Start With The End In Mind. How to facilitate transfer from non-GMP to GMP Manufacturing

Show Notes:

Technology Transfer

I began the interview by asking Avril if she could tell us about her experience and success with technology transfer. Avril explained that technology transfer can be defined as a body of work shared between specialized personnel to achieve an end product. For bioprocess the goal is running a process at the manufacturing site with either no changes or minimal changes from the original process developed. She then described her experiences of transferring process knowledge from a drug development company to a partner or a contract manufacturing organization, from a process development to manufacturing within the same company, and from one manufacturing location to another geographically separate location.

Next we talked about the challenging aspects of moving from a non-GMP lab or pilot plant environment to GMP manufacturing and I asked Avril what makes a process fit for GMP. She explained that the GMP framework is there to guide us but we are ultimately responsible for understanding our product identity, strength, efficacy, & safety, as well as our procedures, equipment, & facilities. All this translates into the expectation from regulatory bodies for product & process knowledge. Within a simple regulatory framework, we are also responsible for determining what our appropriate actions and practices will be.

Then we discussed how process development teams can stay one step ahead and prepare for future GMP work. I asked if she could tell us the top three things to consider. Avril said that since the goal is to develop processes that account for variation to secure robust product output, defining Critical Quality Attributes (CQAs) early ensures that you obtain an end product with the quality that you want. In addition, you will also need to consider the Critical process parameters (CPPS) which are the parameters in the manufacturing process that are important to control in order to meet these CQAs. CPPs are typically established with a target set point for control, along with an acceptable range of variability around that target.

She said the top three things to consider are:

  1. Consider if the operating space at small-scale or in the non-GMP setting will be the same after scale-up and in a GMP environment. Identify scale-independent operating parameters in process development – the easy example is maintaining residence time across scales in chromatography. An often overlooked consideration is the bioburden and product degradation risks associated with large scale.
  2. Use technology platforms to mitigate risks associated with equipment during transfer. Consider technologies that can grow & be flexible across your process development & manufacturing designs. Building process science on similar equipment and with similar operations as manufacturing provides reproducibility. But it can also be simple things, like having the a software platform with similar naming conventions and the ability to compare results files.
  3. Think about regulatory compliance early. Are the raw materials of GMP grade quality? Consider the costs when scale goes up and ensure there is a security of supply program for critical consumables. Do your analytical methods support your final vision for GMP in terms of sensitivity and implementation? Consider multi-attribute methods and how you can simplify the method if it is performed on the manufacturing floor, in an emerging market, or at an outsourced lab. And remember, both the FDA & ICH point to taking a risk-based approach to your CQA & CPP definitions and revisiting your assessment throughout the development life cycle as you gain more understanding of your product and process.

I followed up by asking Avril what else is required for successful process transfer. She explained how teamwork and documentation is key. Also, having team members who specialize in a certain activity add to the likelihood of success. Documenting the formal process transfer plan is useful and should include process transfer objectives, deliverables, timeline, process transfer team responsibilities, and provide an overview of the risks with associated milestones.

Maintaining GMP Manufacturing

I switched topics a bit by asking Avril to talk about maintaining GMP once the process is transferred. She described how understanding material compatibility and documenting cleaning practices are explicit requirements for GMP and very important to maintaining GMP manufacturing. She went on to provide a detailed explanation key criteria including items like maintaining SOPs, validation of facility and equipment, preventative maintenance and staying up to date on industry best practices and optimizing workflows and change overs.

I had a follow up question about tech transfer to an external CMO. I asked her if the top three considerations were the same as she had shared earlier. She told me that transferring to an external partner can make the considerations of teamwork and documentation weighted more. Clarifying the tech transfer business process, communication plan, and responsibilities of team members in a kick-off meeting can help increase the likelihood of success.

She then shared that she started her career at a CMO and that it convinced her that having a good document package that evolves as the transfer progresses is also a key to success. Simplification of documents, clear wording, and thorough review are worth the time and effort. She went on to say that since her CMO days, she has owned, reviewed, approved, and influenced several technology transfer document types. She says she doesn’t have a perfect example yet, but thinks the way information is organized may be dependent on the intent, objectives, and parties involved in the technology transfer project. She advises to keep an open mind, but consider the end result you are trying to achieve and who your audience will be.

In my last question, I wanted to ask Avril about how she support her customers now that she is a vendor and what should they expect from their suppliers. She said that the expectation of suppliers continues to grow as end users face the need for process and product understanding while demonstrating compliance with global guidelines and regulations. She explained that at GE they consider both the early process development needs and final GMP manufacturing requirements in the development of newly launched products like PrismA protein A resin and AKTA pilot 600 chromatography system, and as a result the company is confident that these technologies will help customers as they advance through their product life cycle.

Avril shared a story of how a customer recently told her that they saw her as an extension of their team and that she was contributing to their success. She went on to say that she was very proud of this and that this kind of relationship with customers comes with great responsibility to make a real contribution. By providing central products and equipment to customers, the team at GE realizes that they have a responsibility to contribute to their process knowledge through services and tools like material traceability, scale-up data & examples across our technology platforms, cleaning procedure templates, and change control notifications. The supplier has thorough understanding of the design and operating spaces for the technologies we provide to our customers and we want to make sure this understanding is clearly conveyed and appropriately incorporated into their consideration of good manufacturing practices.

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