1. 11/2/991 CDER’s 21 CFR Part 11 Implementation Study Greg Brolund Associate Director, Office of Information Technology, CDER/FDA

2. 11/2/992 Background u CDER heard many concerns about the implementation of Part 11 n Timing n Legacy Systems n Inconsistent information from FDA n 483’s n etc.

3. 11/2/993 Implementation Recommendation Project u CDER task force directed to make recommendations for implementation of Part 11 n Directed by Dr. Janet Woodcock - May 99 n To be based on an analysis of the issues raised by industry, FDA inspectors, and the software industry.

4. 11/2/994 Pharmaceutical Interviews u u Representatives of four large pharmaceutical firms were interviewed. The groups consisted of people who are involved with the planning and implementation of measures to comply with Part 11 and represented the GxP areas as well as regulatory, legal, and information technology areas.

5. 11/2/995 FDA Interviews u u Two FDA inspectors and several FDA staff familiar with inspections, compliance policy and Part 11 were interviewed.

6. 11/2/996 Software Industry Interviews u u Two major software companies dealing with the pharmaceutical industry were interviewed.

7. 11/2/997 CDER Task Force Analysis u u The CDER task force reviewed the results of the interviews and supporting material. The task force produced the implementation recommendations.

8. 11/2/998 Common Industry Part 11 Activities u u Assess current systems and try to learn as much about the FDA interpretation of the rule as possible. u u Create and internal interpretation based on current business practices, impact of change on system quality, cost of changes, and feasibility of changes to meet the requirements of Part 11. u u Create implementation plans. u u Conduct training of company staff in the meaning of Part 11 and SOPs to comply with Part 11.

9. 11/2/999 Common Industry Concerns u u Why are existing, validated systems that include both paper and electronic components are no longer acceptable? u u Long term archiving of electronic records is not technologically feasible. u u What is the true scope of Part 11?

10. 11/2/9910 Concerns Continued u u Automated audit trails are not feasible for many existing systems and are often not available in new software, especially in manufacturing systems. u u Company systems will take years to be made compliant with the current perceived FDA interpretation of Part 11.

11. 11/2/9911 Concerns Continued u The cost to become Part 11 compliant for a global company is estimated to be > $100 million. u The cost is perceived to far out weigh the benefit.

12. 11/2/9912 FDA Concerns (sample) u Electronic records are easier to falsify than paper records if adequate controls are not in place. u Hybrid systems are difficult to validate and verify u Records must be inspected on site and over long periods of time. Archiving and retrieving the records could be a problem for inspectors.

13. 11/2/9913 FDA Concerns Continued u Paper printouts of electronic records may omit important information. n Changes n Signatures n Analysis parameters

14. 11/2/9914 Two Software Providers u Difficult to know exactly what is required. u Other industries don’t have the same electronic record keeping requirements. u Companies would like FDA to review their interpretation and implementation for Part 11 compliance

15. 11/2/9915 Task Force Recommendations u u Create a Part 11 Implementation Guidance for Industry that addresses specific issues raised by FDA and industry. u u Create a position of Electronic Signature / Electronic Records Ombudsman or Coordinator to coordinate policy, internal and external training, and coordinate answers or clarification for industry and within FDA

16. 11/2/9916 Recommendations u u Conduct public workshops to explain the implementation policy and post appropriate materials on the FDA internet web site. u u Issue clarifications on the existing Computers in Clinical Trials Guidance. u u Create case studies of the characteristics of acceptable systems under the implementation policy without endorsing specific companies or products

17. 11/2/9917 Recommendations u u Provide FDA participants on instrument data interchange standards committees such as those sponsored by ASTM and IUPAC.

18. 11/2/9918 Points to be Addressed in Specific Guidance u Acceptability of u Acceptability of paper records that are generated from electronic data u u Hybrid systems - what kind of hybrid system is acceptable. u u Legacy Systems - describe the characteristic of a legacy system that is acceptable until it can be upgraded. u. u Length of time allowed to phase out legacy systems or marginal hybrid systems.

19. 11/2/9919 Guidance Continued u u Electronic record archiving. Possibilities include printing the records with all available "meta" data. The paper becomes the official archive. u u Scope - describe what records in a process are covered by Part 11. u u Automated audit trails - describe audit trails that are part of a hybrid system. For example, if the electronic data is printed and the printed record is the official record, can changes be made in the usual way to the paper record to satisfy the audit trail requirement?

20. 11/2/9920 Guidance Continued u u Hospital records systems - describe the level of industry control and Part 11 compliance that is expected over systems such as hospital patient record keeping systems that are typically outside of FDA jurisdiction. u u Electronic Signatures - describe the acceptability of systems that use server based electronic signatures in conjunction with standard security and accessibility system controls to verify the identity of the "signer" of the electronic record.

21. 11/2/9921 Current Status u The FDA Office of Regulatory Affairs has been made responsible for FDA’s Part 11 implementation policy. u ORA has been given a copy of the CDER task force report and recommendations.