by Barbara Unger, GMP Quality Expert, and GMP Regulatory Intelligence Editor-in-Chief
One of the most thought-provoking presentations at the recent PDA / FDA meeting in Washington DC was given by Guy Villax, CEO of Hovione Pharmaceuticals. Hovione Pharmaceuticals offers a range of contract services including but not limited to, product development, manufacturing of API and drug products, and analytical support. Guy’s presentation was one of two on the opening day that addressed ‘Current Quality Challenges for Pharmaceutical Executives.’ He began his talk by saying that 60% of small molecule APIs for new NDAs are made by contract manufacturers. I was surprised by the figure. This is clearly different than practices of 15-20 years ago and, according to Guy, represent a migration of CMC knowledge to CDMOs. That alone calls for us to re-evaluate the relationship between CDMO and sponsor firms, particularly for the virtual firms.
Guy addressed four specific areas of concern for him as CEO and provided some thoughts on what might likely emerge in the CDMO space in the future. Let’s take them in turn.
- Supply chain security and fraud remains a significant concern. Supply chains, starting with raw materials and ending with distributed products, are more complex than ever. The ‘fraud’ that Guy discussed was not fraudulent or counterfeit raw materials, APIs, or drug products, but rather fraud perpetrated by service providers. While limited specifics were provided, this includes forged calibration certificates, providers of analytical method validations that re-wrote raw data, and chromatography data system providers that tampered with qualification documentation. This reinforces the position of health authorities that service providers are an extension of your firm, and, as such, the contracting firm is responsible for the quality of their activities. And how do we guard against this type of fraud? In addition to careful selection of contractors, we need to increase our diligence in monitoring their activities. Trust but verify…and then continue to verify. No one cares about your products the same way you do. Anticipate what could go awry and work to prevent it.
- We might now consider a new three-way relationship that includes the FDA (or another health authority), the CDMO, and the sponsor. CDMOs now may have as much, or more, knowledge about the product and expertise regarding manufacturing processes as the sponsor, particularly if the sponsor is a virtual (or near virtual) company. CDMOs are a key player in the success of the product development and commercialization effort. Sponsors are encouraged to keep the CDMO as an active member of the communication effort with the FDA to minimize surprises and unnecessary complications in late stage development. One off agreements with the FDA (or other health authorities) that are not communicated to the CDMO can cause unnecessary strain on the relationship and challenges to the development and manufacturing process.
- The good news is that you have breakthrough therapy designation for your product. The bad news is that you have breakthrough therapy designation for your product. This becomes particularly acute for the CDMO who, along with the sponsor, is now trying to fit two or three years of development and validation work into maybe one year. This is a challenge when a CDMO is not involved with the product, but only becomes more complicated when they are. One of the complications with this situation is that commercialization occurs with batch sizes that are incapable of meeting the market needs. Early discussions with health authorities about post approval scale up needs, processes, and timing are essential.
- And, finally, manufacturing of human drugs, API, and dosage forms are taking on increased importance in product approval. While a complete response letter for a manufacturing issue was rare in the past, 2016 saw fourteen of them. This obviously has a huge financial impact on firms who must wait for approval until the manufacturing issues are resolved.
IN THE FUTURE:
- CDMOs could be a health authorities best friend. The best of the CDMOs have no desire to risk their reputation or jeopardize their business by taking extreme risks for a single product or a single client.
- CDMOs need to strengthen their science and their quality culture to survive and thrive. Both are essential to establish and maintain a solid reputation and trust with regulatory authorities.
- CDMOs need to be early adopters of innovative technologies to better serve their clients.
- CDMOs must provide a high level of service to sponsors, and sponsors should include them in discussions of manufacturing issues with the health authorities. This serves both parties and leads to better outcomes with fewer surprises.
ADDITIONAL THOUGHTS FROM A CEO’s PERSPECTIVE:
- We have NO unskilled employees. It takes everyone performing their responsibilities to be successful, and each job requires a different skill set.
- Discipline and housekeeping are good habits. Personally, they also send a message with first impressions — something you never get a second chance to improve.
- It is important to work at breaking down silos, fostering cross functional activities and interactions, and creating more effective education and training.
- And, finally, it’s most important what you do when things go awry, rather than how you manage when everything is going well. Learn from mistakes. Invest in the identification of root causes and solve the problem rather than continuing to make the same mistakes.
- How do you harness ‘big data’ to best serve the organization? It is clearly an expensive proposition but can provide significant value to the organization. And it is essential for true knowledge management for large, multi-site organizations.
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