Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products (Chemical Substances)
ICH Q6A establishes a harmonised approach to setting specifications — the tests, analytical procedures, and acceptance criteria — for new chemical drug substances and their finished products. It distinguishes universal tests that apply to essentially every product (description, identification, assay, and impurities) from specific tests tied to the dosage form or route. A series of decision trees guides choices on dissolution, particle size, polymorphism, and microbial limits, and the guideline addresses concepts such as periodic or skip testing, parametric release, and the role of the specification within the overall control strategy.
What this does not cover
stated in the document's own scope- It does not cover biotechnological or biological products, whose specifications are addressed by ICH Q6B.
- It does not provide the analytical validation methodology, which is the subject of ICH Q2(R2).
- It does not derive the residual-solvent or elemental-impurity limits themselves, which come from ICH Q3C and ICH Q3D with USP <232>/<233>.
- It does not set the stability data requirements that underpin shelf-life acceptance criteria; those are in ICH Q1A(R2).
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Overview
ICH Q6A is the ICH guideline on specifications for new chemical drug substances and products. A specification is the list of tests, references to analytical procedures, and numerical acceptance criteria that a material must meet to be judged acceptable for its intended use. Q6A frames how those specifications are chosen and justified: which tests are universal, which are specific to the product, and how development data and decision trees drive the selection. It also introduces flexibility such as periodic testing and parametric release, and positions the specification as one element of a wider quality control strategy.
Legal basis & how it acquires force
Q6A is a harmonised ICH guideline that becomes enforceable through regional adoption. The FDA issues it as guidance supporting the specification and analytical requirements underlying a new-drug application and 21 CFR 211 CGMP; the EMA adopts it as a CHMP scientific guideline; PMDA implements it by MHLW notification. Acceptance criteria set under Q6A operate alongside, and generally must be no less stringent than, any applicable compendial monograph in the USP or Ph. Eur., which carry their own legal standing.
Document structure
| Part | Covers |
|---|---|
| Scope and definitions | Application to new chemical substances and products, and the meaning of specification, acceptance criterion, and test procedure. |
| General concepts | Periodic or skip testing, release versus shelf-life criteria, in-process testing, parametric release, and reference standards. |
| Universal tests and criteria | Description, identification, assay, and impurities as tests applying to all new drug substances and products. |
| Specific tests and criteria | Dosage-form and route-specific tests such as dissolution, particle size, polymorphism, water content, and microbial limits. |
| Decision trees | Structured logic for deciding when specific tests are warranted and how to set the associated criteria. |
Key requirements
- Apply the universal tests — description, identification, assay, and impurities — to every new drug substance and product.
- Select specific tests appropriate to the dosage form and route, such as dissolution, disintegration, hardness, uniformity of dosage units, water content, and microbial limits.
- Justify each acceptance criterion against safety, efficacy, batch data, and the stability profile rather than analytical capability alone.
- Use the guideline's decision trees to determine when tests such as dissolution, particle size, polymorphism, and microbial limits are needed.
- Ensure identification tests are specific, and where a single test is not, combine procedures to confirm identity unambiguously.
- Define impurity acceptance criteria consistent with the levels qualified under the ICH Q3 impurity guidelines.
- Where justified, apply concepts such as periodic or skip testing and parametric release, supported by adequate development and validation data.
Implementation tips
- Set acceptance criteria from real batch and stability data, and keep release limits tighter than shelf-life limits so a batch stays in specification through expiry.
- Work the polymorphism and particle-size decision trees during development, and record the outcome even when the conclusion is that no routine test is needed.
- Link each specification attribute to the control strategy so it is clear which risk each test is managing.
- Harmonise the specification with the compendial monograph where one exists, and document any deliberate tightening beyond the pharmacopoeia.
International alignment
Q6A governs chemical (small-molecule) products; its counterpart for biotechnological and biological products is ICH Q6B. It works with the ICH Q3 impurity guidelines, ICH Q2(R2) for analytical validation, and ICH Q1 for the stability data behind shelf-life criteria. It is adopted by FDA, EMA, PMDA, and other ICH members, and its specifications interlock with the compendial standards of USP and Ph. Eur. Newer analytical-lifecycle thinking in ICH Q14 and USP <1220> extends how the procedures behind these specifications are developed and maintained.
ICH Q6A: frequently asked questions
Quick answers to common questions about ICH Q6A.
What are the universal tests in ICH Q6A?
Description, identification, assay, and impurities. These four are expected on essentially every new chemical drug substance and product, with specific tests added according to the dosage form and route of administration.
Does ICH Q6A apply to biologics?
No. Q6A covers new chemical substances and products; the corresponding specifications guideline for biotechnological and biological products is ICH Q6B.
What are the Q6A decision trees for?
They provide structured logic for deciding whether specific tests such as dissolution, particle size, polymorphism, and microbial limits are needed for a given product, and how to establish the associated acceptance criteria.
What is parametric release under Q6A?
It is the release of a batch based on validated in-process and process data — for example sterilisation parameters — in place of a specific finished-product test, where development and validation justify that the attribute is reliably controlled.