Guideline on the requirements for the chemical and ...

1 30 Churchill Place Canary Wharf London E14 5EU United Kingdom An agency of the european union Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website european Medicines Agency, 2017. Reproduction is authorised provided the source is acknowledged. 20 September 2017 EMA/CHMP/QWP/545525/2017 Committee for Medicinal Products for Human Use (CHMP) Guideline on the requirements for the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials Draft agreed by Quality Working Party December 2015 Adopted by CHMP for release for consultation December 2015 Consultation of european Commission ad hoc group on clinical trials February 2016 Start of public consultation 12 April 2016 End of consultation (deadline for comments)

2 12 October 2016 Agreed by Quality Working Party May 2017 Consultation of european Commission ad hoc group on clinical trials June 2017 Adopted by CHMP 14 September 2017 Date for coming into effect 6 months after publication This Guideline replaces the Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials (CHMP/QWP/185401/2004 final) Keywords Guideline , Clinical Trial, Quality Guideline on the requirements for the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials EMA/CHMP/QWP/545525/2017 Page 2/39 Guideline on the requirements for the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials Table of contents 1.

3 Introduction .. 7 Objectives of the Guideline .. 7 Scope of the Guideline .. 7 General points concerning all IMPs .. 7 Submission of data .. 8 General considerations .. 8 2. Information on the chemical and pharmaceutical quality concerning investigational medicinal products in clinical trials .. 8 Drug substance .. 8 General information .. 9 Nomenclature .. 9 Structure .. 9 General 9 Manufacture .. 10 Manufacturer(s) .. 10 Description of manufacturing process and process controls .. 10 Control of materials .. 10 Control of critical steps and intermediates .. 11 Process validation and/or evaluation .. 11 Manufacturing process development .. 11 Characterisation .. 11 Elucidation of structure and other characteristics.

4 11 Impurities .. 11 Control of the Drug Substance .. 12 Specification(s) .. 12 Additional information for phase II and phase III clinical trials .. 12 Analytical 12 Validation of analytical procedures .. 13 Information for phase I clinical trials .. 13 Information for phase II and III clinical trials .. 13 Batch analyses .. 13 Justification of specification(s) .. 13 Reference standards or materials .. 13 Container closure system .. 14 Stability .. 14 Guideline on the requirements for the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials EMA/CHMP/QWP/545525/2017 Page 3/39 Investigational medicinal product under test .. 14 Description and composition of the investigational medicinal product.

5 14 Pharmaceutical development .. 15 Additional information for phase II and phase III clinical trials .. 15 Manufacturing process development .. 15 Manufacture .. 15 Manufacturer(s) .. 15 Batch formula .. 16 Description of manufacturing process and process controls .. 16 Controls of critical steps and intermediates .. 16 Additional information for phase III clinical 16 Process validation and/or evaluation .. 16 Control of excipients .. 17 Specifications .. 17 Analytical procedures .. 17 Validation of the analytical procedures .. 17 Justification of specifications .. 17 Excipients of animal or human origin .. 17 Novel excipients .. 17 Control of the investigational medicinal product .. 17 Specifications.

6 17 Additional information for phase II and phase III clinical trials .. 18 Analytical procedures .. 18 Validation of analytical procedures .. 18 Additional information for phase II and III clinical trials .. 18 Batch analyses .. 18 Characterisation of impurities .. 19 Justification of specification(s) .. 19 Additional information for phase II and phase III clinical trials .. 19 Reference standards or materials .. 19 Container closure system .. 19 Stability .. 19 Information for phase I clinical trials .. 20 Additional information for phase II and phase III clinical trials .. 21 3. Information on the chemical and pharmaceutical quality of authorised, non-modified test and comparator products in clinical trials .. 21 4.

7 Information on the chemical and pharmaceutical quality of modified authorised comparator products in clinical trials .. 21 Modified comparator product .. 21 Description and composition .. 21 Pharmaceutical development .. 22 Manufacture .. 22 Manufacturer(s) related to the modification .. 22 Batch formula .. 22 Guideline on the requirements for the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials EMA/CHMP/QWP/545525/2017 Page 4/39 Description of manufacturing process and process controls .. 22 Control of excipients .. 22 Specifications .. 22 Analytical procedures .. 23 Validation of analytical procedures .. 23 Justification of specifications.

8 23 Excipients of animal or human origin .. 23 Control of the modified comparator product .. 23 Specifications .. 23 Analytical procedures .. 23 Validation of analytical procedures .. 23 Batch analyses .. 24 Characterisation of impurities .. 24 Justification of specification(s) .. 24 Container closure system .. 24 Stability .. 24 5. Information on the chemical and pharmaceutical quality of investigational medicinal products containing existing active substances used in bio-equivalence studies, generics ( chemical substances) .. 25 Drug substance .. 25 General information .. 25 Nomenclature .. 25 Structure .. 25 General Properties .. 26 Manufacture .. 26 Manufacturer(s) .. 26 Description of manufacturing process and process controls.

9 26 Characterisation .. 26 Impurities .. 26 Control of the drug substance .. 26 Specifications .. 26 Analytical 27 Validation of analytical procedures .. 27 Batch analyses .. 27 Justification of specifications .. 27 Reference Standards or materials .. 27 Container closure system .. 27 Stability .. 28 Investigational medicinal product under test .. 28 Description and composition .. 28 Pharmaceutical development .. 28 Manufacture .. 28 Manufacturer(s) .. 28 Batch formula .. 28 Guideline on the requirements for the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials EMA/CHMP/QWP/545525/2017 Page 5/39 Description of manufacturing process and process controls.

10 28 Control of critical steps and intermediates .. 29 Process validation and/or evaluation .. 29 Control of excipients .. 29 Specifications .. 29 Analytical procedures .. 29 Validation of analytical procedures .. 29 Justification of specifications .. 29 Excipients of animal or human origin .. 29 Novel excipients .. 29 Control of the investigational medicinal product .. 30 Specifications .. 30 Analytical procedures .. 30 Validation of analytical procedures .. 30 Batch analyses .. 30 Characterisation of impurities .. 30 Justification of specification(s) .. 30 Reference standards or materials .. 31 Container closure system .. 31 Stability .. 31 6. Information on the chemical and pharmaceutical quality concerning placebo products in clinical trials.