New Frontiers in Contraceptive Research A Blueprint for Action (2004) / Chapter Skim
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3 Product Identification and Development
3 Product Identification and Development
Pages 78-107
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From page 78... ...
Given the documented need for low-cost contraceptives for much of the world's population, the development and testing of such contraceptives are not likely to be achieved by government or public-sector programs alone and will require substantial participation of the pharmaceutical industry. A conundrum lies in the fact that the present lack of financial incentives for the pharmaceutical industry to 78
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From page 79... ...
If it originated and was first tested elsewhere (that is, it was essentially prescreened) , the average success rate with regard to approval by the FDA is 1 in 3; if the product originated in the United States but was first tested abroad, the success rate is 1 in 6; and if it both originated and was first tested in the United iCharles Grudzinskas, Ph.D., drug development consultant, and adjunct professor, Georgetown University, in a presentation at the International Symposium on New Frontiers in Contraceptive Research, Washington, DC, July 15-16, 2003.
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From page 80... ...
. SOURCE: Charles Grudzinskas, drug development consultant and adjunct professor, Georgetown University, in a presentation at the International Symposium on New Frontiers in Contraceptive Research, Washington, DC, July 15-16, 2003.
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From page 81... ...
Furthermore, the FDA recently issued the first guidelines that encourage drug and biologic developers to conduct pharmacogenetic tests during drug development and clarify how FDA will evaluate the resulting data (Food and Drug Administration, 2003~.
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From page 82... ...
82 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH EXAMPLES OF TECHNOLOGICAL ADVANCES IN DRUG DEVELOPMENT Advances in Methods for Production of Pharmaceutical Proteins Biotechnology and pharmaceutical companies are testing a number of human antibodies and other proteins as potential therapeutic compounds. Proteins and peptides are excellent therapeutic agents, as exem
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From page 83... ...
. The most common antibody therapeutics are monoclonal antibodies, which are uniform antibodies that recognize only one specific target.
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From page 84... ...
Monoclonal antibodies 20 7 x 10 Antiviral agents 0.1 4 x 10 Antibiotics 0.1-0.2 6 x 10-5-6 x 10 Natural steroids 0.1 1o-7-lO-9 Contraceptive progestins (synthetic steroids) 0.3-0.6 10-9 SOURCE: Kevin Whaley, director of Antibody Discovery at Epicyte, in a presentation at the International Symposium on New Frontiers in Contraceptive Research, Washington, DC, July 15-16, 2003; Fotherby and Caldwell, 1994; Zeitlin et al., 2000.
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From page 85... ...
, with some products already in clinical trials.3 The production of proteins in transgenic animals could offer several advantages over mammalian cell culture and other more traditional methods of pharmaceutical protein production, including a competitive cost of goods with respect to the price per gram of material and a favorable capital expense structure with respect to both the absolute amount of investment required and the flexibility of the timing of investment. Transgenic animals may also offer the ability to produce biotherapeutics that would not be commercially feasible if they were made in any other system.
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From page 86... ...
A recent survey conducted by the Tufts Center for the Study of Drug Development found that approval success rates for recombinant proteins ranged from 23 to 63 percent globally and from 17 to 58 percent in the United States, depending on the class of agent. Importantly, recombinant proteins in the endocrine class (which would include fertilityrelated products)
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From page 87... ...
Today, 350 companies are devoted to drug delivery,4 and university laboratories as well as traditional pharmaceutical firms are also conducting research. In the case of contraceptive development, researchers have thus far focused primarily on controlled-release forms of drug delivery.5 A major goal of controlled-release drug delivery is to overcome two main challenges: user compliance and side effects.
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From page 88... ...
Novel approaches for administering drugs via these routes include: · Mechanical devices, such as pumps · Chemical pumps · Biosensors · Needle-less devices · Gels · Polymer systems, such as microparticles, fibers, films, and coatings · Nanoparticles to enhance solubility or specificity · Low-molecular-weight excipients (drug vehicles) , such as lipids · Drug solutions and drug suspensions · Chemical reactions In the future, responsive or "smart" materials may also prove useful for drug delivery or as barrier methods (e.g., tubal or vas occlusion)
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From page 89... ...
For example, magnetic substances could be designed as less invasive means of blocking the fallopian tube or vas deferens. STRATEGIES TO FACILITATE CONTRACEPTIVE PRODUCT DEVELOPMENT Discovery of Compounds That Modulate Contraceptive Targets Bridging the juncture between fundamental screens and the initial steps in contraceptive drug development requires special insight and significant risk taking to select the targets for the next and most costly evalu7pKa is the negative logarithm of Ka, the acid ionization constant, which measures the ability of a compound to donate a proton (H+)
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From page 90... ...
facilities and international chemical libraries. Although the pharmaceutical industry has the experience and resources required to accomplish this task, many interested scientists in the public sector lack such experience and resources.
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From page 91... ...
Fifth, redundancy can be useful in the event that supplies of some compounds are depleted from some libraries. Sixth, competition in library access can help ensure compound quality, which is a major issue with chemical libraries.
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From page 94... ...
Acceleration of contraceptive drug discovery would also depend on increased participation by the pharmaceutical industry or an increased ability to fund contract laboratories that partner with not-for-profit organizations to make materials and supplies, conduct analytical testing, and evaluate the pharmacokinetic and toxicological properties of lead molecules. Contract laboratories or university-based consortia with appro
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From page 95... ...
Moving Lead Compounds into Clinical Trials Target discovery research can lead to the identification of molecules with the potential to block the production of functional gametes or a specific stage of the fertilization process, hence showing promise as a contraceptive. Such molecules could be hormonal or nonhormonal in nature.
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From page 96... ...
In an academic setting, applied research for drug development is not considered attractive from a scientific and career development perspective, and only a very few extramural programs might support it. Most extramural funding programs support basic research and innovative target discovery, and they may also support early clinical studies to demonstrate proof of concept in humans.
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From page 97... ...
Concerted efforts between private- and public-sector agencies to fund platforms devoted to contraceptive development should be initiated and expanded. Participation by for-profit organizations could be encouraged by specific incentives such as patent life extension, favored tax status, and indemnification for companies engaged in the development of new contraceptives (see Chapter 5~.
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From page 98... ...
Such markers involve the use of expensive tests, which require skilled investigators and which make huge demands on the time and goodwill of the participants (Croxatto et al., 2002~. The mechanisms of the method dictate which surrogate markers can be used, and the capacity of the marker to reflect sterility accurately
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From page 99... ...
The choice of surrogate markers for sterility may be even more challenging for some of the future potential methods of contraception. A method, for example, that impairs the ability of the egg to be fertilized in vitro would be extremely difficult to assess in more than just a handful of women since the retrieval of eggs is invasive and expensive and carries significant risks for the woman.
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From page 100... ...
Failure to demonstrate superior efficacy jeopardizes the sales of new drugs, reducing the enthusiasm of the pharmaceutical industry to develop them. The development of surrogate markers for unprotected sex might shorten the duration of some studies of barrier methods, which currently require documentation of pregnancy as the end point.
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From page 101... ...
Conversely, short-acting vaginal delivery systems such as tablets, films, or suppositories could also be effective, depending on the molecule. The science of drug delivery systems is constantly evolving and is a technically demanding, highly specialized, and costly endeavor.
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From page 102... ...
A password access system could ensure the necessary limitations on use of the site. Engagement of the Pharmaceutical Industry Given the enormous costs of drug development, the development and testing of novel contraceptives are not likely to be accomplished by government or public-sector programs alone and will require significant participation of the pharmaceutical industry.
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From page 103... ...
The science of drug delivery systems is constantly evolving and is technically demanding, highly specialized, and costly. Although most pharmaceutical companies have dedicated groups with expertise in delivery systems, only a few investigators outside of the pharmaceutical industry specialize in this particular applied science.
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From page 104... ...
Recommendation 5: Implement mechanisms to accelerate contraceptive product development and clinical testing once a lead molecule or concept prototype has been discovered in an academic laboratory by sharing multidisciplinary national and international resources. This objective could be achieved by reestablishing the special projects program (Contraceptive Development Branch)
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From page 105... ...
The provision of incentives such as patent life extension, favored tax status, and indemnification to the pharmaceutical and biotechnology industries to expand their contraceptive research and development programs and their collaborative interactions with the public sector would also aid in the development of contraceptives to meet the needs of populations in both developed and developing countries. Recommendation 6: Develop mechanisms to access, apply, and enhance the technology of drug delivery and formulation science to contraceptive development.
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From page 106... ...
2001. Risks in new drug development: approval success rates for investigational drugs.
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From page 107... ...
2001. Environment-sensitive hydrogels for drug delivery.
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