In the development of biotherapeutics, raw materials are much more than ingredients. They are critical components that can directly influence process robustness, product quality and, ultimately, patient safety.

Yet, unlike drug substances or finished products, raw materials often fall into a regulatory grey area. Many are not manufactured under GMP, suppliers may have limited pharmaceutical documentation, and equivalent grades are not always available. This is particularly true for advanced therapies, cell and gene therapies, and other innovative biologics, where development frequently relies on highly specialized reagents initially intended for research use.

In early-stage biopharmaceutical development, one question comes back time and again from our clients: “Can we use this raw material in GMP manufacturing?”

In reality, things are rarely that simple. The real question is: “Can we scientifically justify that this material is suitable for manufacturing a clinical product?”

Why?

Because international GMP guidelines require manufacturers to ensure that raw materials are appropriate for their intended use. However, they intentionally leave flexibility regarding how this demonstration should be achieved.

This flexibility is essential because every manufacturing process is unique. A raw material that represents a negligible risk in one process may become critical in another depending on its function, its origin, the stage at which it is introduced, or the ability of downstream processing to remove associated risks.

Consequently, qualification cannot rely on a simple checklist or the presence — or absence — of a GMP label. It requires a scientific evaluation considering the specific context of use.

The growing challenge of raw material qualification

Today’s biopharmaceutical products rely on increasingly complex manufacturing processes involving numerous biological and chemical materials.

For each material, several questions must be addressed:

• What is its impact on critical quality attributes?

• Could it introduce impurities, contaminants or adventitious agents?

• How robust is the supplier’s quality system?

• Is there sufficient traceability throughout the supply chain?

• Could changes in manufacturing or sourcing affect product consistency?

• Are appropriate analytical controls available?

• How critical is this material for patient safety?

The problem?

The answers are rarely straightforward. Scientific uncertainty is often unavoidable, especially during early clinical development where knowledge of both the product and the manufacturing process continues to evolve.

Risk assessment: a scientific decision-making framework for CMC success

Rather than searching for impossible certainty, regulatory expectations encourage manufacturers to adopt a science- and risk-based approach.

A structured risk assessment enables teams to:

• Identify potential risks associated with each raw material;

• Evaluate their likelihood and potential impact on product quality and patient safety;

• Prioritize the most critical risks;

• Define proportionate mitigation measures;

• Document and justify decisions in a transparent and scientifically sound manner.

Importantly, risk assessment is not simply a quality exercise performed to satisfy auditors. It is a decision-making tool that supports the entire CMC strategy throughout product development.

As process knowledge increases, the assessment can be refined, allowing qualification strategies to evolve alongside the product lifecycle.

Building a qualification strategy that supports clinical development

An effective qualification strategy combines multiple sources of evidence rather than relying on a single criterion.

Supplier qualification, available quality documentation, certificates of analysis, manufacturing information, change management practices, analytical testing, process knowledge and product-specific considerations all contribute to the overall assessment.

When appropriately documented, this evidence provides the scientific rationale needed to demonstrate that a raw material is suitable for its intended clinical use—even when GMP-grade alternatives are unavailable.

This approach helps developers anticipate regulatory questions, strengthen their CMC documentation and reduce the risk of unexpected issues during clinical development.

How INITS can support biotech companies in this challenge?

At INITS, we support biotech and pharma companies in assessing the suitability of raw materials used in GMP manufacturing for clinical development.

Our approach is based on scientific expertise and risk management. We help our clients to :

• Evaluate the suitability of raw materials within the context of their manufacturing process;

• Perform structured risk assessments tailored to product and process characteristics;

• Identify and prioritize quality and patient safety risks;

• Define pragmatic mitigation plans proportionate to the identified risks;

• Build scientifically justified documentation supporting regulatory expectations.

Our objective is not simply to determine whether a material is acceptable. It is to provide a robust scientific rationale that supports informed CMC decisions and contributes to a successful transition into clinical development.

Because in biotherapies, confidence in the final product begins with confidence in every material used to manufacture it.

If you’re facing raw material qualification challenges, let’s discuss how our risk-based approach can  advance your CMC strategy and accelerate your clinical development.

Reach out to us at hello@inits.fr to explore how INITS can support your next project!