Good Documentation Practices

1. Good Documentation Practices By Mr.Vikram Joshi vikram.joshi@ranbaxy.com

2. “ Quality is never an accident, it is the result of high intention, sincere effort, intelligent direction and skillful execution. It represents the wisest of many alternatives”.

3. DOCUMENTS: - • As discrete packages of recorded information are the tools of quality assurance. • Used to establish standard specification and processes that assures compliance with standard specifications and processes • Quality can not be assured in a regulated industry without good documents and good documentation practices • A document system is an interdependent, interrelated set of documents, each with a defined purpose and a consistent format. • Documentation is a process that involves the systematic interaction of people, events and documents to create the records of the organization / corporation.

4. PURPOSE OF DOCUMENT SYSTEM • “Each manufacturer shall establish effective quality system, instructions and procedures in accordance with the requirements of this part and maintain the established quality system instructions and procedures effectively. • No matter what type of product is developed and produced, it must be safe, effective and fit for its intended use. • Quality characteristics are established in documents. • Documents declare product standards and describe how to monitor, test and judge for compliance with these standards.

5. BASIC REQUIREMENTS FOR ASSURING THE QUALITY • Establish the quality. • Determine which attributes of the resources, process or product are critical to product use or performance. • Chose quality parameters and test methods that are scientifically rigorous and then document them • Maintain the Quality / Monitor the quality Established quality system parameters to be met routinely and asssure control is effective

6. BASIC REQUIREMENTS FOR ASSURING THE QUALITY Manage Charge: • Recording the change and providing appropriate rationale in writing for that change Evidence: • Have written evidence of the established quality standards, of the maintenance and monitoring programs, of the monitoring data and of any changes that occur

7. DOCUMENT SYSTEM BASICS • A document system is an interacting set of documents, each with a defined purpose and consistent document. • The documents can: • Assure that quality standards are consistently met • Communicate these standards to all who interact with product • Interact in a manner that reduce redundancy and increase the flexibility of the system when changes occur

8. A DOCUMENT SYSTEM OF YOUR OWN • The types of documents, number of documents and the level of detail in documents will vary from company to company depending on the following: • The type of product (its classification of risk) • The unique nature of the product, the product delivery system or the manufacturing process • The size of the company • The education and training of the employees • How much the company does (Develops, manufactures, packages, distributes products) • Keep the expectations in corporate documents simple and relevant, make them your own

9. What is Documentation ? To Document each Activity you perform Is it True ? • No, Documentation is a Process, Which comprises of Following : • Recording of Data • Review of Documents • Approval of Documents • Issuance and Disposal of Documents • Retrievability of Documents • Presentation of Documents

10. What is Documentation • The information provided by a creator which provides enough information to establish basis, history and context and to enable its use by others. • It needs to be sufficiently detailed to allow the data creator to use the material in the future, when the data creation process has started to fade from memory. • It also needs to be comprehensive enough to enable others to explore the resource fully, and detailed enough to allow someone who has not been involved in the data creation process to understand the data collection and the process by which it was created."

11. Good Documentation Practices • Just creating documents is not enough; you must follow specific standards when doing so. Following established practices allows everyone who reads your documentation to understand exactly what you mean. • Key documents with the potential to impact product quality must be retained to provide a traceable, historical record of all activities. Documentation must be readily retrievable in order to meet requirements associated with product investigations, periodic product review, or formal audits • It is necessary to document anything that directly impacts a product. Record every procedure you write, form you fill out, and test you perform. Using a standard format eliminates discrepancies between documents from different sources.

12. ESSENTIAL CHARACTERISTICS To design an effective & efficient documentation process first identify the important characteristics of processing event. • The document directing the manufacturing event fulfills current regulatory commitments to the agency; it is appropriately written, reviewed and approved • The directive document is appropriate for the task to be performed • The data is authentic; the individual responsible for performing the work has entered the data on an appropriate data collection document • The data is accurate • The data is complete. There is no missing information, and there is no work as yet uncompleted that will impact the occurrence of the data presented.

13. ESSENTIAL CHARACTERISTICS • The data is legible, consistently recorded and trustworthy • The data collected fulfills expectations (specifications) • The data is accessible to those who need to review it, audit it or use it to perform trending analysis. • The original data and the original documents (manufacturing record) is retrievable for review or audit • The original manufacturing record is secure Proper control of documentation also requires that responsibility for each processing step to be assigned “All documentation should be legible, clean, readily identifiable, retrievable and maintained in facilities that provide a suitable environment to minimize deterioration or damage and to prevent loss”

14. DOCUMENTATION LIFE CYCLE • Document creation, Review Approval: - Authorized document review and approval signatures are responsible for directing the manufacturing, the security, original, approved documents is the responsibility of QA. • Document use & Data collection: - Responsibility of all technicians, engineers, scientists, operating persons who are trained and authorized to collect and record data • Data Verification: - Responsibility of suppervisors, managers and all individuals trained & authorized to review data • Record Review & Product disposition / Approval: - Responsibility of QA or those trained & authorized to review records

15. DOCUMENTATION LIFE CYCLE • Record Achieving:- Records are Accessible, Retrievable, Secure is the responsibility of QA & relevant departments • Record Destruction: - As per SOPs that directs the destruction of documents Every signature associated with documents review & approval, data collection and record review and approval should add value to the document. Every one who signs a document or a record should know what their signature means. Only those individuals trained and authorized to sign documents should sign them.

16. Why Documentation • There is a saying in the pharmaceutical industry: 'if it hasn't been documented, then it hasn't happened!' • Good documentation practice constitutes an essential part of the QA system. • Documentation system must be proactive vehicle of communication. Your documentation is an advertisement for your work.

17. WHY DOCUMENTATION ? Cost for Good Documentation Cost for Poor/No Documentation THEREFORE, DOCUMENTATION BRINGS BUSINESS

18. Here are some selected GDP references from 21CFR58: • All data generated during the conduct of a study, except those that are generated by automated data collection systems, shall be recorded directly, promptly, and legibly in ink. • All data entries shall be dated on the date of entry and signed or initialed by the person entering the data. • Any change in entries shall be made so as not to obscure the original entry, shall indicate the reason for such change, and shall be dated and signed or identified at the time of the change.

19. WHERE DOCUMENTATION ? • Documentation during Project Design, • Documentation during Construction Phase, • Documentation during Commissioning and start-up, • Documentation during Qualification and Validations • Documentation during Commercial Production, • Documentation during Testing and Release, • Documentation for Regulatory submissions. • Documentation beyond………...

20. Types of Documents There are three types of Documents • Commitment Documents : Relationship between industry and the regulatory authorities • Directive Documents : Relationship between the Management and Employees • Record Documents : Relationship between the Employees and the Work they perform

21. Some Examples are : • Commitment Documents : New Drug Applications (NDAs), Drug Master Files (DMFs) etc. • Directive Documents : Specifications, STPs, SOPs, MPRs etc. • Record Documents : Protocols, BPRs, Log Books, Calibration Records etc.

22. DIRECTIVE DOCUMENTS • Working documents that establish the standards for resources, processing, products & quality system • Describe how to do it……??? • Describe how to do routine work • Several types of directive documents • The different types are determined by the specific, functional purpose of the document in the document system • In order to facilitate the development, production, testing and distribution of a product in a defined manner • Reviewed and approved by both management and the individuals responsible for performing the work

23. COMMITMENT DOCUMENTS • Presents corporate goals, expectations and standard of practice • Describes what to do • Consensus of purpose, direction and authorization for projects • Organize the work in a manner that assures efficient and effective work flow • Commitments documents can also be written to establish internal commitments. • These documents such as master plans; organize and prioritize the work in a manner that supports good business practice as well as regulatory compliance

24. COMMITMENT DOCUMENTS • Written to lead and guide the work and workers • To be used as active documents that are consulted and followed routinely • Content must be consistent and rigorous in order to lead and guide the work and the workers • Must describe the work as it will be done • Deviations from regulatory submissions can have signification impact on product quality • Any deviation must be documented and managed

25. What Good Documentation requires : • APPROVAL - 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

26. What Good Documentation requires : • CLARITY - 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

27. What Good Documentation requires : • REGULAR REVIEW AND UPDATE - 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!

28. What Good Documentation requires : • FORMAL PRESENTATION - controlled documents should be prepared in accordance with a written procedure, now a days probably using a computerised documentation control system.

29. What Good Documentation requires : • Records 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.

30. What Good Documentation requires : • 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:

31. Strengths of Good Documentation • Clear Objective of the document • Clarity of Scope • Who should prepare ? Should know ? • Layout of the document in mind • Put pieces together • Explain the activity performed logically • Use short, simple, easy to understand sentences

32. Strengths of Good Documentation • 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 Get your document edited by an expert

33. What are our Major Documents • CCIFs • Failure Investigation & Reports • Planned & Unplanned Deviation Reports • Filling of BPRs • APRs • Validation Protocols & Reports • Raw Data & proper Recording • Log Sheets • Sketches - Diagrams - P&Ids – Schematics • Plant Development Reports • Engineering Documents

34. CCIFs • Incomplete Forms / columns • Justification for change not in line with the changes proposed. • Attachments accompanying the CCIF : • Not attached in sequence • Total no. of pages not mentioned • All annexures not referenced on the CCIF • Annexures do not have reference of CCIF • Unsigned annexures • Items which are not required are left blank (“Not required” to be entered)

35. OOS • Many OOS Results unreported, therefore no investigations • Investigations not thoroughly performed • Investigation should lead to assignable reason, at least probable reasons • Report should include back-up notes on points covered during investigation • Follow SOP on Investigation of OOS result(s)

36. Filling of BPR • Missing signatures & dates • Over-writing without correction, sign, date • No remarks for correction • Control Number not recorded correctly • Time/Date and PC Number recorded in BPR not matching with in-process production Log Books BPRs are the first major Exhibits reviewed by FDA

37. DOCUMENTATION: PROCESSING & CONTROL The documentation process defines the relationship between the corporation and regulatory authorities. (Commitment Documents) • Corporate management and the workers (Directive Documents) • The workers and the work that they perform • The record of the events directed in directive documents is evidence • Records can be used as evidence against a company by FDA- in court

38. DOCUMENTATION: PROCESSING & CONTROL • Evidence can be used by a company to defend it self in court • The quality of the documents can be directly and adversely affected by the quality of the document processing procedures that directs • creation, review, approval, distribution, change and archiving of documents • Every person must be trained to complete documents properly; improper use of the documents can lead to inaccurate, inadequate or incomplete documents

39. The Resources and raw materials of the documentation processes are as follows:- • Directive documents that provide instructions • Data collection documents that provide a format for data collection • Data or information observed or collected from processing events • Operating personals or scientists who have been trained to follow instruction and collect data • Quality of these resources and materials must be assured • These resources / raw materials interact in a systematic manner • Data is collected according to an established process

40. The Resources and raw materials of the documentation processes are as follows:- • To produce the final product data document • Quality of interaction of these resources that can have the greatest impact on the quality of final documentation • Proper design and control of this documentation process is essential • Many things that can go wrong, when moving hundreds of documents through the documentation process • Process controls are added to assure the integrity and reliability of the documentation process

41. Controls are either industry standard or corporate –based controls that help assure efficient and effective processing.

42. DOCUMENT PROCESSING PROCEDURES TO BE SURVEYED • Why are delays occurring? • Is there redundancy in the system?Do records disappear? • Are documents inconsistently completed? • Has the product been released with records missing? Note:- More Control does not necessarily lead to greater order or more security.

43. Following is a list of concerns when designing documented processing control: - • When documents or records are transferred from one department to another or from one building to another the transfer should be recorded • When documents or records are waiting to be processed, they should always be stored in designated location. Apply the same principles to the security of documents during review process • Critical processing steps should be checked include document issue, data collection, document review. More review signatures on a document does not necessarily result in a more through review

44. Records must always be completely identified and this identity should be consistent and easily available. • Every page of every document should be consistently labeled with the document identification number/ code, the document revision number/code, the product identification number / code and product lot number. • Every signature associated with document review and approval should add value to the document • Every one who signs a document or record should know what their signatures means

45. Only those individuals trained and authorized to sign documents should sign them • It remains a challenge in normal systems to know who is trained and authorized to sign what document Note: - This is a fundamental quality assurance requirement for the processing of documents • Databases should be qualified or validated • There should be procedure in place to direct the data entry process

46. Here are some selected GDP references from 21CFR211: • To assure uniformity from batch to batch, master production and control records for each drug product, including each batch size thereof, shall be prepared, dated, and signed (full signature,handwritten) by one person and independently checked, dated, and signed by a second person. • An accurate reproduction of the appropriate master production or control record, checked for accuracy, dated, and signed; • The initials or signature of the person who performs each test and the date (s) the tests were performed... The initials or signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards... Complete records shall be maintained of any modification of an established method employed in testing. Such records shall include the reason for the modification and data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method.

47. Example of typical guidelines found in Good DocumentationPractices/Recordkeeping procedures: • All entries must be clear and legible • Never make erasures or writeovers. Any written error must be crossed out in such a manner that the original information is still legible. Do not scribble out or "whiteout" entries. Thus, the integrity of the record will not be in question. • The crossed out section must be initialed and dated by originator. Corrections must be made adjacent to the deleted entry. • Data may be attached to the page, however, it must be firmly attached. Label, sign and date the attachment. The location of the attachment in the record is indicated with "bridging". Approved methods of bridging are cross hatching or signing across the edge of the attachment and page.

48. Example of typical guidelines found in Good DocumentationPractices/Recordkeeping procedures: • When portions of a page or a complete page remain unused, a single line must be drawn angularly across the unused portion. Sign and date the crossed out section and provide an explanation when necessary. This is not applicable to blank portions on preprinted documents such as MBRs. • Use only black or blue permanent ink. The ink should not run or smear if the record is splashed with liquid. Pencil is not acceptable, since all entries must be permanent and able to be photocopied. • Make the required entries on the record as the work is performed. Do not record information on a separate piece of paper and enter on the record later • All planned and unplanned deviations from the approved production procedure or testing/inspection plan as described in GMP controlled documentation must be documented using a Discrepancy Report. The DR# should be indicated in the record at the location of the change.

49. Example of typical guidelines found in Good DocumentationPractices/Recordkeeping procedures: • Use correct rounding off procedures and significant figures • When a comment or explanation is required, make all statements objective. Avoid personal comments and opinions. • When dating a signature, use the actual day the signature was signed. • If the activity being recorded occurs on more than one day, the record must clearly indicate where the "break" occurred. This can be accomplished by drawing a horizontal line through the procedure at the break" and indicating the new date or making entries that are initiated and dated appropriately. • If a record becomes messy and extremely difficult to read, do not discard. Consult supervisor prior to transcribing the data to a clean record sheet and attaching the original record sheet. Provide an explanation for the transcription.

50. SUMMARY • Documentation must be consistent and systematic • Documentation practices must assure that records meet GMP requirements • Documentation process must be controlled to minimize redundancies in the work flow