Standardization of Pharmaceutical Products PDF

Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment...

Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Production of a Biological Reference Standard Manufacturing Quality released bulk or final container is delivered to Standards and Reagents Services Department Concentration, dilution, lyophilization, formulation and filling of the material (e.g. human coagulation factors) 23  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Production of a Biological Reference Standard Manufacturing Reference (control) standard specific Master Batch Record 24  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Production of a Biological Reference Standard Quality Control Test plans containing specifications for the reference (control) standard Lot Homogeneity Solution Stability Accelerated degradation study Potency assignment against actual reference standard 25  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Production of a Biological Reference Standard Quality Release CoA Certificate of Analysis for the standard Release of the Standard as Control Standard by Standards and Reagents Services Department 26  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Production of a Biological Reference Standard Quality Release Potency assignment (calibration) against primary standard (WHO) Product information containing assigned activity of the new reference 27  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Calibration protocol What about accuracy? Accuracy of the reference standard: Primary standard (WHO): The activity is accurate by definition. 28  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Calibration protocol What about accuracy? Secondary standard: Calibrated against a primary standard the accuracy of its activity result is 100% Accuracy of the reference standard can be defined as: Difference of the experimental result, compared to the actually assigned potency 29  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Calibration protocol What about accuracy? Reference standard is used for different test systems: Significantly different calibration results for different test systems: Potency assignment with one „compromise“value – an inaccuracy will be accepted for all test systems If the difference is too high, the potency will be assigned for every single system 30  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Calibration protocol What about accuracy? By potency assignment the accuracy of test systems can be optimized: Test 1: results too low (accuracy of the test system - recovery: 85%) Test 2: results too high (accuracy of the test system - recovery: 115%) 31  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Calibration protocol What about accuracy? By potency assignment the accuracy of test systems can be optimized: Potency assignment with the mean value will optimize the accuracy of both systems 32  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Performance of the calibration Biological test systems: 4 – 6 dilution levels covering the working range Test design following the design of regular inter-laboratory exercises: A E B D C C D B 33 E A  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Performance of the calibration Tests are performed in different inhouse labs, 6 to 12 tests each, performed on a minimum of two days Samples: Primary Standard Old and new inhouse reference standard Inhouse control standard Product samples (different matrices) 34 Different Reagent lots  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Evaluation of calibration results Comparison between groups (Robustness) Results gained with different reagent lots, from different labs, with different equipment are compared by t-Tests or ANOVA Check for significant differences 35  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Assignment of activity (potency) Potency Assignment is performed by calculating the arithmetical mean value of the experimental results for the new reference standard calibrated against the primary standard (WHO) 36  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Assignment of activity (potency) Potency assignment documentation: Potency Lot number of the standard and assigned value Assigment Testsystem(s) and laboratories Information on possible shifts in the product results Date of the calibration (report) Timeline for the change over to the new standard 37  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Potency assignment Assignment of activity (potency) Change over documentation: Date of change over (announcement about 2 weeks before change) Laboratories, Product Release Department are informed. 38  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Establishment and Maintenance of Biological Reference Standard Calibration and potency assignment of a new lot or product or calibration against a new primary standard Calibration Report Potency assignment documentation Recalculation of the activity of stored bulk material (factor old/new assigned potency) and if necessary retesting of stored bulk material with the new reference material 39  Standardization Specifications for standardized pharmaceutical products Test Procedures and Acceptance Criteria for Product Specification Biotechnological/Biological Products (ICH Q6B) Biological Activity (Potency) Calibration and potency assignment of a new lot or product or calibration against a new primary standard Change over documentation Release of the new lot or new standard product with the new assigned activity by Standards and Reagents Services Department 40