So, you moved your API out of R&D and into the kilo lab where your CDMO created small trial batches, defined process conditions and performed the process studies needed for cGMP production in the plant. The kilo lab is essential since it ensures you’ve got it right when it comes time for large-scale manufacturing. In the kilo lab you’ve created the purest form of the API as possible, under a small-scale, controlled environment and saved costs, by conducting this transitional phase outside of the GMP suite.
But now it’s time to transfer the technology to the plant. This step is crucial, since it’s the start of the long documentation trail that is needed for FDA filings, including the Drug Master File (DMF) and any Investigational New Drug Applications (INDs). But how do you ensure a smooth tech transfer? It becomes more difficult when the transfer is occurring between different CDMOs, which can be located in different countries and which may have very different regulatory controls and processes. But, it often occurs between different sites of the same CDMO, as is often the case with Seqens NA CDMO, which has established specific standard operating procedures (SOPs) to reduce any friction during internal tech transfers.
Regardless of how you choose to source your API project, tech transfer begins with the Master Batch Record, the documentation that defines the manufacturing methods, materials, processes and controls for the manufacture and testing of the API. Once the CDMO demonstrates that there are no issues during the scaling up phase in the kilo lab, it assigns a chemical engineer to work with the kilo lab team in order to prepare a master batch record.
Tech transfer takes teamwork, communication, and problem solving skills. It requires a collaborative team that can anticipate the problems that will occur (or that have occurred) and can work together to solve them. Manufacturing engineers should work directly, on-site with the technical manager to ensure that there is effective communication and collaboration through the critical tech transfer steps.
Consider the following five best practices that your CDMO team should be following to ensure an effective technology transfer.
- Provide a detailed summary of pre-scale-up activities. Technology transfer usually begins with an assessment of the original manufacturer’s key documentation and information – from the procurement of raw materials straight through all other critical process parameters.
- Establish the transfer protocols. Effective transfer protocols outline the critical steps required for manufacture of the API; and also consider the differences in equipment and environments that the API will undergo. The more thoroughly a process is challenged in this early phase, the more robust the process will be moving forward when it is reproduced. This information is included in a validation report, which is essential for FDA approvals.
- Keep safety front and center. One of the most important aspects of process development is attention to safety. During technology transfer, the CDMO’s health & safety team should be directly involved with the R&D and engineering teams, to discuss potential issues with hazardous chemicals, problems with reactor vessels and other dangers. So that extra precautions are taken before the API leaves the kilo lab.
- Address the scale-up challenges. When everyone involved in scale-up of an API understand the challenges, they can more easily address them. Issues such as temperature-sensitivity, the feasibility of replicating processes at a large scale, equipment variations, and GMP requirements in the plant must be considered.
- Don’t let easily avoided issues impact successful transfer. An API can be seriously jeopardized be the smallest particle of residue from a piece of unclean equipment. Yet, it is difficult to have costly equipment dedicated to certain processes without reuse. For this reason, you should have sound processes for cleaning the residues generated after each process.
The need to transfer technology within and among CDMOs in API manufacturing is a common occurrence. Yet seamless tech transfer from the kilo lab to the GMP suite doesn’t just happen overnight. It’s an acquired skill that is honed by successful CDMOs with experience and expertise in all facets of API development – the CDMOs that can anticipate and resolve the potential issues in order to ensure a speedier trip to the GMP plant.
For other articles on technology transfer read, Don’t Let Failure to Communicate Get in the Way of Effective Tech Transfer; or Transferring API Tech to a CDMO? Use this checklist.