The Critical Role of Human Biological Materials in Cell and Gene Therapy (CGT) Manufacturing

Cell therapy has emerged as a transformative modality in modern medicine. Applications such as CAR-T therapies, mesenchymal stromal cell (MSC) products, and hematopoietic stem cell based interventions rely on living human cells to restore cellular function, modulate immune responses, or correct underlying genetic abnormalities.

However, the performance and reproducibility of these advanced therapies depend not only on engineering strategies or bioprocess design, but also on the human-derived biological materials that initiate and support manufacturing. These materials—often overlooked in early program planning—play a decisive role in determining process robustness, safety, and regulatory compliance.

Human-Derived Materials as Determinants of Cell Therapy Performance

Cell therapies can be generated from:

• Autologous cells, isolated directly from the patient
• Allogeneic cells, sourced from qualified healthy donors

In both modalities, the quality, characterization, and consistency of human biological materials directly influence:

• Product safety and purity
• Clinical efficacy
• Manufacturing reproducibility
• Scalability and process transferability
• Readiness for regulatory evaluation

Given the complexity of cell manipulation workflows in CGT manufacturing, controlling also variability at the material level is essential to achieve predictable and reproducible outcomes.

Defining “Human Raw Materials” in CGT Manufacturing

Human biological materials commonly used in cell therapy development include:

• Leukopaks, as starting materials rich in mononuclear cells
• Human serum, used to supplement culture media
• Plasma‑derived proteins, such as human serum albumin (HSA)

These materials impact key bioprocess parameters such as:

• Cell expansion kinetics
• Cell viability and phenotype stability
• Batch‑to‑batch reproducibility

Insufficient donor characterization, high donor‑to‑donor variability, or inadequate traceability can introduce elements of uncertainty that compromise manufacturing reliability and complicate regulatory assessments.

Why Material Quality Is Critical

High quality, well-defined human materials contribute to:

• Improved expansion and viability of T cells and CAR-T products
• Reduced variability in critical process parameters
• Increased lot to lot reproducibility
• Lower risk of clinical or manufacturing deviations

Controlling material variability early in development increases confidence in both clinical outcomes and the long-term performance of the manufacturing platform.

Key Requirements for Human Materials in CGT Manufacturing

To support robust and compliant processes, human-derived materials should meet several scientific and operational criteria:

1. Reliable sourcing and supply continuity
   Stable access to well characterized materials is essential throughout development, validation, and scale up.
2. A robust and diverse donor base
   A controlled and qualified donor pool mitigates supply risk and supports program expansion into late-phase development and commercialization.
3. Format and workflow compatibility
   Offering multiple formats—bottles, bags, fresh, or frozen—supports alignment with different operational models and production schedules.
4. Availability in RUO and GMP grades
   Multiple quality tiers ensure appropriate material selection across discovery, process development, clinical manufacturing, and commercialization. 
5. Consistent, fit for purpose quality attributes
   Standardized specifications and rigorous QC testing underpin reproducible cell performance and reduce process variability.
6. Comprehensive documentation and traceability
   Full traceability—including donor testing, characterization data, and certificate packages—facilitates quality assessments and regulatory submissions.
7. Alignment with regulatory and manufacturing expectations
   Materials must be produced under suitable quality systems and qualified according to their intended role (starting material, ancillary material, excipient).

Meeting these requirements enhances comparability across development stages and supports efficient technology transfer and industrialization.

Regulatory Considerations for Human Biological Materials in CGT

Regulatory expectations differ depending on the classification and intended use of each material.

Starting Materials

Leukopaks, obtained via leukapheresis, represent critical starting materials for many cell and gene therapy products. For clinical use, global regulatory frameworks require:

• Rigorous donor screening
• Defined collection and processing controls
• Full traceability
• Documentation supporting identity and suitability for clinical manufacturing

Appropriate oversight ensures materials meet standards for quality and safety throughout clinical development.

Raw / Ancillary Materials

Ancillary materials contact cells during manufacturing but are not intended to remain in the final product. Examples include:

• Human serum albumin (HSA) — generally considered a very low risk ancillary material when sourced from licensed medicinal products due to its purity and characterization profile.
• Human male AB serum — considered low risk when sourced from well-controlled donor populations under validated quality systems.

Qualification includes assessment of identity, purity, source, safety, and application suitability.

Excipients

Excipients such as therapeutic grade HSA remain in the final formulation and considered a very low risk material when sourced from licensed medicinal products.

Early regulatory alignment reduces program risk, facilitates interactions with health authorities, and supports uninterrupted clinical progression.

Enabling Scalable Manufacturing and Regulatory Readiness

The consistent use of traceable, well-documented human biological materials is integral to building scalable and regulatory ready CGT manufacturing platforms. Materials that meet defined quality expectations:

• Support predictable process performance
• Reduce manufacturing and clinical risk
• Simplify regulatory submissions and agency engagement
• Enable efficient advancement from early phase development to commercial-scale production

Understanding how these materials influence bioprocess performance allows teams to design workflows that are scientifically sound, reproducible, and compatible with long-term scalability.

Explore Our Cell Therapy Solutions

Grifols Bio Supplies offers high-quality biological materials tailored to meet the evolving needs of cell therapy developers—ensuring safety, compliance, and performance from the start.

Contact us to discuss your process requirements and explore our product offerings:

• Contact Form: Send your query through our website at biosuppliesproducts.com/en/request-a-rep
• Email: Reach us directly at biosupplies_contactus@grifols.com.

Grifols: Your ally in cell therapy.

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