The inadequate FDA medical device safety surveillance system: a case study

By Steven Greer, MD

January 25, 2012

I have worn contact lenses for more than twenty years without any problems. But recently, my eyes began to disagree with them. In the course of investigating the possible reasons why, I uncovered some shocking inadequacies of the FDA reporting system meant to detect safety problems in medical devices, and also discovered ongoing problems in the way that Johnson and Johnson (JNJ) deals with medical device safety problems.

In October of 2011, I received a new batch of JNJ-made Acuvue Advance contact lenses (Silicone hydrogel lenses meant to be worn for two weeks), purchased from Utah supplier “1-800-CONTACTS”, which is now affiliated with Walmart in an “alliance” of distribution. I have used that supplier for this specific make and model since 2006. Shortly after receiving a new box in the mail, my eyes became inflamed. This was the first time that I had ever had trouble tolerating contact lenses.

CLARE after JNJ Acuvue Advance contact lens wear

I do not sleep overnight in contact lenses, and when I would awake in the morning many hours after the lenses had been removed, excessive tear production overnight would form a crusty accumulation between my upper and lower lids. The inflammation would resolve approximately 24 hours after discontinuation of wearing the lenses. A catch-all term called CLARE (contact lens acute red eye) is applied to this condition.

In addition to the redness, I had developed a slight twitch in my upper right lid that could be induced consistently when I squinted and closed my lids forcefully. I have no neurological problems and have never before had such a problem. I am on no medications and received a clean bill of health from my last annual physical exam less than 12-months prior to the symptoms.

Being a medical doctor and also a healthcare analyst, I was well aware of the contact lens solution recalls back in 2006 due to manufacturing problems that caused serious eye infections and led to Buasch & Lomb collapsing and being sold to a private equity company. I promptly stopped wearing the contacts and went back to glasses as corrective lenses for myopia. I also proceeded to perform some medical experiments on myself to rule out certain variables.

I gave my eyes about two weeks of “time off” from the contact lenses, then tried wearing them again, using the same Alcon multipurpose solution. The CLARE inflammation returned. I switched to Bausch & Lomb “re-nu”, and the CLARE recurred just the same. I used the lenses straight from the blister-packages without adding any other lens solutions, and the CLARE recurred. All of this experimentation pretty much ruled out bacterial contamination of the contact lenses or lens solution. Although in rare cases, sometimes with counterfeit products, unopened blister packs have been contaminated with pseudomonas bacteria.

Medical doctor “MD” ophthalmology visits (As opposed to OD optometrists) are not covered under most health insurance plans unless there is an emergency room visit. Therefore, at this point of my saga, I unofficially consulted with two ophthalmologist friends of mine in Miami, and a third doctor with whom they put in contact with me up here in New York. Between all of them, their decades of training ranged from Harvard to Duke to Miami.

Based on my description of the problem, the three ophthalmology professors listed some possible etiologies for my CLARE. The contact lens fit (base curve) might have changed over time with long-term lens wear, thereby causing the lenses to be “too tight”, they all said. They also proposed that I might have suddenly developed an allergy even though the lens material had been tolerated by my eyes for many years. They all said that this was “common”.

Knowing medicine as I do, and how some popular diagnoses, not based on good clinical evidence, are nevertheless used when no better theory exists, I was skeptical of the theories being proposed by my friends. I kept searching for a more plausible etiology of my sudden inability to tolerate contact lenses.

Regarding my eyelid twitch, a neurology friend did not have an obvious explanation for it. He did say, however, that some of his residents had experienced the same problem while on long hospital shifts, and that their problems resolved after removing their contact lenses.

Based on my phone and email chats with my doctor friends, and the 1080i HD video of my eyes that I made for them, none of the doctors had included in their very unofficial “differential diagnoses” any manufacturing flaws of the contacts as the etiology of my CLARE. Moreover, the possibility that the lenses were counterfeit was something that never even crossed their minds. Most doctors completely trust that the FDA maintains safe and genuine supplies of drugs and devices.

I also contacted the head of the FDA’s CDRH medical device division, Dr. Jeffrey Shuren, in early December of 2011. I had interviewed him before on The Healthcare Channel. I did not request or expect his help with my personal matter, but was pleasantly surprised to see him escalate my problem to the medical officer in charge of contact lens regulations, Bernard Lepri.

The FDA initiated in December a review of their MAUDE database. This antiquated database system long predates Dr. Shuren’s service at the FDA, and has been criticized in numerous reports as woefully inadequate in detecting safety problems. Medical device malfunctions and medical complaints from patients rarely get reported to the FDA and seldom become recorded in the MAUDE database. Therefore, the statistical sensitivity of the MAUDE data are often very inadequate.

Approximately one month later, in January of 2012, the FDA replied to me with the results of their MAUDE database review. Since 2007, only 18 reports were found that remotely resembled my pattern of symptoms and were also related to my JNJ Acuvue Advance lenses. Those adverse events were mostly more severe and involved corneal ulcerations or blindness.

The FDA’s Bernard Lepri, an optometrist in the Division of Ophthalmic, Neurological and ENT Devices within CDRH, wrote to me the following, “Based upon the information you provided to FDA, we requested a MAUDE database MDR report on Acuvue contact lenses manufactured by Johnson & Johnson (JNJ).  This report of consumer complaints totaled 180 for the period of time ranging from 2007 to December 20, 2011 for Acuvue contact lenses of various different brands and types. Of those 180 consumer complaints over five years, 18 reports were for Acuvue Oasys with Hydraclear. You are wearing Acuvue Advance with Hydraclear: Silicone Hydrogel Lenses; Daily Wear with 2-week replacement…. I reviewed these 18 individual reports. They all reported symptoms such as mucus discharge, sustained but temporary loss of vision associated with superficial punctate keratitis, iritis, corneal infiltrates, giant papillary conjunctivitis, papillae and follicles. Some of the reports also included diagnoses of epidemic keratoconjunctivitis which is not at all related to contact lens wear. These reports all indicated that the individuals wearing these lenses had contracted a variety of different forms of conjunctivitis, allergic, bacterial, and viral.  These are not necessarily the result of a defect in the contact lenses they were wearing but most likely to exposure to pathogens and/or contact lens hygiene practices….The symptoms you described, while problematic and uncomfortable for you do not match the severity described in these 18 reports…. The description of your symptoms and the photograph of your eye (after wearing the lenses a couple of hours) is suspicious of CLARE (contact lens acute red eye) which has numerous etiologies: hypoxia, toxic effects from post-lens tear debris, mechanical irritation from a poor-fitting lens, dehydration of the tear lens while wearing lenses during sleep, solution hypersensitivity or toxicity or a reaction to bacterial toxins. This can occur even in seasoned contact lens wearers.  While the occurrence may be acute, one could have been wearing the lenses for many years before it occurs. If this is indeed the problem you are experiencing, it may be necessary for you to change contact lens materials, brands, and/or care products individually or collectively….To date, there is no recall on the lenses in question.”

In short, the FDA reviewed the matter and concluded that there was no need to actively investigate further by reviewing the JNJ files that are more comprehensive than the “passive” MAUDE database. (I will elaborate on MAUDE later.) The FDA medical officer also seemed to give the JNJ and the Acuvue lens the benefit of the doubt as to the cause of the serious complications reported.

Back to November, 2011: My backups glasses were very old and I began the simple process, or so I thought, of buying new ones. I assumed they would cost just a few hundred bucks. After investigating online sources, and searching in states other than New York with lower costs of living, I was surprised to learn that the state-of-the-art plastic lenses, and quality frames, would set me back $1,000. Mind you, I have a simple non-progressive prescription. (Aside, radio personality Don Imus complained that his more complex RX set him back $3,000 for new glasses). With the help of my friends at the Bascom Palmer Eye Institute in Miami, I had the lenses made at cost, so I saved a few hundred dollars. For comfort reasons, I wanted saddle bridge rimless frames made by a German boutique designer, which I found at World Optical in Downtown New York (The service was excellent).

After approximately two months of wearing glasses and time off from contact lens use, I realized that my annoying right eyelid twitch had gone way. Whether or not the lens inflammation was the cause will never be known for sure.

In January of 2012, I had a new eye exam and contact lens fitting performed by an optometrist at World Optical. The base curve fit of my eyes had indeed not changed, ruling out the “too tight” contact lens theory as an etiology for my CLARE eye problems. My trial fitting of CooperVision Proclear contact lenses, and also of JNJ Acuvue Oasys lenses, went without a hitch and no CLARE was elicited. This sufficiently ruled out the theory of a new-onset allergy to silicone hydrogel materials.

I then did something very unusual. I went back and test wore the old Acuvue Advances that caused my problems in the first place. For the sake of science, and my own curiosity, I became a Guinea pig. Sure enough, my CLARE returned. At this point, it had been determined that I could wear other forms of JNJ and CooperVision silicone hydrogel lenses without trouble, and that my particular batch of Acuvue Advance received in October, 2011 could not be tolerated.

With all of the evidence now implicating my old Acuvue Advance lenses, I did a web search and saw that a different type of the JNJ Acuvue lens was recalled in Asia and Europe due to manufacturing process out of spec causing CLARE in users. More recently, CooperVision also issued a recall relating to out of spec coatings.

Something that I was then starting to consider as well was the possibility that my lenses were counterfeit. My experience as a healthcare analyst made me more suspicious of this than the average doctor, perhaps. I vaguely recalled in the business news reports of counterfeit contact lenses in Asia, and in the U.S. with 1-800-CONTACTS selling bogus CooperVision lenses.

If my offending lenses were not counterfeit, then possibly there was a manufacturing glitch. Not appreciated by most medical professionals in the optical field is that, despite being cheap and “disposable”, contact lenses are actually quite complicated to manufacture. Slight variations in specifications and tolerances can lead to unsafe products.

Also not well appreciated by medical doctors and optometrists is that contact lenses are approved for sale by the FDA without large randomized controlled trials in humans. Contact lenses are considered medium risk “Class 2″ devices and are approved via the controversial 510(k) regulatory pathway obviating human clinical trials. Higher risk “Class 3″ devices, such as coronary stents, require rigorous human clinical trials and the “PMA” regulatory pathway.

I spoke with one of the current FDA officers who evaluates contact lenses, a chemical engineer by training named Joseph Hutter, and he told me that the 510(k) for lenses is unique in that small cohort trials in humans are required when the materials are new or changed. Typically, the size of such a trial would be approximately 60 patients, and parameters such as slit lamp or CLARE are measured. Moreover, the current contact lens classification system used by the FDA, that was designed for lenses before the silicone hydrogel technology of today, was totally inadequate. After cases of blindness related to lens material and press coverage in 2006-07, the FDA developed a new system that was recently implemented (FDA slides).

In the case of the JNJ Acuvue Advance line that caused my problems, the product was found to be accumulating lipids and other “buildup” too rapidly and not allowing proper transmission of moisture to the cornea. In 2005, the Acuvue Oasys line made of a different silicone material, senofilcon A, was launched in order to address these problems. Also, according to a JNJ call center staffer, the Acuvue Advance line was modified in October of 2010 to address the excessive “buildup” and renamed Acuvue Advance “Plus”.

Lipid and calculi deposits on a contact lens. Photo from FDA slides.

The JNJ call center staff are given this explanation for callers as to why the “Plus” was added, “The surface was redesigned to eliminate lipid deposits and buildup.” When I pressed further as to what the “surface changes” were, I learned that the actual hydrophilic polymer embedded within the galyfilcon material was possibly “tweaked”.

Joe Hutter of the FDA contact lens group was nice enough to give me the actual patent number for this process, which is summarized on the USPTO site as, “A wettable silicone hydrogel made by including a high molecular weight hydrophilic polymer into the silicone hydrogel monomer mix is presented. The hydrophilic polymer is entrapped in the hydrogel with little or no covalent bonding between it and the hydrogel matrix.”

If JNJ had made changes to the Acuvue materials, they would have been obligated to file a report, at the least, with the FDA. I spoke at length with the FDA’s Joe Hutter and he searched all the databases at his disposal for any reports from JNJ that indicated JNJ made changes to the Acuvue Advance line. He found nothing since 2010 that would explain any chemical composition or manufacturing changes. There were only a few reports to the FDA from JNJ and they were on simple changes in methods for testing for raw materials.

The Acuvue Advance line has since been phased out and will no longer be sold as of this year. None of these extensive changes to the line that attempted to solve a patient safety matter were ever reported to the FDA as a formal recall, according to the best of the FDA investigator’s searches with whom we spoke. If any reports exist that we missed, they were not well flagged as “manufacturing changes to address patient complaints”. Was this another “stealth recall” for which JNJ has become infamous?

JNJ did not answer our direct questions as to whether they properly notified the FDA of material manufacturing changes, and whether this phasing out of the Acuvue Advance was a “stealth recall”. Instead, the head of corporate communications wrote this, “Dr. Greer, The Vistakon team has provided the following statement in response to your inquiry: “Vistakon regularly reviews our portfolio and makes business decisions about product offerings, with a goal of providing patients and physicians with new and advanced products. Both ACUVUE ADVANCE and ACUVUE ADVANCE Plus Brand Contact Lenses continue to be prescribed by eye care professionals to patients requiring vision correction.”

JNJ is currently under a consent decree of the department of Justice and FDA after it initiated “stealth recalls” of improperly manufactured over-the-counter Motrin, pediatric Tylenol, and other medications. In the medical device division, the company has been investigated for numerous cases of improperly recalling devices, most recently hip implants and diabetes pumps. Congress has strongly criticized the CEO of JNJ, Bill Weldon, during oversight hearings, and the former Deputy Commissioner of the FDA, Joshua Sharfstein, likely lost his job in relation to all of those aforementioned JNJ scandals as Rep. Darrell Issa became his nemesis.

At the time of this report, I have submitted my remaining supply of the offending Acuvue Advance contacts that caused my CLARE inflammation to be analyzed by the FDA and JNJ in order to determine whether they were made to spec and are even genuine JNJ products. The results of those analyses will be reported later, if we can obtain them.

Once all of the evidence gathered had implicated more and more the actual contact lenses as the culprit, as opposed to infectious contamination induced by me, allergies, or poor lens fit, I called 1-800-CONTACTS and was stunned by their handling of the complaint. They were happy to send me replacement contacts, but they did not seem eager to process my medical complaints and forward them on to the FDA or JNJ. Instead, they bounced me to the JNJ call center.

After speaking with numerous call center staff of 1-800-CONTACTS, I learned that the company has no internal database to track incoming complaints that allows a “central command” to spot patterns of problems, like the ones leading to the CooperVision recall. Complaints are kept in individual files. I wondered, what if 1-800-CONTACTS were receiving counterfeit lenses from China? How would they detect this if they did not even record complaints in a fashion that is accessible outside of individual customer charts? How would patterns of complaints about their products be flagged?

I then called the consumer hotline for JNJ contact lens matters and told them my story. They opened a case file and transferred me to a nurse, Gino Likins. I asked him whether he knew of any complaints similar to mine (i.e. CLARE) and he said, “We get them every day.” Knowing that the official FDA search of their MAUDE database since 2007 only revealed 18 complaints, and those were serious adverse events leading to corneal ulceration, etc, I asked him, “Do you report these to the FDA?”. The JNJ nurse said, “No…they are not serious enough”.

Given the fact that JNJ has issued recalls in Europe for Acuvue contact lenses recently, for coating problems that cause CLARE symptoms similar to my complaints, I was flabbergasted to hear the JNJ nurse openly explain that my symptoms were not serious enough to warrant reporting to the FDA. He went on to say, “Just because do not report complaints to the FDA does not mean we do not track them. We have an internal database and monitor trends all the time.”

It was then all becoming apparent to me why the FDA had only found 18 reports since 2007 in their MAUDE database related to Acuvue lenses, and that those were cases of severe eye injury. Neither JNJ, 1-800-CONTACTS, hospitals nor doctors are required to report to the FDA anything less than a “Death, serious injury, or malfunction”. Those three qualities are defined on page 17 and 18 of this FDA regulation. However, for any “complaint”, such as mine to the JNJ contact lens call center, the manufacturer is required to track those in a database and make them available to the FDA upon manufacturing plant inspections.

Usually, it is only after an outbreak of a serious safety problem related to a medical devices and subsequent FDA plant inspections that the full data are ever analyzed. This is what happened in 2006 with the cases of blindness from contact lens infections, and more recently with the JNJ Animus insulin pumps and JNJ metal-on-metal hip implant recalls. In all of those cases, The MAUDE database proved to be woefully inadequate as a source of early detection, particularly when the manufacturer fails to pass along the reports of medical device problems.

In 2008, to address the medical device safety monitoring inadequacies of the passive reporting MAUDE database, the FDA announced the Sentinel Initiative. It was designed as a more “active” database that allows the FDA to proactively search for problems rather than rely on random incoming reports, as MAUDE does. The FDA recently convened a meeting with the Brookings Institute to provide an update on the status of Sentinel, and Harvard’s Dr. Richard Platt was a lead presenter. FDA Commissioner Hamburg also gave an update report to congress in August of 2011.

Dr. Platt explained to me that Sentinel is still in the pilot program phase called Mini-Sentinel headed up by his Harvard Pilgrim Health Care Institute. Rather than a centralized database, it taps into a network of databases controlled by healthcare provider networks that form a “distributed database”. This addresses concerns that some doctors and administrators had in releasing personal information from medical records into a unsecured centralized “Big Brother” database that might violate HIPAA and discourage participation by doctors. Unlike MAUDE, manufacturers do not provide reports of drug or device complications to Sentinel. The data are derived from patient charts at hospital, health insurance databases (Figure 1), and other academic center sources. Also differing from MAUDE, Sentinel tracks drugs, vaccines, and medical devices, not just devices.

Click image to enlarge. The flow chart of safety data in the new Sentinel pilot program

Based on the pilot Mini-Sentinel program, it does not seem any better than the current MAUDE database at detecting problems with contact lenses. The vast majority of health insurance plans do not cover optical care, and patients pay with their own cash to purchase contacts. Therefore, medical charts or insurance reports, two important sources of data for Sentinel, would not be collecting data on unsafe lenses.

I asked Dr. Platt how products sold for cash, outside of insurance plans (e.g. contact lenses, cosmetic dermatology products like Juvederm or Botox, etc.) would be monitored under Sentinel. He explained, “Mini-Sentinel is currently only able to track medical products that are covered by the participating health plans, practices, or certain registries. It hasn’t tackled the items you mention.”

Whether the Sentinel database is ever allowed to be implemented, even with the inadequacies just mentioned, is highly uncertain. It is now four years after introduction and still in the “pilot phase” as the medical device industry thwarts any reforms that increase safety surveillance.

As a healthcare analyst, I am far more cynical of the FDA and medical device industry than the typical practicing doctor, and even I was amazed at how inadequate the safety monitoring systems are for the FDA. In fact, the class action tort lawyers do more to uncover patient complaints and safety problems, after the damage is done, than the FDA does in many cases.

Doctors should add to their textbook differential diagnoses the possibilities of adulterated or counterfeit drugs and devices, as well as malfunctioning devices. “Officially approved by the FDA” is not even remotely a guarantee that a device has been tested in humans and deemed safe.

Johnson and Johnson is the largest medical device maker in the world, and has an egregious track record of violating FDA regulations and the law. The billion in fines JNJ has paid out is just a rounding error for them and the cost of doing business. Criminal charges are rarely brought against a pharmaceutical executive, although a JNJ executive, fittingly, was one of the few to be convicted and jailed. But JNJ is by no means the lone offender. Stryker, Boston Scientific, Abbott, Medtronic, CooperVision, and scores of other medical device companies have all been investigated and prosecuted by the DOJ and FDA for failing to properly report safety problems and issue recalls.

Due to obvious incentives to conceal medical device malfunctions and prevent “recalls”,  and all of the bad press that ensues, manufacturers cannot be trusted to reliably report safety trends to the FDA. Medical doctors remain as the last safety net in the medical device surveillance system, and are encouraged to report all patient complaints related to externally applied devices, such as contact lenses, as well as implantable devices. However, fears of malpractice lawsuits and paperwork hassle cause few doctors to report problems with medical devices.

This takes us full circle back to the federal agencies put in charge to protect the people against unsafe medical devices, which are the FDA taking the lead role and the Department of Justice as the muscle. But congressmen influenced by medical device lobbyists, such as the infamous and now-felon Tom DeLay, often stifle FDA safety regulations.

Senators Grassley, Blumenthal, and Kohl have recently introduced the “The Medical Device Patient Safety Act“. Based on a GAO report, the bill would “Improve post-market surveillance without stifling innovation or scrapping the current 510(k) approval system…and would help the FDA better identify when unsafe devices are on the market, and expedite the recall process once a serious problem is discovered.”

In the 2012 State of the Union speech, President Obama said, “That’s why we need smart regulations to prevent irresponsible behavior. Rules to prevent financial fraud or toxic dumping or faulty medical devices — these don’t destroy the free market. They make the free market work better.” After briefly courting the medical device industry in 2010, the Obama administration seems to be going back to emphasizing safety.

The FDA and inspecting foreign drug manufacturing

March 25, 2010 The Healthcare Channel

The latest troubles for the Genzyme Allston biologics plant resulting in an FDA decree highlight the complicated and expensive process of making biologics in The United States. Manufacturing drugs in China, India, and other locations outside the U.S. (OUS) is cheaper, and arguably less regulated by the FDA. In 2007, it was reported that many unregulated drugs from China were found in the final drug products entering the U.S.

A growing trend has been to outsource drugmaking overseas. Pfizer and AstraZeneca are just two recent examples. Roche will be shutting down the Genentech biologic plants in California and moving operations to Singapore. Most of the aspirin consumed by Americans is now made in China. The FDA Deputy Commissioner Sharfstein testified before Congress that up to 80% of the active ingredients in U.S. drugs are made OUS.

Can the FDA properly inspect OUS plants? Puerto Rican drug plants, much easier to inspect than Asia and India, have been failing inspections. The cases of deadly counterfeit heparin from China came from plants improperly inspected by the FDA.

To address this trend of drug makers outsourcing manufacturing outside of the U.S., farther away from the FDA, the agency has made some changes recently. The HCC asked the FDA about this issue. No individual official was willing to comment about this controversial issue, but a spokesperson replied after assembling answers from various FDA officials:

Q1: What has the FDA recently done to “beef up” outside-US plant inspections?

FDA spokesperson: Last year the agency conducted more foreign inspections in all program areas than at any other time in our history, and achieved an all time high in drug inspections.

In addition, the FDA is taking a systematic approach to ensuring the safety of products manufactured in the foreign arena. Despite having the largest foreign inspection program of any country, our systematic approach includes sampling products at the border, using our information technology to target products for detailed import review, working with foreign governments to promote standards and learn about the firms that are exporting to the U.S., educating industry by issuing guidance documents, and holding our domestic industry accountable for ensuring that their foreign suppliers manufacture products that meet FDA standards.

The HCC: An excerpt from Deputy Commissioner Sharfstein’s testimony further explains changes made:

“First, we are seeking better controls at the point of production, wherever that may be.

We now have permanent FDA offices in Beijing, Shanghai, and Guangzhou, China, in New Delhi and Mumbai, India, in San Jose, Costa Rica, Mexico City, Santiago, Chile, and soon, Amman, Jordan.  These offices enable us to have a regional presence around the world, a home base from which to undertake a range of important activities, including building regulatory capacity.

We now have more than 30 agreements with foreign counterparts to share inspection reports and other nonpublic information that can help us make better decisions about the safety of foreign products.  So if a shipment of contaminated drugs shows up in a port in Italy, we will hear about it swiftly and be on the lookout for products from the same shipper.

Second, we are working with industry to help them strengthen the safety of their supply chains.  In this day and age, companies should be able to effectively demonstrate that safety, quality, and compliance with international and U.S. standards are built into every component of every product and every step of the production process.

There is much more to be done.  As Secretary of Health and Human Services Kathleen Sebelius noted when she appeared before this Committee on February 4, 2010, FDA needs additional tools to move our oversight capabilities into the 21st century.  FDA needs to access regulatory information quickly, hold all parties responsible for the quality of products in the supply chain, and have reasonable and reliable options for enforcement.”

Q2: Regarding biologics, Genentech has closed the US plants and moved them outside the U.S. Is this concerning to you? How will inspection ability change?

FDA spokesperson: The physical location of manufacturing plants is a corporate business decision. It is not something in which companies involve FDA or on which FDA offers opinion. Whether a plant is in New Jersey or New Delhi is to a great degree immaterial to FDA. What is material to FDA is that, if the plant is producing product for the U.S. market, that the production is in accord with U.S. standards and that the product is one that is safe and effective. We have a long history of going wherever we need to go to help ensure that U.S. consumers can be confident in the quality of the products the agency regulates, no matter where they are produced.

Q3: Is this more inconvenient or costly for the FDA?

FDA spokesperson: Globalization is a challenge, and overseas inspections certainly may involve additional resources to handle inspections, especially in areas where the FDA may not already be staffed. Please see the recent testimony of FDA Principal Deputy Director Josh Sharfstein (primarily under “Imports”), as well as links on the FDA’s International page, which describe a number of agency initiatives to deal with worldwide manufacturing developments in the pharmaceutical field.

http://www.fda.gov/NewsEvents/Testimony/ucm203958.htm
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm185769.htm

Q4: What are the reasons given to the FDA for moving these plants?

FDA spokesperson: Companies are not required to give the FDA reasons for why they move manufacturing operations.

The Weekly Summary

January 1^st – January 9^th

In the general news, the December jobs report was mildly disappointing. In politics, New York Governor Andrew Cuomo was sworn in, promising cuts, as did most other new governors, and The White House selected new senior staff, such as Richard Daley to be the Chief of Staff. Amidst the angry tone of the country, a Congresswoman from Arizona was shot in the head, but survived. Six others were killed and approximately 20 were shot. All of this caused the House to postpone plans to vote on repeal of the ACA healthcare law.

In healthcare news, Roche plans to buy Marcadia. BSX plans to acquire Intelect Medical for its Deep Brain Stimulation portfolio.

On the data front, the Lexicon (LXRX) tablet version of its diabetes pill posted good data.

From the FDA, big news was announced first by The Healthcare Channel that Deputy Commissioner Sharfstein was stepping down, likely related to the Rep. Issa committee and the Puerto Rico drug plant debacles. Also, Adventrx (ANX) announced the agency accepted the NDA for its cancer drug Navelbine to treat NSCLC.

Pictures of the Week

More disappointing jobs numbers, but many expect hiring has already increased in January

Joshua Sharfstein, MD: The FDA Transparency Initiative

June 12, 2010

The new FDA administration is undertaking a major policy change whereby the agency will be making documents public that were previously known only to drug and device companies. Communications such as drug “Approvable” or “Complete response” letters, plant inspection letters, warning letters, etc have not been made available to the public. These documents can be useful for the public good in many ways, yet the healthcare industry would prefer that they be confidential for the most part. In addition, safety reports about medical devices and drugs have not been easily found by the public.

The FDA started in 2009 a “Transparency Initiative”, spearheaded by Deputy Commissioner Sharfstein, as part of President Obama’s “Open Government” policy. The FDA is phasing in the changes in a three-part manner. Part 2 was recently released in a summary document that listed the 21 most important recommendations taken from the Part 1 public comment period.

The HCC interviewed Dr. Sharfstein about this plan. Topics discussed include:

• How are adverse event reports on drugs and devices handled now and how could they become more transparent and easier to use?
• When the FDA uses the DOJ or courts, how often is that made public now and how will that change?
• How would plant inspection reports become more public?
• Was the release of the JNJ Puerto Rico plant 483 part of this new transparency policy?
• Will all new drug applications or withdrawals be posted?
• Will the details of why a drug was rejected be made public?

If you do not see the embedded video below, click here

Joshua Sharfstein, MD: Changes at the FDA

Principle Deputy Commissioner of the FDA, Dr. Joshua Sharfstein, discusses changes the FDA is making with the regulatory process for medical device approvals, particularly the 510K route. He also discusses stricter polices handling how healthcare companies must responds to a 483 plant inspection warning letter. Lastly, he touches upon the safety of foreign-made drugs and devices.

The Johnson and Johnson congressional hearing over Motrin/Tylenol recalls

TheHCC Tweets of the September 30^th Congressional hearing over the improper handling of the JNJ recall of Motrin and Tylenol

(First tweets at the top, last ones at the bottom)

JNJ congressional hearing: Goggins explaining why subsequent documents proved her May hearing testimony wrong

Live blog of JNJ hearing: CEO Weldon admits they did not tell FDA of stealth “recall” of Motrin whereby they paid people to buy up product

Live blog of JNJ hearing: Rep Issa accusing JNJ of being too “cozy” with the FDA as the FDA dragged its feet on Tylenol Motrin recalls

JNJ’s Weldon dodged the Rep. Issa question “Are you too cozy with the FDA?”

JNJ CEO Weldon “No sir, cost cutting (did not cause quality lapses)”

Live blog of JNJ hearing: Rep Towns wants McNeill Pres Luther to be fired too

Rep Kucinich calls JNJ CEO testimony “Coached by spin doctors” and “This is a pattern of concealment…not a “mistake”"

$JNJ hearing: Rep Kucinich does not believe that Goggins was unaware of stealth recall, “This testimony is lacking in credibility”

Recall, JNJ fired thousands of employees since 2008, then has outbreak of quality problems, hmmm, connection there?

$JNJ hearing: Rep. Towns upset with Goggins, raising voice, “You twisted my words”

$JNJ hearing: Rep. Towns “What does “soft market withdrawal mean?” CEO replied “I have no idea what that means”

$JNJ hearing: Rep. Kucinich, “Ms. Goggins…you are not telling the truth” about not knowing about stealth Motrin recall

$JNJ hearing: FDA’s Sharfstein “We plan to keep a close eye on (JNJ) until (problems resolved)” “Related criminal investigation”

$JNJ hearing: FDA’s Sharfstein said that the FDA did not know about “stealth” “phantom” recall of Motrin

FDA’s Sharfstein wants the power to recall drugs

$JNJ hearing: FDA’s Sharfstein “further changes (possible)” regarding FDA Puerto Rico Director Torres for the stalling with JNJ plant

$JNJ hearing: Rep. Chaffetz wants to talk to FDA’s Torres but DOJ not allowing bc she is witness to JNJ criminal investigation

FDA has a new head of enforcement, brought over from OIG of HHS

Rep. Issa will Chair the same committee grilling JNJ today, assuming the GOP wins in the Fall elections. He is very critical of JNJ.

Rep. Issa shows 4-inch thick book of FDA inspections of $JNJ Puerto Rico plants and asks FDA why it was not shut down

$JNJ hearing: FDA’s Sharfstein “We knew (JNJ) was re-purchasing (Motrin) product”

Rep. Issa strongly scolds FDA’s Sharfstein

$JNJ hearing: Issa now critical of FDA for still “reviewing” a June 2010 report on $JNJ

Our opinion: FDA’s Torres in Puerto Rico was indeed likely too “cozy” with JNJ. They have gagged her.

Testimonials

Don Berwick, MD, MPP

Harvard pediatrician. Former CEO of IHI. Former Director of CMS (Medicare)

“Great Job, Steve.  I saw one of the segments”

Duke Cameron, MD

Cardiac Surgeon-in-Charge, The Johns Hopkins Hospital

“I must say I am enjoying your (content) more and more.  It is provocative, insightful and direct. Can’t say I agree with your point of view every time but it is a refreshing alternative to the hyped, cloaked advertising that characterizes much of medical news in the media……especially the web.”

Joyce Greenleaf

Regional Inspector General, OIG of the HHS

(The video interview) was great to see–my whole office saw it. Thank you for the opportunity to talk about (our OIG report)

Christopher Attinger, MD

Chair, Department of Wound Healing, Georgetown University Medical Center, surgeon trained in hand, plastic, and vascular surgery at Harvard and NYU, Vietnam purple heart

“I look forward to each new story…keep up the great work!!”

Leonard Saltz, MD

Memorial Sloan-Kettering Cancer Center

“I love this stuff…I don’t always agree with you, but interesting to see what you are saying.”

William Maisel, MD

Harvard, Beth Israel Deaconess Medical Center (now at the FDA)

“I saw your recent interview with the FDA’s Dr. Sharfstein.  You are extremely professional and should consider serving in that role more often.”

Atul Gawande, MD

Surgeon at Harvard’s Dana Farber Cancer Center and Brigham and Women’s Hospital, author, presidential advisor

“Very interesting….you hit this spot on”

Harlan M Krumholz, MD

Professor, Yale School of Medicine

“Thanks – nicely done”

Bill Hawkins

CEO, Medtronic

“Thanks for helping communicate the need with your news network.”

Andy Pollock

The New York Times

“Thanks. Looks like you have some pretty interesting stuff.”

Sanjay Kaul, MD

Professor, Cedars Sinai, UCLA

“Excellent commentary! Balanced and thoughtful.”

Prosper Benhaim, MD

UCLA, Chief of Hand Surgery

“WOW. I am genuinely impressed with how far you have taken this – you have been successful where most would not have been, largely because you didn’t just imitate others but chose to “speak the truth”. Congratulations.”

Peter Bach, MD

Memorial Sloan-Kettering Cancer Center

“You did a tremendous job, and your views are very interesting and not widely understood”

Alicia Mundy

The Wall Street Journal

“Fascinating analysis you did on the drug pricing” “Your story definitely got read on the Hill… it was a terrific read and very clear. Staffers had printed out copies of it I saw in their hands. It got read a lot.”

Brian Jones

Senior VP of Operations, Fox Business Network

“Great story. Congrats!!!  On the front edge as usual”

Charles Payne

Anchor/analyst Fox News, Fox Business Network

“You have been doing great work on this BTW”

David Bahner, MD

ER physician, The Ohio State University medical Center

“I liked how you edited it and had the students scanning as I was answering.  I thought it turned out well. Thanks for the opportunity!!”

Mark Scheonebaum, MD

Johns Hopkins/Top-ranked biotech financial analyst

“Very cool idea. I love it”

Joshua Schimmer, MD MBA

Harvard/financial analyst

“Differentiated take. You do good work”

Roger Sergel

ABC News, healthcare producer

“I thought your analysis of Provenge was excellent. I had heard back from a number of experts about many of those points, but you had very specific data….I cannot stress enough that some of  your written analysis of data and the way you cover the drug industry is what has caused me to make contact with you.”

The biggest healthcare stories of 2009

December 15, 2009

The Healthcare Channel http://thehcc.tv/

2009 had some of the biggest healthcare stories in modern times. We took a stab at selecting the top stories for the year in healthcare business and policy. It was not the best of years, to say the least. Most of the stories were negative, but the biggest stories in the top five were positive. Enjoy.

#16 Head injury in American football: After years of denial, college and pro football leaders are coming to acknowledge that long-term brain injury is a significant problem for the sport. As The HCC first wrote in an Op-Ed, there are discussions of radically changing the rules of the game to prevent running backs from dipping their head, etc. Players are no longer allowed to resume playing after a concussion until their brains have properly healed which takes weeks. This places team benefit at odds with player safety. Bryant Gumbel pioneered this story on his HBO show Real Sport.

Aside, Mr. Gumbel revealed that he has lung cancer. We wish him good luck. Hopefully, the industry events mentioned below will help patients battle cancer and other disease more effectively.

#15 Spine surgery troubles: In 2009, the spine surgery industry was plagued by scandal and negative medical literature which all acted to slow growth. Medtronic’s kyphoplasty revenue shrank after key vertebroplasty papers were published in the NEJM showing that the procedure offered little benefit. The HCC interviewed the author months before the bad results impacted Medtronic.

The Walter Reed InFuse study also hurt spine and Medtronic as Dr. Kuklo reportedly falsified data for a Medtronic trial. All of this led to the dreaded attention of the Senate Finance Committee that the cardiology and psychiatry community have endured.

The HCC was the first to warn of the spine market woes back in May with the article “Big changes for ortho and spine on the way”. The third-quarter Medtronic earnings call confirmed that the negative events took a toll on revenue. Expect more negatives to the market to unfold. Stay tuned.

#14 Amgen denosumab delays: Amgen is still one of the most important companies of the biotech sector despite the changes to its core epo franchise. Much of the value of the company now depends on hope for its new potential blockbuster, denosumab, to treat osteoporosis and bone issues related to cancer. Those plans were dealt several setbacks this year when the FDA delayed approval of denosumab and required further studies for some of the indications. Prior to the delays, The HCC interviewed the two authors of the key NEJM publications this year.

#13 Genzyme’s FDA woes: 2009 was a very bad year for Genzyme as they were placed in the figurative “FDA doghouse” after multiple violations were found at the Allston plant and their Lumizyme drug application was deemed inadequate. All of this opened the door for competitors Shire and Protalix to accelerate their drugs with the FDA. The HCC interviewed former FDA biologics plant inspector John Godshalk who was appropriately pessimistic about Genzyme’s ability to quickly resolve matters.

#12 Crestor JUPITER trial: With generic statins eating into the sales of Lipitor, Crestor, etc, AstraZeneca needed the JUPITER trial to create a new reason for taking statins: to lower C-reactive protein. However, whether targeting CRP results in clinical benefit is quite uncertain, and the early stoppage of JUPITER and other flaws in design made the results quite controversial. The FDA is set to discuss whether to approve the first indication for a statin to be used in normal cholesterol levels. The HCC interviewed Dr. Guyatt about the JUPITER trial.

#11 Percutaneous heart valves: As other traditional medical device markets such as stents, ICDs and spine slow down, one of the emerging new areas of growth is structural heart disease treated by catheter intervention rather than open chest surgery. The HCC featured several stories on percutaneous heart valves and exclusive interviews with the Edwards and Medtronic program leaders.

#10 Avastin failed in the adjuvant setting: The biggest hope for expanding the market for Avastin was the C08 trial that looked at using Avastin in early stage colon cancer after surgical resection (i.e. the adjuvant setting). The study failed as The HCC predicted. With the assimilation of standalone Genentech by Roche, this topic was no longer of much concern to biotech analysts and received less attention. Aside, Roche withdrew from the pharmaceutical group PhRMA and wants to be known as a biotech company now.

#9 Effient (prasugrel) FDA scandals and the poor launch: Starting as an HCC exclusive in February, “FDA Director of New Drugs speaks with The HCC about the prasugrel panel”, the prasugrel advisory committee became a major scandal after it was revealed that Dr. Kaul was disinvited from the roster when Eli Lilly requested he be removed. The PDUFA date was missed twice, as The HCC warned viewers, and the final approval came with onerous black box warnings on bleeding risk and a limited patient population.

#8 FDA overhaul: A new crew took over the FDA when Dr. Hamburg and Dr. Sharfstein were appointed by the incoming Obama administration. Addressing many of the controversies of the Bush FDA, the new sheriff in town began to clamp down on industry biases within the agency that led to some dubious drug and device approvals. The plant inspection process requires faster replies from industry, and the promise to make the FDA more transparent was kept (e.g. publication of the Genzyme warning letter). The HCC interviewed Dr. Sharfstein on these matters.

#7 Senator Grassley and Finance Committee Oversight: For the second year, Senator Grassley’s oversight efforts have made a big impact on the way certain specialties practice. Spine surgery was the newest target this year. Interventional cardiology and psychiatry were victims in 2008. The transparency into industry funding of these groups has translated into major changes in medical meetings and trade shows like the TCT, weakened pricing power for the ortho and spine companies, and has altered the way medical journals operate. The Physician Sunshine Payment Act will be enacted if the Senate healthcare reform bill becomes law. The HCC has been the best source for exclusive stories on these oversight matters.

#6 Cancer risk from medical imaging radiation: In 2009, several respected journal publications hammered home the concept that CT scans and other medical imaging cause thousands of cancers each year. To make the story more horrific, doctors at Cedars Sinai were found to have manually overridden systems to deliver ten-times the safe dose to hundreds of patients. Other medical centers likely made the same mistakes. The HCC was the first to report on this safety concern in 2007, and more recently in an interview with one of the journal authors.

#5 Mammography screening controversy and comparative effectiveness: The AHRQ, a relatively obscure division of The HHS, and its subdivision, the Preventive Services Task Force, made one of the biggest bureaucratic bungles in the history of The HHS by releasing controversial new guidelines to cut back on the number of routine mammography screenings. As mentioned in an Op-Ed Who are bureaucrats behind the mammogram gaffe?, the timing could not have been worse coming during the Senate healthcare reform debate and giving fuel to critics who say that rationing of healthcare will occur if the government takes over. This is all part of a bigger movement to compare the effectiveness of treatments and make resource allocation decisions based on head-to-head comparisons of therapies.

Comparative Effectiveness (CE) was funded in a small way as part of the job stimulus package in 2009. CE poses a threat to the current paradigm of marketing drugs and devices. This will be one of the bigger stories to follow in 2010. The HCC interviewed Sir Michael Rawlins, Chairman of the UK’s CE organization called NICE, and others, during the healthcare reform summit in May. This is still worth watching if you missed it.

#4 Recovery of the stock markets: The dramatic recovery of the stock markets has allowed for the stabilization of the capital markets. Small-cap healthcare companies are no longer liquidating. However, the IPO market is still not quite open for business. Healthcare investment funds are recovering and digging out of the holes from 2008. 2010 might be a fresh start as trillions in cash on the sidelines needs investment vehicles.

#3 Mergers and Acquisitions: 2009 was the biggest year ever for healthcare M&A. Pfizer bought Wyeth. Merck bought Schering Plough. Roche bought Genentech, and the list goes on. The consolidation resulted in massive job cuts and the Wall Street analysts have fewer names to cover. That is about all that was accomplished. Few of the mergers resulted in companies with better growth or better competency at creating drugs in-house.

#2 Swine flu and botched vaccines: Swine flu dominated the news in 2009. The disease turned out to be fairly benign in most people as it became widespread. The latest CDC estimates are that 50 Million people have contracted the disease in the US killing 10,000. The HHS mishandled production of the H1N1 vaccine and supplies were a fraction of what the CDC estimated. The HCC was the first on national TV in April to discuss the important trends to follow (i.e. death rates were more important than geographic spread, etc).

#1 Healthcare reform: The highly dynamic process of passing healthcare reform in the House and the ongoing debate in the Senate have been the biggest stories of the year by far and promise to carry over into 2010. At the time of this publication, the Senate bill has stalled once again.

If a bill passes, the impact to industry should be less severe than expected. Any form of a “public option” seems untenable to key Senators. Also, the drug industry has successfully dodged the feared provision that would have allowed Medicare to negotiate for drug prices.

Those were the big events of 2009. 2010 should be a better year as the cloud of healthcare reform uncertainty lifts and the economy improves. Have a happy new year.