Raw Material Complexities and Strategies with for Advanced Therapies

As cell and gene therapies move from bespoke academic protocols into commercial-scale manufacturing, the raw materials underpinning them are emerging as one of the most consequential and least standardized parts of the supply chain, according to speakers presenting at the 2026 PDA/FDA Joint Regulatory Conference during the Navigating Complexities of Raw Materials in the Manufacturing of Advanced Modalities session.

In her presentation, Aligning Raw Material Strategies with Global Regulatory Expectations, Lori Dingledine, QC Director Microbiological Control and GTIC Operations at Genentech,stressed that while guidance documents set direction, execution is where advanced therapy medicinal product (ATMP) programs succeed or stall.

Raw Material Complexity

Dingledine cautioned against treating ATMP raw material management the way large-molecule biologics have long been handled. There is complexity in the execution, and a large pharma company absorbing an asset through business development faces different practical challenges than a startup defining procedures for the first time. Health authorities, Dingledine argued, should be treated as collaborative partners rather than obstacles, a message that lands well when programs bring robust, data-backed justification to the table.

The FDA treats viral vectors as active drug substances and applies phase-appropriate current good manufacturing practice (CGMP) from early development, while the European Medicines Agency places starting-material compliance under sponsor responsibility, and the Pharmaceuticals and Medical Devices Agency in Japan and the Pharmaceutical Inspection Cooperation Scheme emphasize risk-based quality management and donor screening. Reconciling those expectations starts with clear categorization: starting materials (plasmids, viral vectors, master cell banks, leukapheresis material) versus raw and ancillary materials consumed during manufacturing but absent from the final product, such as research-use-only (RUO)-grade cytokines, growth factors, and single-use consumables.

That RUO-to-GMP gap was a central theme, echoing concerns raised elsewhere in PharmTech's coverage of cell and gene therapy sourcing. As Alengo Nyamay'antu of Polyplus-transfection told PharmTech in Sourcing Success in Cell and Gene Therapy Development, “Raw materials will need to be GMP-compliant for the drug product to reach commercialization, and their supply should be secured.”1 This is a principle the conference session translated into practice: early, deep-dive quality audits of research-grade vendors, dual sourcing where feasible, and formal quality agreements that define specifications and change-notification expectations.

Assessing Risk

Risk assessment ran through every section of the talk, aligning with the tiered, risk-based approach Fouad Atouf described for PharmTech in Managing Risk for Biomanufacturing Raw Materials,2 where United States Pharmacopeia <1043> classifies materials from licensed, low-risk inputs up through high-risk research- and industrial-grade sources. The conference session urged sponsors to revisit risk assessments whenever product strategy shifts and to assign clear internal ownership for reviewing new vendor information.

Supply chain fragility, particularly single-source dependency and cold chain integrity, drew some of the most pointed guidance. A single point of failure can halt manufacturing outright, and temperature excursions during transit can destroy biological activity entirely. The presenter recommended continuous real-time temperature tracking and exclusive partnerships with qualified specialty biopharma couriers.

The session closed on the development-to-operations hand-off, where legacy suppliers inherited through acquisitions, thin quality systems at early-stage companies, and limited GMP experience can create traceability gaps just as programs approach process performance qualification. The fix, the presenter said, is unglamorous but essential: tight, continuous alignment between quality control, quality assurance, and regulatory teams, and global filing coordination so material changes don’t create supply gaps down the line.

References

1. Thomas F. Sourcing success in cell and gene therapy development. Pharmaceutical Technology 2020 Supplement. February 1, 2020. https://www.pharmtech.com/view/sourcing-success-cell-and-gene-therapy-development
2. Atouf F. Managing risk for biomanufacturing raw materials. PharmTech.com. September 6, 2017. https://www.pharmtech.com/view/managing-risk-biomanufacturing-raw-materials