Q&A Expanded Version
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Kessler
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A lot of effort has gone into developing guidance documents toward this end, and now many of these guidances are starting to be implemented, making global harmonization a reality, no longer just a buzzword. There are now systems that enable nations with developed regulatory systems to share audits and adverse-event reports, and to accept certain kinds of premarket applications from the same form. Such systems could be adopted by nations with less-developed regulatory systems, meaning these countries don't have to start from scratch.
One of the people making harmonization happen is Larry Kessler, ScD, GHTF's current chair. (The chair rotates every 18 months among the organization's founding members; currently, the United States holds it.) Kessler is director of CDRH's Office of Science and Engineering Laboratories, which helps the center determine issues of safety and effectiveness through product testing, scientific investigations, and other methods. Before that, he was director of the center's Office of Surveillance and Biometrics, which among other things implemented the user portion of the MDR system. He spoke to MD&DI editor-in-chief Erik Swain in November.
Q: How would you characterize the mission of GHTF, and how close is it to being realized?
A: There are three parts to that answer. The first part of our mission is to develop documents that provide an opportunity for the five founding members (Australia, Canada, Japan, the European Union, and the United States) to bring their regulatory systems closer together. By developing guidance documents, we can help change the regulatory structures to achieve harmonization. The second part is to have these guidance documents serve as a blueprint for countries with underdeveloped regulatory systems, so that they are not in conflict with the rest of the world. The third is that by doing these things, we are helping global trade.
How far along are we? We have had notable success but there is still a long way to go. We have done extremely well in terms of producing documents that can forge consensus and help develop a regulatory system. Australia revised its entire medical device regulatory system based entirely on GHTF guidance documents. What they have done is truly remarkable. Canada has made remarkable strides as well. The EU, the United States, and Japan have made fewer leaps, although the EU has done some good things. The United States has also done a few things, though not as much as it could. CDRH is working on seven guidance documents based on the GHTF model. We are not there yet, but in the next year, we will take significant steps closer to real harmonization.
More proof of accomplishment is the work with the Association of Southeast Asian Nations (ASEAN), which represents countries totaling more than 500 million people. They have instructed their device regulators to convert all regulatory systems to the GHTF model by 2010. There have been significant responses from Singapore, Malaysia, and Thailand. Others are moving ahead more slowly, but they are moving. That is very exciting news. We have also worked with the Asian Harmonization Working Party (AHWP), which covers about 22 nations, including China and India. A number of the AHWP countries are also in ASEAN, but some others have been added. Through these groups, we have the potential to move forward the GHTF model to over half the world's population. ASEAN, plus China and India, is an enormous reach.
Q: GHTF held a conference in October 2007 in Washington, DC. What were the most significant accomplishments of that conference?
A: I would say there were three. First, the steering committee moved forward a document called N33 from Study Group 4. That is now a final document. It recommends a standard audit format for medical device companies. That's a big accomplishment. Companies and regulatory agencies that perform audits can use the same format to process audits for multiple countries without having to repeat them. This will help both regulatory authorities and companies to save resources.
Second, there were significant numbers of people from AHWP and Latin America in attendance; we had 25 representatives from 13 Latin American countries. They were able to present their regulatory situations and progress. In addition, they were able to fit in two days of training by GHTF, including participation in the National Competent Authority Reporting Program. That enables governmental authorities to share significant adverse-event reports with each other and to circulate reports of public health problems caused by adverse events.
The other development was the creation of several small ad hoc groups out of the GHTF steering committee that can tackle certain issues that the study groups might not be able to take on. Previously, we had only two study groups: one on medical device software and one on combination products. We added groups that will focus on GHTF training, construction of a global regulatory model, and medical device nomenclature that can be used worldwide.
Q: How would you characterize collaboration between industry and regulators?
A: The regulators involved have to make a significant commitment to increase adherence to GHTF guidance. By the same token, this has always been a regulatory–industry partnership. I believe industry has not come to the table in terms of submitting STEDs and volunteering for multipurpose audits. They have not used the opportunities that some regulators have provided, and that makes moving forward with harmonization difficult. They are not quite where they need to be. There is room for them to step forward and I would like to see them do so. However, if there is a reason they can't, I would like them to say why. That's really important. My friends in industry may have their reasons. Some companies do not want to be guinea pigs. But if every company takes that stance, what can regulators be expected to do?
Q: What strides has GHTF made as far as sharing adverse-event reports worldwide?
A: The National Competent Authority Program is the vehicle we are using. A number of countries have signed up, including the United States. The program is expanding and every year more reports are being shared. A number of public health issues have been addressed as a direct result of sharing information. That is really good news.
Q: How can risk management principles be applied globally?
A: Risk management as a concept has increased in importance over the years. We are getting very attuned to sophisticated methods of risk management. One vehicle that has driven this is the publication of ISO 14971, “Application of Risk Management to Medical Devices.” Most, if not all, competent authorities have recognized that document, which means we have a consistent way to think about risk. Having said that, ISO 14971 is not a cookbook. It's a framework for considering risk management. I believe its adoption throughout the device world would make an enormous difference.
Q: In the past, you have said that ISO 13485 and FDA's Quality System Regulation are as close as they have ever been to being harmonized. What more can be done, and what does this mean for global medical device manufacturers?
A: I can only give a partial answer. The rest would have to come from the CDRH Office of Compliance. We are moving close to being able to use [multipurpose] audits, especially with the advent of N33. In the language of the FDA Amendments Act of 2007, there is a provision that gives CDRH the opportunity to use 13485 inspections to set priorities. We are trying to find ways to leverage that provision. Companies that pass 13485 inspections with flying colors might not be a high priority for FDA to visit. The Office of Regulatory Affairs is trying to figure out how to use this in a constructive way. However, there are technical differences between the QSR and 13485, and I can't speak to those.
We are launching a pilot multipurpose audit with Canada, but there has not been much interest so far. We found out at the GHTF meeting that in some cases auditors are discouraging clients from such audits because not many auditors have been qualified [in the United States]. That is a legitimate bottleneck. But there are at least seven auditors that have been qualified, and they can do about 20 a year. So we know we could get about 140 scheduled, but the actual number of audits scheduled has been much lower than that. It's a little frustrating.
Q: Will we ever see a truly global harmonization process? Do medical device manufacturers even want that?
A: I believe that device manufacturers hope to use the GHTF model to have premarket authorization from one country and be able to use it as entrance to other markets. That's a good thing. It's hard to do in the United States because our premarket system is different. Many Asian countries are moving in that direction. However, there's a flip side to sharing audit results. For example, if, say, the German notified body fails your product, and these results are shared with others, your product might be pulled off the market around the world. Industry wants the advantage of going on the market all over the world simultaneously, but seems reluctant because of that risk. I can't blame them for being concerned.
Study Group 3 is trying to develop a document that speaks to the unified handling of the significance of quality system differences. For example, the United States uses the word recall to mean a lot of different things. A Class 1 recall means there is an imminent and significant threat to public health. A Class 3 recall can mean something as simple as a labeling change. But recall can indicate product withdrawal in other countries—sometimes one adverse event means you're off the market. That is not good for companies, and it's not good public health. We are trying to sort it out so companies don't get discouraged. We are not there yet.
Q: Will the Summary Technical Documentation (STED) format be adopted?
A: Absolutely. AHWP is working on a version that is almost complete. We are about to finalize the GHTF STED. It has potential for enormous reach, but we are not there yet. Adoption in the United States is still slow. Of the 3500 or so 510(k) applications that came in last year, over 2000 could have been filed in the STED format, but very few were.
We are already seeing its influence on other standards. For example, the third edition of ISO 60601: “Medical Electrical Equipment” almost requires use of ISO 14971 for compliance. Companies that make electrical medical products must have an approach to risk management that is consistent with what ISO 14971 says. We in GHTF are trying to adopt risk management practices from ISO 14971 without appropriating the whole thing, just the parts that are relevant to an audit. That way, auditors know that they can use the risk management approaches from the standard and companies know that they can apply it consistently throughout the total product life cycle. GHTF is addressing quality management systems overlaid with risk management in a way that will make a big difference.
Q: During your term as GHTF chair, you have made beefing up organizational logistics a priority. What sort of progress has been made?
A: First, we have made documents available on our Web site and have made them more transparent. We gave out all the presentations from the GHTF meeting to attendees on memory sticks, and we got the final versions up on the Web site less than a month after. We are revamping the Web site to launch on January 1, 2008. At that time, we will have translated documents available, particularly in Spanish and Portuguese. We have met with China 's SFDA and Shanghai 's FDA to work on translating into Mandarin.
Second, we have set up three more ad hoc groups, which I mentioned earlier. That way makes sense rather than putting all that work on the study groups, which already have so much on their plates. They are getting on track.
Q: What new topics do you anticipate GHTF looking at in the near future?
A: One topic that has come up is exploring the effects on the standards by which conformity assessments are delivered. We are looking at working with the ISO Council Committee on Conformity Assessment (CASCO) to develop standards there, in partnership with the International Accreditation Forum. That may provide a mechanism for countries that don't have an FDA equivalent to guarantee that audits are done by organizations that have been accurately accredited. We are not committed to anything yet, but it looks very promising. We are trying to get an international accreditation standard so we can all be sure that the audits done are high quality.
I would like to see us consider nanoproducts. I would also like to see us address products that move from hospital-based care to home-based care. That is a big issue.
