FDA’s CGT Flexibilities: Clarity for Developers, Complexity for Strategy

Regulatory Flexibility in CGT – What Has Actually Changed?

In January 2026 the US FDA released a press statement[i] and online guidance[ii] codifying its flexible and permissive approach to the regulation of Cell and Gene Therapy (CGT) clinical development. The agency emphasises that this flexibility had been applied previously case-by-case, but in clarifying its position hopes to remove barriers and perceived misconceptions. Its aim is to expedite development and maintain safety, purity and potency.

Already, Sponsors are openly challenging FDA decisions regarding appropriate application of its stated flexibility (e.g. uniQure[iii]). Consultants in eXmoor advise Sponsors of CGTs to take care interpreting the FDA’s stance; although flexibility reduces prescriptive rigidity it increases scientific and safety responsibility. Avoid development decisions enabled by a permissive early flexibility that may hinder progress during later stages of the lifecycle.

Signalling Versus Substance in the FDA Announcement

Much of what has been codified reflects practices that Sponsors have already encountered. What is new is the explicit communication. The FDA’s transparency is welcome, and we recognise its leadership efforts to ensure predictability and consistency during IND and BLA applications.

These are made in the context of President Trump’s executive order 14293[iv] on regulatory relief to promote onshoring of medicine development. For CGT Sponsors, the signalling may be interpreted as a deregulatory shift. Instead, it is a more formal acknowledgement of how the agency already exercises discretion.

From a regulatory relief perspective, there is little that is new in the communication. And the FDA retains its requirement for scientific justifications supporting development decisions.

Early Clinical Manufacturing – Flexibility Is Not the Absence of Control

The first FDA-stated flexible requirement is that for Phase 1 there is no need for CGT products to be made in compliance with current Good Manufacturing Practice (21CFR part 211).

However, unlike other regulated territories, for clinical trials in the USA not only CGT products but all Phase 1 drugs are exempt from complying with current GMP (21 CFR 210.2(c)).

Nevertheless, for CGT early clinical development we urge Sponsors not to neglect GMP thinking. There is a risk that during early stages the FDA’s recent announcement is misread as a relaxation of quality and safety expectations.

In reality, it shifts the burden of defining appropriate controls onto the Sponsor. Unlike other territories, in the USA it is the Sponsor, not the FDA, that is responsible for GMP compliance during IND supply. The FDA does not inspect IND manufacturing sites.

The current guidance for industry[v] is that, although exempt from GMP requirements, the FDA strongly recommends that Phase 1 products are made with GMP compliance. Although non-GMP manufacture may tempt Sponsors seeking rapid Phase 1 entry, the initial speed may later introduce friction in scalability, comparability, data portability and technology transfer. This will hinder patient access to an otherwise promising therapy. And, most importantly, GMP compliance is primarily for patient safety, which is fundamental with sterile and aseptically made parenteral CGT products.

Specification Flexibility and the Maturity of Product Control

In the CGT sector, products are often developed for small patient populations. Batch sizes and numbers are limited. Consequently, early product specifications evolve as data is generated during clinical development.

The FDA guides CGT developers that final specifications are not expected during the IND stage, and flexibility may even be justified at BLA review. Permissive release criteria may be acceptable.

Where there is a strong scientific rationale, specification flexibility is a welcome and well-established part of product development. Nevertheless, we urge Sponsors to recognise the need for batch-to-batch consistency as applied through specifications to avoid undermining the scientific value of trial results.

Specification control eases tension at licensure and enables cross-regional portability. Specification flexibility works best when paired with early understanding of critical quality attributes and a defined trajectory toward commercial robustness.

Process Changes and Comparability – Where Judgement Matters

Specification control and product characterisation also unlocks comparability needed during inevitable process changes.

The January 2026 FDA guidance states that it will accept minor changes without overly stringent and onerous comparability studies. This lacks clear definition and leaves room for interpretation and regulatory uncertainty.

Rational judgement is needed on the scale of change and a minimum acceptable data package. Again, the responsibility shifts to the Sponsor to lead assessments of risks during changes and generate data that enable risk quantification and assessment.

Comparability is not only a regulatory hurdle. It underpins confidence in clinical data continuity. Under-investing early in process and analytical data can make later changes more difficult to defend.

Process Validation Without Fixed Numbers

The FDA also clarified that in some cases there may be no need for three Process Performance Qualification (PPQ) lots. This welcome guidance reflects recognition that rare disease programmes may not support such validation batches, where concurrent validation may be appropriate.

Nevertheless, the agency confirms that the number of PPQ lots must be justified based on process understanding.

The agency is not alone in this approach; EU GMP for Advanced Therapies[vi] provides comparable validation guidance using concurrent approaches or surrogate materials.  

This is a shift in emphasis from numerical PPQ compliance to demonstrable manufacturing knowledge. We advise our clients that the quality of process understanding matters more than the quantity of PPQ lots.

Collating data on critical process parameters and quality attributes during clinical development, as might be included in a PPQ protocol, may be invaluable. To achieve this, associated acceptance criteria must be defined, and strategies for specification control and product characterisation should take these requirements into account.

Implications for Global CGT Development

The FDA’s flexibility communications should make CGT development in the USA more attractive to Sponsors and is aligned with the overall onshoring intent of executive order 14293. However, as the press release makes very clear, there is nothing entirely new in the announcement; the FDA clarifies these flexibilities already exist.

Sponsors may shift their development plans from Asia and other territories to the USA if there is a perceived reduced regulatory burden. There is broad heterogeneity in CMC maturity during early development in the CGT sector.

For Sponsors developing a product with an understood target profile, these flexibility communications may have little impact. Other Sponsors may well perceive the communications as a signal of reduced standards, and this is a risk both for their development programme and trial participants, and for the sector more widely.

The FDA flexibility has occurred during a period of low investor confidence in the CGT sector, driven in part by manufacturability issues. Flex-enabled earlier clinical entry may bolster confidence. In balance, weak CMC foundations can undermine later valuation, and investor clinical-safety concerns quickly spread across modalities.

Globally, regulatory frameworks differ. Outside the USA, competent authority inspectorates ensure GMP compliance during clinical development. Differences in GMP expectations during CGT development may hinder US-manufactured products being used in clinical trials in other jurisdictions, potentially delaying patient access.

More importantly, a Sponsor’s global strategy should not be an afterthought, because early CMC architecture must anticipate cross-regional development and filing.

Flexibility Increases the Importance of Scientific Judgement

The FDA has reduced prescriptive rigidity, not lowered its scientific expectations. Consequently, Sponsors must articulate rationale for what is proportionate and scientifically defensible.

Flexibility is most powerful in the hands of experienced teams with a defined long-term strategy. It is more challenging when used as a shortcut.

Practical Considerations for CGT Developers

Sponsors may be tempted to rush unreadily into CGT development encouraged by permissive flexibility.
We advise our clients to respond with:

Careful understanding of regulatory requirements at each development stage

Applying lifecycle validation thinking early

Developing a proactive comparability strategy supported by robust product characterisation and specification control

Documenting decisions using quality risk management principles

Aligning CMC strategy with global development plans

Engaging actively with regulators during review decisions

Clarity Without Deregulation

We welcome both the FDA’s clarity and flexibility expressed by its January 2026 communications. They provide support for innovation and lend agility to CGT development especially for rare diseases programmes. The FDA has shown leadership in CGT regulations through risk-based guidance.

We recognise the central importance of scientific robustness, and the shift in accountability from regulator to Sponsor when taking advantage of flexibility.

Success for each programme and the CGT sector at large will depend on early strategic alignment. Experienced, integrated thinking across consultancy, development and GMP execution can help ensure that flexibility today supports, rather than complicates, approval tomorrow.

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[i] FDA Increases Flexibility on Requirements for Cell and Gene Therapies to Advance Innovation, January 2026

[ii] Flexible Requirements for Cell and Gene Therapies to Advance Innovation, January 2026

[iii] FDA tells uniQure to conduct another study of Huntington’s gene therapy, March 20206

[iv] Executive Order 14293—Regulatory Relief To Promote Domestic Production of Critical Medicines, May 2025

[v] Guidance for Industry CGMP for Phase 1 Investigational Drugs, July 2008

[vi] Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products, November 2017