Pharma Technology will be Shaped by New Challenges for Product Manufacturing
Rahul Dev
Vice President - India

Pharma technology is rapidly evolving due to requirements and challenges of new products and developments. Biologics and biosimilars and their packaging create more specialised demands for material performance. This article elaborates on the new developments in pharma technology and the Indian market playing a key role with research and development facilities being increasingly built in India.

With the increasing demands for highly sensitive drugs such as biologics and biosimilars, the requirements for drug packaging and elastomer components are ever-evolving and rapidly changing. The number of biologics stored and administered in prefilled syringes today is constantly increasing. This also triggers a growing complexity of formulations and the surge in novel device designs. Due to the sensitivity of biologics during storage and their complexity during administration, packaging requirements of biologics and biosimilars are creating more specialized demands for material performance. Consequently, market trends indicate a growth in fluoropolymer coated elastomeric closures which help to mitigate risks related to drug compatibility and stability. For therapeutic proteins, the exact chemical make-up and threedimensional conformation can influence the efficacy of the drug. As recognized by the (US) Food and Drug Administration1, the interaction of proteins with silicone oil can present a risk to the safety and efficacy of therapeutic proteins. Conformational changes, degradation and/or aggregation can lead to the inefficacy or immunogenicity of the protein, ultimately impeding or preventing the success of the drug. Therefore, many manufacturers of biologics or biosimilars are already relying on fluoropolymer coated closure solutions today.
However, fluoropolymer coatings need special properties which make them as safe and reliable as possible. They are of particular importance to closures and components for pre-filled syringes. In storage, the drugs are in constant contact with the rubber component, e.g.the plunger of a prefilled syringe. When it comes to silicone oil migrating into a prefilled syringe formulation, the plunger has been found to be the larger source of free silicone than the barrel - despite the fact, that more silicone oil is applied to the barrel.2

Low levels of silicone oil particles in coatings for pharmaceutical packaging components provide advantages for every step of the way in terms of application. They not only make the products safer and more efficient; the reduction or elimination of silicone oils in rubber components and closures can also reduce time-to-market. As authorities such as the FDA recognise the risks which extractables and leachables are posing to sensitive medication, low particle levels can accelerate the approval process.

Cleanroom Manufacturing as standard for state-of-the-art facilities

To ensure that (coated) components for pharmaceutical packaging, particularly for biosimilars, are of the highest standard, a look at the manufacturing environment is often worthwhile. A cleanroom manufacturing environment, incorporating state-of-the-art solutions and standards, is crucial. The socalled fully integrated GMP (Good Manufacturing Practice) environment incorporates innovative automated processes and conforms to the highest industry standards. Each zone has been meticulously designed and constructed to prevent bio-contamination and is equipped with material airlocks. State-ofthe-art pass-through washing equipment has its automatic loading side in one zone and its automatic unloading side in a zone of even higher cleanliness. In addition, the latest generations of camera inspection techniques are used. It exceeds the most stringent quality standards of regulatory authorities and is certified to ISO 15378. All production lines operating under the First Line standard are designed to operate under a zero -defect philosophy. The process flow, gowning protocols, personnel and material flow, and state-of-theart automation all result in the lowest endotoxin, bioburden, particulate, and defect levels available in the industry.

India is playing a key role

India is one of the most important drivers in the international pharmaceutical market and will continue to grow and strengthen its position. Currently, the market has the highest number of USFDA approvals and with more companies buying from Indian manufacturers, this development will continue.

Currently, India's role and the role of its pharma companies are quite centered around generic medication and the delivery thereof. However, this doesn't mean that they will continue on this path. Rather we will see a considerable shift towards establishing facilities for research and development. There are several reasons for this: one reason is certainly that the international regulatory authorities have long been observing Indian manufacturing sites closely. On the one hand, this guarantees quality products and a high aspiration for good manufacturing standards. On the other hand, it also creates the desire to further excel in production. The ambition to keep this position as a market leader is strong, resulting in more high-end and state-ofthe-art facilities. This trend is here to stay, as global companies have started to recognize the market's potential.

Many pharma majors are merging with or acquiring Indian pharma companies and are heavily investing in Research & Development. The main focus used to be on production, but now a substantial amount of the annual profits is going into R & D investments. Many of the major global players are also setting up own R & D facilities in India. Next to generics, R & D will become a major stronghold for India in the future.

Datwyler Sealing Solutions is a prime example for introducing high-end products to India. The newly built extension of the current facility in Pune already produces approx. four billion components per year. It will be fully aligned with Datwysler's state-of-the-art manufacturing standard First Line and produce highly complex Omni Flex coated elastomer components, eg, for prefilled syringes. This investment paves the way to introducing new pharma technology to the Indian market. As a result, the market and its biggest customers will be catered to with locallyproduced components, proving that its future and perspectives are set out to be long-lasting and successful .

1. Immunogenicity Assessment for Therapeutic Protein Products, GUIDANCE. Food and Drug Administration, Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER), August 2014.
2. Felsovalyi et al, J Pharm Sci, 2012,Vol 101(12), p 4569.