ANNUAL PRODUCT REVIEW

Transcription

1 ANNUAL PRODUCT REVIEW Patchara Kootiratrakarn Head Pharmacist Senior Director Quality, Regultory Affair & Public Affair Department Definition Annual Product Review A compilation of identified critical data related to licensed products and intermediates manufactured at local site 1

2 Responsibility QA manager Functional area managers Site Annual Product Review committee QA manager to ensure that, responsible for: A system to compile APR s exists, and is managed and maintained APRs are compiled on an annual basis, in compliance with the requirements of SOP Final approval of each APR Evaluate data/ information comprising the APR, to assess trends, identify adverse trends, and determine the need for changes in specifications or manufacturing and or control process 2

3 QA Manager Co ordinate actions arising from information found in the APR, and follow up to implementation >>Responsibility Functional area manager Providing data on time Analysis of data on time Recommendation for improvement as indicated by the SOP >>Responsibility 3

4 Site APR committee Site APR committee comprised of APR Report Author & Authorizer Managing Director QA Manager QC Manager Production Manager Material Management Manager Head Pharmacist Other concerned departments Site APR committee Responsible for Review, evaluate APR and decide on recommendations Approval of each APR Executing the agreed action plan based upon the APR 4

5 How to proceeds? >> Annual Product Review Flowchart Outline of the APR report (1 of 3) Executive summary Introduction and product overview Manufacturing/ process data Review of raw materials and packaging materials Significant and related deviation Analysis of rejection Product testing and trend analysis Stability study and trend analysis 5

6 Outline of the APR report (2 of 3) Review of reference samples and retention samples Review of related changes Validation activities Technical agreements Customer technical complaint/ Medical complaint Product return Product recall Outline of the APR report (3 of 3) Complaint to supplier Regulatory activities Pharmacovigilance information Review of Corrective and Preventive actions Environment monitoring results Observation from external inspection Conclusion and recommendation 6

7 Executive summary Introduction of report Introduction of product Scope of report- product and reviewing period Summary information of number of batches manufactured/ released/ rejected Review of suggestion from last report Review of any significant deviation that may effected to product occurred during the year Review of any major changes effected to product occurred during the year Review of complaint/ ADR Conclusion 7

8 Introduction and product overview Brief process and/or product description Any relevant information to the product Any significant information of the product Manufacturing/ Process Data a comprehensive description of the process under review number and list of batches manufacture and statement of disposition Number of lot reworked, reprocessed and rejected number and list of bulk batches tested Critical in process control parameters 8

9 Critical in process control parameters Critical in process control parameters Yield analysis Defect from visual inspection Sterile filtration parameters Stirring speed & time in formulation and filling steps Filling volume & product homogeneity Time out of refrigerator Review of raw materials and packaging materials Review of raw materials and packaging materials used for the product, Change in new supplier(s) Number and percentage of materials which was not exactly in their prime conditions but was permitted to use This review should also include the results and information of water for injection, WFI 9

10 Non-conformity total number of NC raised during the reviewing period number of process related NC number of analytical OOS results related to NC list of batches and their respective NC number a check to confirm on recurring NC to demonstrate effective corrective action Analysis of rejection Number of batch manufactured, released and rejected with the percentage Reason of rejection Cause of rejection 10

11 Product testing information Review of release test parameters with graphical representation of the trends observed for each parameter Review of critical in-process controls data Summary statement from evaluation of the trends observed Identification of OOS results, and their impact on the overall trends Trend analysis on release data (cont.) Detail of any major changes in the methodology or specification during the reviewing period, and a summary of any supporting validation work Frequency of retesting due to OOS, including clarification on the reason for retesting Stability indicating test methods and trending Frequency of invalid tests for stability- indicating test methods 11

12 Stability study and trend analysis List of product under real time, accelerated stability studies and results List of on-going stability study lot each year and result Identification of OOS result, and their impact on the overall trend Details of any major changes in the methodology or specifications, and a summary of any supporting validation work Review of reference/retention samples A statement with respect to the overall levels of compliance with requirements for retained sample review, any NC observed, and the results of the subsequent investigations. 12

13 Review of Change Control, CC total number of CC proposals ratified during the reviewing period list of batches and their respective CC numbers changes implemented requiring regulatory notification and/or approval system performance with respect to close out of CC proposals Validation Activities validation status and overview of product/ process, for the reviewing period Qualification status of relevant equipment and utilities including the requalification date Media simulation results related to the product under review summary details of any major validation or revalidation exercises conducted during the reviewing period list of validated procedure and their revalidation dates 13

14 Technical agreements Quality technical agreement with subcontractors Quality technical agreement with suppliers Quality technical agreement with manufacturing and laboratory subcontractors Complaints total number of complaints received during the reviewing period number of complaints which, following investigation, found to be justified underlying technical issues found as a result of complaint investigation, and an indication that how the issue was resolved 14

15 Adverse Drug Reaction Complaints total number of ADR complaint received during the reviewing period number of medical complaints which, following investigation, were found to be justified review of all investigation performed for lots associated with AE using the Manufacturing Investigation (MI) report Product return list of product return conducted during the reviewing period review of all quality-related returns number and percentage of returned product problem identified resulting in the return 15

16 Product recall list of product recall conducted during the reviewing period review of all quality-related returns number and percentage of returned product reason for the recall including the statement, if the reason of recall can be linked to NC, CC, or any other immediately obvious reason Complaint to supplier Number and percentage of complaint sent to each supplier Description of finding complaint Recurrence complaints CAPAs proposed by suppliers 16

17 Regulatory activities Review of critical regulatory actions taken by competent authorities that affect GMP status or product license: such as consent decree, warning letters and license suspension Review of marketing authorization variation/ submission (submitted/ granted/ refused) related to the manufacturing and control as well as the equipment and facilities Review of post marketing commitments Pharmacovigilance activities List of ADR cases registered in this reviewing period Analysis of adverse events reports received and the list of manufacturing investigation performed Review of all investigations performed for lots associated with adverse events 17

18 Review of Corrective and Preventive actions Assessment of effectiveness of actions from previous APR reports and a review of outstanding issues from previous year Review of the adequacy of any other previous product, process or equipment corrective actions Environment monitoring results Review of viable parameters results and trending Review of non viable parameters results and trending e.g. on particle count, differential pressure, humidity, temperature 18

19 Observation from external inspection The findings of any audits conducted by external corporate of regulatory agencies during the reviewing period; with a qualifying statement with respect to implementation. Conclusions and suggestions Product/ process improvements Method improvement (including test method) In process or final product specification review Re validation requirements 19

20 Activity Responsibility Gather raw data and analysis Department manager Edit & authorize APR report QA department Review and comments of the draft report Site APR committee Present to SQC QA and related department Conclude for corrective/ preventive action (CAPA) Quality commitee Final approved Site APR committee Implement CAPA Department manager Archiving QA department