Health Editor’s Note: The following is both a link to a podcast and the actual text/script of the interview in the podcast.  This interview is between Marty Makary, M.D./Editor-in-Chief for Medpage Today and Katherine Eban whose most recent book, Bottle of Lies: The Inside Story of the Generic Drug Boom she is being asked to describe. 

Katherine Eban is an investigative journalist who is obviously advertising her most recent book, but there is also a great deal of insider/insightful information we can pick up in this discussion. 

For instance, most generic drugs  (we all use them in the light that they are less expensive) are produced by foreign markets and the FDA gives them a three-month warning before “touring/checking” on said facilities….lots of time to prepare for an inspection and cover-up.  Either listen to or read this article as it is a real eye-opener…..Carol


pharmafactz.com

Podcast: Is That A Centipede I See in My Capsule? 

Marty Makary, MD, MPH, talks with investigative journalist Katherine Eban about the dangers of generic drugs

Marty Makary, MD, MPH: I’m here with Katherine Eban. It’s great to be with you here and great to see you again.

Katherine Eban: Thanks for having me, Marty. It’s nice to be here.

Makary: Katherine is one of our preeminent investigative journalists and has done some incredible work. If you’ve seen the movie The Report, it was, in part, inspired on her Vanity Fair article. She has done incredible work in the generic drug-sourcing world. Her new book, Bottle of Lies, is a New York Times bestseller. She actually is a former New York Times investigative reporter, writes now for Fortune. Gosh, if we had more investigative journalism in healthcare, it would have a tremendous impact on the field.

Eban: I hate to think of today’s world without the investigative journalists we do have, who have exposed so much wrongdoing, but of course, there’s always more work to do. Thank God for the ones we do have and we need more, for sure.

Makary: I’d love to send our surgical residents, for their research years when they spend 2 years in the lab, to spend 2 years doing investigative journalism mentored by you.

Eban: Love it!

Makary: Some of the stuff that you’ve uncovered is just incredible. Now you were a Rhodes Scholar. You went to Brown. Not too shabby. Rhodes Scholar. Oxford. Everyone who has a Rhodes scholarship is required in this scholarship to have some sport and do some athletic piece to their scholarship. Not many people know that. What was your sport?

Eban: I was in the circus.

Makary: [LAUGHTER] That’s a sport?

Eban: I was a clown. Some people say I still am one, but yes.

Makary: In the drug industry, we’re doing research now, you’re still working in a circus.

Eban: I was a clown, and according to the selection committee, I was the first clown that they ever selected.

Makary: [LAUGHTER] I’m just blown away by this book.

Eban: Thank you.

Makary: What tipped you off to get into this space of understanding where the medications we physicians prescribe come from and their safety?

Eban: Most big investigations, at least the ones that I’ve worked on, always begin with some kind of tip or phone call. That phone call, for me, came in 2008. I was contacted by Joe Graedon, who is a host of The People’s Pharmacy.

Makary: The People’s Pharmacy, the podcast.

Eban: Yeah. He is a trained pharmacologist and he said his show was being flooded with complaints by listeners, patients who had taken generic drugs and had relapses when they were switched or suffered side effects. He had taken their complaints to the FDA and officials there basically were dismissive that this was psychosomatic. The color of the pills or the shape was different, but he did not believe that.

Makary: The FDA basically said, “These people are just kind of crazy. There’s nothing there. This is the normal variation of complaints that we get.” He didn’t take that for an answer.

Eban: That’s right. We can come back to this later because I have a theory about it. But the FDA said especially when a pill first goes generic — so you have all these people switching from brand to generic — and that’s when they complained the most. I actually have a theory about why that is we can talk about.

Makary: New production.

Eban: I actually think that the generic drug companies may, in fact, not know how to make the drug when they first launch it.

Makary: Interesting.

Eban: They haven’t tested it properly. They get their approval, they’re first to file, then they go back into the lab and figure out how to actually make it.

Makary: The big take-home I took from this book: most of the generic drugs that we physicians prescribe come from overseas.

Eban: Right.

Makary: It hasn’t always been like that, but that’s the way we have it now. What’s happening overseas is mind-boggling.

Eban: It is really The Jungle for the 21st century, and I say that referring to the Upton Sinclair expose of The Jungle, where he exposed what was happening in U.S. meatpacking plants. But what you have is countries making our lifesaving drugs where they do not have a years’ long, decades’ long regulatory system up and running, and so it is really just a free-for-all. It is just a wild scene in a lot of these overseas plants.

Makary: One patient found a bug. In New Jersey, a patient sent her medication … I think it was an anti-hypertensive medication. She found a live bug in the pill in New Jersey. It was sent by Express Scripts, one of the biggest PBMs [pharmacy benefit managers]. You spent 10 years doing the research for this book. You spent time in China and India. What did you see over there?

Eban: First of all, when I went into these manufacturing plants, my visits were mostly dog-and-pony shows to show me pristine plants.

Makary: They knew you were coming.

Eban: They knew I was coming. They had let me come in, but I saw a very different world within these plants through whistleblowers. I worked with a lot of whistleblowers who had contacted me — or I had made contact with them — who were showing me documents, showing me photographs, giving me really the sort of gory details of what was happening in these plants and the kinds of crazy decisions that were being made like failing drugs, drugs that had glass particles in them were being approved to be dispensed. Broken down, rusted equipment that was leaving metallic fragments in pills. Those were being dispensed.

Illicit use of ingredients. You can’t just swap ingredients. But they had drugs that were dissolving improperly, so they just haphazardly changed things up to try to get better data to show the FDA. All of this was taking place in a kind of lawless regulatory environment. They’re not afraid of their own regulators. They’re afraid of the FDA, but what they have built is an elaborate system to trick the FDA. Our FDA has all but volunteered to be tricked because we announce our inspections in advance overseas. We give 3 months’ notice. They send in data fabrication teams.

Makary: So there’s no surprise visits?

Eban: There are no surprise visits.

Makary: Was there in the past?

Eban: There was a pilot program that my book exposed. I’ll tell you, Congress is very interested in this pilot program because they decided, “limited program, we’re going to do all the visits in India unannounced or short notice.” They did it for a year and a half. Boy! Once they were walking into these plants on short notice, they were finding unbelievable stuff like …

Makary: Like what?

Eban: … sterile manufacturing plants that are just inventing their microbial testing data. They’re supposed to test the air.

Makary: Fabricating.

Eban: Fabricating. FDA inspectors walked into one plant and the microbial testing data was perfect. It all looked great. The air, the water, the surfaces all good. They weren’t testing anything. They just invented this data.

Makary: You describe lizards, snakes, dirty floors, mops used for the bathrooms used in the drug manufacturing facility. Is this sort of an egregious thing of the past or is this an ongoing issue right now?

Eban: This is absolutely ongoing. There is no change and India’s plants have gotten a lot of warning letters from the FDA. The Indian industry is saying, “This is totally in the past. It had to do with this one company, Ranbaxy. There is no evidence to support that whatsoever.” This is an ongoing issue. Nothing has changed. Since my book came out, Congress is probing this. I’ve got to say looking at what’s going on in Washington, my hopes are a little diminished for real change, but that’s what we need.

Makary: Because of the influence of the special interests, general inaction in government?

Eban: We’re in an anti-regulatory era and our regulatory infrastructure is essentially being dismantled around us. The thing is, if anybody was in these plants, there is nobody who’s going to want to take medicine from a sterile manufacturing facility where there is no drainage piping in the bathroom right next to a production area.

Makary: These horrific conditions you’re describing, are these plants still producing medications that we U.S. physicians are prescribing? Because we don’t know the source. Let’s be honest. I write a script. I have no idea where that medication is made and what the plant conditions are.

Eban: Let me just first say, you don’t know where the medication is made because the companies deem it to be proprietary, and that has got to change. There is no reason that we shouldn’t have a country of origin labeling on our finished doses and our active ingredients. The shirt you’re wearing right now is going to tell you where it was made, right? That’s got to change. But you’re right. You can’t know and you should be able to know.

Makary: The surprise visit thing. I’m glad Congress is acting on your book since it hit the New York Times list. That inspires me a little bit, but this simple fix that you’re offering of let’s switch to surprise visits seems so logical. I’ll tell you my little experience. When the Joint Commission comes to a hospital, and they used to do surprise visits, they were getting an interesting cross-section of what’s actually taking place. When they started to announce their visit, hospitals began to put up literally a banner over their front door saying, “Please welcome the Joint Commission.” I received text pages.

Eban: Oh, my God.

Makary: “Please welcome the Joint Commission visiting with us today.” Of course, everyone is on their best behavior, so you kind of lose that ability to assess what’s really happening.

Eban: Right.

Makary: It seems like one simple solution.

Eban: Now, imagine if the Joint Commission called up the hospital and said, “Could you make our hotel reservations for us and send a vehicle to pick up our inspectors at the airport?” because that’s what’s happening overseas with these FDA inspections. It’s nuts, right? The FDA is actually asking the local manufacturing plants to serve as travel agents.

Makary: The plant being inspected by the FDA, by the United States FDA, is making the hotel and travel and car service arrangements?

Eban: Luxury vehicles. They’re sending luxury vehicles to the airport.

Makary: Why not splurge?

Eban: They’re upgrading FDA inspectors’ hotel rooms. They never see a bill. Then they’re arranging trips to the Taj Mahal, massages, offers of gold coins. It’s nuts.

Makary: So separate from the massages.

Eban: [LAUGHTER]

Makary: Maybe we can include massages.

Eban: There’s a lot of massages.

Makary: Is that right?

Eban: Yes.

Makary: Interesting. In general in those countries or offered to the inspectors?

Eban: No, offered to the FDA inspectors.

Makary: Interesting. Is this legal or illegal under U.S. law? Is any part of it legal?

Eban: Right, that’s a really good question. The FDA investigators, who are going overseas, don’t get any special training for this. What they get is the usual ethics training. You’re not allowed to accept a gift that’s over $20, but it all gets very murky. You’re being offered a closing-night banquet, so what do you do at this banquet? Do you take out your credit card? Do you offer cash? How do you end up making sure you’re not accepting anything more than $20? How do you not offend the people who had you there?

Makary: Lipitor is one of those medications that you identify was made — probably is currently being made — with substandard conditions, according to what you write about. The company that raced to make the generic form … and there is a bit of an arms race now to move to generic because of drug pricing. You basically describe how these officials of the generic company rushed the FDA. There was a fistfight in the parking lot of the FDA.

Eban: When I started hearing about these fistfights in the FDA parking lot, I was just blown away, but it made perfect sense. There was this incentive that was built into the generic drug approval process, which is called first to file. Basically what that says is if you’re the first generic company — first being first by seconds — to put down your application at the FDA, and you’re approved to make the drug, you get 6 months of exclusivity on the market. To give you a sense of how much that exclusivity is worth.

Makary: It’s a lot of money.

Eban: It was $600 million for Ranbaxy when it made generic Lipitor. These companies were going in. I started hearing about companies. They’re sending their reps in to the FDA parking lot in stretch limos where they’re taking turns waiting and sleeping. They’re online. They’re pitching tents in the FDA parking lot. Then they’re lining up right at the door. Then the question is when the door opens in the morning, who’s going to be first? I heard about this altercation where a Ranbaxy, I think was it a Mylan rep pushed a Ranbaxy …

Makary: Mylan Pharmaceuticals?

Eban: Yes.

Makary: Well known to the public.

Eban: Yes, pushed a Ranbaxy rep out of the line so that she was in first through the door. I mean a literal altercation. Of course, you hear these stories as an investigative journalist. You’ve got to prove it. There was this memo that the FDA put out, a guidance which basically said, “We are very concerned about these tents that are being pitched in the FDA parking lot for weeks.”

Makary: [LAUGHTER] This is in Silver Spring, Maryland?

Eban: Yeah. You can’t make this stuff up. There’s the memo. There’s the guidance from FDA saying, “We’re concerned about safety in the parking lot, etc.”

Makary: Have you talked to Stephen Hahn, the new FDA commissioner, about any of these issues?

Eban: I have not and I have to say that the FDA was not too chatty with me when I came to them with a whole array of questions. They did respond. They did send statements, but they did not make anybody available for me to talk to when I was closing the book.

Makary: If I make an introduction with you and Stephen Hahn, would you be interested in talking to him?

Eban: I’d love to talk to him, absolutely.

Makary: What do you think he would say? The reason I am asking is oftentimes the FDA and the commissioner, in particular, is the subject of a pile on of blame for problems that stem really from congressional funding because Congress — many of whom are getting paid by special interests — don’t want surprise inspections of plants that produce the majority of generic drugs. They will ensure that that funding stream is not there, and this division, despite the best intentions of those leading the FDA, is not funded. We hear lots of stories about deals and threats and quid pro quos, and of course, this is almost the business of government sometimes. I wonder what he would say to this. He’s a cancer doctor from MD Anderson, good guy.

Eban: I don’t know what he would say, but if he was going to kind of be in line with the talking points of the agency, what he would say is, “We have a risk-based system.” Nobody ever really spells out exactly what the system is, but where we make these careful evaluations. We will do surprise inspections, if need be, and Americans can be confident that their generic drugs are safe. That’s what they say. That’s what they’ve told Congress. Then, of course, any example to the contrary is like, well …

Makary: Has there been any evidence of surprise visits since your book came out?

Eban: I have heard rumblings that they may be starting another pilot program, but they have not changed the policy. Janet Woodcock did testify before Congress, would it be better to do more inspections, to do surprise inspections, yes, but it does seem like a sort of …

Makary: I don’t understand what there is to discuss.

Eban: Right.

Makary: We could have hearings. We could write 15 articles in the medical literature, which is what we tend to do in healthcare. This is so aggravating because we hear about the one-offs and the fraud in healthcare. We learned about the generic drug companies colluding on price in the 60 Minutes piece, but this is the majority of medications that are generic that we U.S. physicians prescribe. What can doctors do about this? If they’re as angry as I am right now, are there any success stories? Are there hospitals that have done anything like the Cleveland Clinic story you mentioned?

Eban: Yes, so there are success stories. Now, let me just say I have infinite respect for physicians, and I recognize how sort of overworked and beleaguered they are often.

Makary: Thank you.

Eban: For me to sit here and give them an assignment of something more they have to consider seems crazy, but I will tell you the story of …

Makary: But if we’re pissed off and we want to do something, what can we do?

Eban: I think, first of all, on a patient level, since my book came out and I have presented to audiences of physicians, and I’ve had some physicians say to me interestingly, “Wow! I thought that when my patients complained they were just being whiners. Now I’ll think about it in a whole different way.” Now, instead of switching to a different kind of therapy, maybe I’m going to switch to a different manufacturer. That is what a fellow named Dr. Harry Lever at the Cleveland Clinic has done. He’s a cardiologist and I tell his story.

Makary: What’s that? Heart? Is that what cardiology is?

Eban: Yes. It is, as a matter of fact. [LAUGHTER]

Makary: Don’t worry. I know what I’m doing here.

Eban: In addition to diagnosing his patients, he started diagnosing the drug supply. He basically felt that his job was to figure out which drugs by which manufacturers were working and which weren’t. Through his vigilance and his recognition of recurring problems with the same manufacturers — many of them foreign, Indian — he began making a difference in the whole health system. He began working with the Cleveland Clinic pharmacists who are really top flight, and they developed a blacklist of manufacturers whose drugs they no longer buy.

Makary: Based on data that their problems are based on reports or suspicions.

Eban: Suspicions and clinical observations. What he said to me is, “We don’t have data,” but what he has is his years of experience and his recognition that there is no other explanation for a stabilized patient to suddenly become unstable except that there was this medication switch. He began tracking that.

Makary: When a doctor has a funny feeling that this medication is not working as it should — whether it’s a side effect profile that doesn’t seem warranted — they can kind of make a note and that formulary committee or P&T [pharmacy and therapeutics] committee, as some hospitals call it, can then look for patterns. You’re saying they basically have done this at the Cleveland Clinic where they’ve identified patterns to say, “We’re not going to use this supplier based in India.”

Eban: That’s right. They were literally finding that there were heart transplant patients who had been stabilized, were taking successful recoveries, were taking tacrolimus. They were taking the brand name immunosuppressant, and they were switched to Dr. Reddy’s tacrolimus. Suddenly, their patients were showing up in the ER with symptoms of organ rejection.

Then my question as an investigative journalist, “Are they the only ones?” There’s not really a lot of data here. Through sources inside the FDA, I was able to dig up a report from Loma Linda from their transplant team saying, “We are finding our patients are becoming unstable only when they’re switched to the Dr. Reddy’s tacrolimus.” Here was a corroborating set of observations from a different transplant center. I thought that was very interesting.

Makary: Is there an opportunity for transparency to help? Let’s say patients, when they go to GoodRx, can see where the medication comes from. The problem is, I guess, you’ve got overseas manufacturing plants that use sound practices and those that you’ve clearly exposed, and it’s not a one-off thing. It is prevalent.

Eban: How they do business.

Makary: Most of them, some, a small fraction?

Eban: Here’s a little dataset. One of the FDA investigators I feature in the book is a guy named Peter Baker, very intrepid investigator. He would go into these plants, and instead of just taking the data printout showing everything was great, he’d look in the computers and he found all of this metadata linked to these hidden tests where they’re pretesting the drugs to try to figure out how to alter the parameters of the test to get good data. He did 86 inspections in India and China over 4 years, and he found evidence of fraud in four-fifths of the plants he inspected. To me, that’s very compelling evidence that this is really endemic. This is how the industry works.

Makary: The FDA does not do its own testing of drugs. Is that correct?

Eban: Right, that is correct.

Makary: They rely on the manufacturers, the pharma companies, to submit their quality and safety profile data.

Eban: Right. An honor system.

Makary: An honor system.

Eban: That’s what we call that. Yes.

Makary: In general, I like honor systems, but this one I’m not sure we can trust them given the track record you described and exposed. Are they being forthcoming about their data and do they keep track of the data, so if something is not safe, that is discoverable?

Eban: They’re supposed to keep track of the data, but the FDA found, in fact, they were destroying data. Now, this sort of boils down to good manufacturing practices and general expectations. But when the FDA went in, they’re very reluctant to enforce to the letter of the regulation and sanction these companies that are violating these regulations. They’re very reluctant to use their own authority, so you have companies that are clear transgressors that have not been brought to justice, as it were.

Katherine Eban: Thanks for having me, Marty. It’s nice to be here.

Makary: Katherine is one of our preeminent investigative journalists and has done some incredible work. If you’ve seen the movie The Report, it was, in part, inspired on her Vanity Fair article. She has done incredible work in the generic drug-sourcing world. Her new book, Bottle of Lies, is a New York Times bestseller. She actually is a former New York Times investigative reporter, writes now for Fortune. Gosh, if we had more investigative journalism in healthcare, it would have a tremendous impact on the field.

Eban: I hate to think of today’s world without the investigative journalists we do have, who have exposed so much wrongdoing, but of course, there’s always more work to do. Thank God for the ones we do have and we need more, for sure.

Makary: I’d love to send our surgical residents, for their research years when they spend 2 years in the lab, to spend 2 years doing investigative journalism mentored by you.

 

Makary: Some of the stuff that you’ve uncovered is just incredible. Now you were a Rhodes Scholar. You went to Brown. Not too shabby. Rhodes Scholar. Oxford. Everyone who has a Rhodes scholarship is required in this scholarship to have some sport and do some athletic piece to their scholarship. Not many people know that. What was your sport?

Eban: I was in the circus.

Makary: [LAUGHTER] That’s a sport?

Eban: I was a clown. Some people say I still am one, but yes.

Makary: In the drug industry, we’re doing research now, you’re still working in a circus.

Eban: I was a clown, and according to the selection committee, I was the first clown that they ever selected.

Makary: [LAUGHTER] I’m just blown away by this book.

Eban: Thank you.

Makary: What tipped you off to get into this space of understanding where the medications we physicians prescribe come from and their safety?

Eban: Most big investigations, at least the ones that I’ve worked on, always begin with some kind of tip or phone call. That phone call, for me, came in 2008. I was contacted by Joe Graedon, who is a host of The People’s Pharmacy.

Makary: The People’s Pharmacy, the podcast.

Eban: Yeah. He is a trained pharmacologist and he said his show was being flooded with complaints by listeners, patients who had taken generic drugs and had relapses when they were switched or suffered side effects. He had taken their complaints to the FDA and officials there basically were dismissive that this was psychosomatic. The color of the pills or the shape was different, but he did not believe that.

Makary: The FDA basically said, “These people are just kind of crazy. There’s nothing there. This is the normal variation of complaints that we get.” He didn’t take that for an answer.

 

Makary: New production.

Eban: I actually think that the generic drug companies may, in fact, not know how to make the drug when they first launch it.

Makary: Interesting.

Eban: They haven’t tested it properly. They get their approval, they’re first to file, then they go back into the lab and figure out how to actually make it.

Makary: The big take-home I took from this book: most of the generic drugs that we physicians prescribe come from overseas.

Eban: Right.

Makary: It hasn’t always been like that, but that’s the way we have it now. What’s happening overseas is mind-boggling.

 

Makary: One patient found a bug. In New Jersey, a patient sent her medication … I think it was an anti-hypertensive medication. She found a live bug in the pill in New Jersey. It was sent by Express Scripts, one of the biggest PBMs [pharmacy benefit managers]. You spent 10 years doing the research for this book. You spent time in China and India. What did you see over there?

 

Makary: They knew you were coming.

Eban: They knew I was coming. They had let me come in, but I saw a very different world within these plants through whistleblowers. I worked with a lot of whistleblowers who had contacted me — or I had made contact with them — who were showing me documents, showing me photographs, giving me really the sort of gory details of what was happening in these plants and the kinds of crazy decisions that were being made like failing drugs, drugs that had glass particles in them were being approved to be dispensed. Broken down, rusted equipment that was leaving metallic fragments in pills. Those were being dispensed.

Illicit use of ingredients. You can’t just swap ingredients. But they had drugs that were dissolving improperly, so they just haphazardly changed things up to try to get better data to show the FDA. All of this was taking place in a kind of lawless regulatory environment. They’re not afraid of their own regulators. They’re afraid of the FDA, but what they have built is an elaborate system to trick the FDA. Our FDA has all but volunteered to be tricked because we announce our inspections in advance overseas. We give 3 months’ notice. They send in data fabrication teams.

Makary: So there’s no surprise visits?

Eban: There’s no surprise visits.

Makary: Was there in the past?

Eban: There was a pilot program that my book exposed. I’ll tell you, Congress is very interested in this pilot program because they decided, “limited program, we’re going to do all the visits in India unannounced or short notice.” They did it for a year and a half. Boy! Once they were walking into these plants on short notice, they were finding unbelievable stuff like …

Makary: Like what?

Eban: … sterile manufacturing plants that are just inventing their microbial testing data. They’re supposed to test the air.

Makary: Fabricating.

Eban: Fabricating. FDA inspectors walked into one plant and the microbial testing data was perfect. It all looked great. The air, the water, the surfaces all good. They weren’t testing anything. They just invented this data.

Makary: You describe lizards, snakes, dirty floors, mops used for the bathrooms used in the drug manufacturing facility. Is this sort of an egregious thing of the past or is this an ongoing issue right now?

 

Makary: Because of the influence of the special interests, general inaction in government?

Eban: We’re in an anti-regulatory era and our regulatory infrastructure is essentially being dismantled around us. The thing is, if anybody was in these plants, there is nobody who’s going to want to take medicine from a sterile manufacturing facility where there is no drainage piping in the bathroom right next to a production area.

Makary: These horrific conditions you’re describing, are these plants still producing medications that we U.S. physicians are prescribing? Because we don’t know the source. Let’s be honest. I write a script. I have no idea where that medication is made and what the plant conditions are.

Eban: Let me just first say, you don’t know where the medication is made because the companies deem it to be proprietary, and that has got to change. There is no reason that we shouldn’t have a country of origin labeling on our finished doses and our active ingredients. The shirt you’re wearing right now is going to tell you where it was made, right? That’s got to change. But you’re right. You can’t know and you should be able to know.

Makary: The surprise visit thing. I’m glad Congress is acting on your book since it hit the New York Times list. That inspires me a little bit, but this simple fix that you’re offering of let’s switch to surprise visits seems so logical. I’ll tell you my little experience. When the Joint Commission comes to a hospital, and they used to do surprise visits, they were getting an interesting cross-section of what’s actually taking place. When they started to announce their visit, hospitals began to put up literally a banner over their front door saying, “Please welcome the Joint Commission.” I received text pages.

 

Makary: “Please welcome the Joint Commission visiting with us today.” Of course, everyone is on their best behavior, so you kind of lose that ability to assess what’s really happening.

Eban: Right.

Makary: It seems like one simple solution.

Eban: Now, imagine if the Joint Commission called up the hospital and said, “Could you make our hotel reservations for us and send a vehicle to pick up our inspectors at the airport?” because that’s what’s happening overseas with these FDA inspections. It’s nuts, right? The FDA is actually asking the local manufacturing plants to serve as travel agents.

Makary: The plant being inspected by the FDA, by the United States FDA, is making the hotel and travel and car service arrangements?

Eban: Luxury vehicles. They’re sending luxury vehicles to the airport.

Makary: Why not splurge?

Eban: They’re upgrading FDA inspectors’ hotel rooms. They never see a bill. Then they’re arranging trips to the Taj Mahal, massages, offers of gold coins. It’s nuts.

Makary: So separate from the massages.

Eban: [LAUGHTER]

Makary: Maybe we can include massages.

Eban: There’s a lot of massages.

Makary: Is that right?

Eban: Yes.

Makary: Interesting. In general in those countries or offered to the inspectors?

Eban: No, offered to the FDA inspectors.

Makary: Interesting. Is this legal or illegal under U.S. law? Is any part of it legal?

Eban: Right, that’s a really good question. The FDA investigators, who are going overseas, don’t get any special training for this. What they get is the usual ethics training. You’re not allowed to accept a gift that’s over $20, but it all gets very murky. You’re being offered a closing-night banquet, so what do you do at this banquet? Do you take out your credit card? Do you offer cash? How do you end up making sure you’re not accepting anything more than $20? How do you not offend the people who had you there?

 

Eban: When I started hearing about these fistfights in the FDA parking lot, I was just blown away, but it made perfect sense. There was this incentive that was built into the generic drug approval process, which is called first to file. Basically what that says is if you’re the first generic company — first being first by seconds — to put down your application at the FDA, and you’re approved to make the drug, you get 6 months of exclusivity on the market. To give you a sense of how much that exclusivity is worth.

Makary: It’s a lot of money.

Eban: It was $600 million for Ranbaxy when it made generic Lipitor. These companies were going in. I started hearing about companies. They’re sending their reps in to the FDA parking lot in stretch limos where they’re taking turns waiting and sleeping. They’re online. They’re pitching tents in the FDA parking lot. Then they’re lining up right at the door. Then the question is when the door opens in the morning, who’s going to be first? I heard about this altercation where a Ranbaxy, I think was it a Mylan rep pushed a Ranbaxy …

Makary: Mylan Pharmaceuticals?

Eban: Yes.

Makary: Well known to the public.

Eban: Yes, pushed a Ranbaxy rep out of the line so that she was in first through the door. I mean a literal altercation. Of course, you hear these stories as an investigative journalist. You’ve got to prove it. There was this memo that the FDA put out, a guidance which basically said, “We are very concerned about these tents that are being pitched in the FDA parking lot for weeks.”

 

Eban: Yeah. You can’t make this stuff up. There’s the memo. There’s the guidance from FDA saying, “We’re concerned about safety in the parking lot, etc.”

Makary: Have you talked to Stephen Hahn, the new FDA commissioner, about any of these issues?

Eban: I have not and I have to say that the FDA was not too chatty with me when I came to them with a whole array of questions. They did respond. They did send statements, but they did not make anybody available for me to talk to when I was closing the book.

Makary: If I make an introduction with you and Stephen Hahn, would you be interested in talking to him?

Eban: I’d love to talk to him, absolutely.

Makary: What do you think he would say? The reason I am asking is oftentimes the FDA and the commissioner, in particular, is the subject of a pile on of blame for problems that stem really from congressional funding because Congress — many of whom are getting paid by special interests — don’t want surprise inspections of plants that produce the majority of generic drugs. They will ensure that that funding stream is not there, and this division, despite the best intentions of those leading the FDA, is not funded. We hear lots of stories about deals and threats and quid pro quos, and of course, this is almost the business of government sometimes. I wonder what he would say to this. He’s a cancer doctor from MD Anderson, good guy.

Eban: I don’t know what he would say, but if he was going to kind of be in line with the talking points of the agency, what he would say is, “We have a risk-based system.” Nobody ever really spells out exactly what the system is, but where we make these careful evaluations. We will do surprise inspections, if need be, and Americans can be confident that their generic drugs are safe. That’s what they say. That’s what they’ve told Congress. Then, of course, any example to the contrary is like, well …

Makary: Has there been any evidence of surprise visits since your book came out?

Eban: I have heard rumblings that they may be starting another pilot program, but they have not changed the policy. Janet Woodcock did testify before Congress, would it be better to do more inspections, to do surprise inspections, yes, but it does seem like a sort of …

 

Eban: Right.

Makary: We could have hearings. We could write 15 articles in the medical literature, which is what we tend to do in healthcare. This is so aggravating because we hear about the one-offs and the fraud in healthcare. We learned about the generic drug companies colluding on price in the 60 Minutes piece, but this is the majority of medications that are generic that we U.S. physicians prescribe. What can doctors do about this? If they’re as angry as I am right now, are there any success stories? Are there hospitals that have done anything like the Cleveland Clinic story you mentioned?

Eban: Yes, so there are success stories. Now, let me just say I have infinite respect for physicians, and I recognize how sort of overworked and beleaguered they are often.

Makary: Thank you.

Eban: For me to sit here and give them an assignment of something more they have to consider seems crazy, but I will tell you the story of …

Makary: But if we’re pissed off and we want to do something, what can we do?

Eban: I think, first of all, on a patient level, since my book came out and I have presented to audiences of physicians, and I’ve had some physicians say to me interestingly, “Wow! I thought that when my patients complained they were just being whiners. Now I’ll think about it in a whole different way.” Now, instead of switching to a different kind of therapy, maybe I’m going to switch to a different manufacturer. That is what a fellow named Dr. Harry Lever at the Cleveland Clinic has done. He’s a cardiologist and I tell his story.

Makary: What’s that? Heart? Is that what cardiology is?

 

Makary: Don’t worry. I know what I’m doing here.

Eban: In addition to diagnosing his patients, he started diagnosing the drug supply. He basically felt that his job was to figure out which drugs by which manufacturers were working and which weren’t. Through his vigilance and his recognition of recurring problems with the same manufacturers — many of them foreign, Indian — he began making a difference in the whole health system. He began working with the Cleveland Clinic pharmacists who are really top flight, and they developed a blacklist of manufacturers whose drugs they no longer buy.

Makary: Based on data that their problems are based on reports or suspicions.

Eban: Suspicions and clinical observations. What he said to me is, “We don’t have data,” but what he has is his years of experience and his recognition that there is no other explanation for a stabilized patient to suddenly become unstable except that there was this medication switch. He began tracking that.

Makary: When a doctor has a funny feeling that this medication is not working as it should — whether it’s a side effect profile that doesn’t seem warranted — they can kind of make a note and that formulary committee or P&T [pharmacy and therapeutics] committee, as some hospitals call it, can then look for patterns. You’re saying they basically have done this at the Cleveland Clinic where they’ve identified patterns to say, “We’re not going to use this supplier based in India.”

Eban: That’s right. They were literally finding that there were heart transplant patients who had been stabilized, were taking successful recoveries, were taking tacrolimus. They were taking the brand name immunosuppressant, and they were switched to Dr. Reddy’s tacrolimus. Suddenly, their patients were showing up in the ER with symptoms of organ rejection.

Then my question as an investigative journalist, “Are they the only ones?” There’s not really a lot of data here. Through sources inside the FDA, I was able to dig up a report from Loma Linda from their transplant team saying, “We are finding our patients are becoming unstable only when they’re switched to the Dr. Reddy’s tacrolimus.” Here was a corroborating set of observations from a different transplant center. I thought that was very interesting.

 

Eban: How they do business.

Makary: Most of them, some, a small fraction?

Eban: Here’s a little dataset. One of the FDA investigators I feature in the book is a guy named Peter Baker, very intrepid investigator. He would go into these plants, and instead of just taking the data printout showing everything was great, he’d look in the computers and he found all of this metadata linked to these hidden tests where they’re pretesting the drugs to try to figure out how to alter the parameters of the test to get good data. He did 86 inspections in India and China over 4 years, and he found evidence of fraud in four-fifths of the plants he inspected. To me, that’s very compelling evidence that this is really endemic. This is how the industry works.

Makary: The FDA does not do its own testing of drugs. Is that correct?

Eban: Right, that is correct.

Makary: They rely on the manufacturers, the pharma companies, to submit their quality and safety profile data.

Eban: Right. An honor system.

Makary: An honor system.

Eban: That’s what we call that. Yes.

Makary: In general, I like honor systems, but this one I’m not sure we can trust them given the track record you described and exposed. Are they being forthcoming about their data and do they keep track of the data, so if something is not safe, that is discoverable?

Eban: They’re supposed to keep track of the data, but the FDA found, in fact, they were destroying data. Now, this sort of boils down to good manufacturing practices and general expectations. But when the FDA went in, they’re very reluctant to enforce to the letter of the regulation and sanction these companies that are violating these regulations. They’re very reluctant to use their own authority, so you have companies that are clear transgressors that have not been brought to justice, as it were.

 

Eban: Right.

Makary: Thanks to the whistleblower culture in the United States, if there’s destruction of data, that tends to get detected. I guess my question is overseas do these plants do secret testing?

Eban: Yes.

Makary: If the tests are not favorable, nobody will ever see it.

Eban: That’s right because what they do is they’ll do secret pretesting. Then, they’ll delete those pretests and then they’ll retest it with the new alteration of parameters and get a great data result. The only way that this was discovered by Peter Baker was because he was able to see evidence of the deleted tests in the metadata. But my God, you were going to rely on him to do that? The other thing that we were relying on and the way Ranbaxy got caught is through a whistleblower named Dinesh Thakur. There is no incentive to be a whistleblower in India. It’s basically a death sentence.

Makary: There’s a lot of back blow.

Eban: Yeah, and there’s no legal protection and there’s no financial upside. I mean, there is no upside to being a whistleblower. He was a whistleblower because he had a conscience that wouldn’t let him sleep and that’s why it got exposed.

Makary: Good for him.

Eban: But without him, without Peter Baker, our regulatory system is not set up to detect criminal behavior. It is set up to encourage good behavior by companies, but it is not set up to detect criminal behavior.

Makary: I think I’m seeing why generic drug companies are more successful from a business standpoint outside of the United States. You can do secret testing that’s not discoverable. There’s very few whistleblower protections. The conditions can be substandard. There’s no surprise inspections. Do you ever just say, “Look, I’m never going to take a generic medication unless I know it’s made in the United States or one of the countries that’s known to have good production standards?” Does it get that extreme?

Eban: There are companies whose drugs I will never take, because I have it in my head, I have that information in my head from my reporting that I know which companies I would like to avoid. I never want my kids to take medication made by those companies. The problem here is what’s a consumer supposed to do? What’s a doctor supposed to do? One of the things that I’ve said. We need big consumer organizations like the AARP, all of these great organizations to do their own testing. Where is the ranking? We rank cars. We rank washing machines. Why isn’t there testing and ranking of generic manufacturers?

Makary: Maybe this is a business idea for you.

Eban: [LAUGHTER]

Makary: Have you thought about talking to some entrepreneurs and have them come up with a credentialing system for generic medications where they would be independent testing, kind of like a UL brand?

Eban: I have had some of those conversations. I’ve had it not because I want to be an entrepreneur, which I don’t and I’m an investigative journalist.

Makary: [LAUGHTER] For people out there who want an early retirement, yacht, whatever the dream is, here’s a business idea.

Eban: Absolutely. It’s like we need a Yelp for generic drugs. What I was thinking was because there is data out there, there are companies like FDAzilla who have all of the data from FDA inspections that they capture and it’s searchable for companies that pay a fee for that. But why isn’t there an app where consumers, when they go into the drugstore, can just search and they can see, “Hey, that is the company that was busted for sterility failures and making up data. I don’t really want to take their drug.”

Makary: Tell us about Circa. This is an exciting thing that some doctors are involved in now, Intermountain Health.

Eban: Civica Rx.

Makary: Civica, sorry.

Eban: The idea with Civica Rx is it’s a non-profit. Let’s just say a non-profit drug manufacturer. Hello! That’s a great idea. Why don’t we get more of those? A non-profit drug manufacturer whose sort of charter mission is to make generic drugs in short supply. The idea was that they would seek out a customer base that was healthcare systems, and they would, with transparency, try to make the drugs in the U.S. and basically sort of tackle both the quality problem and the shortage problem and the cost problem. I think it’s a brilliant idea.

Makary: This way the hospitals can use a trusted source for their medications. This Civica Rx is a new endeavor.

Eban: Yes.

Makary: It could address some of these problems.

Eban: I think it’s a very exciting idea. I think the idea is if you guarantee supply by having these health systems as your customer base — so you have a guaranteed demand — and then you could guarantee supply and set up operations in the U.S. where the quality would be high, it would be well inspected by the FDA. I think it sounds like a tremendous win.

Makary: One final question since you’re an investigative reporter. One of your stories was on bees dying in the United States. Why are bees dying?

Eban: I personally think, and I think there’s a lot of evidence to show that it’s these neonicotinoids, which are these class of pesticides that disorient bees and basically attack their nervous system. We have a very powerful pesticide lobby that has kept those pesticides on the market. I think Europe banned them at some point. I’m not sure what the status is now, but I became a little bit obsessed with the bee death problem. It’s really crazy in that the bee farmers are just being devastated by these pesticides, and I also became such an admirer of bees. I went to a lot of, I don’t know what they’re called, bee farms.

Makary: Bee farms.

Eban: Bee farms. I went to a lot of bee farms and apparently a single bee, even if you have a lot of different hives, they have these little boxes that are different colors. Bees, if they’re not soused with neonicotinoids, can find their way back to their home.

Makary: Interesting. Honey is now being regarded more highly as a health food for many reasons, but I thought that was an interesting piece that you had.

Eban: Thank you.

Makary: All of these articles can be found online at your websiteBottle of Lies is the book. It’s an awesome read. Katherine, great to see you again.

Eban: Thank you for having me. I enjoyed this conversation.

Makary: I think we need more investigative journalism in healthcare, so keep up the great work.

Eban: Thank you very much.

Biography
Carol graduated from Riverside White Cross School of Nursing in Columbus, Ohio and received her diploma as a registered nurse. She attended Bowling Green State University where she received a Bachelor of Arts Degree in History and Literature. She attended the University of Toledo, College of Nursing, and received a Master’s of Nursing Science Degree as an Educator.

She has traveled extensively, is a photographer, and writes on medical issues. Carol has three children RJ, Katherine, and Stephen – two daughters-in-law; Suzy and Katie – two granddaughters; Isabella Marianna and Zoe Olivia – and one grandson, Alexander Paul. She also shares her life with husband Gordon Duff, many cats, two rescue pups, and two guinea pigs.

Carol’s Archives 2009-2013
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