Passing the Rupee

09/23/2013 07:19 AM |

In an interview with in-PharmaTechnologist.com, India’s Deputy Drug Controller, S. Eshwar Reddy, said some pretty honest – and frightening things about his nation’s perspective on global good manufacturing practices (GMP) – or purposeful lack thereof.

When asked if Indian manufacturers -- which produce more than 40 per cent of the API used in the US and Europe -- should be more sympathetic with Western guidelines and regulations, Reddy said the opposite should be true.

He said any additional requirements made are the sole responsibility of the authority which issues them.

“If the importing country has specific GMP requirements, that is their responsibility to audit the facilities. It is the responsibility of the importing country not the exporting country.”

Talk about passing the rupee.

“Being the Indian drug regulatory authority we don’t have any monitoring mechanism of other countries’ regulations. Each country has their own set of laws so Indian regulatory authorities don’t have any control.

So much for global regulatory fraternity.

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No Room at the INN

09/20/2013 10:51 AM |

BioCentury reports that the Generic Pharmaceutical Association has requested (via Citizen's Petition) that the FDA allow biosimilar and interchangeable biologics to use the same international non-proprietary name (INN) as reference biologics. GPhA said requiring different INNs for biosimilars and the original biologic would "inaccurately suggest that these products have meaningful clinical differences for patients."

The petition asserts that FDA lacks legal authority to require separate INNs for biosimilars. GPhA also noted that FDA has allowed originator biologics, including antihemophilic factors, to share an INN even if they differ in manufacturing method.

The agency is developing a guidance document on naming biosimilars and interchangeable biologics. According to Rachel Sherman, CDER’s Director of the Office of Medical, the naming policy will be designed to ensure that products can be tracked and traced, "Pharmacovigilance is our prime concern; we need to know who is getting what." noted Sherman.

Smart money (and savvy public health practice) predicts the petition will be denied.

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The Other Dr. J

09/19/2013 09:17 AM |

Last night I attended an elegant dinner at the New York Public Library (sponsored by Johnson & Johnson and Scientific American) where the 2013 Dr. Paul Janssen Award for Biomedical Research was presented to Dr. David Julius.

Dr. Julius received the award for his role in identifying the molecular mechanisms of touch, pain, and thermosensation. A scientific slam-dunk.

The highlight of the evening wasn’t the chicken and rice pilaf – it was Dr. Julius’ speech where he highlighted the inherent tension (“not conflict”) between the translational research and “curiosity-based science.”

A bold topic in a room filled with J&J’s top brass.

And an important topic for a number of reasons, not the least of which is the steady decrease on NIH funding for academia (a trend likely to continue unless they strike oil in Bethesda) and the nascent uptick in the outsourcing of pharma R&D to ivy-covered halls.

Per Dr. J, academe and industry and Uncle Sam are going to have to find new ways not only to mutually co-exist – but also to fruitfully collaborate.

At the end of the day it’s all about encouraging innovation, both incremental and discontinuous.

(I asked Dr. Julius to send me his remarks, and when they arrive I will be sure to post them.)

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Arms and the Man

09/19/2013 07:57 AM |

During a visit to a facility of leading Indian drugmaker Ranbaxy Laboratories Ltd last year, U.S. inspectors found that a black fiber embedded in a tablet may have been a hair from an employee's arm, according to documents seen by Reuters.  Read More & Comment...

A Decade of D

09/18/2013 09:45 AM |

On a wet and cold December 8, 2003, I sat in Constitution Hall and watched President Bush sign Part D into law. I helped (in my own small way) to make it happen. It’s something of which I’m proud.

Nearly a decade later that pride is stronger than ever. A new, nationally representative survey shows that an overwhelming nine out of 10 seniors with Medicare prescription drug coverage are satisfied.

·      Ninety-seven percent report that their coverage works well, and nearly three out of four seniors say it works “very well.”

Some specifics:

Part D Reliability at Its Highest Level: Those feeling “peace of mind” by having Part D coverage reached an all-time high level of 96 percent this year, with 73 percent saying they feel a “great deal” of peace of mind and 23 percent saying they feel “some” peace of mind.

Multiple Factors Drive High Satisfaction: Of those surveyed, 95 percent say their plan is convenient to use (a six percent increase from 2006), 84 percent say both their premiums and copays are affordable, and 88 percent say that their Part D plan is meeting their expectations.

Seniors Know What to Look for in a Part D Plan: Seniors believe that a variety of factors are important when deciding on a Part D plan. Eighty-eight percent think that the co-pays or coinsurance amounts are important, 86 percent believe that identifying the pharmacies where they could use their benefit to purchase their medicines is important, and 81 percent believe that the quality ratings of the plan are important to examine.

High Satisfaction Seen across Major Demographic Groups: High satisfaction levels within African American (95 percent) and Hispanic (94 percent) constituencies, as well as within various income levels (93 percent for both those earning less than $15,000 per year or more than $50,000 per year), reinforce the overall findings of a successful program. Additionally, 92 percent of men and 89 percent of women are satisfied with their coverage.

Seniors Rely on the Program: This year, 72 percent of beneficiaries said that they’re better off now than before they had Part D coverage – a four percent increase from last year. Eighty-six percent of seniors fear that eliminating Part D would increase their out-of-pocket prescription costs, and without a plan, 62 percent say they would be forced to cut back or eliminate some prescription regimens – a nine percent increase from 2012.

Seniors Would Recommend Coverage to Others: 89 percent of Part D enrollees say they would recommend the program to someone considering Medicare enrollment.

The full survey can be found here.

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Continued Quality Quandary

09/17/2013 09:26 AM |

Per the FDA’s import alert for drugs made in Ranbaxy's Mohali plant in northern India, the agency said it found "significant" violations of manufacturing rules, "including failure to adequately investigate manufacturing problems."

Now at least three of Ranbaxy's eight plants in India are unable to export to the U.S. Among its facilities outside of India, the Gloversville, N.Y., plant received a warning letter from the FDA in December 2009 for manufacturing violations. That facility has since been closed.

For more on this issue, see Indians and Cowboys.

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Indians and Cowboys

09/16/2013 10:29 AM |

Yes, Virginia. Quality counts.

Ranbaxy, the Indian generics manufacturer that recently paid half a billion dollars to settle fraud allegations and quality problems, has just received an FDA import alert against their production facility in Mohali, Punjab state.

The plant was set to make generic versions of blood-pressure pill Diovan.

Ranbaxy facilities in Dewas and Paonta Sahib, India, have both been on the FDA’s import alert list since 2009.

The relevance for more complicated products (like Gleevec) and biosimilars more broadly – is obvious.

According to Bloomberg report, the latest FDA notice “is a surprise,” said Prakash Agarwal, a health-care analyst with CIMB Securities India Pvt. Ltd. “The understanding was that, given the past experience with the two other facilities, the management would be on their toes to resolve these issues.”

Fast and loose is not an option.
 

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My name is Friday. I'm a cop.

09/13/2013 09:16 AM |

TGIF. Now let’s talk about Prescription Drug Monitoring Programs (PDMP) and the intended and unintended consequences thereof.

How wide a net should PDMPs cast before they begin to have the unintended consequence of restricting legitimate patient access? Well, according the general consensus at Tuesday’s Capital Hill conference on Personalized Medicine and Responsible Access to Pain Medication, PDMPs should include Schedules 2-4. To infinity and beyond may make for good soundbites, but makes no practical sense.

What about e-standards for inter-operability with electronic health records? This point was made by Bob Twillman, of the American Academy of Pain Management. Big Data is certainly part of the answer. Knowledge is Power.

And speaking of data – what about data entry? PDMPs should allow not only pharmacists, but also physicians and their staffs to be able to enter and update electronic records. Let’s get real – this is already the reality on the ground. But this must also be matched with proper oversight for both quality control and appropriate access.

This raises the prospect of doing something that Indiana started doing with its PDMP a couple of years ago -- and that a lot of other states want to do. The Hoosier State made it possible for prescribers to communicate with other prescribers about patients—so, if prescriber B sees a patient and discovers that Prescriber A has prescribed before, B can contact A and make arrangements for which one of them is going to follow the patient. Notes also can be left behind for other providers, for instance, if an ER doc gets a doctor shopper, he can leave a note about it so others are forewarned.

What about pharmacists? What’s their role? Should they have broader access to patient data?  Beyond being deputized by the DEA, the pharmacy community must be able to play a more appropriate role as a healthcare professional.

Perhaps one of the toughest issues is the role of abuse deterrent formulations (ADF). Beyond the debate over whether the FDA should insist that all generics be abuse deterrent (and the related IP debate), how should PDMPs instruct physicians and pharmacists? And what about formularies? Can we trust physicians to make the right call? Do all patients need abuse deterrent formulation? And, if not, what are the decision criteria? What about dose and duration limitations?

Or should there be state regulations per ADFs at all? Shouldn’t those decisions reside within the FDA? Can you say federal preemption?

This places both education (of the CME variety) and best practices (developed not just by PDMPs but also by physicians, pharmacists, and patient organizations) front and center. What about REMS training? And what about more precise criteria for what a “pain specialist” or a “pain clinic” even mean? As the saying goes, “if you can’t measure it, then it doesn’t count.”

What about take-back programs? Should they only be limited to opioids? And who should pay for them?

Lastly, amercement. On a state-by-state level, does the punishment fit the crime? Should there be national standards on criminal and civil penalties?

Many tough questions – but they deserve thoughtful and timely answers. It’s time for a focused national dialogue that recognizes the need for effective oversight through the use of Big Data and broader constituent alliances.

The conventional view serves to protect us from the painful job of thinking.

-- John Kenneth Galbraith

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Guidelines, Goalposts, and Genotypes

09/11/2013 09:15 AM |

Pierre Trudeau once said, “There's no place for the state in the bedrooms of the nation.“ But what’s the appropriate place for the state in our nation’s pharmacies and medicine chests – particularly for opioids?

Yesterday was the day to address that question.

First there was the FDA’s announcement of class-wide labeling changes and new post-market study requirements for extended-release and long-acting opioids.

Until now, the FDA had said the drugs were appropriate for the treatment of "moderate-to-severe" pain. The new drug label drops the word "moderate" and says it should be used only to manage "pain severe enough to require daily, around-the clock, long-term treatment." Additionally, FDA is adding a boxed warning on the risk of neonatal opioid withdrawal syndrome.

The agency said manufacturers must conduct one or more post-marketing studies to quantitatively estimate the risks of misuse, abuse, addiction, overdose and death associated with long-term use, as well as a clinical trial to evaluate the risk of developing increased sensitivity to pain with long-term use of extended-release and long-acting opioids. Companies also must conduct a study of "doctor/pharmacy shopping" -- a practice in which patients visit multiple doctors and pharmacies to obtain prescriptions -- and whether it is "suggestive of misuse, abuse and/or addiction." Per a report in BioCentury, “FDA said companies should work together on the post-marketing studies.”

Once the labeling changes are finalized, FDA said it will modify the classwide REMS for extended-release and long-acting opioids. The REMS, which the agency approved in 2012, requires companies to make educational programs available to prescribers at no or nominal cost but does not require prescribers to participate and does not include a prescriber registry.

The other big new was a Capital Hill conference on Personalized Medicine and Responsible Access to Pain Medication (sponsored by the Center for Medicine in the Public Interest – the think tank home of drugwonks.com). I was honored to chair the event.

Speakers included Bob Twillman of the American Academy of Pain Management, Cindy Steinberg of the US Pain Foundation, Stuart Kim of Mallinckrodt Pharmaceuticals, Steve Usdin of BioCentury, syndicated healthcare columnist Judy Foreman, and Professor Charles Inturrisi of Weill Cornell Medical Center.

The speakers and attendees rocked the Rayburn Building. Video of the event will soon be posted on the CMPI website.

I tried to set the tone with my opening comments:

Joshua Lederberg, the Nobel Prize Laureate once observed that the failure of regulatory, legal and political institutions to integrate scientific advances into risk selection and assessment was the most important barrier to improved public health.  

Lederberg noted that in the absence of such changes,  "the precedents affecting the long-term rationale of social policy will be set, not on the basis of well-debated principles, but on the accidents of the first advertised examples."

Policies and regulations that seek to limit risk are often shaped by the immediate fear of sensational events. This perspective is commonly called "The Precautionary Principle" which in various forms asserts that unless innovators can demonstrate that a new technology is risk free, it should be not allowed into the marketplace.  Moreover, any product that could possibly be dangerous at any level should be strictly and severely regulated. 

But precaution is not always safer than the alternatives.

Some current examples of precaution and the public health

·      The National Action Plan for Adverse Drug Event Prevention, just announced in a Sept. 4 Federal Register notice, outlines a comprehensive strategy to reduce AEDs for opioids. Much of the research actions called for by the plan seem designed to decrease prescribing. For instance, the plan calls for research by CDC, NIH and, public-private collaborations to look into adopting adjunctive and behavioral modalities to augment and reduce opioids use for chronic pain;

·      Upscheduling and the relabeling of medicines to treat depression, diabetes, chronic and acute pain;

·      And, finally, the role of tamper-resistant technologies in the appropriate management of pain medicines (both innovator and generic).

It’s also important to consider the DEA’s “Thug Regulation” strategy that results in a decline in appropriate patient access; an increase in regulatory time and cost and, ultimately, a decline in innovation.

The California Medical Association has received reports from physicians that Walgreens pharmacists are refusing to fill controlled substances prescriptions without additional information from the prescriber.

Per dictates from the DEA, Walgreen’s pharmacists are now demanding that physicians provide information on diagnosis, ICD-9 codes, expected length of therapy and previous medications tried and failed.

In other words, tighter restrictions for patients who really need the medications, more paperwork for physicians and a heavier workload for pharmacists. Abusers and criminals rarely follow regulations.

When you have a hammer, every problem looks like a nail. The DEA sees opioid abuse and seeks to minimize access to them. That’s a law enforcement solution. They mean well – but are behaving like a bull in a china shop

Arbitrarily limiting choice is not generally associated with the Scientific Method.

Should regulation be shaped by factors other than science or should advances in medicine and digital information be used to right-size regulation, reduce the excessive reductionism that leads to regulatory overreaction and promote resilience rather than ever increasing restrictions?

Consider the program recently instituted by CVS (and detailed in a recent New England Journal of Medicine Perspective piece) where, via the use of “Big Data” the chain pharmacy identified “outlier prescribers” and took appropriate and responsible actions.

The DEA’s attempt to deputize pharmacists on the one hand and the CVS program on the other raise some interesting questions:

·      What will the role of the 21^st century pharmacist be in improving drug safety and medication adherence via more proactive (and remunerated) patient education?

·      How can pharmacists become better integrated (beyond Med Guides) into the FDA’s Safe Use of Medicines initiative?

·      When will pharmacy synchronization programs really kick into gear, and how will states help to jump-start these important initiatives?

To paraphrase the American political scientist Aaron Wildavsky, we at the Center for Medicine in the Public interest believe in a strategy of resilience based on experience. We must learn from adverse consequences in order to develop a capacity to advance the public health. Variability is the key to survival.

THANK YOU.

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Peg's PAG

09/06/2013 11:48 AM |

From: CDER Center Director

Sent: Friday, September 06, 2013 11:24 AM

To: FDA-CDER-wide

Subject: FDA Establishes the Program Alignment Group

CDER Staff:

In order for FDA to best adapt to the ongoing rapid changes in the regulatory environment, driven by scientific innovation, globalization, the increasing complexity of regulated products, new legal authorities and additional user fee programs, the Commissioner has formed a Program Alignment Group (PAG). Comprised of senior Agency leaders, the PAG is charged with identifying and developing plans to modify FDA’s functions, processes, and possibly its structure in order to address these matters and best achieve mission-critical Agency objectives. This group of senior leaders will achieve this goal by working together to promote the strategic, operational, and resource management alignment needed for FDA to continue to fulfill its mission. 

As a member of the PAG, I am pleased to share with you the email and memo (below) that I received from the Commissioner this morning. This initiative will provide an opportunity for CDER to continue modernization of operations in order to address the challenges noted above and to implement our new legislative responsibilities, including those imposed by the Food and Drug Administration Safety and Innovation Act and the Generic Drug User Fee Amendments of 2012 (GDUFA).

Many of CDER’s current modernization efforts center around the regulation of pharmaceutical quality. Most of you are aware of the proposed elevation of the Office of Generic Drugs to a super office, and the concomitant efforts to establish a new Office of Pharmaceutical Quality (OPQ). The work to establish OPQ will need to be closely coordinated with the Office of Regulatory Affairs (ORA). We recognize that in order to accomplish GDUFA and other commitments, CDER and ORA need to have an integrated program for regulating pharmaceutical quality, with well-defined leads, coherent policy and strategy development, well-designed and coordinated policy implementation, and a de-layered management structure. Moving toward this new model will take time and a level of organizational change across CDER and ORA, including streamlining management and decision making and clarifying roles and responsibilities, metrics and accountability, and decision rights. Similar considerations apply to other inspectional programs.

I am confident that any changes implemented as a result of this evaluation will not only improve efficiency in our program areas and in our collaborations across the Agency, but also provide us with a solid foundation that allows us to continuously adapt to the ever-changing challenges and new demands placed on CDER. This is important as we continue to meet our critical public health and regulatory mission to ensure safe, effective, and high-quality drugs are available to the American public.

I look forward to participating in the PAG discussions. The first report from the PAG is due to the Commissioner in the next several months. FDA will then assess the recommendations and decide how to proceed. I am committed to keeping you informed about the outcome of the PAG’s evaluation; you may expect additional communications from me once the Agency determines its next steps in this process.

Janet Woodcock

From: Hamburg, Margaret


Sent: Friday, September 06, 2013 10:09 AM


To: Dunham, Bernadette M; Landa, Michael; Midthun, Karen; Plaisier, Melinda K; Shuren, Jeff; Solomon, Steven M; Taylor, John M.; Taylor, Michael R; Woodcock, Janet; Zeller, Mitchell


 Subject: Program Alignment Group

Over the past few years, FDA has experienced unparalleled challenges and demands posed by the increasing breadth, depth, and complexity of the products it regulates.  That, combined with significant strides in scientific innovation and increased biomedical discovery, the globalization of the food system and medical supply chains, as well as the expansion in FDA’s regulatory authorities via many new forms of legislation, require the Agency to continue to find ways to ensure that we are meeting our critical public health and regulatory mission. 

Therefore, to be in the best position to effectuate the steps necessary to successfully address these challenges, I am pleased to formally appoint you to the Program Alignment Group (PAG).  The PAG will be comprised of senior Agency leaders charged with identifying and developing plans to modify FDA’s functions and processes in order to address the challenges noted above and to best achieve mission-critical Agency objectives.  This group of senior leaders will attain this goal by working together to promote the strategic, operational, and resource management alignment needed for FDA to continue to fulfill its public health mission. 

More information about the PAG can be found in the attached memorandum.  The group will look at what changes may be necessary from an operational standpoint to transform the Agency from a domestic Agency operating in a globalized world to a truly global Agency fully prepared for a regulatory environment in which product safety and quality know no borders.

I want to thank you, as senior FDA leaders, for engaging in this important work together to move FDA into the future as a modern and globalized public health-regulatory Agency.  I look forward to watching your progress in the months ahead as we embark on this path together.

Margaret A. Hamburg, M.D.

Commissioner of Food and Drugs

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What can (Jerry) Brown do for you?

09/06/2013 10:30 AM |

The California Senate passed a state bill that would impose restrictions on when pharmacists may dispense a biosimilar in place of an innovator product. The California Assembly already passed the bill, which will now be sent to Gov. Jerry Brown. A spokesperson for Brown said the governor does not comment on pending legislation, but Brown will have until Oct. 13 to sign the bill into law.

The California bill would allow substitution of a biosimilar for an innovator product only if FDA declared the biosimilar interchangeable for the specific use; the prescriber had not expressly prohibited use of a biosimilar; the substitution was communicated to patients; the cost to the patient was the same or less than the innovator product; and the pharmacist notified the prescribing physician within five days. The requirement for physician notification would sunset after three years (Jan. 1, 2017). Additionally, the California State Board of Pharmacy would maintain a list of biosimilar products FDA determines to be interchangeable on its website. A spokesperson for the Biotechnology Industry Organization (BIO) said the bill applies only to retail pharmacies.

Despite what you may read in the papers, sometimes legislation that’s supported by innovator pharmaceutical companies is also in the best interest of the public health. This is one of those times.

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Avec Plaisier

09/04/2013 07:27 AM |

Dear Colleagues:

I am very pleased to announce the appointment of Melinda “Mel” Plaisier as the Associate Commissioner for Regulatory Affairs (ACRA), effective immediately.  As many of you know, Melinda has been steadfastly serving in this position in an acting role since October 1, 2012.  During that time, Melinda has led the Office of Regulatory Affairs (ORA), utilizing her deep operational knowledge, her proven leadership skills, and her professional and collaborative demeanor.

Melinda brings a wealth of experience to this position.  She joined FDA in 1995, after serving as a Congressional staffer for more than a decade.  Melinda spent more than 13 years in the Office of the Commissioner where, among other roles, she served as the Associate Commissioner for Legislation, providing executive leadership in directing and managing the Agency’s congressional relations and legislative activities, and the Associate Commissioner for International Programs, where she focused on negotiating international agreements and working with developing nations.  Immediately prior to serving as the Acting ACRA, Melinda served as the Regional Food and Drug Director for ORA’s Central Region for several years.

Melinda will report directly to the Deputy Commissioner for Global Regulatory Operations and Policy and will lead the 4300 extraordinary men and women of ORA who are dedicated to furthering FDA’s public health mission in many important ways, including by inspecting regulated products and manufacturers, by conducting sample analysis on regulated products, and by reviewing imported products offered for entry into the United States.

Going forward, Melinda will play a critical role in helping FDA adapt to the continuing program-based specialization within FDA’s regulated industries and in implementing FDA’s expanded authority in recent groundbreaking legislation in many important areas.  I am confident that Melinda will help position FDA as a public health regulatory agency fully prepared to deal with the many challenges of an increasingly complex global regulatory environment.

Please join me in congratulating Melinda as she assumes this official role.

Sincerely,

Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs   Read More & Comment...

Tweeter Reflux

09/03/2013 09:50 AM |

What part of "unbranded" didn't you understand?

AstraZeneca has pulled paid advertisements on the Associated Press’s Twitter feed after it was made aware that the unbranded content it believed it paid for actually included the name of a prescription drug.

Note – “paid advertisements.”

Per the Pink Sheet, “At first glance, two Aug. 27 tweets sponsored by AstraZeneca read like straightforward disease awareness ads, but when the tweets are expanded, they reveal the name of its acid reflux treatment Nexium(esomeprazole), appearing to place the company in a more heavily regulated landscape.”

On Aug. 27, the Associated Press ran a tweet sponsored by the pharma on the micro-blogging site that permits 140 character messages including links to websites or pictures. The tweet read: “Sponsored Tweet: 15M+ Americans experience #GERD symptoms each day. Visit AstraZeneca’s YouTube channel bit.ly/1aZ6BiK.”

At the bottom of the tweet users can click a “view summary” tab that pulls up an expanded version of that tweet. This expanded version includes a preview of the YouTube site the company links to: “the official YouTube channel of Nexium (esomeprazole mangesium).”

So the question becomes, when these two components are placed side-by-side, are they still the “unbranded tweets” the company thought it was posting?

Per AZ, the tweets are unbranded and were not sent to FDA for approval. The ads did go through all of AstraZenca’s own internal reviews and approvals to ensure compliance with applicable U.S. laws and regulations.

AstraZeneca: “The sponsored tweet we paid for was the tweet text itself. We weren’t aware that additional text would appear under a summary button. We are going to inform the FDA of this as soon as possible. We will also assess if any changes need to be made.”

That’s the key point – it was a “sponsored” tweet. In other words – a paid advertisement. This isn’t about social media. It’s the same issue that arouse over the FDA letters regarding “sponsored” Google links. “Sponsored” means paid – and “paid” is not social media.

So, please hold the hyperbole about the FDA retarding the use of social media.

Speaking of hyperbole, OPDP panjandrum Thomas Abrams said in late June that the long-awaited guidance is one of the highest priorities for the agency in terms of time and resources.

Down boy.

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Entrepreneurial Regulation

08/30/2013 10:20 AM |

Having just returned from meetings with regulatory authorities in Kenya, Jordan, and Saudi Arabia, I am energized that higher levels of pharmaceutical quality and pharmacovigilance are possible.

But it won’t be easy.

Enhanced levels of excellence will require, if not global harmonization, more aggressive partnerships between agencies around the world.

In other words, it’s time to plan and execute a regulatory Marshall Plan to help build, nation-by-nation, global systems for both quality and safety.  Working together to raise the regulatory performance of all nations will help all nations (even the 20% deemed “capable” by the WHO) to create sound foundations to address a multitude of quality and safety dilemmas such the manufacturing of biosimilars, the control of API and excipient quality, pharmacovigilance and, yes, even counterfeiting.

But drug regulation has to go beyond safety and quality and pharmacovigilance. It’s got to embrace innovation. What we need here at home and around the world is a hunger for entrepreneurial regulation.

Entrepreneurial Regulation is a philosophy that allows agencies such as the FDA to be both regulator of and colleague to industry. Expedited pathways are Entrepreneurial Regulation. Special Medical Use is Entrepreneurial Regulation. REMS are Entrepreneurial Regulation. The exercise of enforcement discretion is Entrepreneurial Regulation. More aggressive use of the Reagan/Udall Foundation is Entrepreneurial Regulation. A more central role for the patient voice is Entrepreneurial Regulation.

Entrepreneurial Regulation makes bodies such as the FDA enablers rather than roadblocks to innovation.

One of the key conundrums of Entrepreneurial Regulation is that there is an inherent tension between predictability and innovation.

The foundational principle of PDUFA is predictability – not speed. And that’s been the focus of the conversation: ambiguity vs. predictability. But, when it comes to innovation, ambiguity is inherent. The pathways to innovation are always ambiguous. Innovation is risky – and not only to investors.

And Entrepreneurial Regulation is likewise risky. But as with all matters regulatory, risk must be viewed alongside benefit – to the public health.

Another level of tension is the relationship between research (R) and development (D). Specifically, the lack of respect between the two. Beyond the disproportionate levels of government funding (when’s the last time you heard anyone talk about “doubling” the FDA budget), nascent relationships between academia (“R”) and industry (“D”) are struggling.

The issue of out-sourcing basic research isn’t new – but it’s mighty contentious. And it’s the new reality of drug development. But, if we are to learn any lesson from the CRO experience, it’s that while we say “partnership,” the danger is that it devolves into a vendor-like relationship. It’s the Golden Rule. He who has the gold makes the rules. Will that be acceptable to high-level, big ego Ivy Hall-ers?

And then there’s the issue of academic priorities, specifically tenure. Does industry funding carry the same weight as NIH grants when it comes to advancing a university career? Not at present. That will have to change.

Need drives change. Just as CROs are finally really partnering with pharma to drive the development of personalized medicine, so too must academe and industry collaborate on the continued evolution of pharmaceutical innovation. It will take discipline and focus. It will be risky. And it will take will. There is a confluence of interest.

When it comes to global safety, quality, and pharmacovigilance standards, there’s a general consensus that a high tide floats all boats. When it comes to Entrepreneurial Regulation demands that we honestly address a tough but fundamental question, how can regulatory agencies around the world (FDA-led by both word and deed) focus on what they can do to facilitate collaboration that results in innovation?

Step One is focus.

In the words of entrepreneur extraordinaire Steve Jobs, “I'm convinced that about half of what seperates the successful entrepreneurs from the non-successful ones is pure perserverance."

And, in the case of Entrepreneurial Regulation, failure is not an option.

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Getting darker at night with increasing light towards morning

08/28/2013 09:44 AM |

And for this she bills how much per hour?

From the pages of the Pittsburgh Business Times,

Developing a regulatory strategy is a key first step in bringing a new medical device to market, Regulatory & Quality Solutions LLC President Maria Fagan said Tuesday.

The plan is needed to align stakeholders, making sure executives, investors and others have a shared vision about the purpose and use of the product, Fagan said in addressing a meeting downtown sponsored by the Pittsburgh Technology Council. Included in the plan should be the device’s intent, benefits and target audience of consumers.

“Think through these things early on,” Fagan said. “From a marketing perspective, where do you want to go?”

And, as a word to the wise, spelling also counts.

  Read More & Comment...

Baucus gets Raucous on Indian Trade Shenanigans

08/25/2013 03:11 PM |

CONGRESSIONAL TRADE LEADERS FIGHT INDIA’S UNFAIR TRADE PRACTICES

In Letter to ITC, Members Seek Investigation of Policies that Discriminate Against U.S. Exports

WASHINGTON –Senate Finance Committee Chairman Max Baucus (D-Mont.), Ranking Member Orrin Hatch (R-Utah), House Ways and Means Committee Chairman Dave Camp (R-Mich.) and Ranking Member Sander Levin (D-Mich.) today requested the U.S. International Trade Commission (ITC) investigate India’s unfair trade practices that discriminate against U.S. exports and investment. 

Noting in a letter that U.S. exports to India are low given the size of its market, the congressional leaders asked the ITC to detail policies India has in place that restrict trade and violate intellectual property rights, as well as the effect they have on U.S. exports, businesses and jobs.

The full text of the letter is available below:

The Honorable Irving A. Williamson
Chairman
U.S. International Trade Commission
500 E Street, S.W.
Washington, DC 20436

Dear Chairman Williamson,

We are writing to request that the U.S. International Trade Commission (Commission) conduct an investigation under section 332(g) of the Tariff Act of 1930 (19 U.S.C. §1332(g)) regarding Indian industrial policies that discriminate against U.S. imports and investment for the sake of supporting Indian domestic industries, and the effect that those barriers have on the U.S. economy and U.S. jobs.

India is an important strategic partner of the United States, yet U.S. exports of goods and services to India remain low.  In 2011, U.S. goods exports to India – the world’s second most populous country – were just $22.3 billion.  Similarly, recent data indicates that U.S. private commercial services exports, sales of services by majority U.S.-owned affiliates, and U.S. foreign direct investment (FDI) in India were also low.

India has risen rapidly and lifted millions out of poverty in the wake of its significant market opening reforms and its efforts to seek foreign investment in certain sectors of its economy over the past two decades.  However, India maintains and continues to put in place measures that appear to contradict its stated domestic growth objectives.  For example, India has a complex, non-transparent tariff and fee system and byzantine and overburdensome customs procedures, and it maintains significant tariff and non-tariff barriers to U.S. goods and service participation in sectors including retail and agriculture.  More recently, India has introduced new localization-forcing measures such as local content and technology transfer requirements in the green technology and information and communications technology sectors.   And India has not yet taken action to fully and effectively protect and enforce copyrights, including in the digital environment, and has applied its patent law in a discriminatory manner, particularly against innovative U.S. pharmaceutical companies, so as to advantage its domestic industries.  

Beyond any particular action India has taken, the government has enunciated a broader policy objective to develop and support Indian domestic industries by forcing foreign firms to use local facilities and suppliers and to transfer their intellectual property to Indian entities.  Government documents indicate that India is likely to adopt additional measures to this end, and expand these sorts of measures to additional sectors, creating significant concern and uncertainty for U.S. exporters and investors.

Finally, we are very concerned about the broader impact that India’s trade policy may be having on the global trading system, both in terms of the model it is setting for other countries and the drag it is exerting on multilateral trade negotiations.

Despite the widespread evidence of these existing and anticipated barriers to U.S. exports and investment in India, the U.S. Government has not conducted a comprehensive economic analysis of the effect of Indian trade policies on the U.S. economy and U.S. jobs.  To assist us in better understanding the effects of these existing and anticipated barriers to U.S. exports and investment in India, we request the Commission to provide a report covering the items described below.

Based on a review and analysis of data and information from available sources, including a survey of U.S. firms, we request the Commission to provide:
 

·         An overview of trends and policies in India affecting trade and foreign direct investment in that country’s agriculture, manufacturing and service sectors, as well as the overall business environment.  The overview should take a historic view, but focus on the period since 2003.  It should include examples of changes in tariff and nontariff measures, including measures related to the protection of intellectual property (IP) rights, and other actions taken by India’s government to facilitate or restrict the inflow of trade and FDI.

·         A description of (1) any significant restrictive trade and FDI policies currently maintained or recently adopted by India as identified by USITC research; (2) the sectors in the U.S. economy most affected by these restrictive policies; and (3) the general competitiveness of sectors in India’s economy that are subject to the identified restrictions.
 

·         Several case studies that examine the effects of particular restrictive measures on U.S. firms that export to or invest in India, or that have not done so because of the measures.  To the extent feasible, the case studies should address the impact of the restrictive measures on both large and small and medium-sized enterprises.
 

·         To the extent feasible, a quantitative analysis of the economic effects of India’s identified restrictive measures on the U.S. economy as a whole, on U.S. trade and investment, and on selected sectors of the U.S. economy.
 

·         Based on the survey and analysis of results, and to the extent feasible, a summary of U.S. firms’ perception of (1) recent changes in India’s trade and investment policies in selected sectors and (2) the effects of these changes on U.S. firms’ strategies towards India (e.g., reducing investment or altering product mix), and analysis of whether the effects of these policy changes differ by firms’ characteristics, such as size, IP-intensiveness, or export status.

We request that the Commission deliver the report to us by November 30, 2014. 

In preparing its report, we do not expect the Commission to make findings regarding the legal merits of any Indian laws or policies. 

As we intend to make the report available to the public, we request that the Commission not include confidential business information in the report.

Sincerely,
 

Max Baucus
Chairman, Senate Committee on Finance

Orrin Hatch
Ranking Member, Senate Committee on Finance

Dave Camp
Chairman, House Committee on Ways and Means

Sander Levin
Ranking Member, House Committee on Ways and Means

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340B Minus

08/22/2013 12:50 PM |

From today’s edition of the South Florida Sun-Sentinel:

Some health providers exploiting drug program

Some major American health care providers are padding their bottom lines by exploiting a federal program meant to help low-income patients. This behavior is netting them billions in ill-gotten gains.

And it could be preventing many vulnerable Americans from accessing the low-cost drugs they need to treat and prevent illness.

This abuse needs to be stopped.

In 1992, Congress created a program — known as "340B" — to help caregivers serving disproportionately large numbers of low-income beneficiaries and uninsured patients. Under 340B, drug manufacturers are required to sell their products at a discount to such institutions.  The discounted prescriptions are dispensed either through the caregiver's in-house pharmacy or through a contractual arrangement with an outside pharmacy.

340B has a noble cause. And many of the medications discounted through 340B do in fact go to clinics, hospitals, and medical facilities providing care almost exclusively to uninsured and poor patients.

However, some 340B participants are exploiting the program.

340B only requires caregivers to meet certain minimal thresholds for the number of medically underserved people they treat.  For many hospitals, these eligibility standards are easily reached, and some are benefiting from the program's deep drug discounts while still serving a relatively affluent clientele.

Moreover, participating caregivers are not actually required to pass drug savings along to their patients. The huge discounts they're getting from pharmaceutical manufacturers don't necessarily translate to lower pill prices for uninsured and low-income patients.

Given what we have recently learned about some hospital administrators inflating charges for a broad variety of basic services, there's good reason to believe many sell those discounted drugs at full price to insured patients and then pocket the difference. Indeed, a report by the Raleigh News Observer last year found hospitals that "routinely mark up prices on cancer drugs two to 10 times or more over cost. In some cases, the mark up is far higher."

Meanwhile, the vulnerable patient populations 340B was intended to help are often still stuck struggling to gain access to affordable pharmaceuticals.

In large part because some healthcare providers are abusing the 340B system, the size and cost of the program are ballooning out of control. The Berkeley Research Group estimates the total the total value of all the medicines sold through the program will more than double from $8 billion in 2010 to $19 in 2016.

Such a surge in expenses might very well be worth if it 340B was largely helping needy patients. But it is not clear that this is actually happening. Although 340B was created to help low-income patients obtain the medicines they need, it has turned into a revenue generator for many hospitals.

Caregivers are now allowed to qualify for the program's deep drug discounts without passing along those savings to patients in need. Administrators are getting rich off a well-intentioned public program.

Too many uninsured and poor patients still don't have access to discounted drugs.

340B needs to be fixed.

Peter J. Pitts, a former FDA Associate Commissioner, is President of the Center for Medicine in the Public Interest.

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It only hurts when I tweet

08/21/2013 08:58 AM |

Docs Need to Get Up to Speed, Social Media Advocate Says

By Kristina Fiore, Staff Writer, MedPage Today

Bertalan Mesko, MD, PhD, is counting on old media to convince more clinicians about the value of new media.

The clinical genomics specialist has just published a handbook on social media in clinical practice -- and he hopes it will bring late adopters up to speed with their social-media-savvy colleagues, and even with some of their electronically empowered patients.

While "expert" patients voraciously pursue credible medical information and communities online, clinicians "usually lag behind," Mesko, who is based in Budapest, said in an email exchange with MedPage Today. Instead of disdaining this kind of behavior, doctors need to see themselves as a gatekeeper of vetted online information and activities, he said.

One of the earliest clinician voices on social media, Mesko has been attempting to make that gatekeeper role easier as the founder of Webicina.com, a clearinghouse of sorts for digital and social media resources. He's also a self-described "medical futurist" who blogs at Scienceroll.com.

Mesko answered some questions about the book, "Social Media in Clinical Practice," and about online engagement via email. An edited version of that conversation follows.

MPT: Why the need for a book on social media adoption for clinicians?

Mesko: Social media has been playing an increasingly important role in medical communication as the Internet now has a crucial place in our lives. While patients relatively easily become empowered or expert patients -- the so-called e-patients, as they are really motivated to use digital solutions to get a better care -- medical professionals usually lag behind.

I've been teaching medical students and physicians about the proper use of social media and other digital technologies for years, and my experience is that even if I created a free e-learning platform for them, they stick to the traditional way of learning new things. Therefore, the need for a practical handbook full of examples and step-by-step instructions about using social media platforms was imminent.

MPT: Many clinicians are apprehensive about social media because of HIPAA and patient privacy. What are the challenges here, and how should clinicians address them?

Mesko: Physicians should know exactly the potential limitations and privacy issues caused by the use of social media. [In the book], I describe bad examples and stories related to these crucial issues.

In one example, a patient added me on Facebook and shared her previous medical records with me even though she was not my patient. I rejected the offer and sent her a private e-mail explaining why (that this is a personal online channel, why our relationship would be professional and I don't want to mix these). She perfectly understood.

I had a colleague who rejected the offer and pretended like nothing happened when they next met. He described the situation as quite awkward.

This happens when you don't know the rules of online communication. If we know the rules, just like in real-life communication, the use of social media becomes safe and efficient.

MPT: Can you give examples of some of the more insightful uses of social media that you've seen among doctors?

Mesko: I'm a member of amazing medical communities -- from Google+ to closed Facebook groups -- in which I can discuss clinical issues with peers worldwide. My Twitter channel with over 32,000 followers lets me crowdsource difficult diagnostic problems, and my blog gives me a chance to connect with tens of thousands of medical professionals without limitations. I published papers in peer-reviewed journals after collaborating with co-authors simultaneously in a Google document.

Social media provides us with a lot of opportunities, but only if we know the potential limitations and security issues. Acquiring such knowledge takes years, and my goal with the handbook was to shorten this time significantly for those medical professionals who would like to become a bit more digital, but at the same time use these online tools in a secure way.

MPT: How did you crowdsource a difficult diagnostic problem?

Mesko: The story happened in the fall of 2009; the New York Times wrote about it in early 2010. When professors at the clinic could not find the solution to a complicated medical issue, I sent a tweet to my tens of thousands of medical followers for useful advice. I tweeted this:

"Strange case today in internal medicine rotation: 16-year-old boy with acute pancreatitis (for the 6th! time). Any ideas?"

I received hundreds of amazing responses from all over the world, and in one day we came up with a potential solution. The final diagnosis was microlithiasis, small stones from the gallbladder causing pancreatitis from time to time without obvious causes. The diagnosis was not so simple because of the size of the stones and as a medical student I wanted to use the power of the medical community I had been building for years, so that I might come up with useful suggestions for my professors. It turned out to be a good idea.

MPT: If there was one use of digital or social media that all clinicians should adopt, what would it be?

Mesko: I think communication methods in real life and in the online world are the same. If medical professionals understand this and create a proper online presence, as well as give their patients a chance to communicate with them through certain online channels, the doctor-patient relationship can become more efficient by saving time for both parties.

Using digital technologies, especially social media, is now an integral part of medical communication, and as more and more patients use these platforms, their physicians must be able to deal with this in an evidence-based manner.

MPT: Are there any definite "don'ts" for clinicians online?

Mesko: I tell my medical students they should definitely not do things online which they would never do offline. That's how simple it is.

MPT: What is the "Participatory Medicine Movement" and what should practicing clinicians know about it?

Mesko: As e-patients are motivated to use digital technologies in their health management, they have additional questions about the Internet, such as where to find reliable medical resources about their conditions. Doctors must be able to respond properly and professionally to these questions as well. The Participatory Medicine Movement leads to some changes in the structure of medicine in which medical professionals will become mediators or guides for their patients online.

In order to reach this long-term goal, doctors should learn new tricks, not just about communicating with patients online, but also about keeping themselves up to date more easily.

MPT: Which smartphone apps should every clinician already have downloaded?

Mesko: It very much depends on certain factors such as specialty, the smartphone or tablet you have, and the way you want to use it in practicing medicine. The key point here is curation. Only curated, validated, and quality smartphone apps should be used by physicians, and they should be able to help their own patients identify similarly good apps themselves.

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Obamacare's Losers

08/20/2013 02:24 AM |

Via USA Today:

Johnny Drake's business is losing 2.3 percent of everything it makes because of the Affordable Care Act.

He's the president of Pathfinder Technologies, a small company in Nashville with fewer than 20 employees, that got hit with an excise tax this year because it makes medical devices
.
Medical device manufacturers are among the federal health law losers, those that will have to pay up to cover the cost of implementing it. Others include high-wage earners, tanning salons and, in some cases, working parents and folks with big medical bills. The law generates revenue through a hodgepodge of new taxes, financial penalties and IRS rule changes.

"Every quarter, we're having to send the federal government a flat 2.3 percent of our revenue," Drake said. "I feel like it's double taxation because at the end of the year, we're sending them our federal income tax as well."

Tanning salon owners started having to pay a bigger tax three years ago. Lyvonn Reese, who owns the Hot Spot Tanning salons in the Nashville area, said the 10 percent tax ate away so much of her profit margin that she had no choice but to pass it along. She itemizes "tanning tax" on customer receipts.

Read the article here.

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App-Sense & Pharma Sensibilities

08/16/2013 10:52 AM |

Congressional Quarterly reports that the Food and Drug Administration has yet to give final guidance on which of the growing number of mobile health apps it will regulate. Draft guidance indicates “enforcement discretion” will be taken toward consumer-oriented mobile apps, especially ones that are more high risk. The draft guidance also notes that clinical apps could “present a potential risk to patients if they do not work as intended.” Many health industry groups would like to see a wider regulatory framework on IT in place before the FDA issues specific mobile app guidance.

That sounds familiar.

For a more detailed look at this issue – with particular emphasis on the issue of enforcement discretion see, “A Regulatory App-ening.”

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