Key Manufacturing Actions for ATMPs After 2024–2025 Regulatory Shifts
The past two years reshaped the regulatory landscape for advanced therapy medicinal products (ATMPs) and cell & gene therapies (CGTs). As we enter 2026, manufacturers face both opportunity and urgency: aligning with new standards now will prevent compliance gaps and accelerate patient access later. At Progress, and through our involvement in RSNN and ISPE working groups, we see five areas where action in early 2026 will make a real difference for ATMP programs. Keep in mind that while EMA, FDA, Ph. Eur. and USP define the regulatory baseline; PDA and ISPE guidance documents increasingly shape how companies operationalize these expectations.
Here’s what to prioritize
- Reinforce Raw Material Control and CCS
EMA’s upcoming GMP Part IV revision and FDA’s draft guidance on human- and animal-derived materials demand robust supplier qualification and contamination control strategies (CCS). This is especially critical for ATMPs relying on human- or animal-derived raw materials (e.g. serum, growth factors, plasmids, viral seeds). PDA’s Points to Consider No. 13 adds practical expectations for consumables and single-use systems.
Action: Audit your material supply chains and update your CCS documentation to link raw materials with facility and process controls. - Implement Rapid Microbiology for Short-Life Products
USP Chapters <72> and <73> (effective August 2025) enable faster contamination detection: critical for autologous therapies with tight vein-to-vein timelines. Complementary in Europe, the Ph. Eur. Supplement 11.7 update (e.g. 5.2.12 Raw materials) supports risk‑based microbiology and material controls; together with FDA’s 2024 draft on human‑/animal‑derived materials, this forms a coherent transatlantic approach to rapid release backed by strengthened raw‑material governance.
Action: Implement and validate these methods now to shorten batch release cycles and improve patient turnaround. - Align Clinical-Stage Quality with Lifecycle Goals
EMA’s July 2025 guideline on investigational ATMPs warns that immature early-phase CMC can block future marketing authorization.
Action: Review IND/CTA strategies for comparability and potency planning; ensure analytical methods and change-control frameworks are phase-appropriate. - Prepare for Innovative Trials and Post-Market Data
FDA’s September 2025 drafts encourage adaptive trial designs and real-world evidence collection for innovative trial designs for small patient populations. This means sponsors may use external control arms (e.g., historical data, registries) and decentralized data sources, reducing traditional trial size but increasing reliance on robust product comparability and data integrity.
Action: Build data infrastructure that links manufacturing/QC (e.g. extended sample retention and validated long-term assays) and clinical data (chain-of-identity, potency trends) and prepare for post-approval commitments such as registries and long-term stability monitoring. - Harmonize with New Gene Therapy Standards
Ph. Eur.’s Monograph 3186 and Chapter 5.34 (effective April 2025) formalize EU expectations for AAV, oncolytic HSV, and genetically modified autologous cells.
Action: Update specifications and biosafety documentation to align with these legally binding requirements when using the specified platforms.
Bottom Line for 2026:
Start the year by closing gaps in raw material control, rapid testing, and comparability planning. These topics are also the questions we will discuss at the Dutch ATMP Summit 2026, themed “ATMP 2030 – Future-Proofing Advanced Therapy Manufacturing”, where regulators, developers and manufacturers will share case studies on how they are putting the new regulatory expectations into practice. Progress – Experts in Life Sciences can be a valuable partner in turning these regulatory challenges into actionable strategies by helping you implement robust compliance frameworks and accelerate ATMP development throughout 2026.
For your reference, a selection of documents from 2024–2025 is shown below that CMC teams developing ATMPs should be aware of:
- Considerations for the Development of CAR T‑Cell Products
- Human Gene Therapy Products Incorporating Human Genome Editing
- Draft Guidance: Frequently Asked Questions: Developing Cellular and Gene Therapy Products
- Draft Guidance: Methods and Approaches for Capturing Postapproval Safety and Efficacy Data for Cellular and Gene Therapy Products
- Considerations for the Use of Human‑ and Animal‑Derived Materials and Components in the Manufacture of Cell and Gene Therapy and Tissue‑Engineered Medical Product (2024)
EMA:
- Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials
- Revision of EudraLex Vol. 4, Part IV (ATMP GMP; concept paper, May 2025) to align with the revised Annex 1 (steriles), integrate ICH Q9/Q10, and formalize Contamination Control Strategy (CCS) expectations
ICH:
- Dec 2025: Proposals for future ICH guideline development to support innovative ATMPs and CGT
o E.g. Comparability of Advanced Therapy Medicinal Products (ATMPs) Subject to Changes in Their Manufacturing Process (Annex to ICH Q5E)
European Pharmacopoeia (Ph. Eur.) – A new legal framework
- Monograph 3186 “Gene Therapy Medicinal Products for Human Use”
- 5.34 “Gene therapy medicinal products”
- 5.2.12 “Raw materials of biological origin for the production of cell-based and gene therapy medicinal products” – update in Supplement 11.7 (applicable since 1 August 2025)
US Pharmacopoeia (USP) – in progress
- General Chapter <1067> AAV Gene Therapy Products
- General Chapter <1047> (Gene Therapy Products) in revision (see USP–NF 2025 Commentary (Issue 3)
- New rapid microbiology chapters for short‑life products (official 1 Aug 2025):
o <72> Respiration‑Based Microbiological Methods
o <73> ATP Bioluminescence‑Based Methods
- Draft for new ANSI standards. Standards will be voluntary but may be recommended for use if adopted industry-wide
o Draft mRNA standards (T7 RNA polymerase)
o Draft AAV gene therapy standards
o Draft Lentivral Vector Copy Number (VCN) Standards
PDA – Technical Reports & Points to Conside
- PDA News article (Oct 2025): Everything to Know About Cell and Gene Therapy in 2025
- Points to Consider No. 11 (Feb 2025): Development, Classification, Manufacture, Control, and Testing of Plasmids and Vectors Used in ATMP Production
- Points to Consider No. 13: Materials in ATMP Manufacturing.
- Points to Consider No. 14 (Nov 2025): Manufacturing of ATMPs—Facility Design (Part 1)
- Technical Report No. 81: Cell-Based Therapy Control Strategy
- Revised aseptic‑processing standards (e.g., TR 22, TR 26)
ISPE
- Guide: Advanced Therapy Medicinal Products (ATMPs) – Validation Methods and Controls Throughout the Cell and Gene Therapy Lifecycle
- Guide: ATMPs—Equipment Design & Qualification for Cellular Products
Special ATMP features (May/June 2025 issue): Streamlining the Vein‑to‑Vein Process: The Future of Automated Cell Therapy Manufacturing; Final Preparation of ATMPs at Point of Care; Unlocking ATMPs: Reducing Cost as an Obstacle to Patient Access; Resilience for Cell Therapy Manufacturers
