4 Mistakes You Must Avoid When Outsourcing Vial Fill-Finish

Advances in large molecule therapeutics have led to exciting growth in the biopharmaceutical market. However, they have also increased the demand for aseptic fill-finish, which requires specialized expertise and capabilities to execute. Biotech and pharma companies without the available capacity to perform these activities in-house will need to work with a qualified CDMO for fill-finish support. Fill-finish is a critical step in your path to the clinic, and any errors at this stage could delay clinical trials or even prevent meeting funding milestones. Be sure to avoid these four common pitfalls when outsourcing your fill-finish project.

1. Overestimating CDMO Capacity

Demand for aseptic fill-finish has grown at a quicker rate than CDMOs can keep up with, due to long lead times for equipment installation and qualification. This has created significant challenges for any company that is targeting a specific timeline but has not yet secured capacity at a fill-finish provider. Today, many CDMOs are booking out 9 to 12 months ahead of time. This lead time does not account for the time required to evaluate your potential partners. For example, your evaluation process should include a technical visit to inspect the facility, equipment, and personnel, as well as a quality audit to evaluate compliance with current GMP. During unforeseen events such as the COVID-19 pandemic, comprehensive site visits or quality audits may not be feasible. In those scenarios, a virtual visit and audit are suitable replacements. This process can take several months, meaning that the time from the initial CDMO screening stage to released drug product could be 12 to 18 months. Assuming that CDMO capacity will be available for a near-term date is a mistake to avoid. Prevent unexpected surprises by budgeting enough time to thoroughly evaluate suppliers.

2. Assuming A CDMO Has Analytical Testing Capabilities (Plus The Knowledge And Resources To Successfully Execute Them)

Analytical testing is integral to drug product manufacturing, both in-process during the formulation process and at product release to demonstrate the product was manufactured to specification. If your CDMO does not have access to analytical testing, it will be forced to outsource these important checkpoints, delaying the overall process and potentially adding additional service providers, each requiring qualification. Even CDMOs with in-house analytical labs are not immune to issues, as their labs may be lacking equipment and/or experienced personnel or may be operating over capacity. Avoid these roadblocks by investigating and validating your partner’s analytical capabilities during the technical (or virtual) visit. In-depth evaluation can be expanded during the compliance audit and continue with the tech transfer to their analytical laboratory.

3. Skipping The Engineering Batch

Argonaut always recommends performing an engineering batch. These preliminary non-GMP runs exist to work out the kinks of a project prior to high-stakes production runs. When dealing with expensive drug products, using a fraction of the material, or a surrogate, ahead of time to proactively identify and address issues could save you considerable resources later. Sometimes, to save time or money, companies opt to forego engineering runs and move directly into production. They may feel their CDMO partner has performed similar projects in the past, making this step unnecessary. Yet, the engineering run is essential from a risk mitigation perspective, as it helps identify anything that is incompatible with the process and your product. It is a mistake to assume that your particular drug product will run the same as similar drug products. One common issue is viscosity, where filling equipment settings must be adjusted to accommodate the characteristics of the product. Failure during a production run is costly and creates long delays. Avoid these failures by reserving time and materials to execute an engineering run.

4. Failing To Establish A Successful Relationship With Your Partner

While a CDMO works for you, the relationship cannot be one-sided. A successful partnership relies on open and timely communication, transparency, and a strong foundation of trust. These building blocks facilitate timelines and contribute to the overall ability of each side to meet necessary milestones for the project. A common misstep by sponsors is expecting that a small or single-person team from their side is enough to manage the CDMO project. Each party, both sponsor and CDMO, needs to dedicate the resources necessary to properly execute the project on time. For example, the sponsor’s quality group needs to review and approve documents as they are generated to make sure the project stays on track, while a separate team is responsible for technical aspects. Not resourcing sufficiently could slow progress and negatively impact the overall project success. Additionally, sponsors should enter the partnership ready to thoroughly describe their drug product manufacturing process and process specifications. Providing full technical information in the beginning equips the CDMO with the information needed to design and execute the most appropriate manufacturing process possible. Building a strong partnership and communication pathway with your CDMO gives your project the best chance at success.

Outsourcing a fill-finish project is a long, complex process. It is critical you are knowledgeable of potential missteps along the way and take actions to avoid them. Protect your timeline by allowing an adequate window for CDMO selection and availability, and make sure the partner you choose is equipped for your project. Prevent expensive failures by performing an engineering run prior to production. And, perhaps most importantly, set yourself up for success by building a strong partnership with your supplier. Knowing the mistakes to avoid is key to a successful fill-finish project.