Electronic records rules

FDA. Code of Federal Regulations, Title 21 Food and Drugs, Part 11 Electronic Records Electronic Signatures Final Rule, Fed Regr 62 (54), 13429-13466 (20 March 1997). 

Some fairly common mistakes made in managing electronic SOPs, protocols, and changes to them are listed below. If these can be avoided, the resulting computer system should meet the requirements of the US, Organization for Economic Cooperation and Development (OECD), and Ministry of Health, Labor, and Welfare (MHLW) GLP standards as well as the FDA s Rule on Electronic Record Keeping Electronic Signatures. ... 

When you start working across the Internet, the chromatography data system becomes an open system and the FDA rule requires controls. Using FDA s definition of electronic records, the laboratory chromatography data system generates electronic records. Based upon the definition, laboratories will need to consider more than just the raw data tiles. One must also include the method tiles, mn sequence tiles, and the integration parameters used for the data analysis. The need for a comprehensive audit trail is a critical component of the FDA regulations. The audit trail is an electronic record and is subject to the same controls. 

In 1990, the FDA published the electronic records and signatures rule as an initiative for the pharmaceutical industry. This allowed the use of electronic signatures in lieu of handwritten ones. This initiative opened the door to fully electronic documents. The rule became effective in August 1997 and addresses both electronic records and electronic signatures. 

This regulation including its preamble and the final rule itself detailed the minimal requirements. The interpretation of the rule is stronger than the printed word. The goal of FDA was to require electronic records and e-signatures to be reliable, trustworthy, and available to the Agency for inspection. 

The e-records rule uses many terms that must be understood to grasp fully the intent of the rule. FDA defines electronic records as any combination of text, graphics, data, audio, pictorial, or other information presented in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system . A printout of a computer file is not the actual electronic record itself Electronic records include other relevant data, such as which user made a change, the time and date that the change was made, etc. 

As the EPA moves toward the eventual finalization of its own rule, currently scheduled for finalization in the spring of2003, the pressure will mount for EPA investigators and the regulated community to learn about the benefits of the electronic records and... 

Electronic Records, Electronic Signatures Final Rule, 21 CFR Part 11, Federal Register, Vol. 62, No. 54, US Food and Drug Administration, Rockville, MD (1997). Also available on the World Wide Web http //www.fda.gov/ora/compliance refypartll/default.htm. 

It is beyond the scope of this chapter to discuss and explain how the requirements can be implemented in analytical laboratories. This has been described in a six-article series published in Biopharm [16-21]. We elaborate here on the validation aspect of the rule. Part 11 requires that computer systems used to acquire, evaluate, transmit, and store electronic records should be validated. This is not new, as processes and steps to validate such systems were described earlier in the chapter. FDA s expectations for validation have been described in the Part 11 draft guidance on validation [4]. This guidance makes it very clear that functions as required by Part 11 should be validated in addition to functions that are required to perform an application such as chromatographic instrument control, data acquisition, and evaluation. Specific functions as required by Part 11 are as follows ... 

CFR Part 11 Electronic Records Electronic Signatures Final Rule Federal Register 1997, 62,... 

One of the most important procedures to be developed and followed is the administration and retention of electronic records. Part 11 requires the retention of electronic records in electronic form. For regulated systems in which electronic signatures are not implemented (hybrid systems) the electronic record requirements (Sub-Part B) in Part 11 are applicable, and the electronic records are maintained and retained in electronic form for the period established by the predicate rule. 

This clause applies to legacy systems and the electronic records stored by these systems. The no grandfathering clause indicates that Part 11 provisions relating to record creation do not cover electronic records that are created before the effective date of the rule. These records would not need to be retrospectively altered. 

FDA inspections are conducted for many reasons and the extent of compliance of computer systems with Part 11 may be evaluated during any of these inspections. If applicable, a field investigator will review electronic records in order to evaluate their level of compliance with the predicate rule. At the same time, the investigator may check adequacy of record keeping arrangements for compliance with Part 11. 

FDA, Electronic Records Electronic Signatures Final Rule, 62 Federal Register 13430 (March 20,1997). 

Required electronic records that meet Part 11 are used to satisfy the applicable predicate rule. The following are some basic principles that must be adhered to ... 

In this case, reports are paper-based. The operator/user may record each significant step of the computer-related operation and/or critical outputs. Paper records and associated electronic records are retained, based the requirements of the applicable predicate rule. In hybrid systems, one approach to the signature/records linkage is by referencing the file(s) as part of the report. The reference may include the name, and creation date and time of the files associated with the batch report. Modifications to any referenced electronic file will invalidate the approval of the associated batch report. 

The purpose of the following checklist is to help to determine if a computer system complies with the FDA Rule 21 CFR 21 Part 11 for electronic records and electronic signatures. This audit questionnaire apphes to systems that meet the definition of a closed system as defined in Section 11.3 (b)(4) of the rule and which do not utilize biometrics identification methods. 

The FDA withdrew its last guidance document in the series on electronic copies of electronic records in February 2003. But it did NOT withdraw the 21 CFR Part 11 Rule, which is still in force, and must be complied with the FDA is still inspecting companies for compliance and none of the multi-million dollar fines imposed by the FDA for non-compliance have been revoked. Nor have any of the preceding warning letters been recalled. 

Narrowly focused, the tenets of 21 CFR 11 are indisputable that firms must establish and maintain the integrity of their electronic information. What has been lost is the clear indication of which electronic information the requirements apply to. In my opinion, data generated outside a computerized system, that are manipulated by that system and are ultimately available in hard copy should not be subject to this ruling. Validation of the computerized system should be more than sufficient to establish that the final documentation accurately reflects the input information. In that instance, the computerized system is little more than a tool whose functionality can be readily established, yet firms are endeavoring to assure 21 CFR 11 compliance for numerous systems in which the computer is little more than an adjunct to the cGMP activity and corresponding hard copy. Batch record preparation, SOP and test method archives, and many process equipment control systems are examples of systems in which requirements for 21 CFR 11 compliance appear excessive. A system that processes or communicates data or records and subsequently retains and stores hard copies should not be subject to the 21 CFR 11 requirements. Far too many systems are being unnecessarily held to the very restrictive portions of 21 CFR 11. Electronic record retention as defined in 21 CFR 11 has its place, but not necessarily in every computerized system used within the industry. 

ERSR Agency Charter. Federal Register-Electronic Records Electronic Signatures, Final Rule, March 20,1997. 

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