Understanding the nuances of generics injectables

Express Pharma, in association with West Pharma, recently organised a webinar to understand why emerging generics injectable manufacturers need flexibility and simplicity when dealing with drug containment and delivery. A panel discussion was also held on how COVID-19 impacted the generic pharma market.

Speaking at the webinar, experts highlighted how pharmaceutical sector is at the frontlines to fight the COVID-19 battle, and since many medicines are administered parenterally, the use of glass vials and stoppers as primary container closure systems (CCS) has become crucial.

Milagro E Lopez, Director, Segment Marketing, Generics, West Pharmaceuticals, while presenting his views, informed that in 2020, the global injectable sales grew to $99 billion at a CAGR of four per cent. North America and India are major generic drug manufacturers. “In the US, generics account for approximately 90 per cent of Rx’s dispensed, have over 90 per cent market access, and are dispensed at a high rate,” he added.

He also notified that from FY2018 to FY2019, there was a 26 per cent increase in ANDAs approved by the US Food and Drug Administration (FDA). However, from FY2018 to FY2019, total injectable ANDAs decreased by 19 per cent. In addition, nine companies comprised 35 per cent of all injectable ANDAs in FY2019, and 15 companies comprised 50 per cent. He mentioned that “483s are a concern for Indian generic manufacturers and the volatile generics market needs a product solution designed specifically for generic manufacturers.”

Sharing a brief about AccelTRA Components Program, Lopez mentioned that it is a high-performing next-generation elastomer formula in 4031/45. Meeting global compendia, it helps in delivering quality, speed and simplicity to generic drug manufacturers. It allows generic drug manufacturers to platform one rubber formulation for most of the molecules helping them with inventory management and save cost.

Explaining further about its various aspects, Darshana Chavan, Technical Account Specialist, West Pharmaceutical Packaging India, said, “It meets the market needs by leveraging West expertise to help understand customer needs. It consists of multi-piercing, low particle levels, machinability assessment, extractables characterisation and good lead times, and is compatible with numerous compounds. It is also steam and gamma sterilisable.”

She further mentioned the several factors that influence fragmentation. These can be grouped into three categories- rubber closure (rubber properties), needle (needle properties) and human use (puncturing technique).

Shedding light on the importance of extractables, she said that these are used for selection/qualification for use of materials; necessary to determine targets enabling the development of analytical methods for leachable testing; and useful for quality control for acceptance of container closure system components.

Recent regulatory changes to the container closure systems point to increased regulatory scrutiny and quality standards and manufacturers are faced with supply chain challenges as well.

Moving on to the panel discussion, Dr Alagumurugan Alagarswamy, Director – Injectables/NDDS, Cipla, talked about some of the supply chain risk-mitigation strategies that the pandemic has forced organisations to adopt. He also shed light on how his company changed

the COVID chaos and challenges into an opportunity for India’s pharmaceutical industry, and also mentioned the learnings in supply chain risk-mitigation strategies from an injectables packaging point of view.

“Last year, during March-April, it was a chaos, then we all ran into maintaining our own development programmes in addition to those programmes that we wanted to launch, especially for COVID therapies and other general therapies. Although it was chaos initially, but then we tried to mitigate those with three things. The first thing that we did was making our entire portfolio and doing a forecast analysis and placing orders quite early. The second thing that we did, especially after March 2021 when the FDA published the guidelines on the primary packaging component changes and its supplement criteria for those critical products where we can’t miss the delivery considering the criticality of patients, we supplemented our ANDAs atleast to include the additional sites of the same vendor. Lastly, for COVID-related therapies, especially for India and the rest of the world, we included upfront multiple suppliers considering that we are going to face challenges. We included multiple stoppers and vials in our dossier in those countries wherever we filed. That way, we had the flexibility to move from one supplier to the other between different locations and also there were COVID-related prohibitions that we can’t export to other markets – Remdesivir, for instance. So, we have to manufacture those abroad to support other countries.”

Thereafter, talking about the management of regulatory filings, especially during emergencies, Tridip Mazumder, Associate Director, Packaging Development, Dr Reddy’s Laboratories, said, “Basically, what we understand from the regulatory agencies is that the US and Europe predominantly take the changes of this primary packaging materials in a different way. For instance, when we go to Europe, the way the products and packaging systems are filed, you are given a flexibility. For example, when you are filing a primary packaging material, and you don’t specifically mention many parts of the vendors, you get a chance that if you show an equivalence between the equations, you can move from X vendor to Y vendor, but that’s not true for injectables. On the contrary, the US regulatory agency is flexible and logical. Once you try to establish an equivalance showing a technical comparison, and saying that this is the risk that has already been mitigated and you have the back-up documents available, they tend to accept.”

He further added, “This pandemic has taught us a lot of things and one of the things that we have understood is that it is always better to have common systems for both semi-regulated and regulated markets, so that you are flexible enough in order to switch from one to other, and also get good efficiency in the supply chain management.”

Dipesh Thawani, Deputy General Manager-Packaging Development (PTC), Cadila Healthcare, highlighted how the new guidance on container closure systems released by the USFDA in March this year impacts sterile injectables, and also talked about the importance of having a standard platform for such systems which can be adopted for all products.

He said, “When the pandemic came, there was chaos on how the packaging material supply shortage will be handled and this was the case wherein everybody knew that during the vaccine production, there would be a shortage of components like glass vials, stoppers, etc.; and we know that looking at the population and the vaccine production, entire capacity of the global vendors, majority of the capacity will be utilised, and the priority will be the vaccines and COVID-related products. There was a question about how the situation will be managed.

“In the initial days, FDA also recognised this and it has published the guidance to ease out the prices with respect to supporting the generic companies for COVID-related products. For example, if any ANDA applicant has to submit any ANDA which has less than six months of stability data, FDA has recommended to go through the control correspondence. So, that process established by FDA supports any generic pharma company to file the product on time.”

Kwang Kok Li, Manager for TCS, Generics Market and AP, West Pharmaceutical Services, talked about the transitions/trends in generic injectables packaging that is the move to one single platform or rubber formulation for multiple generic injectable drugs, which is considered the future. However, it is quite possible that innovators might be using old rubber formulations, which might not be compatible to current regulations. She threw light on how West Pharma’s pharma clients in the APAC region, and globally, are adjusting to this trend.

She said, “It is quite coincidental that we came out with the AccelTRA programme before all these COVID challenges came up. A lot of features that it brings mitigate some of these challenges. We have heard of the regulations, and pharma manufacturers looking to qualify various sites of the suppliers. So, this is also something that AccelTRA programme is able to bring. We now have grown to more than 20 plants which has served us well in this pandemic. We are able to increase the capacity at various plants through tech transfers to ensure that we continue to supply our customers and an alignment with these AccelTRA programmes, actually has harmonised as well.

“Pandemic is no excuse to decrease the quality. We ensure that we are able to maintain the quality in these challenging times. Traditionally, the rubber manufacturing process is manual, but we have our own automated process to prevent contamination and increase the quality of the product and cut the processing time for products,” she said.

Post the panel discussion, the panellists and speakers answered questions from the audience. The attendees demonstrated a keen interest in sterile injectables packaging systems, the recent regulations around these systems as well as how West Pharma’s AccelTRA Components Program can address some of these challenges.

A recording of the webinar can be viewed at https://www.expresspharma.in/acceltra-component-program-ensuring-quality-speed-and-simplicity-in-generics-pharma-packaging/

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