FDA Launches Pilot to Allow Some Firms to Avoid Re-Inspections

FDA Launches Pilot to Allow Some Firms to Avoid Re-Inspections

March 27th, 2012 // 12:19 pm @

The Center for Devices and Radiological Health (CDRH) and the Center for Biologics Evaluation and Research (CBER) are testing a Pilot Multi-Purpose Audit Program in 2012 and 2013 that will allow medical device companies under their jurisdiction to voluntarily submit certain audits and receive Agency inspection relief for one year.

The policy was announced in Draft Guidance for Industry, Third Parties and FDA Staff Medical Device ISO 13485:2003 Voluntary Audit Report Submission Program, issued by CDRH/CBER in May 2010, and was discussed in a session of the 2011 PDA/FDA Joint Regulatory Conference.

FDA’s goal is to leverage regulatory audits/for risk-based planning of FDA inspections. This is an important prong of a four-pronged approach outlined in a 2011 FDA “special report” called Pathway to Global Product Safety and Quality. During the opening session of the ‘11 PDA/FDA conference, Deborah Autor, who was on the report drafting team, said, “We really pushed ourselves hard to step back and think about what we needed to do to take a quantum leap forward to really deal with the challenges of globalization, not just for today, but ten years down the road. Even if we were to catch up to today, by the time we got there, the world would have changed. We had to rec ognize that we can’t do it alone.” Autor is the Deputy Commissioner for Global Regulatory, Operations and Policy, U.S. Food and Drug Administration.

Four Prongs to FDA’s Product Safety/Quality Pathway

FDA is developing an international operating model (1) that relies on enhanced intelligence, information sharing, data-driven risk analytics, and the smart allocation of resources through partnerships.

The new approach rests on four core building blocks:

FDA, in close partnership with its foreign counterparts, will assemble global coalitions of regulators dedicated to building and strengthening the product safety net around the world.
With these coalitions, FDA intends to develop a global data information system and network in which regulators worldwide can regularly and proactively share real-time information and resources across markets.
FDA will continue to expand its capabilities in intelligence gathering and use, with an increased focus on risk analytics and thoroughly modernized IT capabilities.
FDA will effectively allocate agency resources based on risk, leveraging the combined efforts of government, industry, and public- and private-sector third parties.

The fourth prong delves into partnering with “public and private third parties,” Autor said. “We need to think about the leverage models we can use so that we can have enough information that we need to have about all these facilities, all these products and all these supply chains all around the world, which are many and very disperse. We anticipate they will be even more so, ten years from now.”

FDA is accepting risk by this strategy, but sees no other choice. “If something goes wrong, and I’ve relied on my counterpart, I can see folks in this country saying, ‘How come you weren’t there? How come you didn’t go to this facility and the EU did?’”

The reality is, she said, FDA does not “have enough resources to be everywhere and if I choose to go everywhere that the EU went, just because I’m worried, for example, that something might go wrong and I might have to account for the fact that I relied on someone else and I choose to do duplicative work, then there is a lot of work that I cannot do.”

Ultimately, Autor said, FDA must “leverage and be effective and efficient so that we are treating like risks in equivalent ways, regardless of where they are located. We need to figure out how to get there. That is the challenge at FDA. That is the big picture and that is where we are going.”

Later during the conference, Kimberly Trautman, Expert on MedicalDevice Quality Systems, CDRH, U.S. FDA, said that the pilot program would apply to companies that receive and choose to share with FDA auidt reports from accredited third parties that adhere to ISO 13485:2003, Medical devices—Quality Management Systems—Requirements for Regulatory Purposes. FDA is recognizing third-party auditors accredited by fellow Global Harmonization Task Force member regulatory authorities:

Canada’s Medical Devices Conformity Assessment System
Australia’s Therapeutic Good Administration
European Union Notified Body Accreditation System
Japan’s Medical Device Ministry of Health, Labour and Welfare

The Global Harmonization Task Force was conceived in 1992 in an effort to achieve greater uniformity between national medical device regulatory systems.

If the information contained in the audit meets the needs of the FDA compliance program, the Agency will give that firm a bye on inspections for a year. However, firms need to submit the report to FDA within 90 days of the close of the audit and must include all reports of ISO 13485 audits that were issued during the preceding 2-year period.

Once the Agency receives the report, the CDRH’s Office of Compliance Field Operations Branch will ask the Office of Regulatory Affairs (ORA) to not inspect the firm for 30 days. During this time, CDRH/OC will reivew the audit report per Compliance Program 7382.845. By the end of the 30 days, CDRH/OC will notify both the firm and the Office of Regulatory Affairs of the result, which could be for the District Office to proceed with the routine GMP inspection or remove the firm/facility from the workplan for one year.

Trautman stressed that the pilot program does not preclude FDA from conducting PMA preapproval inspections or for-cause inspections.

During the next two years, the FDA will determine if the policy is viable. FDA is also “figuring out how many times a firm can sign up [for the program],” according to Trautman.
In the course of her presentation, Trautman gave examples of past FDA information-sharing pilot programs. In 2008, FDA implemented a multi-purpose audit pilot program with Health Canada. Manufacturers who participated in the program had the opportunity to be assessed by a qualified auditing organization that met the regulatory requirements of both the United States and Canada. In 2009, the Agency initiated the Third-party (Accredited Persons) Inspection Program. Trautman said that this program hasn’t been utilized very much as “instead of waiting for FDA to come in for free, now somebody would have to pay [the accredited persons].”

[Editor’s note: The U.S. FDA and the European Medicines Agency announced in December that they are formally adopting the information sharing procedure tested during an “EMA/FDA Joint Inspection Pilot Program.” This program related to GMP inspections of drug product facilities. See related story, p. 46.]

Carmelo Rosa, Supervisory Consumer Safety, CDER, U.S. FDA, agreed that inter-regulatory communication and information sharing with other regulatory authorities is necessary to inspect the more than 3,000 domestic and foreign registered drug manufacturing firms.

“It’s not possible for the FDA to inspect the world as much as we would like to. We need to share information.”

In April 2011, he said that the European Directorate for the Quality of Medicines (EDQM) placed a firm under an import alert. After FDA talked to the EDQM inspectors, FDA was able to place its own alert on the company without manually inspecting it.

Rosa said that many of the items that firms are being cited for are not new. “Things that we found 5-10 years ago are the same things we are finding in our inspections now,” he said. Some of the most important issues that were cited related to inadequate laboratory controls, lack of procedures and QA systems, he said.

Another important issue was related to vendor qualification. Rosa said that that firms are still being cited because of poor or inadequate qualification programs. He shared a 2011 warning letter where the FDA cited a firm with a failure to investigate complaints about oversulfated chondroitin sulfate in its product. The firm also failed to extend the investigation to other lots that used the same crude lot and failed to conduct an audit on its vendor that could have possibly caught the problem.

Rosa said that the Agency is looking to see what the possible cause could be for the repeating deviations. In the meantime, he said that the FDA is working with other agencies to identify compliance issues and collaborating with industry to resolve them.

Diane Alexander, Chief, Biological Drug and Device Compliance Branch, CBER, U.S. FDA, had an interesting admission at the conference. She said there is not a trend in the deficiencies in the untitled and warning letters that CBER sends out. However, Alexander noted that in FY 10 the citations that were issued were “unique” to those that had been listed in the past.

The deviations were:

211.192 – “You failed to thoroughly investigate…”
211.113(b) – “Your firm failed to establish and follow procedures designed to prevent microbial contamination…”
211.94(a) – “You failed to assure that drug product containers or closures are not reactive…”
600.14 – “You failed to report biological product deviations…”
600.12 – “You failed to inform FDA about each change…”

Alexander also identified the top six citations for biological drug intermediates and substances in FY10. Citations were related to: investigations, production and process controls, control of microbiological contamination, equipment cleaning and maintenance, laboratory controls, and control of components.

Alexander reminded the audience that FDA expects voluntary compliance from the industry when significant deficiencies or problems are identified. She said that if voluntary compliance is not achieved, FDA will ensure compliance by issuing a notice of intent to revoke a license or, in the case of domestic firms, a firm injunction.


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