Technology transfer is a critical step in any drug development program, occurring for various reasons and at different development stages. A sponsor may be looking for a contract development and manufacturing organization (CDMO) for clinical trial manufacturing; to transfer a manufacturing process to a larger, commercial-scale CDMO; or to replace a CDMO that has quality issues. The handling of a technology transfer can greatly impact the success of a product’s development and, ultimately, of its commercial manufacturing.
Technology Transfer Defined
WHO guidelines (TRS 961, Annex 7) define technology transfer as “a systematic procedure that is followed in order to pass the documented knowledge and experience gained during development and/or commercialization to an appropriate, responsible and authorized party.” Through this process, a donor site (either a product’s sponsor or a manufacturing site) transmits proprietary knowledge and experience about a product, the associated manufacturing processes, and/or the relevant analytical methods to a receiving manufacturing site. This allows the receiving site to carry out the necessary activities to produce the product at the appropriate scale for the stage of development.
Technology Transfer Goals
The ICH Q10 guidance explains the purpose of technology 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.
In addition to allowing sponsors and manufacturers to transmit program-critical information to one another, technology transfer offers an opportunity to evaluate and redesign or modernize various elements of a company’s analytical methods or manufacturing processes. According to the ICH Q8(R2) guideline, companies have the option to improve product quality by evaluating innovative approaches throughout the product lifestyle. For example, the receiving site can look at a program with a fresh pair of eyes and might determine that a new and more appropriate piece of equipment would streamline the manufacturing process.
Technology Transfer Team
It is important that a technology transfer team be comprised of cross-functional subject matter experts, and the role and responsibilities of each team member should be clearly defined. Both the donor and receiving sites must have personnel from several disciplines involved, including R&D, manufacturing, quality assurance, quality control, and regulatory affairs.
A close relationship and good communication between the donor and receiving sites is also key for a successful technology transfer and a fruitful long-term relationship, which can last for the entirety of product development and into the commercialization stage.
Technology Transfer Documentation and Information
The donor and receiving sites must gather and prepare several documents to ensure a successful technology transfer:
- Technology transfer plan: This describes all the activities to be transferred, the steps to be taken for the transfer, the responsibilities of each group at each site, and the expected outcome.
- Detailed analytical methods: Analytical methods are one of the first elements of a manufacturing process to be transferred. They are also the foundation of technology transfer success because the results of the analyses are used for comparability assessments.
- Manufacturing process description or batch: The manufacturing batch record is the most crucial document in describing the manufacturing process. It is imperative that it be clear, detailed, well-written, and thoroughly reviewed by the donor site for a seamless manufacturing process transfer with all key details transferred appropriately. The manufacturing process transfer team should always include a technical specialist from the donor site, as sometimes the know-how is not well-documented in the batch record.
- Critical process parameters (CPPs): According to ICH Q8(R2), CPPs are parameters that should be monitored or controlled to ensure that a product is of the desired quality. They are generally identified by assessing the extent to which their variation could impact the quality of the drug product. The CPPs and any other important parameters must be identified and taken into account for a successful transfer.
- Critical quality attributes (CQAs): Per ICH Q8(R2), a CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. Having an understanding and control over the product’s CQAs is important during a technology transfer.
- Technical gap analysis: This is a formal documentation of the assessment of known and potential gaps between the donor and receiving sites’ capabilities and of their readiness for the transfer. For example, the analysis will determine if the receiving site has appropriate equipment in place to perform the transferred manufacturing process or analytical methods. The document should include a risk assessment.
- Adequate change control management system: Any changes or adjustments made to the process or equipment should be documented, assessed, and justified with regards to their potential impact on the CQAs and the Quality Target Product Profile (QTPP).
Execution and Verification of Technology Transfer
A technology transfer plan should be executed in stages as appropriate, with documented evidence that each stage is complete before the next stage starts. As an example, the manufacturing of a small-scale batch should be completed, with acceptable results, before an engineering batch at the intended manufacturing scale is produced. The same logical steps should be performed for an analytical method transfer, with familiarization runs being performed and documented before validation runs begin.
A successful technology transfer should always be documented. There should be evidence that the receiving site can routinely reproduce the transferred product, process, or method against a predefined set of acceptance criteria as described in the technology transfer plan, and such evidence should be produced with reference to the product’s QTPP and CQAs. Finally, a comparability assessment is usually performed to confirm the successful completion of the technology transfer.
Camargo’s network of CDMOs allows us to identify the most suitable service providers for your compound, dosage form, or project, and to ensure optimal performance within your timeline and budget. Our in-house CMC experts can advise on formulation and design, handle site inspection and monitoring, design and review protocols, identify the best method validation strategy for FDA and ICH compliance, and provide invaluable strategic insights for manufacturing scale-up. Contact us to learn how we can support your program.
Eric Leblanc, RAC, CAPM
Senior Scientist, CMC Services