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Out of specification shravan

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Out of specification PPT as per practicle approach and reference review with guidelines

Publicada em: Saúde e medicina
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Out of specification shravan

  1. 1. 1 Out of Specification By: Shravan Kumar
  2. 2. 2 Definition If the analytical result(s) of a batch or material is/are falling out side of the established specification ranges, is called / considered as Out of Specification. Or The term OOS test results includes all suspect results that fall outside the predetermined Specification
  3. 3. 3 Out of Specifications There are lot of guidelines are available for defining to handle the OOS products/materials/batches as:  MHRA guideline for OOS  CDER guideline for OOS  PIC/S guideline for OOS
  4. 4. 4 Out of Specifications The OOS may be observed during the analysis of:  Stability study  Finished API  Intermediates  In-process  Raw materials  Packing materials
  5. 5. 5 Out of Specifications OOS found due to the following reasons but not limited to: OOS Laboratory Process related Sample homogeneity
  6. 6. 6 Out of Specifications Laboratory errors: Laboratory errors Method of Analysis Use of Non Calibrated instruments Error in calculation Analyst error Instrument Failure
  7. 7. 7 Out of Specifications Process Related: Process Related Operator Error Equipment Failure Deviation form the validated procedure Quality of Raw material / Intermediate used In-Process Control During Manufacturing
  8. 8. 8 Out of Specifications Homogeneity sample : Sample Homogeneity Sampling error Handlin of samples Pooling of sample
  9. 9. 9 OOS Investigations As per MHRA (EU GMP) Phase – I Investigation (Primary & extended lab investigation) Phase – II Investigation (Manufacturing investigation) Phase – III Investigation (Extended manufacturing, Re-sampling and re-analysis) Procedures of OOS investigations As per CDER (US FDA) Phase – I Investigation (Primary & extended lab investigation) Phase – II Investigation (Manufacturing investigation and re- sampling and re-analysis)
  10. 10. 10 OOS Investigations Phase – I Investigation: Laboratory investigation Laboratory investigation is related to the Quality control department along with rechecking of documents with same analyst and re-testing with different analyst with original sample. Phase – I is sub divided in to two sections as: Phase – Ia (Primary Lab investigation), and Phase -Ib (Extended Lab investigation) As per MHRA (EU GMP)
  11. 11. 11 OOS Investigations Phase – II Investigation: Manufacturing Investigations In manufacturing investigation, production person investigate :  Process parameters  Drying parameters  Input raw materials quality  training of persons  Cleaning of equipment  Environmental information  Contamination & etc…. As per MHRA (EU GMP)
  12. 12. 12 OOS Investigations Phase – III Investigation: Extended Manufacturing Investigations In Phase III investigation, Quality Control / Quality Assurance & Production department investigate the following:  Sampling error by person  Authorized for re sampling (if required)  Re-analysis of re-sampled material with different Analyst  If root cause found, define the CAPA or if not  Diverted the matter to R&D / ADL or PD Lab  Conclusion by all team member (QA, QC, PRD, ADL R&D, PD Lab)  Decide the fate of batch by QA Head As per MHRA (EU GMP)
  13. 13. 13 OOS Investigations Re-testing: The analysis of original sample at the time of phase- I laboratory investigation. Re-sampling: The original batch is sampled by QA second time after QA head authorization for re- analysis. Re-analysis: The analysis of re-sampled material for the verification of results, if manufacturing investigation does not have root cause.
  14. 14. 14 OOS Investigations Phase – I Investigation: Laboratory investigation Laboratory investigation is related to the Quality control department along with rechecking of documents with same analyst and re-testing with different analyst with original sample. Phase – II Investigation: Manufacturing investigation Process related investigation is to be carried out by Production department along with re-sampling and re- analysis. As per CDER (US FDA)
  15. 15. 15 OOS Investigations Phase – I Investigation: Laboratory investigation  Analyst observed the OOS result  Re-calculate the results (if required)  If analytical results remain same  Report the OOS result to QC In-charge  Log the OOS  Start the Primary Laboratory investigation  Review the documents along with solutions as (Potency / STP & Specs / buffer solutions / calibration of instruments / standard solutions / Column efficiency / weights / storage condition of sample and many more)
  16. 16. 16 OOS Investigations Phase – I Investigation: Laboratory investigation  If there is no abnormality observed during the primary lab investigation then  Report same results and considered as valid OOS and report  Quality Head review the primary lab investigation and evaluate for re-testing (if QA Head permits)  Repeat the analysis as thrice with original sample with different analyst  Report the average result of repeat analysis  Report the average result
  17. 17. 17 OOS Investigations Phase – I Investigation: Laboratory investigation  If the result complies  Report as complies and invalidate the OOS  Release the batch  If any of result if not complies (among three)  Report as OOS and continue the OOS  Report to QA head QA head will recommend for the Phase – II investigation (manufacturing investigation)
  18. 18. 18 OOS Investigations Phase – II Investigation: Manufacturing investigation Production persons shall investigate the following:  Input quantity of raw material  Input RM quality  Process parameters details  Critical process parameter details (time / temp)  In-process results  Out put of the material  Re-conciliation of raw materials  Utility pressures  Calibration / Preventive maintenance of equipment  Attached ancillaries status
  19. 19. 19 OOS Investigations Phase – II Investigation: Manufacturing investigation Production persons shall investigate the following:  Cleaning of equipments  Training of personnel  Brain storming with operators  Contamination verifications  Environmental review If there is no assignable cause observed during manufacturing investigations, same is to be reported to Quality Assurance Head.
  20. 20. 20 OOS Investigations Phase – II Investigation: Manufacturing investigation QA, QC and production department will evaluate the investigations and after that:  Sampling procedure review, if suspected  QA head may recommend for re-sampling  QC analyst shall analyze the sample as per STP  Report the result (Pass / Failed)  If Pass  Define the CAPA  Release the Batch  If failed  Reject the batch  Divert the matter to R&D / ADL / PD Lab
  21. 21. 21 OOS Investigations Phase – II Investigation: Manufacturing investigation R&D / ADL / PD Lab shall:  Take the user trial with the material  Investigate the failure based on experiments / experiences  Various types of experiments  To find out the root cause  To identify, is this material can b e reprocessed / reworked  Make a summary report  Defined the corrective actions
  22. 22. 22 OOS Investigations Phase – II Investigation: Manufacturing investigation QA/QC/Production department shall:  QA head shall define the fate of batch for reprocess / rework / destruction  Accept the corrective and preventive actions  Training to all concerned for root cause / corrective action / preventive action  Monitor the activity for corrective actions  Evaluate the results of corrective actions  Implement the preventive actions  Verify the implementation of preventive actions  After satisfactory implementation close the OOS & CAPA
  23. 23. 23 OOS Investigations All these activity for investigation / corrective actions / preventive actions should be recorded and reviewed and archived.
  24. 24. 24 OOS Investigations If OOS batch is to be reprocessed / re-work:  Follow the written approved BMR for re-process / Rework  Sample as per SOP for sampling of material  Analyze the material according to the specification and STP  Evaluate the quality of the batch  Keep this batch for stability (Accelerated / Long term)  Evaluate the stability results of the batch  Communicate the OOS to the customers (as mentioned in to the Quality agreement)
  25. 25. 25 OOS Investigations Impact of OOS on REGULATORY:  Stability study required  OOS should be reported to RA  OOS batch should not be sold to Regulatory market  OOS batch can not be blend with fresh approved batch  OOS batch can not be directly sell to the market
  26. 26. 26 Abbreviations  CDER : Center for drug evaluation and research  OOS : Out of specification  RA : Regulatory affairs  STP : Standard testing procedure  EU-GMP : European good manufacturing practices  PIC/s : Pharmaceutical inspection co-operation scheme
  27. 27. 27 Thank You

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