Development and Manufacture of Drug Substances (Chemical and Biotechnological/Biological Entities)
Provides guidance on the application of QbD concepts to the development and manufacture of drug substances, covering selection of starting materials, control of critical quality attributes, and design space for API processes.
What this does not cover
stated in the document's own scope- Covers development and manufacture of the drug substance; development of the finished drug product is ICH Q8.
- Addresses development and CMC content, not the commercial GMP for API manufacture, which is ICH Q7.
- Covers chemical and biotechnological/biological drug substances, but not the viral-safety evaluation of biotech products, which is ICH Q5A.
- Describes the control strategy and starting-material justification, not the lifecycle-change tools for later CMC changes, which are ICH Q12.
Always verify against the current published text before relying on it for a submission or inspection.
Overview
ICH Q11 addresses the development and manufacture of drug substances — the active substance — for both chemical entities and biotechnological/biological entities. It extends the Quality by Design and risk principles of ICH Q8 and Q9 to the API: it explains how to describe the manufacturing process and its controls, how to link material attributes and process parameters to the drug substance’s critical quality attributes, and how to justify the selection of starting materials, which is one of its most consequential topics. It also covers the design space at the drug-substance level and the information that should appear in the drug-substance sections of the marketing application.
Scope & applicability
Drug substance manufacturers for both small molecule APIs and biological/biotechnological entities. Focuses on the chemistry, manufacturing, and controls (CMC) section of regulatory submissions.
Legal basis & how it acquires force
Q11 is an ICH Quality guideline, finalised at Step 4 in May 2012. An ICH guideline is not itself law; regions implement it. The FDA issued Q11 as a guidance for industry, the EMA adopted it as a scientific guideline, and Japan gives it effect through MHLW. It describes the content of the drug-substance sections (3.2.S) of the ICH Common Technical Document used across the regions, so a sponsor meets the regional filing requirement while Q11 supplies the harmonised expectation for what that content should demonstrate.
Document structure
| Part | Covers |
|---|---|
| Manufacturing process development | Applying enhanced (QbD) and traditional approaches to develop the drug-substance process |
| Selection of starting materials | The general principles for choosing and justifying starting materials for chemical and biological entities |
| Control strategy | Linking CQAs, material attributes, and process parameters into a drug-substance control strategy |
| Process validation and design space | Establishing a drug-substance design space and the approach to process validation |
| Submission of information (3.2.S) | What to present in the drug-substance sections of the marketing application |
| Illustrative examples (Annex) | Worked examples of starting-material selection for chemical and biotechnological substances |
Key requirements
- Scientific justification for proposed starting material selection
- Identification of CQAs for the drug substance
- Development studies establishing critical process parameters
- Linkage between development work and commercial manufacturing controls
Revision notes
May 2012. No revisions. Q&A document (2017) clarified starting material requirements.
Where this control fails
live FDA enforcementLive FDA recalls SPEQ maps to this standard’s topics — a SPEQ interpretation, not an FDA classification.
International alignment
Q11 is the drug-substance counterpart to Q8’s drug-product development, applying the same QbD vocabulary — QTPP, CQAs, design space, control strategy — one level upstream. It relies on the risk method of Q9 and the quality system of Q10, connects to the API GMP guide Q7 for commercial manufacture, and its later Q&A addendum clarified starting-material selection. Its content maps to Module 3 of the ICH CTD used by the FDA, EMA, and PMDA.
ICH Q11: frequently asked questions
Quick answers to common questions about ICH Q11.
What does ICH Q11 cover that ICH Q8 does not?
Q11 applies the Quality by Design and control-strategy concepts to the drug substance (the active), including the selection and justification of starting materials, whereas Q8 covers development of the finished drug product. They are companion guidelines at different points in the process.
Why is starting-material selection so central to ICH Q11?
The chosen starting material defines where GMP and full CMC control begin. Q11 sets general principles for justifying that selection for both chemical and biological entities, and a later Q&A addendum expanded on it, because the decision affects the scope of the control strategy.
Is ICH Q11 legally binding?
Not by itself. It is a harmonised ICH guideline adopted regionally — as FDA guidance, an EMA scientific guideline, and through MHLW in Japan. It describes the drug-substance content of the Common Technical Document.
This standard in practice
Recall domain is a SPEQ mapping of this standard’s topics, not an FDA classification.