Biopharmaceutical Technology Transfer

Introduction

Technology transfer happens during the production life-cycle of biopharmaceuticals. Technology transfer can take place internally within a biopharmaceutical company from the process development to manufacturing teams, from one site to another site, or from one department to another department. It can also take place externally to a different company, either domestic or international. Technology transfer can also happen from one contract service provider (e.g.,  CRO, CDMO, CMO) to another, for examples, when the infrastructure of the initial provider can not suport further scale-up of the biological product clinical or commercial manufacturing requirements. 

ICH Q10 Tech. Transfer:  The goal of technology transfer activities is to transfer product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realization. This knowledge forms the basis for the manufacturing process, control strategy, process validation approach, and ongoing continual improvement. Key Objective:  The key objective of the technology transfer is to run the manufacturing process at the receiving unit with no or minimal changes from the original process developed to a the sending side. Measure of Success:  The ultimate measure of success for commercial technology transfer is regulatory approval of the transferred process at the new site.

Key Challenges

Technology Transfer inherently involve a number of challenges and project specific risks, both from technical perspective as well as logistical perspective. Careful planning, strong technical support team, and effective communication can help overcome many of these challenges, also offering a balance between budget, time, and risk management.

The original quality of the process itself is not robust (e.g., transferability) Original process is inappropriate or difficult to scale-up The process requires certain unit operation or raw materials that do not comply with GMP Differences in the type and capabilities of equipment availablility Poor documentation and ambiguous description of the process that to be transferred Lack of clear and open communication Additional challenge from different country, culture, languages, and/or time zones Aggressive timeline Limited budget

Process and Methodology

The tech. transfer activities usually starts from the transfer of the documents fromm the sending unit to the receiving side, including process description, production protocols, development reports, and any related studies and data. Once it starts and executes, the most responsibilities lies with the technology receiving side. From the receiving side, besides understanding the process and the product requirements, confirming technical feasibility and performance of the designed GMP-scale process by appropriate small scale prototype process would minimize the risk at lower cost, followed by full GMP scale process runs (e.g., engineering runs or technical runs), Informaction from these GMP runs can be used to help further process optimization and re-design, if necessary.

Figure 1. Schematic workflow of technology transfer stages and related activities.

Process validation is a a major activitiy in technology transfer. Process validation is to demonstrates that the receiving unit can deliver product of comparable quality with consistent performance. Both the sending and receiving sides should work together when developing, implementing, and maintaining product lifecycle avalidation activities. The tech. transfer compeletes when the receiving unit successfully pass pre-approval inspection (PAI) and gain regulatory approval.

Conclusion

Technology transfer for biopharmaceuticals is highly complex and can be chanllenging due to differences of sending and receiving sides, such as facilities, equipments, and scale-up requirements. A systematic transfer methodology provides the best chance of success. In addition, careful evaluation of all necessary information, sufficient documentation, defined roles/responsibilities, clear understanding of timelines, goals, and costs are all considerations that can help minimize risks and ensure product realization.

References