By Judy Carmody, Ph.D.
When FDA issued its May 2026 guidance on Chemistry, Manufacturing, and Controls flexibilities for cellular and gene therapy products pursuing a BLA, early coverage focused on what sponsors won’t have to do: no minimum number of PPQ batches, permissive release criteria during early clinical phases, single-lot analytical method validation in appropriate cases, and possible exceptions to reserve sample retention.
It would be easy to read this as a relaxed bar. It isn’t.
This guidance asks for more from CGT developers than a rulebook ever did. It asks for a quality culture capable of earning flexibility rather than being granted one.
This puts two ideas in focus:
- Quality by Design as a scientific discipline.
- Voluntary Quality Assurance (VQA)® culture as the organizational posture that makes QbD operational.
Flexibility Is a Deliverable
The FDA’s language throughout the document is consistent. Sponsors may justify a smaller number of PPQ batches, and they may leverage platform analytical methods across similar products. Sponsors may commit to post-approval reevaluation of acceptance criteria when only a handful of commercial lots exist at submission.
But, each flexibility is conditional on the following:
- A defensible scientific justification.
- Documented process and product understanding.
- Early, ongoing dialogue with the review division.
The flexibility isn’t waiting to be claimed. It’s the output of a quality system that has done the upstream work (i.e., characterization studies, control strategy development, risk assessments, knowledge management) long before the BLA window opens.
Sponsors who invested in QbD principles will be ready to comply with this guidance with assets to deploy.
Sponsors who haven’t, will be required to demonstrate manufacture justification under deadline pressure.
The guidance is least forgiving of exactly that situation.
VQA® Culture:
Where No Specific Regulation Prescribes the Path
A Voluntary QA Culture rests on four foundational pillars: collaboration rather than confrontation, proper education and training, setting proper expectations, and accountability. When applied, these pillars can transform how teams approach method validation, CMC readiness, and regulatory preparation. This approach recognizes that “quality is not overhead—we are part of the product.”
For analytical teams, this means embedding quality thinking into every and all aspects of method development, validation, and lifecycle management. A VQA® culture meets the spirit of what those requirements protect: patient safety, product consistency, scientific integrity.
So, when FDA says it does not specify a minimum number of PPQ batches, it is not waiving the underlying expectation of demonstrated process capability. It is asking sponsors to own that demonstration as a scientific argument as the basis to meet the three requirements noted above. Organizations that thrive under this guidance will:
- Treat process characterization as a continuous activity, not a Phase 3 scramble.
- Document decisions and the reasoning behind them.
- Run risk assessments that inform real choices.
- Use early FDA engagement as a working relationship, not a final exam.
- Invest in the people doing the work.
Proper Culture And Expertise Stop Being Optional
Several flexibilities in the guidance demand real technical sophistication: platform analytical method qualification and validation, comparability risk assessment for manufacturing changes, alternative rapid microbiology methods for sterility testing, stability strategies that leverage clinical lots and similar-product data. Each requires teams who can construct a defensible scientific argument. This is a culture problem before it’s a regulatory problem.
The flexibility FDA offers presumes a workforce capable of designing studies that justify it. In CGT specifically, where manufacturing teams are often small and the science is moving faster than published standards, the gap between “we have an SOP for that” and “we can defend why this approach is appropriate for this product” is exactly the gap a VQA® culture can help close.
A structured QbD approach, analytical method lifecycle management, process validation strategy, and risk-based comparability are no longer “nice-to-haves” under this guidance. They are prerequisites for accessing the flexibilities the guidance offers.
What This Means for Your Program
There is a quiet but significant shift in posture embedded in this guidance. Traditional CMC documents tell sponsors what to submit. This guidance tells sponsors what they can negotiate on the condition that they show up prepared.
For CGT developers working on therapies for serious and life-threatening conditions, the patient access stakes are real. Faster, more flexible CMC pathways exist now in a way they didn’t a few years ago. But they exist for Sponsors who can demonstrate they’ve earned them.
Quality by Design was always about building understanding, not just building products. This guidance makes that bet official.
