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FDA 21 CFR Part 11, Predicate Rules and Environmental Monitoring

July 15, 2022


Even after a quarter century, some misunderstandings remain around 21 CFR Part 11. 


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: 


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. 


Subpart G - Production and Process Controls 

Section 820.70 

  • Contamination control.  Each manufacturer shall establish and maintain procedures to prevent contamination of equipment or product by substances that could reasonably be expected to have an adverse effect on product quality. 
  • 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?”  

Many systems now incorporate the technical features required to support Part 11 compliance but ongoing operational policies, procedures, practices, training and controls are also required. These aspects are the responsibility of the end user company to establish, uphold and maintain. 

Often people view Part 11 compliance as being like a UL listing or CE mark but the FDA does not provide accreditation services to vendor solutions to the Life Sciences industries rendering this view incorrect. 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™ software was 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 the CEMS 21 CFR Part 11 Compliance Statement.

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Topics: Compliance, agencies that monitor pharmacies