Say what?

The growing excitement behind the therapeutic potential of CBD oils must be tempered by a more thoughtful understanding of how these products are regulated by the FDA.

The first thing that manufacturers and marketers of need to know is that CBD is under the Dietary Supplement Health & Education Act (DSHEA). This means many things, but most importantly that CBD is considered (for regulatory purposes) as a food not a drug. This means that CBD products cannot make drug claims.

A drug claim is, “My product reduces pain.” Such claims are backed up by a New Drug Application (NDA) comprised (among other things) of clinical studies that are reviewed by the FDA, resulting in a label claim. Since CBD products aren’t approved via the NDA route, they are not allowed to make these types of claims. If they do, they are in violation of the Food, Drug, & Cosmetics Act. A majority of warning letters sent by the FDA to CBD manufacturers and marketers fall into this category. It’s also relevant to note that product web sites that share patient testimonials that refer to drug-like claims (“Your product cured my pain,” etc.) are similarly violative.

Manufacturing performance is another common way that CBD manufacturers and marketers run afoul of the FDA.  Simply put, if there are substances in the product that are not listed on the label, that product is mislabeled and that is an FDA violation. Similarly, if there are ingredients listed on the label that are not in product, or in an amount other than is listed, that is also a violation.

This doesn’t mean there’s nothing manufacturers and marketers can do to promote the benefits of CBD. Responsible use of Structure/Function Claims provide ample opportunity for FDA compliant communications. According to the FDA, 

“Structure/function claims may describe the role of a nutrient or dietary ingredient intended to affect the normal structure or function of the human body, for example, "calcium builds strong bones." In addition, they may characterize the means by which a nutrient or dietary ingredient acts to maintain such structure or function, for example, "fiber maintains bowel regularity," or "antioxidants maintain cell integrity."  These claims are not pre-approved by FDA, but manufacturers must have substantiation that the claim is truthful and not misleading and must submit a notification with the text of the claim to FDA no later than 30 days after marketing the dietary supplement. 

If a dietary supplement label includes such a claim, it must state in a "disclaimer" that FDA has not evaluated the claim. The disclaimer must also state that the dietary supplement product is not intended to "diagnose, treat, cure or prevent any disease," because only a drug can legally make such a claim. Structure/Function claims may not explicitly or implicitly link the claimed effect of the nutrient or dietary ingredient to a disease or state of health leading to a disease. 

All of this is just for starters. Promoting CBD products is a new frontier and, as with any pioneering endeavor, it requires knowledge of the risks as well as the benefits. And a good place to start is with a solid understanding of FDA regulations.

Peter J. Pitts, a former FDA Associate Commissioner, is the Chief Regulatory Officer at Adherent Health, LLC.

Cannabis Happens

One of the positive side-effects of the opioid crisis is a renewed (and long over-due) focus on new ways to advance pain management. 

One therapy, cannabis, has long been discussed as a legitimate therapeutic alternative – but has been caught up in the debate over its non-medical uses, along with its guilty-by-association cousin, hemp-derived cannabidiol (CBD). Regardless of where you may stand on these issues, we are moving forward. The times they are a-changing. And, as with many advances in healthcare policy, states are presenting themselves as the laboratories of invention.

In New York State, for example, cannabis is now a legal alternative to opioids. The policy, announced July 12th, is a result of emergency regulations filed by New York State Health Commissioner Dr. Howard Zucker. Per Zucker, medical cannabis “has been shown to be an effective treatment for pain that may also reduce the chance of opioid dependence” and that offering providers treatment options other than opioids “is a critical step in combatting the deadly opioid epidemic affecting people across the state.”

The new policy allows patients who have been prescribed opioids to request cannabis as an alternative treatment and adds several new qualifying conditions. The broadened scope of conditions will now cover patients with severe pain that is not classified as “chronic,” and also includes a provision allowing patients with opioid use disorder to use medical cannabis if they are enrolled in a certified treatment program. As part of the new program, patients and caregivers will receive ID cards that can be used along with a government-issued photo ID at registered dispensing facilities.

In addition to the new disease indications, the regulations are designed to increase certifying authority for nurse practitioners and physician assistants, and allows for the approval of five additional organizations to manufacture and dispense. Home delivery will also be permitted.

While the emergency regulations are temporary, the New York State Department of Health has filed to adopt them permanently. Currently cannabis is legally used by 62,256 patients via 1,735 registered practitioners in the existing New York State program. Health officials anticipate a reduction in opioid use and dependence, as well as a significant boost to state coffers, with legal cannabis sales expected to reach $50-$70 million in 2018 (up from $20 million last year). 

But it’s important to understand that there’s no benefit without some risk – and using cannabis for pain management and other disease mitigation isn’t risk-free. Some key issues include:

  • No Current Standard in Quality or Production

There are few guidelines when it comes to how cannabis plants must be raised for dispensaries that sell the drug to patients. Each plant could be vastly different from another grower’s plants, which in turn means that the buds will likely have very different levels of THC or CBD. A joint rolled from one plant will provide a different intensity of a high than another plant, and there is no monitoring of the patient’s use of the drug to ensure that they are finding the right type of plant for their needs.

  • No Dosing Standard

When a patient is prescribed any other type of medication, they are given a dosing schedule by the doctor telling them how much to take, how to take it, and how often. When someone is prescribed cannabis, they get a card that allows them to access dispensaries that sell the drug. They are not given any guidelines about how they should take it or in what amounts – something that would never happen with any other medication.

  • Potential for Help & Harm Through Chronic Use

Chronic smoke inhalation and overdose on edibles are just two of the risks of chronic use of cannabis that we know about. Use of the drug legally for medicinal or recreational purposes has not been studied heavily, so we don’t know the extent of the harm that can come to those who take the drug for long periods of time and/or in large amounts. The California, Colorado, and Nevada experience hasn’t yet impacted rates of use/abuse. Watch this space.

  • Easier Access = Increased Cannabis Abuse

When it becomes easier for people to get cannabis, it means that they use more and have more in their homes. This in turn means that those who don’t have medical cannabis cards – including teens and young adults – have increased access to the drug and may be more inclined to use and abuse it, developing a drug dependency when they may not have otherwise.

  • Legalization Changes Public Opinion of Harm Potential

As more and more states legalize cannabis for medicinal – or recreational – purposes, it gives the impression to those who don’t take the time to do the research that all doses of cannabinoids are harmless. In fact, for all drugs prescribed by a doctor, even prescription pills that are highly addictive like OxyContin and Percodan, the prevailing attitude is that the doctor’s okay makes them safe to use in any way or combination. Many don’t realize that a doctor’s prescription comes with guidelines for usage that must be followed for maximum safety and that since cannabis rarely even comes with this assistance, it is very important “proper use” is supported by education and technology.

For some states, the legalization of cannabis might be further than the populace is currently willing to go. But in these discussions, CBD from industrial hemp is often overlooked; typically produced in accordance with federal guidelines to contain 0.3% THC or less, hemp-derived CBD should be seen as a viable alternative to not only cannabis containing THC but also a variety of treatments that are more expensive, have discouraging side effects, or potential for addiction.

More options are better – but (as the saying goes), if you can’t measure it then it doesn’t count. Broadening cannabis’s legal bona fides for pain treatment isn’t the end of the debate, it is only the beginning. Now we must develop ways to measure its effectiveness and develop ways to capture the real-world evidence that must drive evolving best medical practice and reimbursement policies.

In the immortal words of General George C. Marshall, “When a thing is done, it’s done. Don’t look back. Look forward to your next objective.”

Stay tuned.

Peter J. Pitts, a former FDA Associate Commissioner, is Chief Regulatory Officer at Adherent Health LLC, an independent clinical engagement services company

Real-World Evidence: Nearing the End of the Beginning

The world’s greatest chess players understand that every variable (analytic, contextual, social) is interdependent and relevant. When it comes to healthcare, the goal is value and the denominator Positive Clinical Outcomes “Value” is what you want to pay for. And Real World Evidence helps us to define, capture and understand “value” for patients, payers, and providers. And these truths are as self-evident for drugs as for medical devices.

In the 21st century, the information revolution will shift from the generation of data to figuring out the meaning, purpose and value of the data with the patient’s perspective in mind. The FDA has described factors it would consider when evaluating the relevance, reliability and quality of real world evidence, and also suggests when it might use such data to make decisions about the products it regulates.

Real World Evidence (clinical outcomes data not collected in conventional randomized controlled trials) is the new star on the precision medicine horizon. However, “Big Data” and “Valid Evidence” are not the same thing. It is an important distinction that illuminates a crucial difference. Real World Evidence requires 21st Century Regulatory Science to determine and define new thinking on evidentiary standards. Nobody said it was going to be easy.

The concept driving the future is interoperability; the idea that different systems used by different groups of people can be used for a common purpose because those systems share standards and approaches. For medical device manufacturers who have heretofore devised development strategies based on predicate-based thinking, interoperability will not be as foreign a concept as it might otherwise be to manufacturers of drugs and biologics. And if you’re wondering about the future of combination products, now’s the time to put on your thinking cap.

To paraphrase Winston Churchill, when it comes to actualizing the use of real world evidence, we are nearing the end of the beginning. The road to the use of Real World Evidence is a trail that regulator and regulated must blaze together sometimes heroically and at other times with greater caution.

In the words of the British pundit Ernest Benn,

 “Politics is the art of looking for trouble, finding it whether it exists or not, diagnosing it incorrectly, and applying the wrong remedy.“

Regulators and Device Developers don’t have that option.

So, how much does an uncontrolled Type II Diabetes patient really cost?

Patients with diabetes incur approximately $10,000 more in health-related costs than matched insured patients without diabetes. Those diagnosed with diabetes incur average medical spend of $16,752 per year, with about $9,601 attributed directly to diabetes. That's the average, with many diabetes patients accounting for many times that amount. On a public health level, “care for people with diagnosed diabetes accounts for 25% of all America health care dollars.”

More than 100 million Americans have diabetes or pre-diabetes. Diabetes therapy linked to HbA1c value contracting has yet to achieve scale and remains a largely underutilized, clinically valid cost reduction tool.

While there are many variables, this urgent public health question is just a practical mathematical problem. In the endless pursuit to lower A1c lab values and the Holy Grail of lowering escalating diabetes-related costs, it’s time for insurers and payers to “flip the table” by limiting brand diabetes Rx reimbursement to tiered performance payments for achieving and sustaining validated A1c outcomes on a per patient basis. There’s no other way out. Manufacturers, PBM and payers must demonstrate diabetes formulary value. Pronto!

It’s simple, right?

  1. The good news is that there is no shortage of quality diabetes-controlling generic and biosimilar medicines marketed by the same innovator pharmaceutical companies that also market brand name medicines. AWP? Forget about it. Rather, focus on packages of therapies, and hub-style services, that can be efficiently bundled on a per plan member basis. A payer’s reimbursement reward can be scaled to the degree of success in attaining maintaining, an appropriate A1c goal.
  2. We’ve come a long way from the early days of Medco-style disease management. Digital technology is transforming the practice of patient care, patient engagement, clinical pharmacy, and lab testing. Even beyond EHRs, newer simplified patient-centered clinical engagement platforms now connect providers and payers. Low-cost lab services exist to clinically validate and monitor A1c values directly from a patient’s home. No trip to Quest or Lab Corp, all without a phlebotomist, without an appointment, without a blood draw. All with CAP and CLIA accreditation and diagnostic quality. Continuous A1c outcomes transparency for diabetes populations has arrived.

What’s the catch?

So, instead of asking, how much poorly controlled type II diabetes patients cost, its more strategic to ask "how much is a well-controlled diabetes patient worth to the Payer/Insurer"? To society? To the patient with high deductible plans? To the PBM team managing the diabetes medication formulary? To society?

Reducing the costs of Type II Diabetes is worth a lot to public and private insurers. And manufacturers have the opportunity to shift to higher and more sustainable per patient reimbursement by getting paid primarily through A1c performance contracts for a defined proportion of a plan’s covered lives. That’s real value-based reimbursement.

Can it be done?

Pharma has the tool set right now: 

  1. Brand, generic, and biosimilar diabetes treatment portfolios
  2. Proprietary and licensed patient engagement services and programs
  3. Professionally staffed digital hub service resources designed to efficiently onboard patients, sustain adherence, and to support safe-use of medication

In seamless combination, one patient/insurer/payer at a time, it can be done.

Rob Dhoble


Adherent Health, LLC

FDA and the Digital Divide: The Battle of Proof & Predicate vs. Errors & Upgrades

The FDA's patient focused drug development program is about integrating the "patient voice" in all aspects of the drug development ecosystem. This means the patient voice must continue to evolve beyond "teller of sad stories." Emotion shouldn't play a role in scientific decisions and the plural of anecdote isn't data.

There is a yawning divide between regulatory science and digital development. Digiratti view regulators as stodgy while regulators view digital developers as trigger-happy. There is an unproductive cognitive disconnect.

What is most crucial for the FDA is to understand and consider is how patients (and families and caregivers) view risk and benefit in their own lives ("the real world") rather than in the rarified world of a randomized clinical trial. When we consider the integration of new and exciting digital technologies (ingestible, implantable, portable, app-based, diagnostic, etc.), it's likely that technologists are far more likely to be excited about the possibilities rather than considerate of the risks. The same cannot necessarily be said of regulators/reviewers who reside within a culture of proof and predicate. Technologists inhabit a planet of errors and upgrades. There is no "Beta" approval pathway for the FDA.

For the FDA, risk exists to be minimized while for digital developers risk is an opportunity. Fortunately, there is common ground – and it isn't the technology. It's the public health need for which the technology presents a safe and effective (within the FDA definition of that duality) solution. Interestingly, it's the drug developer who must now play the role of “learned intermediary” between regulator and technologist -- a new and uncomfortable role. But the pay-off is worth the effort for sponsor, regulator and public health advocate -- better patient outcomes through more evolved 21st century technology integration.

Consider Adherence/Compliance, a public health problem of brobdingnagian proportion nowhere more acutely felt than in patients with schizophrenia. That's why products that address new and innovative solutions (such as Abilify MyCite, a pill with a sensor that digitally tracks if patients with schizophrenia  have ingested their medication) are so exciting to developer, regulator and patient alike. It's a real world example that should provide momentum for continued development beyond this one therapeutic area. As real world data becomes available, the FDA will hopefully feel increasingly comfortable expediting similar programs (specifically) and programs with more innovative uses of digital technologies (more broadly).

Positive signals from the FDA will send potent messages to developers that further investment in such clinical programs is worth the investment risk. Positive signals emanating from “the patient voice” will be crucial.

Peter J. Pitts, a former FDA Associate Commissioner, is Chief Regulatory Officer at Adherent Health, LLC

Unleashing the Potential of the CDC Guideline for Opioid Prescribing

When it comes to addressing our national opioid epidemic, there are many opinions, lots of suggestions, high-minded rhetoric, an abundance of media attention, and even a Presidential Commission report replete with thoughtful analysis and recommendations.

And then there’s the on-going debate over the value of the Centers for Disease Control (CDC) Guideline for Prescribing Opioids for Chronic Pain.


It’s always best, when trying to solve a complicated problem, to start at the beginning. Determining when a physician should (per the CDC) “initiate or continue opioids for chronic pain,” is both a logical beginning and a crucial inflection point for what happens afterwards. It’s not about blame. It’s about focusing on the practice of medicine – and the important role prescriber/physicians have in solving the problem.

Admiral Hyman Rickover, the Father of the American Nuclear Navy, said, “Good ideas are not adopted automatically. They must be driven into practice with courageous patience.” Now that we have the CDC Guideline, what are we doing to infuse it into daily medical practice? Posting it on the CDC website is a good start. But it’s not enough. Suggesting it be improved and enhanced (as does the Presidential Commission) is a good idea – but have we already saturated the national opioid ecosystem with the existing guideline? Not even close. What we need to do is create a program to educate prescriber/physicians about the CDC’s 12 recommendations with a measurable goal of 100% recognition.

Is that an impossible dream?  Is it really beyond our collective capabilities to (at minimum) certify that all American opioid prescriber/physicians have a basic knowledge of the CDC Guideline? After all, if doctors are to appropriately fulfill their roles as “learned intermediary,” is it too much to ask, before pen reaches prescription pad, that they have been exposed to the CDC’s suggestions for (1) determining when to initiate or continue opioids for chronic pain, (2) selection, dosage, duration, follow-up, and discontinuation, and (3) assessing risk and addressing harms of opioid use?

Having the Guideline isn’t enough. “Knowing about it” doesn’t cut it either. We must take actions that result in its use. We must work together to ensure that prescriber/physicians know what the Guideline suggests. “Best practice” is of no use unless it results in better practice. What percent of American prescriber/physicians can even say they’ve read it? We don’t know. We need to know.

Step One is a program to determine how far the Guideline has permeated the medical community. This can be done via mobile technology and it can be (indeed must be!) done swiftly to provide us with a benchmark. Our goal should be 100% awareness in 12 months. Too fast? Too slow? There are surely good arguments on both sides. But a year is a finite unit with no fudge factor. Ultimately, we can achieve success – if we want to.

Aggressive and timely physician education is also crucial to protect against the unintended consequence of having the Guideline misused as a blunt instrument to create an epidemic of denying appropriate care to patients in need. Proper “assessment” is not a synonym for denial of proper, patient-focused opioid prescribing.

What are the motivations for prescriber/physicians to become certified? There can be both positive and negative incentives. For example, the Drug Enforcement agency’s (DEA) triennial recertification for opioid prescribing could insist on CDC Guideline certification. (Through the existing REMS programs for ER/LA and IR opioids, mandatory physician (re)certification via the DEA is a potential solution). State medical boards could require it for relicensing, medical schools could include it in their core curriculum; the FDA could include a reference to the CDC Guideline on all opioid product labeling (the size of the print doesn’t minimize the importance of the language); pharmaceutical companies could “detail” the Guideline when their sales representatives visit with physicians.

What about payers? Perhaps insurance companies and Prescription Benefit Managers (PBMs) could lighten the prior-authorization load for “GC” (Guideline Certified) prescriber/physicians. What about slightly higher reimbursement rates from CMS and private payers? What about lower malpractice rates for GC prescribers?

Importantly, individual consumers and patient groups can and should shape such an approach. In the Age of Yelp, a potent tool in the “GC” arsenal would be an app-based public database that patients and caregivers could access to see whether or not a physician is Guideline Certified. Health plans could also make it a mandatory designation for “in network” inclusion.

Who creates the certification program? Who creates the “GC app?” Who launches the research project to determine current knowledge of the CDC Guideline? Who monitors progress? Who promotes the challenge? Who sits at the table? Who chairs the effort? How much will it cost? How is the Guideline reviewed and revised? There are a lot of details to work out.

Opioid abuse is an ecosystem problem that requires an ecosystem solution. To infuse the CDC Guideline into practice will take a village – and a stopwatch.

Public health illuminati, start your engines.

Peter J. Pitts is Chief Regulatory Officer at Adherent Health, LLC

Regulatory Learning from the Real World

In March, the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety and Risk Management Advisory Committee (DSARM) voted 18-8 that Opana ER’s benefits do not outweigh its risks. And on June 8th, the other shoe dropped.

"After careful consideration, the agency is seeking removal based on its concern that the benefits of the drug may no longer outweigh its risks," the agency said in announcing the move. “This is the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse."

The FDA said it was asking Endo to voluntarily cease marketing Opana ER. But it added that if the company refuses, the agency will "take steps to formally require its removal by withdrawing approval."

The FDA said its data indicate that the abuse of the drug has shifted from snorting to injection following reformulation in 2012, which was intended to help the pills resist physical and chemical manipulation. Subsequently, Opana ER was associated with a notorious outbreak of HIV and hepatitis C infection in rural Indiana two years ago, caused by needle-sharing among opioid addicts.

"The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, in a statement. "This action will protect the public from further potential for misuse and abuse of this product."

What can we learn from this action? First, that when a product’s risk/benefit profile is carefully monitored, aggressive action can be taken in a timely manner. But should we need an outbreak of HIV/AIDS and Hep-C to sound the alarm?

Kudos to the FDA for taking appropriate action to protect the public health – but we need more. Specifically, we need the agency to work with sponsors o design more and better early warning mechanisms so that a problematic product can we recalled before dire consequences ensue. That means new and more immediate ways to collect, analyze, and share real-world evidence.

It’s time for apps to take center stage in the battle against opioid abuse.

Peter J. Pitts 

Chief Regulatory Officer

Adherent Health, LLC

Chairman, MHL Standards & Practices Committee

Mooning Healthcare

An interesting post at OhMD discusses: Patient Portal is Dead

A New Study: Healthcare's Digital Divide Ushers in a New Year of Patient Distrust, Black Book Consumer Survey

Showing that “96% of patients report leaving their doctor’s office with limited knowledge of how to use the patient portal. Of the 40% of patients who said they had attempted to use the patient portal in 2016, 83% said it was too complicated to use.” That means only 7% of patients find it simple enough to use, and actually care to use it.

As the folks at OhMD quip, “As a point of reference, 7% of the American population also believes the moon landing was faked, if that helps give you some perspective.

Why? Consumer technology (the apps we all use in our daily lives) typically solve a problem in a very simple way.

As I’ve said before – healthcare app-ens.

Peter J. Pitts 

Chief Regulatory Officer

Adherent Health, LLC

Chairman, MHL Standards & Practices Committee

A Virtual Ounce of Prevention

The best way to reduce opioid abuse is to reduce the number of opioid tablets being dispensed. That means we need smarter physician prescribing habits. According to the results of a Columbia University Medical Center (published in American Journal of Psychiatry), “people with moderate or more severe pain had a 41 percent higher risk of developing prescription opioid use disorders than those without, independent of other demographic and clinical factors.”

In other words, it’s not just fewer opioids for patients with less severe pain or with conditions for which there are non-opioid alternatives (such as fibromyalgia and diabetic neuropathy). It means we need better ways of tracking the patient experience. One solution to narrowing the gap between prescription and outcomes measurement are mobile apps. The gathering and appraisal of real world evidence can expedite identification of problems before they become deadly. If we can identify misuse earlier, we can help eradicate abuse and addiction.

Apps present us with just that opportunity – a virtual ounce of prevention.

Peter J. Pitts

Chief Regulatory Office

Adherent Health, LLC

Chairman, MHL Standards & Practices Committee

Promotional Review Teams—Getting it Right

The 4th Promotional Review Committee Compliance & Best Practices, sponsored by ExL, was chock full of information designed to improve the effectiveness and efficiency of promotional review committees. The event, moderated by John Marcus, Associate Director, Regulatory Affairs at AbbVie, and Rebecca Rivera Torres, MS, RD, CSSD, Senior Promotional Review Associate at United Therapeutics, tackled such thorny issues as overcoming the hurdles of reviewing search engine marketing techniques, reviewing adaptive promotional websites, simplifying the review of co-promoted drugs, approving materials for medical scientific liaisons (MSLs), and reducing late submissions.

“With the FDA regulations ever evolving, this biannual event offers a prime opportunity to discuss innovative promotional ideas that are being implemented now and those on the horizon,” states Torres. “Key members of promotional review committees from across the pharmaceutical and biotech industries come together to brainstorm ideas to resolve issues that arise during the review of sales, marketing, and training materials, with the end goal of optimizing the process for the industry’s benefit.”

Planning Models

“A well-developed review process requires a planning model that meets goals for consistency, efficiency, compliance, and accurate and adequate resources,” states Elizabeth Theophile, Director, Promotional Materials Compliance Management, Commercial Strategic Operations at Sunovion Pharmaceuticals. “This planning model should be implemented early in the process and must have the support of leadership.”

Co-Promoted Products

According to Marcus, early collaboration is key for co-promoted products where the review of promotional materials involves multiple stakeholders. “To simplify the process while building relationships, companies must set early expectations, define roles of each team member, make decisions together, and use previous experiences to explain comments and discuss processes.”

Overcoming Roadblocks

UCB has undertaken a comprehensive effort to create a highly efficient review process that overcomes roadblocks commonly experienced by manufacturers. These can include turnover in marketing teams/agency partners, limited review experience, and incomplete knowledge of advertising/promotional regulations.

“Content creators need to know basic FDA regulations and requirements; company policies and guidelines; product information/data and brand information,” underscores Ariail Roberts, Senior Manager, Review Services at UCB.

According to UCB’s Jan Jeffords-Schenck, Associate Director Review Services, the company is embarking on a comprehensive initiative that begins early in the review process to streamline reviews, reduce duplication, and drive a co-creation mindset among all stakeholders.

Specifically, the initiative combines live onboarding training, formal certification processes, and mentorships for content originators. Additionally, continuing education features stakeholder meetings and webinars to share challenges and best practices, and discuss hot topics and dissect FDA letters. The company is in the process of developing a training curriculum with an entry-level assessment test to quantify baseline knowledge and focus on specific training needs.

FDLI and Mobile Apps

Like the ExL conference, the Food and Drug Law Institute (FDLI) addressed the use of mobile apps in a panel format featuring diverse perspectives from marketing, communications, and policy.

“The FDA is very supportive of apps that advance the public health through promotion of safe use and outcomes support,” says Peter Pitts, a former FDA official who is currently consulting in this area.

Shalu Bhambhani, Business Insights and Operations Manager, Shire Leadership Development Program, adds, “There are so many opportunities to deliver on public health needs for patients, caregivers, and providers.” Bhambhani suggests working with review teams to execute live pre-tests of desired app functionalities in a secure testing environment. “Another best practice is to ensure consistency across teams regarding regulatory compliance requirements. It’s important to level set expectations by training and testing team members to overcome any variations in knowledge and experience which can slow down reviews.”

Alexis Pone, Vice President, Account Supervisor at JUICE Pharma Worldwide, says, “The prospect of developing a new medical app is equal parts exciting and daunting. Marketers often feel paralyzed by pre-conceived notions about regulatory constraints, lack of regulatory digital acumen, and unclear or under-communicated company guidelines, all of which can impede app development.”

On a final note, Pitts, who is now Chief Regulatory Officer at Adherent Health, adds, “There’s a difference between what’s in compliance and what a company views as its own internal best practices.” That needs attention.

Compliance Center by Ilyssa Levins on January 18th, 2017

The Abuse Deterrent Opioid Ecosystem

I've said it before and I'll say it again, addressing opioid abuse and addiction isn't just a formulation problem ... it's a systems problem.


Consider Utah Attorney General Sean Reyes' op-ed on opioid abuse (A smart way to counter prescription drug deaths). There are a few things that need to be added – and amended.


The vast majority of patients using non-abuse deterrent opioids do so safely and as directed. A subset, approximately four percent, abuse. And government statistics show that 78.5% of those who abuse prescription pain medication did not obtain the drugs from a physician in the first place.


Should non-abuse deterrent opioids ultimately disappear from the marketplace? Absolutely. But removing an entire category of generic products when there are no generic abuse deterrent alternatives not only does eradicate the abuse and addiction problem (since even abuse deterrent opioids can be abused) but punishes the millions of Americans who need opioids to address their chronic pain. Insurance companies are not ready to regularly reimburse for new, abuse deterrent formulations – despite steep discounting by manufacturers. The numbers are staggering -- 240,120,330 non-ADF generic opioids were prescribed in 2015 (nearly a quarter of a billion tablets) versus 5,068,398 branded opioids with ADF properties.


Further, payers often implement barriers to the use of branded, on-label non-opioid medicines, relegating these treatments to second line options. 52% of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment as do 43% of patients diagnosed with fibromyalgia and 42% of patients with diabetic peripheral neuropathy even though there are FDA-approved, non-opioid medicines specifically designed and labeled to treat these conditions.


Payers should step up to the public health plate and do the right thing right now.


Should the FDA, as General Reyes suggests, “… commit to following recommendations made by its advisory committees?” No. That is not the role they play. FDA Advisory Committees advise. It is (and should remain) up to the experts at the FDA to make the final decision. Ultimate responsibility must always reside with the regulator. (The FDA advisory committee that reviewed the controversial opioid Zohydro voted 11-2 that there was no evidence to suggest it had greater abuse or addiction potential than any other opioid.) 


Most importantly, a smart public health strategy would be a robust effort to better educate physicians on appropriate prescribing – something the FDA has been calling for regularly. Today the agency announced it will require short-acting opioid pain medications to carry a boxed warning about the serious risks of misuse, abuse, addiction, overdose and death. It’s a good next step – but an even better one would be working with patients, caregivers, and physicians on better use of 21st century technologies (apps, social media, etc.) for tracking and measuring patient understanding and therapeutic outcomes. of safety info perhaps?  Promoting "safe use” can (indeed must) take many forms.


Peter J. Pitts

Chief Regulatory Officer

Adherent Health, LLC

Chairman, MHL Standards & Practices Committee

Safe Use App-ens

Late last year the FDA announced it’s “Safe Use of Drugs” Program. The theory behind the concept of safe use is that drugs can be made “safer” through patient education. A medical product “used as directed” is “safer.”

As former FDA Deputy Commissioner Joshua Sharfstein said, “The aim of the Safe Use Initiative is to identify specific preventable problems related to medication use and identify specific metrics that can measure progress; and to do it all by developing collaborations.”

Patient education is one thing – how to deliver that information is something else. And in the 21st century that means smart phones, tablets, and … mobile apps.

Consider the value of HIPAA-compliant Mobile Health Library (MHL) and the patient user experience.

For one prescription medicine (anonymous here due to client confidentiality), physicians who prescribed the drug also “prescribed” a brand-specific Patient Support App from Mobile Health Library – with important results.

After an initial test period, 4,062 distinct content engagement experiences by 1,200 patients (who received the brand-specific app at time of prescription) interactions with educational content related to Brand Safety Information ranked highest (42%) followed by educational content “about brand” (30%) and educational content “about condition/diagnosis” (28%). 

Per Sharfstein, “Partnerships will be important in the Safe Use Initiative. Clearly the clinical community is an important partner. Pharmacies have a very important role. Insurers should be engaged as they have the access to patients and know what is being prescribed. Pharmaceutical companies also have a vested interest in seeing their medicines used well.”

When it comes to making safe use a reality – mind the MHL app.

Peter J. Pitts

Chief Regulatory Officer

Adherent Health, LLC

Chairman, MHL Standards & Practices Committee

How to make pharma Rx support apps better? Get REAL.

Most Pharma Patient Apps:  Maybe not so good

I’m certainly not the first to describe the generally woeful nature of most patient apps developed for prescription medicines by manufacturers.  Pharmaceutical companies have a lot of apps in the market, and have been making apps for a long time, but their apps aren’t seeing downloads and usage on par with the apps from other industries.”

So what are the specifics?

Approximately two-thirds of apps published by the pharmaceutical industry are only in iOS/Apple device format.  In a world where over 50 percent of the population is using Android and Kindle Fire based devices?  Why?  Colleagues report that many iOS app pilots never quite make it to being full iOS/Google Play/Amazon app store commitments, often due to a lack of meaningful app performance metrics, and changes in marketing management.

Since most existing pharma patient support apps are rarely used (and often quickly deleted), what do prescribers and patients really want?

Privacy. Few Rx patient support apps are privacy protected, are HIPPA-compliant, or even have privacy policies.  When surveyed in late 2012, a SERMO recruited multi-specialty physician panel (results depicted below) reported that patient privacy protection was among the most important patient app benefits desired.

Adherence. Affordability. Education. Feedback. A simple review of pharma app offerings finds that very few apps have most of the attributes that patients, nurses, and their physicians want.   Some patient apps are not for patient support at all, but are reconstituted DTC acquisition mobile websites that offer little if any app-specific functionality or patient support services (Xarelto Patient Center as one example). Some apps remind for dosing or patch rotation (PatchMate, Exelon).  Some apps support planning and tracking of injection sites (Copaxone iTracker).  Some include access to copay savings cards and coupons. Many support some type of branded or unbranded education.   But very few support feedback of patient-reported outcomes. On this very timely topic, recent announcements by Biogen Idec and Novartis preview an emerging reimbursement strategy, with new “table stakes” that include real-world tracking, monitoring, and demonstration of Rx safe-use and outcomes-attainment. 

Biogen Idec recently announced the use and potential expansion of FitBit strategies to track physical activity rates for MS patients taking their MS brands.   Biogen Idec CEO George Scangos says he’s confident his company will be able to provide useful information to doctors, who can then “hopefully intervene earlier, and that should save the payers money and should result in better outcomes for patients.”

Novartis CEO Joe Jimenez went a step further during a speech in November 2014.   As reported by Reuters, “Jimenez is convinced remote monitoring technology will play a central role in this respect, both to help healthcare systems check if patients are improving and also to protect companies that need to ensure they are not penalized for a drug failing if a patient does not take his or her medicine.”  Said Jimenez, "It doesn't mean we will own the technologies, but it does mean the technologies will play an important role in the management of disease." 

For too many in the pharma industry, unfortunately “patient-engagement” still means direct marketing, patient acquisition and website clicks. As more payers become hungry for “real-world” outcomes-attainment tracking of specific pharmaceutical brands, industry Rx Patient Apps must more measurably support medication safe use and health outcomes attainment.  With such apps now having a seat at the reimbursement table, helping to re-define what “preferred” formulary medications really means.


Rob Dhoble

President, Adherent Health LLC


Safe-Use? It’s All About The Base

The joke inside the FDA is that the Brief Summary is like the Holy Roman Empire – neither brief nor a summary. Funny for the FDA – and an important jump-starter for a serious question – how can safety information be more user-friendly . To quote one of my favorite doctors, Dr. Seuss, “Sometimes the questions are complicated and the answers are simple." If it’s all about safe-use, to paraphrase some pop culture, it’s all about the base for both the FDA and pharmaceutical marketers.

The theory behind safe-use is that the best way to make any drug safer, it to ensure it is used as directed. That means putting that information in places and formats that are most accessible to patients. And in 2015 that means mobile apps. New user data from Mobile Health Library (MHL) confirms that, when Important Safety Information (ISI) is made mobile-friendly, it’s regularly accessed by on-treatment patients.

Consider one year’s worth of data for MHL’s patient support app for generic Exemestane. Of all the engagement activities available to the user, “Side Effects & Safety” rank first (at 28%), followed by “Savings & Refills" (16%), “About Condition" (15%), “About Exemestane” (14%), and “Dosing Reminder” (13%).  And the safe-use numbers for branded medicines are even higher. For one medicine (a branded epilepsy treatment), patients are accessing the Med Guide at 90%+ rates.



If it’s about giving the patients what they want – then it needs to be about giving them safety information in the ways they want it. When it comes to safety, it’s time for both the FDA and Big Pharma to start saying “App-y New Year.”

Peter J. Pitts

 Chief Regulatory Officer 

Thinking about apps? Think about your bathroom.

According to an article in Fierce Pharma, “Big Pharma has plenty of apps up for grabs, with companies like Sanofi, Boehringer Ingelheim and Johnson & Johnson rolling out flashy new products to pique consumers' interest. But as it turns out, not too many consumers are downloading them.”


Stand-alone pharma “…apps aren't appealing to the masses. Nearly half of pharma companies are only targeting local markets, distributing their apps in 3 or fewer countries. Drugmakers also tend to build their app portfolios around specific products, rather than tailoring their approaches to fit popular demand. The app market for health tracking, weight loss and fitness management is booming, and pharma companies that cash in on the trend could stand to benefit the most …”.

Here’s another way to look at it, consider your bathroom. How many medicine cabinets do you have? Answer: one. Now think about apps. Why would you want one app for every medicine you take? Wouldn’t one “medicine cabinet” app with all your medicines in it make better sense. One app with information on all your medicines’ safety information, dosing reminders, educational materials, even co-pay cards – and interactive communications with all your various healthcare professionals.

Now think about your weather app. Do you have a different app for every city? Of course not. You have one app with every city you're interested in. Same idea.

That’s the Mobile Health Library value proposition – one health app per patient, not one stand-alone app for every medication. Just like LinkedIn, Facebook, and Yelp.

Peter J. Pitts                                                                                                                                                         Chief Regulatory Officer

The complete Fierce Pharma story can be found here:

It’s an MHL App-ening!

The Food and Drug Administration has ruled that some products of health IT are not the same as medical devices and thus not subject to healthcare regulations. This according to the agency’s April publication of a framework

According to the Federal Times:

The FDA declaration goes even further, noting that even IT products that straddle the line still will be exempt. “For most health IT products that may be considered devices, FDA does not intend to focus its oversight on them,” said Bakul Patel, senior policy advisor for the FDA’s Center for Devices and Radiological Health.


Mobile Medical App is a category of mobile apps defined by FDA as “apps that consist of features of a regulated medical device by using attachments, sensors, or other such methods”.

Some examples of mobile apps that fall in this category include:

  • Mobile apps that connect to medical devices to control them or to display, store, analyze or transmit patient specific medical device data.
  • Mobile apps that transform a mobile platform with device functionality by using attachments, display screens, or sensors.
  • Mobile apps that perform patient specific analysis and provide patient specific diagnosis or treatment recommendations.
  • Mobile apps that use patient specific parameters to calculate dosage or create dosage plans for radiation therapy

Classification of Mobile Medical Apps:

Mobile medical apps have been classified into 3 categories:

Class I: No FDA review required and are considered least risky. For such devices, as long as they meet FDA-set standards they are ready to be marketed.

Class II: They are considered to be moderately risky. This category of devices requires the manufacturer to file pre-market notification. Pre-market notification means that the device manufacturers will be required to notify FDA of their intent to market a medical device at least 90 days in advance.

Class III: They are considered to be highly risky and will be under FDA scanner. Class III devices will need premarket approval. This is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. They may be defined as apps that support human life, play a critical role in preventing impairment of human health, or which presents a potential risk of illness or injury. These devices almost always must be approved by FDA before they are allowed in the market, and typically rely on the evidences obtained through clinical testing (i.e. on humans) to prove that they are safe and effective.

Mobile apps, entities, activities not under purview of FDA regulation

Examples under this category include:

  • Entities that distribute mobile apps such “iTunes App store” or the “Google Play store,” are not considered as medical device distributors by FDA
  • Mobile apps developed solely for non-clinical research, teaching or analysis and not introduced into commercial distribution
  • Mobile apps that are essential e-copies of medical textbooks and reference material
  • Mobile apps used for provider or patient medical training and education
  • Mobile apps used to automate operations in a healthcare setting and not for use in the diagnosis or treatment of disease (i.e., (i.e., dosing reminders, scan-to-refill, e-diaries, sign-and‐send e-forms, and multi- language options)

Mobile apps that function as an electronic health record (EHR) system or personal health record system.


Peter J. Pitts, Ph.D.

Chief Regulatory Officer

EFPIA Goes Mobile

According to the European Federation of Pharmaceutical Industries and Associations new “Manifesto for an Integrated Life Sciences Strategy in Europe,” drug manufacturers in Europe are missing out on opportunities for growth and patient outreach because they are failing to understand the value and potential of mobile health applications.

Per EFPIA’s director general Richard Bergström, “This is going in the direction of better patient compliance, adherence and motivation as well as an emphasis on health literacy and mobile apps … We need to find a way to unlock both the perceived and real regulatory hurdles, because I am not sure that the regulatory barriers are that high, and I think we are just being held back by conservatism.”

Bergström’s views are supported by the EU’s executive European Commission, which launched a Green Paper and consultation on mHealth in April this year. Its purpose is to examine existing barriers and issues related to mHealth deployment and help identify the right way forward to unlock its potential inside the 28-nation system.

Peter J. Pitts, Ph.D.

Chief Regulatory Officer

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"Wiggle" my Aunt Fanny

OPDP reminds us that it's not the platform -- it's the content. (Or in this case, the lack thereof.) 

According to an article in Medical Marketing & Media,

The latest proof that the FDA is not giving social media outreach wiggle room, even though communications guidelines are not due out until this summer, is an untitled letter to Institute Biochimique and US partner Akrimax Pharmaceuticals over a Facebook page for its hypothyroidism drug Tirosint.

Not so fast MM&M.

It seems that, per OPDP, the Facebook page failed to “communicate risk information” and omitted material facts.

There should never be “wiggle room” for that. Not ever – especially for a drug with a boxed warning.

“Wiggle Room?” Hardly.

How about “proper oversight?”


Well done, OPDP.

AB Fab

California Assemblywoman Susan A. Bonilla has partnered with the California Pharmacists Association and the California Healthcare Institute to introduce legislation (AB 2418) that improves the process for medical patients to obtain their prescription drugs and follow their doctor's instructions on taking their medications.

"Poor medication adherence costs the US health system $290 billion dollars in other health care expenditures, such as emergency room visits and unnecessary physician office visits," said Jon Roth, Chief Executive Officer for the California Pharmacists Association. "Assembly member Bonilla's legislation will go a long way to improving medication adherence by allowing patients to receive their medication in a way that is most convenient to them and all those medications to be synchronized with all their other drugs, resulting in the best chance for a patient to successfully complete all of their prescriptions."

Specifically, this bill:

  • Allows patients to opt out of their health plan’s mandatory mail order program if they prefer to obtain their prescription drugs from a community pharmacy.
  • Streamlines prescription medications by placing the patient’s medications on the same refill schedule.
  • Allows patients who run out of prescription eye medications because of accidental spillage or who use more than 70% of their eye drops to be eligible for an early refill.

Pharmacy programs seem to be the best way forward, and there’s hard data to back that up. Case in point – the successful Appointment-Based Model program being used at Thrifty White, a Midwest chain of pharmacies. (For more information on the Thrifty White program, see the article, Adherence and persistence associated with an appointment-based medication synchronization program, from the December 2013 edition of the Journal of the American Pharmacists Association

By creating processes that support and improve patient access to medications; patients experience better health outcomes and improved quality of life. Patients who pick up their medications at their local pharmacy have the opportunity to talk with their pharmacist about how to properly take their medications and to understand the positive benefits of taking their medications.

Peter J. Pitts, Ph.D.

Chief Regulatory Officer

As I See It: Small is the new Big

Small is the new Big.

It's fast becoming an n of 1 world, where every disease is an orphan disease and success is measured by individual outcomes rather than large population studies such as CATIE or ALLHAT or the multitude of programs being funded by PCORI.

Small is the new Big means we must also think differently about pharmacovigilance. While we must continue to capture adverse event data, we must also strive to capture Substandard Pharmaceutical Events (SPEs). SPEs occur when a product does not perform as expected—perhaps because of API or excipient issues. SPEs can arise because of an issue related to therapeutic interchangeability. When it comes to 21st-century pharmacovigilance, we have to both broaden and narrow our views about bioequivalence to the patient level. Small is the new Big.

When it comes to drug development, adaptive clinical trials and companion diagnostics further define the urgency of small-scale thinking.  Demonstrating outcomes on an n of 1 level is crucial not just for 21st century healthcare technology assessment but also for physician pay-for-performance measures and the benefit of actual patients.

There's a lot of lip service paid to the comment that “the era of the blockbuster is over.” Now consider that statement from the perspective of another industry­—in the 21st century would you rather be Blockbuster or Netflix?

Small is the new Big. That means a focus on individual patient outcomes, which means a focus on the individual patient rather than the general population and on long-term care rather than short-term cost.

And it's about time.


Peter J. Pitts, Ph.D.

Chief Regulatory Officer