New drug research, the extraterritorial application of FDA regulations, and the need for international cooperation.

• Author: DuBois, William

ABSTRACT

In recent years, U.S. pharmaceutical companies have expanded their new drug trials beyond the borders of the United States. While the companies have a variety of reasons for making this move, among them may be a desire to avoid Food and Drug Administration (FDA) regulation and monitoring. Lack of adequate supervision of drug trials conducted in the developing world endangers both the subjects of the tests and the consumers in the United States. It is unclear whether the FDA can execute regulatory and supervisory authority abroad. The FDA statute does not clearly authorize the agency to regulate extraterritorially. Applying the presumption against extraterritoriality, the FDA should not, therefore, be allowed to regulate drug testing abroad. Exceptions to the presumption might, however, be applicable. Regardless of whether U.S. courts allow the FDA to bring actions against companies for violations abroad, international cooperation is needed to control drug testing.

TABLE OF CONTENTS I. INTRODUCTION II. THE GLOBALIZATION OF THE DRUG INDUSTRY AND THE FDA'S ATTEMPT TO KEEP PACE A. The Globalization of Pharmaceutical Research B. The FDA's Role in Drug Testing Abroad III. EXTRATERRITORIAL APPLICATION OF U.S. LAW AND THE PRESUMPTION AGAINST EXTRATERRITORIALTY A. Application of the Presumption Against Extraterritoriality in Environmental and Labor Law B. The "Effects Test" Exception to the Presumption Against Extraterritoriality in Antitrust and Securities Law C. Implied Congressional Intent and the Role of the Effects Test in the Extraterritorial Application of U.S. Criminal Law D. Exception for Crimes and Frauds Against the U.S. Government E. Does the Presumption Against Extraterritoriality Survive the Chevron Deference Approach? IV. THE FDA's POWER TO REGULATE U.S. DRUG RESEARCH ABROAD IS LIMITED A. The Food, Drug, and Cosmetic Act Does Not Exhibit a "Clearly Expressed" Congressional Intent for Extraterritorial Application B. Under Congress's Statutory Scheme the FDA Probably Has the Power to Accept Foreign Research Data C. If the FDA Can Accept Foreign Research Data, Then it Can Take Steps to Ensure the Efficacy of the Tests and the Reliability of the Data D. The FDA Probably Lacks the Authority to Regulate the Treatment of Human Subjects in Foreign Clinical Drug Trials V. INTERNATIONAL MECHANISMS PROTECTING HUMAN RESEARCH SUBJECTS OF MEDICAL TESTING ARE NEEDED A. The Difficulties of Regulating Transnational Corporations in the Developing World B. Unilaterally Using U.S. Law to Protect Human Research Subjects Would Violate the Doctrine of International Comity 1. U.S. Law Versus the Power of Developing Countries to Legislate for Themselves 2. The Anti-Democratic Force of Extraterritorial Application of U.S. Law 3. Potential Conflict of U.S. Law with Other Developed-Country Regulatory Practices C. The Role of International Law and the Rights of Human Test Subjects 1. The Status of Research on Humans Under International Law 2. The Lack of Status of Corporate Entities Under International Law D. Nations Must Work Together to Formulate Protections for Human Research Subjects VI. CONCLUSION I. INTRODUCTION

In 1996, Pfizer, a large U.S. drug company, developed a new antibiotic called Trovan. (1) Wall Street analysts predicted that Pfizer could make as much as one billion dollars if Trovan were approved for all of its potential uses. (2) Yet, other drugs in Trovan's class had been found to cause joint damage during animal testing, and questions existed as to whether Trovan could have dangerous side effects in children. (3) To counter these concerns, the company wanted to obtain convincing evidence of the drug's safety for use on children. (4) As it happened, one potential application of Trovan was to treat an epidemic strain of bacterial meningitis. (5) Because spinal meningitis is relatively rare in the United States, the company was unable to find enough U.S. patients to conduct a clinical study on the scale required for full Food and Drug Administration (FDA) approval. (6)

In February 1996, a Pfizer physician learned of a meningitis epidemic in northern Nigeria. (7) Thus, Pfizer quickly obtained approval from the Nigerian government to begin tests. (8) Pfizer opened a clinic in a hospital in Kano, Nigeria that was also occupied by a Doctors Sans Frontiers clinic that was busy treating the epidemic. (9) The two organizations began to compete for hospital space and patients. (10) In the Pfizer experiment, researchers administered Trovan to 100 children, and a comparison drug to 100 other children. (11) Eleven children died in the study, and others suffered severe injuries including deafness and lameness. (12) Pfizer claimed that the fatality rate of the children in the study, and particularly the children treated with Trovan, was better than is typical in U.S. hospitals. (13)

After Pfizer obtained FDA approval for Trovan, many questions were raised regarding Pfizer's research practices. Allegations of failure to obtain consent of human subjects, mistreatment of patients, substandard levels of care, and reckless and inaccurate record keeping were leveled against Pfizer. (14) Children in the control group who improved while receiving a proven anti-meningitis drug were switched to one-third of the recommended dose in what Pfizer claimed was an attempt to "reduce the pain after initial injections" of the medicine. (15) According to a spokesman for the comparison drug's manufacturer, "clinical failures ... and perhaps deaths of children could have resulted from the low dosing." (16) The researchers ceased all treatment at the close of the study, and did not follow up on the long-term effects of the drug on the children who were treated. (17)

A lawsuit has been filed in U.S. federal court on behalf of 30 Nigerian families who claim that their children were "unwitting participants in the `secret testing,'" and who suffered a variety of injuries including brain damage, paralysis, and death. (18) The suit contends that Pfizer's research methods were in violation of FDA regulations--particularly regulations requiring prior approval of the study by the local Nigerian authorities. (19) It also alleges that Pfizer failed to obtain the informed consent of the children and their families as required by FDA regulations and international human rights law. (20)

The FDA reportedly has now opened a criminal inquiry into Pfizer's allegedly improper medical experiments conducted in Nigeria. (21) Should charges result, this would be the first regulatory action brought by the FDA for corporate conduct abroad. (22) If the government brings an action against Pfizer, it could be argued that the United States lacks the extraterritorial jurisdiction necessary to enforce U.S. law. It is unlikely, however, that a criminal prosecution of Pfizer would be based on the statutory provisions on FDA drug approval. (23) Instead, such a prosecution would likely be based on the FDA's regulations concerning human experimentation and foreign clinical drug trials. While Congress has the power to apply U.S. law extraterritorially, (24) the courts have had a mixed response to extraterritorial application of U.S. law without specific congressional authorization. (25)

This Note addresses both the potential criminal prosecution of Pfizer regarding the experimentation Pfizer performed in Nigeria that was not in compliance with FDA regulations, as well as the problem of protecting human research subjects abroad. Part II of the Note discusses the growing problem of protecting human research subjects from reckless and unethical experimentation conducted by U.S. corporations and institutions. A number of recent scandals involving drug trials in the developing world have brought calls for increased regulation and oversight abroad by sponsor nations, such as the United States. (26) Part III examines the current status of extraterritorial application of U.S. law in the absence of a clearly expressed congressional intent to apply the law abroad. Part IV then evaluates the FDA's extraterritorial regulatory activities under the current law. The FDA lacks a clear mandate from Congress to act extraterritorially in a regulatory capacity, but the overall statutory scheme of the FDA and the FDA's need to protect U.S. consumers, provide a basis for allowing some FDA regulatory authority to extend extraterritorially. FDA regulations to be applied extraterritorially, however, must stem from the agency's authority to protect U.S. citizens, rather than a desire to protect the human rights of research subjects abroad.

Part V of this Note addresses the need for alternative approaches to protection of human research subjects abroad, regardless of whether the courts might allow the FDA regulations to be enforced. The doctrine of comity and general democratic principles suggest that the United States should not extend its protection of human research subjects abroad unilaterally. (27) Unilateral action by the United States would rob developing countries of their ability to affect their own policies. It could also cause friction between the United States and EU nations, whose concepts of human rights in drug research differ.

International law already provides a basic individual right to informed consent. (28) Human research subjects in the developing world may best be protected by a legally-enforceable set of international guidelines. These guidelines should be the result of a collaborative effort by both developed and developing nations, and should account for the role of corporate actors. The FDA's mandate clearly allows it to participate in an international collaborative effort.

2. THE GLOBALIZATION OF THE DRUG INDUSTRY AND THE FDA'S ATTEMPT TO KEEP PACE

   1. The Globalization of Pharmaceutical Research

      Protection for human subjects of biomedical research has become a global issue. (29) Transnational drug corporations based in industrialized countries rely on the...