Establishing a globally competitive, compliant and efficient supply chain that can be managed by a smaller set of Big Pharma innovators is a key industry challenge
The recent success of pharmaceutical innovation and the record level of new FDA approvals is driving a vibrant contract development and manufacturing industry (CDMOs). This success, though, must be placed in a broader context to fully appreciate and understand the profound changes that have taken place.
Almost half of the new chemical entities (NCEs) have been designated as orphan drugs, which means they’ll be produced in modest to low volumes. Yet, compared with past blockbusters, many of these new NCEs require a longer convergent or linear route of synthesis. As such, regulators are demanding more cGMP stages and want to implement the regulatory starting materials (RSM) strategy earlier.
Overlay ICH Q11 and the genotoxic impurity (GTI) guideline (M7) and you see a dramatic increase in the generation of data and know-how, experimentation, method development and impurity/GTI tracking. Plus, capacity (size and scale) saturation occurs more quickly now because of the higher number of changeovers. And, finally, compliance for NCEs is made easier and more cost-effective by controlling impurities at the RSM stage.
So, what does this mean? RSM developers and suppliers such as Sai Life Sciences are faced with the challenge of working with a global fine chemical industry that — often — is reluctant to work within a cGMP framework and/or share information. This greatly impacts any efforts to control and manage impurities throughout the RSM process. As such, the need for qualified and competent RSM suppliers who understand and comply with cGMP guidelines is increasing.
The process, analytical R&D resources and skills required to comply with the advanced DoE and QbD tools required under ICH Q11 means that drastic changes in the way this work was done have taken place. The NCE supply chain is becoming much more complex as innovators and cGMP-compliant CMOs now have to work with more RSMs, smaller volumes and, to minimise risk, a second tier of supply considerations, which drastically increases the number of players contributing to a single supply chain.
Recent M&A activity in the traditional CMO industry has prompted several top 25 innovators to reassess their preferred supplier list, selecting those that can address the issues associated with next-generation NCEs in this new regulatory context.
Furthermore, EH&S requirements are now becoming go/no-go criteria. Whereas earlier standards were viewed more pragmatically, there is no forgiveness today and only proven safety measures are accepted as a green light to participate in an NCE supply chain.
Finally, society expects medicines to be delivered at an affordable cost; thus, innovators are forced to deliver NCEs to market faster than the blockbusters of the past to ensure financial justification.
Sai increasingly finds itself supplying the CMOs who then supply the innovator. Once EH&S and compliance requirements have been met, the focus is on speed (compared with unit cost) because, now, NCE supply is an increasingly critical part of new launches and the revenue loss easily outweighs any incremental per kilo price advantage.
The CDMO industry must become better at every step and implement a holistic mindset of collaboration within the supply chain to meet the challenges of getting quality medicines to market in the shortest possible time.
The need for virtual innovators or biotech companies must be recognised as well; they provide a source of NCE innovation for Big Pharma, but CMOs must be prepared to deliver an even more customised service that includes a more consultative and focused approach.
Sai is developing its business model to meet the supply chain challenges facing CMOs, virtual innovators and Big Pharma companies. Complementing its skillset with a formidable workforce and versatile cGMP capacity, the company offers a solid foundation for a successful partnership.