacturer. Therefore we have the best contract manufacturers as our manufacturing partners like Akums, Serum Institute, Theon Pharmaceuticals ,Unique

iotech to name a few. Independent quality testing of every batch  regular audits at the manufacturers is a must for companies to ensure that they get quality products from the contract manufacturers.

According to the president of the Indian Drug Manufacturers' Association (IDMA), S V Veerramani, the overall pharma contract manufacturing industry is growing at 20 per cent, providing a burgeoning opportunity for small and medium enterprises. The current market value is estimated at 50 per cent of the domestic production, which roughly translates to USD 5. billion. Multinationals hold a generous 20-25 per cent stake in the domestic pharmaceutical market. aon o at ot o contact anactn nt

• Increasing consumption of medicines around the world, both in emerging markets as incomes rise and mature markets due to aging of the population • The growing number of biologic drugs in development, many by traditional pharma companies that lack biotech expertise • A more robust pipeline of drug candidates and an increasing rate of FDA DAA approvals • The entrance of numerous small, virtual startups into the market that have no manufacturing capacity • The rise in patent expiries and increasing generics competition, which is driving a greater need for cost efficiencies and access to novel, proprietary technologies for achieving product differentiation.

• And the increasing complexity of both small- and large-molecule drugs, such as antibody-drug conugates (ADCs) and highly potent compounds that require specialized skills and capabilities.

Pharma Bio World

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There are questions, however, as to how long such strong growth can continue.

Merger and acquisition activity has been rampant among both sponsor companies and contract service providers, leading to real consolidation within both sectors.

Several pharma firms have also acquired contract service providers to achieve vertical integration. Others have elected to invest in their own in-house capabilities -often smaller, flexible, multiproduct facilities designed to meet the dynamic needs of today's marketplace.

For the basic manufacture of medical products and drugs, India has a far superior edge over nations such as China, Vietnam and Ireland, due to resources including manpower, technically knowledgeable work force, and World Health Organization-Good Manufacturing Practice- approved production premises.

A substantial 40 per cent lower cost of operation and production is clearly the highlight for multinationals to consider India for their outsourcing needs.

The rising cost of manufacturing and some of the ageing plants of Europe reaching their life cycle conclusion may open 16 ď‚ƒ August 2017

up enormous opportunities to India's companies in contract manufacturing as European companies are also considering to either relocate those units in cost efficient centres like India or to outsource to India manufacturers. Emerging markets, value-added generics (so-called supergenerics), and biosimilars provide other potential opportunities for growth if contract manufacturers have the global reach and technical capabilities necessary to capitalize on them.

compound annual growth rate as efficiency in manufacturing and maturity of business models would lead to containment of cost of manufacturing to a great extent.

The government is also looking at incentivising the upgradation of Schedule M facilities to WHO GMP compliant units with the help of soft loans, which would lead to additional 1000 units being certified WHO-GMP compliant, further corroborating the manufacturing processes.

Also it is estimated that patented drugs worth US$ 85 bn in potential annual sales in the USA would be off patent during the period 2014-2020. Price competitiveness and manufacture of these generic drugs in the most cost efficient manner would be the key drivers boosting the prospects of the Indian players as India is known to have the world's best known lowcost manufacturing centers, with the highest number of US Food and Drug Administration (USFDA) approved manufacturing plants outside the US. The contract manufacturing industry is expected to grow by 17-18 per cent on a

Contact: bosky.c@gmail.com Pharma Bio World

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Technology Transfer during Outsourcing                                         

T

he concept of CRAMS (Contract Research and Manufacturing Services) has its origin in India, as claimed by yderabad based leading CRAMS corporate. CRAMS is essentially rooted in outsourcing of research and/ or manufacturing. Technology is the key element bonding the parties together in any outsourcing venture. Various agencies are projecting high CAR (compounded Average rowth Rate).

CAR expects 18 to 20 per cent growth rate by 2018, while Cygrus Research reports that global pharmaceutical outsourcing worth S8 billion in 2009 and S8 billion in 2012 is expected to grow at a CCR of 47.2 per cent earlier to 62.1 per cent in recent times, being the Indian pharmas CRAM growth rate.

Technavio forecasts Indian CRAM market to grow at CAR of 2.67 per cent during 201 to 2018. Current active players include Biocon, Dishman Pharmaceuticals and Chemicals, Divis aboratories, Jubilant ife Sciences, Piramal ealthcare amongst others. There are CROs such as uintiles, Covance, Parexel, SIRO Clinpharm vying for a piece of the CRAM pie.

In recent times, Rusan Pharma has emerged as a strong CRAM principal manufacturer and technology provided especially for skin patches and technologically advanced inserts and patches. According to BM, CRAMs is expected to touch SD 19 billion by 2018.

 oaa  a CO opakumar Nair Associates 18  August 2017

CRAMs have the key parties, who are the principals who own the facilities / infrastructure and the outsourcers who seek the use of the Principals facilities for conducting research and / or manufacturing. The CRAM relationship commences with an MO followed by or directly with a contractual Agreement specifying the terms and conditions thereof. The most important element of

such agreements is the confidentiality for non-disclosure/non-compete clauses relating to the technologies disclosed by one party to the other. Technology may get disclosed to the outsourcer from the Principal, CRAM organiation, if the product or process involves high technology. On the other hand, if the Outsourcer is possessing the high technology in the product or the process, and the manufacturer is having convectional facility, the non-disclosure and non-compete component of the Contract Agreement becomes very critical for the outsourcer.

Further, once the technology having Intellectual Property (IP) content is disclosed and put to work and practice, new IPs either in the form of incremental infringements meriting new product or process patent applications or any disruptive innovations mined during the operations arising from the CRAM arrangement need to be designed for IP sharing conditions and provisions in the Contract/Agreement. This is the most critical area to be taken cautions drafting in the contract. Very often, when CRAM contracts are signed, the aspects of IP sharing and more importantly, the roadmap for the sharing of the new IP being generated through the operation of the CRAM relationship, does not get the attention it deserves. A few templates, historical disputes and litigations with few examples of technology transfer in outsourcing are discussed hereafter.

Technology transfer in outsourcing is substantially related to intangibles such as Intellectual Properties, know-how, confidential technical information and diagrams of flowchart and hardware. The Technical nowledge as transferred is the key element, which includes formulas, flowcharts, diagrams, drawings, blueprints and operating manuals. Subsequent Pharma Bio World

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improvements on the shop floor of the transferee or outsourced principal party need to be specifically covered with regard to the IP sharing terms. The equipments, reactors, machinery including related software also forms part of the technology transfer. Provisions need to be built in for improvements likely to be made at the outsourcing site in future during operations.

Firewalls for protecting or limiting the dissemination of know-how only to the key persons need to form part of the technology transfer agreements. Nondisclosure to unrelated parties and noncompete clauses need to be incorporated.

Restrictive clauses on territorial jurisdictions and end-use limitations as well as licensing exclusivities also need to be part of the agreement. Agreement need to specify if it is exclusive, nonexclusive or for fixed areas or fields or period of time. Warranties and indemnities also form important clauses to be carefully worded and drafted. Technology transfer fee, royalty, if any, terms of payment such as one time out right lumpsum payment 20 ď‚ƒ August 2017

or/and payments across milestones etc. need to be negotiated, crystallised and incorporated in the agreement without ambiguity. An aspect which is often overlooked is the termination clauses and applicable laws. Option of arbitration or court litigation for settlement of disputes is another area of importance to be incorporated in agreement.

WIPO has conducted a multi-country Survey on Technology Transfer Agreements (TTA). The results of the survey are available on http://www.wipo. int/export/sites/www/ip-competition/en/ studies/tta_survey.pdf. Srijit Mukherjee and Sudipta Bhattacharjee in their wellarticulated article in Journal of Intellectual Property Rights, Vol. 9, May 2004 P-260274, has dealt with "Technology Transfer and the Intellectual Property issues emerging from it - An Analysis from a Development Country Perspective."

The Patents Act, 1970 (of India) as well as most Patent Acts of the countries have provisions on Patent Assignments and licensing to third parties. Patents

being critical components of Technology Transfer, the terms of Patent Assignments or licensing, assures importance in Technology Transfer Agreements (TTAs). Section 68, Section 69 and Rules 90 to 92, cover essential aspects of Patent Assignments and transfer of titles in patent register. An important provision under Patents Act, 1970 to be taken cautionary note of, is Section 140 - "Avoidance of Certain Restrictive Conditions". Very often Technology Transfers involving Patented technologies overlook the provisions in Section 140 while drafting restrictive clauses beyond legal boundaries permissible.

While all precautions and eventualities need to be taken into account while drafting Technology Transfer Agreements, care and caution is recommended to ensure that the terms and conditions are not unduly restrictive beyond legally enforceable limits and contours.

Contact: gopanair@gnaipr.net Pharma Bio World

QbD and Risk Based Approach for Efficient Design of Pharma Plants Te• artice• earates• te• cMP• risk• ased• arac• tards• te• desin• and• aiicatin• • Parma• ants• rdcin• r• te• internatina• markets• Adantaes• er• te• traditina• aiicatin• arac• and• its• imact• n• ant• inestment• and• scede• is• eamined• Te• artice• as• addresses• • t• incrrate• tis• arac• in• te• ear• staes• • rect• eectin• t•maimise•imact

O

ne of the major challenges faced

by Pharma plants globally is getting regulatory approvals and maintaining them. Many plants especially in India are losing their FDA certification during audits due to gaps in documentation and the constant complaint of pharma manufacturing companies is the convoluted and excessive documentation required.

Actually the FDA and the global Pharma community has adopted the Risk based approach to Qualification and Validation which leads to much more clearer and less voluminous documentation. It is high time that the India pharma industry also adopts this approach in a more aggressive manner.

The purpose of this article is to elaborate the QbD ( Quality by Design) and Risk based approach during project execution.

Concerns ith Conventional Approach Conventional approach relies almost revolves around testing of end product quality. While this ensures uniform product quality to consumer, it does not address underlying issues related to deviations in quality. To reach an uniform product quality it resorts to a cumbersome Commissioning, Qualification and Validation process with a very heavy focus on generation of excessive documentation and long paper trails. While from a project execution perspective this substantially inflates the project schedule. While a conventional chemical plant would take -8 months from concept to start-up , a similar complexity Pharma plant would take anywhere upwards of three years. Post startup the plant operations and QA get buried in mountains of procedures and documents. This gives the auditors ample ammunition to identify non-compliances and further to cancel FDA licenses.

hailesh Dhume Principal Consultant Infuse Consulting Pharma Bio World

And just ask anyone to make a modification in the plant post qualification and it looks

as if a disaster has befallen then. Even the biggest of optimization opportunities are knocked off due to regulatory constraints. he QbD Approach So how does the QbD approach help The QbD approach was proposed by FDA at the start of the th century as a methodology to do away with empirical methods in the Pharmaceutical industry and bring in a more scientific and engineered approach.

Quality by Design starts right at the drug development stage. The core of the process are CQA( Critical Quality Attributes) and CPP(Critical Process Parameters).

Critical Quality Attributes (CQA) are chemical, physical, biological and microbiological attributes that can be defined, measured, and continually monitored to ensure final product outputs remain within acceptable quality limits. In simple words these are the quality parameters which would have a direct impact on the drug efficacy.

Critical process parameters (CPP) in pharmaceutical manufacturing are key variables affecting the production process.

CPPs are attributes that are monitored to detect deviations in standardized production operations and product output quality or changes in Critical Quality Attributes.

One example of CQA could be the dissolution of tablet. Lower dissolution of the tablet could reduce the efficacy of the tablet and a higher dissolution could potentially cause side effects. This needs to be established in the early stage development of the product.

Once this value is established , the process parameters which could affect the dosage need to be assessed.

CPPs are then identified for each process step.

For example for the manufacture of tablets one of the key manufacturing steps would be August 2017  21

Granulation. The CPPs for Granulation would be excipient properties, water content post granulation and particle size.

Once the CQA and associated CPPs are identified, the next step would be to identify the Design Space. Design Space is defined as the multidimensional combination and interaction of input variables (eg, material attributes) and process parameters that have been demonstrated to provide assurance of quality. In simple language, it is the range of values within which the CPPs can be varied keeping the CQA within acceptable range.

The design space gives the clear criteria for the design of individual Unit Operations.

Operating within the design space does not involve a change and provides greater flexibility in operating within the FDA regulatory constraints. Only if the operating regime is moving outside of the Design Space regulatory change management process is required.

Design Space can be defined by using three methods

•• Process Modelling - Using first principles of Chemistry, Physics and engineering to create a process model and predict the design space.

•• DOE (Design of Experiments) - Using statistically designed experiments to assess interactions of multiple parameters.

This method is most reliable but can be quite time consuming and expensive.

•• Scale up - Use of semi empirical correlations to translate lab conditions to commercial scales. This might also involve in some cases piloting studies.

Design space definition in most cases might be a combination of any two of the above three methods.

Now that the first step of simplification is completed with the definition of CQA, CPP and Design Space. The next step and the most important is to carry out a Risk Assessment.

22  August 2017

Risk Methodology The conventional CQ&V methodology requires the uniform Qualification and Validation of the complete plant. However the Risk based approach involves assessing the risks associated with each system in the plant with respect to the impact of variation of CPPs on CQAs and classification of each system into;

system has components - Spray dryer, spray dryer feed pumps, air heater, combustion air system. A further detailed risk assessment of the system can classify the components as critical/non-critical. The classification would potentially be

•• Direct Impact •• Indirect Impact •• No Impact

• • Spray dryer - critical • • Spray dryer feed pumps - Non critical • • Air heater - Non critical ( This can be done with a robust control on the air heater outlet temperature) • • Combustion air system - Non critical

Direct Impact system is a system that has a direct impact on product quality. This needs to go through the complete Qualification and Validation exercise.

So with this classification, only the critical components would need a full CQ&V whereas the non- critical components need only to be handled as per Good Engineering Practices.

An Indirect Impact system that is not expected to have a direct impact on product quality, but typically will support a Direct Impact System. These systems are designed and commissioned following Good Engineering Practice only.

With the two level screening, the total plant is drilled down to Direct Impact Critical Components which are the only parts of the plant which would require a full CQ&V.

A no impact system is one that has as the name goes no impact on Product Quality.

So the main process steps like Mixing, Drying, Reaction would be classified as Direct Impact systems. Also some utilities like Clean Steam and Nitrogen which come in contact with the product may be classified as Direct Impact. Most of the Black Utilities would be classified as no impact systems.

Indirect impact systems could be HVAC, cooling water the failure of which could potentially impact the product quality.

There are many established risk assessment methodologies available for the Pharma Risk management process. Risk Methodology needs to be chosen based on the product and process information available.

Classifying the systems in such a way greatly reduces the load of Qualification and Validation and consequently reducing documentation.

Further streamlining of the CQ&V process by further carrying out the Impact Assessment of the individual components of Direct Impact systems.

Let us consider a Spray dryer system classified as a Direct impact system by the System level Impact Assessment. The

Choosing the Right Risk Assessment Method

• • Basic risk assessment If only the basic information on the product and process information is available ( for example only identified CQA and CPP), a simple risk assessment method can be applied like cause and effect analysis or fishbone analysis( Ishikawa diagram).

These methods are very effective in the initial stages of the project where a quick prelimnary assessment is required and these risk assessments can feed into development of the plant validation strategy.

• • FMEA / FMECA/FTA These risk assessment methods can be applied when detailed product and process information is available.

FMEA ( Failure mode Effects Analysis) is a method more focussed on equipment and Pharma Bio World

facilities and their effects on the product and process. In this method the failure modes are identified and risk rated and the risk reduction ideas can be identified for elimination, contain, reduce or control risks. It is very effective to prioritize risks and monitor effectiveness of risk control activities.

FMECA (Failure mode, Effects and Criticality Analysis) is similar to FMEA but more focussed on processes. The method can be used to identify further risks which require control or reduction.

FTA (Fault Tree Analysis) is most useful when effects of multiple causes of failure are to be assessed. It is a qualitative method and relies totally on the person's/ team's expertise in carrying out the FTA.

•• HACCP and HAZOP Hazard analysis and Critical Control Points analysis is the most comprehensive and systematic method to assess risks for Pharma units. It identifies and manages risks associated with physical, chemical and biological hazards. The only constraint with this method is that it requires a thorough knowledge of the Product and Process data. The output of the assessment is identification of Critical Control points.

Hazop is used to analyse the risks associated with deviations from design conditions. It is used more for assessing the safety related risks rather than Quality related risks. It can be used for identifying critical monitoring points in the process.

Leveraging Manufacturer Construction Documents

and

Conducting the risk assessments and identifying the Direct Impact systems and Critical Components early in the project enables leveraging of documents received from the equipment/ instrument suppliers and also the standard construction quality check documents to accelerate the Qualification process.

Pharma Bio World

Le v eraging Manufacturer C onstruction Documents

and

Conventionally the qualification process would start only on Mechanical Completion leading to a situation wherein the plant is technically ready to start production but is constrained in doing so due to extended Qualification process.

With the QbD and Risk assessments in place the preparation of IQ dossiers can start as soon as the supplier documents for the Critical components in Direct Impact systems are received. So the IQ process can be done in parallel with the construction activities. The installation reports from the construction team can be added on to the dossier and IQ dossiers can be signed off in conjunction with the Mechanical completion certificates. Also since the entire plant is split into systems, the IQ can be completed sequentially without waiting for the Mechanical completion of the entire plant.

Advantages of QbD Assessment Approach

and

Risk

For the manufacturer it leads to a faster time to market with a reduced overall development cost. FDA audits are simplified and risk of non-conformances can be greatly reduced. Plant optimization initiatives can be more easily implemented especially for Indirect impact and No impact systems.

For the regulatory bodies, it makes auditing of facilities easier. They can actually focus on real quality issues rather than on paper trails.

For the end users it provides more assurance on the quality of drugs that they are buying and consuming.

this slow adoption of the new methodology.

Firstly most of pharma companies in India are generic drug manufacturers rather than Inventor companies. So the very first step of QbD i.e. identification of CQAs and CPPs becomes a cumbersome and expensive affair.

The second challenge is the fear of change among the Quality Assurance and Operations community. With the ultra strict approach of the FDA auditors the main fear is that any change from established procedure would cause loss of the FDA license and jeopardise production.

The third challenge is the lack of awareness among the Pharma community of the QbD methodology. Sure QbD and Risk assessment are buzz words but there are very few who actually understand the implications of the new method and how to practically start the implementation of the QbD philosophy.

Meeting the Challenges The only way forward for the Indian pharma industry is to quickly adopt to the new FDA norms. The first step towards this would be to increase the awareness among the Pharma community especially regulatory QA. Training should be another area of focus especially for scientists and engineers who form critical links in implementation of QbD. The QbD approach very close co-operation between R&D and Engineering which till date have mostly operated in compartments.

The starting point for greater understanding would definitely be reading and assimilating the key standards namely;

• • ICH Guideline Q8 - Pharmaceutical Development

•• I C H G u i d e l i n e Q 9 - Q u a l i t y R i s k Management

Challenges of the Approach Though the FDA has clearly indicated that this risk based approach is the path forward for the Pharma regulatory process, the uptake of this methodology in India has been slow. There are multiple reasons for

Contact: shailesh.dhume@infuseconsult.com August 2017  23

Increasing the Access to Orphan Drugs and Specialty Medicines                                                                             

Dr Piys Gta Associate Director GNH India 24  August 2017

T

he pharmaceutical industry is one of the most rapidly growing industries in the world and is one of the biggest contributors to a country's economy. According to a report by the PWC, the Indian pharmaceutical industry is on the threshold of becoming a major global market by 2020. It has a growth rate of 15 to 20 per cent CAGR which is expected to touch between USD 50 billion to USD 7 billion in the next decade.

Despite these astonishing numbers, India only produces low-value medicines that are either synthetic in nature which means they either have a chemical origin or a 'Biosimilar drugs' that have biological origins. While the low-value drugs are manufactured in India, the expensive high-end drugs are still being imported.

There are several types of imports which take place in India which include for commercial sale, patient use, test, R&D and clinical trials. For commercial sale, India is fairly in line with the global trends as The Central Drugs Standard Control Organization (the agency which controls the imports) as we have adopted the requirements from the World Health Organization. While this system seems rational on the surface owing to the fact that all medicines need not be stockpiled in every country; the predicament begins while importing high-end drugs for rare or orphan diseases.

India lags far behind in its endeavor to import drugs for orphan diseases. This is because the processes in place are not up to global standards, resulting in every request taking 7-8 months to process.

India has a long way to go in order to get in line with the international import process. India, like any other country, has to import some such medicines that are vital for patients. The problem is further amplified with orphan drugs that are rare

and are not available easily. The rules for import are clear but misunderstood by patients, doctors, and importers as there is barely any information in the public domain that advises on how to import, thereby puzzling the importers regarding the process.

Oran Drgs and teir Aailaility Orphan drugs are pharmaceutical agents that have been developed specifically to treat a rare medical condition and are not easily available worldwide. The condition or disease that manifests itself in patient populations and comprise of a maximum of 6-8 per cent of the world;s population is defined as rare or orphan diseases.

In India, there has been a rapid growth spurt of rare diseases which are attributed to a change in lifestyle, coupled with an increase in affluence and income levels.

The Indian population is now suffering from diseases that were previously unheard of a few decades ago.

Rare diseases such as infantile spinal muscular atrophy, lysosomal storage disorders, patent ductus arteriosus (PDA), familial adenomatous polyposis (FAP), cystic fibrosis, renal cell carcinoma, glioma, and acute myeloid leukemia develop at birth but manifest themselves at a later stage during adulthood. Today there are over 5000 rare diseases classified in the world. At least five new rare diseases are being reported every week in the medical literature.

80 per cent of rare diseases have been purported to have genetic origins. Other rare diseases are the result of bacterial or viral infections and allergies. Some are due to degenerative and proliferative causes. These diseases are rare and the medicines for their treatment and control are not easily available or used.

Pharma Bio World

Disease

Per 100,0

In India

Acatalasmia

3

36,000

Acromegly

5

60,000

Alkaptornuria

3

3,600

Alpa-1 antritrypsin

25

300,000

Grave disease

50

600,000

Parkinson disease

15

180,000

In 1983, the US government passed the Orphan Drugs Act to stimulate research in the treatment of diseases that have been largely ignored by the pharmaceutical industry. Similar laws have been enacted in Japan, Australia, and the European Union. All these laws offer incentives such as shorter clinical trials, extended exclusivity, tax breaks and high rates of regulatory success. They have made it commercially attractive for pharmaceutical companies to invest in the research and development (R&D) required to find a cure for these diseases.

But even if they are incentivized to develop drugs to treat rare diseases, pharmaceutical companies remain beholden to the laws of economics and, given the low demand for orphan drugs, price these drugs as high as they choose to. For example, Rituximab, an orphan oncology drug, is the world's second highest revenue generating drug. While all this may be less of a concern to patients in Western countries, as they are covered by comprehensive healthcare plans, it forces patients in developing countries to deal with the uncomfortable realization that even though a cure exists for their condition, it is unaffordable.

for pharmaceutical manufacturers, the economics of manufacturing these drugs still do not add up. Therefore even though there is an unmet demand from patients, companies are hesitant to manufacture such high-value drugs.

This poses an interesting opportunity for India which is one of the largest manufacturing hubs in the world. The unmet demand coupled with pharmaceutical companies to expand further into this area expose a vast untapped potential this industry is yet to reach. Roughly there are about 6,500- 8,000 rare diseases in India which include Norrie Disease, Wilson Disease, and Arthrogryposis.

The effect of this will be two-pronged- one on manufacturers and the other on the patients themselves. For manufacturers, the market for these drugs may appear small, but this is more than counterbalanced by the revenue opportunities and the quick time-to-market. For patients, the burden of cost will fall entirely on them in the short run which can be avoided in the future with the help of state run incentives for manufacturers. This will allow manufacturers to produce drugs that focus on common medicines and orphan drugs alike and decimate the established system of our health care system is

funded almost solely by patients.

Another systemic problem that will be solved when manufacturing processes are moved to home base is one that arises from the transportation and movement of goods. Importers have taken up the option of using carriers or gray market routes which put patients' lives at risk. This is truer for drugs that have a biological or bio-similar root because external factors such as the proper temperature, storage, and transport of these drugs severely impact the efficacy. As per industry norms and standards, the drugs must be stored between 2-8 0C. If not, the stability of drug could hamper the efficacy and will not deliver the desired results causing it to be the public hazard. Varying temperature, improper storage units, and inappropriate transportation methodology often have fatal consequences on the recipient of these drugs.

Earlier, there were no formal incentives from the government that focuses on developing affordable drugs for common diseases such as oral insulin for preventing or slowing the progression of cardiovascular disease and vaccines and antibiotics for some preventable infectious diseases. Hence, patients with rare diseases rely on imported drugs from other countries which makes it unaffordable

Thalassemia is another perfect example of this phenomenon. Over 10 years back there would be 1 patient in 1000 that suffered from this hereditary hemolytic disease. In a matter of a few years, the number has increased ten folds as 10 in a 1000 people have reported having the disease in some form. However, Pharma Bio World

August 2017 ď‚„ 25

for the common man even if they are available. Organization for Rare Diseases in India (ORDI) intends to work between the Government of India and the Pharma/ Biotech/Diagnostic industry to establish an Orphan Drugs Act (ODA) that will generate incentives for orphan drug developers.

Even though the government has attempted to steps to provide some respite from the complicated import procedures, they must take a step towards not only simplifying the import of life-saving drugs by reducing the number of procedures; but also place heavy embargos on the illegal smuggling of high-value drugs. The rules must be changed to suit the patient in need and not the manufacturers who can wield a price controlled power over these medicines.

The issue of illegal smuggling can be curbed by initiating a "Qualification process" for authorized importers by publishing a list of them in a public domain. This would not be a difficult endeavor as over 75 per cent of pharmaceutical companies are already in the organized sector. Companies will be required to rethink their business models just as governments are restructuring their regulatory intervention. This intervention will ensure that the processes of trading in drugs that are vital to human life in all countries are made simpler.

These acts and regulations in India will not only raise the burden off of the patients but will open the doors to the true potential of the pharmaceutical landscape in our country by giving affordable and accessible drugs to those in need. The health of our population is an important aspect of improving the overall Human Development Index of our country that is currently abysmally low.

WHO-GDP Certification As mentioned before, the illegal transportation of rare drugs poses a 26 ď‚ƒ August 2017

serious public threat to those who consume it because of the lack of proper conditions in which they are moved from one place to another. Counterfeit pharmaceutical products are also a real threat to public health and safety. Consequently, it is essential to protect the pharmaceutical supply chain against the penetration of such products.

In order to curb this, a proper system must not just be established but also implemented. The WHO has set up an international protocol called the WHOGood Distribution Practices (GDP). Good distribution practice (GDP) deals with the guidelines for the proper distribution of medicinal products for human use. GDP is a quality warranty system, which means that procurement, purchasing, storage, distribution, transportation, repackaging, relabeling, documentation and recordkeeping practices are met after stringent audits and protocols.

Internationally accepted pharmaceutical GDP regulations stipulate that distributors of pharmaceutical products must align their operations with the standards. The scheme ensures that consistent quality management systems are in place throughout the entire supply chain, from the early delivery of raw materials to the manufacturing plants, the final shipment of finished drugs to the end user. An independent assessment of compliance with international GDP requirements is the most effective way to establish that a quality management system aligns with GDP guidance. Right from the manufacturer to the doctor's office, GDP supply chain or parameters are to be maintained.

Various persons and entities are often responsible for the handling, In some cases, however, a person or entity involved in the distribution of pharmaceutical products is only involved and is responsible for certain elements of

the distribution process. The guidelines are intended to apply to all steps in the entire distribution/supply chain. The relevant sections should be considered by various role players as applicable to their particular role in the distribution process.

The storage, trade, and distribution of pharmaceutical products are activities that are carried out by various companies, institutions and individuals. The nature of the risks involved may generally, however, be the same as those in the manufacturing environment, e.g. mix-ups, contamination, and cross-contamination.

There are aspects of distribution to which the principles of Good Manufacturing Practice (GMP) should be applied. These include, but are not limited to, storage, distribution, transportation, packaging, labeling, documentation, and record keeping practices. In order to maintain the original quality, every activity in the distribution of pharmaceutical products should be carried out according to the principles of GMP, Good Storage Practice (GSP) and Good Distribution Practice (GDP). If these processes are followed and the protocols are kept in check, there is no doubt that people who are in dire need of medication anywhere in the world will not only receive the drugs on time but also at an affordable cost with the correct efficacy and a value for their money. This will ensure that no person faces a fatal consequence for the lack of medical aid or because of complex trade regimes and will put a complete stop to the illegal smuggling of pharmaceutical products across country borders.

Contact: drone@conceptpr.com Pharma Bio World

GST: Initial Speed Bumps for the Pharmaceutical Industry                                                               

T

he Indian pharmaceutical industry has been a jewel in the crown of Indian exports and despite stiff international competition has been a consistent high performer. The government being cognizant of the importance of the industry has over the years provided sizeable incentives to the industry through export promotion schemes and exemptions. These exemptions provided pharmaceutical companies with significant savings and helped in establishing the commercial arrangements in which the industry has operated and thrived.

The advent of Goods and Service Tax (GST), though welcomed by the pharmaceutical industry is likely to create a few short and medium pain points considering that it's the unfamiliarity with the new law and its impact on certain basic business practices. This is relevant especially in the context of the fact that the pharmaceutical industry is regulated heavily both in terms of operational aspects as well as pricing aspects.

In the following paragraphs, we have highlighted some of the issues which are likely to arise and would require a concerted effort by the companies to plan for as GST matures.

air Bora Partner haitan  Co

ushaar alar Associate haitan  Co Pharma Bio World

) evised Pricin under Anti Profiteerin echanism: The industry for several months prior to introduction of GST filed representations requesting for rectifying the inverted duty structure likely to be created within the industry on account of an 18 rate of GST on Active Pharmaceutical Ingredients (API) and other inputs such as glass products and packaging material. Though Section 54 of the Central Goods and Services Tax Act, 2017 (CGST Act) provides for refund of accumulated tax credits on account of inverted duty structures, the jurisprudence with respect to refunds necessitates the claimant to meet the test of unjust enrichment. Simply put,

this would require a company to not include the unutilized tax credits into its product pricing. This is likely to put the industry in a bind. Firstly, working capital requirements are bound to increase due to the increased input costs and secondly, as a significant number of drugs are price controlled, the manufacturers would not have the regulatory independence to increase the prices, resulting in more pressure on the margins.

Assuming a manufacturer does have the ability to adjust margins and pass on the unabsorbed credits without the end price being changed, it would not be able to claim the refund and further carry the risk of exposing itself to the anti-profiteering provisions.

The anti-profiteering provisions merit some discussion to appreciate the point. The GST laws have introduced the concept of anti-profiteering for the first time in Indian fiscal laws. The essential principle for introduction of the concept is to ensure that any savings made by a business on account of tax savings would translate into reduced prices down the distribution chain and benefitting the eventual customer. The government is cognizant of the wide abuse the provisions can be subjected to and is looking to establish the National Anti-Profiteering Authority (NAPA) and issuing detailed rules to ensure the investigations are objectively undertaken.

However, pending the notification of the rules and the authority, it will be a difficult few quarters for the industry while it waits and watches.

In substance, even if a manufacturer increases the prices of unregulated medicines by foregoing refund of the unabsorbed tax credits, it still may not be excluded from the ambit of the anti-profiteering provisions.

Therefore, this is likely to create a Catch 22 situation for at least a few manufacturers, where their working capital requirements August 2017  27

increase and though theoretically refunds may be available but, if not timely disbursed would create further financial burden on the companies.

The Indian pharmaceutical industry has had a troubling few quarters on account of loss of export earnings, increasing debts and consequent decline in value. It is imperative for the government to look at the industry with the correct perspective and ensure that GST as a regime does not create any further burden but instead works as facilitation tool to help the industry.

2) Overhaul of Export Promotion Schemes: Another aspect related to increased blockage of working capital is the overhaul of export promotion schemes under the Foreign Trade Policy. Previously, incentives under export promotion schemes provided for exemption from payment of all applicable duties and cesses under Customs laws, provided certain exportrelated compliances and realizations were maintained. An important component of these exemptions pertained to countervailing duty, which was a custom duty levied in lieu of Excise duty to ensure a level playing field vis-Ă -vis the domestic industry.

With the implementation of GST, the Ministry of Commerce has revised the export promotion schemes to provide for exemption from basic customs duty, however, the levy of Integrated Goods and Services Tax has not been covered under the exemption.

Accordingly, exporters are required to pay Integrated Goods and Services Tax on exports and seek refund of the same under the mechanism provided under GST laws.

As discussed above, the refund mechanism entails a delay of up to sixty (60) days for sanction of the refund amount and would lead to consequent blockage of working capital for the industry.

3) Elimination of Area Based Exemptions: The industry has invested heavily in setting up manufacturing operations in states such 28 ď‚ƒ August 2017

as Uttarakhand and Himachal Pradesh offering exemptions from Excise duty and sales tax. The central government has unequivocally maintained the position that such area based exemptions would be eliminated under the GST framework and individual ministries and states may take the prerogative to grant refunds to the industry as per the prior scheme.

There are several unanswered questions with respect to the refund mechanism.

The principal issue arises out of the fact that the existing exemptions were origin based, whereas GST is a destination based tax. Therefore, it is uncertain how originating states will compel destination states to grant refunds in the case of inter-state supplies. Further, it is relevant to note that while the central government and the state government levy equal and concurrent taxes on the same transaction, the revenue split between the centre and the state is fixed at 58 rupees vs 42 rupees out of every 100 rupees. The unequal revenue share implies that any smooth refund mechanism will require the centre and the states to agree on a similar sharing of refund burden. Such a solution is not yet forthcoming.

Despite several weeks have elapsed since the GST regime was made effective and with almost INR 19,000 crore in taxes foregone under such area based exemptions in the fiscal year 2017, the stakes are large for the industry and the delay in providing a solution is damaging business interests and sentiments towards the GST regime.

4) Accumulation of Credits on Healthcare Services: Continuing from the erstwhile Service tax regime, the GST framework provides for an unconditional exemption on healthcare services. While this exemption has been notified with a view to keeping healthcare affordable for the public, it also gives rise to inefficiencies in the tax chain. A holistic understanding of the tax inefficiency requires a discussion on the concept of

'composite supply' under GST laws. The term 'composite supply' is understood as follows: "a supply made by a taxable person to a recipient consisting of two or more taxable supplies of goods or services or both, or any combination thereof, which are naturally bundled and supplied in conjunction with each other in the ordinary course of business, one of which is a principal supply."

A plain reading of the definition above clearly shows that the concept of 'composite supply' envisages a natural bunding of two or more goods or services that are supplied together. In this regard, it is pertinent to note that Section 8 of the CGST Act further provides that the levy of tax on a composite supply shall be at the rates applicable to the principal supply.

The term 'principal supply' is defined as the predominant supply in a transaction constituting composite supply.

In the healthcare industry, services are typically provided in conjunction with pharmaceutical products. For example, a patient admitted in a hospital for dengue may receive several services qualifying under the exemption for healthcare services.

However, the treatment of dengue would also entail the administration of drugs and medication that may be taxable at 5 or 12 per cent rate of GST. The industry may face difficulty in identifying the 'principal supply'in the composite supply of healthcare services along with taxable drugs and medications.

In a situation where the authorities take a view that healthcare services are the 'principal supply' and thus the predominant aspect of the supply, the entire composite supply of such healthcare services would be exempt from levy of GST. Accordingly, there will be excessive accumulation of credits with respect to the taxable but ancillary supply of drugs and medication. Such accumulated credits are not refundable as Pharma Bio World

per the express provisions contained under Section 55 of the CGST Act.

             "

) axailit of Supplies eteen Business erticals: arger companies in the pharma industry house several business divisions within the larger corporate entity, such as units dedicated solely for manufacture, research and development, contract research and manufacturing, etc. For the purposes of keeping these segments identifiable, it is common practice to maintain separate books of accounts for such business divisions. Under GST laws, the industry may be evaluating the viability of registering each such business division as a separate 'business vertical'. For reference, the term 'business vertical' under the CGST Act is defined as:

Registration of a business vertical is voluntary and may be undertaken provided the business division fulfils the criteria specified in the definition above. However, a direct implication of registering a business vertical is that such a unit now becomes a distinct entity under GST laws and is treated as a separate taxable person for levy of GST taxes. It is relevant to note that taxable person under GST laws may differ from that under other laws that levy tax only on legal entities. Under the GST, a taxable person includes separately registered business verticals within a single legal entity.

"                           

Accordingly, companies considering registration of separate business verticals should be cognizant of the fact that any supply of goods or services between business verticals would constitute taxable supply and would be subject to levy of GST taxes.

Despite the above challenges, GST promises to usher in a more certain tax regime and if implemented with the same spirit that it has been championed with, it is highly likely that the concerns of trade and industry would be addressed.

There already is evidence that the government is working to ensure that inconveniences are reduced to the extent possible and has issued a few instructions extending the timelines for filing of initial returns. The authors hope that the initial concessions are also followed up with a more nuanced appreciation of the peculiar issues within the pharmaceutical industry to help the sector achieve its potential for the economy.

Contact: titas.duttaperfectrelations.com

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August 2017  29

Recent Advancement in Clinical Trials and Drug Development in Pharmaceutical Industry This article focus on the different phases and recent advancement in clinical trials and drug development of new drugs. There is also a different guidelines if different countries for clinical trials and their descriptions.

Many organization and agencies are responsible for the approval of new drugs. In this article also describe some important points of benefits of clinical trials and drug development, advance technique and clinical research organization structure and its importance.

Most important and new topic regarding health and clinical trials is declaration of Helenski.

Dr Vivek Dave Assistant Professor, Department of Pharmacy Banasthali University

Dr Sachdev ď ™adav Associate Professor (Pharmacology), Department of Pharmacy Banasthali University Ms Smita Kumari Research Scholar, Department of Pharmacy Banasthali University 30 ď‚ƒ August 2017

I

ndia has the maximum number of FDA approved plants outside the US. Clinical trials are imminent bio medical or behavioral investigate study of groups of people that is designed to answer specific questions about bio medical or behavioral interventions. Clinical trials are many times used to find out whether new medical treatment or behavioral interventions are safe, and effective for specific diseases.

Clinical trials contain behavioral human subject's research involving an intervention to modify behavior (growing the use of an intervention, eagerness to pay for an intervention, etc). Human subject researches are to develop or evaluate clinical laboratory tests might be considered to be a clinical trial if the test will be used for medical decision making for the subject or the test itself imposes more than minimal risk for subjects. Clinical trials are medical research to check whether different treatments which are given to different subjects in different diseases are safe or not and method of their working. Trials having types of groups of people in which one is of healthy members of the community, and others involve patients who may be offered the option of being a part of a trial during their care and treatment.

Clinical trials having purpose to find the best ways to decrease disease and the conditions which makes people ill, improved disease state of ill people, increase survival rates or increase the number of people cured, improve or providing good conditions for people living with illness, including reducing problems like side effects of treatments, such as chemotherapy, and diagnose diseases and health troubles. Clinical trials are not all the time method of testing effectiveness and safety of medicines it also an important roles in improving the behavior and standard of living of people. It is also well known methods which embrace educational programmed to increase person's understanding of their medical

situation so they can easily deal with it more effectively, or a psychological treatment, such as cognitive therapy, to treat anxiety or depression. [1] The clinical trials phases and drug development in pharmaceutical industry is shown in [Figure 1].

Phase  The FDA has recently approved "micro dosing," or the "Phase 0 trial," which permits researchers to test a small drug dose in some human volunteers to rapidly weed out drug candidates that are metabolically or biologically ineffective or not. The phase 0 studies are done in humans; it is different from other phase studies. This phase small amount of dose of drug is given to all patients. This study includes more scans and blood samples for the studies. Because drug doses are low, there was also less risk to the patient in phase 0 studies compared to phase I studies. Phase 0 studies help researchers to check the results of drugs in matching to their predicted ones. Problems of absorbance and actions of drug in a body can be easily come out in this phase study.

Phase 0 may help avoid the interruption and expense of finding out years later in phase II or even phase III clinical trials that the drug does not act as it was expected to base on lab studies. Phase 0 studies are not yet being used widely, and there are some drugs for which they would not be helpful. It can be performed with the few people like 20 people. Although they are not a required part of testing a new drug, but are part of an effort to get faster and simplify the process. [2] Phase I Phase I is performed initial human testing in a small group of healthy volunteers. It includes about 20 to 100 healthy volunteers Pharma Bio World

for conducting a study. The main objective of a Phase 1 trial is to find out if the drug is safe in humans or not. Researchers look at the pharmacokinetics of a drug: method of absorbance, method of metabolism and elimination from the body. They also study the drug's pharmacodynamics: chances of side effects, chances of desired effects, this trials helps researchers to find out the safe dose range or effective range of safety and if it is move further it helps in making initially safety of new drugs. An attempt is made to establish the dose range tolerated by volunteers for single and for multiple doses. Phase I trials are sometimes conducted in severely ill patients or in less ill patients when pharmacokinetic issues are addressed. Pharmacokinetic trials are usually measured Phase I trials regardless of when they are conducted during a medicine's development.

Phase II It is studied in a small group of patients Phase II trials gives researchers to evaluate the candidate drug's effectiveness in about 100 to 500 patients with the disease or situation under study, and examine the possible short term side effects and risks related with the drug. They also make every effort to answer some questions like drug is working on desired mechanism or not, Does it improve the condition in question?

Researchers also analyze optimal dose strength and schedules for using the drug.

In Phase II trials, the studies have been conducted in vast groups (100-300) and are designed to analyze working of drug along with Phase I assessment of safety in the larger participants. Genetic testing is very much common if there is enough proof of variation in metabolic rate. the part of phase II is II a whose purpose is to determine the effective dose of drug and how often the drug needs to be taken and the second part II b having purpose of determining the efficacy of drugs. Phase II b trials look at how well the selected dose, or doses, of a drug work (called efficacy). Of course, safety is always closely monitored. Moreover, there have been some trials which are performed in Pharma Bio World

the combined form for both efficacy and toxicity. Drugs that are reasonably safe in phase I can advance to phase II. About twothirds of drugs make it to phase II trials. In fact, phase II trials are usually the makeor-break point for a new drug; development is stopped if it becomes clear that the drug does not work or is too toxic. Sometimes combination of a Phase I trial, a Phase II a trial is meant not only at understanding the safety of a potential drug, but also getting an early read on efficacy and dosage in a small group of patients. The resulting Phase 2b trial would be planned to build on these results in a larger group of patients for the sake of designing a rigorous and focused Phase III trial. [3-4] Phase III Phase III trials researchers includes study the drug candidate in a larger number of patients to generate statistically significant data about safety, efficacy and the overall benefit risk association of the drug. Also helped in the gives information for labeling purposes by which many patients compliance are reduced and increase the proper use of drugs. It is both the costliest and longest trials. Phase III trial, also includes conduction of many other critical studies, including plans for full scale production and preparation of the complex application required for FDA approval. Phase III trials (also called registration trials) are the last step before drug approval. Phase III trials are randomized and controlled they are often international, so that different groups of patients can be studied. Phase III trials look at safety, monitor side effects, and test how well the drug works (usually in comparison to the current standard of care or best treatment available) in a large group (hundreds to thousands of people). They also study the best ways to use a drug, so that the drug's risks and benefits can be seen in, and applied to, a larger and more diverse group of people. Information from phase III trials goes into the labeling of approved drugs, so that doctors and patients can understand more about how to use them. Phase III clinical trials have

been suggested to be designed in order to analyze the efficacy of new drug and its therapeutic effect in clinical practices.

[5-7] Phase III trials have been conducted randomly on large number of patients (3003000 or more), having the target to complete the definite assessment of the new drug, by relationship with the standard drug treatment. Also, due to their longer duration and size, some disadvantages of phase III are as the most expensive, time consuming and difficult to design and run. In phase III trials, the chronic diseases having a period of evaluation related to the time period of the intervention can be used in practice.

[8-9] In common practice, some trials of Phase III are continued until the regulatory submission is depended at the appropriate regulatory agency. Moreover, the collected information are submitted to the "regulatory submission" so that the hope transpires to the sponsor in order to get the approval of marketing the drug. These clinical trials are conducted in patient populations for which the medicine is in the end proposed. Phase IIIa clinical trials generate additional data on both safety and efficacy in relatively large numbers of patients in both controlled and uncontrolled trials. Some clinical trials are also conducted in special groups of patients under which special conditions dictated by the nature of the medicines and diseases. In case of Phase IIIb clinical trials conducted after regulatory submission of an NDA or other dossier, but prior to the medicine's approval and launch. These trials may supplement earlier trials, complete earlier trials, or may be directed toward new types of trials or Phase IV evaluations. This is the period between submission and approval of a regulatory dossier for marketing authorization. [10-12] Phase IV Phase IV, also referred to as Post marketing surveillance, and includes the technical support of the drug after the selling permission of the drug is achieved. The Phase IV studies can be performed with the help of regulatory authority or by sponsoring company for finding a new market of the August 2017 ď‚„ 31

drug. Such trails have been designed to find out if any long term adverse effect over a much large population of patients for a longer period of time, that were not possible during Phase II and phase III trials, has been noted. However, the whole process of the drug from the lab to this point takes about 12-18 years approximately. After medicines are marketed then this trials are taken place for the determination of the safety and efficacy of the drug dosages. Comparison of different formulations, dosages, and duration of treatment, medicine interactions, and other medicine may be evaluated. It also includes new age groups, races, and other types of patients can be study. Some important aspects of this phase study are discovery and meaning of previously unknown or ineffectually quantified adverse reactions and related risk factors.

Regulatory authorities may ask for longer follow up or for more information about drug safety and efficacy, in groups that were disqualified for, or underrepresented in, earlier trials. Often Post marketing trials look at women and children, people with advanced liver disease, people from certain

racial and ethnic groups, or people with other illnesses. Sometimes post marketing trials look at different doses and durations of treatment to see if there is a better way to use a drug or a combination of drugs. [10-12]

MCC etc guidelines. Some countries their organization, guidelines and descriptions are showed in Table 1.

Phase V

Clinical trials offer distinct economic benefits to large pharmaceutical companies who are looking to decrease their time to market on new products and save at the same time. They makes strong development skills as demonstrated in the international market APIs and dosage forms, decrease R&D cost, Cost of industrialized is 40-50 per cent decreases as compared to western countries, Large patient population providing a diverse pool for clinical trials for NCEs, High quality telecom and IT infrastructure, Most excellently, Indian companies have adapted to international regulatory, norms & respect IPR.

Phase V is also termed as "translational research" to refer the effectiveness and group of people based research studies. It is new to find the interrogation of a new clinical treatment into a large number of public health practices. Generally, the Phase V trials have been considered as the field research and it is particularly designed to test generalization of the mechanism to a large sample. [12] Guidelines for Clinical Different Countries

Trials

in

As we know that different countries having different guidelines and rules for their works, same for clinical trials having different guidelines in different countries like for united state having USFDA, for INDIA having CDSCO, South Africa having

Benefits of clinical trials

Organization Structure of CRO CRO project manager supervises investigator initiated, multicenter clinical studies. The role of project manager to associate and

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



United State (FDA)

1) 6 organization center-CBER, CDRH, CDER, CFSAN, Center for tobacco products, Center for veterinary products.

2) One research centre-NCTR c) 2 offices -ORA AND OCI

a) 21 CFR part 50 b)21CFR part 54 c)21CFR part 56 d)21CFR part 312

                    

32  August 2017

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United Kingdom (MHRA)





a) Regulation 28

a) Good clinical practice and protection of clinical trials subjects.

I)Schedule 1 a) Conduct of trials in accordance with clinical trials authorization etc. a) Urgent safety measures. a) Suspension of termination o clinical trials.

b)Regulation 29 c)Regulation 30 d)Regulation 31

ICH

a)Business management group b)Executive support unit c)Office of complementary medicines d)Office of devices ,blood and tissues, office of laboratories and scientific services, office of manufacturing quality, office of medicines safety monitoring quality ,office of medicines safety monitoring, office of non prescription medicines, office of prescription medicines.

Australia(T a)TGA national GA) manager i)First assistant secretary market authorization division ii)Principle medicine advisor iii) First assistant secretary monitoring &compliance division iv)Principal legal advisor v) First assistant secretary support division.

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a)E7 b)E8 c)E9 d)E10 e)E11

a)Studies in support of special population : Geriatrics a)General consideration for clinical trials a)Statistical principle for clinical trials a)Choice of control group and related issues a) Clinical investigation of medicinal products in the pediatrics population.

a)Business management group b)Executive support unit c)Office of complementary medicines d)Office of devices ,blood and tissues, office of laboratories and scientific services, office of manufacturing quality, office of medicines safety monitoring quality ,office of medicines safety monitoring, office of non prescription medicines, office of prescription medicines.

August 2017  33

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

WHO

a)Director general b)Secretariat c)World health assembly d)Executive board members e)Technical and administrative

a) Provision and prerequisites for clinical trials. b) The protocol c)Protection of trial subjects d) Responsibilities of the investigator. e) Responsibilities of the sponsor. f) Responsibilities of the monitor. g) Monitoring of safety. h) Record-keeping and handling of data. i)Statistics and calculations j)Handling of and accountability for pharmaceutical products k)Role of the drug regulatory authority.

INDIA CDSCO

a)Drugs controller-deputy drug controller-drug inspector-supporting staff b) Drugs testing laboratory-govt. analyst-analyst-supporting staff.

a)Approval of new drugs and clinical trials b)Import registration and licensing c)Licensing approving of blood banks, LVPs, vaccines, r-DNA, products &some medical devices (CLAA scheme) d)Amendment to D&C act and rules e)Grants of test license, personal license, NOCs for export f) Testing of new drugs.

a)E7 b)E8 c)E9 d)E10 e)E11

Canada

South Africa (MCC)





a)Studies in support of special population : Geriatrics a)General consideration for clinical trials a)Statistical principle for clinical trials a)Choice of control group and related issues a) Clinical investigation of medicinal products in the pediatrics population

a)Medicines control medicines committee b)Complementary medicines committee c)Veterinary clinical committee d)Analytical committee e)Biological committee f)Clinical committee g)Clinical trials committee h)Pharmaceutical/ bioavailability committee i) Pharmacovigilance committee j)Scheduling committee

Table 1: Guidelines for Clinical Trials in Different Countries 34  August 2017

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Adaptive design

Figure 1: Clinical trial phases and drug development in pharmaceutical industry.

monitors a specific multicenter clinical study by conducting site initiation qualification visits, monitoring clinical trials to guarantee protocol adherence and compliance, conducting study initiation, monitoring close out site visits. Control investigation sites and project team. The CRO coordinator organizes clinical research activity such as recruitment, enrollments, informed consent processes, site initiation visit, the research coordinator is also responsible for hosting monitor visit and is knowledgeable in all regulatory guidelines. Trainer facilitates orientation training programs for all new CRO employees, ensures that training for all staff is up to date, and act as resource for CRO staff. Clinical research supervisor manages a CRO team. Who conduct clinical trials in adult and involve pharmacokinetics, pharmacodynamics, medical devices, or observation studies. Regulatory specialist assumes a central and key supportive role for all studies conducted under the auspices of CRO. A regulatory specialist also assist the study coordinators with the preparation, review and submission of all protocols, amendments, informed consent document, annual review, and safety report, submitted to the institutional review board.

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Business manager provide administrative and financial management services for CRO. Ensuring that business operations are meeting the needs of the study coordinators and its clients. The organization structure is shown in [Figure 2].

SOME RECENT ADVANCING NEW TECHNOLOGIES IN CLINICAL TRIALS Biomarkers/surrogate markers A surrogate end point is defined as a marker intended to substitute for a clinically significant end point that measures directly how a patient feels, functions, or survives.

Biomarkers and surrogate outcomes are used throughout the development, testing, and ongoing positioning of medical therapeutics. The term surrogate literally means a substitute for, replacement, proxy, so some additional outcome is expressed or implied. The relationship between prognostic factors and surrogate markers may also be a source of confusion. This heterogeneity of nomenclature, content, and inference in surrogate therapeutics obscures the meaning of what is being measured and its genuine influence on patient. [13-14]

An adaptive design is defined as a study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data from subjects in the study. Changes are based on pre-specified decision rules that supported the notion that. However, the FDA defined adaptive design more generally by interpreting as 'prospective' any adaptations designed 'before data were examined in an unblended manner by any personnel involved in planning the revision' Making planned, well defined changes in key clinical trial design parameters, during trial execution based on data from that trial, to achieve goals of validity, scientific efficiency, and safety, [15] An adaptation may carry out one of the following categories a) allotment rule, b) example rule, c) Stopping, d) Starting, e) long-lasting rule, f) conclusion rule, g) flawless designs. [16] Bayesian adaptive designs A Bayesian adaptive design includes a study of comparison of two-armed clinical trial using decision speculative approaches. A loss function is special to consider the cost for each patient, and the costs of making incorrect decisions at the end of a trial. It helps in analysis and decision to continue or eliminate the method of trials which based on the currently safety, efficacy and costs. The maximum numbers of interim analyses are not pre-fixed but can be decided adaptively by the experimental data. We derive explicit connections between the loss function and the frequentist error rates, so that the desired frequents properties can be maintained for regulatory settings.

The operating characteristics of the design are able to be evaluated on frequentist grounds. Comparisons of the proposed design with existing ones are carried out

by Extensive simulations. The design is general sufficient to accommodate both continuous and discrete types of data.

August 2017 ď‚„ 35

Data Mining in Crucial Path of Research It includes research advocates are gradually more playing a main role in designing clinical trials that are patient focused and likely to lead to important changes in clinical practice. The purpose of studies is to be sure that clinical trials are designed in a way that will lead to unambiguous results (i.e., are effective at answering research questions). We also want to be sure that the trails should be succeeding as fast as in an affluently as possible and that the patients also get the best possible treatment who volunteers to be in trials (i.e., the trials achieve the highest ethical standards).

These goals are often at cross aim; thus, clinical trial designs generally represent a compromise.

Micro dosing study Micro dosing (phase-0) studies help by condensing the time periods of to phase-I studies by earlier evaluation of human pharmacology of a new test substance, they also help in the early selection of hopeful compounds for further increase before the traditional phase 1 trials, they help in overall speeding up in the process of drug development by focusing only on the promising compounds, they decrease the unnecessary exposure of the participants in the trial to the not so hopeful compounds, they decrease risk of human toxicity owing to the low dose of the test substance and less duration of administration/ exposure to the drug. In traditional phase I trials having dose rapidly study whereas in such trials single dose administration is involved Also, such trials mostly involve they also having lesser risks, decreased preclinical safety package than the traditional phase 1 studies, less number of animals is used, overall time of drug development is reduced, this methodology helps in early selection of the smarter and more promising lead molecules hence, the more effective drugs reach to the market earlier, small amount of the test drug is needed ,the test drug may be prepared as per the principles of the Good Laboratory Practices (GLP) unlike Good Manufacturing 36 ď‚ƒ August 2017

Figure 2: Organization structure of CRO.

Practices (GMP) compliance as required for the traditional phase-I studies any route of administration is possible, the drug can be tested in the sensitive population like women in their reproductive age, patients with renal impairment, cancer patients, etc, this approach can help in studying the test drug for its modulator effects on the targets in a tumor, in the discovery of endogenous biomarkers for evaluating the quantitative effects of the test drug, by this study the not so promising molecules can be eliminated earlier, by which also help in saving costs, in establishing the likely pharmacological dose and by which also helped determining the first dose for the subsequent phase-1 study ,the PK data for initial dose selection can be obtained in nearly six months as compared to nearly 18 months in case of straight phase-1 studies, and they may help in selecting the best animal species for the long term toxicological studies based on the inference drawn from the micro dose metabolite profiling data. [17-19] Declaration of Helsinki 1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including

2.

3.

4.

5.

research on identifiable human material and data. The Declaration is intended to be read as a whole and each of its constituent paragraphs should not be applied without consideration of all other relevant paragraphs.

Although the Declaration is addressed primarily to physicians, the WMA encourages other participants in medical research involving human subjects to adopt these principles.

It is the duty of the physician to promote and safeguard the health of patients, including those who are involved in medical research. The physician's knowledge and conscience are dedicated to the fulfillment of this duty.

The Declaration of Geneva of the WMA binds the physician with the words, "The health of my patient will be my first consideration," and the International Code of Medical Ethics declares that, "A physician shall act in the patient's best interest when providing medical care."

Medical progress is based on research that ultimately must include studies involving human subjects. Populations that are underrepresented in medical research should be provided appropriate access to participation in research.

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6. In medical research involving human subjects, the well-being of the individual research subject must take precedence over all other interests.

7. The primary purpose of medical research involving human subjects is to understand the causes, development and effects of diseases and improve preventive, diagnostic and therapeutic interventions (methods, procedures and treatments). Even the best current interventions must be evaluated continually through research for their safety, effectiveness, efficiency, accessibility and quality.

8. In medical practice and in medical research, most interventions involve risks and burdens.

9. Medical research is subject to ethical standards that promote respect for all human subjects and protect their health and rights. Some research populations are particularly vulnerable and need special protection. These include those who cannot give or refuse consent for themselves and those who may be vulnerable to coercion or undue influence.

10. Physicians should consider the ethical, legal and regulatory norms and standards for research involving human subjects in their own countries as well as applicable international norms and standards. No national or international ethical, legal or regulatory requirement should reduce or eliminate any of the protections for research subjects set forth in this Declaration. [20] Reference 1. Preparing for an FDA medical Device Sponsor Inspection. http://www.fda. gov/ downloads/ Training/CDRHLearn/ UCM176843.pdf.

2. LoRusso PM. Phase 0 clinical trials: an answer to drug development stagnation?

Journal of Clinical Oncology 2009; 27:2586-2588.

3. DeMets D, Friedman L, and Furberg C. Fundamentals of Clinical Trials.

Springer 4th Edition, ISBN 2010; 978: 4419-1585.

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4. Editors. Phase 0 trials: a platform for drug development? The Lancet 2009; 374:176.

5. CDER. "Exploratory IND Studies".

Guidance for Industry, Investigators, and Reviewers. Food and Drug Administration 2010.

6. Adil ES. The Myth of Equipoise in Phase 1 Clinical Trials. Medscape J Med 2008; 10: 254.

7. Guidance for Institutional Review Boards and Clinical Investigators. Food and Drug Administration 2007.

8. Paul J, Seib R, Prescott T. The Internet and Clinical Trials: Background, Online Resources, Examples and Issues. J Med Int Res 2005; 7:e5.

9. 9. Melinda C. Experimental Labour Offshoring Clinical Trials to China East Asian Science, Technology and Society.

An Int J 2008; 2:73-92.

V, Peterson AM. 10. Poole Pharmacotherapeutics for Advanced Practice: A Practical Approach, 2005; Lippincott Williams & Wilkins. ISBN 0-7817-5784-3. Rogers MA. What are the phases of intervention research?

American Speech- Language-Hearing Association; 2013.

11. Brantner CP. Estimating the Cost of New Drug Development: Is It Really $802 Million? Health Affairs 2006; 25:420-8.

12. Rogers MA. What are the phases of intervention research? American SpeechLanguage-Hearing Association 2013.

13. Ajay S, Bhatt A: Knowledge and skills at the study site - requirements for clinical research professionals in India: A Survey. CR Focus. 2008; 19:36-9.

14. Ware JE Jr, Snow KK, Kosinski M, Gandek B. SF-36 health survey: manual and interpretation guide. Boston: The Health Institute, New England Medical Center1993.

15. Chow SC, Chang M, Pong A: "Statistical consideration of adaptive methods in clinical development". Journal of Biopharmaceutical Statistics 2005; 15:575-591.

16. Dragalin V. 'Adaptive Designs: Terminology and Classification', Drug Information Journal 2006; 40 (4)"425-435.

17. Garner RC, Lappin G. The phase0 microdosing concept. Br J Clinical Pharmacol 2006; 61: 367-70.

18. Sandhu P, Vogel JS, Rose MJ, Ubick EA, Brunner JE, Wallace MA, et al. Evaluation of microdosing strategies for studies in preclinical drug development: Demonstration of linear pharmacokinetics in dogs of a nucleoside analog over a 50- fold dose range. Drug Metab Dispos; 2004; 32:1254-9.

19. Vuong LT, Ruckle JL, Blood AB, Reid MJ, Wasnich RD, Synal HA, et al.

Use of accelerator mass spectrometry to measure the pharmacokinetics and peripheral blood mononuclear cell concentrations of zidovudine. J Pharmaceutical Sci 2008;97:2833-43.

20. Declaration of Helsinki, World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects, Bulletin of the World Health Organization, 2001; 79: 373-374.

Contact: sachdev_y@yahoo.com August 2017 ď‚„ 37

Serialization: Coding and Marking is Paramount to Readiness                               

W

ith serialization deadlines fast approaching, a staggering amount of pharmaceutical manufacturers and contract packagers are not fully prepared to meet the stringent requirements for compliance. A number of reports have been commissioned to identify the extent of this issue, with the consensus being reached that some  to  per cent of European pharma companies are not compliant with the Falsified Medicines Directive (FMD) and some  to  per cent of US companies not compliant with the Drug Supply Chain Security Act (DSCSA).

This begs the question why are approximately one third of companies not ready for these major legislative changes There are a number of reasons, not least the fact that implementing serialization is a complex cross-functional project. Many departments must coordinate effectively, from production, IT and Marketing to Engineering and Quality, and often a steering committee is required to coordinate activities. To implement such a major change over several lines, or in many instances across multiple plants, is a slow process. This has been exacerbated by end users requesting help from track and trace providers with increasingly short deadlines - creating a bottleneck for the skilled resources available.

hierry Protas Global Pharma Director Videojet Technologies 38  August 2017

This does not mean that pharmaceutical manufacturers should stand still on the issue, as there are many elements that can be addressed that must be implemented regardless. One critical aspect that can be considered and implemented ahead of time is the way in which products are coded and marked on the production line - an operational aspect on which effective serialization hinges.

Coding and Marking is Essentia Given the complexity of a serialization project, coding and marking solutions can sometimes be assumed to be a minor player on the stage. owever, although printing operations may appear on the surface to be a simple element, they are crucial to the success of a serialization project.

Without a camera-readable code, all further process steps cannot be carried out and therefore serialization fails. If a printer is not capable of producing camera-readable serialization codes reliably, invalid printed packages need be reworked manually or, worse, codes become unreadable at some point along the supply chain and the invalid packages are not allowed to be released to the market. This can have harmful consequences for patients' health and can lead to costly losses in terms of sales revenue. Proven code quality is therefore the cornerstone of every successful serialization project.

In the case of prescription drugs that fall under serialization legislation, the vast majority are packaged using folding cartons. This means that companies looking for effective coding and marking solutions must find the optimum combination of coder to carton substrate in order to achieve high quality, consistently readable codes.

chieving the timate Comination o Code to Carton With countless variations of folding cartons available, manufacturers and contract packagers seldom use the same packaging across the board. Code quality, therefore, is mutually dependent on the coding technology, ink type and Pharma Bio World

carton type. Through the identification of challenges faced by the market and the reaction of experts with practical solutions, it is now possible for pharmaceutical companies to take advantage of a joint service provided by Videojet and an independent foundation that effectively ensures the best possible combination of code to carton. This can significantly reduce the risk of issues deriving from inferior code quality, such as scanning issues and ultimately wastage as a result.

Connectivity and Data Management

A number of factors can influence the longevity of a code, depending on how that code has been applied to the packaging material. In the pharmaceutical industry, thermal inkjet (TIJ) or laser technologies are often preferred for code application. Laser technology provides fast, permanent marks that are ideal for high throughput applications. They use virtually no consumables and offer very high uptime advantages. Thermal inkjet (TIJ) is by far the most common application in the pharmaceutical industry. It is easy to implement and maintain and offers superior print quality with clean, no-mess operation and solidstate electronics requiring no controller maintenance. TIJ printers allow for more complex coding options and the ability to print linear bar codes, alternate fonts, logos, and 2-dimensional codes such as GS1 DataMatrix and QR codes.

Asynchronous communications is a good example of intelligent data management and how coding and marking systems can integrate with the flow of information.

Advanced software allows the printer to send unsolicited information to the line control system, providing the dual benefits of active notification of a printer event and reduced network traffic. As a result, faster notifications can be achieved, which increases potential throughput on the line.

When evaluating code clarity it is critical to assess the resistance of colors under the influence of light - particularly sunlight with high UV levels, and also how codes cope with abrasion - either on production lines, in transit or in the pharmacy store itself. Water resistance too is a key element, as condensation can often form in pharmaceutical manufacturing environments, particularly in cold chains.

All of these elements can be stringently tested under laboratory conditions to ensure the best possible combination is recommended in terms of coder technology and inks if required.

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The way in which a system interacts with the production line must also be taken firmly into consideration, alongside the need for that system to be easy to integrate and to handle serialization data effectively. The ability to purchase and implement serialization-ready solutions makes this a very straightforward process where coding and marking is concerned, and the benefits are wide ranging.

Buffer management, too, is a key area of consideration. Serialization solutions vary in their requirements for printer memory, therefore printers must be configurable to print unbuffered - where variable data is received and printed one record at a time - and buffered, where many records are sent to the printer at once but printed only once each. When using a buffer, an unexpected line stoppage can result in unused codes unless an intelligent coding device can communicate which numbers are still available for use. This is especially relevant in countries where manufacturers may have to purchase serial numbers, enabling manufacturers to reclaim unused codes and ultimately safeguard against wastage.

Finally, by utilizing Unicode encoding technology, over 1m characters can be encoded, unlocking access to a huge range of global languages. This is vital as, given the global markets served by the pharmaceutical industry, manufacturers

need to have the capability to represent an extensive number of characters across Arabic, Cyrillic and pan-Asian languages.

In all instances, ensure your coding and marking provider is able to offer full Installation Qualification (IQ) and Operational Qualification (OQ) packages.

This will guarantee that the systems installed are not only set up according to your specific parameters, but are also able to deliver what is expected on an operational level.

Working with EDxpert Partners Pharmaceutical companies who align themselves with an expert coding and marking provider can often reap the benefits of the relationships that company has with OEMs and Track & Trace providers. As coding and marking is such an integral element of serialization, there is often a reliance on these suppliers for the successful completion of projects, therefore certain elements of a project can sometimes be expedited. Videojet, through its commitment to its customers and ongoing relationships, constantly supports its partners to help them through the implementation phase, bringing to the table elements such as the testing facility for code assurance and other elements of advanced technical support. In addition, given the broad reach of pharmaceutical companies and their often global operations, the company's pharmaceutical experts - whether they be sales engineers or technical support specialists - are available worldwide to cover international serialization projects.

Pharmaceutical companies do not have a choice where compliance is concerned outside of losing business as a result of lack of preparedness. Take steps today, engage with expert partners, and reap the rewards through operational preparedness.

Contact: itan@abipr.com August 2017 ď‚„ 39

Doctor’s Perspective

Prevention of Stroke in Atrial Fibrillation: One of the Major Roles of Oral Anticoagulants What is Atrial Fibrillation?

Atrial fibrillation is a heart disease where heart rate is irregular and often rapid. Atrial fibrillation occurs because of the altered electrical signals in the upper chambers (atria) of the heart. The normal heart rate which ranges between 60-100 beats per minute is increased to about 100-175 beats per minute.

Age and Other Risk Factors for Atrial Fibrillation Heart diseases or other systemic diseases can cause atrial fibrillation. The other risk factors include age, hypertension and alcohol consumption. Elderly people have higher risk of atrial fibrillation compared to younger people. In some people, family history of atrial fibrillation may be present.

The RE-LY Atrial Fibrillation Registry involving 15,400 patients with atrial fibrillation in the emergency departments from 46 countries including India showed large differences in the age group as well as other risk factors. The average age of patients in this global registry was 65.9 years. Vora and colleagues have recently published the results of the national atrial fibrillation registry by the Indian Heart Rhythm Society involving 1537 patients.

This study from 24 centers across India showed that atrial fibrillation is common in both genders. The proportion of male and females in this registry was 48.5 and 51.5 per cent respectively. Average age of Indian patients with atrial fibrillation was 54.7 years. These data suggest that the Indian patients with atrial fibrillation are younger.

Hypertension and rheumatic heart disease are risk factors for atrial fibrillation. In the RE-LY Atrial Fibrillation Registry and the national atrial fibrillation registry by the Indian Heart Rhythm Society, prevalence of hypertension was 41.6 and 31.4 per cent 40  August 2017

respectively. Rheumatic heart disease was present in 31.5 per cent Indian patients with atrial fibrillation in the global registry whereas it was found in 47.6 per cent in the Indian registry.

Complications of Atrial Fibrillaiton Two important complications associated with atrial fibrillation are stroke and heart failure.

• • Stroke: In atrial fibrillation, atria do not contract normally resulting in an increased risk of blood clots forming.

The clot can travel to the brain resulting in stroke which an important cause of death and disability. Up to 20 per cent of patients may die because of stroke while the rates of disability are much higher.

• • Heart failure: Uncontrolled atrial fibrillation can result in heart failure.

Assessment of Risk of Stroke in Patients with Atrial Fibrillation Validated scoring systems (eg, The CHADS2, CHA2DS2-VASc) are available to assess the potential risk of stroke in patients with atrial fibrillation. The factors considered for calculation of risk include age of the patient, presence of congestive heart failure, diabetes, history of stroke or other vascular disease, and gender.

Management of Atrial Fibrillation and Prevention of Stroke Broadly, the management of atrial fibrillation consists of giving medicines to normalize and maintain the heart rate, to prevent stroke by using blood thinners and to treat underlying causes of atrial fibrilltion. There are several guidelines and consensus statements for the prevention of stroke in

atrial fibrillation. There are international guidelines (eg, NICE, The American College of Cardiology, American Heart Association, Heart Rhythm Society) available for the management of atrial fibrillation. In addition, in 2015, the Indian consensus guidance on stroke prevention in atrial fibrillation was published in the Indian Heart Journal. This year, consensus of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation was published in the Journal of Arrhythmia.

Use of O ral Anticoagu la n t s ( Blo o d Thinners) for Prevention of Stroke in Atrial Fibrillation With the help of scoring systems, patients at low risk of stroke are separated from those who are at high risk of developing stroke. Oral anticoagulants are used for prevention of stroke in high risk patients.

Initiation of the oral anticoagulants is taken based on the scores using validated tools.

Administration of oral anticoagulants lowers the risk of stroke by about 50-70 per cent.

Oral anticoagulants are broadly divided into two types; vitamin K antagonists (eg, warfarin) and newer oral anticoagulants.

The newer agents are further subdivided into two types direct factor Xa inhibitors (eg, rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (eg, dabigatran ).

Use of oral anticoagulants for prevention of atrial fibrillation is well accepted across the world including in India. In the national atrial fibrillation registry by the Indian Heart Rhythm Society, oral anticoagulants were used in 70 per cent patients with atrial fibrillation.

Use of newer Oral Anticoagulants for Prevention of Stroke In Atrial Fibrillation New anticoagulants offer several benefits over warfarin, for the physician as well as Pharma Bio World

Doctor’s Perspective patient. The major advantages include lesser risk of drug interactions and drugfood interactions and no need of routine anticoagulation monitoring. In several large clinical trials efficacy of newer anticoagulants in preventing stroke in atrial fibrillation has been established. Considering advantages over warfarin and proven efficacy, there has been significant interest for using newer oral anticoagulants for stroke prevention in patients with atrial fibrillation.

Rational Use of Oral Anticoagulants One of the major problems associated with use of all oral anticoagulants is the increased risk of bleeding. Although oral anticoagulants are prescribed after assessment of individual risk and balancing the risk versus benefits, in some situations control of bleeding remains a concern. For example, management of bleeding is a

concern with use of all oral anticoagulants in patients requiring emergency surgery or interventional procedure or an uncontrolled/ life-threatening bleeding. In these patients reversal of the anticoagulant effect may be needed. Reversal agents or antidotes play a very important role in reversing the anticoagulant effect and this may reduce the risk of morbidity and mortality.

Idarucizumab can rapidly reverse the action of dabigatran. Dabigatran is the first newer oral anticoagulant for which a reversal agent is approved whereas for other newer oral anticoagulants, reversal agents are being evaluated. Availability of specific reversal agent may increase physician's confidence in using oral anticoagulants resulting in better patient outcomes.

For warfarin, vitamin K and concentrated blood products are considered antidotes.

However, all newer anticoagulants except dabigatran have a limitation today in this regards. Specific reversal agents are not available for newer oral anticoagulants except dabigatran. In 2015, idarucizumab, a humanized monoclonal antibody fragment was approved by the USFDA for emergency surgery or urgent procedures and also in life-threatening or uncontrolled bleeding.

Idarucizumab is now approved in India.

Overall, the benefit of stroke prevention is greater than the risk of bleeding associated with the intake of oral anticoagulants.

Joanne van Ryn Senior Medical Advisor Dept. of Cardiovascular Medicine Boehringer Ingelheim

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Think of Burkert during Injection , Eating Medicines, Dialysis , Root Canal for You Teeth , etc !

B

urkert is one of the leading manufacturer of various measurement and control instruments for the fluid application such as pharmaceutical , food & beverage , cosmetics , Dairy Industry , Brewery application , Medical equipment manufacturing , Drinking water ,etc

Burkert Contromatic pvt Ltd is established in India as 100 per cent subsidiary of Burkert Fluid Control Systems Germany. The Headquarter situated in Chennai , a major automobile hub in India. We have further developed satellite branches across major industrial sector & OEM based cities and Channel partners throughout the nation with high expertise.

Burkert well known for its manufacture and supply for Hygienic segments such as Pharmaceutical , Bio Pharmaceutical , Food & Beverage , Cosmetics , etc.

As being well trained expertise on above segments we wish to speak many pharmaceutical language on many applications such as process automation, Clean in place, fermentation, heat treatment, Dosing, filling, chromatography, etc.

42  August 2017

Here we could see how we contribute to the pharmaceutical processing application in terms of components & systems with innovative solutions.

Innovative Solution with Hydroforming Technology Diaphragm Valve plays vital role in pharmaceutical processing applications such as fermenter, Sterile injectable, Pure water skid , etc . Main reason behind using diaphragm valves because of its unique design with Zero Dead leg design. Most of the pharmaceutical industry uses forged body diaphragm valve as standard option due to the surface finishing with electro polish technology of Ra ≤ 0.4 µ m. The entire pharmaceutical and cosmetics industry are bored with forged body as no innovation happened so far.

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design of new Tube body diaphragm valve with Hydroforming technology.

This technology brings with light weight diaphragm tube body valve which change the way of pharmaceutical industry thinking with forged body valves.

This hydroformed technology tube body more environmental friendly compare to foreged and cast body diaphragm valve.

Burkert patented environmental friendly tube body valve reduces carbon foot print of production by minimizing raw material mass. At the same time this technology reduces manufacturing time during heating and cooling in SIP / CIP cycles due to excessive thermal mass.

This suits to cast bodies which could be lower thermal mass than forged bodies but though heavier than hydroformed tube body diaphragm valves. However cast bodies are not recommend pharmaceutical as it increase product contamination risk due to casting impurities possibility.

Burkert's unique tube valve body has a remarkably lighter thermal mass than forged and cast alternatives - up to 75 per cent for a 2-inch-valve. During laboratory testing, we found steam rate savings of up to 53.8 per cent per valve (with a temperature delta of 100 K). Multiply this energy saving with the number of valves in your plant - and then multiply again with the number of CIP/SIP cycles per year! The manufacturing process is also

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designed to be more environmentally- on both sides on the surface of the tube. friendly. When manufacturing a DN 25 These lamb waves couple out to the cast valve body, almost 7,000 grams liquid (mode conversation) and change of CO 2 are released the value for the to a compression wave in the liquid. This new Burkert tube valve body is just over is used technology based on propagation of seismic earthquake waves. We have 2,000 grams. patented this technology for inline Innovative Solution with coutic ave measurement of flow using SAW. Technology for low eaurement This is just simple tube where measuring In every pharmaceutical formulation elements are placed inside the tubing plant Water For Injection skid would and makes more suitable for hygienic be available for processing application. design with surface clean. This leads Pure water which passed through this no contamination of microbial for Water skid in cost and the volume for the same for Injection applications. Due to this should be measured in order identifies design flow meter has very light weight the significant usage cost analysis. Due compared to similar principle of Coriolis to the pure water nature it has lower technology flow transmitters. conductivity than 5 µ S/cm. As existing present technology in the world EMF flow measurement of Electromagnetic Flow transmitter could detect the flow rate with minimum conductivity of 5 µ S/cm but less than this range it fails to measure. As everyone forced to choose for Coriolis principle which doesn't comes under Hygienic standards.

We have introduced new principle of Surface Acoustic Wave ( SAW ) measurement technology. On the surface of solid bodies like the earth we have SAW named Rayleigh waves which propagate. If it's not solid body but a plate or as we use it a tube surface the SAW is called Lamb Waves, which move Pharma Bio World

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Hygiene-compliant, Flexible and Reliable The requirements are tough for the food and packaging industry: hygiene-compliant design, flexibility, short conversion times and high levels of plant availability are increasingly important features for machines and systems. In these user industries, protecting employees is still a priority, but the safety systems need to be adapted to the individual applications and contribute to the efficiency of the production processes

I

n the food and packaging industries, equipment and facilities often operate with very high speed and short cycles.

Safety systems from Schmersal are tailored to these requirements: they are characterised by their hygiene-compliant application and reliably guarantee high plant availability.

One example is the RFID- based safety sensor system developed by Schmersal. As a contactless system, they are particularly suitable for hygiene-sensitive areas.

Another advantage is that the sensors detect potential offset in the safety doors and can trigger a signal accordingly on an early basis. This prevents unplanned downtimes of the machine or plant.

These days, machines need to be more flexible than ever before. Product life cycles are shorter and both retailers and consumers want a wider range of products and packaging. This is why modern filling and packaging machines are often modular in design, as this allows more flexible reaction to market requirements.

installed either centrally in the control cabinet or on a decentralised basis. The decentralised modules communicate with the compact controller via Ethernet SDDC (Safe Device to Device Communication).

There is also the option of monitoring up to 12 axes safely by means of comprehensive functions using the "Safe Drive Monitoring"module (SDM).

This means the safe drive monitoring can be integrated into the compact control system with all the relevant functions.

Safety systems reliably guarantee high plant availability - these include opto-electronic safety solutions such as light grids.

adapted to the individual application.

How this is implemented and applied by the designers of packaging machines is demonstrated by the new generation of the Schmersal safety controller known as This safety system can easily be adjusted "Protect PSC1". to a wide range of different applications. In standalone machines for meat processing, e.g. on cutters and bowl cutters, the smaller variant of the central module PSC1-C-10 is used. In this case, it is fitted with the SDM option for safe axle monitoring, the memory card to save the application programmes and a fieldbus communication system for functional control. Along with the emergency stop button and a safety interlock for the bowl cover, safety sensors for safe axle monitoring on the mixing and cutting The key components of this control system tool are also integrated into the safety are two freely programmable compact circuit. On complex machines such as the controllers (PSC1-C-10 and PSC1 -C- combined filling and packaging systems, 100). In the basic version, both have 14 designers often select a decentralised Siegfried RĂźttger Industry Manager Food & Packaging, safe inputs (up to PL e in accordance with control architecture.

K.A. Schmersal GmbH & Co. KG, Wuppertal ISO 13849 or SIL 3 according to IEC Packaging manufacturers also want quick 61508), 4 safe semiconductor outputs, format changes so that a very wide range two safe relay outputs, two signalling of package sizes can be manufactured Contact: outputs and two pulse outputs for sensors efficiently. These requirements have Schmersal India Pvt Ltd. implications for machine safety. Plot No G-7/1, Ranjangaon MIDC with contacts.

Tal: Shirur, Dist: Pune - 412 220, Maharashtra Increased flexibility can be achieved by Phone: 02138-614743 For both variants, safe I/O expansion using programmable control systems info-in@schmersal.com modules are available which can be which allow the safety functions to be www.schmersal.in 44 ď‚ƒ August 2017

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marketing initiative

Shimadzu Launches its New Nexis Gc

S

himadzu Corporation, Japan, such as petrochemicals, fine chemicals, has launched the Next Industry environmental testing, pharmaceuticals, Standard Gas Chromatograph - food products, electronics/ Nexis GC-2030 - in the Indian market, semiconductors, and flavorings. With as part of its global launch. Shimadzu the growing concern about safety and launched its first gas chromatograph to minimize any impact on both humans over 60 years ago and today is one of the and the environment, there is increasing world's fastest growing chromatography demand for analyzing trace impurities in companies. The launch of this new product raw materials and analyzing the gases is in line with its focus on continuous emitted from products. innovation and introduction of market leading technologies. Toshvin Analytical, The Nexis GC-2030 has been designed authorized distributor of Shimadzu based on the concept of superior usability Analytical instruments in India since 1970, and expandability for accommodating organized a series of product launch a wide variety of applications. The new seminars in Ahmedabad, Bangalore & user interface features a full-color LCD Mumbai, which were attended by over touch panel that provides intuitive and operability.

The 450 customers.

Mr. Manoj Kantak, easy-to-understand included software allows access of Executive Director, Toshvin Analytical, Mr. Yoshiyuki Fujino, Managing Director, laboratory instruments from a smartphone Shimadzu Analytical India & Mr. Takaaki or tablet computer, which enables remote Hiraoka, Product Manager, Shimadzu instrument monitoring regardless of the operating environment. In addition, the Japan were present to grace the event. maintenance required for Nexis GC is Gas chromatographs are used for R&D significantly reduced through the unique and quality control in a wide range of fields, "ClickTek" technology where no tools are

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required to open and close the sample injection port, attach and detach columns, or exchange split lines.

To accommodate a wide variety of analytical applications, the Nexis GC2030 can be equipped with any of a family of high-sensitivity detectors, such as the barrier discharge ionization detector (BID) or a flame ionization detector (FID) that offers the world's highest sensitivity.

In addition to the high reproducibility achieved by the new flow controller, it provides automatic gas leak check and self-diagnostic functions that ensure high reliability. Further, Nexis GC 2030 has Improved compatibility with specialized analyzers (System GCs) tailored to user needs which help reduce costs and space requirements, and increase analysis productivity.

August 2017 ď‚„ 45

press release Dr. Reddy’s & CHD Bioscience Ink Commercialization Deal                                                                                                                                                                                                                                                                                                                                  

PolyPid Completes Enrollment in Phase Ib/II Study of D-PLEX PolyPid Ltd., a c biopharma company with an initial focus on the prevention and treatment of post-surgical site infections, has announced the completion of enrollment in its Phase Ib/II study of D-PLEX (Doxycycline/ Polymer-Lipid Encapsulation Matrix), the lead product candidate, for the prevention of post-cardiac surgery sternal infection. D-PLEX is a secured antibiotic drug reservoir that provides a safe and effective local antibacterial prevention and treatment measure during surgical procedures.

Sternal infection following cardiac surgery is an unmet medical need and one of the most significant complications following open cardiac surgery, which, according to known literature, has a mortality rate of up to  40 per cent.

46  August 2017

The Phase Ib/II study of D-PLEX is a prospective, multi-center, two-part trial evaluating the safety and efficacy of D-PLEX in the prevention of sternal infection post-cardiac surgery. The study is being conducted in Israel on a total of 80 patients. PolyPid expects first line data on all patients in this trial to be available by the end of 2017. The Company intends to seek regulatory approvals in the U.S. and Europe in 2018 to conduct a Phase III trial of D-PLEX in prevention of post-cardiac surgery sternal infection.

To date PolyPid has treated more than 100 patients with its PLEX based anti-infective products. Preliminary data from studies in orthopedic indications showed no infections in the treated organ. Moreover, D-PLEX was safe with no adverse events related to the product.

PharmaLytica 2017                                                                                                                                                                                                                                                                                                                                                                      Pharma Bio World

press release Praj Recognised by IIMM for its Supply Chain Management Practices

                      

                                                   

                                                                                

                                                                                                                                                                                                          

BASF Expands Pharmaceutical Technical Lab                                                                                                                   Pharma Bio World

Dr Rao V S V Vadlamudi Elected President of Commonwealth Pharmacists Association                                                                                                                                                                                                                                                                                                                                                    August 2017  47

Gravity Feed Metal Detector Gravity feed metal detector metaltrap SS30-GF is an eddy current based digital metal detection system designed for pharma, chemical and food industry for detecting metal contamination in powder and granules.

The rejection mechanism used is pneumatically operated Diverter type as it is full proof and allow product containing large lumps to be checked without problem of blockage.

For more information, please contact:

Technofour Electronics Pvt Ltd Gat No: 3 (PT). 5 (PT), 243 (PT), Kasurdi (Kheba) Khed Shivapur-Saswad Road, Post: Khed Shivapur, Tal: Bhor Dist: Pune, Maharashtra 412 205 Tel: 02113-305200, 305246, Fax: 91-02113-305250 E-mail: pcssales@tepl.co.in / teplinbox@gmail.com

Multi-mill Shefa Industries offers multi-mill which is used in pharma industry is also used in chemical and cosmetic industries.

The company uses pharma grade SS to manufacture the range of multimill. The durable and high performing multi-mill can also be offered in customised specifications.

For more information, please contact: Shefa Industries Gala No: 1, U K Quari Compound Gandhi Nagar, Vikhroli (W) Mumbai 400 083 Tel: 022-25942473 E-mail: shefaindustries@yahoo.co.in

Level Sensors CeramTec offers a drip chamber level sensor solution to deliver superior measurement accuracy and performance in medical applications.Designed in response to the needs of medical device manufacturers as well as CE and FDA regulations, including haemodialysis machines and other liquid/blood handling applications. Featuring ultrasonic technology, the level sensor can easily distinguish between liquid and foam, unlike capacitive sensors, helping to ensure that the presence of non-liquid materials does not interfere with the accuracy of measurements.

For flexible chambers of approx 20 mm dia the level sensor is designed to clip firmly on to the chamber and can be easily removed as required. The level sensor can be suspended from the chamber or alternatively, mounted to the machine via screw fitting and subsequently positioned against the chamber. Furthermore, it has been specially engineered to ensure continuous operation in temperatures of up to 105°C and can even withstand up to 130°C. Finally, the level sensor is designed to be easily cleaned with most commonly used medical cleaning agents and is sealed to IP67.

For rigid chambers, a derivative of this level sensor has been made that dry couples to the chamber and can transmit through most plastics, glass and even aluminium. This design utilises the electronics and sensing elements from the sensor, which can then be housed in a mount that is available in a wide range of dimensions and can be tailored to meet individual customer requirements.

Because of the compact nature of the level sensors elements, multiple levels can be monitored as close as 4 mm apart, giving continuous feedback to the machine which can then be used to control pump speed.

For more information, please contact:

CeramTec India Innovative Ceramic Engg Pvt Ltd CeramTec Subsidiary, 506, Gera Imperium 2 EDC Patto Plaza, Panaji, Goa 403 001 Tel: 0832-2970050 E-mail: info@ceramtec.in

48 ď‚ƒ August 2017

Pharma Bio World

Sundaram Technologies offers online/offline carton handling system with negligible vibration.

The company provides a vacuum belt (offline) from start to end to hold the cartons at their place to avoid them from moving while printing the batch code/barcode. The complete system is without any change of parts and can print at a high speed of 200 cartons per minute. One can print cartons of 50 to 250 mm size on the same belt without any change of parts and guide adjustment.

For more information, please contact: Sundaram Technologies F-339 Raghuleela Mega Mall Boraspada Road, Kandivli (W) Mumbai 400 067 Tel: 022-42661121

IPC Bin Loaders The IPC bin loaders are used for the transfer of materials in a dust-free manner without human touch in pharma industries to load powder into RMG bowls, etc.

Available in standard cGMP and customised models with SS-304/316/316L contact parts.

It minimises the overall amount of handling of materials that occurs in manufacturing and other such processes.Facilitates automation capability and dust-free product transfer. It helps to control containment and cross-contamination and is provided with butterfly valve for discharge.

It is available in different capacities ranging from 25 to 1,500 litres.

For more information, please contact:

IPEC Engg Pvt Ltd Plot No: 5175, GIDC, Ankleshwar Gujarat 393 002 Tel: 02646-221175 Telefax: 91-02646-225175 E-mail: md@ipecengg.com / marketing@ipecengg.com

Pharma Bio World

V-Blender GMP compliant, contact parts manufactured in SS. The V shape ensures good rolling and crossmixing. A-shaped frames provide stability of structure. Main drive provided with variable frequency drive to control blender RPM. It has a start-stop arrangement to ensure that the blender always stops in an upright position. Internal baffles ensure good blending and break lumps. Intensifier bars can be provided.

Guard rails are provided with limit switch for safety. PLC/HMI based control panel.

For more information, please contact:

Kunal Machines 104 Kothari Indl Estate Next to Asian Paints, LBS Marg, Bhandup (W) Mumbai 400 078 Tel: 022-61271111, 67251949 E-mail: kunalmachines@gmail.com

Fluoro Elastomer Tube (FKM) Imachemton is fluoropolymer tubing (popularly known as Viton tubing) especially designed for highly corrosive chemicals and solvents used in pharma industries. It is manufactured in dedicated controlled environment to comply critical food and pharma grade standards.

Imachemton has excellent resistance to alcohols, acids, halogenated solvents (Ex. IPA & MDC). It has greater flame and fire resistance. Its service temperature is -15°C to +250°C. It is available in 60 Shore A and 70 Shore A hardness. It is also available in black and off-white colour. It is double polybag packaged in standard pack size of 25 metre (custom packing sizes available). It’s Extractable and Leachable data available upon request. It is phthalate-free.

For more information, please contact: Ami Polymer Pvt Ltd 319 Mahesh Indl Estate, Opp: Silver Park Mira-Bhayander Road, Mira Road (E) Thane, Maharashtra 401 104 Tel: 022-28555107, 28555631, 28555914 E-mail: mktg@amipolymer.com

August 2017  49

FROM MAIL

Online/Offline Carton Handling System

Under Driven Cone Mill Under driven technology meets all your requirements of over driven cone mill with additional advantages including easier inline integration, compact design, unhindered inline product flow for quicker discharge.Easily interchangeable parts can cover same unit into rotary sifter applying centrifugal principal for sifting. Advanced compact design with higher throughput allows milling with table top models for R&D labs.Under driven design can be readily installed in through the wall concept.

For more information, please contact: Tapasya Engg Works Pvt Ltd Plot A/212, Road No: 30, Wagle Indl Estate Thane, Maharashtra 400 604 Tel: 022-61579400 Fax: 91-022-25825243 E-mail: sales@tapasyaindia.net

Pneumatic Stirrers Shefa Industries offers a qualitative assortment of automatic and manual pneumatic stirrer which can be operated automatically as well as manually depending on the requirement. Besides, these automatic and manual pneumatic stirrers are designed as per the clients’ specifications in terms of size, dimensions and capacities.

Pneumatic stirrer is operated on pneumatic compressor air for homogeneous mixing of paint, to avoid settling heavy particles, metallic particles, resin, pigmentation, etc, at the bottom of the container. Stirrer can be mounted on sand, PFT and container.

For more information, please contact: Shefa Industries Gala No: 1, U K Quari Compound Gandhi Nagar, Vikhroli (W) Mumbai 400 083 Tel: 022-25942473 E-mail: shefaindustries@yahoo.co.in

SS Seamless & Welded Pipes, Tubes, “U” Tubes, Foil, Coil, Flanges & Fittings Suraj Ltd, an ISO-9001, 14000, BS OHS 18001 Certified Company are one of the leading manufacturers and exporters of SS seamless and welded pipes, tubes, “U” tubes, instrumentation tubes, foil, coil, flanges and fittings in various sizes, specifications and grades, and also as per customer’s requirements. Suraj has strong presence in the global market.Materials are all austenitic, ferritic, duplex and super duplex SS; specification as per ASTM, ASME, EN, NFA, JIS Standard; size range from 6.0 to 323.9 mm OD; thickness 0.8 to 25 mm; pipe length up to 12 metre long; and tube length up to 30 metre long. Specialization - heat exchangers, heating elements, surface condensers, automotive digestors, instrumentation tubing and fluid piping.It finds application in refinery, petrochemical, LP HP heaters, food, pharma, fertilizer, oil and gas, breweries sugar and ship building.Suraj also holds various Certificates for quality in accordance with AD2000 MERKBLATT W0 and Pressure Equipment Directives (PED) 97/23/EC from TUV, NORD and supply their above products under all national and international third party inspection authorities. Suraj also have their own testing laboratories to undertake various tests such as hydro, eddy current, PMI, IGC, UT, RT, spectro-analysis, mechanical properties and many others as per customers’ specification and requirements.

For more information, please contact:

Suraj Ltd Suraj House, Opp: Usmanpura Garden Ashram Road, Ahmedabad, Gujarat 380 014 Tel: 079-27540720, 27540721, Fax: 91-079-27540722 E-mail: suraj@surajgroup.com

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Pharma Bio World

Anchor/Gate Type Impeller Anchors/Gate Type impellers are close-clearance impellers that fit the contour of the vessel.

These impellers provide adequate mixing under the laminar flow conditions encountered in high viscosity applications for heat transfer.

These impellers sweep the whole wall surface of the vessel and agitate most of the fluid batch through physical contact.

Anchor impellers are used for liquid viscosities between 5,000 and 50,000 cP. When reaction/mixing homogeneity is required, other types of impellers are recommended.

For more information, please contact: FEDA Inc B/37 Maruti Indl Estate Plot No: 59/1/2/3, Phase 1, GIDC Vatva Ahmedabad, Gujarat 382 445 E-mail: ashok.chaurasia@fedainc.com

Ultrasonic Cleaner/Bath Citizen ultrasonic units are used in industrial and analytical laboratories. With their high power, optimised parameter settings and strict parameter monitoring and assisted by a large range of useful accessories the ultrasonic units guarantee safe and reliable results for the multi-faceted laboratory applications. The Citizen’s laboratory equipment is complete with a full programmable of cleaning chemicals developed and produced in their own laboratory.

Citizen ultrasonic cleaners are extremely versatile. They can also be used in laboratory applications for cell separation, mixing emulsifying, sample preparation and degassing of liquids. The demands of light industrial workflow require an ultrasonic bath that can stand up to the challenge.

Their baths are perfect for deep cleaning to remove dirst, grease, waxes and oils from light industrial parts and components of all kinds.

For more information, please contact:

Citizen Scale (I) Pvt Ltd Citizen House, Unit No: E-2, Plot No: 11, WICEL Opp: SEEPZ Gate No: 1, Andheri (E) Mumbai 400 093 Tel: 022-42437700 E-mail: sales@citizenscales.com

Standardized Chemical Pump with Magnetic Coupling KSB Pumps Ltd offers Magnochem pumps in India. These standardized chemical pumps with magnetic coupling are suitable for handling aggressive, toxic, explosive, valuable, flammable, malodorous or harmful fluids in the chemical, petrochemical and general industries.

Magnochem - horizontal, seal-less volute casing pumps in back pull-out design with magnetic drive confirms to ISO 2858 / ISO 5199. Magnochem pumps are Atex compliant also. Its broad range of variants offers excellent flexibility. Pumps are optimally designed for excellent energyefficiency and offers maintenance-free long life.

Magnochem pumps are available in 26 different sizes and are designed for 40 bar operating pressure and have capacity to pump liquid up to 300 cu meters per hour at head of 150 meters. To cater to wide range of applications; hydraulic components of Magnochem are available in different grades of SS and it can withstand fluid temperature between -90 and +300 oC.

For more information, please contact: KSB Pumps Ltd Mumbai-Pune Road, Pimpri Pune, Maharashtra 411 018 Tel: 020-27101241 E-mail: bipin.kode@ksb.com

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Conta Bin Blender Customers can avail of their superior quality conta bin blender. These bin blenders are appreciated by large number of clients due to high quality and durability. These products are available in the market at most economical rates. Conta bin blenders are used for mixing, lubricating and blending in pharma, food, chemical, ceramics, plastics and other allied industries of dry powder.

For more information, please contact: Shefa Industries Gala No: 1, U K Quari Compound Gandhi Nagar, Vikhroli (W) Mumbai 400 083 Tel: 022-25942473 E-mail: shefaindustries@yahoo.co.in

Vials S h r e e Naina Glass provides a comprehensive range of USP Type 1, tubular glass vials with filling capacity from 1 to 100 ml in flint and amber colour. Vials can be produced as per ISO Standard or can be customised as per customers’ needs with the help of their in-house design team.

Their vials are 100 per cent camera inspected for all critical parameters and are packed in clean room condition with 0.3 u Heppa filters and double skin AHUs ensuring a dust-free environment.

For more information, please contact: Shree Naina Glass Village Katha Dist: Solan Himachal Pradesh Tel: 01795-245326, 246776

52  August 2017

Check Weigher Check weigher CW1200-01 system provides 100 per cent online weighing, ensuring compliance with international standards of pharma, food, chemical and cosmetic industries. Check weigher CW 1299 also improves production line profitability through significant reduction in product give-away. The entire system is made from SS and designed for easy removal for cleaning purposes.

For more information, please contact:

Technofour Electronics Pvt Ltd Gat No: 3 (PT), 5 (PT), 243 (PT), Kasurdi (Kheba) Khed Shivapur Saswad Road, Post: Khed Shivapur Tal: Bhor, Dist: Pune, Maharashtra 412 205 Tel: 02113-305200, 305246, Fax: 91-2113-305250 E-mail: pcssales@tepl.co.in / teplinbox@gmail.com

Triple Quadrupole Mass Spectrometer For labs looking for the next step up in triple quadrupole GC-MS/MS productivity, the Thermo Scientific TSQ 8000 Evo triple quadrupole mass spectrometer provides more capacity, more information, more compounds and more results per unit of time for higher levels of productivity and efficiency in analytical workflows. Unlike other GC triple quadrupole mass spectrometers that require extensive, time consuming method setup, the TSQ 8000 Evo GC-MS/MS has purpose-built software, AutoSRM, for automated SRM method creation, optimisation and management from full scan to the complete analytical method setup. It is fast, simple and reliable.

For more information, please contact:

Thermo Fisher Scientific India Pvt Ltd 102, 104, Delphi ‘C’ Wing Hiranandani Business Park, Powai, Mumbai 400 076 Tel: 022-67429494 Fax: 91-022-67429495 E-mail: sagar.chavan@thermofisher.com

Pharma Bio World

Cold Form Blister Foil ACG Pharmapack offers ALUMPACK, a cold form base foil made from validated raw material sources that are compliant to the global regulatory standards of the pharma market.The foil serves as an ultra-high barrier packaging solution against moisture, light, oxygen and other gases assuring product protection and increased shelf life.Feature high degree of mechanical and dimensional stability by adding additional layer to the standard laminates.It has excellent sealability with common lidding material, possibility of surface and reverse-printing to enhance aesthetic appeal. Consistent performance on machine maximises production reliability.

For more information, please contact: ACG Pharmapack Pvt Ltd SciTech Centre, 7 Prabhat Nagar Jogeshwari (W), Mumbai 400 102 Tel: 022-30462832 E-mail: sales.ph@acg-world.com

Large Desiccant Paks Sorbead India offers a complete line of pharma grade large desiccant paks called Unit Paks, which are manufactured using DuPont Tyvek and several custom substrates like kraft or cloth.

DuPont Tyvek is made of spun-bonded Olefin and is intended for packaging of substances, which are meant to remain stable and not get mixed with other products. It has outstanding porous microbial barrier and is non-leaching and odourless. It meets US FDA and EU Standards. Also, Mil Spec 3464 Type I & II.It finds application in packaging of API, other pharma goods, aerospace, machinery, shipping of electronics and many more.

For more information, please contact:

Sorbead India 306-307 Prayosha Complex Next to Hyundai Motors Chhani Jakat Naka, Vadodara, Gujarat 390 024 Tel: 0756-7688877, 0265-2761041 E-mail: sales@sorbeadindia.com / sales@swambe.com

Pharma Bio World

Precision Piezo Stage Aerotech’s QFOCUS QF50 piezo nanopositioning stage is designed for highperformance microscope objective and optics positioning. It offers 400 μm closed loop and 450 μm open loop travel, high speed, 0.01% linearity, sub-nanometer resolution, and 4 nm bi-directional repeatability. The QF-50 accommodates optical instruments and next-generation laser micromachining applications. Due to a high-stiffness mechanical design, the QF-50 can outperform competitive piezo scanner offerings with larger, higher numerical aperture (NA) objectives. The QF-50 is ideal for optical positioning applications requiring high precision and throughput coupled with long travels.Optional closed-loop feedback using a unique capacitive sensor design allows for subnanometer resolution and high linearity. Unlike foil strain gauges or piezoresistive sensors, capacitive sensors provide a direct measurement of the positioning carriage for superior accuracy and repeatability When coupled with Aerotech’s Q-series controllers and drives, the QF-50 demonstrates sub-nanometer positioning resolution and in-position stability (jitter) while maintaining high positioning bandwidth. Advanced software options, such as Dynamic Controls Toolbox and Motion Designer, provide a variety of highly-effective, easy-to-use tools including Iterative Learning Control, Harmonic Cancellation and Command Shaping, providing improved tracking errors and faster step-and-settle times. OEM drive options are also available.

The QF-50 is available with threaded adapters to fit most microscopes and objectives. The microscope turret mounting allows fast and simple positioning at any desired orientation. In addition, tapped holes on the stage body provide alternative mounting for custom interfaces in machines or other optical instruments. The QF50 is available with a clear aperture of 29 mm as standard. Custom stage designs, travels, and threaded adapters are available.

For more information, please contact:

Aerotech, Inc 101 Zeta Drive Pittsburgh, PA 15238-2811 U.S.A. Tel: +1 (412) 967 6854 E-mail: smclane@aerotech.com / jbala@aerotech.com

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Pilot Fermenter for Lab & Pilot-scale Cultivation of APIs Bosch offers a new pilot fermenter for the cultivation of active pharma ingredients (APIs) on laboratory and pilot scale.

Depending on the selected mixer, the fermenter can process batch sizes from eight or 13 litres up to 50 litres. In addition, reactor sizes for 100 and 200 litres are available for pilot and small industrial batches.

Moreover, the system can be equipped with several interchangeable mixing elements designed for different cell types and process controls. The mixer regulates the inflow of liquids or gases needed for cell cultivation. The feeding of process media takes place fully automatically. Further, the system periphery can be expanded to include additional peristaltic pumps, so that additional process fluids can be dosed.

Since the pilot fermenter is equipped with a gentle rotary pump and a second reactor vessel, it supports batch and fed-batch processes, as well as perfusion and continuous processing.

For more information, please contact: Commha Consulting PoststraĂ&#x;e 48 D-69115 Heidelberg, Germany Tel: +49 6221 18779-27 / F -11 E-mail: bosch@commhaconsulting.com

AUGUST 8 Real-Time PCR System Agilent Technologies Inc offers AriaDx Real-Time PCR System. AriaDx is the only modular real-time PCR instrument on the market intended for in vitro diagnostic use. Real-time polymerase chain reaction (PCR) is routinely used in laboratories to help identify pathogens, genotype infectious agents and for cancer diagnostics.Based on a history of providing precision qPCR technology, the new AriaDx Real-Time PCR System has been designed and manufactured to ISO13485 Standards and is CE marked for use in in vitro diagnostics. Whereas the Stratagene qPCR products portfolio primarily catered to customers in basic research, the launch of AriaDx now extends the portfolio from its use in research to also include diagnostics. The unique modular design of customer-changeable optics in the instrument enables laboratories to use AriaDx with just one optical cartridge, and add more (up to six) as required. The touchscreen and accompanying analysis software is intuitive, and incorporates customer-favoured features from the Stratagene Mx Series while further increasing and streamlining analysis capabilities.AriaDx is versatile in its functionality and can be used for assays detecting gene expression, allele discrimination and genotyping. Such assays are primarily used in identifying the causative agent of an infection and in gene mutation analysis for cancer diagnostics.The open platform of AriaDx makes it compatible to existing fast chemistry-based assays that are DNA binding and probe-based. This feature enables assay developers and partners with optimized reaction chemistries to quickly validate their assays on the AriaDx. For more information, please contact:

Agilent Technologies Inc 5301 Stevens Creek Blvd Santa Clara, CA 95051, U.S.A. Tel: +1 408-553-2005 E-mail: victoria.wadsworth-hansen@agilent.com

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Lab-Grade Undercounter Refrigerators The Thermo Scientific TSX505 Series undercounter refrigerators will debut. As the only current labgrade undercounter refrigerators using thermoelectric devices in place of compressor technology for variable speed control, these refrigerators regulate their internal temperatures more effectively to provide ideal storage conditions for the most demanding applications. Powered by compressor-free V-Drive technology, featuring synchronized temperature management (STeM), internal conditions are actively monitored and maintained at the desired temperature. This includes constant monitoring of, and adjustments during, door-openings to minimize the negative impact of temperature fluctuations on samples. In combination, V-Drive and STeM provide uninterrupted temperature stability and uniformity throughout the internal chamber. Furthermore, the new TSX505 refrigerators consume up to 37 per cent less energy than other models, translating to an average annual cost reduction of up to 30 per cent. The compressor-less technology of the TSX 505 refrigerator also overcomes the common challenge of ‘humming’ experienced with many lab-grade refrigerators through its whisper-quiet operation at just 35 dBA. This means that the unit can be kept in work areas without disturbing personnel or nearby patients. In addition, with no internal protrusions, such as overhead fans, users can benefit from up to double the storage space compared to similar models.

The undercounter refrigerators use environmentally-friendly refrigerants in compliance with the US Environmental Protection Agency’s (EPA) Significant New Alternatives Policy (SNAP). Data logging capabilities are easily enabled through a USB port, allowing users to monitor storage conditions in a timely and efficient manner.

For more information, please contact:

Thermo Fisher Scientific India Pvt Ltd 102, 104, Delphi ‘C’ Wing Hiranandani Business Park, Powai, Mumbai 400 076 Tel: 022-67429494, Fax: 91-022-67429495 E-mail: sagar.chavan@thermofisher.com

Leakproof Vials The new Samco Clicktainer vials are designed for the secure collection and handling of fluid, solid and powder samples, including urine, sputum and stool specimens. They bear the CE mark and are compliant with applicable FDA regulations. They also are 95 kPa leak and pressure tested in accordance with standards BS EN 14401 and 14254, respectively, and are tested to support their use in hospital pneumatic transport systems. Available in 120 and 90 mL formats with an optional built-in temperature strip, users simply turn the lid gently past the lock symbol and an audible ‘click’ sound will signify the lid is fully sealed. The click mechanism is also tactile, and clear markers on the lid and vial also indicate when the lid is correctly closed. As such, users can be confident their samples are safe, while the durable tab design reduces the risk of torn gloves or break-off leading to potential contamination of the sample.

The wide 53 mm opening is designed for easy specimen collection and handling, and the cap is available in multiple colours for sample differentiation and management. In addition, the vials are available gamma irradiated to a sterility assurance level (SAL) of 10 -6 for routine microbiology and more sensitive applications or non-sterile for general use.The Clicktainer vials are compliant with For more information, please contact:

Thermo Fisher Scientific India Pvt Ltd 102, 104, Delphi ‘C’ Wing, Hiranandani Business Park, Powai Mumbai 400 076 Tel: 022-67429494, Fax: 91-022-67429495 E-mail: sagar.chavan@thermofisher.com

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events diary                                                                                 

                                                                                     

     

 

           

            

                                                                                     

                             





             

56  August 2017

                                                

Pharma Bio World

bookshelf Outsourcing Biopharma R&D to India (Paperback) Author: P R Chowdhury Price: USD 221.93 No of pages: 130 pages The trend of outsourcing to India for research and development is catching on fast. Over the last decade, worldwide pharmaceutical and biotechnology companies have made India their choice for a research destination. Initially R&D was inclined more towards developing products for the Indian market within the country. This led to several multinational companies opening up production plants in India, primarily due to the globalization of the Indian economy and offshoring jobs to India. Alongside, several global pharma-biotech majors ascertained large market requirements within the country and capitalized on the advantage of serving Indian customers. Strategies were devised to optimize operational expenses with the setting up of on-site R&D to develop products for local requirements. In view of this, this book seeks to explore various nuances of the outsourcing sector with respect to biopharma in India.

Outsourcing Clinical Development: Strategies for Working with CROs and Other Partners (Hardcover) Authors: Jane Baguley (Author), Jane E Winter (Editor) Price: USD 131.87 No of pages: 192 pages The challenges facing large pharmaceutical companies are stark: sales are slowing, and research and development costs are rising. There is an overwhelming need to reduce development costs by as much as 30-40%, while at the same time significantly shortening development cycle times.

Pharmaceutical spend on outsourcing faces double-digit growth for the next three to five years and yet, if outsourcing is to meet these challenges, new models of collaborative and cooperative working are needed now. Outsourcing Clinical Development offers a guide to these new models and to future clinical outsourcing strategy. There is advice on the basis for an outsourcing strategy and guidance on how to work most productively with CROs (contract research organisations); geographical issues, including working in low-cost environments, are also covered.

Outsourcing of R&D in the Pharmaceutical Industry: From Conceptualization to Implementation of the Strategic Sourcing Process (Hardcover) Author: Bianca Piachaud Price: USD 35.10 No of pages: 192 pages This book examines the strategic aspects of outsourcing in relation to the firm. It provides a holistic view of the outsourcing process, starting with conceptualisation, through to implementation and management of the process. Although the book is based on a case study of the pharmaceutical industry, the general principles derived from the Strategic Sourcing Model are generic in nature and the model can be applied to instances of outsourcing in other industries.

Pharma Bio World

August 2017 ď‚„ 57

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Pharma Bio World

                                                            