Mark Mansour, Partner, Bryan Cave, LLP
FDA May Ask for Rescission Authority for 510(k) Clearances
CDRH Director Jeffrey Shuren has stated that, as the agency considers proposed changes to the 510(k) process, it may request additional authority from lawmakers, including 510(k) rescission authority. The agency has said that it is challenged by a lack of robust ability to rescind device clearances. Industry officials argue that any new powers should be limited and restrained, while patient advocates praise rescission authority as an important step towards strengthening the safety of devices cleared through the 510(k) process.
Devicemakers Worried About Bayh’s Retirement
Devicemakers with facilities in Indiana, including Boston Scientific, DePuy Orthopaedics, Medtronic and Zimmer, have expressed concern about losing support in the Senate following Sen. Evan Bayh’s retirement at the end of this year. In announcing his decision to step down, Bayh touted his advocacy for device companies as a major accomplishment; the industry employs more than 45,000 in the state.
FDA Appoints Two to Tobacco Panel
Reports are stating that the FDA has selected Jack Henningfield, VP for research and health policy at Pinney Associates, which works on behalf of GlaxoSmithKline, and Neal L. Benowitz, a UC San Francisco professor who has consulted for GlaxoSmithKline and Pfizer, to a panel responsible for regulating the tobacco industry.
China Health Reform Spending Benefits Device Manufacturers
The $125 billion in spending by the Chinese government to start a national health insurance system is benefiting manufacturers of medical devices, including makers of imaging and diagnostic equipment. $41 billion of this amount is being spent to build 31,000 hospitals and equip them with diagnostic and imaging equipment.
Mark Mansour is a partner in the firm, Bryan Cave, LLP
Brad Ryba, Publisher, www.my510k.com
Much has changed in the FDA over the past year, and it appears more change is to come. Issues surrounding device approvals under the 510(k) process were front-and-center in a public meeting this past Thursday. The meeting was titled by the FDA, “Strengthening the Center for Devices and Radiological Health’s 510(k) Review Process” and the agenda included a full day of discussion. FDA invited 30 speakers including industry executives, physicians, and policy advocates. Preceding the speakers, FDA did make some presentations citing its challenges under the current system. This was followed by a round-table discussion, along with some open Q&A sessions. From this meeting, it seemed two clearly differing agendas will shape policy changes over the coming months.
The FDA was clearly laying out the case for why it wants to make changes, while trying to broaden its powers beyond the current 510(k) process. When Dr. Donna-Bea Tillman, Director for CDRH Office of Device Evaluation made her presentation, she seemed to be open minded, stating that, “Trying to find the right balance between a regulatory process that enables us to foster innovation and at the same time ensures reasonable assurance of safety and effectiveness is the challenge we are here to talk about today.” Christy Foreman, CDRH Deputy Director for Engineering and Science Review was a bit more wary of industry, particularly in areas where FDA does not have as much authority. She contended, “Submission for [510(k) ] modifications are based on firm’s determination regarding the effect on safety and effectiveness. ” Ms. Foreman seemed to be hinting that this was an area she and FDA wanted to see addressed. Their concern is that documentation for incremental device changes is currently only kept in a firm’s internal files rather than defaulting to an FDA evaluation. Many other suggestions by FDA speakers indicated that The Agency wants increased oversight into clinical trials and labeling regulation. Further, the Director of 510(k) staff, Heather Rosecrans suggested that FDA needs broader powers to more easily rescind a 510(k) clearance if necessary. Many more comments and side issues emerged during the presentations, and these comments did not go unanswered by the industry representatives in attendance.
Most of the participants from the medical device industry advocated for the continuation of the 510(k) process, with a focus on consistency and transparency. Medtronic’s Chief Regulatory Officer, Susan Alpert highlighted the result of a cumbersome 510(k) process citing, “Our products go more quickly into other markets under other schemes than under this scheme”. She and her counterparts at the round-table discussion offered several suggestions to help the program evolve, while stressing that the current process works well for the majority of devices. Putting it another way, Craig Coombs, Head of Coombs Medical Device Consulting argued, “It’s not the 510(k) process. It’s what our interpretations are… predictability is really what needs to be there in order for us to comply.” These messages were echoed by many of the other industry speakers, and it is clear that this topic will continue to receive much further discussion.
FDA will continue to hear comments on the 510(k) process, and a Working Group is scheduled to submit its report to CDRH Director, Jeff Shuren, by the end of May 2010. The docket for comments on 510(k) process will remain open until Mar. 19, 2010. Comments are also being compiled by the community at my510k.com and on Twitter. While suggestions are being taken by FDA, their position seems clear that “Strengthening the 510(k) Review Process” means getting tougher on industry.
Mark Mansour, Partner, Bryan Cave, LLP
The past several months have brought forth numerous bits of news, pronouncements, expressions of concern and general uncertainty about the device regulatory regime, but also about FDA’s regulatory paradigm in general. The recent piece in the New York Times regarding disagreement about the diabetes drug Avandia and the controversy involving accusations of conflict of interest by CDER head Janet Woodcock in the consideration of competing applications for enoxaperin, in the wake of last year’s resignation of Dan Schultz at CDER has led many to wonder where FDA is going under Dr. Margaret Hamburg.
Clearly, the new leadership at FDA is now acutely aware of the number and scale of the issues confronting FDA. In their overwhelming majority, the scientists and technical specialists at FDA are dedicated and committed individuals. At the higher levels, however, FDA has suffered from a series of problems, none more troubling in its long-term implications for the future of the industries it regulates, than its absence of imagination.
The FDA’s approach to science is rooted in statistical models, and those models and the people who analyze their results are wholly unwilling (as a matter of culture) to do finely tuned, meaningful risk-benefit analysis. Several years ago, FDA’s own internal assessment cautioned that this blind reliance on statistical analysis will render it entirely incapable of assessing a new generation of complex devices, medications and combinations. The FDA is earning a reputation for inability to approve a product either safely or accurately, because it evaluates products in a statistical vacuum, without regard to societal benefit, need or even real-world safety variables.
There is some hope to be found in the fact that CDRH recently admitted that it needed new methods and new thinking, precisely along these lines. That represents a refreshing start, but it will only make a difference if it is inculcated in FDA’s culture as a whole. Dr. Hamburg has quite a challenge ahead of her.
Mark Mansour is a partner in the firm, Bryan Cave, LLP
Mark Mansour, Partner, Bryan Cave, LLP
FDA Seeks Comments on Proposed Information Collections
The FDA has announced an opportunity for public comment on several proposed collections of information. The agency is seeking comment on information collection requirements relating to shipment of nonsterile devices that are to be sterilized elsewhere or are shipped to other establishments for further processing, labeling, or repacking. The agency is also seeking comments on a new exception from the general requirements for informed consent to permit the use of investigational in vitro diagnostic devices to identify chemical, biological, radiological, or nuclear agents without informed consent in certain circumstances. The agency also seeks comments on its Guidance for Industry on How to Submit a Protocol Without Data in Electronic Format to the Center for Veterinary Medicine. Comments are due by April 19, 2010.
In addition, the agency is seeking comments on Antimicrobial Animal Drug Distribution Reports and on its Guidance for Humanitarian Device Exemption Holders, Institutional Review Boards, Clinical Investigators, and Food and Drug Administration Staff: Humanitarian Device Exemption Regulation: Questions and Answers. Comments are due by March 22, 2010.
FDA Seeks Comments on Proposed Data Falsification Rule
The FDA is proposing to amend its regulations to require sponsors to report information indicating that any person has, or may have, engaged in the falsification of data in the course of reporting study results, or in the course of proposing, designing, performing, recording, supervising, or reviewing studies that involve human subjects or animal subjects conducted by or on behalf of a sponsor or relied on by a sponsor. Comments on the proposed rule are due by May 20, 2010. More information is available here.
Court of Appeals Agrees to Delay E-Cigarette Decision
A federal court of appeals has agreed to stay the decision of the U.S. District Court for the District of Columbia that lifted FDA restrictions on e-cigarettes. The court ruled last month that the FDA misused its authority when it classified e-cigarettes as a drug-device combination and placed the products under an import alert.
Drug Companies May Have to Wait Longer for REMS Final Guidance
It is being reported that the final guidance on risk evaluation and mitigation strategies (REMS) may be delayed, as the CDER staff developing the recommendations must also review all proposed REMS from drugmakers.
Companies Comment on Proposed Combination Products Rule
Manufacturers of combination products, including Johnson & Johnson, have submitted comments on the FDA’s proposed rule on good manufacturing practices (GMPs) for combination products, saying that the rule needs more guidance and should better address legacy products.
Mark Mansour is a partner in the firm, Bryan Cave, LLP
In Washington, D.C., experts tracking the political shifting sands often advise you to watch what someone does, not what they say. Applying that to the FDA suggests the agency is starting to take risk management enforcement a bit more seriously.
Here’s a good example. Earlier this week (Feb. 16) the agency approved a risk management program to inform healthcare providers and their patients about the risks of a class of drugs called Erythropoiesis-Stimulating Agents (ESAs) manufactured by Amgen Inc. The company’s risk management program or Risk Evaluation and Mitigation Strategy (REMS), requires health care professionals to provide their patients receiving an ESA with a Medication Guide that contains information for patients on how to safely use a drug.
And earlier this month, the agency requested a 23% hike in its budget to help it more aggressively pursue food, drug and device safety (plus its new tobacco initiative).
More action and more dollars could add up to a more active FDA in 2010.
Make sure to read our previous post: Risk Management Matures Beyond the Spreadsheet
Brad Ryba, Publisher, www.my510k.com
Before all this talk of “Snowmaggedon”, a beaming headline posted late last week stating that, “FDA Issues Guidance to Help Streamline Medical Device Clinical Trials”. If you were hoping to learn how it works, you were in for a statistics lesson on Bayesian methods for designing studies and analyzing clinical data. (Wait, don’t leave!) Good news is you don’t need a statistics lesson, to simplify the main point. FDA is now advocating the use of prior clinical data and even post-market data from a prior device to justify shorter clinical studies and/or smaller sample sizes. This is a huge change from the same Agency that has demanded more data and more time to review device approval applications. How can this be? Why does Bayesian probability allow us to do this? The answer is not rocket science.
Bayes’ Law basically views probability as just “degree of belief” that an event will occur today, given knowledge of prior events. Think of it this way…Have you ever “tried” to flip heads on a coin, or roll an 8 with dice? How is this possible, if the probability of coins and dice are already known? Since we know the physical act of flipping the coin can affect its outcome, it may not be a simple 50-50 probability. The Bayesian idea of prior beliefs, allow us to set constraints and make conclusions beyond the actual data. Humans are quite good at intuitively making predictions on very little information. Bayes just put this into mathematical notation. (not to diminish the significance of Bayes’ Law in any way.)
Now, before this starts to sound like a “free pass” to shorter clinicals, be sure to finish reading the FDA guidance. Once again for the sake of time, we can summarize… It makes sense that statistical theory cannot replace sound clinical science. The FDA is quick to caution that patient data from prior studies rarely are 1-to-1 exchangeable with the patients in the current study. Instead, a test can be applied to find their “borrow strength” from the previous studies. Also, FDA will require that you still submit to their reviewers, your rationale for considering such prior clinical data. All of the same requirements apply when filing for an Investigational Device Exemption (IDE), and all methods and assumptions will need to be reviewed before the study can begin.
That said, the fact that good prior information on clinical device use exists, and that a Bayesian approach may enable smaller-sized or shorter-duration trials is welcome news to the industry. In the official press release, FDA Commissioner, Dr. Margaret Hamburg says, “This is a terrific example of regulatory science in practice at FDA.” We at my510k.com hope to see these kinds of developments continue, balancing regulation enforcement with sound scientific practices.
Join the community at Brad Ryba’s website: http://www.my510k.com
Mark Mansour, Partner, Bryan Cave, LLP
CDRH Publishes Strategic Priorities for 2010
CDRH has published its 2010 Strategic Priorities. The four major identified priorities of CDRH include: fully implementing a total product life cycle approach, enhancing communication and transparency, strengthening the workforce and workplace, and facilitating innovation and addressing unmet public health needs. Within these priorities, CDRH has set forth a timeline, in which it states that it intends to begin implementation of the recommendations of the 510(k) Working Group by September 30, 2010. Director Jeffrey Shuren has indicated that he plans to review public comments from a meeting this month and the findings of an internal review, to be completed this summer, before making any proposals. In its notice announcing this month’s meeting on the 510(k) process, the FDA stated that it is seeking comments pertaining to four areas: predicate devices; new technologies and scientific evidence; practices for managing the high volume of 510(k) submissions; and post-market surveillance.
CDRH has also announced that it intends to launch a “Unique Device Identification” (UDI) system by Sept. 30, 2013.
FDA Moves Radiological Devices Branch to OIVD
FDA Commissioner Margaret Hamburg has signed orders to officially move the Radiological Devices Branch to the Office of In Vitro Diagnostic Device Evaluation and Safety, a result of long-term discrepancies between how in vitro and in vivo diagnostics have been regulated by FDA. OIVD will now house four product divisions – the division of chemistry and toxicology devices; immunology and hematology devices; microbiology devices; and radiological devices.
FDA Enforcement Letters on Marketing Campaigns Doubled in 2009
An FDA official has stated that the agency sent 41 enforcement letters in 2009 related to questionable drug-marketing campaigns, almost twice as many as it issued in 2008.
Mark Mansour is a partner in the firm, Bryan Cave, LLP
