Biosimilars Ahead, Proceed with Caution

Posted under Affordable Care Act, Affordable Care Act (ACA), biosimilars, Blog, Companies, Diagnostics, FDA, FDA Guidance, Food and Drug Administration, Funding, Health, Health Care, healthcare, Medical Devices, Medical Supply, Pharmaceuticals, regulatory pathway for biosimilars, Startups, Universities, Videos by biotechnow@bio.org (Biotechnology Industry Organization)

By Richard M. Dolinar, M.D., Chairman, Alliance for Safe Biologic Medicines

In today’s budget-constrained world, the goal for health care is not only to save lives but also to save money. On Friday, May 11, the Food and Drug Administration (FDA) will hold a one-day public hearing on important medicines, known as biosimilars, that are under FDA consideration to come to the United States (U.S.) and offer the opportunity to help achieve the second prong of the health care goal: to save money. However, similar to any new medicine approval, patient safety must be paramount.

Biosimilars are attempted copies of innovative biotech medicines that have been available in the U.S. for a number of years. As members of the biotech community know, biologics have revolutionized the treatment of many serious and life threatening diseases in the short history of this industry. Biosimilars offer the hope of bringing life saving biologic drugs from the bench to the bedside in a cost effective manner and serve as another tool in the toolbox of healthcare providers. Unlike traditional pharmaceutical drugs that are made from chemicals and have structures that are well characterized, most biologics are made from living cells, with highly complex structures that are not easily understood, characterized or replicated. As a result, biosimilar medicines differ from generic drugs in that they are “similar to” but not exact copies of the innovator drug they attempt to replicate.

In 2010, the Patient Protection and Affordable Care Act (PPACA) granted the FDA the authority to approve biosimilars. Later that year the agency began consulting with patient groups, physicians and industry to exchange information that would eventually lead to the approval of biosimilars in the U.S. A few months ago the FDA took the first concrete step to create a pathway and issued draft guidance. The public hearing on Friday will allow stakeholders to provide testimony in response to the draft guidance and I am honored to be able to speak on behalf of the Alliance for Safe Biologic Medicines (ASBM).

In addition to my day job seeing patients as a practicing endocrinologist, I serve as the Chairman of ASBM, an organization that is working to raise awareness of biologics and biosimilars, as well as the important steps that should be taken to ensure safe use of these important medicines.   Our organization is composed of diverse healthcare groups—from patients to physicians, medical innovators, and others who have come together to ensure that patient safety is at the forefront of the biosimilars policy discussion.  We were pleased but not surprised to see the FDA lay out a science-based approach in the draft guidance largely building on the foundation laid by the European Medicines Agency (EMA).

The EMA began to establish the first formal regulatory pathway for biosimilars in 2003 and has gathered much data over the past 8 years that can, at a minimum help inform the development of policy in the U.S.  Policy makers should take advantage of this opportunity to learn from their experiences, both positive and negative.

We must also acknowledge that are differences between the EMA and FDA approach most notably in the area of “interchangeability” where the FDA has the authority to designate a biosimilar as interchangeable with its reference product and the EMA does not. This difference is not insignificant for patients in the U.S. because in theory it could lead to biosimilars being automatically substituted for the originator product by the pharmacist without consulting the prescribing physician. In the draft guidance the FDA signaled that it is not ready to prescribe a path to interchangeability at this time, and instead indicated that additional guidance will be necessary to better understand the challenges involved.

Differences aside, there is much to learn from the EMA experience and we believe that it provides a solid blueprint for the FDA to follow. At a minimum, ASBM members believe that the FDA must require biosimilar manufacturers to conduct clinical studies and produce analytical data sufficient to reassure patients and doctors that their products are safe. We also believe that unique nonproprietary names must be assigned to all biologic therapies so that physicians and patients know what caused an adverse event if one occurs.  Finally, as a practicing physician it is imperative that doctors and patients should be able to carefully choose the best course of treatment rather than have legislators and regulators decide for them.

For nearly 18 months, ASBM has been working to educate the public and policymakers about the great promise that biosimilars offer to patients in the U.S. Our message has been relatively simple, making lower cost medicines available to patients should be a priority but their availability must come with the absolute assurance that they are first and foremost safe. Our organization and its members have written Op-Eds, conducted webinars and hosted policy forums to exchange information about the issues and challenges associated with biosimilars. I am proud of the work we have done but ultimately realize as the late great Karen Carpenter sang so many years ago “we’ve only just begun.”

You can find more information at safebiologics.org, find us on Facebook or follow us on Twitter @SAFEbiologics.

Industry Regulatory Issues to be Highlighted at 2012 BIO International Convention

Posted under 2012 BIO International Convention, biosimilars, biotech regulation, Blog, Companies, Diagnostics, Events, FDA, Food and Drug Administration, Funding, Medical Devices, Medical Supply, PDUFA, Pharmaceuticals, regulation, Startups, Universities, Videos by biotechnow@bio.org (Biotechnology Industry Organization)

In the words of BIO’s Andrew Emmett, Managing Director, Science & Regulatory Affairs, ‘2012 is shaping up to be a momentous year for FDA reform.’ From the reauthorization of the Prescription Drug User Fee Act (PDUFA V) to modernizing and expediting the approval of new drugs and biologics, implementing the new biosimilars pathways and addressing the growing global drug shortage crisis, all eyes are on the current regulatory environment and its role in supporting innovation.

The 2012 BIO International Convention will return to Boston, MA and the Boston Convention and Exhibition Center, June 18-21, 2012 and will feature a breakout session track on regulatory issues.

Attendees can expect the Achieving Regulatory Approval and Compliance educational track to feature leading Food & Drug Administration (FDA) leaders who will share their prospective priorities, senior European medical agency executives discussing international and harmonization issues as well as major biotechnology and pharmaceutical companies exploring best practices and addressing questions.

With drug development a long and costly process, speakers will also address how companies can continue to innovate and attract investor capital.

Highlights include:

FDA Town Hall

Tuesday, June 19, 2:00 p.m. – 3:30 p.m.

Speakers: Karen Midthun, MD, Director, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA) and Janet Woodcock, Center for Drug Evaluation and Research, Food and Drug Administration (FDA)

PDUFA V: Impact on Innovation, Patients, and Modern Medicines – Super Session

Wednesday, June 20, 3:30 p.m. – 5:15 p.m.

Moderator: Steve Usdin, Washington Editor, BioCentury, Co-host, BioCentury This Week

Speakers: Marc Boutin, JD, Executive Vice President and Chief Operating Officer, National Health Council, Peter Greenleaf, President, MedImmune, and Margaret Hamburg, M.D., Commissioner of Food and Drug Administration (FDA)

Analysis and Impact of PDUFA V: What Regulatory Affairs Professionals Need to Know

Tuesday, June 19, 8:30 a.m. – 9:45 a.m.

Moderator:  Janet Jenkins-Showalter, Senior Regulatory Group Director, Genzyme, A Member of the Roche Group

Speakers:  Andrew Emmett, Managing Director, Science and Regulatory Affairs, Biotechnology Industry Organization, Kay Holcombe, Senior Policy Advisor, Genzyme, a Sanofi Company, and Patrick Frey, Director, Office of Planning and Analysis, Center for Drug Evaluation and Research (CDER), Food and Drug Administration

Interchangeable Biosimilars: Distinguishing between Aspiration and Achievement

Thursday, June 21, 8:30 a.m. – 9:45 a.m.

Moderator:  Ramsey Baghdadi, Senior Editor, The RPM Report

Speakers: Erika Lietzan, Special Counsel, Covington & Burling LLP, Joseph Miletich, Senior Vice President, Research and Development, Amgen, Gregory Schimizzi, Co-Founder, Carolina Arthritis, Coalition of State Rheumatology Organizations and Jan Wyatt, Patient Advocate, Arthritis Foundation

Biological Product Pediatric Development in the US: Implementation of PREA and BPCIA

Monday, June 18, 3:45 p.m. – 5:00 p.m.

Moderator: Chin Koerner, Executive Director, Novartis Pharmaceuticals

Speakers: Barbara Buch, MD, Supervisory Medical Officer, Center for Biologics and Evaluation Research, Food and Drug Administration (FDA), Sharon Olmstead, Vice President, Novartis Pharmaceuticals and Karen Weiss, Vice President, Janssen Research and Development

To learn more about the Achieving Regulatory Approval and Compliance educational track and get the most up-to-date program and speaker information, visit http://convention.bio.org/program/.

What Parallel Review Means for Manufacturers

Posted under Blog, CMS, Companies, Diagnostics, FDA, FDA approval, Food and Drug Administration, Funding, Health, manufacturing, Medical Devices, Medical Supply, Pharmaceuticals, Startups, Universities, Videos by biotechnow@bio.org (Biotechnology Industry Organization)

By Stephen Rothenberg, J.D. and Matt Levy, J.D., Numerof & Associates, Inc. (NAI)

Currently, the FDA and CMS consider new medical products in series; after FDA approval or clearance, CMS begins consideration of a National Coverage Determination (NCD), if requested by an interested stakeholder. Any party seeking drug approval (e.g., manufacturers, suppliers, providers, medical professional organizations, and Medicare beneficiaries) may initiate a request for an NCD. In addition, CMS may initiate a request for an NCD when there is debate over the benefit of a drug, or other controversy. CMS waits for the FDA to complete its process first, ostensibly because it doesn’t want to spend time on a product that ultimately doesn’t receive approval or clearance.

Serial review also ensures that CMS can meet its statutory requirement to complete the NCD within nine to twelve months of starting the process, even if a manufacturer should stumble upon a roadblock in obtaining FDA approval. As a result, serial review has the potential to delay a sponsor’s ability to receive Medicare coverage, which can, in turn, delay the public’s access to new medical products. Not only does this impact Medicare recipients, but commercial insurers often follow – and wait for – the lead of CMS in their own coverage decisions. The delay could potentially affect anyone who might benefit from the drug.

To address this issue, the FDA and CMS jointly announced on September 17, 2010 their intent to institute a process for cooperation and concurrent review of medical products. The proposed approach would give CMS the go-ahead to begin considering a request for an NCD before the FDA has completed its review of the product’s safety and effectiveness.

The agencies expect that this overlapping review process and sharing of data and resources would reduce the time between FDA approval or clearance and the CMS NCD to ensure coverage and subsequent reimbursement for Medicare beneficiaries (the “approval-to-payment” time).

FDA and CMS believe that a parallel review process will also provide efficiencies in the creation and submission of clinical study data. In the current framework, the FDA and CMS frequently require different clinical data, so it’s not uncommon for sponsors to have to conduct different studies for each agency, adding to the cost of both development and review. CMS and the FDA believe that a cooperative and collaborative parallel review will allow sponsors to develop clinical study designs that could provide data to address both FDA and CMS questions (i.e. economic and clinical value).

While those in the biotech and pharmaceutical industries may want to reduce the time between FDA market approval and CMS approval for national payment, there are potential downsides. Critics are concerned that parallel review would be difficult to implement, especially given the respective mandates of the FDA and CMS. The FDA bases approval on safety and efficacy, relying on randomized placebo-controlled trials; whereas CMS pays for “reasonable and necessary” products, based on the totality of evidence within the Medicare population only. Is it appropriate to comingle these different mandates and considerations? What might manufacturers risk if their proprietary information is shared with CMS, an agency without a statutory requirement to safeguard third party proprietary information (or, arguably, a related cultural imperative to do so)? Would statutory duties be violated if CMS rulings influence FDA decisions?

Additionally, comments submitted to the Department of Health and Human Services (HHS) expressed concern that joint FDA and CMS requirements for clinical trials could be cumbersome and costly, and CMS does not have the resources needed to process NCDs at the rate the FDA approves new products. Others felt that collaborating only for NCDs limited the actual benefits, especially since local coverage determinations (“LCDs”) cover a substantial number of new medical products (possibly even more than NCDs).

Despite these concerns, there is a lot of well-deserved enthusiasm for the prospect of securing reimbursement more quickly. Initial interest in some type of process for seeking reimbursement in parallel with FDA review started after Johnson & Johnson was able to secure Medicare reimbursement for its Cordis Cypher drug-eluting stent immediately upon FDA approval in 2003, based on interactions with CMS during the PMA process. In this case, Johnson & Johnson worked with CMS proactively during the product approval process to secure reimbursement more quickly, but the potential to improve time-to-market resonated with stakeholders within both agencies as well as other manufacturers. In recent years, companies have begun to realize the need to put more emphasis on collecting economic and clinical data prior to FDA approval to support reimbursement.

Given that CMS’ reimbursement concerns will become an element in the FDA’s determination of the product’s safety and market clearance, and that implementation of the shared information activities undoubtedly will have unexpected and unintended consequences, industry leaders should prepare for the potential implications. Economic and clinical value data will be increasingly important for both regulatory approval and coverage.

While the agencies have not specifically responded to the very valid concerns expressed during the review period, the FDA and CMS did announce the start of a parallel review pilot for medical devices this week. In light of indicators like the proposed cooperative and collaborative review process and the fact that agencies in Europe are already dealing with these issues, there does seem to be a growing trend toward the FDA stepping outside of its traditional mandate, and considering factors like necessity of drugs — not just safety and efficacy — in their approval decisions. The value bar is being raised for drugs, and biotech companies should proactively prepare to demonstrate robust economic and clinical value propositions for their products, because regardless of what CMS and the FDA decide to do regarding the proposed concurrent review, their increasing collaboration has implications for biotech companies.

Stephen Rothenberg, J.D. is a Consultant, and Matt Levy, J.D., is a Business Analyst at Numerof & Associates, Inc. (NAI). NAI is a strategic management consulting firm focused on organizations in dynamic, rapidly changing industries. We bring a unique cross-disciplinary approach to a broad range of engagements designed to sharpen strategic focus, increase revenues, reduce costs, and enhance customer value. For more information, visit our website at www.nai-consulting.com. Mr. Rothenberg and Mr. Levy can be reached via email at info@nai-consulting.com or by phone 314-997-1587.

Managing in a Cost-Constrained Environment

Posted under biopharma companies, biotech industry, Biotechnology Industry, Blog, Business and Investments, Business of Biotech, Companies, Diagnostics, FDA, Food and Drug Administration, Funding, Medical Devices, Medical Supply, patent, Pharmaceuticals, Startups, Universities, Videos by biotechnow@bio.org (Biotechnology Industry Organization)

By Jill E. Sackman, D.V.M., Ph.D., Senior Consultant, and Matt Levy, J.D., Business Analyst, at Numerof & Associates, Inc. (NAI)

The pharmaceutical industry has entered a critical period of transition. Business models that have proven remarkably successful over the past 20 years are now encountering major challenges. As biotech companies grapple with the leading symptoms of these challenges – pricing pressures, pipeline productivity concerns, a growing public distrust, and greater political and regulatory scrutiny – it is becoming increasingly clear that a profound shift is underway in what it takes to be successful in this environment.

Biotech business strategy has tended to emphasize market size above all else. This has been translated into a focus on blockbuster drugs and mega mergers, passing on “singles” and “doubles” in the quest for “home run” opportunities. Heavy reliance on such home runs raises the inherent risks, costs, and time involved in clinical development, especially in an environment of heightened regulatory scrutiny. At the same time, the pharmaceutical industry’s increasing reliance on external sources of novel compounds has bid up the price of the compounds, further exacerbating the cost and risk of drug development — and as a result, the public backlash over rising drug costs.

The natural dynamics of maturing markets have become increasingly problematic. With a tradition of reliance on patent protection, brand-focused pharmaceutical companies cannot avoid competing with their own past success. Once generic equivalents are available, the economic attractiveness of other, new branded drugs for a given disease declines rapidly, particularly drugs in the same class. While new drugs typically offer some important advantages over existing therapies, these advantages must offset massive price differentials when compared to generics.

With the management of healthcare costs reaching crisis proportions, payers are raising the bar … insisting on hard evidence of clinical and economic value in comparison to therapies that already exist. In practice, the FDA has also begun factoring unofficial requirements for superior clinical value into the approval process. In this environment, innovation and differentiation play a more significant role than ever before.

Many biotech companies have implemented changes to their R&D process and capabilities. Most haven’t gone far enough. Sustainable leadership in this market requires a radically different development engine. The key requirement is to build a scientific foundation for highly differentiated and sustainable franchises around selected disease states — based on integrated diagnostic and therapeutic capability, extensive product portfolios that address needs over a disease continuum, strategic market insight, and in-depth preclinical and clinical expertise.

While excellent science must be a given, it is not enough by itself.  Biotech companies will also need to master several critical building blocks:

• Build critical supporting infrastructure and core competencies in strategic marketing, economic and clinical value, and portfolio management. Most development programs have appropriate focus on the pathway for regulatory approval of new products. In the current market environment, it is equally important to make optimal decisions on which compounds to move forward, which indications to pursue and in what order, how to position products competitively based on relative economic and clinical value, and what evidence needs to be generated in support of the value proposition.  Most companies do not currently have the capabilities in place at a sufficiently sophisticated level to do this work well.

• Integrate development programs more effectively to improve the risk/return profile of the pipeline.  Without constant diligence, R&D practices easily devolve in ways that run counter to effective program management.  One common example is the evolution of organizational silos that limit effective engagement across critical boundaries, such as the division of preclinical and clinical research.  Companies must thoughtfully redesign processes, redefine roles, and ensure competencies are in place to capture the benefits of integration.

• Reduce clinical development costs through integrated global programs, comprehensive outsourcing strategies, and improved program management capabilities. In addition to making wise portfolio management decisions, companies must find ways to take cost and risk out of their product development process.  Most of the easy savings have already been found. The next steps will require more sophisticated program management capabilities at a strategic and operational level to streamline programs, access lower-cost resources, and leverage global synergies while remaining responsive to local market needs.

Realistic implementation of any major organizational transformation also needs to limit the risks of disrupting the current business. Fortunately, you don’t need to execute a monolithic solution all at once.  Instead, you can select one or two “lead” therapeutic areas to build true franchise capabilities in alignment with your commercial strategy.  Because a siloed organization will not be able to execute such an integrated approach, you must break down barriers across the company and build new, cross-cutting capabilities around your franchise focus.

Leaders throughout the biotech industry need to be proactive in their preparation for a market where new winners and losers will be determined based on their ability to create a new product development infrastructure — one that delivers new products with differentiated economic and clinical value propositions … with lower risks and costs.

Jill E. Sackman, D.V.M., Ph.D. is a Senior Consultant, and Matt Levy, J.D., is a Business Analyst at Numerof & Associates, Inc. (NAI). NAI is a strategic management consulting firm focused on organizations in dynamic, rapidly changing industries. We bring a unique cross-disciplinary approach to a broad range of engagements designed to sharpen strategic focus, increase revenues, reduce costs, and enhance customer value. For more information, visit our website at www.nai-consulting.com. Dr. Sackman and Mr. Levy can be reached via email at info@nai-consulting.com or by phone 314-997-1587.