Abstract: PAREXEL International Corporation is one of the largest providers of contract clinical development services in the world. Headquartered in Boston, Massachusetts, the 15-year-old company has 20 offices in 10 countries to help biotechnology and pharmaceutical companies develop and market new therapeutic agents. Currently, PAREXEL works closely with numerous biotechnology companies to shepherd their products through the challenging regulatory maze. PAREXEL’s clinical and regulatory staff has authored and contributed to many INDs, PLAs, ELAs, BLAs, and marketing authorization applications to date and is a frequent liaison for biotechnology companies with the FDA’s Center for Biologics Evaluation and Research (CBER) and other regulatory agencies around the world. Today, there are more than 1,300 biotechnology companies researching and developing therapeutic products in the U.S. alone; 290 biotechnology products were approved between 1990 to 1996, and an estimated 270 biotechnology products are currently in human trials. Biotechnology is one of the most research-intensive industries in the world. The U.S. biotechnology industry spent $7.7 billion in research and development in 1996. According to a previous study for the U.S. Office of Technology Assessment, it costs from $200 million to $350 million and takes from 7 to 12 years for a product to move through the drug development and Food and Drug Administration (FDA) approval process. This article focuses on the regulatory and clinical issues affecting the development of biologics today and identifies trends that are shaping the future of how these therapeutics are developed.

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: In July 1993, Eli Lilly & Company (Lilly) suspended a clinical trial of Fialuridine (FIAU), a promising new treatment for hepatitis B, because of serious adverse effects suffered by participants in the clinical trial. Ultimately, it was determined that five participants (out of 15) in the clinical trial died as a result of pancreatic and liver damage associated with the use of the drug. The FIAU tragedy received extensive media coverage and was the subject of exhaustive reviews by the U.S. Food and Drug Administration (FDA), the National Institutes of Health, the National Academy of Sciences, and citizens groups. The FDA task force review led to controversial proposed reforms in the rules governing the conduct of new drug clinical trials. Not surprisingly, the FIAU trials also led to the filing of a number of lawsuits against Lilly. Concern over the impact of such litigation on the conduct of clinical trials led the National Academy of Sciences in its report to recommend congressional adoption of a no-fault compensation system for participants in investigational drug studies. The FIAU saga and subsequent litigation, as well as other recent cases involving participants in new drug clinical trials, raise serious questions about the impact of tort litigation on the conduct of such studies, with important ramifications for the development of new drugs and medical devices.

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: Led by the Office of the U.S. Trade Representative (USTR) and the Department of Commerce, the U.S. government has concluded a series of formal talks with the European Union (EU), led by Directorate-General I (External Relations) of the European Commission. The talks achieved a tentative agreement, entitled "Agreement on Mutual Recognition between the United States of America and the European Community" (Agreement), which may lead to the recognition of conformity assessment procedures in the product areas of pharmaceutical good manufacturing practices (GMPs) and medical devices. When the Agreement is finalized, it will be the first mutual recognition agreement (MRA) that the U.S. government has entered into, and the MRA will be an important achievement in that it directly addresses two important public interests: health and safety protection and international trade. The U.S. Food and Drug Administration (FDA) soon will publish in the Federal Register a proposed rule to finalize the parts of the Agreement that cover products regulated by FDA. When finalized, the Agreement will describe FDA commitments regarding the conditions under which the agency will apply the results of conformity assessment procedures performed by EU member state (MS) regulatory authorities related to pharmaceutical GMPs.

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: The U.S. Department of Health and Human Services (DHHS) regulations require that all human subjects research supported by DHHS be reviewed and approved by a locaI institutional review board (IRB).1 With few exceptions, investigators may not involve human subjects in research without their informed consent, and additional safeguards are required when subjects are likely to be vulnerable to coercion or undue influence. Institutions that receive DHHS funding must enter into an "Assurance" of compliance with the Office for Protection from Research Risks (OPRR), which has the authority for oversight and implementation of the human subjects regulations. As discussed more fully in the article, assurances are of a contract nature in that they formally commit the institution to adherence to the regulations and the ethics standards relevant to research on human subjects. This article addresses the application of human subject protections in biomedical research.

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: The mission of the National Institutes of Health (NIH) is to advance knowledge in the biomedical and behavioral sciences in order to improve the understanding and treatment of human diseases. The NIH, a primary government agency, is part of the U.S. Public Health Service (PHS), an agency within the Department of Health and Human Services (DHHS). Indeed, the NIH has a long and distinguished history of rapidly applying basic scientific discoveries in the laboratory to the design and conduct of clinical research at the bedside. A major obligation of the NIH is to provide leadership not only in scientific discovery but also in maintaining high ethical standards in its research activities, particularly those involving human subjects. The agency’s philosophy is that sound ethical practices go hand-in-hand with scientifically valid research involving human subjects. Scientific investigators at the NIH and within the NIH’s Intramural Research Program (IRP) conduct and/or collaborate in many research activities, not only on the NIH Bethesda campus, but also throughout the U.S. and abroad. The NIH assumes that its researchers share the agency’s commitment to high-quality research that promotes the rights and welfare of research subjects. As such, the NIH has organized a system of policies and procedures to help IRP investigators understand and fulfill their responsibilities when they conduct or collaborate in research involving humans at the NIH or elsewhere. This article provides an overview of the NIH’s policies and procedures for the conduct of research involving human subjects.

 ©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: On March 18, 1997, the Massachusetts Biotechnology Council (MBC) used its annual meeting, Stages of Biotech Growth: Evolving Through Experience, to profile finance, deal, and product strategies for biotechnology industry executives. More than twenty renowned industry experts candidly shared their experiences with colleagues in eight focused forums. Part I of this Special Feature, published in the premiere issue of the The Journal of BioLaw & Business, presented the forums on early-state issues: New Financing Strategies; Is Virtual a Virtue?; Early Stage Partnership Models; and Exit Strategies: Going Public or Acquisition? In this issue, we present Part II of the Special Feature, which embodies the forums focused on later-stage issues: Crossroads: How Strategic Decisions Affect Future Options; Managing Wall Street Expectations; The Approval Process: Myths and Realities; and New Product Launches: The Impact on Companies.

CROSSROADS: HOW STRATEGIC DECISIONS AFFECT FUTURE OPTIONS

I. Case Study: The Transformation of "Millennium Research" to "Millennium Pharmaceuticals"
Steven H. Holtzman

Case Study: The Impact of Deal-Making on Corporate Identity
Michael M. Tarnow

II. MANAGING WALL STREET EXPECTATIONS
The Importance of Investing in Social Capital
David K. Stone

An Investor’s Perspective on Management and Managing Wall Street Expectations
Sarah Gordon-Wild

Case Study: PerSeptive Biosystems, Inc.
Noubar B. Afeyan

III. THE APPROVAL PROCESS: MYTHS & REALITIES
Genzyme’s Experience: FDA Reforms in the Context of Reality
Alison Lawton

Case Study: Recombinant Factor IX
Frederick T. Gates, III

The FDA Reform Process: Separating Fact from Fiction
Michael Beatrice

IV. NEW PRODUCT LAUNCHES: THE IMPACT ON COMPANIES
Case Study: Impact of the AVONEX® Launch on Biogen, Inc.
Mark Leuchtenberger

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: During the period between the early 1980s to the mid-1990s, the U.S. was distinguished from most other developed countries by its lack of a national-level public body to assist the government in its policy-making on topics of biomedical ethics. While Canada, Denmark, France, Spain, and other countries regularly sought advice from public commissions on issues ranging from reproductive technologies to euthanasia, the U.S. relied on myriad state commissions, court decisions, and academic bodies. The result was a pattern of policy-making that was slower and more unpredictable than that of its peers. With the 1996 appointment of the National Bioethics Advisory Commission (NBAC) by President Clinton, there has been a change in the process of U.S. public policy development. This article provides an overview of the NABC and highlights recent areas of focus and related recommendations.

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: The International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) was established in 1990 as a joint regulatory/industry project. The founding objective was to improve, through harmonization, the efficiency of the process for developing and registering new medicinal products in Europe, Japan, and the United States (US) in order to minimize delay and make these products available to patients. The purpose of this article is to provide an overview of the ICH and to discuss the elements essential to its ongoing success. The fundamental message is that harmonization is a meaningful goal, and it can be fully realized if the ICH is provided with continued support.

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: On September 23, 1997, the New England District of the Food and Drug Administration (FDA) hosted the first of two biotechnology grassroots meetings, entitled "FDA Grassroots Meeting for the Biotechnology Industry in the Northeast Region." The objective of this meeting was to create a forum for dialogue between the FDA and industry on the district level that would result in a meaningful information exchange about FDA operations and, in particular, new programs. Multiple interactive sessions were organized along four tracks: (1) communication involving the diversity of biotechnology products; (2) the pre-approval inspection process; (3) the inspection environment after product approval; and (4) overall communications with the FDA field offices. This article provides an overview of the FDA’s mission and accomplishments during the past several decades and also addresses how the FDA intends to respond to the opportunities and challenges posed by the accomplishments of the biotechnology industry and to realize its mission well into the next century.

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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Abstract: In the fast-paced field of biotechnology research, the financing costs of creating new products leaves little room for error in clinical design and testing. The use of computer simulations to improve the design, quality, and effectiveness of clinical trials has the potential to reduce costs and enhance the safety and speed of translating research into clinical practice. For clinical trials ranging from a single patient to thousands, simulation software enables researchers to design, pre-test, and modify study parameters before conducting active live trials. In addition, computer simulation allows researchers to better understand the complex relationships between variables such as study design, dosing, sample approach, and biological models. This article also investigates the legal implications of inadequate design and testing in the clinical trial process. It presents two areas of legal exposure: (1) from products liability suits arising out of the clinical trial process and after the drug has reached the market and (2) from securities fraud cases arising out of a drop in the company’s stock after bad news emerges from clinical trials.

©1997 by The Journal of BioLaw & Business. All Rights Reserved.

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