Don’t Let Failure to Communicate Get in the Way of Effective Technology Transfer in API Manufacturing

What happens when a pharmaceutical company wants to change from an existing manufacturing site to a new manufacturing site? Or from one process stage or manufacturing facility to another? One of the challenges is making sure that the chemical process gets shared and essentially “transferred” to the next phase – usually from R&D to full-scale production in a GMP manufacturing environment.

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The process of technology transfer can be an arduous one that takes teamwork, communication, and most importantly, the ability to see the 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) overseas which may have its own set of processes and regulations.

Below is an overview of the key steps for ensuring a smooth and effective technology transfer:

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 CMOs 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.

Here at PCI Synthesis, where we have R&D facilities in Devens, Mass., and manufacturing operations in Newburyport, Mass., our manufacturing engineers work directly, on-site with the technical manager in Devens, during optimization and scale-up, to ensure that there is effective communication and collaboration through these critical steps, before being transferred to the GMP suite in Newburyport. 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 chemist in Devens comes to Newburyport 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.

This same on-site collaboration should occur whenever possible with sponsoring organizations and different Contract Research Organizations (CROs) or other CMOs they may have utilized. We recommend that all of our clients send their engineers or project managers to our facilities to assist with the technology transfer and make sure everyone has the same information and can operate as a team.

Other considerations for effective technology transfer, include:

• 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 points 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. Particularly for contract manufacturing organizations (CMOs), it is difficult to have equipment dedicated to certain processes, so 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.

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 CMO 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.

The technology transfer process is a pivotal step in the process of developing APIs for commercial use. Vital information must be gathered and documents shared to ensure a continuum of excellence in each stage of the project. As with many projects, documentation and communication enable not only smoother, faster development, but also more assurance that potentially dangerous mistakes are not made because of a failure to communicate.

For other articles on tech transfer, check out: “Transferring API Technology to a CMO? Use This Checklist”; “Technology Transfer to a CMO Process Development and technology transfer is much more than simply optimizing the process to the needs of ideal chemistry. What works best is if scientists on both sides interact directly to ensure an accurate transfer of the technology”; “Do’s and Don’ts of API Technology Transfer in Phases 1, 2 and 3 Clinical Trials”; and “Tech Transfer from a Project Management Perspective The importance of communication.”

If you have questions about other ways companies can ensure sound and efficient technology transfer, let us know. We’d love to hear from you. Contact us at 978-462-5555 or http://info@pcisynthesis.com.