QUALITY SYSTEMS

Quality Management Systems
MQA 102T
Pharmaceutical quality assurance (PQA)
M.Pharm 1st year
Annamalai University

1. QUALITY SYSTEMS Presented by : M.Suruthi M.Pharmacy 1 st year Pharmaceutical quality assurance Annamalai university Submitted to : Dr.K.Devi,M.Pharm.,Ph.D Assistant professor Department of pharmacy Annamalai university 1

2. CHANGE MANAGEMENT Definition It is defined as the methods and manners in which a company describes and implements change within both its internal and external processes. 2

3. Process involved in change management 3

4. BENEFITS Improved communication Increased productivity Reduced stress Improved decision making It can also help improve employee confidence and create a more positive environment 4

5. CHANGE CONTROL Definition : It is a set of processes and controls that mitigate risk of impacts to projects due to variation. Change control is a specific element of the overall change management procedure ; while change management refer to the complete span of a particular change procedure. 5

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7. OUT OF SPECIFICATION (OOS) Definition : If the analytical results of a batch or material is / are failing 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. 7

8. There are lot of guidelines are available for defining to handle the oos products/materials/batches etc. MHRA (medicine and health care products regulatory agency) guideline for oos CDER (center for drug evaluation and research) guideline for oos 8

9. The oos may be observed during the analysis of : Stability study Finished API Intermediates In – process Raw materials Packing materials 9

10. OOS found due to the following reasons but not limited to : 10

11. Laboratory errors Method of analysis Use of non calibrated instruments Error in calculation Analyst error Instrument failure 11

12. Process related Operator error Equipment failure Deviation from the validated procedure Quality of raw material or intermediate used. In-process control during manufacturing. Homogeneity sample Sampling error . Handling of sample. 12

13. Procedure of oos investigation As per MHRA (EU GMP) As per CDER (US FDA) Phase -1 investigation (primary & extended lab investigation) Phase -1 investigation (primary & extended lab investigation) Phase -2 investigation (manufacturing investigation) Phase-2 investigation (manufacturing investigation and re-sampling and re-analysis) Phase -3 investigation (extended manufacturing ,re-sampling and re-analysis) 13

14. Phase-1 investigation laboratory investigation Laboratory investigation is related to QC(quality control) department along with re-checking of documents with same analyst and re-testing with different analyst with original sample. 14

15. Phase-2 investigation Manufacturing investigations In manufacturing investigation , production person investigate : 15

16. Phase-3 investigation: Extended manufacturing investigations In phase-3 investigation, QC or QA & production department investigation the following: 16

17. As per CDER (US FDA) Phase-1 Investigation: Laboratory investigation laboratory investigation is related to the QC department along with rechecking of documents with same analyst and re-testing with different analyst with original sample. Phase-2 Investigation: Manufacturing investigation process related investigation is to be carried out by production department along with re-sampling and re- analysis. 17

18. Phase 1 investigation: Laboratory investigation 18

19. 19 To be continued

20. 20 To be continued

21. Phase -2 Investigation : Manufacturing investigation Production person shall investigate the following : Input quantity of raw material Process parameters details Critical process parameter details (time\ temperature) In-process details Output of the material Utility pressure 21

22. Calibration \ preventive maintenance of equipments Cleaning of equipments Training of personnel Brain storming with operators Contamination verifications Environmental reviews If there is no assignable cause observed during manufacturing investigations, same is to be reported to QA head. 22 To be continued

23. 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 ( software test plan ) Report the result pass or fail If pass, # Define CAPA # Release the batch If failed, # Reject the batch # Divert the matter to R&D,PD(process development) lab 23

24. R&D\Process Development lab shall : Take the user trail with the material Investigate the failure based on experiments\experience. To find out the root cause To identify ,is this material can be reprocessed \ reworked Make a summary report Defined the corrective actions 24

25. QA & QC \ Production department shall QA head shall define the fate of batch for reprocess \ rework \ destruction Accept the CAPA Training to all concerned for root cause \ CAPA Monitor the activity and Evaluate the results of corrective actions Implement and Verify the implementation of preventive actions After satisfactory implementation close the OOS & CAPA All these activity for investigation\ prevention actions should be recorded , reviewed and archived. 25

26. If OOS batch is to be responded / reworked Follow the written approval BMR(batch manufacturing record) for reprocess/rework Sample as per SOP for sampling of material Analyze the material according to the specification and STP(standard testing procedure) Evaluate the quality of the batch Keep this batch for stability Evaluate the stability results of the batch Communicate the OOS to the customers 26

27. Impact of OOS on regulatory OOS should be reported to RA ( regulatory affairs) OOS batch should not be sold to regulatory market OOA batch can not be blend with fresh approved batch OOS batch can not be directly sell to the market 27

28. Out of trend(OOT) Definition: Out of trend is defined as a result of a sequence of the analytical results which conform to the specifications but not in the expected trend with respect to the initial or expected result. The main purpose of OOT is to lay down a procedure for managing out-of-trend results in active raw material, finished product , stability study, environmental monitoring & water trend in pharmaceutical industries. 28

29. During investigation if the cause of the OOT results is indentified as a laboratory error the executive QC should carry out the repeat analysis with a fresh sample and fresh standard preparation if required. And if the purpose of the OOT result isn’t the diagnosed as a laboratory error then the head of the QC will suggest re-analysis to conform OOT outcomes. The analyst must hold the record of the re-evaluation effect in the work sheet. If the cause of the re-analysis the initial evaluation need to be suggested. Out of Trend procedures 29

30. In the case of raw material , the head quality control ought to overview the OOT outcomes and forward them to QA and prevent the re-occurance of such incidence. In the case of finished products, the head QC should review the OOT results and forward them to QA and the production team for investigation to take a final decision. Based on the investigation report, the head QC takes the final decision. 30 To be continued

31. Complaints – evaluation & handling Complaints – definition: “Complaints is defined as statement that is something wrong or not good enough, which shows customer dissatisfaction about the company and the product ”. Example- complaint about the packaging materials . Advantages : Sustained improvement of quality of product and process. Maintaining good relation with customers. 31

32. WHO GMP guidelines 32

33. Classification of quality defects 33

34. Time period for investigation after receipt of complaint: Key points for handling complaints Don’t take it personally. Never act on a complaint without hearing two sides story. Set the time frame. Keep notes. 34

35. Steps involve in handling complaints 35

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38. Investigation and determination of root cause : It is a type of problem solving method by recognizing the root cause of a problem. The main aim is that to prevent repetition of problem. This is not quick process or not include easy steps, generally requires to discuss with the person who knows the best process. Also required for problem identification through audits and by test reports. 38

39. Process of root cause analysis By using the different problem solving methods in root cause analysis need to be identifying process for cause of problem process as - Who should work on evaluating the problem ? Define the problem? What is it ? When did it happened ? Where did it happen ? How overall goals affected ? – keep it simple – make an outline - people see problems differently What will be done ? 39

40. Corrective and preventive actions (CAPA) when the root cause of problem is identified need to apply a specific corrective action to prevent it form happening again. Select and apply the action to remove the problem and prevent the recurrence. Corrective action Aimed at removing the cause of product failures and nonconformities in an effort to prevent their future recurrence. 40

41. Preventive action 41

42. Corrective action Vs preventive action 42

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44. To aware safety of the customer, most of industries focus on taking preventive measures, established one internal product recall team and applying QC steps to reduced the risk or to prevent product recall cost. Product recall will be done by various sources including manufacturers, wholesalers, retailers and customer. 44

45. Approach of product recall team If a product recall is there or recall is on progress the prepare a product recall action plan which followed to recalled procedure . 45

46. Annual product review (APR) Purpose : APR is an evaluation conducted annually to assess the quality standard of each drug product with a view to verify the consistency of existing process and to check the appropriateness of current specifications and to highlight any trend in order to determine the need to change any drug product 46

47. Production analysis Quality investigations Change management Specifications & test results Stability studies Component quality Market activities Regulatory assessment Validated status GMP agreements 47

48. APR summary report format The APR includes cover page , subsection, summary and reference. 48

49. APR conclusions and rating Where a report is related “ acceptable with conditions” or “ unacceptable” the report should be forwarded to executive management for review. 49

50. APR report approval Each APR report having signed off with – The QA manager The regulatory affairs manager Production \ operations manager Other groups who may be affected by any change 50

51. Batch review and batch release Purpose : For approval and release of the finished product batch establish the process. The Batch Record Review is  an essential tool for assuring the quality of a pharmaceutical process. 51

52. Responsibility : Executive ,QA or the production department is responsible for receiving the batch record for its completeness and accuracy. Head production is responsible for completion and review of batch release product. Head, QC responsible for completion and review of analytical \ microbiology records. QA is responsible for the review of analytical \ microbiology data in either hard or soft copy. 52

53. Process of batch release 53

54. Review of batch records Officer or executive of QA review the documents of both batch manufacturing and batch packaging record for any deficiency which affect on quality of the product or customer safety \ marketing. Condition for batch release : For batch manufactured and sold by the company for the India region only shall permitted by conditional transfer. There is no permission given to another party to sell the product After approval of the contract then there will be planned for conditional transfer. Product from export market then conditional transfer not allowed. 54

55. Concept of IPQC (IN-PROCESS QUALITY CONTROL) Objectives of IPQC To develop the technical procedure used in manufacturing process. Control and enhance efficacy of finished products. Investigation of raw material, instrument, environmental, process , evaluation and packaging etc. 55

56. IPQC for parenteral products To check the bulk solution prior to fill for drug content , pH, colour, Clarity of solution. Pyrogen test leakage test. physical evaluation. IPQC for solid dosage form Drug content determination . Weight variation of tablets and capsules . During manufacturing process check the disintegration or dissolution time hardness friability of tablets 56

57. IPQC for semisolid dosage form: Uniformity and homogeneity of drug content. Determine the particle size of preparation. Check the appearance Viscosity Specific gravity Sedimentation volume 57

58. Documentation and evaluation of data 58

59. Area clearance and line clearance 59

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61. REFERENCE: https://www.slideshare.net/shravandubey2/out-of-specification-shravan https://www.slideshare.net/FarukHossen12/out-of-specifications https://www.slideshare.net/MayuriMore15/complaints-in-quality-management-system https://www.slideshare.net/pranav10/root-cause-analysis-12547191 https://www.slideshare.net/POURNIMABHALEKAR/ipqc-71238255 The Theory and Practice of Industrial Pharmacy by Leon Lachman A text book of quality management system by Dr. Md. Rageeb Md usman , snehal s.abhang 61

62. 62 Thank you