Part 11 comliance: top tips for maximum efficiency


Part 11 of Title 21 of the Code of Federal Regulations (CFR) provides guidance for maintaining electronic records and providing governance regarding electronic signatures in all process documentation throughout the discovery, development and manufacture of an Active Pharmaceutical Ingredient (API), New Chemical Entity (NCE) or a medical device.

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Yet Part 11 is a topic very broad in its definition with lots of ambiguity that is continuing to be ironed out so that companies can really understand what constitutes proper compliance. This article provides insights into navigating Part 11 of Title 21.

Currently, the FDA defines electronic record to mean: “any combination of text, graphics, data, audio, pictorial, or other information represented in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.”

Ensuring Part 11 compliance can be an extremely time-consuming task. Yet, since the guidance came out in 1997, much has changed and thanks to advanced technology, it is perhaps a more efficient and more automated task than it was in the past.

Basically, the core documentation that is tracked is the project’s “master records” or “raw data” and the second that record or data is generated, it becomes an electronic record subject to compliance with Part 11.

So how can companies make sure they comply with Part 11 as efficiently and effectively as possible? Here are three tips:

  1. Use third-party resources. Everyone knows that Contract Manufacturing Organizations (CMOs) are first and foremost hired for their scientific and chemical development capabilities – not their IT skills. To ensure Part 11 compliance, it pays to hire an independent consultant who can advise on the best software and technology to facilitate compliance, and help with the implementation and validation processes.
  2. Ensure advanced security. All personnel using the system should be properly identified, and their credentials serve as an electronic signature. Likewise, all data stored in the system must maintain a comprehensive audit trail for any changes or usage documentation. Access to electronic records should be controlled by a unique login, with username and password. Additionally, if users are logged out for a period of inactivity, they should be locked out of the system.  This should be the case if they enter the wrong password more than several times.
  3. Lead by quality assurance. A dedicated quality assurance team should lead all Part 11 efforts, leveraging an electronic quality management system to keep an effective audit trail of compliance. At PCI Synthesis, we’ve developed a proprietary system which generates and controls key information on processes, calibrations and corrective actions. Since we use it to support cGMP manufacturing operations, this software also is subject to full qualification and validation for use in the company’s network.

As API manufacturers follow the direction of most other life-science industries and increasingly move to paperless operations, the controls and procedures for electronic documents and signatures will become even more paramount. At PCI, there are three critical areas that will be Part 11 compliant as we move away from paper-based systems:

  • Analytical testing lab. Here at PCI Synthesis we have standard operating procedures (SOPs) for maintaining electronic analytical data, test methods and investigations. We use validated software to generate and store testing data on a qualified computer network. For methods, existing pen and ink copies will be replaced by electronic notebooks.
  • Quality management systems. This is an area where we are working toward Part 11 compliance. These systems maintain all the SOPs, processes and controls that have been put in place across the organization. As more and more software providers offer advanced systems that help companies automatically maintain electronic quality documentation, costs will continue to decline and maintaining such systems will be easier and more affordable.
  • Manufacturing controls. This is perhaps the most complex area for going paperless, since it involves the manufacturing equipment on the plant floor. For most CMOs it means a major investment in completely revamped manufacturing infrastructure, such as using automated equipment, or replacing manual control of heating, cooling, etc., with computer-controlled mechanisms. In a Part 11-compliant environment a computer would do this automatically, yet require a multimillion dollar investment.

The move to electronic documentation to replace paper and ink is certainly making chemical manufacturing processes more efficient. Ensuring Part 11 compliance, however, is key to ensuring not only a visible documentation trail, but ultimately safe and effective products.

Stay tuned for a follow-up blog to address the seven questions to ask your CMO about its data integrity and Part 11 compliance procedures. In the meantime, please consider signing up for our newsletter.