USAGE OF EXPIRED DRUGS: When paramedics ran out of a critical drug used to treat irregular heartbeats, the Bend Fire Department in Central Oregon resorted to using expired medications. Medications are only guaranteed to work as intended until their expiration date. When stored properly, most expired drugs won’t be harmful to patients but will become less effective with time, according to medical professionals and according to the Associated Press, Oregon health officials began allowing ambulances to carry expired drugs, and southern Nevada has extended the expiration dates for drugs in short supply. Arizona has stopped penalizing ambulance crews for running out of mandated medications.

THE PROGRESS:  While there are still drug shortages in affect, the United States government and the FDA has begun to play an active role in trying to help the drug shortage problem. New acts signed into law by Barack Obama will speed up the review process of new drugs that could be used in the place of others not currently available. The act will also increase the communication between the drug manufacturing companies and the FDA so that the FDA is ready to help these companies avoid shortages. Furthermore, the FDA has begun to import drugs from abroad that were not yet available in the United States. With these continued efforts it is hoped that the drug shortages will begin to lower. (Source: www.cnn.com)

PRESCRIPTION USER FEE ACT:  The Prescription User Fee Act was first passed in 1992 and has been renewed several times and was renewed most recently this year in the hopes that it would help to alleviate the drug shortage problem in the United States. The act allows the Food and Drug Administration to collect fees from companies that produce particular drugs and biological products in the hopes that it will speed up reviews of new drugs and therapies. In 2012 the act was renewed for another five years and an early warning system for possible drug shortages was also added to the legislation. Under the early warning system, manufacturing companies will have to notify the FDA at least six months before discontinuing a drug or if there are any foreseeable disruptions in the manufacturing process that might make a particular drug be in short supply. Hopefully with warning the FDA will be able to prevent a drug shortage by either helping the company rectify the issue or finding another source of the drug. (Source: www.ama-assn.org)

Real Admiral, Sandra Kweder, M.D., Deputy Director of FDA Office of New Drugs, discusses the current drug shortage problem and what is being done to help the issue.


What is the current situation with the drug shortage problem?

Dr. Kweder:  The current situation is that we are in the midst of what we see as a crisis of drug shortages in this country. We have been in the thick of this for about three years now. The drugs that are in shortage change on an almost daily basis, but the volume really isn’t changing; it’s pretty constant.

This is a really loaded question but, why is this problem happening? What’s behind it?

Dr. Kweder: There are a lot of people who are trying to understand why this is happening now and a lot of people smarter than me who’ve looked at things like economic factors, the industry that makes drugs, as well as pricing for generics and Medicare. From our perspective at FDA what we see is the problem rooted in the manufacturing sector. Really drugs go in to shortage because companies have difficulty making them pure and simple.

Why are they having difficulty?

Dr. Kweder: Again that’s something that remains a question, but what we see when we look at why and as we work with companies is they are mostly having problems with maintaining quality of the production of these drugs themselves. There are a variety of reasons for that.  One of the things that is pretty clear is that most of the drugs that have been in storage, not all of them but most of them are in the generic sector, they’re often older drugs. The majority of these drugs are sterile injectables and sterile injectables require very specific, meticulous, controlled manufacturing systems. When plants and production facilities are not well maintained and updated they start to break down. That’s what we’re seeing with that sector of the market today.

Can you talk about the quality issue with the product?

Dr. Kweder:  The cause of quality issues with the products that we have seen is the kinds of things that are serious concerns to doctors and patients. So for example, we have seen fungus growing in IV bags, we’ve seen bacterial contamination, antitoxin contamination. We have examples of metal shards in IV solution and with glass shards in IV solution; we have precipitate forming in the IV bags or the vials for injection, in one case because the actual active ingredient in the product was reacting to the rubber stopper in the vile.  Those are the kind of things that when we say quality problems are some of the most concerning. We have other examples that are on a more systemic nature in companies where they are getting reports of adverse effects with their products related to quality and they have no system for following up to figure out whether or not this is a continuous problem; they just have nothing in place. Those raised big red flags, and those are the kinds of products that I as a physician do not want my patients getting and I as a patient would never want to be put in position of receiving.

I wonder why in the last few years it seems like those issues are more common than maybe what they were up here, though we didn’t have a drug shortage.

Dr. Kweder: We’re trying to understand why there has been a change. As we see the change, the real slope in the curve probably started around 2006-2007 and it’s really unclear. One of the things that the ASPE (Assistant Secretary for Planning and Evaluation) report did show was 2007 seems to be a banner year for sudden surge in generics, in products turning generic. So there seems to have been at that point in time a real increase in the generic market, so that plants were operating more and more continuously. If you have a plant and the American public is counting on you to make an important product, one of the things that you need to be able to do is make sure that you have built into your operating schedule enough downtime for idle capacity time in order to institute important repairs, routine maintenance, and really maintaining meticulously quality. That is especially important in facilities that manufacture sterile injectable products. These facilities are amazing to see; every little tiny step needs to be meticulously controlled and it takes time to do that kind of upkeep. If you’re in production mode all of the time, when are you going to do that? That’s one of the things that we’ve seen. Now, is that the cause? It’s certainly an association that we're seeing.

What are some of the drugs that are experiencing the most shortages now?

Dr. Kweder: It’s been interesting to watch, we’ve seen shortages seem to affect certain sectors of the market in succession. For about a year and a half one of the biggest clinical errors that were affected was oncology. It stands to reason because cancer treatments are most often intravenous; they’re sterile injectable products. There seems to be in some of the biggest producers of the sterile injectables we’re having for cancer are having problems. That seems to have abated somewhat and things have improved. We’ve been able to identify alternate sources of product by working with alternate companies to increase production. Antimicrobials also have been pretty heavily affected, but that seems to have been in smaller periods of time. I would say currently one of the biggest areas where I’ve seen problems is with anesthetic drugs; drugs used in operating rooms and emergency rooms, including some of the parental intravenous pain products.

What is the FDA’s role in remedying this problem?

Dr. Kweder: Our role is to do as much as we can to understand when there is a problem or even more importantly a potential problem so that we can try to prevent shortages in the first place; that is number one. If we can’t prevent the shortage we take many steps to try and mitigate the shortage by working with other companies and helping the original company that may be having a production problem resolve that so they can resume business as usual. So our work comes in several stages, and in order to do that we need companies to tell us when they’re running in to difficulties. Getting companies to do that has been something that we’ve spent a lot of time building relationships with the industry over the past five years to do. So if you’re a company and you think you’re going to have a little problem on the production line, you are not required to tell FDA about that. There’s no regulation that requires that except in very narrow circumstances and your instinct is probably not to call FDA. It’s kind of not intuitive that that’s what a company would want to do, but as we’ve built relationships with these companies through our drug shortage program they’ve begun to do that because they know that the public is counting on their production of a particular product. So, they’ve learned that if they contact us we may be able to help them not go in to a shortage in the first place, and if there is going to be a shortage, help them get out of it; so early notification has been key. The one question is, well what can we do to help a company address a problem they’re having? One thing we can do is they may call us and tell us that they foresee a problem getting raw materials. They have an application and it’s becoming critical and if they can’t get that raw material they’re going to have to stop production.  However, they have an application in house with FDA in the generic drugs office where they applied six months ago to be able to utilize an alternative supplier from another part of the world for that active ingredient and it’s sitting in the queue in the back lot. If we know that we will immediately pull that application and put it to the front of the queue and it will get addressed expeditiously so there may never be a shortage. So that’s a simple example. The other thing that we can do is if they tell us, look we’re having problems and whatever the problem is we think we’re going to have to do x, y, and z we may be down for a while. FDA knows who all the alternate manufacturers are who have the other parts of the market and we will go to them and ask if they have the capacity to increase their production and how much lead time do they need in order to increase production. Often if they can they will. What they want to know is how long do I need to do this for and I’ll say we’ll keep you posted. And we’ll look at what the market is and how much they need to make to be able to supply the market readily. That’s another example of something that we can do.

So it sounds like it’s just good communication.

Dr. Kweder:  Communication is critical, but we also need other companies who are willing to step in and help and we’ve had great success with that. All of these companies have their own challenges and they’ve been really good about stepping in when asked if they can, but they can’t always do it. For example, some of them can’t produce certain products; they don’t have an approved application to produce it or they don’t have the appropriate facility to do it. A good example of that would be a cytotoxic agent. Chemotherapy agents have to be made on a really separate part of the plant and you can’t make other products on those production lines. So a company that isn’t in the cytotoxic business can’t step in and help produce cancer drugs probably, at least not easily and without a lot of lead time and investment in equipment. The other things that we’ve been able to do is we work with our regulatory counterparts in other countries to see if there are alternative sources of product that we could import. Sometimes U.S. companies make product here for shipment overseas that for whatever reason they’ve never bothered to have approved here, but they have it approved in another country and it’s essentially the same. We will look at what the inspections for that have been and they might be able to ramp up production of that product. Or we look to alternative suppliers of product in other countries and we allow temporary importation of that product until the producer here can come back on line.

You mentioned that a drug company doesn’t have to tell you if they foresee a drug shortage, do you think they should have to tell you?

Dr. Kweder:  Today certain companies are required to tell FDA. If they make a product that is to treat a serious and life threatening condition they are required to report potential for a shortage to FDA. That’s new and that is a law that was passed by the Congress just this past summer, and that is really going to help us greatly. Since late 2011 we’ve seen a great increase in the number of companies reporting to us voluntarily. That occurred because of an executive order issued by President Obama encouraging that and it’s been great. We’ve seen a six fold increase in reports to us about potential shortages, but now the new law requires companies to do that.

The FDA cannot force a company to make a medication?

Dr. Kweder:  That’s right. We cannot force anyone to make anything.

So how does reducing profit margins on certain drugs effect the shortage situation?