PROCESS VALIDATION - ACTUAL REGULATION, PERFORMING AND INSPECTION

1. PROCESS VALIDATION - ACTUAL REGULATION, PERFORMING AND INSPECTION

2. Eurasian Economic Commission​​ decision № 77 new revision • Annex 15 harmonization with EMA regulation • Main idea: inclusion of the principles ofICH (Q8, Q9, Q10) in Annex 15. • ICH Q8 Pharmaceutical Development • ICH Q10 Pharmaceutical Quality System • ICH Q8 Pharmaceutical Development • ICH Q9 Quality Risk Management Knowledge management Design space Risk-based approaches

3. Eurasian Economic Commission​​ decision № 77 new revision • Key changes in Annex 15: • Documentation • Qualification • Process and Cleaning Validation • New sections: • Ongoing Process Verification during Lifecycle • Verification of Transportation • Validation of Packaging • Qualification of Utilities • Validation of Test Methods Planning and documentation for Qualification and Validation Added information on the qualification stages Major revision of the Process and Cleaning Validation sections

4. Manufacturing process validation Cleaning Validation Harmonization withEurasian Economic Commission​​ decision № 19 Toxicological evaluation Prospective validation Traditional approach Appropriate number of times based on a risk assessment Continuous Process Verification Hybrid Approach Concurrent validation Where there is strong risk – benefit to the patient Retrospective validation? Not acceptable!

5. Deficiencies • There are no manufacturing process validation or cleaning validation. • There are no justification for concurrent process validation approach. • There are no justification for CPP’s. • The evaluation of the risk to quality is not based on scientific knowledge, experience with the process. • Cleaning validation was performed with out toxicological evaluation.

6. Deficiencies • Cleaning validation was performed with out microbiological or bacterial endotoxins consideration. • There are no drug product testing results in manufacturing process validation report. • Less than three consecutive batches were manufactured during manufacturing process validation. • There are no results for few acceptance criteria mentioned in validation protocol.

7. Thank you! QUESTIONS PLEASE!