FDA Lawyers Blog

This week The Venture Café in Cambridge, Massachusetts hosts Life Sciences Week with a special focus on life science research in the Greater Boston area. Featured life science research speakers include Akrivis (ADAPT™ technology, which allows cancer detection much earlier by increasing the sensitivity of early biomarker detection and enabling the medical imaging of millimeter-sized cancer tumors), Human Metabolome Technologies (metabolome profiling for tumor metabolism, biomarker discovery and production optimization), Advirna (powerful and innovative tools to regulate activity of genes inside living cells), Heartbt Foundation (newly-developing non-profit seeking to boost translational research by bridging medical, professionals, big pharma, researchers, NGOs, the general public, and others), Extend Biosciences (startup biotech company with a platform technology that enables the development of long-acting peptide based drugs), Anchor Therapeutics (pre-clinical stage drug discovery company advancing Pepducin Technology, a novel approach towards allosteric modulators of G-protein coupled receptors), Lab Central (soon-to-open facility to house up to 65 scientists, in 20 individual lab stations and 9 private lab suites in the heart of Kendall Square), and Cellanyx (biomarker-based diagnostic biopsy test to determine oncogenic and metastatic potential for prostate tumors). The Venture Café will also host a Roundtable of Life Sciences Entrepreneurship in Massachusetts, featuring Peter Abair of the Massachusetts Biotechnology Council ("MassBio"), Pamela Norton from the Mass Life Sciences Center, and Peter Parker of Lab Central.

Written by Brian J. Malkin

Other Posts By This Author

During Life Sciences Week, FLH Partner Brian J. Malkin will host Office Hours from 3-5pm EST along with several other service providers in the healthcare field. Mr. Malkin's Office Hours description reads:

Chat with Brian J. Malkin, Partner at Frommer Lawrence & Haug LLP. Brian specializes in FDA-regulated products, in particular pharmaceutical, biotechnology products and biosimilars. Discuss intellectual property, pathways for FDA approval, as well as life cycle management and due diligence investigations. Brian frequently speaks on a variety of IP- and FDA-oriented topics, and is editor of the FDA Lawyers Blog.

This blog is a second part to a blog here, describing Annual Conference for the Food and Drug Law Institute ("FDLI") held on April 23 and 24, 2013, its in Washington, D.C.

On the first day, FLH Partner Brian J. Malkin spoke on a panel discussing the priorities for the Center for Biologics Evaluation and Research ("CBER"). The two key CBER presentations came from Diane Maloney, J.D.., Associate Director for Policy, and Mary Malarkey, Director, Office of Compliance and Biologics Quality. The panel also included Michael S. Reilly, Executive Director, Alliance for Safe Biologic Medicines, and Mark S. Robbins, Ph.D., Vice President, Clinical Regulatory Affairs, DiaMedica USA, Inc. and was moderated by Scott Cunningham, Partner, Covington & Burling LLP. A key issue raised by panel was the status of biosimilars. Reilly, for example, was concerned that there may be misinformation about biosimilars, especially because there is no public information concerning biosimilars applications being considered in the United States. Malkin asked when FDA planned to issue additional guidance, because FDA's guidance has so far been very general and concerns pre-investigational or pre-biosimilars application stages, not the key issues of interchangeability and naming that have been debated. Maloney explained that CBER and the Center for Drug Evaluation and Research ("CDER") have been discussing strategy, even though there still have been no filed biosimilar applications, and would issue additional guidances. At the same time, Malkin and others acknowledged that at the state level, legislators have been passing bills that specifically prohibit substitution of biosimilars for their referenced counterpart, unless FDA deems the biosimilar "interchangeable" and naming issues and more persist.

Written by Brian J. Malkin

Other Posts By This Author

A question was raised about a pending Citizen Petition that includes an argument that it was a taking for biosimilar applicants to file applications referencing biologic products before the passage of the Biologics Price Competition and Innovation Act ("BPCIA") (March 23, 2010). In this Petition, Abbott argued that before this date, when biologics license applications ("BLAs") were submitted, their sponsors had "reasonable, investment-backed expectations that the trade secrets in their applications would not be used to approve competing products." Abbott asserts, therefore, that FDA's use of trade secrets in these BLAs to support biosimilar approvals "would constitute a taking under the Fifth Amendment to the U.S. Constitution. FDA should not implement the BPCIA in any manner that would raise constitutional issue." While most panel members declined to respond, Malkin hazarded a guess that based on comments FDA has made (see for example here) and in the context of FDA's Citizen Petition response for a similar issue concerning 505(b)(2) new drug applications (where a similar takings argument has been made), FDA wanted to decide that there was no "taking," but FDA has not answered the petition in part because no biosimilar application has been filed to date.

On April 23 and 24, 2013, the Food and Drug Law Institute ("FDLI") held its Annual Conference in Washington, D.C. As expected, FDLI's Conference featured the FDA Commissioner, Margaret A. Hamburg, M.D., presentations from leaders from all of FDA's Centers and the Chief Counsel, Elizabeth Dickinson, and leaders from industry, academia, and the legal bar. Unlike previous years, however, there were far fewer FDA attendees due to budget cuts, and FDA seemed more reluctant to use the Conference as a platform for announcing new policy or initiatives.

Hamburg kicked off the Conference with her recognition that FDA's budget was cut, along with other government agencies, noting that it would make times tight but that there are no planned furloughs. Hamburg said that this fiscal year, FDA lost about $209 million-$126 million in budget authority and $83 million in user fees. FDA will continue to collect user fees, but FDA cannot use them this fiscal year due to the sequesteration issue. Hamburg said that the reduced budget would mean reductions in programs but did not specify which ones. Yet, at the same time, Hamburg emphasized that FDA has been busy implementing its new regulatory authorities, including the new Center for Tobacco Products and authorities in the Food and Drug Administration Safety and Innovation Act ("FDASIA").

Written by Brian J. Malkin

Other Posts By This Author

Hamburg stressed that it has become more and more apparent that its regulated industries need to build quality in their products. She highlighted that quality issues have caused two out of three drug shortages, and FDA has uncovered "shockingly unsafe drugs" at compounding pharmacies. Over the past several months, Hamburg explained, FDA has been inspecting compounding pharmacies and has found unidentified black particles in what were supposed to be sterile injectable products, rust and mold in sterile rooms, and products being processed with bare hands. At the same time, FDA has encountered increased resistance during its inspections, resulting in at least two cases needing administrative warrants. Hamburg said that FDA believes there should be a distinction between traditional and nontraditional compounding--traditional is individualized to patient; nontraditional is sterile product prepared out of state compounded and anticipated without a prescription. For nontraditional compounding, FDA has asked Congress for more clear FDA authority to monitor and examine records in the "patchwork" of compounding rules.

Next week, FLH Partner Brian J. Malkin will speak at Center for Biologics Evaluation and Research ("CBER") Panel at FDLI's Annual Meeting held in Washington, D.C. on April 23-24. The CBER Panel will be held on the first day of the Conference, Tuesday, April 23, from 2-3:30 p.m. FDLI has posted the key two presentations by CBER Representatives Diane Maloney, Esq., Associate Director for Policy, and Mary Malarkey, Director, Office of Compliance and Biologics Quality. The panel will be moderated by Scott Cunningham, Partner, Covington & Burling LLP, and also includes Michael S. Reilly, Executive Director, Alliance for Safe Biologic Medicines, and Mark S. Robbins, Ph.D., Vice President, Clinical Regulatory Affairs, DiaMedica USA, Inc.

As demonstrated by the presentations already posted by Maloney and Malarkey, the panel has a lot of ground to cover, and we as panel members have been providing feedback for additional topics to address as time permits. All of us hope for a lively discussion following the initial presentations and hope to see you there!

Written by Brian J. Malkin

Other Posts By This Author

FDLI's Annual Conference is the largest (750+ attendees expected) and longest running conference for the FDA-regulated industry, which now includes tobacco products. FDLI's program brings together experts from the Federal Government, industry, private sector bar, consulting organizations, and academia in one place to discuss legal, regulatory, policy, and economic issues falling in FDA's vast authority. FDA Commissioner, Margaret A. Hamburg, M.D., will provide the Keynote Address the first day, with other plenary sessions featuring FDA's top regulatory and compliance officials, breakouts for all of FDA's centers and a sessions featuring compliance and liability issues. The next day features top cases in food and drug law, concurrent breakouts in emerging issues, an address from FDA's Chief Counsel, Elizabeth Dickinson, and plenary sessions in interagency dynamics and the role of the media in food and drug law, regulation, and policy.

On March 14-15, the Massachusetts Biotechnology Council ("MassBio") held its Annual Meeting in Cambridge, Massachusetts. The Meeting also featured a Keynote from FDA Commissioner Margaret A. Hamburg, M.D. (see related blog here). Key themes at the Meeting were the importance of the Cambridge/Boston biotechnology community for advancing new therapies and the unique resources available in the area that have made it an industry leader. Some of the Cambridge/Boston advantages discussed were the intellectual research capital (local universities such as Harvard and Massachusetts Institute of Technology), venture capital, and local biotechnology businesses, such as Biogen Idec and Genzyme, as well as other biotechnology companies that now have offices in the Cambridge/Boston area and are seeking partnerships to develop new products, such as AstraZeneca, Pfizer, Merck, Novo Nordisk, and Sanofi.

On the second day, Hamburg described here "special affection" for the Cambridge/Boston region dating back to her days at Harvard, saying that she hopes D.C. "would be as efficient and congenial as here." Hamburg said that the Cambridge/Boston region is a life sciences enterprise fueled by top notch research and medical care with the top five NIH-funded hospitals and a "biotech supercluster second to none" with "a remarkable 500 biotech and pharma companies here, and some thirty venture capital firms."

Written by Brian J. Malkin

Other Posts By This Author

Hamburg described FDA as striving for true collaboration and regulatory flexibility with industry, including MassBio, and has been hearing that industry wants more clarity, certainty, transparency with decisions. Hamburg said that FDA is trying to have creative approaches--not a one size-fits-all approach. To this end, Hamburg described approaches that FDA has taken with four new products from the Massachusetts area: 1) Inclusig® for two rare forms of leukemia, 2) Juxtapid® (an orphan drug), 3) Linzess® for irritable bowl syndrome, and 4) Kalydeco® for cystic fibrosis. In addition, Hamburg highlighted new provisions in the Food and Drug Administration Safety and Innovation Act ("FDASIA") for expedited approvals, citing 31 breakthrough therapy designation requests, of which 9 have been granted, 10 denied, 11 pending, and 1 withdrawn. To help with more companies taking advantage of this new process, FDA will be publishing a new guidance shortly, Hamburg announced.

On March 14-15, the Massachusetts Biotechnology Council ("MassBio") held its Annual Meeting in Cambridge, Massachusetts. The Meeting featured key topics such as biosimilars and a Keynote from John Crowley, Chairman and CEO of Amicus Therapeutics.

On the first day of the conference, Crowley exemplified many of the speakers' entry in biotechnology, which originated with a family member or friend with a disease requiring development of a biotechnology product. For Crowley, it was his two children Megan and Patrick, were diagnosed with a severe neuromuscular disorder, Glycogen storage disease type II, known as Pompe's disease. Rather that sitting still to wait for a cure, Crowley became involved in the process, first moving to Princeton, New Jersey, to be close to doctors specializing in the disease and leaving his job with Bristol-Myers Squibb. He later took a position as CEO of Novazyme Pharmaceuticals, a biotechnology research company located in Oklahoma City founded by Dr. William Canfield, which was conducting research on a new experimental treatment for the disease. Novazyme was acquired by Genzyme Corporation, which was then the world's third largest biotechnology company. Crowley was put in charge of Genzyme's global Pompe program, becoming the largest research and development effort in the company's history.

Written by Brian J. Malkin

Other Posts By This Author

Through these efforts, an experimental enzyme replacement therapy was developed, and Megan and Patrick Crowley received the therapy, which Crowley credits with saving his children's lives. Crowley went on to become President and CEO of Orexigen Therapeutics and was named the President and CEO of Amicus Therapeutics, based in Cranbury, New Jersey, which he helped take public in 2007. Crowley's efforts were documented in a Wall Street Journal article and other publications, which ultimately resulted in Harrison Ford working to bring the story to life in a major motion picture, Extraordinary Measures.

Written by Brian J. Malkin

Other Posts By This Author

The last day of the Generic Pharmaceutical Association ("GPhA") 2013 Annual Meeting also featured an FDA Keynote Address by FDA Commissioner Margaret A. Hamburg, M.D. For a summary of public sessions from Day Two, please see the previous blog here; a summary of the CEOs Unplugged session may be found here.

Video streaming by Ustream

Following the CEOs Unplugged session on day three, Hamburg delivered her Keynote Address. Hamburg said that GPhA was one of the few organizations that she has chosen to address each year since becoming Commissioner, "because of the dynamic character of this group, your prominent role in the nation's health care system and the importance of the work you do." Celebrating GDUFA and the FDA Safety and Innovation Act ("FDASIA"), Hamburg emphasized that FDA is making "quality one of the highest priorities this year," hoping that GPhA's members do the same. Despite generic drug companies providing 85 percent of all prescriptions filled, some studies have suggested that many physicians still have "negative perceptions about the quality of generic medicines," which Hamburg said was "troublesome - and assuredly not fair."

Hamburg reported "impressive strides in implementing GDUFA," explaining that FDA got the word out of new requirements and fees early, resulting in the collection of almost $125 million in fiscal year 2013 user fees to help brining in staff and other resources to help reduce the backlog of ANDAs above 2,500 applications with median review times at about 31 months. FDA has assembled a list of about 2,000 facilities supplying generic drugs to the U.S. following self-identification procedures.

Written by Brian J. Malkin

Other Posts By This Author

The last day of the Generic Pharmaceutical Association ("GPhA") 2013 Annual Meeting featured a program known as "CEOs Unplugged" and an FDA Keynote Address by FDA Commissioner Margaret A. Hamburg, M.D. For a summary of public sessions from Day Two, see the previous blog here. This blog focuses on the CEOs Unplugged session. A subsequent blog will cover FDA's Keynote Address.

The CEOs selected for this year's program included Donald DeGolyer, President, Sandoz, Inc., Tony Mauro, President, Mylan, North America, Thomas Moore, President, Hospira USA, Allan Oberman, President and CEO, Teva Americas Generics, and Siggi Olafsson, President, Actavis Pharma.

Perhaps Oberman summed up the overall themes best when he acknowledged that the lines between innovator and generics are beginning to blur, where generic medicines are becoming more complex, and generic manufacturers are increasingly seeking a niche to compete in. The CEOs noted that none of the same CEOs were on the stage five years ago, which signals just how much the key players and CEOs have been changing. Other comments Oberman made included: (1) he hoped the Generic Drug User Fee Act ("GDUFA") approval and efficacy measures would be used effectively and manufacturing sites outside the U.S. would be under similar scrutiny as in the U.S., (2) no one is really planning for shortages, but it is important to have effective communication to prevent them in particular with FDA, (3) industry needs to stop "fear mongering" to figure out when biosimilars will be approved or interchangeable--some people will take biosimilars and others will not, just as with generic drugs, (4) more mergers in the generic pharmaceutical industry should be expected, especially in emerging markets, (5) generic pharmaceuticals should be more available in the eastern part of the world where access to medicine may still be restricted, which provides more growth opportunities, and (6) traditional generic manufacturers should consider either developing new molecular entities or combining older generics in ways to improve convenience, safety, or effectiveness.

Written by Brian J. Malkin

Other Posts By This Author

On February 20-22, 2013, the Generic Pharmaceutical Association ("GPhA") held its 2013 Annual Meeting attracting over 600 attendees to see how the nation's health and regulatory issues will impact the generic industry and consumers who use generic medicines. While some events are for GPhA members only, a majority of the events are open to all attendees and were held in a single room or exhibit hall. Most of the main events were held in a slickly-decorated room filled with stars, comets, and planets.

While the Meeting covered a lot of territory, recurrent themes appeared to emphasize that the generic industry has come of age, where it joins its big-pharma brothers in having an office on par level with the Office of New Drugs ("OND") in FDA's Center for Drug Evaluation and Research ("CDER") and now pays user fees to speed up generic drug approvals. GPhA's members announced that they are ready to develop high quality generic versions of specialty pharmaceuticals and biologics, some of which may require the expenditure of hundreds or more millions of dollars to develop, obtain approval for, and market. At the same time, GPhA appears to hold onto the notions that that they can continue to settle cases with reverse payments that the Federal Trade Commission ("FTC") views as so-called "pay-for-delay" settlements that are presumptively anticompetitive. GPhA also believes that manufacturers should be allowed to sell generic versions of products with the same labeling as the innovator, when the innovator or generic companies that manufacture and sell the product are aware of safety information not presently included in the FDA-approved labeling.

Kicking off the meeting with a "State of the Association", GPhA President and CEO Ralph G. Neas described generic drugs as the "backbone of the pharmaceutical industry." Neas expressed the Association's confidence that FDA will "come through" and help the industry understand what will be expected of it to develop biosimilars and interchangeable biosimilars, which are the future to save lives and money.

On February 13 and 14, 2013, Leerink Swann ("Leerink") held its annual Global Healthcare Conference at the Waldorf-Astoria Hotel in New York, New York. Each year the Conference highlights emerging themes and controversies in healthcare, where Leerink's equity analysts present surveys and moderate discussions with MEDACorp Key Opinion Leaders and industry specialists to provide unique and timely insights. MEDACorp is Leerink's network of 30,000 healthcare professionals including key opinion leaders, practitioners, clinicians, and hospital administrators. In between the main panels, senior management from some of the companies identified by Leerink as the most prominent and promising deliver "fireside chats" and presentations with company updates, including discussions of new products in their pipeline under review. This year the sole sponsor of Leerink's Global Healthcare Conference was Latham & Watkins LLP.

Headlining the Conference was a Keynote Address entitled "Innovating Medical Product Development - FDA and Other Forward Looking Trends" delivered by Vicki L. Seyfert-Margolis, Ph.D. Seyfert-Margolis just recently was the Senior Advisor for Science Innovation and Policy in FDA's Office of the Commissioner. Seyfert-Margolis is currently Chief Science and Strategy Officer for Precision Health, which provides services, infrastructure, and technologies to companies developing personalized medicines.

Written by Brian J. Malkin

Other Posts By This Author

Seyfert-Margolis worked for about three and a half years in FDA's Office of the Commissioner, where she led the effort to help develop a more coherent policy for companion diagnostic and personalized medicine, including developing guidances for personalized medicine such as "In Vitro Companion Diagnostic Devices" and "Qualification Process for
Drug Development Tools". While at FDA, Seyfert-Margolis looked at why companies were not seeing as many returns from their investments in research and development, noting that it was not FDA's "fault" for less new chemical entity filings, because FDA can only review or approve products that are filed in new applications.

This Thursday, FLH Partner Brian J. Malkin will host Legal Office Hours at The Venture Café in Cambridge, Massachusetts. Mr. Malkin's Legal Office Hours description reads:

Learn how you can protect your start-up with patent and trademark protection from intellectual property Partner Brian J. Malkin, Frommer Lawrence & Haug LLP. Mr. Malkin is an expert on FDA-regulated products, in particular pharmaceutical/biotechnology products and biosimilars, and can discuss pathways for FDA approval, as well as life cycle management and due diligence investigations. Mr. Malkin recently published a chapter on biosimilars, has a primer on the drug and biologics approval process, frequently speaks on a variety of IP- and FDA-oriented topics, and is the editor of FDA Lawyers Blog, a blog that focuses on legal and scientific developments for FDA-regulated products.

The Venture Café was created to provide a resource for the Boston entrepreneurial and innovation communities. Our mission is to enable fresh and useful conversations.

Cambridge is a fountain of innovative spirit, spirit that needs a framework to reach its full potential. The Venture Café serves as a nexus for helping innovators and entrepreneurs find one another and collaborate to bring their dreams to reality.

Even in this digital world, it's important to have a physical space. Shared physical spaces provide common meeting ground and a forum for semi-serendipitous encounters that often foster brainstorming and drive creativity. Meeting in person establishes the trust that's so crucial to working together, particularly on risky, underfunded projects. The Venture Café can provide the framework upon which numerous experimental "applications" can be nurtured and launched.

On January 24 to a packed house, the Food, Drug and Cosmetic Law Section of the New York State Bar held its annual meeting. This year, the agenda featured presentations on medical devices, a Supreme Court update, an in-house/outside counsel panel to discuss effective relations for FDA/regulatory advice, a discussion of the Federal Sunshine Act, and "A View from the Inside" retrospective of some hot issues at FDA from a recent high-level official at FDA, including the new food and pharmacy initiatives under development.

In the Supreme Court update called "Pivotal Court Cases for FDA Practitioners 2012-2013 Updates", FLH Partner Brian J. Malkin, spoke on two cases to watch in the first quarter of 2013, Mutual Pharm. Co., Inc. v. Bartlett , No. 12-142 (U.S., cert. granted Nov. 30, 2012, argument scheduled Mar. 19, 2013) and Bowman v. Monsanto Co., No. 11-796 (U.S., cert. granted Oct. 5, 2012, argument scheduled Feb. 19, 2013). The question presented in Mutual v. Bartlett is:

Whether the First Circuit erred when it created a circuit split and held--in clear conflict with this Court's decisions in Pliva, Inc. v. Mensing, 131 S. Ct. 2567 (2011); Riegel v. Medtronic, Inc., 552 U.S. 312 (2008); and Cipollone v. Liggett Group, Inc., 505 U.S. 504 (1992)--that federal law does not preempt state law design-defect claims targeting generic pharmaceutical products because the conceded conflict between such claims and the federal laws governing generic pharmaceutical design allegedly can be avoided if the makers of generic pharmaceuticals simply stop making their products.

Written by Brian J. Malkin

Other Posts By This Author

Bowman v. Monsanto is a case that my firm, Frommer Lawrence & Haug LLP, is arguing on behalf of petitioner Bowman, where the question presented is:

Patent exhaustion delimits rights of patent holders by eliminating the right to control or prohibit use of the invention after an authorized sale. In this case, the Federal Circuit refused to find exhaustion where a farmer used seeds purchased in an authorized sale for their natural and foreseeable purpose--namely, for planting. The question presented is: Whether the Federal Circuit erred by (1) refusing to find patent exhaustion in patented seeds even after an authorized sale and by (2) creating an exception to the doctrine of patent exhaustion for self-replicating technologies?

Mr. Malkin's summaries of these two cases may be found here. His presentation for these two cases, including topics for consideration by the Food, Drug, and Cosmetic Section may be found here.

Today, FDA Center Officials from the Center for Drug Evaluation and Research ("CDER"), the Center for Biologics Evaluation and Research ("CBER"), and the Center for Devices and Radiologic Health ("CDRH") provided an overview of upcoming biotechnology issues to the TechCouncil of Maryland, MdBio / MdTech at a full house in Bethesda, Maryland.

Representing CDER, Steven Kozlowski, M.D., Director of the Office of Biotechnology Products, Office of Pharmaceutical Science, said that his Office, which regulates monoclonal antibodies and therapeutic proteins, has been primarily concerned with the mechanism of action and potential for immunogenicity for these products. Describing a triad of research and development, application review, and inspections, Kozlowksi described his Office's challenges as often concerning "too many notes" for biologics--discerning which notes matter, given that technology has come up with ways to further characterize products and reveal more notes.

Written by Brian J. Malkin

Other Posts By This Author

Kozlowski said that through the life cycle continuum of a biotechnology product, it is the applicant's responsibility to make sure that biotechnology products are manufactured using the best available science to prevent issues such as viral contamination that can cause plant shut downs and shortages. To help prevent such issues, FDA is further integrating its review and compliance functions, in part with the use of new user fee authorizations. For biosimilars, FDA recognizes the studies necessary for approval will depend on the analytics and results from those analytics, comparing the innovator's product to the proposed biosimilar product.

On December 12, FDA held a meeting of its Drug Safety and Risk Management ("DSaRM") Advisory Committee regarding development of a framework for addressing what risk evaluation and mitigation strategies ("REMS") are appropriate for teratogenic drugs. Teratogenic drugs are drugs that may cause birth defects for developing fetuses. The Food and Drug Administration Amendments Act ("FDAAA") requires FDA to bring to the DSaRM Advisory Committee for review at least one drug with Elements to Assure Safe Use ("ETASU"), and this was the topic chosen for 2012.

According to the opening remarks, FDA has recognized that over the years, its approach regarding the development of risk management programs for teratogenic drugs "appears to be inconsistent." The DSaRM Advisory Committee began with FDA presentations, continued with stakeholder presentations from industry, prescribers, patients, and then ended with the full committee's discussion of the questions to address:

Written by Brian Malkin

Other Posts By This Author

FDA's proposed framework would take as intrinsic factors: (1) scientific evidence of teratogenicity (biological plausibility, non-clinical data, and human data) and (2) drug-product related factors (characteristic of the drug product, efficacy, and safety profile). The proposed extrinsic factors to consider in the framework are (1) drug product-related factors (actual drug use), (2) clinical-use related factors (characteristics of medical condition, patient population profile, and context of care), (3) regulatory factors (regulatory precedent, previous REMS experience, availability of new REMS tools), and (4) anticipated consequences of REMS.

On November 28-29, 2012, the American Conference Institute ("ACI") held in Boston, Massachusetts, its inaugural conference: "Orphan Drugs and Rare Diseases: Maximizing Opportunities and Overcoming Stumbling Blocks in the Designation and Development Process". The Conference was well attended and featured a pre-conference boot camp on the Orphan Drug Act as well as a post-conference master class on overcoming clinical trial challenges and proving the safety and efficacy for orphan drugs.

One highlight of the conference was Timothy R. Cote, M.D., M.P.H., Principal, Cote Orphan Consulting (Director of FDA's Office of Orphan Drug Products Development (2007-2011)). Cote provided a back drop for how the Orphan Drug Act came about, emphasizing that while for each individual disease the afflicted patient population is small, when all of the orphan diseases are pooled together, actually the population is sizable and a rapidly-growing area. Dr. Cote described orphan drug development as a "high touch" field where the need for new therapies are often driven by families with afflicted members and typical "big pharma" strategies are less effective. Calling it "scrappy not crappy" science, Cote explained that unlike big pharma projects that involve thousands of patients and hundreds of millions of dollars to develop new therapies, orphan drugs often can be developed for under $10 million--in part because there are so few patients who are candidates for clinical studies and treatment. Cote said while approximately 60% of orphan drug designation requests are approved, the success stories are the products that obtain new drug application approval and win the highly-coveted seven-year exclusivity for the first orphan indication ("a horse race"). More importantly, the basic research required to find cures for orphan drugs often provides valuable medical knowledge in how our bodies work, which he called "pharma karma."

Written by Brian Malkin

Other Posts By This Author

Another highlight of the conference was Christopher-Paul Milne, D.V.M., M.P.H., J.D., Associate Director, Tufts Center for the Study of Drug Development, Tufts University. Milne said that while the initial orphan market was thought of as relatively small, there are often higher rates of return than more "mainstream" diseases, particularly for diseases with more options for treatment. One phenomena that he tracked was the "ultra orphans," where the orphan population for treatment, which is restricted to less than 200,000 when applied for orphan drug designation in the United States, can get closer to the 200,000 number, and sometimes can expand to more mainstream numbers, if the therapy is later found to have non-orphan treatment options. While certain disease areas such as various cancers have good orphan drug representation, other therapeutic areas, such as neurology, have had less success stories, Milne reported. Milne added that amidst the tension of competition versus collaboration, it has often been important for unlikely partners to work together, with the help and motivation of patient groups, such as the National Organization for Rare Diseases ("NORD").