Computer system validations

computer system validation
Good automated Pratices
GAMP5-Quality risk managment

1. Computerized system validation Presenter: Amruta Balekundri M.Pharm 2 nd semester, Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi. 1

2. CONTENTS Computerized system validation Electronic records and Digital signatures as per CFR 21 part 11 GAMP GAMP 5 --Quality Risk Management 2

3. Computer System Validation(CSV) Computer system installed in the corporations are validated to assure that: 1.Systems are developed according to quality software engineering principles. 2 . Systems meet the business needs of their users 3 . Continue to operate correctly and reliably throughout their life cycle. we can say that CSV provides documented proof that the system (e.g. hardware, software, peripherals and networks) will repeatedly and reliably do what it is designed to do, is “fit-for-purpose”, and complies with the applicable rules and regulations 3

4. Regulatory Requirements In 1983, FDA published a guide to the inspection of Computerized Systems in Pharmaceutical Processing, also known as the ‘bluebook’ (FDA 1983). FDA introduced 21 CFR Part 11 for rules on the use of electronic records and electronic signatures (FDA 1997). Part 11 applies to electronic records and electronic signatures that persons create, modify, maintain, archive, retrieve, or transmit under any records or signature requirement set forth in the Federal Food, Drug, and Cosmetic Act, the Public Health Service Act (PHS Act), or any FDA regulation. 4

5. What is 21 CFR Part 11? 21 CFR Part 11 : Allow the industry to use electronic records and signatures alternatively to paper records and hand-written signatures 21 CFR Part 11 applies: - To all FDA regulated environments - When using computers in the creation, modification, archiving, retrieval or transmission of data or records To records required by predicate rules – GLP, GCP, GMP – that impact patient safety. 5

6. Purpose of Part 11 Ensure data is not corrupted or lost. Data is secure. Approvals cannot be repudiated(rejected). Changes to data can be traced. Attempts to falsify records are made difficult and can be detected. 6

7. PART 11 ELECTRONIC RECORDS ELECTRONIC SIGNATURES : Subpart A--General Provisions 11.1- Scope. 11.2 - Implementation. 11.3 - Definitions Subpart B—Electronic Records 11.10 - Controls for closed systems. 11.30 - Controls for open systems. 11.50 - Signature manifestations. 11.70 - Signature/record linking. 7

8. PART 11 ELECTRONIC RECORDS ELECTRONIC SIGNATURES : Subpart C--Electronic Signatures 11.100 - General requirements. 11.200 - Electronic signature components and controls. 11.300 - Controls for identification codes/passwords 8

9. 11.1 Scope a) electronic records to be trustworthy, reliable, and generally equivalent to paper records. b) records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted, c) electronic signatures to be equivalent to full handwritten signatures, initials, and other general signings ,effective on or after August 20, 1997. d) Electronic records may be use in lieu(instead) of paper records e) Computer systems (including hardware and software) 9 Sub part A General provisions

10. 11.2 Implementation. For records required to be maintained but not submitted to the agency. For records submitted to the agency 1) The requirements of this part are met 2) document to be submitted have been identified in public docket No. 92S–0251 10 Sub part A General provisions Sub part A General provisions

11. 11.3 Definitions Agency means the Food and Drug Administration. Biometrics means a method of verifying an individual’s identity based on measurement of the individual’s physical feature(s) or repeatable action(s) where those features and/or actions are both unique to that individual and measurable . Closed system means an environment in which system access is controlled by persons who are responsible for the content of electronic records that are on the system. 11 Sub part A General provisions

12. 11.3 Definitions Digital signature means an electronic signature based upon cryptographic methods of originator authentication, computed by using a set of rules and a set of parameters such that the identity of the signer. Electronic record means any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system. Open system means an environment in which system access is not controlled by persons who are responsible for the content of electronic records that are on the system. 12 Sub part A General provisions

13. 11.10 Controls for closed systems Controls designed to ensure the authenticity, integrity and, when appropriate, the confidentiality of electronic records a) Validation of systems b) Accurate and complete copies c) Protection of records by ready retrieval d) Limiting system access e) Audit trails 13 Sub part B Electronic Records

14. 11.10 Controls for closed systems f) Operational system checks g) Authority checks h) Device (e.g., terminal) checks Education, training, and experience J) Written policies K) Documentation Distribution of, access and system operation and maintenance. Revision and change control. 14 Sub part B Electronic Records

15. a)Validation of systems Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discover invalid or altered records. 15 Sub part B Electronic Records Sub part B Electronic Records

16. b) Accurate and complete copies The ability to generate accurate and complete copies of records in both human readable and electronic form suitable for inspection, review, and copying by the agency. Persons should contact the agency if there are any questions regarding the ability of the agency to perform such review and copying of the electronic records. 16 Sub part B Electronic Records

17. c) Protection of records by ready retrieval Protection of records to enable their accurate and ready retrieval throughout the records retention period. d) Limiting System Access Limiting system access to authorized individuals 17 Sub part B Electronic Records

18. e) Audit Trails Use of secure, computer-generated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify, or delete electronic records. Record changes shall not obscure previously recorded information. Such audit trail documentation shall be retained for a period at least as long as that required for the subject electronic records and shall be available for agency review and copying. 18 Sub part B Electronic Records

19. f) Operation Check Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate. Empower 3 software uses Wizards to ensure proper sequencing. New Project Wizard Processing Method Wizard Sample Set Method Wizard Backup Project Wizard Restore Project Wizard 19 Sub part B Electronic Records

20. g) Authority Check Use of authority checks to ensure that only authorized individuals can use the system, electronically sign a record, access the operation or computer system input or output device, alter a record, or perform the operation at hand. 20 Sub part B Electronic Records

21. h) Device Check Use of device (e.g., terminal) checks to determine, as appropriate, the validity of the source of data input or operational instruction. If it is a requirement of the system that data input or instructions can only come from specific input devices (e.g. instruments, terminals); does the system check for the correct device? 21 Sub part B Electronic Records

22. i ) Education, training, and experience Determination that persons who develop, maintain, or use electronic record/electronic signature systems have the education, training, and experience to perform their assigned tasks. 22 Sub part B Electronic Records

23. j) Written Policies The establishment of/and adherence to, written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures, in order to determine record and signature falsification . Written policies shall be party of user account open with user sign and statement “I am accountable and responsible for actions initiated under my electronic signature in order to determine record and signature falsification” . 23 Sub part B Electronic Records

24. k) Documentation Use of appropriate controls over systems documentation including: (1) Adequate controls over the distribution of access to, and use of documentation for system operation and maintenance. (2) Revision and change control procedures to maintain an audit trail that documents time- sequenced development and modification of systems documentation Distribution of access annexure System operation and maintenance log Revision procedure Change control procedure Audit trial with Time sequenced 24 Sub part B Electronic Records

25. 11.30 Controls for open systems Persons who use open systems to create, modify, maintain, or transmit electronic records shall employ procedures and controls designed to ensure the authenticity, integrity, and, as appropriate, the confidentiality of electronic records from the point of their creation to the point of their receipt. Such procedures and controls shall include those identified in § 11.10, as appropriate, and additional measures such as document encryption and use of appropriate digital signature standards to ensure, as necessary under the circumstances, record authenticity, integrity, and confidentiality. 25 Sub part B Electronic Records

26. 11.50 Signature manifestations. Signed electronic records shall contain information associated with the signing that clearly indicates all of the following: The printed name of the signer; The date and time when the signature was executed; The meaning (such as review, approval, responsibility, or authorship) associated with the signature. b) The items identified in paragraphs (a)(1), (a)(2), and (a)(3) of this section shall be subject to the same controls as for electronic records and shall be included as part of any human readable form of the electronic record (such as electronic display or printout). 26 Sub part B Electronic Records

27. 11.70 Signature/record linking. Electronic signatures and handwritten signatures executed to electronic records shall be linked to their respective electronic records to ensure that the signatures cannot be excised, copied, or otherwise transferred to falsify an electronic record by ordinary means. 27 Sub part B Electronic Records

28. 11.100 General requirements a) Unique : Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else. b)Verify the identity : Before an organization establishes, assigns, certifies, or otherwise sanctions an individual’s electronic signature, or any element of such electronic signature, the organization shall verify the identity of the individual. At the time of joining that activity done by HR Department . For vendor in service agreement need to be clarification. 28 Sub part C Electronic Signatures

29. 11.100 General requirements c) Certify to the agency :Persons using electronic signatures shall, prior to or at the time of such use, certify to the agency that the electronic signatures in their system, used on or after August 20, 1997, are intended to be the legally binding equivalent of traditional handwritten signatures. The certification shall be submitted in paper form and signed with a traditional handwritten signature, to the Office of Regional Operations (HFC–100), 5600 Fishers Lane, Rockville, MD 20857. 2) Persons using electronic signatures shall, upon agency request, provide additional certification or testimony that a specific electronic signature is the legally binding equivalent of the signer’s handwritten signature. For 11.2 Implementation. b) For records submitted to the agency 29 Sub part C Electronic Signatures

30. 11.200 Electronic Signatures components and controls a) Non Biometric :Electronic signatures that are not based upon biometrics shall-- (1) Employ at least two distinct identification components such as an identification code and password. ( i ) When an individual executes a series of signings during a single, continuous period of controlled system access, the first signing shall be executed using all electronic signature components; subsequent signings shall be executed using at least one electronic signature component that is only executable by, and designed to be used only by, the individual. 30 Sub part C Electronic Signatures

31. 11.200 Electronic Signatures components and controls (ii) When an individual executes one or more signings not performed during a single, continuous period of controlled system access, each signing shall be executed using all of the electronic signature components. 2) Be used only by their genuine owners; 3) Be administered and executed to ensure that attempted use of an individual’s electronic signature by anyone other than its genuine owner requires collaboration of two or more individuals. 31 Sub part C Electronic Signatures

32. 11.200 Electronic Signatures components and controls b) Biometric --Electronic signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than their genuine owners. 32 Sub part C Electronic Signatures

33. 11.300 Controls for identification codes/ passwords Persons who use electronic signatures based upon use of identification codes in combination with passwords shall employ controls to ensure their security and integrity. Such controls shall include: a) Uniqueness --Maintaining the uniqueness of each combined identification code and password, such that no two individuals have the same combination of identification code and password. 33 Sub part C Electronic Signatures

34. 11.300 Controls for identification codes/ passwords b) Code and password Periodically Checked --Ensuring that identification code and password issuances are periodically checked, recalled, or revised (e.g., to cover such events as password aging).  c) Loss management --Following loss management procedures to electronically de-authorize lost, stolen, missing, or otherwise potentially compromised tokens, cards, and other devices that bear or generate identification code or password information, and to issue temporary or permanent replacements using suitable, rigorous. 34 Sub part C Electronic Signatures

35. 11.300 Controls for identification codes/ passwords d) Safeguard to prevent unauthorized --Use of transaction safeguards to prevent unauthorized use of passwords and/or identification codes, and to detect and report in an immediate and urgent manner any attempts at their unauthorized use to the system security unit, and, as appropriate, to organizational management.   e) Periodic testing of devices --Initial and periodic testing of devices, such as tokens or cards, that bear or generate identification code or password information to ensure that they function properly and have not been altered in an unauthorized manner. 35 Sub part C Electronic Signatures

36. GAMP – Good Automated Manufacturing Practices It was founded in 1991 and is a trademark of the International Society for Pharmaceutical Engineering (ISPE). GAMP-5 was launched in 2008 and includes a set of procedures that help to ensure automation equipment/software meets required quality standards. 36

37. GAMP – Good Automated Manufacturing Practices Quality by design is a central principle of GAMP and advocates that quality is built into each stage of the manufacturing process. All aspects of production from the raw materials, facility and equipment to the training and hygiene of staff are covered by GAMP recommendations  Although Good Automated Manufacturing Practice (GAMP) is not legislation, it’s an important guideline for companies involved in the development and/or implementation of automated production systems. 37

38. GAMP Objectives GAMP® guidance aims to achieve computerized systems that are fit for intended use and meet current regulatory requirements, by building upon existing industry good practice in an efficient and effective manner. 38

39. Guidance It is not a prescriptive method or a standard , but.. Pragmatic guidance Approaches Tools for the practitioner Applied with expertise and good judgment 39

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43. GAMP- Main Body Overview Key Concepts Life Cycle Quality Risk Management Regulated Company Activities Supplier Activities Efficiency Improvements 43

44. 5 Key Concepts Life Cycle Approach Within a QMS Scaleable Life Cycle Activities Process and Product Understanding Science-Based Quality Risk Management Leveraging Supplier Involvement 44

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46. Product and Process Understanding • Basis of science- and risk-based decisions • Focus on critical aspects – Identify – Specify – Verify • Critical Quality Attributes / Critical Process Parameters. 46

47. Life Cycle Approach Within a QMS • Suitable Life Cycle. –Intrinsic to QMS • Continuous improvement. Life cycle approach is fundamental to GAMP 5. 47

48. GAMP V Model Transition 48

49. Scaleable Life Cycle Activities Scalability is based on -- • Risk • Complexity and Novelty • Supplier 49

50. Science Based Quality Risk Management Review Based on ICH Q9 Assessment Control Communication Focus on patient Safety product quality data integrity 50

51. Leveraging Supplier Involvement Activities: • Requirements gathering • Risk assessments • Functional / other specifications • Configuration • Testing • Support and maintenance Principles: Assess: – Suitability – Accuracy – Completeness • Flexibility: – Format – Structure 51

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53. Compatibility with Other Standards ASTM(  American Society for Testing and Materials ) E2500 Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment. 53

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55. Stages Within the Project Phase • Planning • Specification, configuration, and coding • Verification • Reporting and release. 55

56. Planning • Activities • Responsibilities • Procedures • Timelines 56

57. Specification, Configuration, &Coding • Specifications allow – Development – Verification – Maintenance Number and level of detail varies. Defined processes. 57

58. Verification • Testing • Reviews • Identify defects 58

59. Supporting Processes • Risk Management • Change and Configuration Management • Design Review • Traceability • Document Management 59

60. Design Review • Planned • Systematic Identify Defects • Corrective Action • Scaleable – Rigor/Extent – Documentation 60

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63. GAMP 5 Quality Risk Management 63

64. Critical Processes • Generate, manipulate, or control data supporting regulatory safety and efficacy submissions • Control critical parameters in preclinical, clinical,development , and manufacturing • Control or provide information for product release • Control information required in case of product recall • Control adverse event or complaint recording or reporting • Support pharmacovigilance 64

65. Five step risk management approach 65

66. Step 1:Initial assessment An initial assessment should be performed based on an understanding of the business process. The understanding can be derived from user requirements, design specifications, operating procedures, regulatory requirements, and known functional areas. The assessment should include a decision on whether the system is GxP regulated and include an overall assessment of the system impact. 66

67. Step 2 – Identify Functions with Impact on Patient Safety, Product Quality, and Data Integrity Building upon the information obtained in Step 1, the specific functions that have impact on patient safety, product quality, and data integrity can be identified and addressed. It must be remembered that no function can be assessed as having higher risk or impact than the process itself. 67

68. Step 3 – Perform Functional Risk Assessments and Identify Controls The functions identified in the previous step can now be analyzed by considering possible hazards and what controls may be needed to minimize potential harm. A company’s risk tolerance is also a factor to be considered when selecting possible controls. 68

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70. Step 4 – Implement and Verify Appropriate Testing and Controls Once the severity and risk are understood, the appropriate level of challenge testing can be selected. The concept of planning testing and selecting controls based on assessed risk and impact. 70

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72. Step 5 – Review Risks and Monitor Controls Once the controls are implemented, they need to be monitored. The implementation of the controls may reduce the level of effort for many current activities, such as audits, assessments, documentation, testing, and even the degree of quality unit involvement. 72

73. Conclusion The GAMP 5 QRM strategy offers a pragmatic approach to computer systems compliance. It avoids reliance on a single standard that can be excessive and/or inadequate, and is consistent with ICH Q9 and has incorporated some elements from ISO-14971. It is a framework that is flexible and scalable and assists with the identification and application of appropriate controls where they are needed. 73

74. REFERENCES GAMP 5 Quality Risk Management Approach by Kevin C. Martin and Dr. Arthur (Randy) Perez https://www.hpra.ie/docs/default-source/default-document-library/5-2-cleaning-validation.pdf?sfvrsn=0 ProPharmaGroup /overview-of-computerized-systems-compliance-using-the-gamp-5-guide https://www.pharmout.net/downloads/white-paper-computer-system-validation.pdf https://www.researchgate.net/publication/215485194_Computer_Software_Validation_In_Pharmaceuticals 74

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