Pharmaceutical Documentation

A Study on Documentation Maintenance in the Pharmaceutical Industry which includes the main records to be maintained and the quality attributes to be studied about the Quality Management System. Quality attributes include the study of quality audit, quality review, and quality documentation.

1. DOCUMENTATION MAINTENANCE IN THE PHARMACEUTICAL INDUSTRY Ms. TENY SARA THOMAS MOUNT ZION COLLEGE OF PHARMACEUTICAL SCIENCES AND RESEARCH, ADOOR, KERALA ASSISTANT PROFESSOR B.PHARM SIXTH SEMESTER PHARMACEUTICAL QUALITY ASSURANCE UNIT IV – CHAPT 2

2. CONTENTS Documentation Batch Formula Record Master Formula Record Distribution Records Quality Audit Quality Review Quality Documentation Standard Operating Procedures Reports and Documentation

3. DOCUMENTATION Document – is a piece of written, printed or electronic matter that provides information or evidence or that serves as an official record. Documentation – documentation is any communicable material that is used to describe, explain or instruct regarding some attributes of an object, system or procedure. Documentation can be divided into two – Documents and Records Documentation provides both: Information on when, where, who, why and how the task was completed. Evidence providing that the tasks have been completed as they should be.

4. NEED OF DOCUMENTATION Documentation is the cornerstone of any company’s quality management system and is an essential GMP requirement . Ensures product quality and safety. Impacts the level of success in manufacturing quality products. Defines specifications and procedures for all materials and method of manufacture and control. To ensure that all personal concern with manufacture know what to do and when to do it. To ensure that authorized persons have all information necessary to decide whether or not to release a batch of a drug for sale. To ensure availability of the data needed for validation, review and statistical analysis.

5. DOCUMENTATION REVIEW Documentation system should provide for a periodic review, and revision of any document. Such revised versions shall also be approved by the authorized persons. Updated versions shall also be superseding the previous editions. Outdated document shall be immediately removed from active use and copy retained only for reference. If documentation is through electronic data processing system there shall be adequate systems in place to check and ensure the correctness of data and record changes.

6. CHARACTERISTICS OF A DOCUMENT For effective use of documents, they should be designed and prepared with utmost care. Each document shall:- Have a clear title. Have an identification number Be approved by authorized person Have the date of issue Have a due date of revision List to whom it has been issued.

7. BATCH FORMULA RECORD

8. DEFINITION OF BATCH A specific quantity of a product that has uniform character and quality and is produced according to one manufacturing order made at the same time Eg . a batch of paracetamol tablets

9. BATCH FORMULA RECORD DEFINITION :- Batch manufacturing record is a written document of the batch, prepared during pharmaceutical manufacturing process. Also contains Batch Manufacturing Record (BMR) . Contains actual data and step by step process for manufacturing each batch. A proof that batches were properly made and checked by quality control personnel. Prepared for each intermediate and active pharmaceutical ingredient and should include complete information relating to the production and control of each batch.

10. Structure of BMR varies from company to company, it is possible to highlight their common element. BMR should be checked before issuance to assure that it is the correct version. Before any processing begins, a check should be performed and recorded to ensure that the equipment and workstation are clear of previous products, documents, or materials not required for the planned process and that the equipment is clear and suitable for use.

11. BMR normally contain information that relates to the following aspects of the manufacture of a batch of product:- Dates of start and finish of manufacture. List all materials and the amount used. List of packaging materials used. Identity of each equipment used. Description of Labelling. Details of steps completed in the manufacturing process and times of completion. Details of any sampling done, in-process and laboratory test results. Initials of the person responsible at every stage. Details and results of all in-process checks. Reference to any equipment used. Batch yield and reconciliation. Any deviations noted, its evaluation and investigation conducted. Quality control information.

12. BMR FORMAT A good BMR format should contain following parts:- Batch Record :- A very first page of the BMR has all records about the batch as batch number, batch size, composition, master formula record from which the weight of the batch was referred, shelf life, storage conditions, manufacturing license number, manufacturing date, expiry date, date of starting and date of completion. General instruction for manufacturing:- health and safety instructions to the operators and the manufacturing chemist are written those should be followed during the manufacturing process regarding the material and equipments used during manufacturing.

13. 3. Equipment Cleaning Record:- checklist of the cleaning of all equipments is prepared, those are used in the manufacturing of the batch and date of cleaning. Cleaning of the equipments should be checked by the QA department. 4. Bill of Materials:- list of the raw materials should have the quantity of the materials with their analytical report numbers. Weights of the materials should be verified by QA. E.g. if tablets are coated then coating material should be included. 5. Yield: - yield of the batch should be calculated at the end of every stage to calculate the process loss. Final yield should be calculated at the end of the manufacturing that should not be less than 99%.

14. 6. Manufacturing Process:- should be written step by step in easy language. Milling, sifting, drying, lubrication, compression, coating and packing having all instruction with process time should be written. Checklist for line clearance should also be attached before starting every process. After completion of the every stage, tablets must be checked for the compliance of the specification of that stage. Results should be attached with the batch manufacturing record. 7. Abbreviations:- used in the document should be made to understand BMR easily. 8. History of Chances:- at the end, the document should have list of the changes in the document including the revision number and the date of change.

15. REVIEW OF BMR All BMR are received by QA immediately after the batch is completed. QA personnel checks the following:- Correctness of entries. Conformance to manufacturing instructions. Occurrence of deviations, if any deviations are found whether it has been made with proper authorization and documentation. Signature in all pages of BMR. Presence of dispensing cards. Calculation of yields. Reconciliation of primary and secondary packing materials. Signature of production manager. Attachment of in-process reports and specimens of packing materials After review of BMR sign and date of review will be written on BMR. Also finished product analysis report, microbiological report and product release certificate will be attached to BPR.

16. MASTER FORMULA RECORD

17. MASTER FORMULA RECORD DEFINITION :- A document or set of documents specifying the starting materials with their quantities and the packaging materials, together with a description of the procedures and precautions required to produce a specified quantity of a finished product as well as the processing instructions, including the in-process controls.

18. Master formula record (MFR) is a master document for any pharmaceutical product. Contains all information about the manufacturing process for the product. Prepared by the research and development team of the company. Used as reference standard for preparing batch manufacturing record (BMR) by manufacturing units. Prepared and endorsed by technical staff i.e. head of production and quality control. MFR is also called Master Manufacturing Record , Master Production Record.

19. CONTENTS OF THE MASTER FORMULA RECORD 1. The name of the product together with product reference code relating to its specifications. 2. The patent or proprietary name of the product along with the generic name, a description of the dosage form, strength, composition of the product and batch size. 3.A statement of the processing location and the principal equipment to be used. 4.Name, quantity, and reference number of all the starting materials to be used. Mention shall be made of many substance that may disappear in the course of processing. 5.A statement of the expected final yield with the acceptable limits, and of relevant intermediate yields, where applicable.

20. 6.The methods or reference to the methods, to be used for preparing the critical equipments including cleaning, assembling, calibrating and sterilising. 7.Detailed stepwise processing instructions and the time taken for each step. 8.The instructions for in-process controls with their limits. 9.The requirements for storage conditions of the products, including the container, labelling, and special storage conditions where applicable. 10.Any special precautions to be observed. 11.Packing details and specimen labels.

21. PREPARATION OF A MFR Primary responsibility is of the formulation and development department Secondary responsibility is of the quality assurance. After preparation, it should be received by the head of the production, quality control department and the research and development department. Preparation of an MFR can be divided into Two Parts:- Packaging part Manufacturing part

22. The first page of both the section will have the following details:- Name, address and logo of the company Dosage form Brand and generic name Product code Label claim:- this should include all ingredients and the text included in the product. Product description Shelf life Pack and batch size Storage conditions

23. MANUFACTURING PART – Shall include:- Processes to be monitored. List of equipments, machines, utensils Special precautions to be taken for the product during manufacturing and packing. Batch manufacturing formula Statement of yield with the acceptable limits In – process quality checks during and at the end of every important step Method used for preparing, cleaning, assembling, and operating various equipments. Requirements of storage conditions

24. PACKAGING PART – Shall include:- Complete list of packaging materials required for a standard batch size, including quantities, sizes and types Includes line clearance checking during batch packaging operations. Includes reconciliation of printed and unprinted packaging materials with acceptable limits. Includes destruction of excess or rejected printed packaging materials Includes description of packaging operation and the equipments to be used for packing.

25. SAMPLE MASTER FORMULA RECORD PRODUCT CODE - MASTER BMR NO PAGE NO DICLOFENAC SODIUM TABLET (100mg) BATCH NO:- BATCH SIZE:- MANUFACTURING DATE:- EXPIRY DATE:- LABEL CLAIM EACH UNCOATED TABLET CONTAINS:- Ingredients Quantity for each batch Overages added Reference of MFR NO :- MANUFACTURING DATE:- REVISION NO:- REVISION PERIOD:- EXPIRY DATE:- PACK BLISTER PACK MFG LICENCSE NO BMR ISSUED BY ABD DATE BMR RECEIVED BY AND DATE PREPARED BY CHECKED BY APPROVED BY AUTHORIZED BY SIGN OF QA OFFICER SIGN OF PRODUCTION MANAGER SIGN OF QA MANGER SIGN OF GM

26. DISTRIBUTION RECORD

27. DISTRIBUTION RECORD DEFINITION :- Distribution records are written data related to distribution of drug products from the manufacturer to the distributors. The complete data regarding all batches of drug products should be maintained.

28. Distribution procedure shall include the following:- A procedure whereby the oldest approved stock of a drug product is distributed first. Deviation from this requirement is permitted if such deviation is temporary and appropriate. A system by which the distribution of each lot of drug product can be readily determined to facilitate its recall if necessary. The manufacturer must maintain records of all distribution transactions involving in process or finished goods. A variety of distribution recording system must be utilized.

29. WHO GULIDELINES FOR DISTRIBUTION RECORDS The title, nature and purpose of each document should be clearly stated. Content of document should be clear and unambiguous, in an orderly manner and easy to check. Documents should be completed, approved, signed, and dated by an appropriate authorized person. Establish and maintain procedures for the identification, collection, indexing, storage, maintenance, disposal, and access to all applicable documentation. All records must be readily retrievable, stored, and retained.

30. There should be compliance with the national legislative requirements with regard to nature & content of document. Documents should be reviewed regularly and kept up to date. Methods should exist for transfer of information if required. Records should be kept readily available upon request. In the case of temperature sensitivity pharmaceutical products, records of investigations and actions should be retained for at least one year after the expiry date of the product. Where the records are generated and kept in a electronic format, their back ups should, be available, to prevent any accidental data loss.

31. CONTENTS OF A DISTRIBUTION RECORD A distribution record contains:- Name and strength of the product. Description of dosage form. Name and address of the consignee. Date and quantity shipped. Lot and control number of the drug. The dates of commencement and ceasing of distribution of a a specific lot of product. Invoices, bills, customer receipts, internal warehouse storage and inventory control records – maintained for 3 years after distribution process has been completed.

32. Product Information Describe the product being transferred to a new owner. (E.g. Drug name, manufacturer, lot number, strength, dosage form) Transaction Information Describe the sale, transfer, return, of the product. (E.g. quantity, invoice number, invoice date) Distribution Information Describes the party selling or transfering ownership of the product. (E.g. business name, and name and signature of the person) Recipient Information Describes the party receiving the product. (E.g. business name and address, date received, name and signature of the person)

33. STANDARD OPERATING PROCEDURES

34. DEFINITION:- A SOP is a set of written instructions that document a routine or repetitive activity which is followed by the employees in the organisation SOP’s are integral part of a successful quality system. Backbone of the pharmaceutical industry. Provides information to perform a job properly and consistently, in order to achieve pre-determined specification and quality end-result. Ensures that processes continued uninterrupted and are completed on a prescribed schedule.

35. BENEFITS OF HAVING SOP’s Ensures that no failures occurs in manufacturing and other processes that would harm anyone. Serve as a training document for teaching users about the process of which the SOP is written. Serves as a checklist for auditors. SOP’s should serve as a strong basis when detailed audit checklists are developed. To serve as an historical record of the whole process which is done and have a basis of that when the process is changed. Serve as an explanation of steps in process so they can be reviewed in accident investigations. A good SOP gives a basis from which to being investigating accidents.

36. WRITING STYLE OF SOP’s SOP’s shall be written in a concise, step by step, easy to read and follow format. Information should not be complicated. The active voice and present verb tense should be used. Should be simple and short. Routine procedures that are short and require few decisions can be written using simple steps format. Long procedures consisting of more than 10 steps, with few decisions should be written along with graphical format or hierarchical steps. Procedures that require many decisions should be written along with flow chart. Requirement for document identification and control, accountability and traceability responsibility must be included with every SOP. This can be achieved by providing consistent format.

37. TYPES OF SOP’s

38. CONTENTS OF SOP’s 1. TITLE PAGE First page or cover page of each SOP should contain the following information. A title that clearly identifies the activity or procedure. An SOP identification number Date of issue and date of revision The signatures and dates of those individuals who prepared and approved the SOP. 2. TABLE OF CONTENTS To locate the information. To denote changes or revisions made.

39. 3. PROCEDURES The following topics are included:- Scope :- describing the purpose of process or procedure. Summary of Method Definitions :- identifying abbreviations, definitions. Health and Safety Warnings – indicating operations that could result in personal injury and loss. Cautions :- indicating activities that could result in damage and deterioration. Personnel Qualifications/Responsibilities :- including minimum experience the user should have to complete the task. Steps:- including the procedures to accomplish calibration, standardisation, sample collection, handling and preparation, data acquisition and calculations etc. Data and record management

40. 4. QUALITY CONTROL AND QUALITY ASSURANCE SECTION Designed to allow self verification of the quality and consistency of the work. Describes the preparation of appropriate QC procedures and materials that are required to demonstrate successful performance of the method. Describe the frequency of the required QC checks. 5. REFERENCE SECTION Documents that interface with the SOP should be fully referenced , such as related SOP’s, published literature, or methods manuals. Citations shall also be included.

41. SAMPLE OF A SOP

42. SOP PROCESS

43. 1. PREPARING A SOP EQUIPMENT MANUFACTURERS SAFETY PERSONNEL ENVIRONMENTAL PERSONNEL Technical Initiation, Performance the Maintenance on Equipment and the Job

44. 2. SOP REVIEW AND APPROVAL SOP’s should be reviewed by one or more individuals with appropriate training and experience with the process especially helpful if draft SOPs are actually tested by individuals other than the original writer before the SOPs are finalized.

45. 3. FREQUENCY OF REVISIONS AND REVIEWS SOP’s need to remain current to be useful. Therefore, whenever procedures are changed, SOP’s should be updated and reapproved. If desired, modify only the pertinent section of an SOP and indicate the change date/ revision number. SOP’s should also be systematically reviewed on a periodic basis, e.g. every 1-2 years, to ensure that the policies and procedures remain current and appropriate, or to determine whether the SOP’s are even needed.

46. 4. IMPLEMENTING SOP The most important step for implementing the SOP is in working area, train or retrain the user. Everyone should follow the procedure exactly with each and every step in detail, it is very important to train the user otherwise individual may interpret meaning in different ways. While training the user trainer should share the reason why, SOP must be performed correctly. People are much more to follow when they understand importance of procedure. Trainer should explain and demonstrate how each step in the SOP will be performed and should assure them this will increase quality of product by providing safety and accuracy which will ultimately increase the confidence of the user.

47. 5. MANAGEMENT OF SOP Organisation shall have SOP on preparation, approval, revision and control of SOP for better control and management of SOP’s. Generally, administrative aspects of the SOP system, such as distribution and filling are well managed. On other hand, overall system management, frequently characterized by the lack of a system owner, is generally poor. If a system owner exists at all, his or her responsibilities are limited.

48. QUALITY AUDIT

49. DEFINITIONS AUDIT :- An official inspection of an organisations accounts, by an independent body, to make sure that all departments are following a documented system of recording processes and transactions. QAULITY AUDIT :- is defined as a systematic and independent examination to determine whether quality activities and related results comply with planned arrangements, and whether these arrangements are implemented effectively and are suitable to achieve objectives.

50. Quality audit is an independent evaluation performed to review if activities are performed in a manner to comply with set objectives defined in the company’s quality system. Helps to uncover problem areas Timely correction of issues Provide confidence that the organisation is performing under effective control. Looks for outstanding emphasis on customer satisfaction Builds interdepartmental trust, understanding and communication Establish and monitor capability of supplier to deliver goods and services

51. PREPARATION OF AN AUDIT Define audit objectives Define audit scope Define audit resources Define audit criteria Prepare and distribute an audit notification to auditee Gather and understand relevant documents Prepare a work plan i.e. audit plan

52. PRINCIPLES OF AN AUDIT Ethical conduct :- foundation of professionalism, trust, integrity, confidentiality are essential to auditing. Fair presentation :- obligation to report truthfully and accurately Due professional care :- application of diligence and judgement in auditing. Evidence based approach :- the rational method for reaching reliable and reproducible audit conclusions in a systematic audit process.

53. INTERNAL AUDIT (IA) Internal audit requires the company to look into its own systems, procedures, activities so as to ensure that the company’s quality standards. IA is done by auditors who work for the company. Provides management with the information on whether or not their policies are being met, if the system is efficient and effective as it should be and whether any changes are needed. Internal Audit is also called as Self Inspection. Performed routinely as well as on special occasions. E.g. in the case of product recalls or repeated rejections. Activities carried out by different departments and Documents maintained by these departments are mainly audited in IA.

54. EXTERNAL AUDIT (EA) This is an audit that a company performs on its own suppliers or subcontractors External auditors are separate from the company, hired by a supplier or customer to ensure that the audited company meets their quality standards. External audits can be done by quality consultants specializing in the quality standards for those organisations. Ensures confidence in the partnership arrangement and the requirements are understood. Reduces the risk of failure

55. PRODUCT / PROCESS AUDIT PRODUCT AUDIT – a product quality audit verifies that a physical product meets design specifications and other quality measurements. The physical dimensions, product testing or destructive testing, checking the calibration and test equipment are measured to verify that the product meets quality standards. PROCESS AUDIT – a process audit verifies that a documented process meets quality standards. This process could be a manufacturing process or service process. An analysis of elements of a process and appraisal of completeness, correctness of condition and probable effectiveness are done to measure process audit.

56. REGULATORY AUDIT (RA) Audits are carried out by regulatory bodies against relevant regulations for the manufacture and supply of pharmaceutical products. National regulatory bodies, such as the Medicines Control agency (MCA) in United Kingdom, and FDA in the USA, are statutorily responsible for carrying out such audits. These audits may be announced as manufacturers are expected to be complying with GMP at all times. Regulatory inspectors are extensively trained and are knowledgeable and professional. They are relevantly qualified and have a minimum of five years experience. Failure to pass a regulatory audit can lead to restrictions or withdrawal of a manufacturing or import/export licence.

57. SYSTEM AUDIT – A documented activity performed to verify, by examination and evaluation of objective evidence, that applicable elements of the quality system are suitable and have been developed, documented, and effectively implemented in accordance with GMP. SECOND PARTY AUDIT – external audits done by a company that has an contract with the audited firm. THIRD PARTY AUDITS – external audits done by an organisation that has an contract with the company.

58. AUDIT LIFE CYCLE

59. METHODS OF AN AUDIT HORIZONTAL AUDITING:- involves examination of each functional area of an organisation to verify adequacy and implementation of quality. This is used for internal system auditing and second and third party assessment when it is necessary to establish if a quality management system has been installed and is being implemented and maintained. VERTICAL AUDITING:- involves examining functional areas of an organisation that are actively contributing to a specific work package or contractual requirement. RANDOM AUDITING:- e xamines the various aspects of an organisations operation as determined by the auditor and due to the need to closely examine a particular actively or generally probe the system in a random manner.

60. ELEMENTS OF AN AUDIT Expectations and philosophies Audit formats and approaches Written criteria and SOP Planned periodic frequency for audit Specially trained personnel Report audit finding

61. EXPECTATIONS & PHILOSOPHIES Senior management establishes the fundamental expectations of audit. Upper level management must establish the realistic goals and objectives. Use of formal written master plan approved by the management.

62. AUDIT FORMAT AND APPROACHES Manual GMP audit methods can be divided into following categories:- Checklist format- series of questions or instructions are grouped into logical order. Blocks may be used to record answer and space may be provided to make comments. GMP Regulation Format – basic elements which are subparts of regulation are :- organisation and personnel, buildings and facilities, equipments, production, processing and packaging records, lab controls, and records and reports. System Analysis Method- this method applies to potential problems likely to affect the quality of the product. These FDA investigators describe the organised method for determining the potential problems.

63. WRITTEN CRITERIA & SOP This has to be established defining which audit data or elements are to be considered in the assessment of program performance. Formal written SOP’s should fully describe the details for carrying out the various audit functions like: - responsibility for audit data review, personnel responsible for recommendation, decisions concerning corrective actions. Effective use of written criteria to ensure that conditions and practices are under suitable state of control. All SOP’s should be established.

64. PLANNED PERIODIC FREQUENCY Each firm must establish the optimum time interval between audits based on several important factors like :- intended purpose, objectives, scope and depth, prior history of audit finding Two types of visits can be done depending on the type of the audit:- announced and un-announced visit.

65. SPECIALLY TRAINED PERSONNEL All personnel's should be well trained about the factors that deserve systemic attention:- Defining audit or qualification Documentation training skills and experience Selecting audit teams Maintaining audit or awareness levels.

66. REPORT AUDIT FINIDNG Audit reports should contain complete details of the program detected. Corrective action is taken to eliminate problems and to measure the overall adequacy of the audit program. There are two important reporting phases:- Preliminary reports during the audit. Final report to the management.

67. QUALITY REVIEW (QR)

68. The USFDA requires that the quality standards of each drug product must be evaluated at least once a year. And these requirements can be met through the performance of a Quality Review. Quality Review is the evaluation of a given product’s quality to verify that the existing processes used in its manufacture are consistently producing the desired quality product. A representative number of batches must be selected, and a review must be done of the documents associated with them to check for adherence to specifications. Both approved and rejected batches must be a part of this study. Along with this, it is also important to evaluate any complaints received regarding the same product batches, or any returns or recalls that have been associated with those batches.

69. Quality Review includes the review of :- Starting materials Packaging materials Critical in-process controls Critical equipment qualifications Finished product test results Stability studies CAPA effectiveness Returns/recalls Change control procedures Market complaints Failed batches Previous batches reviews

70. SIGNIFICANCE OF QUALITY REVIEW Verify the consistency of the existing manufacturing process and minimize the risks to pharmaceutical products which will be helpful for the companies to develop their products consistently of best quality on yearly basis. Determines the quality and process defects. Determines improvements in the analytical methods and manufacturing process Reviews quality of raw materials and packing material used for the product. Indicates the area of potential risk. Based on the results of the review, revalidation or CAPA may be undertaken.

71. PHASES OF QUALITY REVIEW PHASE 1 – PREPARATION PHASE 2 – THE REVIEW MEETING PHASE 3 – THE FOLLOW - UP

72. PHASE 1 – PREPARATION This phase precedes the actual review meeting. It is the responsibility of the chairman and presenter to organise the quality review and notify all those invited.

73. PHASE 2 – THE REVIEW MEETING The central phase of the quality review process is the review meeting itself. During the review meeting, the emphasis should be on error detection, in line with the criteria, and only limited discussion of corrective action should occur.

74. PHASE 3 – THE FOLLOW - UP Following the quality review meeting, there should be a follow – up period during which the errors identified at the review that were committed to the follow-up action list are rectified and signed off.

75. QUALITY REVIEW ACCORDING TO REGULATORY AGENCIES EUROPEAN COMMISSION Quality review comes under EU guidelines to GMP QR is conducted with the objective of verifying the consistency of the process. Conducted and documented annually to include :- review of critical in-process control and API test, all batches that failed to meet specifications, critical deviations, any changes in the processes or analytical methods, all quality related returns, complaints, recalls and adequacy of corrective actions. Results should be evaluated and an assessment of whether corrective action or revalidation should be taken. Reasons of corrective action should be documented. Where no changes have been made, a QR confirms that the system is consistently producing meeting its specifications.

76. UNITED STATES 21 CFR states about general requirements for any production, control, or distribution and all the records related shall be retained for at least 1 year after expiry date and 3 years after distribution of a product batch. Written procedures shall be established and followed for :- a review of representative number of batches, approved or rejected, complaints, returned and recalled goods. :- to assure that the responsible officials are aware of their duties and they are done accordingly. Production record review states about all the complaint files related to the product. Reprocessing of any product shall not be done, without the review and approval of the quality control unit.

77. QUALITY DOCUMENTATION (QD)

78. Documentation plays a vital role in Quality Management System. Documents are mirrors that show the actual image of any pharmaceutical company. Defines the manufacturer’s system of information and control the minimization of the risk of misinterpretation and errors. Documentation is an essential part of Quality Assurance and is related to Good Manufacturing Practices. Personnel concerned with manufacturing should know the information to decide whether to release the batch or not for sale. Documents should be approved, signed, dated by appropriate and authorized person. Documents should be regularly reviewed and kept up to date and if any, alterations are made in their entry shall be signed with date.

79. QUALITY DOCUMENTATION HIERARCHY

80. QUALITY MANUAL Top tier in the hierarchy Outlines the companies goals, mission and vision High level document approved by the upper management. Completely explains each and every requirement of ISO 9001. Quality manual should include the following contents:- title and table of contents, scope of QMS, quality policy and objectives, QMS descriptions, To communicate management’s expectations for quality to the organisation. Includes the regulations to be followed by the company such as USFDA guidelines/ICH guidelines/ Schedule M requirements.

81. QUALITY POLICY A policy represents a declarative statement by an organisation. State the commitment of the organisation to quality and continual improvement. Defines the quality objectives to which the organisations strives. Policy should provide an outline for creating, stating, and measuring the performance of the quality objectives.

82. QUALITY PROCEDURE Describes how the quality system will be implemented, methods to be used, who should do what, when, and where. Quality procedures can have different formats and structures. Quality procedures should include :- title, purpose, scope, responsibilities and authorities, records, document control (identification of changes, date of review, approval), description of activities (elements of procedures)

83. QUALITY WORK INSTRUCTIONS Specific to departments, and spell out details of how each task is to be done. Detailed instructions are given, and may include diagrams, job sheets etc. In the pharmaceutical industry, this is represented by SOP’s. Work instructions includes :- the manner in which the work will be done, equipment and tools used, environment associated with work, material handling requirements, safety alerts for employees, critical process and product parameters, methods for verifying that the product meets specifications.

84. QUALITY RECORDS Final tier in the quality documentation system. Quality records are objective evidence to prove that the quality policy, procedures and work instructions have been implemented as directed. In the pharmaceutical field, this includes batch manufacturing records, QC test reports, validation documents etc.

85. RECORDS & DOCUMENTS

86. Documentation and records used throughout the manufacturing process, as well as supporting processes must meet the basic requirements of Good Documentation Process. These requirements include:- Batch record forms, bills of materials Specifications, protocols and policies SOP’s, work instructions, checklists, forms, log sheets Certificate of analyses or compliance Technical transfer reports, agreements, and reports Validation document, validation protocol and reports, test methods, training assessments, confidentiality agreements Audit plans, quality manual, quality system related documents Electronic and hard copy quality records Personnel related documents, facility related documents, test material documents, manufacturing and packaging instructions.

87. Laboratory Control Records should include complete data derived from all tests conducted to ensure compliance with established specifications and standards i.e. it may include the following:- Description of samples received Statement of reference method used Statement of weight or measure of sample Complete record of all raw data generated Record of all calculations Statement of test results Signature of the person who performed the test Any modification, or any periodic calibration of instruments All stability test Out of specification investigations

88. Batch Production Record Review Written procedures should be established and followed for the review and approval of batch production to determine the compliance of the intermediate or API with established specifications before a batch is released or distributed. All deviation, investigations, out of specifications reports should be reviewed as part of the batch record review before the batch is released. Distribution Records should be maintained and must include, the batch number, quantity produced, name, address, and contact details of customer, quantity supplied, and the date of the supply.