Effective technology transfer protocols share the knowledge and capability of a given API manufacturing process and lay the foundation for the next stage of development. They also enable Contract Development and Manufacturing Organizations (CDMOs) to plan, allocate resources and successfully complete the work.
Manufacturers of Active Pharmaceutical Ingredients (APIs) often must transfer technology to another site or firm, or have technology transferred to them. But how can they rest assured that in the process, critical information is not lost and that valuable time is not wasted in the switch? This is where technology transfer comes into play. Having a proven technology transfer protocol in place can make a world of difference – not only in ensuring a smooth process, but also in helping to win the confidence and trust of the sponsoring firm, as well as other contractors involved with the project.
Yet, the process of technology transfer can be a time-consuming and complex one that takes teamwork, communication, and most importantly, the ability to anticipate and resolve potential obstacles that could arise during technology transfer. Often, a chemical process is being transferred not only to a different company with different processes, internal protocols and staff, but it can often be the transfer of a project from a Contract Manufacturing Organization (CMO) located overseas which may have its own set of processes, regulations and ways of doing business.
Regardless of the transfer location, key considerations can ensure a smooth and effective technology transfer.
Saving Time and Money with Strong Sponsor/CMO Partnership
Perhaps one of the most critical requirements of an effective technology transfer is effective communication and sharing of information from the sponsoring organization. Sponsors should openly share batch records, as well as information on obstacles and challenges along the way. They should not hold anything back.
Often, the CDMO is being hired when an overseas or another manufacturer failed, so the project can be seriously delayed, with lots of time and money already having been spent. As much as possible, organizations should strive to not reinvent the wheel, but work to leverage already accrued knowledge to move the project along as quickly and accurately as possible.
Detailed Process Summary
Assuming that the raw materials and Active Pharmaceutical Ingredient (API) remain the same and are procured from the same supplier, a technology transfer usually begins with an assessment of the original manufacturer’s information -- from raw materials through critical process parameters.
Good CDMOs work hard to develop transfer protocols in such a way that critical steps and even equipment differences are adequately challenged. It may be necessary to develop new operating procedures for the product, in which case one or more batches may be required at this stage. The more thoroughly a process is challenged in this early phase, the more robust that process will be moving forward to ensure reproducible quality. This information is included in a validation report, which is essential to FDA approvals.
If possible, a good practice is to have manufacturing engineers work directly with the technical manager during optimization and scale-up, to ensure that there is effective communication and collaboration through all the critical steps, before being transferred to a Good Manufacturing Practice (GMP) suite. Working together the process chemists and GMP specialists would all be on the same page when it comes to the raw materials being used, writing the master batch record for the process to be introduced and ensuring the appropriate analytics are in place.
Once the detailed process summary is in place, the R&D chemists should come to the GMP suite to help get the scale-up process started, working with the engineers to make sure the right equipment, vessels and other instruments are used to run the process.
At each stage this type of on-site collaboration should occur whenever possible so that everyone has the same information and can operate as a team.
Other considerations for effective technology transfer, include:
- Safety. With any large scale manufacturing business, one of the most important aspects of process development is attention to safety. During technology transfer, a meeting between the R&D team, engineering team, and the health & safety team must occur in order to determine possible dangerous scenarios during manufacturing. Some chemicals can be hazardous to the operators who are managing the reactor vessels, so extra care must be taken to protect them.
- Cleaning. Since it is difficult to have equipment dedicated to certain processes, during technology transfer there must be a method for cleaning the residues generated by each process. This ensures that after a successful campaign, the equipment can be changed over to be used in the manufacturing of a different product. Developing a cleaning process includes identification of an effective cleaning solvent, noting areas inside the equipment that are difficult to clean, and developing a way to successfully identify the residues inside of a cleaning sample.
Effective technology transfer is both integral and critical to drug discovery and development for new chemical products. As companies increasingly turn to CDMOs for drug development and manufacture, ensuring a continuum of excellence in each stage of the process, with properly recorded and documented activities is key to seamless operations, as well as long-term success.
Ed Price is President of PCI Synthesis (www.pcisynthesis.com), a pharmaceutical development CDMO based in Newburyport, MA and the largest small molecule drug substance manufacturer in New England.
PCI Synthesis is also a commercial manufacturer of NCEs, generic active pharmaceutical ingredients (APIs), and other specialty chemical products for the medical device industry. PCI Synthesis provides emerging and midsized pharmaceutical companies access to the expertise needed to develop and manufacture complex small molecules.