Spring Intro 2023

03/03/2023

• Control of drug product (Specifications/Justification, Analytical Procedures/Validation, Batch Analyses) Common Deficiencies – 3.2.P.5 • Specification for impurities not in line with ICH Q3B  Limits are wider  No limits included for unknown/known impurities • Absence of tests not justified • Specification not upgraded in compliance with current Ph. Eur. requirements regarding pharmaceutical forms, e.g.  parenteral solutions - implement a test and acceptance criteria for sub-visible particles (Ph. Eur. 2.9.19)  Tablets – uniformity of dosage content (Ph. Eur. Tablets) etc. • Widening of the release and end of shelf-life specification not supported by batch/stability data – tightening achievable

03/03/2023

41

41

Common Deficiencies – 3.2.P.5 (ctd.) • Control of drug product (Specifications/Justification, Analytical Procedures/Validation, Batch Analyses) • The water level proposed for the tablets at the end of shelf life is at X% – no evidence provided that this has no effect on the microbiological quality of the finished product. • Identification by a single chromatographic retention time proposed. It is not regarded as being specific (In line with ICH guideline a second ID test should be included). • Validation not submitted in accordance with Analytical Validation/Methodology (ICH Q2A/B) • Range proposed, but no validation data for the range is presented in the robustness section of the method validation, e.g. • For HPLC method a flow rate range of 1-2ml/min is specified, however no validation data for this range is presented in the robustness section of the HPLC method validation. Unless further justified the target flow rate should be specified and any range should be appropriately validated. • No quantitative values presented for related substances, bacterial endotoxins etc., instead “complies” is stated

03/03/2023

42

42

21