When it comes to jurisdiction over compounding pharmacies, Senator Lamar Alexander (R, TN), wants someone “on the flag pole” responsible for ensuring that non-traditional compounders meet set federal standards.

Alexander proposed allowing FDA to designate state boards of pharmacy as the primary regulator, if they are willing and able. If the state regulators proved unable or made mistakes, FDA would have the ability to take over regulation.

 FDA Commissioner Hamburg gave that idea a positive nod, saying it was one model that could be explored, but she still wants federal regulations to assure consistency.

“I think it should be made explicit,” she said. “I think for non-traditional compounding there should be federal standards that apply to certain types of practices that go to issues of quality and safety.”

FDA said those facilities should be required to submit to inspections, report adverse events and register with the agency.

On the House side, Tom Harkin (D, IA), suggested that compounding facilities shipping across state lines should come under FDA scrutiny. Other ideas included using a volume threshold and prescription records.

If the FDA gets more responsibility – which is looking increasingly likely -- they will also need more funding. Otherwise this is all just C-SPAN rhetoric.

Did somebody say “sequestration?”

The election may be over, but the malarkey continues.

The most recent Marlarkey Alert comes to us courtesy of the New York Times editorial page.

In defense of the IPAB, the Gray Lady editorializes:

The board, known as the Independent Payment Advisory Board, has been the subject of false attacks over the past few years by Republicans who claim that it will ration care, disrupt doctor-patient relationships, and tell patients what treatments they can receive. That is an outlandish way to describe a board that is prohibited by law from making any recommendations to ration care, raise premiums, increase cost-sharing, restrict benefits or limit eligibility.

That’s malarkey.

Medicare spending is expected to be $575.7 billion this year, jumping to over $1 trillion by 2022, as the country ages. Over the next 75 years, the program is projected to accumulate a $38 trillion budget shortfall.

Much of this enormous price tag goes towards financing Medicare Parts A (hospital insurance) and B (medical services -- including diagnostic tests and doctor visits). And yet, IPAB has no authority over either. And the board can’t make any substantive structural changes. Neither the fee-for-service structure nor enrollee premiums and fees can be altered.

The board’s only viable option is to further ratchet down reimbursement rates for Medicare providers, especially doctors, who are already losing money on Medicare patients. Indeed, the financial burden of too-low payments under Medicare has driven 17 percent of doctors and 31 percent of primary care physicians across the country out of the Medicare program altogether, according to a study from the American Medical Association.

If rates fall any lower, seniors will have an increasingly difficult time securing doctor appointments. Visits will be cut short to squeeze in patients and care compromised. 

Lawmakers must cast aside IPAB’s flawed approach (and the media malarkey surrounding it) and focus instead on innovative initiatives that address the program’s real cost-drivers while protecting seniors’ access to care.

There is no greater disaster than greed.

 – Lao-tzu

The tragic deaths caused by the current drug compounding scandal could so easily have been avoided. The root cause wasn’t a drug shortage – it was greed.

A new effort by Representatives Ed Markey (D, MA), Henry Waxman (D, CA), John Dingell (D, MI), Frank Pallone, Jr. (D, NJ), Diana DeGette (D, CO), and Anna Eschoo (D, CA) is aimed at getting to the bottom of the problem by investigating the roles of the players in this horrible drama – specifically the actions of Group Purchasing Organizations (GPOs).

Mr. Markey: “As Congress fully investigates all the causes of the tragic meningitis outbreak in an effort to protect patients in the future, we need to look at the role GPOs play in the occurrence of drug shortages that could lead to increased reliance on compounding pharmacies.”

 “Through our investigation into drug shortages and the meningitis outbreak, we have discovered that medical professionals have increasingly been turning to compounding pharmacies for their prescription needs,” said Mr. Dingell. “It is important we study every potential cause of this outbreak in order to get to the bottom of this health crisis.  I look forward to working with my colleagues in the coming weeks to explore legislative approaches that will address this matter.”

Representative DeGette: “While we've begun to address drug shortages legislatively, it is clear we must aggressively investigate the factors that led to this deadly outbreak and determine possible remedies, so we can take steps to save patients lives.”

“If group purchasing organizations are taking advantage of their unique role in facilitating a safe and reliable drug supply, then we need to know about it,” said Representative Eshoo.

Mr. Waxman, “In light of the tragedy of the meningitis outbreak linked to contaminated compounded drugs, we need to look carefully at all factors that might be contributing to the increasing use of compounded drugs by hospitals and other health care providers.”

“This initiative is a courageous step forward in addressing the foundational reasons behind both the tragedies caused by drug compounding and the broader issue of preventable drug shortages,” said Peter J. Pitts, President, Center for Medicine in the Public Interest and a former FDA Associate Commissioner. “The anticompetitive manipulation of American healthcare by GPOs is an urgent topic for congressional action.”

The full Congressional release can be found here.

BioCentury reports:

FDA issues first breakthrough designation

FDA has "recently" issued the first breakthrough drug designation, Janet Woodcock, director of the Center for Drug Evaluation and Research, said on Wednesday. She said the agency cannot disclose the sponsor or drug candidate. The breakthrough designation, created by the FDA Safety and Innovation Act, commits FDA to collaborate with a sponsor to accelerate product testing and development.

"Drug manufacturing could be the rate limiting step" for implementing the breakthrough drug pathway, Woodcock said at a meeting sponsored by Friends of Cancer Research and the Brookings Institution's Engelberg Center for Health Care Reform. FDA will work with sponsors to improve the chances that manufacturing is scaled-up and approved at the time when breakthrough drugs are approved, she added.

Mirror, mirror on the wall – whose delaying innovation most of all?

Should the new third leg of the FDA review process be … investment considerations?

Jonathan Leff, managing director of Warburg Pincus LLC, believes that the FDA should consider the cost of drug development when making its regulatory decisions.

At a conference on rare diseases conference sponsored by the Drug Information Association and National Organization for Rare Disorders, Leff said FDA should think about the effects of its demands on sponsors, such as the additional cost another efficacy trial would create should the agency demand it.

That’s a bad idea. While there are many things the FDA can and should do that would result in lower drug development costs – the issue has no place in the regulatory review process. It is as inappropriate a third leg as comparative effectiveness. The regulatory process must rest on the twin pillars of safety and efficacy.

Leff does not agree. “We must recognize that if a system is set up to ensure safety and efficacy and no mechanisms are designed into it to take the economic burden into account, we should expect to see as an unintended consequence, exactly what we have seen, which is relentlessly increasing time and cost.”

"Because of that time and cost, venture investors and pharma companies are now unable to make new investments to initiate development of many promising new therapies and as a result the next generation of potential breakthrough treatments … may never have a chance.”

Indeed, we are seeing an increase in time and cost – and these are serious roadblocks to continued investment in innovation. But whether this is entirely the fault of the FDA is not as simple as Leff makes it seem. He’s parroting the party line of those who choose to blame their developmental failures on the FDA. There is a medical device to address this myopia – it’s called a mirror.

Mr. Leff is only repeating the broader opinion of the investor community. The National Venture Capital Association's (NVCA) Medical Innovation & Competitiveness Coalition found that 39% of firms reduced investment in life sciences companies over the last three years. The same percentage expects to further decrease investment over the next three years. The venture capitalists surveyed largely blamed the Food and Drug Administration's restrictions and regulatory challenges for this trend.

Pharmaceutical companies must evaluate their level of responsibility for shrinking investment expenditures. If they want venture capitalists to continue investing in medical research and development, they must produce high-quality drugs worthy of FDA approval – and stop whining when their “miracle drugs” require more clinical evidence.

The solution isn’t for the FDA to weigh the financial investments of biopharmaceutical companies in its regulatory decision process. The solution is to make the regulatory process more predictable.

A quarter-century ago, the success rate for a new drug used was about 14 percent. Today, a new medicinal compound entering Phase 1 testing — often after more than a decade of preclinical screening and evaluation — is estimated to have only an 8 percent chance of reaching the market. For very innovative and unproven technologies, the probability of a product’s ability to make it to the market is even lower. We must work together to turn that around.

When Thomas Edison was asked why he was so successful, he responded, “Because I fail so much faster than everyone else.” Consider the implications if the FDA could help companies fail faster. Using the lower end of the Tufts University estimate of the average pre-tax cost of new drug development, $802 million:

• A 10 percent improvement in predicting failure before clinical trials could save $100 million in development costs.
• Shifting 5 percent of clinical failures to Phase 1, the earliest stage, from Phase 3, the latest stage, reduces out of pocket costs for developers by $15-$20 million.
• Shifting of failures to Phase 1 from Phase 2, the middle stage, would reduce their out of pocket costs by $12-$21 million.

All of these dollars could then be reinvested in other innovative development programs for new life-saving medicines.

For all that modern science has to offer, developing new treatments is still very much an art, in which hunches, intuition, and luck play a critical role. The odds are long. But for more medicine that is affordable and innovative, we need up-to-date regulations that compliment the drug trial process in order to take these chances, which is precisely the mission of the FDA’s Reagan-Udall Foundation.

 “I’ll tell you as a venture capitalist, I have been forced to not make investments in rare disease opportunities that we might have or almost certainly would have invested in 10 years ago because of a perception that if we do a clinical trial, and given all the unknowns in this area, miss slightly on the statistical goals, that would be game over for that development program,” he said during the conference.

That may be so. But drug reviews are not and should not be predicated on the calculations of venture capitalists.

But that doesn’t mean maintaining the status quo is acceptable.

Matt Arnold at Medical Marketing & Media asks a few good questions about some tough post-election ACA issues.

How will IPAB cut spending, and who will sit on it?

More than nudging the country towards insurance universality, the guts of the ACA are comprised largely of deeply wonky schemes to try and “bend the curve” of healthcare spending. And then there's the Independent Payment Advisory Board, a scheme with teeth. Nobody's sure exactly how this broadly-drawn entity will operate, but the 15-member board -- for which members must be nominated by the President, in consultation with both parties' Congressional leaders, and approved by the Senate -- will have the power to impose spending cuts on Medicare when the program's spending outpaces projected growth and when Congress fails to pass cuts to offset those increases. Initial cuts will fall on doctors and pharmas, with hospitals and hospices coming in for cuts later on. Critics fear it will evolve into a federal formulary-setting body like the UK's NICE, restricting access to drugs deemed more costly than they're worth (fun fact: Sarah Palin called it “Death Panel-like). The legislation contains language specifically prohibiting the board from rationing care or limiting benefits, but opponents argue it will result in de facto rationing.  Republicans are fiercely opposed, along with enough Democrats that repeal is a real possibility, say some Congress-watchers. The board is scheduled to issue its first report in January, 2014, so nominations should be forthcoming soon.

How will CMS reset perverse incentives for provision of medical services?

One of the main goals of the ACA as to shift the US healthcare system away from an incentive structure that rewards quantity – of diagnostic tests and procedures and products, via reimbursement – and towards one that rewards quality, of health outcomes, patient feedback, etc. One way to do that could be through a UK-style comparative effectiveness regime of the sort that industry advocates feared PCORI (the Patient Centered Outcomes Research Institute) would become (early indications are that PCORI will be operating at a much more macro level than ‘Prescribe this, not this'). Another might be a risk-sharing scheme (AKA “Expanded Access”) in which pharmas and federal programs establish a measure of success for a therapy and companies reimburse the government when their products fail to meet that standard. In other words, will we measure for clinical effectiveness or for cost-effectiveness? 

What will the particulars of the Physician Payment Sunshine Act legislation that got rolled into the ACA look like?

The Centers for Medicare and Medicaid Services blew past its initial October 2011 deadline to issue guidelines on data collection, having bigger fish to fry – like setting up Obamacare's health exchanges. CMS then pushed back the start date for mandatory data collection to January, 2013. A final rule is expected by the end of the year, but nothing says CMS couldn't hit snooze again. The big question is preemption – will the ACA trump state laws, and if so, will it favor the more lax or the more draconian among them? Also, will the law require health insurers (including government) to report payments to physicians for things like academic detailing and switching patients to generics?

Will Democrats get anywhere in their efforts to limit biologics exclusivity to seven years?

The White House dearly wanted biologics exclusivity limited to seven years. The Administration got rolled by biopharmas, which succeeded in getting it set at 12 years, but the White House never stopped pushing to dial it back. With a fiscal reckoning fast approaching, everything is on the table, and the biopharma lobbies will be playing some serious defense.

How about that non-interference clause? 

Vice President Biden, in his debate with Rep. Paul Ryan, suggested he wouldn't mind another bite at a provision in the Medicare Part D prescription drug benefit law explicitly prohibiting the government from butting into negotiations between companies and private plans that administer the benefit. “If they allow Medicare to bargain for the cost of drugs like Medicaid can, that would save $156 billion right off the bat,” said Biden, whose party's left flank has tried and failed repeatedly to dislodge the clause. Given solid Republican control of the House, it seems unlikely that they might succeed now, but again, everything is on the table, and the politics of prescription drug prices are ever tricky.

Matt's complete article can be found here.
 

December 7, 2011 is a day that will live in regulatory infamy. That’s when Secretary of Health and Human Services Kathleen Sebelius overruled the FDA decision on the over-the-counter status of emergency contraception.

By reversing an FDA decision, the Secretary set a dangerous precedent for all-comers to lobby Congress, the HHS and the White House on any and all FDA decisions—directly inserting politics into what must be a scientifically driven process.

On December 13, 2011, Senators Patty Murray and Maria Cantwell and a dozen other Senate Democrats asked the Obama administration to produce scientific justification for its decision to block girls 16 and younger from buying the emergency contraceptive Plan B over the counter.

In a letter to U. S. Department of Health and Human Services Secretary Kathleen Sebelius Tuesday, the 14 lawmakers said they wanted "medical and scientific evidence" behind Sebelius's unprecedented decision to overrule the Food and Drug Administration and block younger teenagers from buying the so-called "morning after pill" without a prescription.

Senator Murray also called for a Senate hearing on the topic. She asked the Secretary to testify in front of a Senate committee to explain her scientific views on the matter. Senator Murray stated, “I want to know what the scientific evidence is that the secretary made this decision on in overriding the FDA … Pharmaceutical companies here in this country make some very expensive decisions, and they need to know that the FDA is going to base a decision based on science.”

The hearing hasn’t happened yet.

Will it happen now that the election is over?

It should. And the hearing should broaden its scope to address the ability of the Secretary of Health and Human Services to reverse FDA decisions and whether the FDA Commissioner should serve a congressionally mandated six-year term in order to ensure the position is “above” the political fray – similar to that of the Director of the FBI—and then approved by the Senate.

Let the person chosen as FDA Commissioner serve as free of the political current as possible.

And a Senate hearing would be a good place to start.  

“For our district and for our country, the debate on Obamacare is over,” declared Bill Foster, a Democrat elected Tuesday to the House from a suburban Chicago district.

Not so fast.

As the New York Times reports, “Now comes another big hurdle: making it work.”

Jeff Goldsmith, a health industry analyst based in Virginia, offers a more pragmatic assessment, “If you actually are going to implement this law, people need to know what’s in it — not just the puppies-and-ice-cream parts.”

And, as any owner of a new puppy can attest -- it’s messier than it looks.

Aliter catuli longe olent, aliter sues.

It seems that, in Missouri, the natural way to stop an ObamaCare-mandated state health exchange is to insist it be put to a vote. (Under the Patient Protection and Affordable Care Act, states have until 2014 to establish state-based insurance exchanges that may be run by the state, the federal government or through a partnership of both.)

On Election Day the Show Me State passed Proposition E, prohibiting the governor or any state agency from establishing or operating state-based health insurance exchanges unless and until they are authorized either by the legislature or by popular vote. Proposition E allows taxpayers to sue any Missouri state worker or agency involved with any part of the exchange process not required by federal law.

The next four years are going to be a battle over whether or not Uncle Sam continues to morph into Uncle Sam, MD.

Consider:

Uncle Sam as our nation’s largest payor.

Uncle Sam as funder of comparative effectiveness research.

Uncle Sam as “academic” detailer of comparative effectiveness research.

Uncle Sam as determiner of Essential Health Benefits.

Consider the continued disempowered physicians, patients -- and states (which are the true laboratories for healthcare delivery innovation).

Consider a battle royale over whether or not comparative effectiveness should become a third leg for FDA approvals (in addition to safety and efficacy).

Consider whether CMS reimbursement will move to a value-based reimbursement model, setting up the foundation for a US version of Britain's NICE. (Remember Don Berwick?)

Consider Medicare and Medicaid adopting the NHS model of "expanded access" (formerly known as "risk sharing") wherein reimbursement is granted -- but if predefined patient outcomes aren’t achieved, the pharmaceutical company reimburses CMS. Hm.

Consider FDA Commissioner Peggy Hamburg.  Will she stay or will she go? (I predict she will stay.)

I predict that (regardless of who gets elected) IPAB gets revoked on the Hill. IPAB is a slippery slope to broader government price controls, so it should be good riddance to dangerous rubbish – if the President doesn’t veto this first congressional rebuke to ObamaCare.

And what of the legitimacy of Billy Tauzin’s famous ACA “deal?” Will there be legislative action to revoke the Non-Interference Clause (as mentioned by Vice President Biden -- although not by name -- during the Vice Presidential debate)? Unlikely.

Will the President continue to push for 7 years of data exclusivity for biologics (as opposed to the 12 currently allowed under the ACA?) Will he have the chutzpah to claim he is pro-innovation if he does?

Will we have to endure another foolish waste-of-time debate over drug importation?

And did somebody say “Doc Fix?”

Ladies and Gentlemen, fasten your seatbelts and start your engines.

Those who believe that they are exclusively in the right are generally those who achieve something. -- Aldous Huxley

Rather than speculating as to where the FDA may go in a post-PDUFA V world, it's important to focus on where it has already gone. Without much attention or fanfare, the agency has established a new review board within the Center for Drug Evaluation and Research – the CDER Exclusivity Board. Its goal is to help the agency make consistent findings on whether products should be granted periods of marketing exclusivity.

The board began meeting in November 2011. It is comprised of agency employees from the Office of Regulatory Policy, the Office of Medical Policy, the Office of New Drugs, the Office of Pharmaceutical Sciences, the Office of Executive Programs in CDER and the Office of the Chief Counsel.

The focus is on five-year new chemical entity exclusivity, three-year new clinical trial exclusivity, and exclusivity for biological products, according to a brief description posted on the agency’s website.

“The board will not review or make recommendations with respect to all exclusivity determinations in these areas, but will assist the center in resolving certain matters, including issues that arise in the context of specific requests for exclusivity,” the web page states.

The board generally meets once or twice a month. Members review written submissions from sponsors and board members participate in meetings with sponsors regarding exclusivity determinations for their products.

Some exclusivity matters fall outside the board’s purview: The body generally will not make recommendations for 180-day generic drug exclusivity, seven-year orphan drug exclusivity, or six-month pediatric exclusivity. But it will work with other offices and groups within FDA that are responsible for dealing with these exclusivity determinations as needed.

Your PDUFA dollars at work.
 

Matt Herper of Forbes, in his article, Why Presidents Don't Shape The FDA, writes:

Generally speaking, Democrats like Obama want to ensure that medicines are safe and are less concerned with being friendly to the pharmaceutical industry, and Republicans like Romney believe in lowering regulatory barriers and getting medicines to market faster. But the reality is no president makes the FDA his top priority — which means that the agency is often shaped as much by the opposition as by the commander in chief.

In the bigger picture, this is an illustration that when it comes to reshaping federal agencies, Presidents are not as powerful as you might think — and a reminder that just because a politician campaigns for a change does not mean that he or she will be able to execute it.

The important truth to remember is that the FDA is an agency driven be career staff.  Of the 11,000 or so employees, under a dozen are political appointments (including the Commissioner). And all of those Schedule Cs reside within the Office of the Commissioner. That means 100% of employees in every FDA center are career government workers. Put another way – drugs are being reviewed exclusively by career employees.

To refer to the “Obama FDA” or the “Bush FDA” or a future "Romney FDA" is valid only insofar as the presidentially-appointed  Commissioner sets an agenda. And that is if the Commissioner has an agenda and (most importantly) can enlist senior career officials to buy into it.

During my tenure at the FDA, Commissioner Mark McClellan was able to convince the career leadership that the role of the agency was to be regulator and colleague to industry and, most importantly, change-agent. I believe we had many successes because of this agenda – and the public health was well served.

The most important tool any President has to impact the performance of the FDA is in his choice of an FDA Commissioner. And that appointment must be confirmed by the United States Senate.

Herper concludes:

From an FDA perspective here, the lesson may be that it’s best to insulate the agency from politics as much as possible. One way to do that, according to Peter Pitts of the Center for Medicine in the Public Interest, would be to put FDA commissioners on six-year terms, protecting them from political churn.

More to the point, a six-year term would allow a Commissioner to more fully pursue his or her agenda.

Neither President Obama or Governor Romney has demonstrated any interest in a fixed term for the Commissioner.  At least not yet.

While many on the East Coast are thinking about electrical power, a new global study by the IMS Institute for Healthcare Informatics shows that the use of healthcare IT to increase medication adherence could be a key factor in saving some $500 billion in healthcare spending worldwide -- and that a key factor is the power of information.

“Harnessing available information to set priorities, monitor progress and support behavior change among healthcare stakeholders – including policymakers, payers, clinicians, nurses, pharmacists and patients – is a vital first step,” he said.

Aitken said the increasing use of data in healthcare makes this a good time to apply the levers suggested by the study to lower healthcare costs, which are:

• Increase medicine adherence by addressing patient beliefs and behaviors at the point of prescription and during medicine intake.
• Ensure timely medicine use that prevents avoidable and costly consequences among patients with highly prevalent diseases that increase in severity if diagnosis and treatment are delayed.
• Optimize antibiotic use to turn the tide on rising antimicrobial resistance worldwide due to the misuse and overuse of antibiotics.
• Prevent medication errors throughout the medicine provision pathway, from prescription to administration.
• Use low-cost and safe generic drugs where available to leverage the under-exploited opportunity in post-patent expiry markets.
• Manage polypharmacy where the concurrent use of multiple medicines, particularly among the elderly, risks costly complications and adverse events.

“Not all of this is new. Adherence is not new,” he added. What is new, however, is the ability to use data and predictive modeling to find which patients best respond to what type of medication adherence reminders, he said. Some need a visit from a nurse, which is more costly than using a text or a tweet. Predictive modeling can help an organization use resources wisely to get the most adherence from patients.

The study also focuses on two key factors critical to driving improvement across the six levers: multi-stakeholder engagement and … the power of information.

Knowledge is Power.

The study can be found here.

Dear FDA Colleagues:

I would like to make you all aware of an upcoming transition within the Office of the Commissioner.  Effective November 5, 2012, Jeanne Ireland will be leaving her post as head of the Office of Legislation (OL) to assume a new role as Senior Advisor to the Commissioner within the immediate office.  In that new role, Jeanne will manage high priority projects and, in the short term, will continue to manage the legislative/oversight issues surrounding the recent meningitis outbreak and related pharmacy compounding issues.  Michele Mital has graciously agreed to serve as Acting Associate Commissioner for Legislation and will oversee and manage all other aspects of OL.

For the past three years, Jeanne has been a terrific asset to the Agency in her leadership role in OL, and she has numerous legislative successes under her belt, including most recently the sweeping Food Safety Modernization Act and the Food and Drug Administration Safety and Innovation Act, which included the reauthorization of the prescription drug and medical device user fee programs and for the first time created new user fee programs for generic drugs and biosimilars.  I am sorry to lose Jeanne in this important role, but I am thrilled that she will be assisting us in her new capacity.  I therefore would like to congratulate and thank Jeanne for her prior achievements and to welcome her to the immediate office.  I also would like to thank Michele for taking the reins in OL.

Sincerely,

Margaret A. Hamburg, M.D.

Commissioner of Food and Drugs

It was nice being at a meeting of regulatory professionals where "ED" meant something other than the expected.

Specifically, I was at the annual RAPS meeting in Seattle where the theme of the conference was "Elevate" (as in "raise the level of your game) -- and "ED" referred to "enforcement discretion."

FDA judgment was certainly on the minds of panelists (myself included) during the session on mobile apps as medical devices. At present, there are some 17,828 healthcare and fitness apps and 14,558 that can be deemed “medical.” As Vice President Biden said, “It’s a big f**kin’ deal.”

But when is an app a medical device and when is it not? Not surprisingly, it depends.

Does the app replace paper-based data collection (for example from a blood glucose meter), or does it bring to bear the power of an algorithm that takes raw data and turns it into a diagnosis with treatment recommendations?

What is the level of impact the app might have on a patient's condition. Is the app designed to assist in patient self-management?

Is the app an accessory to a regulated medical device?

Many questions, all of which lead us back to the question of enforcement discretion.

Consider the Draft Guidance for Industry and Food and Drug Administration Staff - Mobile Medical Applications   issued on: July 21, 2011 – specifically, footnotes 12 and 13: 

(12) … the FDA intends to exercise its discretion to decline to pursue enforcement actions for violations of the FD&C Act and applicable regulations by a manufacturer of a mobile medical app, as specified in this guidance. This does not constitute a change in the requirements of the FD&C Act or any applicable regulations. 

(13) The FDA's review of these products indicates that the majority of these other mobile apps that may meet the definition of a medical device have functionality either to automate common medical knowledge available in the medical literature or to allow individuals to self-manage their disease or condition. Many of these mobile medical apps also automate common clinician's diagnostic and treatment tasks using simple general purpose tools, including spreadsheets, timers, or other general computer applications, by performing logging and tracking. For example, mobile medical apps that: log, track, and graph manually-entered (keyed in) data that lead to reminders or alarms; act as data viewers for patient education; organize, store, and display personal health data, such as lab results, doctor visits, dosages, calories consumed, etc.; or allow for general dose over the counter (OTC) lookups and use drug labeling to provide information that is typically available on a drug label, e.g., acetaminophen dosage for children and adults.

Now consider the “Mobile medical apps Proposed Scope for Oversight” issued by CDRH. It’s a pyramid divided into three parts:

The top of the pyramid includes mobile medical apps that are traditional medical devices or a part or an extension of a traditional medical device. Clearly within the scope of being regulated as medical devices.

The middle section includes patient self- management apps and simple tracking or trending apps not intended for treating/adjusting medication. This is the area, as defined by CDRH, for enforcement discretion

The bottom section are devices that are not deemed “mobile medical apps” and, as such, have no regulatory requirements.

FYI, per SEC. 201(h)  [321] of FD&C Act:

(a) the term "device" means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is

(1)  recognized in the official National Formulary, or the United  States Pharmacopeia, or any supplement to them,

(2)  intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or

(3)  intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its principal intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its principal intended purposes.

A light regulatory hand allows for innovation to flourish. But will CDRH be flexible enough in its approach to disruptive app-based technologies. "Signs point to yes" -- but developers seeking greater predictability are only somewhat assuaged by such a Magic 8 Ball approach to agency policy.

We're in early days.  

Another "ED" variable is the intended use of an app -- something that is the responsibility of the developer, not the FDA. And discretion is the better part of valor. In short, to thine own self be true.

And what about "human factors" such as user/device interface or the environment in which that interface takes place? Bedroom or operating room? What about user-error mitigation?

And then there's the issue of validation testing.

We've come a long way from the "popsicle-stick-or-tongue-depressor" conversation -- and we've got a long way to go.  As Walter O'Malley (the man who moved the Brooklyn Dodgers to Los Angeles) once opined, "The future is just one damned thing after another."

Something to be thankful for.

Arithmetic is being able to count up to twenty without taking off your shoes.

-- Mickey Mouse

To help reviewers better understand patient perspectives, FDA will conduct four public meetings per year on different disease areas during the five-year PDUFA cycle. That equals 20 meetings on 20 different disease areas. The information gleaned from these sessions is expected to help reviewers better understand patient needs and risk tolerance and to help spur further research.

(FDA agreed as part of the reauthorization to better incorporate patient opinions about risk tolerance and other drug development issues into its approval decisions.)

But, under the headline of “no good deed goes unpunished,” FDA is working to allay advocates’ fears that the 20 disease areas selected for public meetings will be the agency’s sole focus over the next five years.

FDA has developed a list of 39 candidate topics for the meetings, about one-third of them rare diseases – but, according reportage in the Pink Sheet, “it drew the ire of some patient groups.” Diane Dorman, NORD’s vice president of public policy said that the agency’s list has pitted disease organizations against each other.

But according to the always thoughtful Theresa Mullin (CDER’s Director of Planning and Informatics), the disease manifest “is not is any sort of priority list for FDA. According to Mullin,the proposed diseases were chosen in part because existing measures are inadequate.

“This is not to try to address all the important diseases, just ones where, in fact, we don’t have very good clinical measures, we don’t have good objective measures now, and we need to develop the best measures we can to encourage drug development,” she said.

Mullin mentioned chronic fatigue syndrome as an example because it does not have a definitive set of symptoms and obtaining more patient information would help develop more drugs for the treatment armamentarium.

The FDA is also convening several “consultation meetings” with patient stakeholders to talk about drug development issues and help formulate the direction of the disease-specific public meetings. Topics will include: resolving conflicting opinions among stakeholders, balancing the priorities of different disease areas within FDA’s limited resources, and ensuring groups outside the Washington D.C. area gain equal access to the talks.

Talk about 20/20 vision!

Yali Friedman, Publisher and Chief Editor of the Journal of Commercial Biotechnology, has an interesting and important essay on how advances in personalized medicine may have the unintended consequence of accelerating the call for US price controls – resulting in fewer new life-saving treatments.

Friedman writes:

Personalized medicine—prescription of drugs most likely to benefit and least likely to harm individual or groups of patients—promises welcome positive changes to healthcare. It may, however, also have negative sequelae originating from incompatibilities with the current healthcare delivery system and the need for regulatory and policy changes to accommodate personalized medicine.

His full article, Will personalized medicine be a driver for widespread price controls, can be found here.

Good article in the Wall Street Journal about the FDA’s efforts to make not-yet-approved medicines available to patients with life threatening conditions.

If you are a subscriber to the WSJ, the article can be found here.

Kudos to the agency – and well deserved.

Last year, nearly 1,200 patients received treatment with experimental drugs through the compassionate-use program for conditions including hepatitis C, cancer and rare diseases like cystic fibrosis. That is up from about 1,000 patients in 2010, the first year the agency compiled data on the program. The FDA says it has been trying to increase participation, including by helping to set up a Web-based seminar that trains doctors how to make use of the program.

The agency allows manufacturers to make their drugs available, but can't require them to do so, and some companies are reluctant to participate before their products have received marketing approval. The FDA says it has been working to win over more companies. It revised its regulations in 2009 to effectively open the program to a greater number of small drug manufacturers. Most companies that provide drugs for the program do so free of charge, but some seek to recoup their expenses, the FDA says. Health insurers generally don't reimburse patients for the cost of the drugs.

"We get calls from family members and there's this sense these are miracle drugs," says Richard Klein, who heads the FDA's Office of Special Health Issues.

In fact, Mr. Klein says, "you can die faster" if there's an adverse reaction to a drug. And even it if does work, it might only add weeks or months to a patient's life, he says.

OSHI doesn’t get a lot of media coverage, nor do they seek it out. But the work they do is crucial to the mission of the FDA – and to the patients they help.

Bravo.

Milton Friedman once said that the FDA was “obsessed with safety.” Some view that as a badge of honor, others not so much.

Two recent FDA advisory committee votes should please both groups.

An FDA panel recently voted 9-6 to recommend approval for Genzyme’s mipomersen for homozygous familial hypercholesterolemia. The positive vote came despite serious hepatic and other risks -- as long as every effort is made to prevent off-label use. A key mitigating factor was disease severity.

Benefit/Risk at its finest.

A second recent adcomm vote (13-2 in favor of approval for Aegerion’s lomitapide for homozygous familial hypercholesterolemia) also points to a more “needs-focused” philosophy and the committee also recommended a REMS targeted off-label use.

Safe Use is the new normal.