Pharmaceutical GuidelinesQuality · Careers · Tools
SearchQMS formsResume builderFresher jobs

ICH Q6A Specifications for New Drug Substances and Products

Last reviewed 16 Oct 2026 · 7 min read

Contents
  1. Purpose and scope
  2. How to develop a specification
  3. Tests generally considered
  4. Additional drug-substance tests
  5. Distinguish substance impurities from product degradants
  6. Records and retention
  7. Frequently asked questions
  8. Does ICH Q6A prescribe one acceptance limit for each test?
  9. Must every test be performed on every batch?
  10. Does this guideline cover biologic products?
  11. Which impurity guideline should I consult?
  12. Related reading
  13. References

In short: ICH Q6A explains how applicants select and justify test procedures and acceptance criteria for new chemically synthesised drug substances and products. It describes generally applicable tests and additional tests that may be appropriate for a particular material or dosage form; it does not supply one universal specification for every product.

Purpose and scope

A specification is the controlled set of tests, analytical procedures, and acceptance criteria used to judge whether a drug substance or product is suitable for its intended use. ICH Q6A addresses registration specifications for new chemically synthesised drug substances and products. It is guidance for specification design, not a ready-made set of limits to copy into every product file.

As of 16 October 2026, ICH lists Q6A (Step 4, 6 October 1999) as the current final guideline. The ICH 2026 work plan lists the Q6(R1) revision project as expected to reach Step 2 in November 2026. That is a planned milestone, not an effective revised guideline; check the ICH site for later drafts and adoption updates before relying on this summary.

How to develop a specification

The applicant proposes the tests, methods, and criteria. Each item should have a scientific rationale. ICH Q6A identifies relevant evidence such as development and manufacturing data, pharmacopoeial standards, results from batches used in toxicology or clinical studies, process validation, and stability data. Consider expected analytical and manufacturing variability. If several sites will make the material, confirm that the proposed criteria can be met across those sites.

Do not set criteria simply to enclose the results from a small set of early batches. Use the available development, scale-up, validation, and stability evidence to support a range that controls meaningful quality attributes. If a test is omitted, the rationale should be supported by development data and, where appropriate, process-validation evidence.

A specification can identify release tests, in-process tests, and justified periodic or skip tests. It should state which tests are performed for each batch and which are performed on another justified schedule. Material must still meet the listed acceptance criteria when a periodic test is performed. Changes after a marketing application is approved may require regulatory action; the route depends on the region and the approved dossier.

Tests generally considered

ICH Q6A lists description, identification, assay, and impurity testing as generally applicable categories for new drug substances and new drug products. The specific method and criterion depend on the material, dosage form, analytical capability, and development evidence.

Test categoryWhat the specification should establish
DescriptionA concise description of the material or dosage form and acceptable appearance. A change during storage or manufacture should be assessed; use a quantitative colour test when justified.
IdentificationA method that can distinguish the intended substance from likely related compounds. A single chromatographic retention time by itself may not provide enough specificity; orthogonal methods or a combined technique may be justified.
AssayA suitable, stability-indicating measure of content or strength. A method may also quantify impurities if it is appropriate for both purposes. A non-specific assay needs supporting procedures that provide overall specificity.
ImpuritiesControls for relevant organic, inorganic, and degradation-related impurities, with the applicable impurity guidance used for the substance or product. Residual solvents are addressed separately under ICH Q3C.

These categories do not define universal numerical acceptance limits. Justify each limit for the specific product and use the current applicable regional requirements and guidance.

Additional drug-substance tests

Select additional tests when the material’s physical or chemical properties can affect quality, performance, or stability. Depending on the case, the specification may include:

  • Physicochemical properties, such as solution pH, melting range, or refractive index, when these attributes are useful for control.
  • Particle-size distribution when particle size can affect dissolution, bioavailability, or stability for the intended product.
  • Solid-state form when polymorphs, hydrates, solvates, or amorphous material differ in a way that affects product performance, bioavailability, or stability. A surrogate product-performance test may be more suitable than a direct polymorph limit in some cases.
  • Chiral identity, assay, or impurity controls for optically active substances, selected according to the substance and the risk of stereochemical change or substitution.
  • Water content when the substance is hygroscopic, moisture-sensitive, or a defined hydrate. A water-specific method may be preferable where loss on drying would not distinguish water from other volatile material.
  • Inorganic impurities based on knowledge of the process, including catalysts where relevant. Choose a suitable method and criteria for the impurity being controlled.
  • Microbiological limits or other microbiological tests when warranted by the substance, process, and intended use. The type of test and criteria should be justified; they are not the same for every drug substance.

For a predominantly single-enantiomer drug substance, ICH Q6A treats the opposite enantiomer under stereochemistry-specific principles because general impurity thresholds may be difficult to quantify at those levels. Consider the appropriate control in both the substance and resulting product rather than applying a generic threshold without analysis.

Distinguish substance impurities from product degradants

Use the guidance that matches the impurity source. ICH Q3A(R2), Impurities in New Drug Substances (2006) addresses impurities in new chemically synthesised drug substances. ICH Q3B(R2), Impurities in New Drug Products (2006) focuses on degradation products in the product, including products formed through interaction with excipients or the immediate container-closure system. A process impurity controlled in the drug substance is not automatically a product degradation impurity; assess whether it can also arise or increase during product manufacture or storage.

ICH Q3C(R9), Impurities: Guideline for Residual Solvents (2024) covers residual solvents in substances, excipients, and products. The current guideline directs testing when manufacturing or purification processes are known to result in solvent presence, and recognises that solvent controls may be supported by suitable calculations or product testing. ICH’s 2026 work plan lists a further Q3C(R10) revision with a Step 4 milestone anticipated for December 2026, so verify the current revision before using solvent-specific limits.

Records and retention

Keep the approved specification, supporting rationale, method references, batch and stability data, reviews, and change history in controlled records. For batch-associated records, retain them at least 1 year after expiry of the respective product batch. EU GMP Part I Chapter 4 §4.11 (Revision 1, 2011) requires batch documentation for 1 year after expiry or 5 years after Qualified Person certification, whichever is longer. 21 CFR 211.180(a), eCFR current as of 14 October 2026, requires covered batch-associated records to be retained at least 1 year after expiry. Apply any longer period required by local law or the marketing authorisation.

Frequently asked questions

Does ICH Q6A prescribe one acceptance limit for each test?

No. It describes test categories and principles for setting criteria. Justify each product’s limits with appropriate development, manufacturing, analytical, and stability evidence, and consult the current impurity-specific guidance where applicable.

Must every test be performed on every batch?

Not always. A specification may include periodic or skip tests if the routine testing schedule is stated and justified. The material must meet the criterion when that test is performed.

Does this guideline cover biologic products?

No. Q6A concerns chemically synthesised substances and products. Check the applicable modality-specific guidance and regional requirements for biologics or other excluded product types.

Which impurity guideline should I consult?

Use Q3A for new drug-substance impurities, Q3B for new drug-product degradation products, and Q3C for residual solvents. The impurity’s origin and where it is controlled determine which guidance is relevant.

See also: OOS investigation: Phase I laboratory assessment, OOS investigation: Phase II and III, and specification and packaging-material documentation practices.

References

  1. International Council for Harmonisation. Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances, ICH Q6A, current Step 4 version (6 October 1999). Official guideline PDF.
  2. International Council for Harmonisation. Impurities in New Drug Substances, ICH Q3A(R2), current Step 4 version (25 October 2006). Official guideline PDF.
  3. International Council for Harmonisation. Impurities in New Drug Products, ICH Q3B(R2), current Step 4 version (2 June 2006). Official guideline PDF.
  4. International Council for Harmonisation. Impurities: Guideline for Residual Solvents, ICH Q3C(R9), current Step 4 version (24 January 2024). Official guideline PDF.
  5. International Council for Harmonisation. ICH Association Work Plan 2026, approved November 2025, Q6(R1) and Q3C(R10) anticipated milestones. Official work plan PDF.
  6. Electronic Code of Federal Regulations. 21 CFR 211.180(a), General requirements, Title 21 current as of 14 October 2026. Current section.
  7. European Commission. EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice, Part I, Chapter 4, Documentation, Revision 1 (effective 30 June 2011), §4.11. Official chapter PDF.

Related articles