In the last quarter of 2011, the pace at OPDM had picked up a bit having issued 9 letters. However, over time, the pace seems to have slowed a bit from year to year.  And during the first quarter of 2012 there were a total of 6 letters issued, 1 WL and 5 NOV letters.

The 6 letters contained 18 violations by my count.  One of the most notable things from this quarter however was in the frequency of some violations and lack of others.  The minimization or omission of risk information has almost invariably been by far the most frequent violation cited in regulatory action letters.  One of the less common violations is the promotion of an unapproved use.

However, this quarter there were only two Minimization or Omission of Risk violations noted, but there were two also for unapproved use promotion.  Here is the complete breakdown:

• Overstatement of Efficacy – 6
• Unsubstantiated Claims – 5
• Promotion of Unapproved Use – 2
• Omission or Risk Minimization – 2
• Omission of Material Facts – 2
• Broadening of Indication – 1

The vehicles that carried the communications involved 3 traditional print items, 2 digital (Websites) and 1 oral statement made by a presenter.

With the frequency of violations this quarter in overstatement of efficacy and unsubstantiated claims, it appeared that a common pitfall was the description of patient experiences that, while they may have been accurate, went beyond what the typical patient experience might be or went beyond what was reflected in the label.

We are in May.  Hard to believe.  I am thinking that there are many signs of a long, hot summer.  Just what we need in an election year.

In the meantime, here are a few things that happened this week:

• CMS Announces Delay in Sunshine Act Reporting – You may remember that CMS already missed one important deadline for implementing the provisions of the Sunshine Act in October 2011 for publishing a proposed rule which CMS eventually did do in December.  Recall also that recently Senators Charles Grassley and Herbert Kohl sent a letter to CMS expressing their desire that the agency issue a final rule no later than June 2012 on the collection of data, but that is not happening.  In a blog post on May 3, CMS let it be known that they received over 300 comments on the proposed rule during the comment period.  Saying they would issue a final rule “later this year” CMS also stated that data collection would not begin before January 2013.
• FDA Approves Gaucher Disease Drug – The agency announced this week that it was approving a new orphan drug Elelyso (taliglucerase alfa) – a long-term enzyme replacement therapy for treatment of Gaucher disease. Gaucher disease affects about 6000 people in the U.S. and causes a build up of fatty materials in various organs.  The drug is manufactured by Pfizer.
• Facebook Pushes Organ Donation – Apparently there is  ”Like” button for almost everything – after an initiative that allows folks on Facebook to opt into organ donations, several states saw a spike in willing donors.  When you think about it, Facebook does have lots more people in their ranks than the Department of Motor Vehicles.
• The i’s Have It – i-Phone App Approved for Blood Glucose Monitoring – As many regular readers may know, I have a device that hooks up to my i-Pad to take my blood pressure.  Well now diabetics have i-support as well with the approval of the new Sanofi US blood glucose monitoring system.  It is the first FDA cleared blood glucose meter to directly connect with an iPhone or iPod touch.  Check out the multi-media news release for photos, video and more.

That’s it for me this week.  Have a good one everybody.

However, one of the collateral benefits of such a report is that in reading it, one gets a good deal of context for understanding how things work.  FDA is a huge agency and there is a tremendous amount of nuance to the various parts of its operations.  There are many printed materials scattered throughout the Web site that often explain policies and procedures, and there are helpful statistics, but they are not often found in one spot.  By reading this report, one gets some insights without having to perform the search  - a true treasure trove of information.

For example:

• User fees have become a larger part of FDA’s funding for drugs – rising from 26.1 percent of costs in FY 1993 to 61.5 percent in FY 2010;
• The fee for the review of an application (NDA or BLA) that requires clinical data is $1,841,500 and half that if it does not require clinical data in FY 2012;
• A sponsor does not need to request priority review, FDA assesses all applications for priority review eligibility and if it is granted, the sponsor is notified within 60 days of the start of the review period;
• FDA convenes an advisory committee meeting for all applications for NMEs and original BLAs unless an adequate justification is documented explaining the decision not to hold a meeting (though the details of where one finds this were not included…);
• If a sponsor gets a Complete Response Letter (CRL) and resubmits, the review of the resubmission is covered under the user fee paid with the original submission and is either a Class 1 or Class 2 resubmission;
• A Class 1 resubmission contain only certain information such as draft or final printed labeling, safety or stability updates, or other minor clarifying information;
• FDA may consider a sponsor’s failure to take action within a year after the issuance of a CRL to be a request to withdraw unless an extension has been requested in writing.

Those are a few of the interesting factoids picked up by reading the report.  Of course, if you read the report, you also get the download of the main subject matter – how well FDA is doing on approval times – which is “pretty good.”

For some, it may be an abstract notion – the idea that some drugs may be in short supply.  For patients, however, who may face the hard reality of those shortages and for the physicians who treat them, it is far from abstract.

Late in 2011, the IMS Institute for Health Informatics decided to take a look at the issue through a lens of their own making to see if the problem could be better defined.  Through its extensive collection of prescription data, IMS can analyze a wealth of information to provide important insights into our consumption and use of medications in the U.S., and compiling it into a report.

The resulting report was entitled “Drug Shortages:  A Closer Look at Products, Suppliers and Volume Volatility” and what it found was that the drug shortage problem is very concentrated among certain types of drugs – generics and injectables.  Late last week, I had the opportunity to ask Murray Aitken, Executive Director of the IMS Institute for Healthcare Informatics, what made the IMS outlook unique, about the key findings, and what could help not only in the early detection of drug shortages, but in their prevention in the first place.

Here is the podcast of our discussion where I asked what unique ability IMS brought to the table in assessing the situation and what insights resulted.

See also FDA’s Web page on Drug Shortages

That is how many Warning Letters the agency sent out last Friday to manufacturers and distributors of dietary supplements.  The specific focus of the letters was products that were being marketed containing dimethylamylamine, also known as DMAA, sold as a “natural stimulant”.

The list contains 10 different manufacturers covering 15 separate products.

The specific violation cited in the letters was that current law states that when supplements contain dietary ingredients not marketed before October 15, 1994, manufacturers must submit the new ingredient for use as a New Dietary Ingredient, notifying FDA of evidence that supports a conclusion that use is safe.  The agency said in the letters that this requirement had not been met.

Further the agency stated that the synthetic DMAA could not be a “dietary ingredient” under Dietary Supplement Health and Education Act of 1994 (DSHEA) which defines a dietary ingredient as a “vitamin, mineral, amino acid, herb or other botanical, a dietary substance for use by man to supplement the diet, or a concentrate, a metabolite, constituent, extract or combination of these substances.”

FDA has been known in the past to send out a flock of letters at once to stake out a policy decision.

The action appears some time in coming.  DMAA has been marketed as a supplement appealing to fitness buffs seeking extra energy. The Army Times reported in December 2011 that the Department of Defense was pulling DMAA containing products from on-base sales pending a review of side effects after some the experiences of some soldiers.

More information on how the agency regulates dietary supplement is contained on an overview page at the FDA site.

In the meantime, here is a bit of what happened this week (I’ve still been keeping track):

• Doctors and Social Media in the UK – According to an editorial in The Lancet this week, the General Medical Council which oversees the practice of medicine in the U.K. issued a draft guidance for comment on the use of social media by physicians for consultation.  The draft covers a number of issues related to patient confidentiality, appropriate conduct, and the like.  An editorial in The Lancet notes that accepting patients as friends on Facebook is particularly discouraged, though notes that it is important that physicians look for ways to seize the opportunities offered by social media to help steer patients who have gravitated there for information and not to solely focus on the risks.
• Bayer Gets Pintresting - And speaking of social media, this is a story that ran earlier this month but too interesting not to mention.  Here at Eye on FDA for some time, I have been tracking the involvement of pharma companies in blogging, Facebook, YouTube and of course, Twitter.  With the emergence of Pintrest, many have wondered if there is utilization there for pharma.  According to an article in MedCity News, Bayer is pioneering an effort in the new platform. According to the article, the company has established three bulletin boards – one on sustainability, one on innovation and one on the breadth of the corporation.  It will be interesting to see whether others follow and how they will utilize it to engage stakeholders.
• FDA Approves New Orphan Drugs – Two drugs were approved by the agency this week of note, both on the 26th.  The first was GSK’s Votrient, already approved for advanced kidney cancer,  for use in treatment of advanced soft tissue sarcoma, an orphan disease with about 10,000 cases in the U.S. annually.  In addition, this week FDA approved Novartis’ Afinitor for the treatment of non-cancerous kidney tumors – also an orphan disease. Afinitor was also previously approved to treat advanced renal cell carcinoma.

That’s it for me this week.  Have a good weekend everyone.  Good to be back!

“We are disappointed that regulations implementing the Sunshine Act were not complete by the statutory deadline of October 1, 2011.  We request that the final rule on implementation be released no later than June of this year so that partial data collection for 2012 can commence.”

In addition, there was some specific direction.  In the letter they urge that CMS define very specific categories for payments and urged a removal of a catchall “other” category that could serve to obscure the nature of some transactions.  In addition, the Senators took issue with the proposed yearly schedule for correcting mis-reporting to the public site stating rather that errors should be corrected as the error becomes known.

Additionally the letter expressed concern regarding the design of the Web site that will serve as the vehicle for reporting the information to the public.  Given the potential for public attention to the information – and the many ways that information can be interpreted – the Web site clearly takes on as important a role as the very type of data that is collected.  Therefore, the letter urged that the site be thorough and user-friendly complete with definitions to understanding the nature of the transactions and all of the entities involved.

The letter closes by posing a set of particular questions:

1. Can CMS commit to completing a final rule by this summer so that data collection can begin in 2012?
2. Since CMS missed the initial required Congressional deadline, has CMS increased the resources or personnel assigned to the implementation of the Sunshine Act, including a dedicated information technology lead?
3. Will CMS commit to issuing an RFP to begin designing the website?
4. Does CMS have a dedicated working group assigned to the implementation of the Sunshine Act, and what technical expertise and program areas are represented?
5. Does CMS have a public education and outreach plan to raise awareness of the new law with the provider community and with health care consumers?
6. Has CMS allocated dedicated implementation funds for the Physician Payment Sunshine Act?

While these are questions posed by the Senators to CMS, medical product manufacturers may do well to ask themselves variations along these lines.  Many have voluntarily begun to report data on their Web sites, but that may have to be changed to more accurately reflect the categories and prominence of the CMS undertaking.  How will mistakes in reporting be dealt with?  How will patients and providers be educated?  Even as CMS ponders its response to these inquiries, it is a good time for all to consider what form individual company responses will take.

And here is a little bit of what changed this week:

• Warning Letter for Aeroshot! – In late February Eye on FDA reported that the agency was looking closely at the product Aeroshot – an “inhalable” caffeine.  Now in early March, that effort took the form of a warning letter issued by the agency to the manufacturer.  In addition to the letter, to drive the point home with the consuming public, FDA also undertook the somewhat unusual step of issuing a press release about the letter.  Among other things, one of the concerns the agency stated was the fact that the label refers to “breathable energy” which may actually lead consumers to try to inhale the product when it is meant for ingestion by swallowing.
• More on the Evolving OTC Switch Environment – Also here on Eye, I recently wrote about the potential for change in the OTC switch environment.  On the heels of that posting, a few days later reports surfaced stating that FDA was actively considering new proposals that could liberalize access to many medications for chronic conditions such as diabetes, high blood pressure and high cholesterol.
• Euro Docs on Twitter – My friend Bertalan Mesko a/k/a Berci this week reported in his blog Science Roll about a list compiled by Andrew Spong that listed European physicians on Twitter, along with other social media assets such as blogs that Berci then turned into an nifty interactive map.  Check it out as well as the overall Twitter list of Docs listed at TwitterDocs.net.
• FDA Approves Surfaxin for Premature Infants -Discovery Laboratories won approval from FDA for its treatment Surfaxin (lucinactant) to be used for the prevention of respiratory distress syndrome in premature infants.  It is the fifth drug approved in the U.S. to treat RDS, one of which is no longer marketed.
• Happy Birthday to Me – Eye on FDA Turns 6 – Eye on FDA officially enters its 7th year of chatting to you about FDA stuff.  Hard to believe but six years ago, Facebook was just getting started and Twitter was not even aflutter.  It has been great fun to watch communications change so dramatically and see how we have adapted to the change (and in the case of some – have not).  I am grateful to all the thousands of subscribers and followers on Twitter, and look forward to keeping my Eye on FDA in the future.  Thanks everyone!

That’s it for me.  Have a great weekend everyone!

Drugs

• In FY 2011, FDA approved 35 innovative drugs, among the highest number in a year in the past decade with the exception of 2009;
• Of the 35 new drugs approved last year, 34 met their PDUFA date;
• Of the 57 novel drugs approved by both FDA and the EU between 2006 and 2010, 75% were approved first in the U.S. and all 23 cancer drugs were approved in the U.S. first;
• For priority review products approved between 2006 and 2010, FDA’s median time to approval was six months (183 days), more than twice as fast as the EU time to approve those drugs, which took a median time of 13.2 months (403 days);
• For standard review of drugs, FDA’s median time to approval was 13 months (396 days), which is 53 days faster than the EU time to approval of 14.7 months (449 days);
• Nearly 40% of the drugs American take are made overseas;
• 80% of active pharmaceutical ingredients are imported into the U.S.

Food

• FDA is responsible for regulating the safety of four-fifths of the nation’s food supply;
• FDA-regulated imported food products come from more than 300,000 foreign facilities located in 200 countries;
• Food imports have increased nine-fold since 1993;
• 70% of seafood and 35% of fresh produce in the U.S. comes from foreign countries

Devices

• Approximately one-half of the medical devices used in the U.S. are imported;
• FDA completes 90% of its 510(k) reviews in 90 days or less

The FY 2013 budget weighs in at $4.5 billion for FDA which is an increase of 17% over the previous year – 98% of which is to be covered through increases in existing user fees and bringing new user fees on line.  One point Commissioner Hamburg stressed repeated is that the world is changing rapidly and certainly the budget request and some of these statistics bear that out clearly.

The switch of Prilosec to OTC status was significant for many reasons, other than the size of the market, as it represented a treatment that addressed not a symptom (I have a headache – pill=better) but a condition (heartburn bothers me = pill over the course of time).  Could consumers understand the difference?  Apparently, but at the time, there was debate.

The standard that is looked for in a switch is candidate rests on whether a person can read and understand the label and use the product without the intervention of a “learned intermediary” (your doctor, physician assistant or nurse practitioner).

Statins have tried and failed to make the switch from RX to OTC. Two primary things held them back.  First, one’s cholesterol level is not something one can diagnose on one’s own – hence the need for the learned intermediary.  Second, a patient on statin therapy is supposed to have blood tests every six months to assess whether or not there is any liver function issue.

Recently, two things are in the works that could change the picture for statins from a regulatory perspective.  First, FDA has scheduled a meeting for later this month on the future of OTCs. And second, last week FDA indicated that the label for statins could be changed to remove the requirement for liver monitoring for people taking statins.

The removal of the monitoring requirement for statins addresses in part the second of the two obstacles for statins.  Now all we need is an app for one’s i-Pad that gets a cholesterol reading – or an app that records one’s cholesterol level from the physician so that when one goes to pick up an OTC statin, one has information that can be discussed with a pharmacist, perhaps under a new paradigm arrived at during FDA’s upcoming meeting.

Granted along with the new label change, there have also been some concerns expressed about statins.  How it plays out is unclear, but one thing that is clear is that between improved technologies and an altered regulatory framework, consumers may get more choices in self treatment in the future – though there is bound to be debate.