Taking a Peek at Transparency – An FDA Pilot Program

Yesterday, Commissioner Scott Gottlieb announced a new effort on the part of the agency aimed at increasing transparency around clinical trials, a goal long sought by many patient advocates, particularly outside the U.S. 

Specifically, FDA is introducing a pilot program that will publish “clinical study reports” – reports prepared by drug sponsors that provide “bottom line information” on both the methods and results of clinical trials. The announcement acknowledges that while currently summaries written by FDA’s medical reviewers are released by FDA when a drug is approved, the format might challenge stakeholders who are looking for information. 

The pilot program, to begin this month, will involve the posting of portions of clinical trail summaries from the pivotal trials that were submitted by FDA from drug sponsors and will involve the summaries of 9 companies who volunteer the use of their new drug applications and that participation will include a range of therapeutic categories. 

One thing not mentioned in the announcement was the issue of complete response letters (CRLs).  For a long time now, many stakeholders have advocated that CRLs, now considered proprietary, be made public in the interests of greater transparency.

Other questions with respect to the program that were not addressed in the announcement were its anticipated length – how long the program will take to have 9 volunteers, and any outline as to how the success of the program will be evaluated and what steps, if successful, will be taken to make the program permanent.  Finally, if made permanent, would participation continue to be on a volunteer basis?

For many stakeholders, as seen in some of the response on Twitter, this initiative is not going far enough and there are critics who feel it needs to be a broader effort, especially with respect to the CRL issue. One thing, however, that is clear (pun intended) when it comes to transparency is that when you open the door a little, it is pretty hard to close it again. With the advent of the pilot program, it would seem difficult for FDA to go back unless the evaluation of this pilot is absolutely dismal. The arc of progress is with greater transparency. 

If interested, there was also a panel discussion held yesterday morning by the Johns Hopkins Bloomberg School of Public Health – A Forum on Transparency at the U.S. FDA that included two panels and a keynote from Commissioner Gottlieb. 

Photo by Samuel Zeller on Unsplash

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Weekly Roundup 1.12.18

As we ease into the new year cycle, 2018 is still waking up. Many of FDA’s web pages are not yet updated to reflect that the new year even exists. The weather is erratic, with low low temperatures one day and rather high a few days later. The flu season is flourishing. Comfort food is a good idea. But if you are not cold and not hot and not sick, here are a few of the things that were of interest this week. 

  • FDA Takes Action on Cough and Cold Meds with Opioids – In another in a growing list of actions taken by FDA to address some aspect of the opioid epidemic, the agency announced this week that it was moving to require safety label changes to prescription cough and cold opioid medicines containing codiene or hydrocodone so that (1) they be labeled only for use in adults aged 18 years and older and (2) have additional safety information for adult use, including an expanded Boxed Warning. For the under-18 population, the agency stated that the risks no longer outweigh the potential benefits. 
  • AdComm Votes on Testosterone Replacement Therapies – The Bone, Reproductive and Urologic Drugs Advisory Committee met for two days this week to consider NDAs for two testosterone replacement therapies.  On January 9 and 10, the committee met to consider two separate applications for oral testosterone undecanoate capsules – for the proposed indication of testosterone replacement in males for conditions associated with a deficiency or absense of endogenous testosterone: Primary hypogonadism, congenital or acquired, and hypogonadotropic hypogonadism, congenital or acquired. Neither got an approval recommendation from the committee with the first drug Jatenzo getting a nearly split 9 Yes/10 No vote and the following day Tlando seeing a 6 Yes/3 NO vote against approval.  
  • AdComm Votes for NCFB Treatment – In a separate meeting of the Antimicrobial Drugs Advisory Committee there was evaluation of another compound, this one to treat Non-Cystic Fibrosis Bronchiectasis. The vote was 12 No/3 Yes/1 abstain in response to the ultimate question of the demonstration of safety and efficacy. The company said in its release that the action date would be January 26.  As with all advisory committee outcomes, FDA is not obliged to follow the recommendation of its committees.  This makes an AdComm track record for 2018 at 0/3. 

That’s it for me this week folks. Have a good, long weekend. 

Upcoming Events to Keep an Eye on This Week

Regulatory Developments in Pharma/Biotech/Devices

Photograph Courtesy of Lynne Bertram



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Advisory Committee Activity for 2017

Having worked with a lot of companies to prepare for an FDA Advisory Committee (AdComm) , I track the activities of the committees in a database marking outcomes, votes and other characteristics. As part of a look-back series as we begin the new year, it seemed like a good area to provide an assessment – the profile of advisory committees for the past year and how it compares to the year before.

And in fact, looking back over 2017, AdComms did take on a slightly different complexion from the previous year.

  • Total Meetings – In 2016 there were 22 meetings by committees that involved votes to consider new drug applications. By contrast in 2017, there was only one more meeting – a total of 23 scheduled where new products were being considered. However, one of those meetings ended up being withdrawn by the company and one of them was withdrawn by FDA (the agency thereafter approved the product without the meeting being held), meaning that there were 21 actual votes for the year.
  • Which Committees Met With What Frequency – A total of 12 of the 18 human drug advisory committees met during 2016, with the most frequent being among the Psychopharmacologic, the Arthritis, the Endocrinological and the Anesthetic Committees at 3 meetings each. However, in 2017 there were only 8 committees meeting and there was far less of a spread. The lion’s share – 9 meetings – were by Oncologic Drugs Advisory Committee, followed by the Arthritis and Psychopharmacologic Committees at 3 each. In 2016 there were 4 joint meetings of committees and in 2017 there were 5 – in all circumstances these were joint meetings with the Drug Safety and Risk Management Advisory Committee (the other common joint meeting is between the Nonprescription Drugs Advisory Committee with a second committee that may have subject matter focus over the RX version of the drug).
  • Votes Up and Down – Of the 2016 meetings, 19 (86 percent) had votes that recommended approval and just 3 had votes that did not. That positive vote percentage slipped a bit in 2017.  Of the 21 meetings where votes were taken to recommend approval or not, the committees voted in favor of an approval recommendation 15 times (72 percent) and voted against a recommendation of approval 6 times. 
  • Disagreements between AdComms and FDA –  Frequently people have a question as to how often there is discordance between the recommendation of an AdComm and the FDA. Looking back through all AdComms from 2012, discord has happened on average about 10-11 percent of the time.  However, both 2016 and 2017 were slightly out of the norm. In 2016 there were 3 instances where the panels recommended approval, but FDA did not approve the products – at least immediately, and there was 1 situation where the panel did not recommend approval, but FDA went ahead and approved the product anyway, a rate that was above the norm.  In 2017, there was only a single example of a committee recommending approval where FDA did not approve (due to a plant inspection issue). There was also only 1 example where an AdComm did not recommend (actually an evenly split vote) approval, but FDA did approve, a rate that was below the norm. 

So what do these differences mean?  Are there trends to discern?  Does the fact that FDA and the AdComms had fewer disagreements between them signify a new trend? Probably not. Are there other trends to pay attention to?  Certainly the large number of meetings of the Oncologic Drugs Advisory Committee is important. But the bottom line is that the premium put on action by FDA this year is to manage the regulatory process in a way that facilitates quick consideration. Each committee meeting is like a snowflake – they are pretty unique – and depend on a variety of circumstances, most importantly the data and the presentation of it. This past year marked a banner year for approvals. As FDA shifts gears with the advent of 21st Century implementation and a new commissioner, the track record for 2018 in terms of both AdComms and approvals will be very telling.  But that will have to wait for January 2019.  


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Weekly Roundup 1.5.18

Welcome to the first Weekly Roundup of the year! The fact that it was a short week and one in which the East Coast and a good deal of the South were experiencing a weather challenge means that there was not as much action as might otherwise be happening. But I am taking advantage of the rather slow week to make a few observations as we make the transition from the sleepy holiday time to our regular course of business as well as providing the latest out of FDA.

  • Commissioner Announces New Steps to Speed Generics – In what has been a regular event now, Commissioner Gottlieb issued a media statement outlining new steps to enhance review of generic drugs that are part of the Drug Competition Action Plan announced in June, 2017. The new steps being announced are in relation to one of the three goals of that plan – to improve the efficiency and predictability of the review process in order to reduce the time of the review and lessen the number of review cycles that the company must go through in applying. To that end, the agency issued a draft guidance entitled “Good ANDA Submission Practices” to review common deficiencies in applications for prospective applicants. In addition, the agency issued a companion piece for staff in the Manual of Policies and Procedures (MAPP) that was intended to formalize a more streamlined process from the staff side. During confirmation hearings one area of concern voiced by several policymakers was the cost of pharmaceuticals. While FDA is limited in what it can do on pricing, the swift approval of generics is one means to bring down costs and Commissioner Gottlieb noted that FDA took action on more applications in the last six months of 2017 than in any other 6-month period in the agency’s history. 
  • OPDP Issues Warning Letter – With the close of 2018, enforcement by OPDP as expressed by the issuance of Warning or Untitled letters hit an all time low after trending lower the past few years. While it is still possible for a 2017 letter to be posted, in mid-December FDA issued its fourth letter of the year. The letter was a Warning Letter and the subject was an Exhibit panel used to convey information about a weight loss treatment in medical meetings where risk information was not included despite several risks and restrictions in the label of the product. It is the second letter of the year addressing an Exhibit Panel and the second letter of the year for a weight loss treatment. The letter can be found here. Also consistent with an on-going trend, all four of the letters were addressed to companies not in the top 50 list of pharmas. 
  • AdComm Schedules – The new year begins with four advisory meetings currently scheduled beginning as soon as next week (see below for the most immediate). The FDA added the new 2018 Advisory Committee Tentative Meetings Page on the agency website, but did not list any potential dates for meetings. In years gone by, FDA would post the entire calendar year’s worth of tentative dates so that one could see where each committee was planning – at least tentatively – to have a meeting and thereby giving the panel members, and us, the ability to plan. It appears now, however, that the future dates are not being carved out. In fact, even though there are some committees already slated to meet, for CDER this page is now failing to mention even those dates. In short, this page no longer appears to have any relevance over the more up-to-date page of FDA Scheduled Advisory Committee Meetings

Upcoming Events to Keep an Eye on This Week

Regulatory Developments in Pharma/Biotech/Devices

Photograph courtesy of Robert Barrett

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Biggest FDA Developments for 2017

As we begin the new year, it is time toassess the previous year and consider what really mattered when all is said and done. We’ve perhaps already done this on a personal level, but here is my take on an FDA level. 

One thing is certain, it has been a busy year for FDA and on many levels, it was a game-changing time. There were many more approvals of new molecular entities during 2017 (46) than there were last year and the total number just exceeded that of 2015 which was a huge year for approvals (45). And it is not just the number of approvals, but there have been a number of “firsts” this year, including the first prescription app for use in treating opioid addiction. 

The fact that more is happening has been reflected perhaps by the issuance of many more agency press releases this year by far over last year – 164 for 2017 compared to 122 for 2016. Many of the releases this year were special statements by the Commissioner to provide additional commentary on developments at the agency. 

And so among all that activity, here comes my pick for the top five developments at/by FDA for this past year.

 1.  Approvals in Cancer Treatments –  Reviewing the list of approvals of new molecular entities for 2015, FDA has approved 12 new cancer-related treatments which is 8 more than were announced by FDA in 2016 and nearly as many as were approved in the banner year of 2015. It is not just the number of cancer treatment approvals, but the scope as well. There were a large number of approvals aimed at types of blood based cancers – AML/leukemia as well as breast cancer and the approval of the first biosimilar for use in breast and stomach cancer. In addition, the agency granted accelerated approval for a treatment indicated for any solid tumor that has a specific genetic feature – the first time an approval was based not on the location of the tumor, but rather on a common biomarker.  

2.  CAR-T Approval – Related to the above, not a drug treatment but a cell-based gene therapy, the approval of the first CAR-T Therapy  in August of this year merits its own category given the degree to which it  evolves cancer treatment. A long-sought goal of cancer therapy has been to unleash the ability of the immune system itself to resist the cancer. CAR-T manages just that. While the earliest work has been successful in blood borne cancers, there is reason to hope that there might one day be used in solid tumors. Each dose is customized and is created using the patient’s own T-Cells, genetically modified to include a new gene that targets and kills cancer cells and is then re–introduced to the patient. The August approval was for the treatment of acute lymphoblastic leukemia (ALL) and the second approval in October was for certain types of B-Cell lymphoma.  CAR-T represents a big change.

3.  Digital Health Package – While FDA has been extremely slow in anticipating and adapting to developments in social and digital media from a communications point of view, the agency has been much more responsive to developments in digital health. In July the agency announced a framework to facilitate the development and approval of digital health devices by releasing the Digital Health Innovation Action Plan which included a program for developers of devices and software to be pre-certified, shifting from a focus solely on the device to the entity that is developing it, characterizing the balance that FDA is seeking to strike between fostering innovation in fast-paced sector with ensuring high quality and safety of products. The companies chosen for pre-certification were announced in September, and FDA will be holding a two-day public meeting later this month .  

4.  Regenerative Medicine Policy – “We’re at the beginning of a paradigm change in medicine with the promise of being able to facilitate regeneration of parts of the human body, where cells and tissues can be engineered to grow health, functional organs to replace diseased ones; new genes can be introduced into the body to combat disease; and adult stem cells can generate replacements for cells that are lost to injury or disease. This is no longer the stuff of science fiction. This is the practical promise of modern applications of regenerative medicine.” These were the words of Commissioner Gottlieb as FDA announced its comprehensive regenerative medicine policy with the issuance of four final and draft guidance documents designed to add clarity to FDA’s regulation of this space. The objective of the policy is to move FDA forward, as in other areas, in taking a risk-based approach to regulation. At the same time, earlier in the year FDA issued a warning to a stem cell practitioner and has a web page dedicated to helping consumers understand the potential harms that may exist with unapproved approaches. 

5.  Confirmation of Dr. Scott Gottlieb as Commissioner – Since assuming his post, the new Commissioner of the Food and Drug Administration, Dr. Gottlieb has demonstrated both breadth and depth when it comes to taking charge of this mammoth agency. Over the course of his initial months he has set into motion a range of activity on multiple fronts that includes various aspects of dealing with the opioid epidemic, seeing to easing the path for generic drugs, two issues that were of particular concern during his confirmation process.  As noted above, he has also begun processes that are designed to facilitate the development of new types of devices and to address the changing landscape of treatment. 

Beyond the scope of activity is the impact. There is a real attempt at implementing a cultural change and mindset of the agency – from doing things the way that things have traditionally been done to comprehensively laying out a path to a risk-based approach to regulatory oversight, focusing resources on those areas where the greatest risk is involved with the objective of enhancing innovation while maintaining a balance with safety and efficacy, and not just in drugs and devices, but across the board. While the 21st Century Cures Act has been a legislative mandate along those lines, he has long been a proponent of a risk-based approach and his tenure at FDA is very likely to leave a large footprint. Finally, not only has he set out to put policy into motion, he is taking expanded steps to communicate the change not only through frequent blog posts, but as recently noted in a posting here on Eye on FDA, by issuing clarifying statements in addition to agency press releases that detail for stakeholders the steps that the agency is taking. 



Cancer Cell – NIH Image Gallery; CAR-T Schematic – National Cancer Institute; Stem Cell Photo- NIH Stem Cell Information; Dr. Scott Gottlieb – Senate HELP Committee

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