Latest Drugwonks' Blog

Making Drug Manufacturing Great Again

  • 04.21.2017
  • Peter Pitts
From the pages of Investor’s Business Daily

Making Drug Manufacturing Great Again

President Trump wants to lower drug prices and reinvigorate domestic pharmaceutical manufacturing.  Bravo. But standing in the way is the inside-the-Beltway gospel that preaches that regulators love ambiguity.

As a former FDA associate commissioner, I can affirm that's true. Vagueness gives the agency almost unlimited authority to do whatever it wants.
But, when it comes to the FDA, it's predictability in pursuit of the public health that's important. And nowhere is this truer or more timely than when it comes to the oversight of drug manufacturing.

Drug manufacturing isn't sexy to the general public and rarely makes headlines — unless something goes wrong. Recalls make headlines. Adherence to current good manufacturing practices (GMPs) do not.

A few years ago I had the chance to visit Pfizer's Kalamazoo production facility. What impressed me more than the gee-whiz production aspects of the facility (of which there were plenty) was the dedication of the people who work there — top to bottom.

It actually reminded me a lot of the FDA. Long-term employees dedicated to serving the public health through dedication to quality. And they all took it very personally. Just like at the FDA, the Pfizer folks were on personal missions of quality. There was a lot of pride on display.

Mr. President — there hasn't been an exodus of pharma manufacturing to foreign shores. In fact, when I visited the Kalamazoo facility they were exporting (among other things) the active pharmaceutical ingredient (or API, the actual drug substance) for methyl prednisolone (a corticosteroid long off patent) to both China and India.

A U.S. manufacturing facility of an innovative biopharmaceutical company that exports drugs to China and India for profit?  What's wrong with this picture? Well, as it turns out, it's what's right — innovation through manufacturing prowess, organic chemistry smarts and green technology. Better. Faster. Cheaper.

Pharma's always bragging about its ever-growing investment in R&D. But when was the last time you heard about investments in domestic manufacturing? Probably never.

And when was the last time you read about enhanced drug safety through good manufacturing processes and cooperation between industry and the FDA? Not recently. That's a shame because they're both important stories.

The president's nomination of Dr. Scott Gottlieb to be the next FDA commissioner likely portends a more holistic view of drug regulation. I served with Scott for two years at the agency. Not only is he a voice for greater regulatory predictability, he's also a silo-buster.

Having previously served as deputy commissioner, he understands the need for greater interdepartmental cooperation. In other words, it's not just about better utilization of expedited review pathways or better use of real-world data, or enhanced post-market surveillance, or more robust off-label communications. It's about making the process work for patients.

But manufacturing is all about process. Modernized pharmaceutical manufacturing isn't only about ensuring and enhancing quality for finished medicines, it's also about making America's pharmaceutical factories globally competitive players in the production of API (like Pfizer's plant in Kalamazoo) and excipients (the ingredients other than the API that are included in the manufacturing process or are contained in a finished pharmaceutical product.)

And the more complicated the drug, the more complicated the active pharmaceuticals and other ingredients. American know-how and dedication to GMPs present a wonderful opportunity for our domestic facilities to thrive. Quality manufacturing is our unique proposition vis-a-vis less expensive operations overseas.

FDA regulation of medicine manufacturing is also a crucial piece of the solution to preventing future drug shortages. According to a 2012 report from the House Committee on Oversight and Government Reform, by hastily ramping up manufacturing enforcement actions, the FDA "effectively shut down 30% of the total manufacturing capacity at four of the country's largest producers of generic injectable medications."

Resolving this problem will require the FDA to work with manufacturers to find practical, science-based solutions to quality-control issues that neither compromise safety nor slow down production. Regulatory discretion is often the better part of valor.

Enforcement of savvy manufacturing quality control is crucial, but an equally important (and often ignored) aspect of the FDA's mission is to advance America's pharmaceutical production acumen by being both regulator of and partner with industry.

That's a winning combination: the best and the brightest from industry and government together with the best production capabilities in the world. The keys to the kingdom are on the table.

Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest.

DTC Fair Balance ... for Lawyers!

  • 04.17.2017
  • Peter Pitts
House Judiciary Committee Chairman, Rep. Bob Goodlatte (R/VA.) wants drug side-effect ads that are run by lawyers to include a warning that patients should talk with their doctors before adjusting medication, the Wall Street Journal reports. Along with the American Medical Association and some drug companies, he contends the ads are to blame for patients suffering harm or even dying after dropping treatment.

PDUFA Reauthorization. Discuss.

  • 04.14.2017
  • Peter Pitts
House, Senate Health Committee Leaders Release Discussion Draft of FDA User Fees Reauthorization

WASHINGTON, DC – The leaders of the Senate and House health committees today released a discussion draft of bipartisan legislation reauthorizing the Food and Drug Administration user fee agreements.

The Food and Drug Administration (FDA) Reauthorization Act of 2017 renews FDA's authority to collect user fees from the makers of prescription brand drugs, medical devices, generic drugs and biosimilars, and several vital programs at the FDA. The 2012 prescription drug user fee amendments (PDUFA), medical device user fee amendments (MDUFA), generic drug user fee amendments (GDUFA), and biosimilar user fee amendments (BsUFA) all must be updated and reauthorized by Congress before the current user fee agreements expire on September 30.

If the agreements are not reauthorized before the August work period, the agency will be forced to send layoff notices to more than 5,000 FDA employees. A delay in reauthorizing these agreements would delay the reviews of critical drugs and devices.

“We are fully committed to a timely reauthorization of the agreements and are well on our way,” said Energy and Commerce Committee Chairman Greg Walden (R-OR). “This represents another opportunity to help expedite the review and approval of new cures and treatments for patients, and we must prioritize it. As this process proceeds, I look forward to continued discussions with my colleagues in the House on other member priorities that could strengthen this important legislation.”

"The swift reauthorization of these user fee agreements is critical to making sure FDA has the resources and personnel it needs to ensure timely review and approval of safe and effective medical treatments,” said Energy and Commerce Committee Ranking Member Frank Pallone, Jr. (D-NJ). “These carefully negotiated agreements encourage innovation, improve our regulatory review process, and provide certainty to both patients and industry. I look forward to working with my colleagues to move this legislation through Congress and to the President's desk.”

“If we do not move quickly to reauthorize these agreements, in late July, the FDA will be forced to begin sending layoff notices to more than 5,000 employees to notify them that they may lose their job in 60 days,” said Senate Health, Education, Labor and Pensions Committee Chairman Lamar Alexander (R-TN). “The sooner we reauthorize the agreements, the better – to give patients, reviewers, and companies certainty. In addition to harming patients and families that rely on medical innovation, a delay in reauthorizing the user fees would threaten biomedical industry jobs and America’s global leadership in biomedical innovation.”

“I’m encouraged by our bipartisan work to reauthorize these agreements to advance safe, effective, and innovative medical products,” said Senate Health, Education, Labor and Pensions Committee Ranking Member Patty Murray (D-WA). “Patients and families nationwide are relying on us to ensure FDA can continue its vital work without interruption. I hope that we can continue to put partisanship aside and advance this important legislation.”

The FDA Reauthorization Act of 2017:

Updates and reauthorizes the user fee programs, which, in Fiscal Year 2016, accounted for 70 percent of the brand drug review budget, 36 percent of the medical device review budget, 75 percent of the generic drug review budget, and 29 percent of the biosimilar review budget.

Reflects the recommendations sent by FDA to Congress in January, which were based on over a year of negotiations and discussions with industry, Congress, patients, and other stakeholders.

Implements the four user fee agreements authorized by FDARA, which support the goals of the 21st Century Cures act and advance key bipartisan priorities:

Prescription Drug User Fee Amendments (PDUFA VI): Enhances patient-focused drug development, supports biomarker development and qualification, dedicates staff to assist in the development and review of rare disease drugs, sets clear timelines and improves guidance for drug and device combination products, and evaluates ways to modernize the clinical trial process.

Medical Device User Fee Amendments (MDUFA IV): Enhances the patient voice in the device development process, supports the collection of real world evidence on the safety and effectiveness of devices, and improves the review process for  “de novo” devices—low- to moderate-risk devices that are the first of their kind.

Generic Drug User Fee Amendments (GDUFA II): Improves the fee structure to support small businesses, provides goal dates for all outstanding generic applications, and establishes priority review timelines.

Biosimilar User Fee Amendments (BsUFA II): Continues to build the biosimilars program, and supports guidance for product developers.

CLICK HERE for the text of the discussion draft, HERE for a section-by-section summary of the discussion draft, and HERE for a one-pager. Health committee leaders ask that stakeholders who wish to comment on the contents of this draft please submit to by April 28th.


  • 04.12.2017
  • Peter Pitts
It's time to go beyond FDAMA 114.

Representative Brett Guthrie (R/KY) introduced the Pharmaceutical Information Exchange (PIE) Act of 2017 (H.R.2026). The bill incorporates the multi-stakeholder consensus recommendations developed during a forum sponsored by the Academy of Managed Care Pharmacy. The legislation would allow biopharmaceutical manufacturers to proactively share clinical and economic information with population health decision makers on emerging therapies in advance of Food and Drug Administration (FDA) approval, an area that is significantly restricted by current federal laws and FDA regulations.

Expediting Complex Geneics

  • 04.06.2017
  • Peter Pitts
It's not about speed, it's about predictability.

The way to expedite complex generics is by making the process predictable. Predictability = more development programs = competition = lower prices.
European, national, and regional authorities should invest in awareness-raising campaigns to increase public knowledge about medicinal safety and adverse drug reaction (ADR) reporting.
This is one of the main findings of the study “Pharmacovigilance in the European Union: Practical implementation across Member States” from the University of Duisburg-Essen which assesses the functioning of EU pharmacovigilance legislation.
The report focuses on adverse drug reaction (ADR) reporting of biologicals in six EU Member States - the UK, Finland, France, Poland, Portugal, and Germany. Since the 1990s, legislation at the EU level has strengthened medicinal safety in general, and particularly the reporting of ADRs. However, transposition problems remain in some EU Member States when it comes to medicinal safety.
ADRs account for 5% of all hospital admissions, cause around 200,000 deaths per year in the EU, and cost roughly €80 billion.
Almost 85% of EU rules are not transposed on time, and occasionally come with a delay of more than two years. Although patients are given a strong role within the new EU pharmacovigilance legislation, they lack awareness, and this leads to ADRs going unreported.
The report argues that ADR reporting should be viewed as a key responsibility for healthcare professionals and not as a failure or lead to reputational damage. They should also be properly trained and targeted by awareness-raising campaigns to ensure they are aware of the importance of medicinal safety to public health and feel comfortable in reporting ADRs without fear of liability and/or failure.
Patients also have a critical role to play, and Member States should enable patients to report ADRs online, and connectivity of IT systems between general practitioners, hospitals, pharmacies, and the national competent authority should be improved.
A key solution identified by the report is to put in place awareness raising programmes aimed at both patients and healthcare professionals to increase knowledge about medicinal safety and highlight the role it can play to ensure public health.
The report will be shared with EU Member States, the EU Institutions, and key stakeholders, with the aim of ensuring the recommendations are taken up by governments, and that the EU legislation can be properly implemented across Europe.

Scott STAT!

  • 04.05.2017
  • Peter Pitts
“I think Scott is very much for good regulation, and very much against bad regulation,” Pitts said. “Importantly, he recognizes where FDA core mission stops, and where mission creep begins — and that’s an important finesse he’d bring to the commissioner’s chair.”
Via STAT News:
 Gottlieb’s pledge to uphold ‘gold standard’ raises red flags
When Dr. Scott Gottlieb pledged at his confirmation hearing to uphold a “gold standard of safety and efficacy” at the Food and Drug Administration, he raised an important question:

What exactly does he mean by that?
Traditionally, “gold standard” refers to robust, randomized controlled clinical trials. But there’s enormous pressure on the FDA — from pharma companies and Congress, for starters — to accept other kinds of evidence, perhaps even patient anecdotes, to determine whether experimental drugs work. And President Trump is promising to speed drug approvals.
So when Gottlieb said: “I think there are ways to modernize clinical studies without sacrificing the gold standard,” he raised red flags.
“I don’t think he was using the phase ‘gold standard’ in the way that most of us who think about the agency for a living understand it,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis.
“I think he views adaptive clinical trial design as in keeping with that gold standard,” Sachs said.
And that’s the rub, because modifying clinical trial standards has many people concerned. Reshma Ramachandran, co-chair of the National Physicians Alliance’s FDA task force, says she, too, doesn’t know what Gottlieb meant by “gold standard” — but isn’t optimistic about his interpretation.
She pointed out that Gottlieb has criticized the use of adequate and well-controlled Phase 3 trials in the past, saying they’ve needlessly delayed access to important drugs.
“That seems to indicate that his idea of ‘gold standard’ means sacrificing safety and efficacy you’d expect from FDA in favor of expediting an approval pathway,” Ramachandran said.

Joshua Wallach, a research fellow at Yale’s Collaboration for Research Integrity and Transparency, had similar worries.

“I’m concerned: I don’t want a complete erosion of the quality of clinical trial evidence that’s required from industry,” Wallach said. “There’s definitely a movement still toward deregulation — and lowering of evidentiary standards.”
Wallach is afraid, in particular, of changes to clinical trial endpoints. Modernizing the clinical trial process might force trials to lean on surrogate endpoints. That could mean assessing an experimental drug based on whether it has some interim effect (like improving a dementia patient’s performance on a memory test) rather than whether it meets more significant long-term goals (like prolonging that patient’s ability to complete daily tasks). It could also open the door to pharma companies scouring their clinical trial data to find metrics that look good — and presenting those to the FDA, even if the trial was originally designed to answer an entirely different question.
“I’m worried about seeing more small, crappy trials that don’t actually tell you anything about efficacy and safety — which are extremely important before drugs can be approved or marketed,” Wallach said.
Part of upholding the FDA’s gold standard could involve respecting and keeping on career staff, Sachs said. And for that, she gives Gottlieb high marks.
“I think he understands the importance of a strong, well-resourced FDA,” Sachs said. “I don’t think he will burn it all down. I don’t think he’s inclined to destroy the agency from within.”
Peter Pitts, president of the nonprofit Center for Medicine in the Public Interest, saw another glimmer of good news in the confirmation hearing: He said he thinks Gottlieb’s definition of “gold standard” includes keeping FDA funding strong.
“The president and his team understand that you can’t get more for less — and that’s especially true on staffing,” said Pitts, who was a former associate commissioner of FDA and worked with Gottlieb at the agency for two years. “And Scott came pretty close to saying he was against a reduction of budget.”
Pitts added that he was impressed by Gottlieb’s performance at the hearing.
“I think Scott is very much for good regulation, and very much against bad regulation,” Pitts said. “Importantly, he recognizes where FDA core mission stops, and where mission creep begins — and that’s an important finesse he’d bring to the commissioner’s chair.”
Arizona is first state to pass a law allowing drug makers to promote off-label uses

Ed Silverman @Pharmalot

In what some observers are calling a misguided effort, Arizona has become the first state in the nation to pass a law allowing drug makers to promote their medicines for so-called off-label uses — so long as the information given doctors is truthful.

Interestingly, the law was hatched by the Goldwater Institute, the same think tank that spearheaded the controversial Right to Try laws designed to give patients early access to experimental medicines. And the think tank is vowing to duplicate that campaign by introducing off-label bills around the country.

This move comes amid rising pressure on the Food and Drug Administration to loosen regulations for off-label promotions, which is one of the most contentious issues to roil both the agency and the pharmaceutical industry. At issue is a fierce debate over patient safety and free speech.

Doctors can prescribe a medicine for an off-label — or unapproved — use, but drug makers have battled restrictions on their ability to distribute such information, such as reprints of medical studies. The companies believe free speech is being curtailed and have lobbied Congress and the FDA to loosen regulations. For its part, the FDA worries public health can be jeopardized by promotions that go too far.

Significantly, drug makers were emboldened by a pair of court rulings in recent years that determined companies can disseminate off-label information, so long as it is truthful and not misleading. However, one of those decisions, which was issued by a federal appeals court, only extends to Connecticut, New York, and Vermont, creating uncertainty about whether the issue would be tested elsewhere.

The FDA, meanwhile, has not yet taken any action.

In fact, the agency held a two-day, public meeting last November. But two months ago, the FDA issued a memo that, instead of suggesting possible solutions, simply summarized key points framing the long-running debate and carefully rebuffed many of the suggestions made by drug makers and others that support expanding pharmaceutical marketing.

And so the Goldwater Institute is trying to force the issue with the Free Speech in Medicine Act.

“Curbing the exchange of information about off-label treatments by those with the most knowledge about the drug’s uses, risks, and side effects not only prevents patients from receiving the best possible care; it violates the constitutional right to free speech,” said Christina Sandefur, the executive vice president of the Goldwater Institute, in a statement.

While the Goldwater Institute plans to take its “model law” to other state legislatures, so far, similar bills have not yet been introduced elsewhere, according to Richard Cauchi, health program director at the National Conference of State Legislatures.

Meanwhile, though, one former FDA official, who has publicly urged the FDA to loosen its regulations, believes such state laws would be useless, because they would be preempted by federal law that allows the FDA to issue guidance documents and rules about various activities and requirements.

“It’s nice that the Arizona legislature thinks disseminating off-label information is a good thing, but it’s not their jurisdiction to say so,” said Peter Pitts, a former FDA associate commissioner who heads the Center for Medicine in the Public Interest, a think tank that is funded, in part, by the pharmaceutical industry. “I don’t think a challenge in court would last more than five minutes.”

Nonetheless, one consumer advocate, who opposes widening the ability of drug makers to promote off-label uses, fully expects the Goldwater Institute to persist.

“I don’t think the law will change the landscape, but they’re seeking to gin up public attention and become a stepping-stone to try to get Congress to pass laws that would accomplish the same thing on a national level,” said Michael Carome, who heads Public Citizen.  “I suspect that’s the ultimate goal.”

As for the Right to Try campaign, 33 states have so far passed such laws and, recently, bills were introduced in the US House and the Senate. Critics say these bills are wrongheaded for trying to cut the FDA out of the process, since regulatory oversight would be removed and drug makers are actually the ultimate gatekeepers for deciding access to their drugs.
STAT News is one of my favorite sites for medical and health news.   The reporting is great and the journalists are open, thoughtful and smart.   

Every once in a while there will be clunker like the following article about Scott Gottlieb:

Trump’s FDA nominee pledges to untangle his ties to 25 biopharma companies

"President Trump’s pick to lead the Food and Drug Administration has promised to recuse himself from agency decisions on more than 25 companies to which he has ties.

Dr. Scott Gottlieb, who is deeply entrenched in the industry he may soon regulate, plans to resign from his roles in investment banking, venture capital, and as a consultant to drug companies within 90 days of his Senate confirmation. At the same time, he’ll sell off his shares in a host of biotech companies.

And for one year after those resignations, Gottlieb will stay out of any FDA deliberations related to those companies, which include GlaxoSmithKline, Bristol-Myers Squibb, and Vertex Pharmaceuticals."

Deeply entrenched?  Untangling of ties?  From 25 -- count em, 25 -- companies? Sounds suspicious.  Should we ask Carrie Matheson to get to the bottom of Gottlieb's consulting activities?  

A less breathless and narrative driven article could have noted that Scott's recusals and divesting of industry related investments and associations are no different than what any other nominee for FDA commissioner has done, including Rob Califf and Peggy Hamburg.   And no one was keeping score of how many companies they consulted for or held stock in.  Or that Gottlieb has made increasing the number of generic drugs that compete against medicines made by companies he advised a top priority? 

To be fair,  when I wrote to STAT News editor Rebecca Robbins raising my belief that the article was more narrative than reporting she responded that the intent was not to reinforce a narrative peddled those who regard Dr. Gottlieb as a pharma pawn.  

But there is this as well: "The 44-year-old physician has traced an unusual career path, pivoting from Wall Street to a role at the FDA and then embarking on a lucrative career as an investor and adviser." 

Who else thinks that this article will spur more attacks and spawn similar pieces from other news outlets that will include quotes from anti-industry critics such as Public Citizen who have already smeared Scott?


ICER recently had a meeting to discuss its latest study: "Targeted Immune Modulators for Rheumatoid Arthritis: Effectiveness & Value." It is no different than any other ICER report:  It concludes no medicine is cost effective and it uses methodology that no economist can replicate.   ICER reports are the cold fusion experiments of health care economics. 

I have released a report discussing the impact of ICERs approach on patients.  It concludes that applying ICER's cost-effectiveness standard to all biologics developed for RA since 2000 (none are cost-effective according to ICER) would have harmed a lot of people with RA.

Between 1999 and 2014 there would have been 46689 more deaths under an ICER regime.   Additionally, research suggests that since 1999 the life expectancy of people with RA who used new medicines could expect to live 10 years longer than those not treated.   Hence under an ICER regime people with RA would have 466894 fewer life years (46689 x 10).  

Going forward, ICER claims new RA drugs are not cost effective either.  

ICER estimates that only 97000 people year for five years (486000) with RA would get two new drugs it reviewed: baricitinib and sarilumab.  Both medicines were tested in people with RA whose disease didn’t respond to any other treatments or couldn’t tolerate any other medicines.  

ICER fails to disclose how they arrived at the estimate that 97000 people a year would use new drugs. Further, it assumes – without any support – that 70% of new users on baricitinib would come from patients using sarilumab and 30% would come from another biologic -- adalimumab--that it claims isn't cost effective either. 

In doing so, ICER assumed that 50% of these patients were moderate-to-severe cases, and 50% of this subset had failed initial treatment with non-biologic RA drugs such as methotrexate.  ICER states: "Applying these proportions to the projected 2016 US population resulted in an estimate of approximately 486,000 patients in the US over a five-year period.”

But this assumption is flawed. A recent study found that 50 percent of all RA patients failed to respond to their second-line biologics. Further, many other patients will stop responding to any therapy.   Finally, ICER did not consider that many people with RA do not benefit from any other medicines.  So, there is little basis to assume that two new medicines would not be used more widely as well as claim that one would replace the other.  

If the 97000 limit is applied, 398000 people with RA a year would be denied medicines that improve their condition and could likely increase their life expectancy. ICER limits would cost RA patients up to 250900 life years over that time. 

You can access the entire study here

Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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