Developing New Contraceptives Obstacles and Opportunities (1990) / Chapter Skim
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7 Regulation and Contraceptive Development
7 Regulation and Contraceptive Development
Pages 89-117
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From page 89... ...
Some analysts contend that the regulatory climate in the United States has impeded the U.S. pharmaceutical industry's willingness to pursue innovations in contraceptive development (Isaacs and Holt, 1987a; Greep et al., 1976; Djerassi, 1987, 1981~.
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From page 90... ...
Many drug formulations are discarded during the development process because of concern about safety, efficacy, feasibility of delivery, or marketability. In drug development generally, FDA approval is sought for only 1 out of every 10,000 new chemicals synthesized in the laboratory.
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From page 91... ...
1,000 people, to establish effectiveness Fertility and Maternal Health Drugs Advisory Committee makes recommendations to FDA ~ 6 months-1 year | 1 to complete ~ | 6 months-2 years l to complete | t'~L~UIIbII ~ll~liv~ll~ '4 PHASE lil includes > 1,000 people, to confirm safety, effectiveness, 1-4 years and dosage; trials often continue to complete during NDA evaluation NEW DRUG APPLICATION (NDA) 2 months-7 years to process | ~ FDA APPROVAL FOR MARKETING I HI POSTMARKETI NG SURVEI LLANCE O drug sponsor activity O drug sponsor application O FDA activity & FDA evaluation technical trials require approval by the Institutional Review Board (IRB)
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From page 92... ...
Human clinical testing of new contraceptive drugs is divided into three phases: Phase I studies are usually conducted on a small number of volunteers and are used to determine the safe dose range, the absorption process, and possible levels of toxicity; Phase II studies provide more information about the drug's safety as well as efficacy in carefully selected subjects; and Phase III studies, which may involve several hundred or more participants, are used to establish the drug's safety and efficacy in actual clinical use. Clinical trials for new drugs take an average of five years, but they may continue for as many as 10 years (FDA, 1988~.
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From page 93... ...
Replicating this experience of widespread, long-term use of oral contraceptives in clinical trials for other methods is not yet possible. Long-term safety issues related to new systemic contraceptive methods will not be completely resolved until they have been in general use for many years.
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From page 94... ...
Most recently, Congress passed the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub.
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From page 95... ...
The questions raised relate to the appropriateness of using these animals as experimental models for humans. Changes in toxicological and clinical testing requirements for contraceptive steroids implemented in 1987, however, have eliminated some of the controversial dog and monkey testing requirements.
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From page 96... ...
FDA requirements for toxicological testing in animal subjects have been revised over the past 20 years. In 1968 the deputy director of the FDA's Office of New Drugs summarized the agency's requirements for toxicological testing of new contraceptive drugs (Goldenthal, 1968:14~: We are currently requiring, as a minimum, a one-year toxicity study conducted in a rodent and the dog prior to initial clinical evaluation of [oral contraceptives]
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From page 97... ...
FDA testing requirements for contraceptive steroids now conform more closely to the requirements for other drugs, with the exception of the 3-year dog studies required for contraceptive drugs. The former requirements for 7-year beagle and 10-year monkey studies were particularly burdensome for sponsors of new contraceptives.
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From page 99... ...
In 1978 the FDA formally determined that DepoProvera had not met the agency's safety standards. The FDA's reasons included the results in the first beagle study, its finding that there was no patient population in the United States that needed the drug, and its doubts about the feasibility of postmarketing surveillance in the United States to assess the risks of the drug.
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From page 100... ...
The Appropriateness of Current Safety Requirements for Contraceptive Drugs The FDA's requirements for tests of contraceptive drugs in beagles and monkeys reflect a demand for proof of safety that applies to all drugs but is, perhaps, uniquely burdensome to sponsors of contraceptives. The statutory requirement for "adequate tests by all methods reasonably applicable to show whether or not [the]
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From page 101... ...
If a drug demonstrably offers unique dramatic benefits if, for example, it literally saves lives or cures a severely disabling disease and has no substitute-it is fairly easy to conclude that this risk of the unknown is worth taking. Is such a risk worth taking, however, in the case of a contraceptive drug, even one with a unique method of administration that offers unique convenience?
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From page 102... ...
In fact, contraceptive effectiveness has been relatively easy to establish and, consequently, the general requirements for proof of effectiveness have not adversely affected contraceptive innovation in any distinctive way. Issues have arisen regarding the minimal effective dose of some contraceptive drugs, however, and regulatory approval of reduced doses of some products in the United States has lagged behind similar approvals in Europe.
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From page 103... ...
risks of cancer or other chronic diseases might rationally be accepted by a woman for whom effective contraception (or effective contraception by a particular mode) is of very great present value, perhaps because other contraceptive methods are not likely to be completely effective over the long term or are simply unacceptable for cultural, religious, or other reasons and pregnancy itself could present a grave medical risk.
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From page 104... ...
. In deciding whether a contraceptive drug presenting some chronic risks should be approved for marketing to the general population, most of whom can, with medical advice, make a well-informed decision, the weight the FDA should give to the special vulnerabilities of particular groups within the population has been a particular concern.
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From page 105... ...
However, FDA requirements for data on a product's safety and effectiveness and the length of time needed for FDA review have contributed to a reduction in the length of time from the date of FDA approval until the date of patent expiration (the effective patent life) of new products.
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From page 106... ...
The Drug Price Competition and Patent Term Restoration Act of 1984 (the 1984 DPC-PTR Act) was enacted to help alleviate problems of short effective patent life for drugs and medical devices.
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From page 107... ...
Examples of Class III devices include tubal occlusion plugs, sterilization clips, and inert IUDs. The factors that determine whether a
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From page 109... ...
For contraceptive products approved between 1962 and 1987, it is possible to calculate the mean duration between the date an NDA was received by the FDA and the date it was approved for marketing. For oral contraceptives (96 different formulations)
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From page 110... ...
At present, postmarketing surveillance systems for contraceptive products are not adequate. No long-term epidemiological studies of the health risks and benefits of the new oral contraceptive formulations that have been introduced during the past two decades in the United States are under way.
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From page 111... ...
This approach is viewed by the drug industry as superior to the establishment of a complex supranational European regulatory agency. Some European drug industry experts view the FDA's revision of its toxicological and clinical testing requirements for new contraceptive steroids as a very positive development.
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From page 112... ...
market, as well as its potential for higher profits than Europe, regulatory changes in the United States may affect contraceptive development activities in Europe as well as in the United States. The United States is not the only country that has seen a decline in the effective patent life of contraceptives and other pharmaceuticals.
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From page 113... ...
There has been some discussion about establishing uniform international drug regulations, but to date little interest in this has been shown by pharmaceutical companies or national drug regulatory agencies (Rowe, 1983~. Since many countries do not have strong drug regulatory agencies and since the regulatory requirements and procedures of other countries vary widely, some have proposed that WHO regulate at least some products.
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From page 114... ...
Rather, we view it as an effort to make the FDA's regulation of contraceptive drugs and devices more similar to its regulation of other drugs and devices. The committee does not believe that the proposed change would justify, or would bring about, any reduction in public confidence in the effectiveness or safety of contraceptive products.
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From page 115... ...
should have no effect on the rules of products liability that should otherwise be applicable to contraceptive products (see Chapter 8~. Contraceptive effectiveness helps women not only avoid unwanted pregnancy, but also avoid the medical risks that, for some women, would be associated with pregnancy and childbirth.
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From page 116... ...
The committee recommends that the FDA continue to evaluate ways to improve the toxicological and clinical trial requirements for contraceptive agents. Although the committee believes that it is too early to assess the effects of the Drug Price Competition and Patent Term Restoration Act, further study of effective patent life is needed and a report on the effects of the act, with particular reference to contraceptives, should be undertaken in the mid-1990s.
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From page 117... ...
The FDA needs to consider both effectiveness in clinical trials and effectiveness in general use in its approval process for contraceptive drugs. A contraceptive that has a low risk of unwanted pregnancy in actual use is an effective product.
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