What FDA Safety Rule? Steve Goldman Explains
4 CommentsBy Ed Silverman // November 1st, 2007 // 6:40 am
The FDA Amendments Act may have just been enacted, but that doesn’t mean all safety issues have been resolved. Depending upon who you speak with about the agency, you can hear lingering concerns and complaints about unfinished business. One such issue is a proposed rule on safety reporting requirements for drugs and biologics, which was released by the FDA for comment in 2003. Designed to update industry pre-and postmarketing safety reporting requirements, the proposed rule has languished with no announced timetable for finalization and implementation.
We chatted by phone and e-mail with Stephen Goldman, a physician and former FDA MedWatch Medical Director who is now an independent industry consultant. While at the agency, he participated in drafting the 2003 proposed rule, and recently published an article* about this important, but overlooked topic in The Food and Drug Law Journal. In this paper, he openly voices concern that the failure to finalize the proposed rule leaves industry in a quandary, which by extension impacts public health in the US. Here’s what he had to say…
Pharmalot: Why is this proposed rule significant?
Goldman: You have to take a broad view. Most companies operate on both national and international levels, so that regulations that impact a company in one country or region affect what goes on elsewhere. As a result, you’ve got to be well aware of regulations and other regulatory requirements in the US, Europe, Japan and other sectors. However, over the past few years, there’s been clear separation in the pace at which updating and finalization of safety reporting requirements have occurred in the US and European Union.
The proposed rule is a document that had been worked on for many years before being issued. As the regulatory rewrite of pre- and post-marketing rules for safety reporting, it’s clearly a major document. But it was released in March 2003, and the comment period ended in October 2003. Here we are, four years later, and the undecided status of the updated pre- and postmarketing safety reporting regulations for drugs and biologics continues unabated.
Pharmalot: What exactly is the problem with the reporting requirement in the US?
Goldman: While there have been several excellent safety-related documents released by FDA over the past few years (such as three risk minimization guidances issued in March 2005), current regulations don’t reflect the state-of-the-art in clinical trial safety or postmarketing pharmacovigilance. In addition, it’s regulations, not guidances, that establish the ground rules for inspections performed by the FDA.
Despite all the activity regarding drug safety in the US, there’s been very little, if any, discussion of inspectional programs for pre-marketing clinical trial safety and post-marketing pharmacovigilance. While certainly constructive in many respects, the new FDA Amendments Act doesn’t address concerns about the lack of action involving regulations, or the need for increased funding and personnel dedicated to FDA’s compliance programs.
Pharmalot: What are the implications?
Goldman: It’s an important public health issue, because it makes it harder for industry to do the right thing. Look, industry safety specialists are well aware of what’s considered state-of-the-art in pre-marketing clinical trial safety and postmarketing pharmacovigilance, and are committed to performing their work using standards which are constantly evolving due to new techniques and accruing knowledge.
It’s the current overarching pharmacovigilance regulatory document in Europe (known as Volume 9a), the FDA’s Proposed Rule, European Clinical Trial Directive and the applicable guidance documents that provide standards, rather than current FDA regulations that don’t reflect pre- and postmarketing safety in 2007. However, should a US-based senior-level safety professional in a pharmaceutical company need increased personnel and funding to perform premarketing and postmarketing safety and risk management activities that are consistent with the latest standards, a finalized rule can’t be cited for support and justification to non-safety upper management.
Pharmalot: So the lack of a finalized rule puts US patients at a disadvantage?
Goldman: I’m saying that both the ongoing lack of finalized pre- and postmarketing safety reporting regulations and lack of optimal funding and resources for FDA’s safety-related inspectional programs have implications for public health. Both the industry’s need to perform its mandated safety functions, and the FDA’s associated compliance activities, need to be based on the latest standards and practices in order for the likelihood of safe use of effective pharmaceuticals to be enhanced.
* The Food and Drug Law Journal, Volume 62, Issue 3. Provided with permission from FDLI
Tom
I spent a good chunk of 2003 reviewing the draft safety law. While ambitious and well-intended, much of it went in the opposite direction from what multi-national companies really need to optimize safety: harmonization of requirements so they don’t need to create one process for the FDA and one for the rest of the world. The law gave the impression of trying to adopt ICH standards, but it was laced with strange caveats and individual pet peeves that generated thousands of comments and clarification requests from the pharma industry and medical community. Since 2003, companies have increasingly used the standards of the European Medicines Agency (EMEA) to develop their pharmacovigilance and risk management procedures. This is unfortunate, because the FDA regulations and guidance usually are more pragmatic and transparent than those of the Europeans (the 2003 rule excepted!). Unfortunately, it takes our U.S. agency 10 years to complete a regulatory overhaul, and in the eyes of many the EMEA and the UK’s MHRA have dislodged it as the world’s leading drugs regulator.
Arnold
I too devoted a lot of time reviewing the 2003 draft Rule and submitted, on behalf of an organization, 45 pages of comments, mostly critical. For example, many of us believe that the proposals concerning medication errors are ill conceived, unnecessarily burdensome, and will not imporve public health. Although it has been more than four years since its issuance, there are good reasons for the delay in its finalization: the comments from various sources raised significant concerns and disagreements with many of the proposals, which were judged by most of us as contrary to the stated objectives of the Rule, among which was the international harmonization of practices. I believe there are serious ongoing debates within the Agency regarding many of the proposals. It is unfortunate that FDA has not tried to separate out some of the major proposals for separate finalization and implementation, such as those involving electronic reporting, coding terminology (MedDRA), PSURs, and others. I, for one, believe that the Rule should not be finalized without major modifications.
Grief
I have not read the document, but Mr. Goldman is saying that not only does a document need to be passed, amended or not, after four years, but that the FDA does not have enough resources to do the job even if/when it is passed. If this is the case, why was the recent PDUFA/Drug Safety bill passed by a near unanimous majority of the House and Senate?
David
I too submitted many comments to the proposed rule, and find myself in practically complete agreement with Arnold that the rule should not be finalized without major modifications. The FDA idiosyncrasies buried in the document would make life even more difficult rather than easier for the dedicated folks dealing with pharmacovigilance, pharmacoepidemiology and risk management in the US. While some safety specialists, as Dr. Goldman points out, may face difficulties in obtaining all the needed resources to optimize the functioning of their drug safety departments, the finalization of the proposed rule would only make the burden more difficult to carry. It would add some requirements that have little or no documented evidence supporting the concept that they would improve patient safety. Particular attention needs to be paid to some of the definitions, e.g., contractor, that would result in absurd requirements for the regulated industry, as well as to the FDA use of certain definitions adopted by ICH, instead of the reporting requirements agreed to by the same expert working group. The additional requirements for “always expedited†reports for certain events such as “seizures†would impose an additional workload on both industry and the agency (about 3-4% of the total reports included in the AERs data set publicly available are coded as seizure), and some are so poorly defined (“sclerosing syndromes†which has no match in MedDRA terminology or 59 different PT’s with including the string “sclerosâ€) that would make it counter productive or extremely difficult to implement. The addition of the always expedited proposal, given the submission of more than 350,000 reports a year of which about 10,500 could be expected to include a patient with a seizure, might be expected (assuming each case could be adequately assessed in 15 minutes) to require at least 2625 man hours for review of these cases at the FDA. Finding the funds for such additional resources both in the industry and at the FDA should be justified by scientific evidence that it would result in improved patient safety.