Volume 52 Issue 2
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Table of Contents
> Introduction
> An FDA Perspective on the Drug Development Process
> Why Are Drug Development Programs Growing in
Size and Cost? A View From Industry
> Science and Regulatory Rituals Associated With
the Drug Development Process
> Drug Development: Improving the Process
> Does Your Corporate Culture Contribute to the
Problem?
> Managing Organizational Interfaces
> How Do You Get to Regulatory/Marketing Balance?
> Opportunities in Phase IV to Improve Drug Development
> Medical Device Software Regulation: An Industry
Perspective
> CBER Status on Reform Initiatives: Industry
Reactions and Comments
> An Overview of International Harmonization
> FDA Implementation of Standards Developed by
the International Conference on Harmonization
> A Critical Examination of the Post-Daubert ScientificEvidence Landscape
Introduction—Drug Development: Who Knows Where the Time Goes?
Issue: 52 Food and Drug Law Journal 141 (1997)
In June 1996 the Food and Drug Law Institute, the Food and Drug Administration's Center for Drug Evaluation and Research, and the Center for Drug Development Science at Georgetown University cosponsored a conference designed to explore all facets of contemporary new drug development. This meeting was held in the Leavey Conference Center at Georgetown University, and is referred to as the "Georgetown Conference." The motivation for the program was the widely-held belief that the time and expense requirements for the development of new medicines in the United States are greater than they need to be. A broad range of topics was addressed by speakers from FDA, academia, and the pharmaceutical industry. This report summarizes some of the key points made during the meeting and its conclusions.
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An FDA Perspective on the Drug Development Process
Author: Janet Woodcock
Issue: 52 Food and Drug Law Journal 145 (1997)
The drug development process is a highly complex enterprise involving
the participation of many diverse parties. Drug development time likewise
depends not only on the Food and Drug Administration (FDA), but also
on the contributions of various parties including industry drug developers,
marketing departments, academia, and world-wide regulatory agencies.
FDA, in the past, has not been as aware of drug development issues
as it could be, partly because drug development time and cost were
regarded as economic issues and therefore not part of the agency's
public health responsibility. Recently the agency has launched initiatives
facilitating drug development through the International Conference
on Harmonization. Other examples include clarification of policy on
clinical holds and promotion of early and frequent interaction with
sponsors.
This article explores three questions. First, what does FDA, specifically
the Center for Drug Evaluation and Research, know about the issues
surrounding drug development times, strategies, and costs? Second,
how do FDA activities and standards impact these areas? And finally,
how can FDA further facilitate drug development?
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Why Are Drug Development Programs Growing in Size and Cost? A View From Industry
Author: John F. Niblack
Issue: 52 Food and Drug Law Journal 151 (1997)
New drug development costs continue to rise, primarily as the result of marked increases in the size and scope of drug development programs. The larger development programs are needed to satisfy the information demands of a large number of data "consumers," consisting of government regulators, formulary managers, leaders in academic medicine, practicing physicians, patients, and the commercial sponsor's management and shareholders. These customers generally seek data that demonstrates high safety, differentiating efficacy, and maximal value for money for any new drug entering the marketplace. The amount of information needed also is affected by conservative scientific and regulatory attitudes. Limitations on the effective market life of a new drug have forced sponsors to conduct longer, more complex clinical trials to maximize the differentiating features and indications of a new drug at first launch. All of these factors contribute to the inflation of new drug development costs, with no relief in sight.
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Science and Regulatory Rituals Associated With the Drug Development Process
Author: Larry R. Versteegh
Issue: 52 Food and Drug Law Journal 155 (1997)
Drug development is a lengthy and highly complex process that is driven not only by scientific considerations, but also to a significant degree by regulatory requirements. Recently, much effort has been focused on evaluating the approaches utilized by industry and the regulatory requirements to find areas that could be eliminated or changed in such a way as to speed the drug development process. This article identifies and discusses a number of such opportunities in the preclinical, clinical, statistical, and legal/regulatory disciplines.
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Drug Development: Improving the Process
Author: Carl C. Peck
Issue: 52 Food and Drug Law Journal 163 (1997)
The process of clinical drug development can be improved significantly by making better use of the data that are collected, a change that may lead eventually to more judicious and more limited collection of data relative to current practices. Contemporary drug development programs often comprise a large number of clinical trials, with an enormous number of observations made within those trials. Many observers believe that the number of trials and quality of observations are excessive. The analysis of data from completed clinical trials is often slow and ill-timed for influencing the remainder of drug development and for optimizing doses. If this statement is true, the economics of this ever more competitive industry would dictate that these practices cannot persist into the next century.
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Does Your Corporate Culture Contribute to the Problem?
Author: Robert E. Desjardins
Issue: 52 Food and Drug Law Journal 169 (1997)
New drug development is a complex and rapidly-changing process with a high level of cross-functional interdependency. These characteristics create a need for both scientific and managerial excellence. The pharmaceutical industry has responded more vigorously to the scientific challenge than it has to the managerial demands of research and development. Consequently, most pharmaceutical research and development organizations maintain a traditional functional area orientation, with power and influence residing predominantly in line management. The culture associated with this managerial paradigm is not optimal for the cross-functional integration needed in new drug development. A culture that supports strong project management, encourages diversity, generates a sense of shared values, and an overall commitment to managerial excellence as well as scientific excellence is proposed as a more effective approach to managing these complex processes. By creating such an environment it is possible to improve the speed and effectiveness of the drug development process.
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Managing Organizational Interfaces
Author: Thomas J. Allen
Issue: 52 Food and Drug Law Journal 173 (1997)
This article will review several points of interest for those in the business of developing pharmaceutical products. Discussed first is general management theory, the theory of structuring an organization for research and development. Then some data from the pharmaceutical industry will be compared with data from other industries. With regard to organizational structures for research and development, there is a trade-off that must be made between the knowledge and coordination sides of an organization. I will refer to a three-parameter model that will determine the structure of the organization needed for product development. The article will then discuss the matrix organization that results, and the balance of power that is necessary in a matrix organization.
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How Do You Get to Regulatory/Marketing Balance?
Author: Timothy R. Franson
Issue: 52 Food and Drug Law Journal 179 (1997)
This article will review the concept of desired balance in regulatory and marketing information, distinguishing it from other development aspects, such as initial product access (launch) interface and health care environmental change, some of which has been addressed by others during this seminar. The article will touch on the topic of how regulatory and industry interests interrelate within a provincial framework for information management and accountability that is fair and equitable to all interested parties. The article will conclude with the concept of "enlightened enablement," which proposes tiered access to information that is related to the sophistication of the intended recipient(s). Because communication, or the lack thereof, has proved to be an impediment to progress in seeking shared understanding on these matters, the importance of proper orientation and perspective to the subject of balanced information requirements and access must be emphasized.
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Opportunities in Phase IV to Improve Drug Development
Author: Raymond L. Woosley
Issue: 52 Food and Drug Law Journal 185 (1997)
Pharmaceuticals have improved dramatically the quality and duration of healthy life for the American public. Nevertheless, the overall environment for new drug development is less than satisfactory, resulting in limitations in the potential benefits from medications. Deficiencies in the "soil" in which new drugs are "planted" result in slow drug development, in some cases reaching twelve to fifteen years, and restrictions in the marketplace, such as restrictive formularies, therapeutic switches, and prior authorization. The problems in phase IV are actually "opportunities" that can be addressed by investing in research and educational programs that lead to rational therapeutics. A collaboration between the pharmaceutical industry and those universities with expertise in therapeutics is suggested as a means to improve the environment for drug use by the public. Centers for Education and Research in Therapeutics could play such a role.
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Medical Device Software Regulation: An Industry Perspective
Author: Dee Simons
Issue: 52 Food and Drug Law Journal 189 (1997)
Software embedded in a medical device historically has been regulated by the Food and Drug Administration (FDA) as part of the parent device. Many other types of software found in today's medical environment, however, are not embedded in a medical device. Some of this software is not regulated, while other kinds of software have not been identified adequately as regulated devices to manufacturers or FDA reviewers. In September 1996, FDA and the National Library of Medicine cosponsored a public workshop to better define the kinds of medical software not embedded in a medical device that should be regulated, and the degree of regulatory control required for such software. While there is a legitimate need to regulate some of these software products as medical devices, there are medical software systems that should not be regulated, because they only replace pens, paper, and manual recordkeeping systems. Other types of medical software do not directly affect patient diagnosis or treatment and carry a very low risk. The Health Industry Manufacturers Association (HIMA) advocates a common-sense approach when constructing a regulatory framework for medical software, so that the least degree of regulatory control is exercised for low-risk software that does not have direct impact on patient care. This position was put forth in a presentation given at the September 1996 workshop as part of HIMA's response to four discussion papers distributed by FDA prior to the meeting.
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CBER Status on Reform Initiatives: Industry Reactions and Comments
Author: Martin Page
Issue: 52 Food and Drug Law Journal 193 (1997)
Reforms that are of the greatest interest to emerging companies are those leading to earlier approval of new products, such as harmonization of requirements and a rapid review process. Food and Drug Administration's (FDA's) participation in global harmonization discussions has been beneficial, and the Center for Biologics Evaluation and Research (CBER) has been a willing participant in the drug development process. Several regulatory reforms relate to well-characterized biotechnology products, for example, elimination of both separate establishment license applications and the requirement for CBER batch-release, although the rationale for excluding in vitro diagnostic products from the definition of well-characterized biotechnology products is not clear. FDA guidance on demonstration of comparability of human biological products also should lead to significant time and cost savings. Constructive dialogs have occurred among industry and CBER's Advertising and Promotional Labeling Staff with respect to promotional items, but the guidance on dissemination of journal articles seems unnecessarily restrictive. There are more complex areas that require agency guidance, including use of the Internet for promotion. While FDA reforms have been helpful to date, sustained and sensible dialog between interested parties is the most productive way to continue the process.
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An Overview of International Cooperation
Author: Sharon Smith Holston
Issue: 52 Food and Drug Law Journal 197 (1997)
The Food and Drug Administration (FDA) is responding to the globalization of production and consumption, and the fast-growing imports of regulated products by stepping up its cooperation with regulatory authorities abroad. Traditionally, the agency's foreign contacts were limited to information exchanges and technical assistance, which usually was provided under the auspices of the World Health Organization and other international forums. In the past twenty years, however, FDA has found it necessary to negotiate approximately fifty memoranda of understanding that commit foreign governments to enforce FDA standards in products exported to the United States. Since 1990, the agency also has taken a lead in establishing multinational organizations whose goal is to harmonize regulatory procedures and product standards. FDA's latest foreign project is an attempt to negotiate an agreement with the European Union for mutual exchange of plant inspections for good manufacturing practices. The agency, which has several offices pursuing various aspects of its foreign policy, expects that the international cooperation will result in faster and more efficient regulatory processes, and better public health protection for everyone.
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FDA Implementation of Standards Developed by the International Conference on Harmonisation
Author: Paul M. Booth
Issue: 52 Food and Drug Law Journal 203 (1997)
In an effort to reduce both the time and costs of new drug approval in the world's three largest pharmaceutical markets, the International Conference on Harmonisation (ICH) was founded in 1989 to negotiate common standards for regulation of pharmaceutical products within the United States, Europe, and Japan. The regulatory bodies overseeing drug approval in these three regions, as well as the pharmaceutical manufacturers trade associations in each area, are cosponsors of ICH. The fundamental goals of ICH, therefore, are to reduce the costs associated with gaining regulatory approval of a new drug and to increase patient access to new drugs by streamlining the approval process. This article examines the reasons for the Food and Drug Administration's (FDA's) support of ICH and analyzes the agency's approach to the implementation of ICH Guidelines. The article also questions the statutory and administrative authority under which FDA adopts ICH Guidelines in the United States, and evaluates whether FDA's mode of implementing the Guidelines requires that ICH be considered an advisory committee subject to the requirements of the Federal Advisory Committee Act. The article concludes that although the ICH process is committed to laudable goals, it should be modified to allow greater participation by all affected parties.
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A Critical Examination of the Post-Daubert Scientific Evidence Landscape
Author: Jay P. Kesan
Issue: 52 Food and Drug Law Journal 225 (1997)
In 1993, the Supreme Court offered its first pronouncement on the
admissibility of scientific evidence in Daubert v. Merrell Dow Pharmaceuticals,
Inc. A unanimous Court held that the seventy-year old Frye "general
acceptance" test for the admissibility of scientific evidence
had been superseded by the Federal Rules of Evidence. In Daubert,
the Court also outlined a gatekeeping role for the trial judge to
ensure that an expert's testimony is both reliable and relevant.
This article discusses the Supreme Court's opinion in Daubert and
highlights the fundamental compromise at the heart of this decision.
Part III presents a temporal model to describe the development of
scientific knowledge. This model supplies a framework within which
post-Daubert decisions can be analyzed, and explains the inconsistent
landscape of post-Daubert decisions. Part III also delineates the
weight and admissibility elements in expert scientific testimony by
parsing the testimony into four sequential components. These components
then are examined in the context of post-Daubert cases. Part IV argues
that an administrative tribunal, as opposed to generalist trial judges,
is more likely to achieve uniform and consistent application of Daubert
to scientific expert testimony.
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