Guest: Jennifer Hayne, VP & Head of Biologics Analytics Services at Catalent
In this technical deep dive of the Out of the Lab podcast, we explore the often-overlooked nuances of transferring assays from early-stage research into a GMP (Good Manufacturing Practice) environment.
Jennifer from Catalent joins us to discuss why "common sense" in a research lab doesn't always translate to a scalable manufacturing process. We break down the trends in missing documentation, the impact of human variability on results, and how to future-proof your protocols.
Key Topics Covered:
The Language of Science:
Why qualitative terms like "gently resuspend" create variability and how to replace them with specific, measurable steps.
Modality Trends:
Comparing the "de novo" nature of cell therapy with the emerging platform approaches in gene therapy.
The Antibody Renaissance:
How bispecifics and ADCs (Antibody Drug Conjugates) are requiring more complex technical discussions than traditional antibodies once did.
Scientist-to-Scientist Collaboration:
When documentation isn't enough, how Catalent uses site visits to identify hidden sources of variability.
Best Practices for Future Transfers:
- Why you need at least two sources for critical raw materials.
- Testing the "limits" of your assay (e.g., what happens at 10 minutes instead of 5?).
- Designing for the 8-hour workday vs. the 48-hour postdoc marathon.
Show Notes
00:02 - Introduction
Nicholas Crudele welcomes Jennifer, VP at Catalent, to discuss trends in incoming procedures and assay transfers.
00:39 - Identifying Incomplete Documentation
Early-stage clients often have incomplete documentation from a GMP perspective, even if it is sufficient to run an initial assay.
A significant trend in missing information is the lack of specificity for individual steps, often due to assumptions made by early-stage researchers.
02:18 - Human Variability and Standardized Techniques
Human variability is a major factor in lab results, as different individuals may perform tasks like pipetting or vegetable cutting differently.
GMP scientists can help identify where increased specificity is needed to control this variability.
Vague qualitative terms, such as "gently resuspend," are a common source of misunderstanding.
04:46 - Best Practices for Resolving Variability
Labs use stringent techniques to reduce variability, such as changing vague language to specific instructions (e.g., "invert the tube three times").
If standardized techniques are insufficient, scientist-to-scientist collaboration, including site visits to observe techniques firsthand, is the next step.
07:27 - Modality-Specific Challenges
Cell Therapy: Every assay is often unique (denovo) and requires technical discussion and experimentation. These materials are sensitive with short shelf lives.
Gene Therapy: This modality is increasingly using more stable, platform-type approaches with less variability.
Antibodies: While established, new innovations like bispecifics and ADCs are requiring closer technical discussions than in the past.
09:37 - The Benefits of Platform Technologies
Platform approaches allow for faster and more cost-effective processes by repeating established exercises with minor changes.
Working with the same lab over time allows for better tracking and quicker resolution of recurring method challenges.
11:47 - Advice for Future Tech Transfers
Raw Materials: Ensure critical raw materials are not single-sourced; ideally, have at least two tested sources to avoid supply chain disruptions.
Test Assay Limits: Experiment with the timing and limitations of steps (e.g., what happens if a five-minute step is done for ten minutes?) and document the findings for the service provider.
Staffing Realities: Consider the practicality of running assays long-term; designs requiring 48 hours of continuous attention are expensive to staff in a traditional GMP lab.
