Even after a quarter century, some misunderstandings remain around 21 CFR Part 11.
Background
FDA 21 CFR Part 11 (Part 11) was enacted in August of 1997, almost 25 years ago. After the initial fanfare (work on this standard started in 1991) a period of concern and confusion arose regarding its scope and applicability. After extensive industry consultation the FDA issued new guidance in 2003 which allowed end-users and vendors alike to focus their efforts more productively and, in-turn benefit from the move from paper to electronic record keeping. These benefits include:
- Improved ability for organizations to analyze trends, problems, etc., enhancing internal evaluation and quality control
- Reduced data entry errors, due to automated checks
- Reduced costs of storage space
- Reduced shipping costs and processing time of data transmission to FDA
- More efficient FDA reviews and approvals of FDA-regulated products
The principle of these new guidelines was to concentrate on electronic records proving compliance with the relevant pre-existing Predicate Rules.
Predicate Rules
Definition:A Predicate Rule is any FDA regulation that requires a company to maintain certain records and submit specific information to the agency as part of compliance.
Examples include: Current Good Manufacturing Practices (cGMP) 21 CFR Parts 210 and 211; Good Laboratory Practices (GLP) 21 CFR Part 58; Good Clinical Practices (GCP) collectively known as GxPs and for Medical Devices, the Quality System Regulation, 21 CFR 820.
The types of records to be kept and their retention periods are determined by the Predicate Rules that apply to your company product type and associated critical parameters.
Specific references to critical environmental parameters within these regulations include:
PART 211: CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS
Subpart C: Buildings and Facilities
Sec. 211.42 Design and construction features.
Aseptic processing, which includes as appropriate:
- Temperature and humidity controls
- A system for monitoring environmental conditions
Sec. 211.46 Ventilation, air filtration, air heating and cooling.
Equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing, or holding of a drug product.
Part 820: QUALITY SYSTEM REGULATION – MEDICAL DEVICES
Subpart G - Production and Process Controls
Section 820.70
- Contamination control.每个制造商应建立和保持程序，以防止设备或产品受到可能对产品质量产生不利影响的物质的污染。
- Environmental control.Where environmental conditions could reasonably be expected to have an adverse effect on product quality, the manufacturer shall establish and maintain procedures to adequately control these environmental conditions. Environmental control system(s) shall be periodically inspected to verify that the system, including necessary equipment, is adequate and functioning properly. These activities shall be documented and reviewed.
Predicate Rules are not prescriptive in terms of how compliance should be achieved, they provide the “What” not the “How” of compliance responsibility. Thankfully, abundant guidance documents, vendor solutions and extensive industry experience exist.
A Common Misunderstanding
To this day, a common question asked of vendors is “Does your system comply with 21 CFR Part 11?”
许多系统现在都包含了支持第11部分的技术特性，但是还需要持续的操作政策、程序、实践、培训和控制。这些方面都是终端用户公司建立、维护和维护的责任。
通常人们认为第11部分合规就像UL清单或CE标志，但FDA不为生命科学行业的供应商解决方案提供认证服务，因此这种观点是不正确的。No system, out-of-the-box, is Part 11 compliant but a surprising number of vendors continue to make such claims.
A more informed response to the question of Part 11 compliance, involves a comprehensive discussion centered around Predicate Rules, record types, critical parameters, risk assessment and how a particular system supports the specific requirements. This type of conversation is a great deal more enlightening and valuable for both parties.
Environmental Monitoring
Setra CEMS™ softwarewas designed to support compliance with Part 11 as part of its fundamental purpose to monitor, record, report and alarm upon critical parameters. To learn more, download theCEMS 21 CFR Part 11 Compliance Statement.
