1. DOCUMENTATION Presented By- Shivani Gupta M.Pharm (pharmacology)1 Sem I.P.S. College of pharmacy 2. OBJECTIVE The objective of this presentation to emphasis the importance of documentation for industries and describe the protocols regarding this also their management. 3. DOCUMENT & DOCUMENTATION •Document is written statement of proof The document can Assure that quality standards are consistently met. Communicate these standards all who interact with project. A Document System is an interacting set of documents, each with a defined purpose and consistent document. 4. TYPES OF DOCUMENTS Commitment Document Relationship between industry and the regulatory authorities. Directive document Relationship between management and employee Record document Relationship between the employee and the work they perform. 5. DOCUMENTATION is a process that involve the systematic interaction of people, events and document to create the records of the organisation/corporate Documentation is the key to GMP compliance and ensures traceability of all development, manufacturing, and testing activities. Documentation provides the route for auditors to assess the overall quality of operations within a company and the final product. 6. THE 10 GOLDEN RULES OF GMP 1 Get the facility design right from the start 2 Validate processes 3 Write good procedures and follow them 4 Identify who does what 5 Keep good records 6 Train and develop staff 7 Practice good hygiene 8 Maintain facilities and equipment 9 Build quality into the whole product lifecycle 10 Perform regular audits 7. LIST OF THE MOST COMMON TYPES OF DOCUMENTS USED FOR GMP DOCUMENT DESCRIPTION Quality manual A global company document that describes, in paragraph form, the regulations and/or parts of the regulations that the company is Required to follow Policies Documents that describe in general terms, and not with step-by-step instructions, how specific GMP aspects (such as security, documentation, health, and responsibilities) will be implemented. (SOPs) Step-by-step instructions for performing operational tasks or activities. Batch Records These documents are typically used and completed by the manufacturing department. Batch records provide step-by-step instructions for production-related tasks and activities, besides including areas on the batch record itself for documenting such tasks. 8. Test methods These documents are typically used and completed by the quality control (QC) department. Test methods provide step-by-step instructions for testing supplies, materials, products, and other production-related tasks and activities, e.g., environmental monitoring of the GMP facility. Test methods typically contain forms that have to be filled in at the end of the procedure; this is for documenting the testing and the results of the testing. Specifications: Documents that list the requirements that a supply, material, or product must meet before being released for use or sale. The QC department will compare their test results to specifications to determine if they pass the test. Logbooks Bound collection of forms used to document activities. Typically, logbooks are used for documenting the operation, maintenance, and calibration of a piece of equipment. Logbooks are also used to record critical activities, e.g., monitoring of clean rooms, solution preparation, recording of deviation, change controls and its corrective action assignment. 9. OBJECTIVE & IMPORTENCE OF DOCUMENTATION OBJECTIVE• Define the manufacturer’s information system and control strategies clear. •Minimises the risk of misinterpretation and errors. •Confirmation of task performed. •Tracing the batch history of any product IMPORTENCE• Good documentation is an essential part of quality assurance system and must be as requirement of GMP. •Define the specifications of each product •Ensure the quality • Ensures that the responsible authorities, have knowledge of the work carried out. 10. HIERARCHICAL DOCUMENT SYSTEM 11. INCLUSIONS OF DOCUMENTATION Revised schedule M has the following elements which are related to documentation:---- Records Labels Specifications And Testing Procedures Master Formulae Packaging Instructions Batch Production and Control records (BPCR) / Batch Manufacturing Records Batch Packaging Records (BPR) Standard Operating Procedures (SOPs) 11 12. Introduction In pharma industry, Labels are used for identification and/or status of container, equipment and premises. Labels should be unambiguous and in format approved by the company. Sometimes colored labels are used to indicate status. For Example, colored labels for starting materials according to their status: Quarantine Yellow Approved Green Rejected Red 12 13. Label of finished product • Name of product • Ingredients • Net Content • Batch number • Expiry date • Storage condition • Information about manufacturing company (Lice. No. and Address) 13 14. Label of reference standard • Name of material • Potency • Date of preparation • Batch number • Shelf-life • Storage condition 14 15. • Introduction • Specifications for Raw Materials • Specifications for Finished Product • Specifications for Packaging Materials • Testing Procedures HNSIPER 15 16. INTRODUCTION It is a list of detailed requirements with which product/material used or procedure followed during manufacture need to conform. They serve as basis for quality evaluation. Specifications should be available for : • Raw Materials • Finished Products • Packaging Materials First twos can be referred from their individual monographs from pharmacopoeia. If standard data is not available in pharmacopoeia, then manufacturer can write specification himself. Specifications for packaging materials such as plastic or glass containers and closers etcetera, are not given by any monograph. However certain requirements have been laid down for them in appendix-11 of I.P. 16 17. Bureau of Indian Standards (BIS) has prepared specifications for various packaging materials. These specifications are given prefix as “IS”, means ‘Indian Standard’. There are 18210 numbers of Indian Standards.* Certain specifications amongst them are specifically prepared for pharmaceutical industry, while the rest are general specifications. 17 18. SPECIFICATIONS FOR RAW MATERIALS Generic and chemical name of material Trade name or product code established any manufacturer Description Name of pharmacopoeia or any other recognized book of standards in which monograph appears or INN (International Non-proprietary Name). Approved supplier Frequency of testing of stored material Special precautions to be taken during storage including safety aspects Date of Issue of specifications 18 19. SPECIFICATIONS FOR FINISHED PRODUCT Generic name of product Trade name Dosage form and Strength Description (Color, State, Dimension, Taste) Physical properties ( Weight/Volume (with limit), pH,Viscosity, Density, Hardness, Friability, Disintegration time, Dissolution Time etcetera) Name of Pharmacopoeia as a reference Date of Expiry Precautions during storage including safety aspects Date of issue of specification 19 20. SPECIFICATIONS FOR PACKAGING MATERIALS Below mentioned Indian standards may referred, while preparing specifications for packaging materials: Number of IS Specification for IS 7803 Plastic Containers IS 3692 Rubber Closures IS 1776 Folding Box Board IS 2771 Corrugated Box IS 3101 Collapsible Tubes IS 7852 Eye Ointment Tubes IS 10133 Glass Bottles IS 8970 Paper Aluminum Foil IS 8393 Pilfer Proof Closures IS 1984 Glass Vials 20 21. TESTING PROCEDURES These are nothing but the procedures for testing raw materials, intermediated and finished products. These procedures are basically based on Pharmaceutics and Analytical techniques. While preparing these procedures Various pharmacopoeia (like IP, BP, JP, EP, USP etc) and other recognized books of standards like drug and cosmetics rules, USNF, other authoritative books on analysis of drugs. 21 22. FORMAT FOR STANDARD TESTING PROCEDURE Name : Pages: Code No. : Shelf Life : Status : Effective Date : STP No. : Review Period : Prepared By Checked By Approved By Signature Date 22 23. • Definition • Preparation of Mater Formulae • Description • Sample of Master Formulae HNSIPER 23 24. Definition Master formulae also can be said and written as ‘Master Formula Record’, ‘Manufacturing Formula’, ‘Master Production and Control Record’ (MPCR) etcetera. It is defined as “An approved master document that describes the full process of manufacturing for the batch of specific product.” It includes all the materials used in any batch manufacturing and step by step process of manufacturing. 24 25. PREPARATION OF MATER FORMULAE Master formulae can be prepared by competent technical staff. It should be reviewed by the heads of production, quality control department and research & development. 25 26. Description Name and Strength of the product along with dosage form MFR No. A complete list of all ingredients with their quantity Description of Containers, Closures and Packaging materials to be used Description of all Vessels and Equipments used in the process Processing and Packaging Instructions IPQCs to be exercised during processing and packaging Precautions to be taken during manufacture and storage of semifinished product including any special storage conditions Reference 26 27. SAMPLE OF MASTER FORMULAE 27 28. • Definition • Notes about BPCR • Contents of BPCR • Sample For BPCR HNSIPER 28 29. Definition Batch Processing Record can also be said as Batch Manufacturing Record (BPCR) . It is defined as – “The Batch Manufacturing Record (BPCR) is the necessary quality and GMP documentation for tracing the complete cycle of manufacture of a batch or lot.” 29 30. CONTENTS OF BPCR The name and batch number of the product Dates and times of commencement, of significant intermediate stages and of completion of production Identification (initials) of the operator(s) who performed each significant step of the process and, where appropriate, the name of any person who checked these operations Quantities of each starting material actually weighed A record of the in-process controls and the initials of the person(s) carrying them The product yield obtained at different and pertinent stages of manufacture Notes on special problems including details, with signed authorization for any deviation from the Manufacturing Formula and Processing Instructions Approval by the person responsible for the processing operations. 30 31. HNSIPER 31 32. INTRODUCTION In fact, BPR is a part of BPCR. These records are based on packaging instructions. One important operation that should be carried out before packaging operation is line purging (clearance). 32 33. CONTENTS OF BPR Name, Batch number and Qty. of bulk finished product to be packed Theoretical and Actual Yield and Reconciliation The date and time of the packaging operation The name of responsible person and his initials Details of packaging instructions like equipments and packaging lines used Qty. along with identification of different printed packaging materials issued, used, destroyed and/or returned to store and reconciliation In any case of problems, if any deviation made, written authorization for the same 33 34. HNSIPER 34 35. INTRODUCTION Site Master File is a document, which gives a complete information regarding a site of pharmaceutical plant. This document generally should not be very massive, like running into more than 100 pages. M.H.R.A. (Medicines and Healthcare products Regulatory Agency), a government agency of U.K., has given certain guidelines for length of the format for it. 35 36. INCLUSIONS OF SMF The Information about Company Personnel Premises and Equipment Documentation Production Quality Control Contract manufacture and analysis Distribution, Complaints and Product Recalls Regulatory inspections and self-inspections Details of Annual Product Review Change Control System Technical Quality Agreement for Contract Manufacturing (Technical Agreement, Quality Agreement) 36 37. PROTOCOL 38. Sub-part A-General Provision Sub-part B•Responsibilities of QC unit •Available facility of QC unit •List of critical instruments •Quality control manual •Training manual •Attendance records of trainee •Training evaluation records •List of employees •Organogrammes •Job description •SOP on appropriate clothing and protective apparels. •SOP on practice of good sanitation and health habits. •SOP on entry procedures to factory and various department. •SOP on pre & post employment medical check-up of employees. •Records of consultants. 39. Sub-part C •Statement of formulation & their volumes •Plans of the facility •Area specifications of building, facilities. •SOP on buying & facility cleaning and sanitation •SOP on building & facility maintenance •SOP on maintain of environmental condition •SOP on cleaning & disinfection of aseptic areas & equipments. •Statement of lighting requirements in the facility •HVAC system •Plumbing diagram •SOP on sewage and refuse handling •Diagram of washing and toilet facilities. •SOP on pests, rodent, birds, insects and vermin control •Job description of sanitary inspector 40. Subpart D•Equipment description list •Equipment M.O.C. List •SOP on cleaning, operation & maintenance of each and every identified equipment. •SOP on records of calibration •List of filters for injectables. 41. Subpart –E •SOP on receipt and storage of R.M./P.M. •List of RM/PM with their storage •SOP on sampling of RM/PM •SOP on tasting and approval or rejection of materials •SOP on re-testing of approve material. •SOP on handling of rejected materials. •List of primary packaging materials and their composition. •SOP on testing of closure system. •SOP on cleaning, sterilization and depyrigenating the container and closures. •SOP and record on vendor certification. 42. Sub-Part-F •SOP on change control procedure •SOP on dispensing of batch materials. •List of critical phases of operation where yield should be checked. •Equipment identification record •SOP on sampling and testing of in process materials. •SOP on time limitation on production. •SOP on validation of sterilization process. •SOP on reprocessing of materials 43. Sub-Part G •SOP on receipt identification, storage, handling, sampling, examination testing of labelling & packaging materials. •SOP on issue of printed packaging materials •SOP on IPQC during packaging and labelling operation •SOP on expiration dating. Sub-Part-H •SOP on quarantine of finished products before release by QC. •SOP on storage of finished products under appropriate condition of temperature, humidity and light. •SOP on distribution of finished products. 44. Sub-part I•Written specification •SOP on calibration •SOP on validation •SOP on stability testing •SOP on special testing requirements •SOP on reserve samples •Records of laboratory animals •SOP on penicillin contamination 45. Sub-part J •Equipment cleaning, use and maintenance log •Material receiving record •Results of examination and testing of materials •Material inventory record •Records of disposition of rejected materials •Master production and control record. •Batch production and control record •Production record review. •QC laboratory record should have all the documents listed in 211.194 distribution record. •SOP on complaints and their reports/records. 46. Sub-part K •SOP on handling of returned product. •SOP n handling of salvaging. 47. MAINTENANCE OF RECORDS 47 48. USE OF MAINTENANCE RECORDS The use of maintenance records is particularly important in a factory setting, where a large number of expensive machines are used daily. These records can help make sure that any appropriate equipment maintenance or plant maintenance has been completed so that plant operations will run smoothly. For instance, a maintenance log detailing any repairs or service upkeep may be kept on a factory machine. This log can help avoid accidents or plant shut-downs resulting from defective equipment 48 49. MAINTENANCE RECORD MANAGEMENT Maintenance record management can be important for a number of reasons: Good records help department managers and employees ensure that a piece of equipment is performing in line with any manufacturer warranties. Maintenance records also help companies track when a piece of equipment needs to undergo preventive maintenance. If a company gets sued in relation to a faulty piece of equipment, maintenance records can be essential in supporting the company's case. 49 50. RECORD KEEPING REQUIREMENS 50 51. RECORD KEEPING Records provide history of a batch 1. Name and address of supplier of each drug product with date 2. Name and address of purchaser of each drug product with date 3. Supplier or purchaser licensed 4. Retention of order forms, copy of delivery notes, stores receipt, and issue vouchers ,and book of records (controlled drugs book/prescription drugs book) on the premises as provided for in the drug laws. 5. Accuracy of records kept. 51 52. PURPOSE AND PRINCIPLE OF RECORDS Scientific Regulatory requirement Business purpose Maintenance of Records is the essential part of quality assurance system Records must be free from errors 52 53. RETENTION OF RECORDS Records should be kept in such a way that activities concerning the production and quality control of active pharmaceutical ingredients are traceable. Records should be retained for at least one year after the expiry of the finished product or for a specified period if there is no expiry date. 53 54. RECORDS MAINTENANCE The functions of records maintenance include the following essential components: Organizing and filing records Identifying which records to retain, and for how long 54 55. CONCLUSION Documentation is necessary in pharmaceutical industry Documentation is a key area for companies in the pharmaceutical industry. The United States Food and Drug Administration (FDA)-the governmental agency, that is responsible for overseeing the industry, requires extensive documentation for every manufacturing and packaging lot of all pharmaceutical products. The FDA mandates documentation for the sake of accountability and traceability. This practice is to ensure safe and effective pharmaceutical products.