Harmonization of international regulatory requirements for medical devices began in 1992 with the founding of the Global Harmonization Task Force (GHTF). There were five founding regulatory bodies: 1) US FDA, 2) Health Canada, 3) European Commission, 4) Therapeutics Goods Administration of Australia, and 5) Ministry of Health, Labour and Welfare in Japan. The organization created many guidance documents for the medical device industry, and members of the GHTF organization also participated in the development of ISO 13485 that was released in 1996. GHTF was disbanded in late 2012, and it has been replaced by the International Medical Device Regulators Forum (IMDRF) (http://bit.ly/IMDRFDoc), and IMDRF maintains the documentation created by GHTF.
In 1996, when ISO 13485 was released, Health Canada made certification to ISO 13485 mandatory for all medical device manufacturers that wanted to distribute in Canada. Health Canada’s requirement for ISO 13485 certification resulted in the widespread adoption of ISO 13485 certification throughout the world. At the same time, the US FDA chose to publish its Quality System Regulations (http://bit.ly/21CFR820-compliance). The QSR is very similar to ISO 13485, but there are minor differences beyond the obvious reorganization of the requirements.
FDA Modernization Act of 1997
Under the FDA Modernization Act of 1997, the FDA implemented a 3rd party review program for 510(k) reviews and inspections (http://bit.ly/3rd-party-implementation). This program involves “Accredited Persons” (AP) that have been trained by the FDA and work for a third-party consulting firm, registrar, or Notified Body. The FDA expanded the pilot program for 510(k) reviews to include most 510(K) devices (http://bit.ly/3rd-Party-Review-List). Unfortunately, even though there was great interest from third-parties to participate in the program, there was little interest from manufacturers. After more than a decade, only the following seven third-party organizations have managed to get an Accredited Person (AP) to complete the qualification process so that they can perform inspections independently:
- Orion Registrar
- TUV SUD
- TUV Rheinland
The FDA continues to experiment with different approaches to international harmonization. In 2003, Health Canada (HC) signed a memorandum of understanding between Health Canada (HC) and the U.S. In 2006, the FDA launched the pilot, Multi-purpose Audit Program (pMAP) (http://bit.ly/HC-FDA-pMAP). Third-party auditors performed ten combined audits. The conclusions and recommendations resulting from the pMAP were posted on the FDA website in 2010. One of the recommendations was to develop a guidance document for the format and content of regulatory reports. Therefore, in 2011, GD211 (http://bit.ly/GD211-report) was released by HC, and several videos were posted on the FDA website by HC and the US FDA for training (http://bit.ly/CDRH-Learn-Course-list).
Once the 14 recognized registrars had managed to train their CMDCAS auditors (http://bit.ly/CMDCAS) on the GD211 report format, the FDA announced the Voluntary Audit Report Submission Pilot Program (http://bit.ly/Voluntary-Audit-Report). For eligible companies, they may submit a regulatory report in the GD211 format, and the FDA will remove the manufacturer from the routine workload for FDA inspections. A few companies have taken advantage of this and successfully avoided a routine inspection for 12 months.
FDA’s New Pilot Program
Recently, the FDA announced a new Voluntary Compliance Improvement Program Pilot (http://bit.ly/FDA-VCIP). This new program is a small pilot that will allow 3-5 manufacturers to select a third party (to be approved by the FDA) to help them identify areas for compliance improvement and initiate corrective actions. Identification of areas for improvement would presumably be determined during a mock-FDA inspection performed by the third party, but this is not explained in the FDA announcement. This program is available by invitation only, but it appears to be a significant departure from the AP program and voluntary submission of GD211 audit reports.
IMDRF is finally starting to have an impact on the harmonization of medical device inspections. In January 2014, the FDA began accepting inspection reports from the Medical Device Single-Audit Program Pilot (MDSAP) as a substitute for routine agency reports. Kim Trautman at the FDA is the IMDRF representative chairing the program, and her presentation announcing the program can be downloaded at the following website link: http://bit.ly/IMDRF-MDSAP. This program should be extremely popular with manufacturers because the MDSAP reports can also be used to meet requirements for inspections by Japan’s MHLW and Brazil’s ANVISA. ANVISA has a massive backlog of inspections due to a strike by government workers, and many companies were forced to file a lawsuit against ANVISA to accelerate the inspection prioritization. The challenge with the MDSAP will be to train and qualify third parties to conduct the audits correctly.