If you work in the life sciences industry, or any domain classified as being subject to GxP, you are aware of the regulatory frameworks within which your organization must operate. Among them is the FDA’s Title 21, CFR Part 11, (Electronic Records; Electronic Signatures) commonly known as "Part 11", and one of the most recognised of all regulations. In practice, "Part 11" applies to drug and medical device manufacturers, biotech companies, biologic products’ developers, CRO's (Contract Research Organization) and other industries regulated by the Food and Drug Administration (FDA), with a few exceptions.
In this blog, we will explain "Part 11", the reasons that led to the need for this regulation, and why following it is not only crucial to maintain compliance, but also beneficial to your organization’s operations. Next, we will describe how to know if "Part 11" applies to you as a regulated organization, then we will provide tips, reminders, and helpful resources to help you develop and support your understanding.
What is Title CFR 21, “Part 11”, where does it come from and why is it important?
"Part 11" is a regulatory framework that governs how companies manage their electronic records and electronic signatures. The regulation establishes a framework to manage records and electronic signatures in order to meet the statutory inspection requirements of the FDA, so they can be deemed trustworthy, reliable and generally equivalent to paper records and handwritten signatures executed on paper. This regulation asks for controls to be implemented by regulated organizations regarding computerized software and systems involved in the processing of electronic records that predicate rules require them to maintain. Examples of such systems could be Enterprise Resource Planning (ERP) systems, Quality Management Systems (QMS), or any other computerized system, where a predicate rule corresponds to any requirement set out by the regulator.
Why does “Part 11” exist?
Basically, “Part 11” exists as a regulatory response to safety concerns regarding the management of the distribution, storage and retrieval of records by manufacturers of biotechnology, drugs and medical equipment in the digital age. It is also aimed at reducing the enormous cost that these companies carry while maintaining paper filing systems to satisfy the regulatory agencies. A key goal is ultimately enabling these businesses to introduce a controlled transition to electronic systems and digitized processes.
Why compliance to "Part 11" is it important?
Regulatory compliance is not something that is usually approached with enthusiasm. Nonetheless, “Part 11” plays an important role in protecting the industry against non-compliant players and associated missteps in quality assurance. Although compliance with “Part 11” can seem demanding, it is important to remember that its purpose is the liberation of regulated industries vis-à-vis their paper documents constraints, the standardization of compliance and the opening of a way for companies to speed up their operations with electronic records and electronic signature management systems. In addition, software solutions designed to facilitate “Part 11” compliance are now available.
Some advantages of “Part 11” compliance are:
Better operational efficiency
Cost reduction - Massive savings on warehouse space
Stronger system security
On the other hand, the failure by regulated organizations to comply with "Part 11” can result in injunctions or decrees that can be extremely harmful for a product or a company, leading in some cases to a production or import ban. Before reaching this point, even the warning letters of the regulator can lead to dramatic losses in the share value of a company when they are made public. Moreover, it reduces the trust and loyalty of clients and consumers.
How to know if the "Part 11" refers to a system used by your organization?
“Part 11” applies whenever the records required under the predicate rules need to be generated, modified, stored, transferred, or viewed electronically. As a general rule, you can say that systems are subject to "Part 11" if the documents and data "managed" by the systems are:
Submitted to FDA
Relevant for an inspection of the FDA concerning any other regulation
What are electronic records and which ones are subject to "Part 11"?
An electronic record is a combination of text, graphic, data, audio, images, or other information in a digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.
"Part 11" applies to all electronic records created, modified, maintained, archived, retrieved or transmitted, and used to meet GxP requirements, and / or any records requirement defined by the FDA. For life science companies, these standards apply to all phases of their process, including the research, manufacture and distribution of products and services.
Electronic records and systems subject to electronic record requirements include, but are not limited to, the following:
Computer systems used to store or archive batch records, non-clinical study data or surveillance data
Electronic Document Management Systems (EDMS)
Material Requirements Planning (MRP) / Enterprise Resource Planning (ERP) Systems
Laboratory Information Management Systems (LIMS)
Equipment Data used in GMP Manufacturing
Data from systems containing clinical data
Standard Operating Procedures (SOPs)
Master Batch Records (MRB) and Batch Records (BR)
Design History File (DHF), Device Master Record (DMR), and Device History Record (DHR)
Trial Master Files (TMF) and Investigator Site Files (ISF)
Quality Manual, Policies, Procedures and Work Instructions
Preventive maintenance records
Protocols and validation reports
Certain records must be kept, without necessarily being submitted to regulatory authorities. In this case, the organization can use computerized systems to keep their records electronically (instead of paper), as long as it can demonstrate that these electronic records comply with “Part 11”.
For records that need to be submitted to the regulator, the organization can do so electronically as long as the following two conditions are met:
Compliance with Title 21 CFR Part 11 is demonstrated and documented
The regulator can accept this type of recordings electronically. It is up to the regulatory company to inquire to ensure that the records it wishes to submit electronically are in an acceptable format for the regulator.
Tips and Reminders for organizations GxP and their stakeholders
1. ‘’Part 11’’ does not replace predicate rules.
The predicate rules, which require organizations to keep records in the first place, are still in effect. If electronic records are unreadable, inaccessible, or corrupted, manufacturers are invariably subject to these requirements.
2. “Part 11’’ does not require the use of electronic systems and electronic records.
Instead, it establishes the criteria by which companies in the regulated industries must use these electronic systems and records in a controlled manner that ensures that company data and processes are as reliable and secure as paper records and handwritten signatures.
3. No supplier can guarantee their software is fully ‘’Part 11’’ compliant.
‘’Part 11" does not only establish technical requirements, but it also establishes organizational controls, and those cannot be bought. The administrative controls are defined by the organization using the software. The procedural controls such as managing alerts, employee’s training, and the content of standard operating procedures rely upon the regulated organization. The supplier can, at best, declare that its system complies with “Part 11”, if and only if, it is used in a manner consistent with regulations in place.
The "Part 11" legislation increasingly continues to influence the operations of regulated organizations, and these organizations are responsible for the continued compliance of their business processes. Time and statistics show that technological advancement along with operational gains are the reasons why the safest and most cost-effective approach is to invest early in Title 21 CFR Part 11 compliance. The first step is determining what your electronic records are. In other words, what computer systems are used to create, modify, store, archive, retrieve or transmit information required by the regulator?
Whether you have a deep expertise in the regulatory environment or simply the desire to learn more, the overview of "Part 11" covered in this blog puts forward the definition of the regulation, and the associated benefits obtained through its compliance.