Donated human cells are the starting point for most cell and gene therapies. Before accepting a vial, bag or tissue sample, cell and gene therapy developers should ask three questions: is donor consent fit for purpose; was the right testing performed; and can chain of custody and chain of identity be reconstructed end to end?

Simon Boa at Bramble Bio

Imagine discovering late in development that donor consent does not cover commercial use, infectious disease results cannot be linked to the donation code or the route from collection centre to cell bank cannot be reconstructed. The issue is no longer administrative: it can affect release; regulatory acceptability; investor confidence and patient access.

Cell and gene therapy (CGT) continues to redefine the future of modern medicine, offering potentially curative approaches for diseases that were previously considered untreatable. From early mesenchymal stem cell therapies to next-generation CAR-T products, the sector has experienced rapid scientific and commercial growth, in particular over the last decade.

At the end of 2025 more than 2,100 active clinical trials were ongoing globally within the CGT space.1 While substantial advances have been made in manufacturing technologies, analytical platforms, supply chain logistics and regulatory understanding, one critical factor continues to be overlooked: where did your cells originate from?

For CGT developers, chemistry, manufacturing and control, and quality teams, procurement leads and regulatory professionals, this article focuses on three checks before accepting cellular starting material: donor consent; donor and material testing; and chain of custody/chain of identity.

With almost 60% of all CGT products being launched within the past five years, the importance of controlling and understanding these complex starting materials has become as critical as ever in CGT development.2,3

In the context of CGT manufacturing, starting material typically refers to the biological material used at the beginning of the manufacturing process. Dependent on the therapy type, this may include:

• Donor or patient tissues, such as leukapheresis material, bone marrow and perinatal tissues

• Donor or patient cells, such as T cells, haematopoietic stem/progenitor cells, natural killer cells, mesenchymal stromal cells and tumour-infiltrating lymphocytes

• Donor or patient cell banks, such as pluripotent stem cells (PSCs), which can be created from other cell types (iPSCs) and can then be differentiated into the final cell type.

There are several other starting materials, such as: biologically derived and recombinant proteins; serum-derived products; plasmids; viral vectors and their associated cell banks (typically HEK293). Guidance for such materials can be found elsewhere.4,5,6

Right at the start of the process are hospitals or dedicated collection centres. To ensure the safety of the donor and of the material that they are donating, such facilities must follow various compliant procedures, including:

• Assurance of donor health, safety and privacy throughout the donation procedure

• Staff must have completed a suitable training programme and have appropriate agreements in place to undertake collection procedures

• Standard operating procedures (SOPs) must be followed covering donor history, identity, consent, selection, testing, packaging, labelling and transport

• Implementation of SOPs to minimise contamination in the facility, materials and equipment

• Proper identification and traceability management of the donated material in a dedicated register.7

For CGT developers, the key point is that collection centre compliance is not proven by a generic ‘good manufacturing practice (GMP) compliant’ statement. Developers should be able to audit the underlying procedures.

Regardless of whether the material is donated for autologous or allogeneic purposes, the donor must be tested for a minimal panel of pathogens, with further tests dependent on a risk-based assessment. These tests are normally conducted at the time of donation on a blood sample from the donor.

A positive result for an autologous donor does not preclude the use of the material, however, it may require special handling and isolation to protect against cross-contamination. For allogeneic donors, a healthcare professional reviews their health and medical history to identify and screen out persons whose donation could present a health risk to others.

The minimum tests required include screening for HIV 1 and 2, hepatitis B and C and syphilis.7,8 Depending on potential exposure, testing for malaria and Trypanosoma may also be required. Regulatory expectations may differ between autologous and allogeneic programmes and between competent authorities. Developers should ask whether the testing strategy fits the donor population, collection geography and intended market.

Regardless of whether the donor is a patient or a volunteer, their consent must be gained before any collection procedure can be performed. Such consents are normally regulated by the country’s relevant authority, such as the Center for Biologics Evaluation and Research, US, the Human Tissue Authority, UK, and in Europe under the country competent authority, subject to EU-wide SoHO regulations.9 In addition to national regulations, there are often additional consent forms required by the hospital or collection centre.10

The donor must be fully informed about the procedure, the need for the procedure and any potential side effects or complications that may arise. Furthermore, their consent must be gained in relation to storage, testing and potential use of the donated material – and that may include whether it may be used for R&D, clinical or commercial use.

Although personal information about allogeneic donors is blinded to drug developers who may use the resulting cells to advance their therapeutic, all the donors’ details and relevant health history are recorded by the hospital/collection centre within a dedicated registry. It is important for any CGT developer to select a reputable centre for such collections and to satisfy themselves that suitable consents have been gained. Sometimes this is not straightforward since the cells may have passed through several organisations before reaching them. For example, a vial of iPS cells from a catalogue company, may have been induced by another organisation who sourced the donor cells from yet another organisation. Following that trail back to the original donor consent forms can be extremely challenging, but it’s incumbent upon the innovator to do so.

Poorly structured or missing consents can be an extremely costly mistake, even 70 years later, as per the case of HeLa cells from Henrietta Lacks.11 With whole genome sequencing now commonplace and costing only a few hundred dollars, it’s entirely feasible that for example, a match to an iPSC line could be discovered, either inadvertently or on purpose, by the original donor. If that iPSC line results in a successful therapy, the developer must be confident that original consent can withstand ethical, legal and reputational scrutiny.

From the moment a donor or patient is identified, there must be a clear and complete record linking that individual to the material collected, the samples taken for testing, the consent obtained, the viral testing data generated and the cell or tissue produced for the start of CGT manufacturing. This requires robust donor identification, donation codes, procurement records, test results, consent documentation and suitability assessments, all of which must be protected from unauthorised access, amendment and retained in a retrievable form for at least 30 years.

Chain of custody (COC) and chain of identity (COI) and are fundamental controls that protect product quality, patient safety and regulatory acceptability. Every step in the journey of the donated material – collection, packaging, labelling, transportation, receipt, quarantine, verification and acceptance – must be documented so that it is clear who handled the cells, when and where they were handled, under what conditions and whether all specifications were met. For autologous therapies in particular, any break in this chain could mean that the wrong material is manufactured for, or returned to, the wrong patient. For allogeneic materials, the same principles allow donor eligibility, testing status, storage conditions and provenance to be reconstructed if quality, safety or regulatory issues arise.

At this point in the process, the cells or tissues have safely reached the first point of manufacture, with checks to ensure safety, traceability and compliance. However, far more work is required. To begin with, the material will need to be processed, either to physically dissociate the cells from tissue via dissection and/or enzymatic treatment, or to purify the required cell type. In addition, a significant number of analytical assessments need to be performed including: cell viability and count; sterility; absence of mycoplasma and endotoxins; cell adherence and immunophenotyping – the latter for initial identity and purity. Depending on the application, further assessments including potency and functional assays will be required.

Asking whether cells are ‘GMP compliant’ is not enough. The better question is whether the provider can demonstrate that the specific donor-to-starting-material pathway is suitable for the intended programme.

If a provider cannot answer these questions or provide evidence, it may be safer to qualify another provider before the material becomes embedded in the programme.

Human cellular starting material is not a commodity input. It carries donor-specific variability, ethical obligations, regulatory requirements and long-term commercial risk. Addressing consent, testing, COC and COI early helps avoid late-stage surprises and strengthens manufacturing, regulatory review and patient safety.

The three questions every CGT developer should ask are simple: Can I see the consent basis? Can I see the donor and material testing package? Can I reconstruct COC and COI? If any answer is unclear, the programme may carry more risk than appears.

References:

1. Visit: alliancerm.org/wp-content/uploads/2026/05/Sector- Snapshot-Q4-2025_01.pdf

2. Visit: fda.gov/vaccines-blood-biologics/cellular-genetherapy-products/approved-cellular-and-gene-therapyproducts

3. Visit: bioinformant.com/u-s-fda-approved-cell-and-genetherapies/

4. Visit: ema.europa.eu/en/documents/scientific-guideline/ guideline-human-cell-based-medicinal-products_en.pdf

5. Visit: fda.gov/media/73624/download

6. Visit: fda.gov/media/113760/download

7. Visit: eur-lex.europa.eu/eli/dir/2006/17/oj/eng

8. Visit: ecfr.gov/current/title-21/section-1271.75

9. Visit: health.ec.europa.eu/blood-tissues-cells-and-organs/ soho-regulation_en

10. Visit: ema.europa.eu/en/documents/scientific-guideline/reflection-paper-stem-cell-based-medicinal-products_ en.pdf

11. Visit: fdli.org/2023/08/lacks-v-thermo-fisher-scientific-incan-extraordinary-event-from-more-than-70-years-ago/

Simon Boa is the managing director of Bramble Bio, bringing over 20 years of leadership in the life sciences sector with a particular emphasis on commercialisation, strategic market expansion and innovative business creation. He has a proven track record of delivering above-market growth for global organisations, including Thermo Fisher Scientific, Merck and Becton Dickinson, through a strong focus on client value creation. He has a PhD in epigenetics from the Roslin Institute/Edinburgh University, UK, and an MBA from Warwick University, UK, specialising in M&A and finance.