ICH Q6B Specifications: test procedures and acceptance criteria for biotechnological/biological products – Scientific guideline

ICH Q6B gives general principles for setting specifications for certain biotechnological and biological products, especially proteins and polypeptides, their derivatives, and products that contain them. A specification is a list of tests, references to analytical procedures, and acceptance criteria. Q6B treats specifications as one part of a broader control strategy, not a standalone quality measure.

Q6B is most directly relevant to protein-based biotechnology products. It is not a direct technical guide for many modern gene therapy or nucleic acid products. However, its basic principles on how to think about specifications are still useful, and later guidance may refer back to those principles.

What Q6B applies to

ICH Q6B applies mainly to proteins and polypeptides, their derivatives, and products of which they are components. This includes products made using recombinant or non-recombinant cell culture expression systems. In some cases, it may also be relevant to proteins and polypeptides isolated from tissues or body fluids.

What Q6B does not cover

Q6B does not cover antibiotics, synthetic peptides and polypeptides, heparins, vitamins, cell metabolites, DNA products, allergenic extracts, conventional vaccines, cells, whole blood, or cellular blood components.

Specifications are not full characterization

Q6B distinguishes between full characterization and routine specifications. Development work may use a broad set of analytical studies to understand the product. Only some of those tests become routine specification tests. The final specification should focus on tests that are meaningful for confirming identity, quality, purity, strength, and where relevant, potency.

Specifications must be justified

Acceptance criteria should be based on product knowledge and data. Q6B does not support setting limits only because a process happens to deliver certain results. Specifications should reflect manufacturing consistency, stability, and experience from development and clinical lots.

Categories commonly addressed under Q6B

Physicochemical properties
Q6B expects specifications to consider physicochemical attributes that are important for identity, consistency, and product quality. 

Biological activity
A relevant potency or biological activity measure is an important part of the specification framework for many biotechnology-derived products.

Immunochemical properties
These are considered where relevant to product identity or function, especially for antibody-based products.

Purity and impurities
Q6B expects consideration of both product-related variants and process-related impurities.

Quantity
The amount of active substance should be determined using a suitable and justified analytical approach.

Drug substance and drug product

Q6B applies to both drug substance and drug product specifications. Drug product specifications may include additional tests related to the finished formulation, presentation, and container system. In practice, finished product control may also include pharmacopoeial tests where applicable, such as sterility, endotoxins, particulate matter, or volume-related tests.

Relevance to newer modalities

Q6B predates many current gene therapy and nucleic acid product classes. It should not be treated as a direct technical guide for attributes such as vector genome integrity, poly(A) tail heterogeneity, residual plasmid DNA, or empty and full capsid ratio. Still, the underlying logic for structuring and justifying specifications still applies