Pharmacy Courses

Top 10 Deficiencies in New Applications for CEP for Chemical Purity

From this article you can learn how to avoid top 10 deficiencies in new application for CEP for chemical purity to ensure a successful approval process.

1) Ensure consistency & accuracy in synthetic substances with a detailed flow diagram & comprehensive presentation of all starting materials & intermediates. Reviewers will check for consistency in S.2.2, S.2.3 & S.2.4. [Follow ICH Q7 guidelines].

2) and 4) Appropriate acceptance criteria for impurities in starting materials and isolated intermediates, and how they should be justified based on fate and the carryover. Reviewers expect identification and specifying major & recurrent impurities & addressing discrepancies in mass balance for the quality of the final substance.

3) Specific requirements for CEP applicants regarding potential mutagenic impurities in the manufacturing process. Follow the principles of ICH M7 & propose a suitable control strategy to ensure the safety of substance. Find out how to determine the Threshold of Toxicological Concern and justify your chosen control option with appropriate studies & data. 

5) Ensure quality &safety by providing proper specifications for raw materials used in manufacturing final substances. EDQM guidelines must be met for materials of fish origin or peptones. Don't overlook the impact of late-stage materials on impurity profiles. Find about acceptable acceptance criteria from EDQM PA/PH/CEP (24) 10.

6) EU guidelines for reprocessing and recovery of active substances in CEP applications. Provide a detailed description and define triggers for reprocessing & properly identify points of recovery and reintroduction in the manufacturing process.

7) Safety of new CEP applications with a comprehensive risk assessment for nitrosamine presence. Follow ICH Q9 and ICH M7 guidelines as well as the EMA Q&A document and its Appendix 1. Address risks from manufacturing process, materials, and degradation. Stay informed on nitrosamine formation & carryover. 

8) Importance of discussing related substances in Ph. Eur. monographs & the need to address all impurities, including those not listed in the transparency list. Discover how the LOD/LOQ values can support statements such as 'not detected' or 'less than LOQ' in controlling impurities. 

9) Residual solvents in pharmaceutical manufacturing & the importance of providing LOD/LOQ values for 'not detected' or 'less than LOQ' statements. Understand the origin of impurities and how to clarify common solvents. CEP applicants must address Class 1 solvents as potential contaminants and adhere to ICH Q3c Annex 1 requirements.

10) Selection of appropriate starting materials for pharmaceutical production, as outlined in ICH Q11 and its associated Q&A document. Understand the guidelines and reasons for selecting acceptable starting materials, explained in detail in the dossier's Section S.2.3. Identification of structural components as reagents is not acceptable - follow ICH Q11 and identify them as starting materials.

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Resource Person: Bharathi Kodali

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