The wait and suspense for the United States Food and Drug Administration’s (FDA) plans to harmonize and modernize the way quality systems are regulated in the US may soon be over after repeated delays. However, it is possible that COVID-19 could be the cause of yet another delay. We’re talking about the replacement of 21 CFR Part 820 and more.

The FDA originally published a Notice of Proposed Rule Making (NPRN) in May 2018. The abstract from Regulation Identifier Number (RIN) 0910-AH99 states: “FDA intends to harmonize and modernize the Quality System regulation for medical devices. The revisions will update the existing requirements with the specifications of an international consensus standard for medical device manufactures, ISO 13485:2016. The revisions are intended to promote the use of more modern risk management principles and reduce regulatory burdens on device manufacturers and importers by harmonizing domestic and international requirements.” The NPRM is currently at the Proposed Rule Stage with an action date in October 2020. A panel committee meeting will be held after issuance of the proposed rule.

The FDA lists the following benefits of adopting ISO 13485:

• ISO 13485:2016 is already used by Regulatory Authorities in other countries as a basis for their QMS requirements; therefore, one globally harmonized system will allow for opportunities:
  • To work closer with foreign regulatory authorities and facilitate regulatory convergence on QMS
  • For medical device manufacturers to have a more globally harmonized QMS
• Deltas between the QS regulation and ISO 13485:2016 are minor:
  • Gain more than we lose
  • More robust QMS principles in many areas
  • Better guidance
  • Stronger ties to risk management principles and ISO 14971

Understanding 21 CFR Part 820 and ISO 13485:2016

FDA’s Title 21 Code of Federal Regulation (CFR) Part 820 Quality System Regulation is the current quality system for medical devices used by the FDA and is applicable to manufacturers of finished medical devices sold in the US, including imported products. Only parts of the requirement may apply, depending on the class of the medical device. Based on their demonstrated compliance with this regulation, organizations can market medical devices commercially in the U.S. Quality System Regulation (QSR) 21 CFR 820 has fallen behind as regulatory expectations have evolved.

ISO 13485:2016 is a standard based upon ISO 9001:2008 and is specific to the design and manufacture of medical devices. It applies to medical device manufacturers and their suppliers. Compliance with this standard is currently voluntary in the US but required in some countries. Third party registrars, also known as Certified Bodies (CB), conduct audits to ensure conformance. The FDA enforces 21 CFR 820, but the Medical Device Single Audit Program (MDSAP) allows CB to audit FDA guidelines.

While there are many similarities, ISO 13485:2016 is more up to date than 21 CFR 820. The 2016 revision placed more emphasis on quality management systems (QMS) across the entire supply chain and addressed the total product lifecycle of medical devices.

The original ISO 13485:1996 was estimated to have 90% convergence with 21 CFR 820. The intervening standard, ISO 13485:2003, boosted the perceived alignment to around 93%. The medical device regulatory processes have progressed a lot since 2003. Risk management and the associated risk-based decision-making processes have become a focus for the entire medical device industry at both the product and process levels. Increased regulatory emphasis on product safety, requirements for risk management, and improvement of reporting systems to regulatory bodies led the latest revision of ISO 13485 in 2016. The revision was made to help users meet common regulatory requirements. The FDA participated in the revision of ISO 13485:2016, recognizing it is more convenient for industries to develop a QMS if the needs of different countries are the same. The FDA and other countries’ medical device regulatory agencies can more easily use and discuss inspection reports because the requirements are similar. Because the FDA was instrumental in the revision of ISO 13485, most of the Part 820 regulation requirements are covered in ISO 13485:2016. However, there are some requirements that are not stated explicitly in ISO 13485, such as the Device History Record (FDA Part 820.184). The ISO 13485:2016 standard’s Control of Records (Clause 4.2.5), Planning of Product Realization (Clause 7.1), and Identification (Clause 7.5.8) implicitly relate to the requirements of Device History Record. A table is provided below to help translate requirements between the two documents.

In general, the 2016 revision to ISO 13485 has closed the gap with FDA expectations and the FDA now feels that the time is right for 21 CFR 820 to be replaced with ISO 13485:2016 Quality Management Systems for Medical Devices, the international standard for quality management for the medical device sector. It is expected that ISO 13485 will become the FDA’s mandatory QMS after the transition.

Making the Transition

This transition will be very beneficial and an unprecedented step for global harmonization. When US and international standards vary, it can increase the difficulty and cost of record keeping. The FDA’s adoption of the international standard can help reduce these costs and make it easier for US companies to comply internationally. It will also simplify the QMS of companies seeking FDA approval for their medical devices and makes international trade and business easier. ISO 13485:2016 has already become the medical device single audit program for EU, Australia, Brazil, Canada, and Japan.

The task is formidable – a presentation published by the FDA states:

• FDA recognizes there will be a significant impact on FDA for implementation. For example:
  • Training on ISO 13485 requirements, interpretation, best practices, etc. to CDRH staff and ORA investigators and compliance officers
  • Changes to the inspection model (QSIT)
  • Revisions/updates to numerous documents
  • Changes to IT systems
• Transition period will likely be a few years

The Association for the Advancement of Medical Instrumentation (AAMI) Technical Information Report (TIR) AAMI TIR102:2019 serves as the officially recognized bi-directional mapping tool for the medical device industry. It outlines the comparative analysis between ISO 13485:2016 and 21 CFR 820 QSR and vice versa. This tool was developed by AAMI with FDA participation.

Those medical device manufacturers and suppliers who have yet to address ISO 13485:2016 should begin assessing their QMS to determine gaps in meeting the guidelines. Clarkston Consulting has an experienced cadre of medical device professionals who can help you plan for and execute the transition of requirements when they are announced by the FDA. It’s never too early to start planning.