Annual product reviews

review of annual product in pharmaceutical industry

1. Annual product reviews Submitted By, Syed Shakeeb Ahmed 1 st M. Pharm Dept of Quality Assurance JSSCP, Mysuru Submitted To, Dr. Gowrav M.P Lecturer Dept of Pharmaceutics JSSCP, Mysuru 1

2. Annual product review is an evaluation conducted annually to assess the quality standard of each drug product with the view to verify the consistency of existing process and to check the appropriateness of current specifications and to highlight any tends in order to determine the need to change any drug product specifications or the manufacturing processes or control procedures. Annual product review is done for the products which are manufactured in U. S. market. 2 What is APR ?

3. Objectives: To assess drug product performance annually and to determine need for any change in drug product specification and or manufacturing process and control procedures . 3

4. Importance of APR: It verifies the consistency of the existing manufacturing processes. It determines the quality and process defects of the products It determines the defects and possible improvements of the methods and process. It reviews the quality of the raw material and packaging material which is used for the product Mainly it indicates the quality of material . To determine the consistency of the quality of the product the in-process parameters and the finished product results are reviewed. Quantity of the final product is reviewed by trending the yield of every batch The determination of the Corrective and preventive actions and their impact on product quality are also reviewed. 4

5. Basic Contents of Annual Product Quality Review: A review of starting materials including packaging materials used in the product, especially those from new sources. A review of critical in-process controls and finished product results. A review of all batches that failed to meet established specification(s) and their investigation. A review of all significant deviations or nonconformances , their related investigations, and the effectiveness of resultant corrective and preventative actions taken. A review of all changes carried out to the processes or analytical methods. A review of Marketing Authorisation variations submitted/granted/ refused, including those for third country (export only) dossiers. 5

6. A review of the results of the stability monitoring programme and any adverse trends. A review of all quality-related returns, complaints and recalls and the investigations performed at the time. A review of adequacy of any other previous product process or equipment corrective actions. For new marketing authorisations and variations to marketing authorisations , a review of postmarketing commitments. The qualification status of relevant equipment and utilities, e.g. HVAC, water, compressed gases, etc. 6

7. Control sample review of the product. Batches taken for reprocessing/reworking, if any . Different pack size of the product offered in the market . If any experiment is conducted to improve yield or quality of product in consultation with R&D Purified water & environmental monitoring Status of Technical agreement Status of process & Cleaning validation Adverse Drug Events 7

8. Why are APR’s required? GMP Requirements for APRs are found in in 21 CFR 211.180(e) and includes: Written procedure Review of every batch (or representative) to determine the need for changes in specifications or manufacturing or control procedures Review of complaints Review of recalls Review of returned or salvaged products Review of investigations 8

9. Benefits: Assess needed changes in product specifications. Assess needed changes in manufacturing or control procedures . Determine if validation or revalidation is needed. Identify product improvement or cost reduction opportunities. Confirm change control systems. Provide a preparation tool for FDA inspections. Communicate product and process status to management 9

10. ANALYTICAL AND INSPECTION DATA: Finished product & in process analytical data of relevant critical parameters as mentioned below , but not limited to , shall be evaluated for all the batches. Tablets: Water Content / Moisture Content Dissolution/Dissolution Profile Hardness Disintegration Test Impurities/Related Substances Residual Solvent Assay Total Microbial Count. 10

11. capsules: Water Content / Moisture Content Dissolution DT Impurities / Related Substances Assay. 3. Pellets: Water Content / Moisture Content Drug Release in Acid Phase Drug Release in Buffer Phase Assay Impurities/Related Substances Dissolution 11

12. 4. Soft Gel Capsules : Water Content / Moisture Content LOD of shell DT Impurities / Related Substances Assay Total Microbial Count. 5. Powder :- Water Content Assay Impurities/Related Substances. 12

13. 13 6. Gel : pH Density Assay Impurities/Related Substances Viscosity Total Microbial Count. 7. Ointment/Cream : pH Assay Impurities/Related Substances Total Microbial Count.

14. 8. Liquid : pH wt. /ml or Specific Gravity Viscosity Assay Impurities/Related Substances Total Microbial Count . 14

15. 9. Injectables : pH wt./ml or Specific Gravity Viscosity Assay Impurities/Related Substances Particulate matter Colour Sodium Chloride content (if any) Bacterial Antitoxin Test. 15

16. Critical process parameters: Critical process parameters during granulation stage: For tablets 16 Sl no. Parameters 1 Mixing Impeller speed Chopper speed 2 Drying Duration of drying Inlet temp Outlet temp LOD 3 Hardness 4 Thickness 5 Disintegration time 6 Individual weight and average weight

17. Critical Process parameters during Coating Stage: Inlet temperature Outlet temperature Atomisation pressure Spray gun distance Pan RPM Weight buildup per tablet 17

18. 18 Review of Yield For each batch compile the percentage yield obtained at all critical stages and total percentage yield of the batch. Statistical graphs for Analytical data, Inspection data and Yield shall be prepared. Market complaints & related investigations In this section if any market complaints are came during this review period and related investigation to be mentioned All rejected batches / product failures & related investigations. In this section if any market complaints are came during this review period and related investigation to be mentioned

19. 19 All deviations, incidents, OOS and change control Summary of all deviations, Incidents and OOS during the time frame of the APR Summary of all change controls during the time frame of the APR. Results of the stability monitoring program. The APR also covers all stability parameters of all batches on stability, which represents the manufactured batches for distribution . These data is trended , reviewed and compared from previous years APRs to assure that no negative trend has developed and the expiry period is still appropriate Product recall and related information Any Batches withdrawn or recalled or regulatory alerts made for the marketed product during the time frame of the APR are listed along with the reason for the withdrawal or recall.

20. Summary of Returned goods and salvaged goods, if any. Summary of Control sample of the product . Summary of different pack size of the product. If any experiment is conducted to improve yield or quality of product in consultation with R&D Purified water & environmental monitoring Status of Technical agreement Status of process & Cleaning validation Adverse Drug Events 20

21. FDA Inspections: Expectations for Annual Product Reviews Develop a comprehensive SOP – the SOP should be comprehensive and specific. Follow the SOP – failure to follow the SOP will almost always result in concerns from investigators . Include all required and “expected” elements in the APR . Identify and implement corrective or improvement actions – the routine assignment of corrective or improvement actions signals that you take the process seriously, and as originally intended by the authors of the GMP regulations. 21

22. Follow-up on actions – a system to assure that actions occurred and were effective is essential . Assure that the quality unit reviews and approves the APR – most firms require QA approval on APRs . Involve management in the process – the higher the level of involvement and interest in the process, the more APRs can be used as a tool for process control and product improvement. 22

23. 23 Thank you