pharmacy.pngCompounding pharmacies have been on FDA’s priority list since the 61 deaths and 749 cases of fungal infections from steroid injections contaminated during manufacture by New England Compounding Center (“NECC”), last fall. When appearing before Congress last November, FDA Commissioner Margaret A. Hamburg, M.D. plead a lack of regulatory authority in the wake of the Western States U.S. Supreme Court decision. Arguably, it is unclear if Western States struck down just the regulation of advertisements (as industry has contended) leaving the regulatory structure untouched or if it invalidated the authorization of compounding pharmacies (as FDA has contended, since the 9th circuit held the provisions not-severable and that decision was affirmed), leaving compounding pharmacies technically illegal but ignored by FDA regulatory discretion. Either way, FDA appeared to retain certain regulatory authority over compounding pharmacies, but FDA’s scope was unclear.

Congress did not want to leave the deaths resulting from compounded drugs alone, so S. 959 was proposed to fix the problem, despite the lack of clarity what problem needed to be fixed. Among other things, S. 959 would forbid compounding pharmacies to copy FDA-approved but nonpatented medicines. But do we want all medications (including compounded drugs) to require premarketing approval? Do we want more frequent inspections of compounding pharmacies, and if so how do we pay for it? Do we just want someone to be held responsible–who: FDA, pharmacy boards, or someone else?

The basic dilemma is simple: we want safe and effective medicines, but we also want them at a price that we can afford. Compounding pharmacies may provide certain formulations of medicines without the overhead and costs related to commercially-manufactured and regulated medications. In some instances, compounding pharmacies may be able to offer medications with the same active compounds used in conventional drugs but with different inactive ingredients at lower costs than commercial medications. When such pharmacies are too small, few people realize the benefits of customized medications due to availability or cost. When they are too big, they are viewed as traditional drug manufacturers by FDA, leading to questions about what regulatory oversight is appropriate or warranted.
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globalmap.pngThe Global Clinical Risk Management and Regulatory Policy Conference will take place in Alexandria, Virginia on July 11-12, 2013. Throughout the two-day program, executives from industry will have an opportunity to discuss and debate the many challenges associated with profiling the risk of products as well as minimizing these risks and meeting regulatory expectations. With a well-rounded speaking platform that includes not only industry representation but also regulatory bodies, legal perspectives and the healthcare professional, participants will have an unrivaled opportunity to engage, network and learn from leading executives and corporations.

As with all Q1 programs, the focus of the event will not only lie upon the educational content, but also providing attendees with an opportunity to network and build relationships across this highly dynamic and evolving market. For conference sponsors supporting this program, the event will be an ideal vehicle for both learning more about advanced RMPs, but also an opportunity to disseminate information regarding products and services supporting pharmaceutical risk management.


  • Harmonizing risk management strategies for global markets
  • Measuring the effectiveness of approved REMS & RMP
  • Working with regulatory agencies to revise risk plans
  • Forecasting the FDA’s next steps in determining REMS drug safety improvement
  • Strengthening benefit-risk analysis on an international scale
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    Q1 ProductionisOn July 11-12, Q1 Productions (“Dedicated to Quality First®) will be hosting in Alexandria, Virginia, its Global Clinical Risk Management & Regulatory Policy Program: Implementation of Advanced Risk Management Plans that Increase the Effectiveness of Risk Assessment and Mitigation, while Increasing Drug Safety and Meeting Regulatory Policy & Guidance on a Global Level. FLH Partner Brian J. Malkin is featured to speak on July 11 with the topic: “Developing a Single, Shared REMS in a Collaborative Setting”. The session description for Mr. Malkin’s presentation states:

    The FDA approves single, shared REMS for product categories with similar risk management programs to help relieve some of the burden on healthcare providers and pharmacies. The development of shared REMS requires that multiple companies and the FDA work in tandem to unify data and risk minimization systems, a model which some companies have also used to help organize risk management plans internationally. By ensuring a strong cross-corporate collaboration, internal regulatory policies, data analysis and communication systems can be synchronized internationally for advanced risk management programs.

    • Structuring lines of communication within shared REMS network

    DNAMoney.pngOn June 27, the Massachusetts Biotechnology Council (“MassBio”) featured its second Forum in the series “Adventures in Biotech: Stories of Success (and Failure): A Six-Part Series: June-October 2013, called “Financing the Dream: Avenues for Raising Capital”. The presenters included: Jeff Arnold, President and CEO, Arnold Strategies, LLC; Bernard Davitian, Vice President, Business Development Licensing & Structured Investments, Sanofi-Genzyme BioVentures; Michelle Dipp, M.D., Ph.D., Co-Founder and CEO, OvaScience; and Guy Macdonald, President and CEO, Tetraphase Pharmaceuticals with moderators Marc R. Cote, Chief Operating Officer, Accellient Partners, LLC & Chief Financial Officer, Synchroneuron Inc. and John Hession, Partner, Venture Capital Financings & Emerging Companies Practice Groups, Cooley LLP. Frommer Lawrence & Haug LLP is an active member of MassBio and attended this Forum.

    Arnold described the process how “angels do drugs,” for example, repurposing previously-approved therapies for new uses, which may involve lower risk and capital and a clear opportunity for exit. An angel investor or angel (also known as a business angel or informal investor) is an affluent individual who provides capital for a business start-up, usually in exchange for convertible debt or ownership equity. With angel investing, opportunities generally require financings under $5 million with no venture capital in the plan and value-creating milestones early on. Some advantages of angel investing, Arnold explained, are rolling closes with easy follow-ons and more is typically owned at exit. Angel investing, however, requires more investors (40+) that have more involvement than a board member on a venture capital fund. Building a syndicate requires finding a champion and applying to several groups simultaneously with drug candidates in one or more incubators for development. The angel investors are looking for a clear exit strategy, typically within 3-6 years, which often takes longer for pharmaceutical/biotechnology products. On angel money, clinical studies may get as far as phase 2 but never go to all phase 3 studies; at this stage, the projects require big pharmaceutical manufacturer support to continue.

    Arnold noted that grant funding, such as grants from the National Institutes of Health (“NIH”), will help to generate interest in the product(s) but obtaining angel money requires frequent and continuous networking. Many prospects will not advance to a true diligence, e.g., there are 8 Mass Medical meetings a year with about a dozen new plans a month; at each meeting there are about 200 proposals evaluated, and three proposals are presented at each meeting with only one advancing to a true diligence.

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    On June 27, 2013, the Center for Drug Evaluation and Research (“CDER”) held its popular two-part “CDER Town Hall” at the Drug Information Association’s (“DIA’s”) 49th Annual Meeting at the Boston Convention and Exhibition Center. Highlights of the first day are provided here; highlights of other selected other leading up to the CDER Town Hall on the final day are provided here.



    During the CDER Town Hall, key leaders from CDER were on deck to answer questions from the audience. Below are some of the topics addressed in the second part, which featured from FDA: Gerald J. Dal Pan, M.D., Director, Office of Surveillance and Epidemiology, CDER; John K. Jenkins, M.D., Director, Office of New Drugs, CDER; Justina A. Molzon, J.D., M.Pharm., CAPT, USPHS, Associate Center Director for International Programs, CDER; Christine M.V. Moore, Ph.D., Acting Director, Office of New Drug Quality Assessment, Office of Pharmaceutical Science, CDER, Robert T. O’Neill, Ph.D., Senior Statistical Advisor, Office of Translational Sciences, CDER; and Robert J. Temple, M.D., Deputy Center Director for Clinical Science, CDER.

    Clinical Trials

    Regarding increasing patient involvement in clinical trials, O’Neill thought that it was long overdue to have patients more involved in the clinical trial process but acknowledged there would be potential logistical issues. For example, current informed consent forms may need to be reevaluated. In addition, the role of subjects needs to be better understood, including provisions for follow up information. Right now, he explained, it is unclear to the extent there are “trial hoppers”, i.e., subjects who drop out and try other experimental products or unblind the study by discovering they are taking the test drug or placebo, and how this affects trial outcomes. Getting patients more involved in the clinical trial process could help to identify these individuals across studies for treatment products for the same indications.
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    Boston Convention Center and Exposition Hall.pngOn June 24-27, 2013, the Drug Information Association (“DIA”) held its 49th Annual Meeting at the Boston Convention and Exhibition Center. Highlights of the first day are provided here. DIA’s Annual Meeting continued with a variety of other presentations on topics such as personalized medicine, orphan drugs, developing treatments for Alzheimer’s Disease, biosimilars, and more. Some of topics covered are described below.

    Orphan Drugs

    One of the themes of the conference was orphan drugs and personalized medicine. To those ends, several speakers advocated for FDA guidance on designing clinical trials for orphan drugs, going from a handful of patients to approval, as well as designing clinical trials for personalized therapies.


    While there are biosimilars in emerging markets, it remains unclear how useful the information would be for product development in the United States. First, many of the biosimilars in emerging markets were approved prior to regulatory rules or guidance in those markets. Second, most of the biosimilar manufacturers in emerging markets have since designed or are working on modifications to their biosimilars, in particular their clinical development plans, to meet the requirements of FDA, the European Medicines Agency (“EMA”), and similar industrialized, regulatory authorities. To the extent biosimilars marketed in emerging countries have been analyzed, there were potency variations in tested epoetins from 48-163% in mice, many had high amount of aggregates, and many failed to meet EMA specifications. But in emerging markets, the innovator counterpart to biosimilars may not be available for comparison, leading to higher patient acceptance and government support, e.g., China has had biosimilars for more than 20 years. In China, however, biosimilars were regulated similar to small molecules until 2007, when China established a China FDA in 2007, which is currently creating a defined pathway for biosimilars under the new regime. Brazil, Mexico, Argentina, India, and Korea also have marketed biosimilar products with varying degrees of regulation and standardization.
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    On June 24-27, 2013, the Drug Information Association (“DIA”) held its 49th Annual Meeting at the Boston Convention and Exhibition Center. The DIA President for the coming year, Minnie Baylor-Henry, Worldwide Vice President, Regulatory Affairs, Johnson & Johnson Medical Devices & Diagnostics, described 2013 as the year of the patient, and she hopes to see the focus on patients driving medicine to transform medical care in the coming years. DIA’s Annual Meeting Chair, Susan A. Milligan, J.D., M.D., Vice President, Global Regulatory Therapeutic Area Head, Genentech, Inc. A Member of the Roche Group, challenged meeting attendees to “step out of your comfort zone” and volunteer and think innovatively, act collaboratively, network to build new relationships, and help to improve patient care.



    Along these lines and following the introductory comments, the Annual Meeting kicked off with a Keynote from Daniel Kraft, M.D., Executive Director, FutureMed. Kraft has over 20 years of experience in clinical practice, biomedical research, and healthcare innovation, including some of his own inventions. FutureMed is a program that explores convergent, exponentially, developing technologies and their potential in biomedicine and healthcare. Kraft also recently founded IntelliMedicine, focused on enabling connected, data-driven, and integerated personalized medicine. Kraft’s message to the attendees was that technology is moving medical care exponentially, principally from an information technology perspective.

    From Kraft’s perspective, we have already reached the option of personalized medicine by virtue of the types of devices that can be used to collect real-time information from patients to create “dashboards” of information for vital signs to adjust medical care. Kraft demonstrated an example where a heart-rate monitor can provide information to smartphones and a physician’s office to determine what type and dose of medication is appropriate for a particular patient without the need to visit a doctor following periodic consultations. As additional examples, Kraft explained that toy drones can be used to deliver medicine, especially in hard-to-reach areas, and Skype can be used to conduct “mini physicals” via the Internet. In the works, and to some extent already being utilized, are smartpills that can see real-time images of a patient’s gastrointestinal tract and deliver medicine via a smarphone application at precise times rather than relying on previous drug delivery mechanisms such as resident time or pH in the gastrointestinal tract.
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    Thumbnail image for supreme court.jpgOn June 24, the U.S. Supreme Court decided to shield generic manufacturers from product liability suits in Mutual Pharmaceutical v. Bartlett. The Court held that a generic manufacturer could not be held liable for a design-defect claim on a small molecule, pharmaceutical product, because the claim was preempted by the Federal Food, Drug, and Cosmetic Act (“FD&C Act”).

    Karen Bartlett met with her physician to treat her shoulder pain. Her physician prescribed Clinoril® (suldinac), and she was dispensed a generic version marketed by Mutual Pharmaceuticals (“Mutual”). Unexpectedly, Bartlett suffered a rare and devastating reaction to the drug. Even after months of treatment, she was left severely disfigured and almost entirely blind.

    As we blogged previously, Bartlett sued Mutual in New Hampshire under a state design-defect theory of product liability. Like many states, New Hampshire borrowed its design-defect cause of action from the Restatement (Second) of Torts. Under this theory, Bartlett alleged that the active ingredient sulindac was inherently and unreasonably dangerous.
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    FLH Partner Brian J. Malkin will be attending the Drug Information Association’s (“DIA’s”) Annual Meeting in Boston, which is being held on June 23-27, 2013. DIA’s Annual Meeting draws more than 7,000 life science professionals from all levels of disciplines involved in the discovery, development, and life cycle of medical products. Mr. Malkin is committed to collaborating with other life science professionals to facilitate innovation that leads to the development of safe and effective medical products and therapies to patients. DIA’s Annual Meeting features over 250 educational programs with over 800 speakers, over 450 exhibitors, and various networking events and lunches to help these life science professionals learn how to perform their roles more effectively and forge new productive relationships. Mr. Malkin looks forward to meeting you there and welcomes individuals or companies wishing a meeting to contact him via e-mail at

    Thumbnail image for Thumbnail image for orphan drug.bmpOn June 12, 2013, FDA issued a Final Rule amending the 1992 Orphan Drug Regulations to implement the Orphan Drug Act. The Final Rule largely reflects the 2011 Proposed Rule (see our previous blog on the draft rule here) to amend the Orphan Drug Regulations with several changes for clarity and accuracy. FDA explicitly stated that the Final Rule has no effect on the scope of, or eligibility for, orphan-drug-exclusive approval, because it merely clarifies existing and longstanding FDA practices. The Final Rule will take effect on August 12, 2013.

    The two most important amendments and clarifications in the final rule are the new definition of “orphan subset” and the various clinical superiority requirements for designation requests and exclusive approvals for a subsequent drug for the same use or indication.

    To qualify as an “orphan subset” drug (21 CFR §316.3(b)(13)), the drug sponsor must show that while the drug is safe and effective in the orphan subset population, the drug is not suitable for use in those persons outside of the orphan subset (i.e., those persons who have the same non-rare disease or condition). Such non-suitability must be based on either a pharmacokinetic property (such as toxicity and mechanism of action), or previous clinical experience with the drug.
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