Addressing Prescription Drug Shortages

MS. DIANE REHM

10:06:54
Thanks for joining us. I'm Diane Rehm. President Obama signed an executive order earlier this week, which many hope will address America's increasingly critical medical drug supply shortage. Here with me to look at why doctors are having, increasingly, to find alternatives or delay treatment and the impact on patients: Gardiner Harris of The New York Times, Sandra Kweder from the Food and Drug Administration, and Dr. Christopher Lawlor from the Children's National Medical Center.

MS. DIANE REHM

10:07:40
Throughout the hour, we'll be taking your calls. I'm sure many of you have experienced the shortages we'll be talking about. I must say, I, myself, have run into this recently. Do join us, 800-433-8850. Send us your email to drshow@wamu.org. Join us on Facebook or Twitter. Good morning to all of you.

MR. GARDINER HARRIS

10:08:16
Good morning, Diane.

DR. SANDRA KWEDER

10:08:16
Good morning.

DR. CHRISTOPHER LAWLOR

10:08:16
Good morning.

REHM

10:08:17
Gardiner Harris, tell us how many drugs are facing shortages and what types of illnesses are affected.

HARRIS

10:08:28
So, right now, Sandy probably would know this better than I do, but it's about 130 at the moment. There have been as many as 180, I believe, short this year. It's a record amount. These numbers keep edging up year after year after year, Diane, which is why there's sort of -- we've reached sort of a panic stage at this point. Chris, who's a pediatric oncologist, is here to talk about, you know, one of the terrible drugs that would short this year, which is for treating childhood leukemia.

HARRIS

10:09:03
I mean, many of these diseases that these drugs are meant to treat are actually -- they're deadly diseases, but they're curable if you have the right medicines. And then, suddenly, to have drugs that, frankly, have been around for decades -- some of these medicines, you know, came out originally in the 1960s -- and then, suddenly, to have them not there for physicians like Chris is just an absolutely astonishing situation. So it is why the government, in the person of Sandy and her organization at the FDA and now even President Obama, is organizing so fiercely to try to fix.

REHM

10:09:40
Sandra Kweder, what's causing the shortages?

KWEDER

10:09:45
Well, at a very basic level, most of the problems that are resulting in shortages of these products have to do with problems at the manufacturing firms. Most of these drugs are -- that are in shortage are drugs that are, as you've already heard, older products. These are generic drugs that have been around for a long time. The good thing about them is that they are tried and true therapies that people count on. The ones of particular concern are also what are called sterile injectable drugs.

KWEDER

10:10:25
They're mostly drugs that have to be injected into a vein. They're not oral medicines -- although there are shortages of them as well. Producing sterile injectable drugs is very complicated. There are a limited number of generic manufacturers who can produce these, and they have to be produced in very specialized facilities. The facilities are aging, and to bring them up to current manufacturing standards is difficult and costly.

REHM

10:10:57
How many of these injectables are being manufactured outside of this country?

KWEDER

10:11:05
The ones that we're talking about are predominantly U.S.-manufactured.

REHM

10:11:09
All right. And is there a question of the margin of profit involved with the generics?

KWEDER

10:11:20
I think where that may come into play is -- has to do more generally with how the generic industry makes decisions about what to make and how much to make. With regard to the individual shortages, I don't think that's a factor.

HARRIS

10:11:38
I mean, Diane, what's happening here is there's this increasing array of drugs that we use in this country. There are something like 5,000 different prescription medicines that have been approved for use, and while -- meanwhile, the generic drug industry has narrowed down -- it used to be the generic drug industry was made up of all this sort of small mom-and-pop players who sort of competed fiercely and overlapped with each other.

HARRIS

10:12:01
But what's happened in the last 20 years is that the generic drug industry has gone down to just a handful of players. Ninety percent of these -- more than 90 percent of these drugs are made by seven companies, and, in fact...

KWEDER

10:12:12
Seven, right.

HARRIS

10:12:13
...the majority of the drugs are made by just three. And so you have very few players. They have very few facilities. If something goes wrong in one of those facilities, a huge number of drugs end up being affected. And in the vast majority of these medicines, 90 percent of the supply of a particular medicine is made by one manufacturer.

HARRIS

10:12:34
So if that one manufacturer has a bad inspection, has something go wrong with their suppliers -- and while these drugs are made in the United States, Diane, the crucial ingredients of them, the active pharmaceutical ingredients, are merely all made in China and India in these mammoth plants that, frankly, are rarely inspected by Sandy's fellows out of the FDA.

REHM

10:12:56
At the FDA.

HARRIS

10:12:56
And so there are these enormous supply lines -- and, basically, what's happened is there's just a number of things than can go wrong at any given moment...

KWEDER

10:13:05
At any given moment.

HARRIS

10:13:06
...and the whole thing can fall apart.

REHM

10:13:07
Dr. Lawlor, have you seen these kinds of drug shortages in the past? If so, how have you dealt with them back then?

LAWLOR

10:13:17
Well, in the past, it was very, very rare for you to hear from the pharmacy or from any hospital administration to say that there is a drug shortage. And in that point in time, people would try to determine what the next fallback would be or how they would be able to procure the drug from another method. Now, almost on a weekly basis, you get information sent to you at any hospital across the country to say, here are the lists of the following 100 or 150 drugs that we have in short supply.

LAWLOR

10:13:46
And as Gardiner mentions, it's not that easy to have another of the seven or another of the three pharmaceutical companies ramp up production in any meaningful way to impact your patient right then and there. So it is a very big problem across the country, both for pediatric oncologists, adult oncologists. And other drugs are, as Sandy mentions, sterile injectables, things, antibiotics, other cardiac medicines -- and so what physicians across the country are having to do is when they hear, oh, my gosh, my...

REHM

10:14:18
Something -- right.

LAWLOR

10:14:18
...drug isn't available. What am I going to do?

REHM

10:14:19
Right, right. Now, Sandy, some people have said that the FDA's burdensome quality control regulations are part of the problem here. How do you see it?

KWEDER

10:14:36
I think the -- what's in -- we hear -- we do hear that a lot, and, you know, we -- our pharmaceutical supply in this country is really the gold standard for the rest of the world. You know, we are -- you know, I, as a patient, or my patients when I see them, when they get something from the pharmacy or injected in the hospital, they can be assured that this a high-quality product, that what's -- everybody -- that somebody knows what's in it, that it doesn't have metal shards in it or isn't contaminated.

KWEDER

10:15:08
But those standards -- the quality standards have not changed in 40 years. They are the same. What is a challenge, though, is when you have aging facilities to try and maintain those standards just like we all do in our homes. Trying to keep the place up to snuff requires continual reinvestment and at some time -- at some point, you got to do a wholesale renovation.

REHM

10:15:32
Dr. Sandra Kweder, she is deputy director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research. Dr. Christopher Lawlor is a pediatric oncologist at Children's National Medical Center. Gardiner Harris is science reporter for The New York Times, author of the mystery novel "Hazard." And if you'd like to join us, 800-433-8850. Send us your email to drshow@wamu.org. Join us on Facebook or Twitter.

REHM

10:16:17
When you think about the kinds of drugs most being affected, you talked about pediatric oncology drugs, you talked about cancer drugs. What other kinds of drugs are being affected here?

HARRIS

10:16:38
Well, there are the anesthesia drugs, which are the, you know, crucial drugs for use in the hospital. These are nearly all hospital drugs, Diane, because, of course, they have to be administered. And let me just sort of say, you know, there are people out there who are criticizing FDA standards on this, but you are out of your mind if you do not want high standards on injectable medicines. You know, if you get a contamination event with an...

REHM

10:17:03
What kind of contamination are you talking?

LAWLOR

10:17:05
Bacterial contamination -- these things will kill you really fast.

REHM

10:17:09
Even slivers of...

HARRIS

10:17:13
Glass and...

KWEDER

10:17:13
Glass, metal shavings, fungus.

HARRIS

10:17:15
Metal shavings, right.

LAWLOR

10:17:16
And we're dealing with immune compromised patients when we're talking about these things (unintelligible) drugs.

KWEDER

10:17:18
Oftentimes -- I mean, these are people sick people.

REHM

10:17:21
So...

HARRIS

10:17:22
So you would go into septic shock, you know, in five minutes if you get...

REHM

10:17:25
But not even know why?

HARRIS

10:17:27
Well, oftentimes, exactly...

REHM

10:17:27
Yeah.

HARRIS

10:17:28
...and until it's too late. So you want very high standards when it comes to these medicines.

REHM

10:17:34
But wouldn't you have to have the FDA examining those pharmaceuticals or the ingredients thereof coming from China and elsewhere to be truly certain?

KWEDER

10:17:48
And we do. We do examine them. We inspect -- we do inspections in some of those -- in those foreign facilities that make these products. And we also inspect the U.S. plants on a regular basis, a periodic basis, to make sure that they are doing their job -- and they do -- assuring that the products that they are importing, when we're not in those foreign plants, are pure and not contaminated.

HARRIS

10:18:12
Wait, Diane, they don't come close to -- I love Sandy here, but they don't come close to the amount of inspections that they need to do in some of these foreign plants. But they're about to get the money to do it from the industry itself.

REHM

10:18:22
Gardiner Harris of The New York Times. We'll take a short break. We'll take your calls when we come back.

REHM

10:20:03
And welcome back. We're talking about the shortage of a number of very important generic drugs. Joining us now from Cape Town, South Africa, is Heather Bresch. She is president of a company, a generic drug producer. It's the third largest generic drug producer in the world and largest global generics company headquartered here in the U.S. Good morning to you, Heather. Thanks for joining us.

MS. HEATHER BRESCH

10:20:43
Sure. Thanks for having me.

REHM

10:20:44
Can you talk about why you see the generic drug industry struggling to meet demand?

BRESCH

10:20:55
Sure. And, you know, I had the opportunity to listen to a little bit of the conversation prior to your break, and, you know, I do think there's a couple of misperceptions. I know there was a discussion about the process as being complex and the generic industry sometimes has a hard time meeting the complexities and so forth of these products. And I, you know, would like to just remind people that the brand industry, the brand and generic alike, the entire pharmaceutical industry has faced these shortages and the market disruptions.

BRESCH

10:21:27
And many, many times, the brand industry is still making the products for generic companies. So, you know, as many of you know on the phone, the recall, the market disruptions have as much as the brand industry as the generics. And so many times, the -- once the product does goes go generic so brand companies can fill their facilities, they continue to make the product and put the generic label on it.

BRESCH

10:21:49
So it's very tough to distinguish the brand from generic from a manufacturing perspective because most plants are making those brand and generic products. So it is true that, when a facility is hit, it'll affect many products. But I wanted to just clarify that it's not -- it would be very difficult to say something's just a generic manufacturing facility. I think, you know, what you were touching upon right before the break, which is FDA's resources or lack thereof, to truly meet the demands of our global industry today.

BRESCH

10:22:21
Eighty percent of the raw materials that are brought in, or that are used for products, come in from outside the U.S., and 40 percent of the finished dosage form come from outside the U.S. And, you know, it's well-known that the FDA, the inspection rate in 2009, according to GAL, FDA was only able to inspect about 11 percent of foreign facilities. So the reality is we have a very vulnerable supply chain.

BRESCH

10:22:47
And I think what, you know, one of the issues that's manifesting itself is that very vulnerable supply chain, and what we as the generic industry stepped up -- and, again, this would go across to the entire industry for a successful -- with Capitol Hill is that FDA absolutely needs to become globalized. And instead of operating under a 1938 law that is very antiquated and very domestic and give FDA the resources and the -- really, the teeth they need to strengthen our supply chain, and in the long-run, I think would very much go to alleviating these drug shortages.

BRESCH

10:23:25
And I know that's not an overnight solution, but it's going to just continue to compound. I think one of the doctors earlier was talking about, every year, it just gets worse and worse. And until we fix the core of the problem, that compounding issue is going to continue. So we've come up with a proposal that will give FDA about $300 million a year, about $1.5 billion over the next five years to allow them to truly globalize in the sense that the resource and the manpower necessary to help strengthen the supply chain we have today.

REHM

10:23:59
Sandra Kweder, how much is that $1.5 billion going to help?

KWEDER

10:24:07
I think it will help tremendously in assuring sort of the integrity of the drug supply chain. There is absolutely no question about that. How much it will impact the current situation we're talking about today related to drug shortages is another question. There are certainly elements of that that will, where a shortage is -- has approximate cost, an inavailability of active pharmaceutical ingredient, you know, from -- because it comes from a foreign, not previously inspected source where -- to replace one. Then, that's where that comes in.

KWEDER

10:24:44
The shortage situation today, however, the vast majority of shortages that we're seeing in the U.S. are related to production problems here in the U.S. They -- a very small percentage have to do with inavailability of ingredients. So it's related, the inspection, being able to speed up the inspection process so that when plants are doing things to try and address shortages, we can get in there quickly with our resources. These -- this new program that Heather is describing absolutely will help. Will it make an immediate impact on shortages? I'm a little skeptical about that.

REHM

10:25:26
Do you actually believe that foreign manufacturers from China, India would allow, would agree to having the U.S. FDA begin to examine -- investigate their plans?

KWEDER

10:25:43
Well, we already do to some extent.

REHM

10:25:45
To some extent.

KWEDER

10:25:46
We -- to some extent, we do. Their willingness to allow for that has increased in recent years as we have built relationships with other countries. The FDA now has offices in many of those countries and are trying to, you know, build cooperation and trust with local authorities to really facilitate our ability to go into these plants.

REHM

10:26:08
Heather Bresch, what I'm confused about is that shortages in supply has driven up prices. But higher prices don't seem to encourage more supply. Why is that?

BRESCH

10:26:28
Well, you know, I think, obviously, you know, when you go back to, unfortunately, to the basic supply and demand economics, you know, there are situations that don't -- and especially given the regulated nature of our business -- that don't immediately -- that demand doesn't immediately return supply. So I think that when, you know -- I agree with what was just said, and, like I said, it's not a short-term fix. I think that when you look at the shortage issue, what happens is sometimes -- and, especially, we're talking about some of these older products -- prices, it had become so hypercompetitive.

BRESCH

10:27:03
Sometimes, you know, we take something good and take it a little bit too far, as far as how cheap we want products to be able to be, and if, you know, if it's 10 cents, it should be able to be 5 cents. And, unfortunately, that, over the years, we (word?) a lot of players that can't continue to make product or these complicated sterile products at such low margins, and then you end up just having a couple of players.

BRESCH

10:27:30
And then if someone has an issue and there's a shortage, and to get -- to spend the (word?) and to get a facility to have higher capacity takes time and takes money for the prices just to go back to, you know, dirt cheap. So I think that, again...

REHM

10:27:47
Go ahead, Dr. Lawlor.

LAWLOR

10:27:49
I was just going to also comment, apart from just typical supply and demand economics as well, speaking from the pediatric oncology world, our demand is hopefully going to be somewhat consistent. A lot of the pediatric diseases are what we would term orphan diseases and that, I believe, there's not that many children each year diagnosed with cancer. While it is huge to that individual patient and that family, we are not going to have 100,000 pediatric cancer diagnoses.

LAWLOR

10:28:16
And so they're sometimes are not the same incentives. We're not talking about the new cholesterol-lowering drug or the new dyspepsia drug or anything like that. These are critical medicines for children with cancer that, again, would be life-saving. So as we rethink this whole process, you know, to have incentives for some of these orphan diseases is also important where the demand is not going to fluctuate rapidly hopefully.

HARRIS

10:28:40
Right. I mean, Diane, my conservative friends don't really like to hear this, but supply and demand just doesn't work in this situation. The demand is absolutely static. You know absolutely from year to year how many kids are going to get this cancer. It's the same year and year. And supply, as Heather talked about, is absolutely static because it takes two, three, four years to sort of set up these plants, get your supplies going. And so nothing is going to solve this situation in the immediate term. This is all long-term stuff.

HARRIS

10:29:06
And I think the other point that we have to make here is that, as Heather talks -- Heather's company is the only large company with a very large plant in the United States anymore. But the way things have happened is that all of the key -- a lot of the key manufacturing has gone abroad and that these shortages are a symptom of sort of a frightening situation in the United States where, increasingly, the strategic assets like -- you know, we don't make antibiotics in the United States anymore.

HARRIS

10:29:33
We don't make all kinds of absolutely essential medicines, or at least we don't make the active pharmaceutical ingredient, which is the key part of these medicines. And so while we sort of can stamp the pills here and we can sort of put together the injectable medicine, you know, there's no way we're going to be able to do that without these ingredients from India and China. And Heather, actually, the woman on the phone, is the one who negotiated this deal to get the FDA more money to inspect these, in part, because she is at a disadvantage. She has this mammoth facility in Morgantown, W.Va.

HARRIS

10:30:11
She has, basically, FDA inspectors living in her facility there, whereas her competitors, who make it in these India and China plants, see these FDA inspectors once in a blue moon. You know, you read some of these inspection reports from these FDA guys who go to these Chinese plants, and they don't even know how to get there. So, you know, there are real big, strategic issues going on here that these shortages are just a small part of.

REHM

10:30:37
So what is the...

BRESCH

10:30:38
No. And, Gardiner…

REHM

10:30:40
Go ahead, Heather.

BRESCH

10:30:42
I was just going to say, you know, I certainly appreciate that. And, obviously, the fight that we've taken to Capitol Hill is very much around American competitiveness. And, you know, he's right. We have an extremely large facility, one of the largest in the United States, and, unfortunately, we're very disincentivized to keep large manufacturing facilities or expand our manufacturing in the United States. I mean, we are growing all over the world. I have 25 facilities around the world.

BRESCH

10:31:08
And the United States, because of not applying the same standard to foreign facilities as they do U.S. facilities, it's, you know, a reverse carom. It's a disadvantage, and it's an unlevel playing field.

HARRIS

10:31:23
But -- and that's because the law in the United States requires FDA to inspect plants in the United States once...

REHM

10:31:30
In the U.S.

HARRIS

10:31:31
...once every two years.

REHM

10:31:32
Yeah.

KWEDER

10:31:32
Right.

HARRIS

10:31:32
It does not have a similar statutory requirement for foreign plants.

KWEDER

10:31:36
Overseas. That's right.

HARRIS

10:31:38
So FDA will go six, seven, eight years, sometimes, between inspections. And, in fact, at its present rate, it would take FDA 13 years to inspect all these foreign plants going into the United States.

REHM

10:31:48
Okay. So what you've got is a Congress that is trying to eliminate regulations, eliminate more of what the FDA does. So is the money that Heather is talking about going to make a huge difference in the inspection of Chinese, Indian plants?

KWEDER

10:32:15
I think that it will make a difference.

BRESCH

10:32:16
It is.

KWEDER

10:32:16
Absolutely, it will make a difference.

REHM

10:32:19
Go ahead.

BRESCH

10:32:19
Not only would make a difference, but what -- the important piece that still needs to be done -- and Congress has to do this -- is change the 1938 law. So everything that Gardiner just described is because that law that's still -- you know, 1938 was a long time ago, and this world was a much different place. Considering that that's the law that still governs the FDA should tell you how antiquated it is.

BRESCH

10:32:42
So that's the law because it was written very domestically that says every two years the U.S. manufacture. We want that law to say every two years, if you're selling products in the U.S., you're held to the same standard. So the...

HARRIS

10:32:54
And -- right. And let's -- the larger political point here is that when you hear the Republican presidential candidates sort of talk about how regulations are bringing this country down and it's the economy, you know, think of Sandy Kweder sitting here. You know, Sandy Kweder is a regulator, and FDA is probably the one regulatory agency that touches Americans more than any other.

KWEDER

10:33:16
Any place.

HARRIS

10:33:17
It regulates 25 cents of every dollar, and it just got new regulations to make food safer. It looks over drugs. And the Congress wants to cut its budget because of this whole thing going on in Congress.

REHM

10:33:33
Gardiner Harris of The New York Times and Heather Bresch. She is president of Mylan. Thank you so much, Heather, for joining us.

BRESCH

10:33:45
Yeah. Thank you. Thank you for having me.

REHM

10:33:47
And you're listening to "The Diane Rehm Show." It's time to open the phones, 800-433-8850. Richard in Salem, Mass., good morning. You're on the air.

RICHARD

10:34:05
Good morning, Diane, and good morning, panelists.

REHM

10:34:07
Good morning, sir.

RICHARD

10:34:09
I'm an internist, a general internist, in Massachusetts. And there's a related topic, I think, of great interest to many people, although they don't know about it yet, but it's related to the topic at hand. Because of, I gather, 1960 rules or changes within the FDA, a certain number of generic drugs have now been taken off of the shelf. In particular, an example would be colchicine, which cost literally pennies per pill -- maybe 5 or 6 cents or so -- which is no longer available as a generic.

RICHARD

10:34:47
There is now only one brand name, colchicine, exactly the same molecule, which costs in the neighborhood of $5 or $6 a pill. Colchicine is used commonly in the treatment of gouty conditions, very common disorder. And it's also used in very important situations for more unusual diseases. I think it would be very interesting to hear how this has come about.

REHM

10:35:17
Dr. Kweder.

KWEDER

10:35:18
Sure. I'll be happy to address that. That's an interesting question and point. What -- it's really not related to the shortages topic. However, there are many drugs on the U.S. market that are -- have never been approved by FDA. There are manufacturers out there who make drugs that we all commonly use, have taken. The colchicine generic that came off the market was one of those. It was made by a company that had never had an application.

KWEDER

10:35:50
Basically, they were illegally marketing the drug. When a new company came to the agency and wanted to have their product approved and do the proper studies to assess the correct dose -- and, in fact, they found that the dose needed was much less than was commonly used in medical practice and far safer -- FDA was then able to go to the company that was illegally marketing the product and asked them to come off the market.

REHM

10:36:17
How did...

KWEDER

10:36:18
The consequence of that, however, is you've got a new brand name drug out there that can now charge a lot more.

REHM

10:36:24
How did the illegally marketed drug get on the market?

KWEDER

10:36:29
Most of them have been there for decades.

HARRIS

10:36:32
It's a scandal, Diane. And I'm sorry. I sort of have -- I'm the exact opposite side of the caller. I mean, listen. I'm very sympathetic. There have been multiple cases where, you know, a new branded drug comes on. It clears out all of the old unapproved generics, and they jack up their prices...

KWEDER

10:36:51
Yep.

HARRIS

10:36:51
...enormously. And it's -- and they just reap these huge gains, and it's terrible. But the fact that there are literally hundreds of drugs that are on the American market that have never been approved by the FDA...

KWEDER

10:37:04
Right.

HARRIS

10:37:04
...never been examined by anybody, is just unreal, and it's across all kinds of different sort of disease states. And you can't even believe it.

REHM

10:37:15
Dr. Lawlor.

LAWLOR

10:37:15
And then that goes to pediatrics in general...

KWEDER

10:37:18
Right.

LAWLOR

10:37:18
...in that as a lot of the pharmaceutical companies are developing their drugs, there's a certain expenditure that has to be made to vet it. And, usually, that's done with an adult population. The medicines having less application for children, there's not that incentive to test them to the same degree.

REHM

10:37:33
Dr. Christopher Lawlor, he is a pediatric oncologist at Children's National Medical Center. Short break. Right back.

REHM

10:40:02
And as we talk about the shortage of drugs, generics specifically, in this country, we're going to bring on someone who has been very directly affected. Jay Cuetara, good morning to you, sir.

MR. JAY CUETARA

10:40:21
Good morning, Diane.

REHM

10:40:22
Thank you for joining us. Tell us your story.

CUETARA

10:40:27
Well, sure. I was diagnosed in April of 2009 with stage four rectal cancer. And I'm being treated at UC San Francisco's Helen Diller Cancer Center and, over the past two years, have had several rounds of chemo. And this past August, as I was going for my sixth cycle of chemotherapy, after being pre-medicated and getting ready for the actual infusion, it turns out that the 5-FU, which is a fluorouracil drug injectable, sterile injectable, was not available. And as a result, I was not able to have my chemotherapy that day.

REHM

10:41:05
Wow. So was there a substitute? What did you do?

CUETARA

10:41:12
No. Unfortunately, there is no substitute for it as you're going through an existing round of chemo. There is a substitute that can be made at the beginning of a round, but not while you're in a round of chemo. So, in this particular case, I could not have chemo that day and would -- had to wait until UCSF had the drug again. And luckily, in my case, they were able to acquire the drug the following week. So my chemo was only delayed one week.

CUETARA

10:41:41
And for me, in my particular situation, it wasn't as pretty good deal as it is for other cancer patients who have leukemia or breast cancer or in a situation where they're -- they need to have their chemo on a very regular basis is what's going to make the difference between them being cured of the cancer or their cancer being life-prolonging.

REHM

10:42:04
Dr. Lawlor, can you speak to that?

LAWLOR

10:42:07
Absolutely. One of the worst things that we have to do as physicians is certainly tell a parent that their child has cancer, and then imagine that you would have to tell the parent that the medication that their child might need is not available. That might only -- might even be worse. So we have to try to be as proactive as possible in identifying the shortages as they're coming through, working very closely with the pharmacy at your institution to find out if there's a substitute available that has the same equivalent properties.

LAWLOR

10:42:38
And then, again, it's -- I am very sorry that, you know, he had to go through this, to start a chemotherapy cycle and then, partway through, not be able to complete it. Staying on schedule has been shown to be very important in affecting cures, and you certainly don't want to be messing around with that.

REHM

10:42:53
Dr. Kweder, how much advance notice is the FDA given that a drug will not be available?

KWEDER

10:43:03
We often find out at the same time as the clinicians do because if a product --you know, someone can't get it, we take reports from pharmacists. We take reports from patients. Anyone who wants to call us about a potential about an existing shortage, we'll take reports. Where we can do the most is when we are aware of a company having problem -- production problems or any kind of problem that might result in a shortage.

KWEDER

10:43:34
So, for example, if a company has to shut a plant down for a month to do routine maintenance -- this is just making this up -- it's going to -- and they haven't planned for an adequate supply to be putting forward to wholesalers and facilities, if we know about that in advance, we can work to find alternative suppliers and suggest to them that they may need to increase their production. But that requires advance notice.

REHM

10:44:08
Jay, tell me how you are now.

CUETARA

10:44:11
Well, fortunately, Diane, I'm doing great. I'm asymptomatic. And even though it's stage four, I'm still working full-time and, you know, feeling fine. I'm just very concerned with those folks that are -- you know, have very specific cancers or are in situations where they require that -- their chemo cocktail on a very regular basis and are not able to receive it.

REHM

10:44:31
I think Dr. Lawlor has a comment.

LAWLOR

10:44:33
And just touching on that from the pediatric oncology world through our participation at -- with the Children's Oncology Group and national protocols, Children's National as well as some other institutions have been able to achieve cure for the common leukemias in over 90 percent of patients. But those patients are treated on clinical trials. In order to be on the clinical trial, you need to have access to all the medicines on that trial.

LAWLOR

10:44:58
And so if you are short a particular chemotherapy medicine, you're not able to enroll someone on that study. So apart from the immediate at-the-bedside impact, it also have -- may have an impact in slowing down the results that we get from our clinical studies in order to push that 90 to 95 to try and cure more patients.

KWEDER

10:45:15
And this has been a big -- this has been recognized as an important problem by the NIH and other companies that are trying to do trials of new products.

REHM

10:45:23
Jay Cuetara, thank you so much for joining us. I hope your health stays strong.

CUETARA

10:45:30
Thanks, Diane.

REHM

10:45:31
Thank you. And let's go now to Paul in DeRuyter, N.Y. Good morning. You're on the air.

PAUL

10:45:41
Good morning, Diane. And thanks for the opportunity to talk to you and to your panel.

REHM

10:45:45
Certainly, sir.

PAUL

10:45:46
I'm a 40-year veteran of the pharmaceutical industry, recently retired from Bristol-Myers Squibb Company in Syracuse. And as such, I am keenly aware of the antibiotics situation in this country. Basically, your New York Times panelist stated earlier in your show that none of the molecules...

HARRIS

10:46:06
You were the last to make it.

KWEDER

10:46:07
That's right.

PAUL

10:46:08
Yes. None of the molecules necessary to make penicillin and cephalosporins are produced in this country anymore, the active pharmaceutical ingredients. And...

HARRIS

10:46:17
The last plant was the one -- was your plant up in Syracuse.

PAUL

10:46:20
Yes. We were the world leader in making antibiotics.

HARRIS

10:46:22
You closed in 2004. Right.

PAUL

10:46:24
Yes. And my mind goes back to the problem we had with the heparin. A couple of years ago, the FDA commissioner's feet were held to the fire by a Senate investigating committee when several people in this country died because the Chinese manufacturer deliberately used the wrong molecular form of heparin, and it killed a bunch of people.

PAUL

10:46:47
Now, can you imagine yourself as an auditor going to China to try to figure out some of these companies if they're dealing unscrupulously and avoiding the GMPs, deliberately trying to produce something to save money, knowing so well that it might be hazardous? First of all, all the documentation would be in Chinese. You need a skilled interpreter to help with that. And there's no way, even if the documentation were in English, that you could find that except for extensive testing of the APIs in the finished products and the input raw materials.

HARRIS

10:47:22
Well, I mean, what happened in that case, Diane, was it was absolutely deliberate contamination where people who did that knew that they were going to kill people because, you know, in most of these sort of situations, of course, people take the shortcuts in the -- for instance, we remember the case where the peanuts were contaminated. Well, they just had a terrible plant where bird dung was able to sort of get into the plant and contaminate the plant. But they didn't do anything deliberate.

LAWLOR

10:47:48
In the case of the heparin, these people actually knew the test that was being used to sort of determine whether it was real heparin. And they came up with a fake that they knew could pass the test. So it was actually a very deliberate fraud.

REHM

10:48:03
Okay. So we go back to Paul's question as to how the FDA could possibly get in there, could discover, could prevent an accident of that magnitude from happening.

KWEDER

10:48:22
I think the answer to the heparin situation is extremely complicated there. The product in question was -- is very unusual.

HARRIS

10:48:34
It's made from pig intestines, Diane.

KWEDER

10:48:35
From pig intestines, coming from a variety of sources and pig farms in China.

LAWLOR

10:48:40
Hundreds of pig farms across the thousands -- across China, right. And, in fact, the FDA was not allowed to investigate. The Chinese authorities did not let FDA people in there.

KWEDER

10:48:49
We could not investigate to understand.

REHM

10:48:51
But then how could you allow that drug on the market?

KWEDER

10:48:57
What was happening was that we -- because we couldn't investigate those places, we -- there were requirements to test heparin for purity. The standard -- and there is -- was a standard test for heparin for purity of the product coming in, and all the manufacturers, U.S. and worldwide, utilize that test to assess the purity of the drug product. But the substitute for the active ingredient that was being used to meet production quotas in China mimicked the heparin molecule and could basically skirt by the test.

HARRIS

10:49:32
Right. But this is the point, Diane, which is that testing the ingredients does not assure safety. It never has.

KWEDER

10:49:39
No. You have to go to the source.

HARRIS

10:49:40
The FDA knows this. This is why the FDA desperately wants to inspect these plants...

KWEDER

10:49:44
That's right.

HARRIS

10:49:45
...has not been able to for decades because of money.

REHM

10:49:46
But how -- but, thinking about Paul's points -- number one, documents in Chinese, number two, substitutions, complications -- how can we ever know for sure a drug is what the Chinese or the Indians say it is?

KWEDER

10:50:09
I think one solution is broader inspections. Two is making sure that at every step of the process there are quality checks. And that's what the FDA regulations really try to do is at every step of the process, be doing quality checks. Some people call that being pointy-headed and bureaucratic, but there are always opportunities for things like heparin, for substitutions, you know, cutting corners. What we require is verification -- trust but verify, just like a teenager, but it's not -- there is -- this is not a substitute for some of the other things. But building quality in is essential.

HARRIS

10:50:51
We're in a frightening situation. And Paul from Bristol-Myers, you know, the frightening thing from high perspective is, you know, I've covered Bristol-Myers for 13 years, and, you know, I know the guys over there. And I went to them when they closed this plant, or I went to them after they closed the plant and said, you know, by the way, did anybody come to you from the sort of U.S. government and say, hey, you know, it might actually be a good idea to have some facility in the United States that can actually make antibiotics, which are obviously, unbelievably crucial.

HARRIS

10:51:20
And they sort of shrug their shoulders and said no. And so we are losing -- in fact, we already have lost the critical capacity to make all the kind of medicines that keep people alive. If we ever get in trouble with the Chinese for a few weeks even and we stop getting these crucial ingredients from the Chinese and the Indians for a little while, the health care system in the United States will collapse.

REHM

10:51:44
All right. To Tulsa, Okla. Good morning, Larry.

LARRY

10:51:49
Good morning, Diane. How are you doing today?

REHM

10:51:50
Fine. Thank you. Go right ahead, sir.

LARRY

10:51:54
Yes. Hi. My issue is that I was diagnosed as an 11-year-old with having HDDD, hyper displacement disorder. And as an adult, I have continued taking Adderall. And I was just informed by my pharmacist that the drug will no longer be available, and, in fact, I was one of the last patients to receive the dosage that was left at the pharmacy. They -- well, they don't expect to be receiving Adderall anytime soon.

REHM

10:52:30
What do you think of that, Dr. Lawlor?

LAWLOR

10:52:33
I think it's, unfortunately, a situation that's becoming more and more common across the country. I'm not sure about that specific medicine, but this is, you know, the ramification...

REHM

10:52:43
Have you heard that, Gardiner?

HARRIS

10:52:44
Yeah. I mean, I think that, Diane, it's a sort of situation of a different sort of dosage. There's actually -- Adderall XR is still being sold, so you get the immediate release dosage that they are sort of phasing out where that they continue to sell the sustained dosage of, you know -- these are the sort of oddities that happen when you have 4-, 5,000 different pharmaceuticals that are being sold. Some things get phased out, and some things stay.

REHM

10:53:10
And you're listening to "The Diane Rehm Show." To Thomas in Cincinnati, Ohio. Good morning. You're on the air.

THOMAS

10:53:20
Oh, this is me then?

REHM

10:53:21
Yes, this is you.

THOMAS

10:53:22
Okay. Okay. Great, good, good, good. 'Cause I know I don't have much time.

REHM

10:53:26
You sure don't.

THOMAS

10:53:27
It's very -- there has been a breakdown in the social contract between the drug companies and the people of the United States. They lied to us, the drug companies. They said, if we're allowed to make these egregious products on popular drugs, oh, we'll put back money into the less profitable drugs. They never did. We know where the money is. They were -- these companies were allowed to make billions upon billions of dollars, billions of which they put in to keep feathering their own nests. They were under -- I want to say copyright, but they were also under patent protection.

THOMAS

10:54:06
They couldn't have made that money without the protection of the U.S. government. And as I agree with one of your spokespeople that said about how the supply-siders got it wrong, he's absolutely right.

REHM

10:54:19
All right, sir. I thank...

HARRIS

10:54:21
So Diane, there are some solutions to this problem that our lefty caller here would have preferred that the administration didn't actually do. You know, there...

REHM

10:54:30
Why did you call him a lefty?

REHM

10:54:32
He may represent a great many people out there.

HARRIS

10:54:36
I -- well, absolutely. I think of, you know, only journalists are thought of lower than drug companies in this country, so that, you know, what the administration was considering, for instance, is, you know, is a stockpile of some of these medicines. They would actually stockpile the dry ingredients of these medicines, so that if they went in short supply, it would be a relatively easy thing to put them into an injectable form.

HARRIS

10:55:01
There is a group of oncologists, some of Chris' colleagues, who are considering forming a not-for-profit drug maker to produce some of these medicines in a constant supply so that they'll always be available. And, of course, there were some, you know, thought within the government even to create sort of a government production facility. These are obviously -- tend to be on the left side of the spectrum sort of thoughts.

HARRIS

10:55:24
The Obama administration, already under attack for health care reform, and Obama is frequently referred to as a socialist in the right. I don't think that they ever really thought that these sorts of solutions would sort of pass muster in this political environment. But there is no doubt that there are clear sort of failings in the private sector in these situations, and there are suggested solutions that would -- that, perhaps, would do other things.

REHM

10:55:50
All right. And two quick emails. Karen writes, "It's not just these injectables that people are talking about. I have chronic migraines. The only medicine that's worked for me for many years is now unavailable, Midrin." And Karen in Baltimore writes, "I've been a nurse for 35 years, I've never seen shortages like those we are encountering -- anti-nausea, narcotics, chemotherapeutics, vasopressors. Every week, there's something else we're short of."

HARRIS

10:56:30
That's right.

REHM

10:56:31
And that's where we have to leave it. I hope you all will continue your good work in this area. And I hope that the FDA has the opportunity to expand its reach so that the American people are protected from global -- what can we call it? -- misbehavior. Sandra Kweder is deputy director in the FDA, Dr. Christopher Lawlor is at the Children's National Medical Center, Gardiner Harris of The New York Times. Thank you, all.

HARRIS

10:57:15
Thank you very much.

LAWLOR

10:57:15
Thanks, Diane.

KWEDER

10:57:15
Thank you.

REHM

10:57:16
Thanks for listening. I'm Diane Rehm.

ANNOUNCER

10:57:19
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