Documentation

the topic documentation include their need their importance, purpose of documentation, feature of documentation, classification of records

1. Documentation Ravish Yadav

2. Introduction It is a piece of paper/ memorandum containing information or matter, evidence of a process or instructions to carry out a procedure. It is an integral part of: GMP (GDP) QA system ISO 9000 requirement 2

3. Documentation Prime necessity in quality assurance Statutory requirements as per schedule U of Drug and Cosmetics Act

4. Need It is a comprehensive system so designed, written, implemented and controlled so as to provide information on each and every aspect of QC or QA. It is about establishing written instructions for significant activities, following those instructions in practice and making records of those activities. 4

5. It defines system of information and control so that risks so inherent in misinterpretation and/ or error in oral communication are minimized. It strengthens quality and its consistency in all goods and services as those responsible for specific operation have clear unambiguous instructions to follow. 5

6. Importance of documentation in quality assurance Scientific purpose Written protocol- identifies material to be used, conditions to be used and data to be obtained. Conclusion drawn from the analysis of data whether or not a product has a therapeutic merit. If favorable conclusion then, product is suitable for marketing.

7. 2. Regulatory Purposes Maintaining of some records-legal requirement by US FDA cGMP or Schedule U Documents generated during manufacturing of drug constitutes legal evidence which may be used to decide how well a firm fulfills its legal obligations. Important for parenteral drug manufacture as FDA investigators routinely check validation data for sterilization process. Information contained in records must be able to answer questions of regulatory officials regarding identity, quality, purity, safety and effectiveness of product.

8. 3. Business Purpose Records generated in conjunction with the production of a drug Neither required by the law nor needed to demonstrate the quality of product Supplementary to the processing of the batch Prepared from raw data generated during manufacture of individual batches Intention- improving efficiency and obtaining cost saving Information – useful for providing reports of production status and for determining labor standards, overhead costs and degree of success in meeting standards of quality

9. Requirements of a document Evidence of proof of activities Helps in traceability Helps in correction and prevention of faults Helps in creating awareness Required for audits Legal requirement (GMP) 9

10. Features of documents Documents should be designed, prepared, reviewed and distributed with care. They should comply with relevant parts of manufacturing and marketing authorization. Documents should be approved, signed and dated by appropriate authorised persons. It should have an identification number. No documents should be changed without authorisation. 10

11. Documents should have unambiguous contents. Title, nature and purpose should be clearly stated. They should be laid out in orderly fashion and should be easy to check. Reproduced document should be clear and legible. The reproduction of working documents from master documents must not allow any error to be introduced through the reproduction process. 11

12. Documents should be reviewed regularly and should be kept up to date. When a document is revised, a system should exist to prevent intentional use of superseded version. Such reviewed documents should be approved, signed and dated by authorised persons. 12

13. Whenever document requires entry of data, those entries should be clear, legible and indelible. Sufficient space should be provided for such entries. Such entries should be signed and dated by person making the entry. Any alteration made to a document should be singed and dated. The alteration should permit the reading of original information. Wherever appropriate, reason for alteration should be recorded. Each document should have date of issue and due date of revision 13

14. Records should be made or completed when any action is taken and in such a way that all significant activities concerning the manufacture of pharmaceutical products are traceable. Records and associated SOPs should be retained for at least one year after expiry date of finished product. Data must be recorded by electronic data processing systems or by photographic or other reliable means. Master formulae and detailed SOP should be available and accuracy of records should be checked. 14

15. Only authorized person should modify the data in computer and a record of changes and deletions should be maintained. Access should be restricted by passwords or other means. Batch records electronically stored should be protected by back-up transfer. During the period of retention, the data are readily available. Old documents should be discarded. All departments should be informed of given revised additions. 15

16. Any change in data which will cause change in end product quality must be cancelled. A list of all receiving departments should be made whenever each document is received by different departments. The receiving department should check the following aspects: Whether they have been given a new document Whether they are using new documents Whether they have discarded the old document. 16

17. Types of documents 17

18. Records – must reflex accuracy, totality, simplicity, efficiency, reliability, low cost, efficacy. They also include reports. Procedural manual – e.g. Departmental manuals, SOP Functional document or apex manual – Quality policy manual, labels of finished products, intermediates etc. 18

19. Thus, document should indicate: Accuracy Simplicity Efficiency Reliability Low cost 19

20. Criteria for documentation Nature of document should be clearly understood. Easily adoptable Precise Sufficient space available for all entries Written in ink No overwriting allowed Should be update Periodically reviewed for modification All documents should be designed in concurrence with QA department Should be approved by QA Head

21. Requirements of good documentation Approval Clarity Regular review and update Formal presentation Records 21

22. Approval 22 This applies particularly to work instructions, procedures, manufacturing formulae and specifications. Approval should be by the relevant technical, management and quality personnel, to ensure that documents comply with the principles of GMP and the specific product marketing and manufacturing authorisations

23. Clarity 23 They should not be open to misinterpretation by the users. They should be written in a way that makes them easy to check, particularly when they will form part of a product manufacturing history. Good documentation design will help to minimize errors

24. Regular review and update 24 Documents must be kept up-to-date with changes in regulations or processes and should be distributed in a controlled manner to ensure that only the most recent versions are available for use. They must also be available to those who need them, where they need them!

25. Formal presentation 25 Controlled documents should be prepared in accordance with a written procedure, now a days probably using a computerised documentation control system.

26. Records 26 Should be made at the time of each action - do not rely on memory for their completion. Records relating to manufacturing or testing operations should be kept for at least one year after their expiry. If documents or data are stored electronically, the computer system must be validated to assure data security and integrity. Provisions must also be made to retrieve the stored data, possibly years after they have been generated

27. Strengths of Good Documentation 27 Clear Objective of the document Clarity of Scope Who should prepare? Layout of the document in mind Explain the activity performed logically Use short, simple, easy to understand sentences Maintain flow of script Match script to the sequence of events of the activity Use correct data format Meaningful data will give meaningful information Draw neat and correct inference Conclusion & Summary

28. Classification of records Pre-production records Production records Post-production records

29. Pre-production records Material receipt records RM analytical record Material stock and utilization Material requisition record Others

30. Material receipt record Name of the item Date of receipt Name of manufacturer Name of supplier Quantity received No. of containers Manufacturing lot no. Expiry/ re-test date

31. RM analytical record Material receiving no. Manufacturers description Standard name Date of receipt Total quantity received Name of manufacturer Name of supplier Manufacturing lot no. Sampling date Sampled by No. of containers and quantity sampled Tests or assay carried out Approval or rejection Expert staff sign (approval)

32. Material stock record Store keeper receives the material, opens packs and find the damage and records following. Date of receipt Name of material Supplier’s name Supplier’s Batch no. Quantity of and containers Batch no of receiving company Exp. Date if any The records are sent to QA to sample raw material. Samples are sampled according to sampling plan.

33. Material utilization record Standard name of material Code no. Receiving report no. Quantity issued for manufacturing purpose Sign of staff responsible for receipt and issue of materials

34. Material requisition record Standard name of material Code no. Quantity required for batch Material receiving no. Batch/ lot no. Signature of weigher and checker for quantities Sign of senior receiver in production department

35. Packing material SAMPLING Sampling plan Method of sampling Instructions for sampling b. STORES RECORDS Name of material Quantity received Supplier’s name c. ANALYSIS RECORDS Approved specification/ blue prints should be available Procedures of testing to be followed

36. Production records MFR BMR Intermediate and bulk products Filling and packaging record Others

37. Intermediate and bulk products Stages at which to take sample. Method of sampling. Approved specifications & method of analysis. Information of processing department.

38. Filling or packaging record Name of product Batch/ lot no. Batch/ lot size Control release no. No. of total containers filled in various sizes Date of commencement and completing of filling Observations in connection with all in-process controls Theoretical quantities of printed material required Actual quantities of printed material received with sign Date of commencement and completing of packing Quantity of defective packings and their disposal Sign of responsible staff and supervisors Balance of unused packing material and its disposal

39. Others Batch analytical record Product approval record

40. Post-production records Packing records Records of shelf life studies Complaint records Distribution records Product recall records Others

41. Packing records List of approved packaging components with standard cards of each item Batch ticket Name of product Batch No Strength Pack size Number

42. Pack weight Volume Quantity received from packing Mfg. date and Exp. Date Yield against standard yield Rejection percentage Details of in process control and observations Date of commencement and completion of packing

43. Shelf life records (stability studies records) Address of manufacturer Summary of stability testing Name of product Packing material Details of batch included in the study i.e. batch no., batch size, type of batch (experimental/ production) Storage condition i.e. temperature, humidity, light Results of testing Test Result after months 0 1 2 3 6 12 other Conclusion Name of analyst Sign of analyst Sign of QC head with date

44. Distribution records To facilitate effective records, the records should include all details such as Name of person to whom supplied. Batch no. Quantity Destination Challan no.

45. Complaint records Name of product Batch/ lot no. Date of manufacture and expiry Date of receiving complaint Details of complaint i.e. place of origin, name of the person filing the complaint Nature of complaint Observation with regards to condition and examination of control or reference sample Analysis of complaint Action taken for withdrawal of complaint batch Action required to be taken to prevent recurrence of complaint

46. Miscellaneous records Instrument calibration records Validation records Installation qualification Operational qualification Computer validation Process validation Supplier validation Analytical validation Vendor approval records

47. Environmental monitoring records Equipment cleaning and maintenance records Sanitation records Pest control measures Training of personnel Reprocessing records Returned goods documentation Salvaging documents

48. Administrative and personnel records Training records Consultant records Health records

49. Reports Secondary documents Prepared from information contained in one or more records Help in drawing conclusion from records Two types Internally generated reports Externally generated reports

50. Internally generated record Investigations of deviation Description of discrepancy or failure Efforts taken to locate the cause Results of efforts Conclusion drawn Action taken Reports of analysis – to be sent to government agencies Trend analysis – the quality standard of each drug annually

51. Internal audits Recalls No. of consignees notified and method of notification No. of consignees responding No. of consignees not responding Quantity of recalled material on hand no. of effectiveness checks performed and their results Estimated time frame for completion Report of disposition of material

52. Externally generated reports Report of analysis – RM supplier, PM supplier, outside labs Complaints and adverse reactions Inspection results

53. Master documentation file Provides complete history of product Active component characteristics Material specification Analytical method Stability reports Product specifications Equipment specification FP specification Stability reports Process specifications Qualification protocols Plant qualification reports Process data MFR

54. Retention of records Reports pertaining to production/ manufacturing – depends on shelf life of product Records pertaining to components, containers, closures, labeling etc – 1 year after expiry of batch in which they were used

55. Maintenance of documents The Management Representative (MR) for the system is responsible for maintaining documents. His duties: He will have records and lists of distribution of all the documents Any change in data which is going to affect the end product quality must be cancelled. 55

56. Document life cycle 56

57. Retrieval of documents cGMP requires that the production and control records be available for review and inspection Thus, a well defined system needed Two types of system Manual system Automated system

58. Manual system Individual file jacket for each product Jackets identified with batch no. Filed consecutively by batch no. in a central facility Contains originals (copies permitted) Requires considerable amount of space

59. Automated systems Computerisation associated with lab, storage, manufacturing etc Should be routinely inspected and validated Changes by authorised personnel only Backup file mandatory Hard copy to be maintained