[1]In recent years, drug shortages have been a recurring problem. The latest list [2] from the Food and Drug Administration totals nearly 70 medicines in short supply, including the Nasonex allergy drug and the Bystolic blood pressure pill. Hoping to better predict shortages before they happen, the FDA proposed new guidelines [3] that could go into effect next year and require drug makers to provide specific data about their production facilities, including quality complaints, in advance or instead of inspections.
The agency claims this information will help root out the kinds of quality-control problems that lead to product shortages, but drug makers are irate [4]. They argue the program will become expensive because most companies do not compile data uniformly. They also worry about the extent to which they are held responsible for contract manufacturers. And they complain there are penalties for not complying, even though the FDA says the program will be voluntary.
We spoke with Janet Woodcock, who heads the FDA’s Center for Drug Evaluation and Research, about the agency proposal and her reaction to industry concerns. This is an edited version…
Pharmalot: What’s the problem with how quality-control data are collected now?
Woodcock: We have to manage an inventory of drugs that are made in the U.S. and all over the world and, sometimes, at three to four sites sequentially. What we’ve traditionally done is we’ve assessed quality of a manufacturing site by periodic inspection, and those have been every two years or less in the U.S. but much longer overseas. Many years ago it struck us that, in other industries – like automotive, chemicals, semiconductors – the companies have tight control over manufacturing and keep metrics about how well they’re doing. So it seems to us that having more quantitative and objective data to evaluate manufacturing performances at every given process is beneficial.
Pharmalot: How would the suggested measures help address drug shortages?
Woodcock: We think reliability is one of the attributes of manufacturing quality. You shouldn’t have shortages caused by reliability problems. You can have shortages from supplier problems or something else. But this [approach] should diminish shortages, because it allows us to intervene early to prevent shortages. You know, when you have a trend, you try to intervene before you have an explosion.
Pharmalot: What would FDA do if the data foretells an issue?
Woodcock: We’ll be able to predict [if companies] are going to get into trouble, but we shouldn’t have to intervene. We want them to intervene, and by proposing these metrics, we’ve succeeded in moving discussion away from compliance to good manufacturing practices to what is the quality of the manufacturing.
Pharmalot: Drug makers say the FDA lacks statutory authority to implement the guidance. Are they wrong?
Woodcock: Only the courts can, ultimately, determine things like that. But we obviously wouldn’t propose the guidance if we didn’t think it was backed by strong legal support. As we noted in the guidance, we’re working off statutory language recently introduced by Congress that gives us the power to request records in lieu of inspection.
Pharmalot: Another issue being raised is that many drug makers outsource production. So, who takes responsibility for reporting their data?
Woodcock: It is complicated, because of complex supply chains. At the end of day, an application holder [a company that is seeking product approval] is responsible to the FDA. Right now, addressing such problems is not part of this scheme. We’re just trying to standardize metrics. Once we get standards, we’ll figure out how to determine responsibility.
Pharmalot: How will you use the data?
Woodcock: Right now, we have a model for surveillance and inspections that ranks firms and puts them on a list. One of the big factors is whether we visited recently, but another factor is the complexity of a shortage. So we’ll have results of inspections and if there were problems, we want to come back more frequently.
Pharmalot: Why aren’t you making the data public?
Woodcock: If there’s something that we don’t understand, we don’t want to make other people not understand that. For example, biologics are much harder to make than smaller molecule drugs. We could have a situation that would be ripe for misinterpretation and false conclusions. There are also confidentiality issues.
Pharmalot: So we’d have to file a Freedom of Information Act request?
Woodcock: You could.