7 Focus Areas To Establish A Win-Win Relationship With Your CDMO
By Jim Morris and Don DeRoo
You’ve completed the CDMO selection process and identified the firm that will help you bring your product to the market. The CDMO’s leadership team is experienced, knowledgeable, and eager to work with you. But working with a CDMO doesn’t always go as planned; there may be unexpected problems, delays, and disagreements. This article outlines those factors that will impact project success and set up a “win-win” relationship with the selected CDMO.
1. Regulatory Compliance
The most basic requirement for success is meeting regulatory expectations. 21 CFR 200.10, Contract Facilities, states that “FDA considers the CMO as an extension of the client.”1 FDA’s guidance on Contract Manufacturing Arrangements for Drugs: Quality Agreements2 provides further detail on how to meet FDA expectations.
It’s critical that both parties understand their roles and execute responsibilities regarding compliance with the current good manufacturing practice (cGMP) regulations. The quality agreement, which outlines these roles and responsibilities, should be implemented early in the process, prior to the execution of any GMP activities at the CDMO. Both the CDMO and sponsor are responsible for adherence to GMPs, with the CDMO executing this responsibility as defined by the CDMO quality management system and delineated in the quality agreement with the project sponsor.
We know that the development and manufacturing of a new drug is an enormously complex endeavor. It typically requires the knowledge, skill, and experience of both the sponsor and CDMO to bring a new drug to market. You shouldn’t view your CDMO as simply a vendor but, rather, as a strategic partner. In turn, the CDMO should view your success as their success, and do what’s necessary to make your firm successful.
2. A Governance Structure
One of the first actions to be taken after contracting a CDMO is to set up a governance structure with integrated sponsor/CDMO teams appropriate to the scale and complexity of the work. The governance structure will likely change over time, with the initial focus on teams addressing product/process development and tech transfer, later ramping up marketing application(s) and product licensure teams, and finally commercial manufacturing and supply chain teams. Throughout all stages, quality assurance will have a key role.
For large and complex projects, a multi-tiered approach is appropriate, with a senior management steering committee responsible for high-level project strategy, mid-level management teams responsible for a mix of strategy and tactics, and “shop-level” teams responsible for project execution. Consistent and timely documentation and communication of decisions and actions will help ensure that everyone is pulling in the same direction.
3. Transparency And Trust
Both parties need to provide all the information and data required to execute the scope of work. This may include internal product development reports and information from other CDMOs that have previously worked on the product/process. The CDMO will very likely save time and work more efficiently if prior issues are fully disclosed. Any issues the CDMO uncovers later in the project that lead the CDMO to believe negative information was withheld will quickly erode trust. On the other hand, if the CDMO runs up against problems or delays at any stage, they must quickly communicate these issues. In most cases, the CDMO should be able to propose a plan to address the issue(s).
Building trust is like “money in the bank” in that it typically takes time and effort to build up and will be of benefit when a problem arises. So, take the time to build personal relationships with the individuals at your CDMO. Inevitably, problems will arise and when they do, the trust that’s in place will be invaluable.
4. Effective Project Management
Designating a single point of contact at the sponsor and CDMO is an effective way to facilitate the flow of information in a fast-paced environment. For large, complex projects, it’s beneficial for both the sponsor and CDMO to have dedicated, experienced project managers to coordinate and track activities against a timeline.
Furthermore, oversight of project expenses against the estimated budget is essential. Early-stage development programs are often best managed using a time and materials approach, whereas CDMO support of late-stage projects is generally well defined and an experienced CDMO will manage against an agreed budget effectively. Ideally, finance or procurement personnel with the sponsor and CDMO are in regular contact, working in parallel with the technical teams.
5. Tech Transfer Best Practices
The success of technology transfer depends on how well the sponsor understands its molecule, the manufacturing process, and the extent to which they share that knowledge with the CDMO. A tech transfer is most likely to be successful when the sending site (sponsor) assumes primary responsibility for the transfer.
There are essentially two types of tech transfers:
- The first involves transfer of a well-defined process that may already be in place at another CDMO or at the sponsor’s facilities. This type of transfer should be relatively straightforward; nevertheless, one should not be complacent. Even what appear to be very minor or nonexistent differences between processes and process equipment may result in the CDMO’s product being different from the existing product. Comparability studies are usually required when a product is manufactured at more than one location.
- The second type of tech transfer, during which process development (i.e., scale-up and/or process optimization) and tech transfer occur simultaneously, is significantly more complex and will take more time to complete.
In either case, successful tech transfer requires that all available process and molecule data, historic and current, are made available.
One of the best ways to maximize knowledge transfer is to create a joint tech transfer team with experienced representatives. CDMO staff should initially travel to the sponsor site for meetings. When manufacturing runs and analytical tests start to be performed at the CDMO, the sponsor should travel to the CDMO site to witness activities and be on hand to work with the CDMO when technical issues arise. As a former head of quality, I (Don DeRoo) can relate an experience where a sponsor from Asia was reluctant to send their technical team to assist with the tech transfer. After months of setbacks, video calls, and meetings, we were still unable to consistently manufacture the product. Finally, the sponsor sent personnel to work alongside our manufacturing team for several weeks, during which time we were able to identify steps in the customer approved batch record requiring more detail to ensure consistency. After the batch records were revised to include additional process details, the tech transfer was completed without further delay.
6. Regulatory Submission And Site Inspection
The CMC section of the application is usually drafted by the CDMO and approved by the sponsor. All other sections are typically the responsibility of the sponsor. Completing the required studies for a given product and delivery system requires subject matter-specific knowledge and experience. It is essential that personnel from the CDMO and sponsor have the experience to assess risk, handle a wide range of technical/analytical issues, and dialogue with regulatory agencies. Upon eventual submission for regulatory approval, FDA will likely contact the CDMO to request an inspection while manufacturing of the product is underway. The sponsor and CDMO should work together to prepare, pulling together all documentation likely to be requested by FDA, such as production batch records, lists of deviations and change controls, process validation reports, etc.
The sponsor should have technical quality and regulatory representatives on-site during the inspection to answer any questions directed to the sponsor, but the primary focus of FDA will be the CDMO. Being honest and transparent with the FDA is always the best policy. If a 483 is issued, the CDMO will draft the response, with review by the sponsor where appropriate.
7. Maintaining The Partnership
The sponsor–CDMO partnership must be able to withstand changes in personnel at the CDMO and the sponsor company. The quality agreement should be reviewed on a regular basis to ensure it reflects changes in the relationship between the parties.
Quality and delivery metrics should be jointly developed to measure performance and provide input for improvement programs. Metrics should include items such as deviations per batch, batch release time, and process yield and should have agreed-upon targets. Metrics should be distributed in advance of business review meetings, with corrective actions identified for those metrics that demonstrate a potential lack of adequate control.
Conclusion
The FDA considers your CDMO to be an extension of the sponsor’s firm. Therefore, the sponsor shares responsibility for quality and regulatory compliance with the CDMO. If both parties are working together to meet regulatory expectations and are open and honest with the FDA, inspections shouldn’t be a stressful experience.
It’s important to work with your CDMO as a partner, building trust and solving problems together while working at each other’s sites. In most cases, the product development and tech transfer phases of the product life cycle are the most critical. Problems left unresolved at these stages will take more time and resources to fix at later stages.
At the commercial manufacturing stage, continue to build the partnership with your CDMO. Implement KPIs and meet regularly with your CDMO to review status and make improvements. Aim to strengthen the partnership over time so that the win-win relationship translates not only to project success, but also customer/patient benefit and satisfaction.
References
- https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-200/subpart-A/section-200.10
- https://www.fda.gov/media/86193/download
About The Authors:
Jim Morris is founder and principal consultant at IQS Consulting. Previously, he was vice president of NSF’s Pharma-Biotech Consulting practice.
Don DeRoo is a pharmaceutical quality and regulatory consultant. Previously, he was site head of quality at Lonza Portsmouth NH and has served as global head of quality (biologics) and head of cell therapy operations.