Search: Sharfstein

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 Weekly Summary

January 1st – January 9th

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

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.

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 Johnson and Johnson congressional hearing over Motrin/Tylenol recalls

TheHCC Tweets of the September 30th 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.


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

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.