Pharmaceutical documentation himanshu

B PHARMA 6TH SEM
PHRAMACEUTICAL QUALITY ASSURANCE
Pharmaceutical documentation
Need of documentation
Objectives of documents
Scope
Documentation lifecycle
Types of documents
Characteristic of document
Documentation review
Documents model
Standard operating procedures (sop’s)
Master formula record
Batch formula record
Quality audit plan and reports
Specification and test procedures

1. PHARMACEUTICAL DOCUMENTATION 1 Himanshu Kamboj Assistant Professor

2. CONTENTS 2 Introduction Need of documentation Objectives of documents Scope Documentation lifecycle Types of documents Characteristic of document Documentation review Documents model Standard operating procedures (sop’s) Master formula record Batch formula record Quality audit plan and reports Specification and test procedures

3. The 10 golden rules of GMP 3

4. INTRODUCTION 4 Documentation is the cornerstone of any company’s quality management system and is an essential GMP requirement. It is critical that anyone dealing with GMP documents and documentation systems understand the regulatory requirements and adopts best practice. It defines a system of information and control so that risks inherent in misinterpretation and/or error in oral communication are minimized .

5. NEED OF DOCUMENTATION 5 Mandatory as per regulatory guidelines Keep track of activities Evidence to face legal issues Maintains a historical record

6. OBJECTIVES OF DOCUMENTS 6 To define the 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 the information necessary to decide whether or not to realize a batch of a drug for sale. To ensure the existence of documented evidence, trace ability, and to provide records and an audit trail that will permit investigation. It ensures the availability of the data needed for validation, review and statistical analysis.

7. SCOPE Good documentation encompasses practically all the aspect of pharmaceutical production: Building And Premises: Installation, Validation , Cleaning And Maintenance Personnel: Training, Hygiene Etc Equipment : Installation , Calibration , Validation , Maintenance , Cleaning Materials : Specification, Testing, Ware-housing, Use, Rejection/Disposal. Processing : Individual Steps In The Process Of Manufacturing Including Controls Thereof. Finished Goods: Specifications, Testing, Storage, Distribution, and Rejection/Disposal. 7

8. DOCUMENTATION LIFECYCLE 8

9. TIERS OF DOCUMENTATION(ISO 9001:2008) 9

10. Types of documents 10 Quality manual L ogbooks Specifications Test methods Standard operating p r oce d u r es (SOPs) Polic i es Batch records

11. CHARACTERISTIC OF DOCUMENT 11 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.

12. “Where the documents carry instructions” 12 The instructions shall be precise and not ambiguous. They shall be for each individual step and not combined. E.g. Weigh the materials; charge the weighed materials into the blend (iii)Instructions shall be in imperative mood.

13. “Where entry of any data is expected” 13 Sufficient space shall be provided for making the entry. Heading shall clearly indicate what is to be entered, and who is responsible. All entries shall be in ink. All entries shall be clear and legible. Person making the entries shall confirm the entry by initialing/signing the same. An error in entry shall be so corrected that the original (wrong) entry is not lost. Such correction shall also be initialed and dated. Where necessary, reason for correction shall also be recorded, initialed and dated

14. DOCUMENTATION REVIEW Documentation system should provide for a periodic review, and revision, if necessary, of any document, or part thereof. Such revised versions shall also be approved by the authorized persons. Updated/revised versions shall also be superseding the previous edition, and the document shall clearly indicate this. Outdate/superseded document shall be immediately removed from active use, and copy retained only for reference. 14

15. ELECTRONIC DATA 15 If documentation is through electronic data processing system (computerized system) there shall be adequate, reliable systems in place: To check and ensure correctness of data. To record changes (addition/deletion) That meets other regulation requirement, if any

16. “DOCUMENTS” MODEL 16 D = Design, development, deviations, dossiers and Drug Master Files for regulated markets, distribution records O = Operational procedures/techniques/methods, Out of specifications (OOS), Out of trend (OOT) C = Cleaning, calibration, controls, complaints, containers and closures, contamination and change control U = User requirement specifications, utilities like water systems, HVAC, AHU etc. M = Man, materials, machines, methods, maintenance, manufacturing operations and controls, monitoring, master formula, manuals (quality, safety and environment), medical records E = Engineering control and practices, Environment control, Equipment qualification documents N = Non-routine activities, New products and substances T = Technology transfer, training, testing, Trend analysis, Technical dossiers supplier qualification, S = SOPs, safety practices, sanitation, storage, self-inspection, standardization, specifications and standard test procedures and site master file

17. STANDARD OPERATING PROCEDURES (SOP’S) 17 A typical Pharmaceutical Industry has an average of 1200- 1300 SOPs. A Parenteral Drug Association (PDA) survey found that a typical pharmaceutical company must manage an average of 1250 SOPs. A Standard Operating Procedure (SOP) is a set of written instructions that document a routine or repetitive activity which is followed by employees in an organization. The development and use of SOPs are an integral part of a successful quality system. It provides information to perform a job properly, and consistently in order to achieve pre-determined specification and quality end-result .

18. BENEFITS OF SOP 18 To provide people with all the safety, health, environmental and operational information necessary to perform a job properly. To ensure that production operations are performed consistently to maintain quality control of processes and products. To ensure that processes continue uninterrupted and are completed on a prescribed schedule. To ensure that no failures occur in manufacturing and other processes that would harm anyone in the surrounding community To ensure that approved procedures are followed in compliance with company and government regulations. To serve as a training document for teaching users about the process for which the SOP was written To serve as a checklist for co-workers who observe job performance to reinforce proper performance. To serve as a checklist for auditors. To serve as an historical record of the how, why and when of steps in an existing process so there is a factual basis for revising those steps when a process or equipment are changed.

19. SOP PROCESS 19 Preparation Review and Approval Frequency of Revisions and Reviews Checklists Document Control D o cument Tracking and Archival

20. “How to write?” 20 OBJECTIVE: To lay down procedure for the preparation of Standard Operating Procedures. SCOPE: This procedure is applicable to all the SOP’s throughout the organization. RESPONSIBILITY: Person Performing: Respective HOD’s of concerning departments Person Monitoring: QA officer/ HOD QA PROCEDURE: All SOP’s shall be computer typed using Times New Roman font.

21. “How to write?” 21 Format of SOP shall be as per Annexure SOP/QA/002/1. Each SOP has: Header, Signature block and Body Header: Present on all the pages of SOP and includes Company Logo, Name, address & Concerned Dept.: Company Logo, CHARAK Pharma Limited, Wagholi-Pune & Name of Concerned Department.

22. “How to write?” 22 Document Type : STANDARD OPERATING PROCEDURE (In capital bold letters of font size 14) Ref. No.: It is like SOP/DC/YYY-Z Where DC depicts the department code as below: PE: Personnel Department PD : Production Department MT : Maintenance Department QA : Quality Assurance Department QC : Quality Control Department ST : Store Department PU : Purchase Department YYY is the sequential number starting from 001 for each department. And Z is the revision status, starting from 0 for the original version and 1 for the next version and so on. (In capital letters of font size 12).

23. “How to write?” 23 Supersedes : It is the Ref. No. of the earlier version. (In capital letters of font size 12). Effective Date : It is the date from which the SOP shall be put in use. The date format has to be DD/MM/YYYY, where DD indicates the date, MM indicates the month & YYYY indicates the year (e.g. 01/11/2007). Date shall be written with blue indelible ink pen. Review Date: It is the Month & Year during which the SOP shall be revised e.g. 21/2013, written with blue indelible ink pen. It shall be maximum 2 years from the effective date. Page No.: It is like X OF Y. Where X is the individual page number and Y is the total number of pages. (In capital letters of font size 12)

24. “How to write?” 24 Title : It shall be clear and descriptive. (In bold capital letters of font size 12). Signature Block: It shall be below the header and only on the first page of the SOP. (Titles in the rows & columns shall be in bold letters & other text in normal letters of font size 12. Name and designation shall be typed. And signature and date shall be put in blue indelible ink pen) Prepared by: Signature with date, name and designation of the person from user department who has drafted the SOP. Verified by: Signature with date, name and designation of the HOD or the person from user department who has verified the draft of the SOP. Authorized by: Signature with date, name and designation of the person authorizing SOP, DGM QA or HOD QA.

25. “How to write?” 25 BODY : It shall contain the subject matter, which is written in the following manner. (Subtitles in capital bold letters and text matter in normal letters of font size 12). Objective: It shall define the purpose of the SOP. Scope: It shall define the area of application. Responsibility: It shall specify the person responsible for carrying out and monitoring the activity as per the SOP.

26. “How to write?” 26 PROCEDURE : It shall give all steps required by the process in a proper sequence and instructions to be followed while carrying out the activity so as to achieve the desired goals. Procedure shall be: Logically lay out. Written in the imperative (authoritative) tense. User friendly. Simple to understand and in plain unambiguous English. To the point with no unnecessary information. In standardized terminology.

27. “How to write?” 27 ABBREVIATION: This shall include list of abbreviations used and their meaning. ANNEXURE: This shall include list of annexure attached. REFERENCE: This shall include list of reference documents. ABBREVIATION: HOD : Head of the Department SOP : Standard Operating Procedure. QA : Quality Assurance DGM : Deputy General Manager ANNEXURE: Annexure – SOP/QA/002/1 - ‘Standard Operating Procedure’ Form. REFERENCE: SOP issuance logbook Standard SOP format.

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29. MASTER FORMULA RECORD 29 Master formula record (MFR) is a master document for any pharmaceutical product. It contains all information about the manufacturing process for the product. MFR is prepared by the research and development team of the company and all other documents like BMR and BPR (Batch packaging record) are prepared using MFR by the manufacturing units .

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31. PREPARATION OF MFR 31 Product details Flow chart Equi p ment S p ecial instructions Calculations M anufacturi ng process Pac k a g ing process Yield

32. BATCH FORMULA RECORD 32 A batch manufacturing record is a document designed to provide a complete record of the manufacturing history of a batch of product. The US Food and Drug administration defines a batch as “a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture”.

33. PREPARATION OF BMR 33 They normally contain information that relates to the following aspects of the manufacture of a batch of product: Dates of start and finish of manufacture. Lists all materials used and amounts of each used. Lists of packaging materials used. Details of the steps completed in the manufacturing process and times of completion. 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. Quality Control information.

34. QUALITY AUDIT PLAN AND REPORTS 34 Conducting internal audits (self inspections) and external audits of suppliers and outsourcing operations are key elements of a good quality system. One aspect of a quality system that is identified in the recently released International Conference on Harmonisation (ICH) Q10, “Pharmaceutical Quality System”, and in other quality system standards such as ISO 9001 , is that of conducting audits as a means of evaluating compliance with the objectives of the quality system. Implementation of the quality management system model defined in ICH Q10 should result in achievement of the three main objectives stated in ICH Q10: Achieve product realization , establish and maintain a state of control , and facilitate continual improvement .

35. Documentation and communication 35 The audit results should be documented and communicated to management. The method of documentation and communication including the security and confidentiality of the audit reports should be defined in the procedure. It is important to remember that those responsible for the audited operation should always receive a copy of the report, including outsourcing management and supplier management. Such reports should clearly describe the audit team observations including specific examples when possible. If commitments have been made to implement corrective actions, such commitments should be included in the report. Security of audit reports should be strictly enforced and distribution of the report should be limited. When providing audit reports to external sources such as outsourcing companies or suppliers, a subset of the internal report may be provided as long as the observations are included

36. SPECIFICATION AND TEST PROCEDURES 36 A specification is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described . It establishes the set of criteria to which a drug substance or drug product should conform to be considered acceptable for its intended use. "Conformance to specifications" means that the drug substance and / or drug product, when tested according to the listed analytical procedures, will meet the listed acceptance criteria. Specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities as conditions of approval.

37. Periodic or skip testing 37 Release vs. shelf-life acc e pta n c e criteria In-process tests Design and development c o nsid e r at i o ns Limited data available at filing Pa r ame tr ic release Alt e r na tiv e p ro c e d u r e s Pha r ma c op o e ial tests and acceptance criteria Evolving t e c hn o l o gie s Ref e r e n c e standard

38. PROTOCOLS AND REPORTS 38 A protocol is a written statement to conduct the process along with the procedure, test method, equipment handling, specifications, acceptance criteria, report and approval. The report summarizes all results, gives recommendations for fixing errors and/or improving the overall quality of the speech corpus and gives an executive summary.

39. DISTRIBUTION RECORDS 39 Distribution forms an important activity of the integrated supply chain management of pharmaceutical products. Various persons and entities are often responsible for the handling storage and distribution of such products. The guidelines are intended to apply to all steps in the entire distribution/supply chain Permanent information, written or electronic, should exist for each stored product indicating recommended storage conditions, any precautions to be observed and retest dates. P h armac op o eia l requi reme n ts a n d c u rr en t n ati o n a l reg u lat i o n s c o n cer n i ng l abels a n d containers should be respected at all times. P r o c edure s s h o u ld be i n pla c e for t e m p eratu r e mapp i n g, sec u r i ty servi c e s at the warehouse, destruction of unsaleable stocks and on retention of the records.

40. ELECTRONIC DATA 40 Electronic data can stand for data in general that is exchanged via electronic communication lines digital data in particular Data (computing), i.e. computer - processable data as opposed to executable code The Pharmaceutical industries are in a highly regulated environment, hence it requires effective document management processes. Having timely accurate data is critical for the success of any company. Data has never been easy to manage, and is especially true in pharmaceutical industry. Note that electronic information includes everything such as emails, adverse event reports, complaints, batch records, quality control records - everything that is stored electronically. Several technologies are being used currently in pharmaceutical industry to manage their huge volumes of data generated on daily basis.

41. THANK YOU 41