Thu October 25, 2012
After Meningitis Deaths, A Look At Drug Safety
Originally published on Thu October 25, 2012 11:26 am
NEAL CONAN, HOST:
This is TALK OF THE NATION. I'm Neal Conan in Washington. Two dozen dead and hundreds sickened from contaminated drugs with probably more to come. The outbreak of fungal meningitis has scared many thousands more who received injections of what may have been tainted steroids from a now-closed facility in Massachusetts, which called itself a compounding pharmacy.
Under the law, compounding pharmacies are supposed to fill specific prescriptions for individual patients. This one sent bulk shipments across the country, including 14,000 doses of the potentially tainted steroids to 23 states. Compounding pharmacies fall largely under state laws, which drug manufacturers come under the stringent supervision of the FDA.
If this case raises questions for you about drug safety, give us a call, 800-989-8255. Email us, firstname.lastname@example.org. You can also join the conversation on our website. That's at npr.org. Click on TALK OF THE NATION. Later in the program, the fight to wipe polio off the face of the Earth, but first NPR science - excuse me, NPR health science correspondent Richard Knox joins us from his office in Massachusetts. And Richard, always nice to have you on the program with us.
RICHARD KNOX, BYLINE: Thanks, Neal, nice to be here.
CONAN: And we learned of the 24th victim earlier today, and the Centers for Disease Control released another update about an hour ago. What can you tell us?
KNOX: The latest total number of fungal infections is 328, it was 317 yesterday. It involves 18 states, now, South Carolina has reported its first case. There were 23 states that we're told, originally, got contaminated lots of this drug. Twenty-four deaths, as you say - which is the same as yesterday.
There were 323 cases of either fungal meningitis or stroke, and the other five were infections of the joints. It's - we can expect, as you say, for these case counts to go up for a while to go.
CONAN: One of the distressing things in your reporting, nothing to do with your reporting, is we learn that this is a very slow developing infection. You can develop an illness months after you've gotten the shot.
KNOX: Yeah, that makes it very difficult for patients and doctors to know when we're out of the woods. I think it's important to say, as the CDC said yesterday, that six weeks after the exposure is the main period of risk, and that period will end on November 8th, you know, later next week, about a week from today.
That doesn't mean that there won't be any more cases after that.
CONAN: It's two weeks from today, Richard, but go ahead.
KNOX: I'm sorry.
CONAN: All of us are focused on November 6th, which is 12 weeks - 12 days away from today.
KNOX: It can't come any too soon, can it? Yeah, but I mean after November 8, then that - we'll be mostly out of danger, but there still could be cases because, as you say, it's slow-growing, people respond differently, people may have had different doses of the fungus in whatever they got. And back a decade ago or so, there was another case, very similar to this one, involving many smaller people and - a smaller number of people in North Carolina.
And they were seeing cases as long as five months after the exposure. So it could drag on. But the main bulk of cases should taper off maybe around Thanksgiving or so.
CONAN: And there was a difficulty some of the doctors you were talking with expressed with - they don't really know what to do with treatment for these people who may or may not have meningitis.
KNOX: Well, diagnosis and treatment are both big problems for a lot of doctors and a lot of patients out there. I mean, you know, we've talked about these 328 cases so far, but really that's the tip of a big iceberg. There were 14,000 people across these 23 states who were exposed or potentially exposed to the infected methoprednisone. It's a steroid that's used to treat back pain.
And then there may be other patients who are getting other drugs from this company who may also get infected. So we don't really know the total size of the universe of people out there who may have gotten infected, but you can bet that thousands of people out there have been calling their doctors and saying, you know, I have a headache, I have a stiff neck, I got an injection, I don't know whether it's from this company, what should I do.
Doctors have to make judgments about when a patient should get a spinal tap to see whether there's any evidence of infection, and that's not a casual procedure. I've never had one, but I'm told it's unpleasant, and you don't want to do it casually at all.
And then if somebody has an elevated white count, a fellow I talked to the other day who's the mayor of a little town, a small town in New Hampshire, had the drug from this company, got a spinal tap. There was an excess, but not a great excess, of white cells in his cerebral spinal fluid, which indicated he might have infected. So he started an IV. He's had hallucinations from the drug, which is pretty common.
He doesn't know how long he'll have to stay on it, three months, six months, they don't really know. And, you know, he's getting IV'd five hours a day. There are a lot of patients out there who are really worried and who are exposed to toxic drug and uncomfortable diagnostic procedures.
CONAN: Richard Knox is with us, NPR health and science correspondent. If this outbreak of fungal meningitis has you concerned about the safety of our drugs, give us a call, 800-989-8255. Email us, email@example.com. Rick's(ph) on the line, Rick calling from Reno.
RICK: Hi, what is the danger to patients who, like myself, would need, say, an injection of a steroidal product into my knee? I have water in the knee and an inflammatory situation that props up now and then. And so I just wondered: Is there a danger in that regard?
KNOX: Well, there have been four, I think, four or five cases of fungal infection involving injections into the joints: knee, elbow, hip. And they're among these 328 known cases so far. But, of course, those all resulted from patients who got injections of the drug from - the steroid from this company.
After September 26, that was recalled. There shouldn't be anybody getting any steroid from this company. You know, that's not to say there aren't any risks out there that was don't know about, but I think it's - if you're looking ahead, you probably are pretty safe.
RICK: Thank you.
CONAN: Thanks for the call, and that raises the question of we know the company has been closed, they're not manufacturing anything anymore, but where's the investigation headed?
KNOX: There's a federal criminal investigation, which is unusual, and then there's a Massachusetts investigation that's also involved at the FDA and the CDC. We don't know much about what the federal investigation is showing; it just started, and they don't talk about it. But Massachusetts has been actually pretty open about their preliminary results.
Two weeks ago, Governor Deval Patrick declared that this company, New England Compounding Center, had misled state officials by producing in bulk and shipping nationally without a valid prescription for each patient. Just this week, officials released here in Massachusetts the results of a preliminary investigation that was pretty harrowing, as one reporter called it.
It reported that, as the state had said, that the company's operating beyond the scope of their license by acting as a manufacturer, that it shipped orders from the suspect lots of drugs days before getting back their own test results to confirm the sterility. They weren't sterilizing the drugs for long enough to guarantee that they'd be sterile.
There was black mold in several sealed vials of the fungus that were still at the company. The mats, the floor mats at the entry to the sterile room were filthy. There was leaking, a leaking boiler in the room next to the clean room, with standing water on the floor. I mean, and they said this is - they haven't even really concluded what the root cause of all this was. But clearly there were multiple problems.
CONAN: And this sort of thing, had this been a manufacturer instead of a compounding pharmacy, would there have been government inspectors to say wait a minute, you've got to clean that up?
KNOX: Well, we'd like to think so. Yes, they would have had the authority to go in. There would have been regular inspections. And the federal Food and Drug Administration regulations governing manufacture of drugs are much more stringent. Generally speaking with these companies, these compounding pharmacies, which range in all kinds of different sizes, but generally speaking they're not inspected unless a complaint or a problem has arisen.
And often they're not inspected at all without warning. So the regulation is really a whole lot different.
CONAN: Let's see if we can go next to - this is Ted(ph), Ted with us from San Antonio.
TED: Hey, how are you doing?
CONAN: Good, thanks.
TED: So what I want to know is, I feel like the patients aren't being protected here. I don't hear where they're listing the doctors that oversee this, these bad batches. And then also why aren't they, you know, having like a recall notice going out to all the patients so they know hey, you may have received a bad dosage of this thing, so be aware of, you know, any - because like you're saying, it can take six weeks to get this onset.
And if you had something a month, where you're having headaches and a stiff neck, how would you know?
KNOX: Yeah, that's been a big problem. Well, there is, as of this week, I think yesterday, I believe, the FDA has posted on its website, and you can get it, a list of all of the doctors and clinics and hospitals that received drugs from New England Compounding Center and the drugs that they did get, it's like 300-and-some pages long, it's, you know, thousands of drugs.
I don't think there's any practical way for the government to know the names of the patients who got the drugs. I think they have to go through the doctor who prescribed it and, you know, the hospital or clinic that gave it. But they are saying that - go ahead.
TED: No, I was going to say, I mean, at that point you would think that the physicians would then in turn, you know, find out who, who received steroid injections during this, you know, couple-month period or whatever it was that these tainted batches were released out and then notify their patients.
But, you know, I'm not sure if that's something that's being done or, you know, maybe this kind of opens the door for a good procedure or a process for medications and keeping track of patients who are taking these medications because you never know. I mean, the next bad batch could come out from, you know, an FDA-approved piece that all of a sudden has a bad, you know, whatever's wrong with it.
CONAN: Tracking is a big issue. Thank you, Ted.
TED: Thank you.
KNOX: Yes, well, actually, the CDC has been saying, and the FDA have been saying for several weeks now please, if you have any symptoms, and I can run through them, some of them if you'd like, that might indicate meningitis of fungal infection, see your doctor immediately, tell them if you've had an injection recently, even if you don't - obviously wouldn't know, probably, where the medicine came from.
But - and so they're urging doctors to contact patients who have had injection, urging patients to report to the doctors. Obviously, people could slip through.
CONAN: We're talking about who makes our medicine and how safe it is or not. If this case raises questions for you about drug safety, give us a call, 800-989-8255. Email us, firstname.lastname@example.org. Stay with us. I'm Neal Conan. It's the TALK OF THE NATION from NPR News.
(SOUNDBITE OF MUSIC)
CONAN: This is TALK OF THE NATION from NPR News. I'm Neal Conan. Health officials fear cases of fungal meningitis linked to contaminated steroid shots could continue to climb through Thanksgiving. The fungus involved in this case rarely affects humans. It's so rare, doctors don't know its incubation period, which could be months.
We're talking today about what went wrong in this case of a particular compounding pharmacy in Massachusetts, about who makes our drugs and whose job it is to make sure those drugs are safe. If this case raises questions for you about drug safety, give us a call, 800-989-8255. Email email@example.com. You can also join the conversation at our website. That's at npr.org. Click on TALK OF THE NATION.
Our guest is NPR health and science correspondent Richard Knox. Joining us now from member station WBUR in Boston is Kevin Outterson, an associate professor of health law and bioethics at Boston University, editor-in-chief of the Journal of Law, Medicine and Ethics. And it's good to have you with us.
KEVIN OUTTERSON: Good afternoon.
CONAN: And I wanted to ask you: How far - how much of an outlier, at least as far as we can tell, was this one particular compounding pharmacy?
OUTTERSON: Compounding pharmacies fall into a very gray area in terms of regulation. So in that regard they're not unusual. But certainly we don't have many examples of compounding pharmacies with this level of fungal contamination, and certainly not with this many people that are sick and who have died.
CONAN: Are there many compounding pharmacies like this one that ship products out of state in bulk?
CONAN: And so it's a - these are several of them, at least, that are pretty fair-sized manufacturers? That's a loaded word, but that's what they are?
OUTTERSON: When you're Pfizer, Merck or one of the big drug companies, and you want to build a drug plant, it's registered with the FDA, and the FDA inspects it in advance. There's all sorts of rules. For a compounding pharmacy, I can't answer your question because we don't know exactly how many compounding pharmacies are shipping large quantities across state lines.
CONAN: So there's a gap in regulation that allows them to do this?
OUTTERSON: Absolutely. The FDA in 1992 began to expand regulation of compounding pharmacies, and the pharmacies responded, and they were able to get a law passed by Congress in 1997 which kind of channeled the FDA's ability. But that law itself was challenged, went all the way to the Supreme Court. A pharmacy who didn't like the law challenged it.
And in 2002, the Supreme Court effectively struck down the entire law. Since then, the FDA has been on fairly uncertain ground when it comes to trying to aggressively identify, in advance of a problem, compounding pharmacies that are violating the law.
CONAN: And so there - you would think that these compounding pharmacies were primarily neighborhood operations with - well, this particular patient has an allergy to the preservative that's in this eye medication, can you make up a special batch?
OUTTERSON: That's exactly what this batch was supposed to be from New England Compounding Center. The drug is commercially available. It's made by Pfizer. There's been no indications that Pfizer had a problem. It's also manufactured today by two generic companies, no indications of problems there.
But the New England Compounding Center was required by FDA rules to make something that was slightly different, and so what they did, amazingly, is that they left out the preservative. The preservative was left out so they could say it was a different product designed for patients who had perhaps an allergy to the alcohol used as a preservative.
But in retrospect, keeping a preservative out of this drug was a very bad move.
KNOX: I'm sorry, I just wanted to add a point of information here on that very thing. I think Professor Outterson is exactly right that when you're leaving a preservative out of something, then you have especially stringent need to make sure that it's sterile because there isn't any preservative there to, you know, preserve sterility.
However, I'm told that the reason that they leave preservative out of drugs that are in steroids in particular, that are intended to be injected into the spine, is that the preservatives that are used in the commercially available products can be toxic to nerve cells, and so that's why there's a special demand for preservative-free methoprednisone.
CONAN: Let me ask another question, though, about procedure. Sterility, we think you boil it in water for a few minutes, it should be fine. It's apparently a lot more complicated than that. You were describing, Richard, these clean rooms where these preparations are compounded.
KNOX: Yes, I mean if you - these fungi are out in the environment, I mean although it's extremely rare to have it cause human infection. They are out in the dirt in the grasses and so on, and so a spore can be carried into a room, and it can be - you know, obviously they're invisible. They can multiple. They can get - contaminate the equipment, the people involved.
And so you have to be really very stringent to keep that from happening and to make sure that you know if it's happening so that you can, you know, stop and clean everything up.
CONAN: And Kevin Outterson, these kinds of procedures are not cheap.
OUTTERSON: No, they're not. The Massachusetts Interim Report had some very interesting details on this. It appears that there's not a good record of these particular batches being sterilized for the full period of time that's indicated by the pharmacy regulations. And when they began the actual physical inspection of the pharmacy, when they went out there - I'll have to look at the date - they found employees cleaning things and a strong smell of bleach, indicating that the company was trying to clean things up, you know, because the inspectors were on the way.
The other thing that's safe here or that relates to safety is in addition to sterilizing, they're supposed to take an adequate number of samples from each batch and send it to an independent laboratory. And the Wall Street Journal reported yesterday that apparently this batch, or at least one of them, went to the Analytic Research Laboratories in Oklahoma City, but a very inadequate number of samples were tested out of the batch, statistically not nearly enough to establish that the whole batch was actually safe.
CONAN: Let's see if we can get a caller in on the conversation. Let's go to Anthony, Anthony with us from Park City in Utah.
ANTHONY: Hi, thanks for having me on the show. My wife and I have a small compounding pharmacy here in Park City, Utah, and we're very dismayed about this story because we feel that obviously these - the compounder in New England was operating far outside of the parameters of a true compounding pharmacy and by doing so casting the entire industry in a bad light.
CONAN: There's an email on a similar point, Anthony, this from Judy in Boise: I'm concerned that all compounding pharmacies will be mistrusted after this terrible episode. We have here in Boise at least two locally owned, highly professional compounding pharmacies that fill individual prescriptions and are invaluable, as I know from personal experience with a healing compound after surgery for skin cancer and a medication compounded for a pet dog.
And so should, Kevin Outterson, all compounding pharmacies be tainted with the New England Compounding Center's brush?
OUTTERSON: I think most Americans before a couple weeks had never heard of a compounding pharmacy. So really it's quite unfortunate that the entire industry is being tainted by what happened at NECC. I don't think that anyone in Congress is considering regulating at the federal level the traditional, local compounding of drugs.
So while it's a public relations disaster of the first order of magnitude for the entire industry, I think your caller and the email, it's unlikely that the FDA wants to really get involved in that local type of business.
CONAN: Richard, though, it's fair to say that there is an industry lobbying group which has been active in working against the approval of regulations that might cover the industry.
KNOX: Yeah, and I think we're going to see a lot of lobbying as this goes forward. I do think it's - let me just make one point about compounding pharmacies, because as Kevin says, you know, until recently nobody knew about them. You get a drug that's prescribed by your doctor, you think, well, it must be good, it must have gone through all kinds of usual regulation, I can trust it.
The compounding pharmacies are a pretty wide spectrum of operations. Many, many hospitals do, you know, compound drugs. Some pharmacies out there make up drugs to order for particular patients and particular needs, and there are many firms like this one in Park City that are, you know, perfectly respectable and conscientious and important firms.
Hospitals and doctors rely on these places to provide a fairly substantial fraction of drugs, and often they're critical drugs for patients who need to have special compounding. So it would be really unfortunate if all this led to, you know, obstructions of that necessary process.
But obviously the industry, you know, trade organizations, can be expected to fight federal regulation, which imposes a lot more strict standards and processes and procedures that would be onerous for a lot of their members.
CONAN: Anthony, might it be reasonable for compounding pharmacies like yours to avoid regulations, to say, well, OK, then we will not ship across state lines?
ANTHONY: Well, I think that another point that goes hand-in-hand with all this is the difference between sterile compounding, where there's a medication being injected directly into the bloodstream, versus a non-sterile, like a topical cream or something that's ingested or a suppository, things along those lines, where the risk factors are much lower.
And a lot of these small compounders don't deal with sterile medication. They intentionally forego that and deal with other types of applications. And I think that's an important distinction to be made; also, of course, only preparing compounds per a doctor's prescriptive order and not doing what these guys in New England were doing.
CONAN: I understand. And Kevin Outterson, that's already supposed to be in the rules, but might these other restrictions that might be common sense, if you want to be a compounding pharmacy, don't ship across state lines and don't try to make sterile medicines?
ANTHONY: Yeah, I think the problem for...
CONAN: Excuse me, I was asking Kevin Outterson, forgive me.
ANTHONY: Oh, I'm sorry.
CONAN: That's OK.
OUTTERSON: I'm sure that's on the menu in Congress, you know, probably after the election, to take a good look at this and look at those choices. But lobbying also affected a lot of things that happened in the past, and so this very pharmacy in Massachusetts, NECC, the compounding pharmacy, for the exact drug that we're talking about, there was a series of regulatory actions taken by the State Board of Pharmacy in 2002 and 2006, when Mitt Romney was governor, which decided not to file a consent decree, which would have caused a lot of scrutiny of this pharmacy.
And they pulled back, despite the investigator's suggestion, you know, recommendation to file a consent decree, and we really don't know much about the political lobbying effort that went on behind the scenes on that.
We also have, you know, publicly reported as well the donations from one of the owners of this pharmacy in a fundraiser not that long ago for Senator Scott Brown at one of the owner's houses. So there's just a lot of, you know, politics that goes into regulating an industry like this.
But I think after this outbreak, it's going to be very difficult for them to have political lobbying as usual. It's going to be a different ballgame in Congress.
CONAN: Richard Knox, I think it's also fair to say that the Obama administration, during the Obama administration there had been some thought of regulation affecting compounding pharmacies but backed off for fear of raising the cost of drugs.
KNOX: I hear that. I haven't reported that directly, so I don't know that whole story. I do find that one interesting aspect of all this is that people seem to be, including government officials, seem to be surprised, at least in public, that there was this pharmacy shipping in such bulk and, you know, nationally, basically.
But that really shouldn't be any surprise. They've been doing it for years. They've been doing it in broad daylight. They market their product at meetings. I think people in the pharmacy business know that there are these companies out there. So it really shouldn't have come as any surprise that this was happening. And I think that one of the big questions now is whether the states can realistically regulate companies that are engaged in that kind of business.
I mean many state pharmacy boards, I'm told, don't even have their own staff of inspectors. They share inspectors with the cosmetology and the barbers and the, you know, contractors and stuff. This is a pretty specialized and highly technical realm, and if you're going to regulate carefully and appropriately, it requires more expertise than many states, and more personnel, than many states have.
CONAN: Richard Knox, NPR's health and science correspondent; also with us, Kevin Outterson, associate professor of health and law and bioethics at Boston University, editor-in-chief of the Journal of Law, Medicine and Ethics. You're listening to TALK OF THE NATION from NPR News.
Another caller from San Antonio, Barbara's on the line with us.
BARBARA: Hi, two quick questions. I'm wondering if those unfortunate people that died maybe had compromised immune systems, and that's what, you know, had them pass away as opposed to just getting sick. And then I'm also wondering if the people running this pharmacy might be - they might face criminal charges. That's it.
CONAN: On that first point, Richard, I've read, I think, in your reporting, most of the people taking these injections tended to be older. I don't know about compromised immune systems.
KNOX: Yes, there's a lot we don't know about the population involved, both who died and those who got seriously ill. I think probably it's a good bet that many of them were older. But I don't think all of them were. I think the first case was a man in his 50s who died. His case report was published in the New Journal - by the New England Journal last week, and it makes for very grim reading, just massive destruction of brain tissue and both hemorrhagic and strokes and strokes caused by blood clots. It was just really a mess.
And so I don't think we can assume it was only older people with compromised immunity.
CONAN: And Kevin Outterson, on criminal charges - I know you're a professor of health law, but maybe you can help us out here.
OUTTERSON: If I could say something briefly about the case report in the New England Journal, the 50-year-old man was there for back pain, and he was not taking any, you know, immune drugs whatsoever. His immune system was normal and healthy in the report.
An interesting thing is that the medical literature is unable to support, is unable to find any clear evidence of efficacy of using these types of steroid drugs to eliminate back pain. It's been a controversy for 15 years in the literature, and there was a report in the New England Journal in 1991, and dozens of studies since then, unable to find, you know, efficacy for this procedure.
So it's - one of the other tragedies of this is that these people have died doing a process that may or may not have helped them at all for their underlying back pain. As for criminal charges, it will require, obviously, evidence of intent. But the fact that when the Massachusetts investigators arrived in late September out at the plant, they found them trying to clean things up with bleach, I think will - may be able to show some intent on behalf of the owners to hide what had happened.
CONAN: Barbara, thanks very much for the phone call.
BARBARA: Thank you.
CONAN: And Kevin Outterson, appreciate your time today.
OUTTERSON: Thank you.
CONAN: Again Kevin Outterson of the - professor of health and law and bioethics at Boston University and editor-in-chief of the Journal of Law, Medicine and Ethics, with us from member station WBUR. Richard Knox with us from his home office in Dorchester, Massachusetts. Always good to have you with us, Richard.
KNOX: Thanks, Neal, any time. Transcript provided by NPR, Copyright National Public Radio.