Expediting EPCMV to Fast Track Facilities

Consider our earlier example of a project that overlapped conceptual design with clinical studies for a vaccine. There were other activities we were also able to stack. Before preliminary engineering was complete, we brought in procurement and released construction on enabling works packages. While early construction activities were underway, we overlapped the final design. This way, when the design was complete and issued for construction, the construction manager was already aware of the project scope and was able to line up the next steps of equipment and material buyout, as well as line up the building trades.

Likewise, toward the end of the construction phase when the project was substantially complete, we overlapped producing engineering punch lists for construction with the CQV team executing I/OQ protocols.

With an estimated total facility size in mind, the client can begin to evaluate where their new process will be housed. They could start a market search for an existing facility appropriately sized to house the process with the necessary utilities, clear height, and other requirements. In some regions of the country, there is a tremendous amount of space available to lease that could be repurposed, thus avoiding a more costly and time-consuming greenfield approach.

The client might also consider at this time whether they can renovate an existing space they already occupy or even start down the path of constructing a new greenfield facility if that is deemed necessary or desired. The point is, establishing the size needed for the process allows the facility design to move forward in parallel with a design of the interior fit-up. Thus, the overall time to market for the molecule can be reduced.

This type of decision will also depend on the technology platform being used to produce a vaccine. Retrofitting an existing facility could be ideal to supplement the production of a novel therapeutic vaccine platform, for which the drug substance volumes are relatively small owing to their high potency. On the other hand, for cell culture-based vaccines, the larger volumes may require building a new facility—you’re just not going to easily find a 200,000-square foot facility that can be repurposed.

For large-volume processing, it can make sense to outsource to a CMO, but this is not always a straightforward decision. A company typically hands off a fully developed process to a CMO, simply contracting its space and labour expertise. But in the case where a client is still developing or scaling up/out the process, handing it off to a CMO simultaneously may require a CMO flexible enough to adapt their processes and procedures to meet those of the client. There are many CMOs capable of this, but it is a new way of working together that needs to be considered. Also, partnering with a CMO means sharing technology and IP that a company might not otherwise want to share.

A company may choose to spread the risk by doing both: they might build in a facility they own and, in parallel, design and construct the process in a CMO facility. The speed at which the industry is currently moving to develop these vaccines means that the technology transfer is being done differently than it has been traditionally.

We can start an equipment list, especially for long-lead items, roughly around the same time that we first estimate our client’s square footage requirements, for example, during the initial programming phase. Clients usually have a good idea of their primary process equipment needs and we categorize these early into an equipment list to establish a procurement plan.

This plan feeds directly into the overall project timeline. We identify purchase lead times for each item, which informs an integrated project schedule and identifies when they buy equipment to meet the end date of construction. Starting the procurement process early will allow for joining long-lead equipment vendor production queues before the final lock-down of equipment size and features. This occurs while the facility design is underway.

The beginning of a validation life cycle is the generation of user requirements (URS), a foundational document crucial for a smooth quality risk management (QRM) and CQV process. The URSs identify and document product process and knowledge, which are the critical parameters that must be validated in the end. More often than one would imagine, URSs are not developed on time, which ultimately leads to the prolonging of qualification execution. Involving the CQV team early allows validation experts to work with the proper subject matter experts to develop these important documents.

There is a multitude of CQV guidance available, and every approach is a little different. The sooner an approach can be developed and implemented via a validation master plan (VMP) the better. The EPCMV validation team can develop the approach and VMP.