The search has begun for long-acting contraceptives
With funding from the Bill & Melinda Gates Foundation of Seattle, Durham, NC-based FHI 360 has launched its Contraceptive Technology Innovation Initiative to develop innovative, long-acting contraceptives to help expand choice and access for women most in need in low-income countries. The Initiative will expand current work to develop a longer-acting injectable contraceptive and research funded by the U.S. Agency for International Development to develop a new biodegradable contraceptive implant.
It is estimated that 222 million women around the world have an unmet need for modern contraception.1 Since long-acting forms of contraception don’t require regular resupply from a provider or action from users, they are ideal in settings where access to healthcare services is limited. While existing long-acting methods have better continuation and adherence rates than shorter-acting methods and are cost-effective, they might be unaffordable for women in resource-challenged countries, or they might not meet women’s needs or preferences.
There is a need for new long-acting contraceptive options that will fill existing gaps and increase choices for women, notes Laneta Dorflinger, PhD, Initiative director. "In recent decades, there has been limited investment in contraceptive research and development," noted Dorflinger in a statement accompanying the project launch. "We applaud the Gates Foundation’s long-term vision, which looks not only to meet the needs of women today through efforts such as FP 2020 (a global partnership of governments, non-profit organizations, and the private sector to enable 120 million more women and girls to use contraceptives by 2020) but also to ensure that we can meet the needs of women tomorrow by making longer-term investments in innovative product development."
A biodegradable implant?
With research funded by the US Agency for International Development (USAID), FHI 360 is pressing forwarding in developing a highly effective biodegradable contraceptive implant. Prototypes are being designed now to last approximately 18 months, and have a short "tail" — the time between when the method becomes less effective and when blood levels of the progestin (contraceptive hormone) decline to undetectable, says Dorflinger. This characteristic is important to ensure a rapid and predictable return to fertility, she explains.
"During the period of effectiveness, ideally the progestin release from the implant will be zero order,’ so that blood levels are quite constant, but remain above a threshold to ensure high effectiveness," states Dorflinger. "Finally, the implant should be easily removable for at least some period of time in the event that a woman has unwanted and intolerable side effects."
With such a target product profile in mind, a substantial technological challenge will be to develop a drug delivery system that will provide constant release for the intended duration, but then have release rates drop to zero quite quickly, observes Dorflinger.
"Formulating this drug delivery in a way that allows for removal, if desired, without the implant fragmenting will be a second challenge," she notes. "Advances in sustained release delivery systems and biodegradable polymer technology make us optimistic that we will be able to reach these two goals."
2-rod implant progresses
FHI 360 continues to work with Sino-implant (II), a highly effective, low-cost, subdermal contraceptive implant composed of two thin, flexible, silicone rods, each containing 75 mg of levonorgestrel. The two rods are inserted under the skin of a woman’s arm by a trained healthcare provider and are labeled for four years of use, at which point they have to be removed. The annual pregnancy rate for the Chinese-manufactured implant method is listed below 1%. It is not available in the United States.
FHI 360 is providing technical assistance to facilitate the device’s global introduction, including conducting independent quality testing, negotiating public-sector price-ceiling agreements, supporting the World Health Organization prequalification application process, and working with distributors to secure national regulatory approvals. It also is leading a new clinical trial in the Dominican Republic, which will supplement existing clinical evidence, and is collaborating on post-marketing surveillance studies in four countries with support from the Gates Foundation and USAID.
A longer-acting shot?
FHI 360 is continuing its work on the development of a longer-acting injectable contraceptive, says Vera Halpern, MD, FHI 360 scientist. (To read about its efforts, see the Contraceptive Technology Update article, "Longer-acting method that is injectable probed," March 2013, p. 28.)
Since mid-2013, an additional research project has been selected for proof-of-concept testing under the initiative, says Halpern. Researchers at Orbis Biosciences of Kansas City, KS, led by principal investigator Nathan Dormer, PhD, are evaluating poly(lactic-co-glycolic) microspheres manufactured using Orbis Biosciences’ proprietary Precision Particle Fabrication technology and releasing etonogestrel. Orbis Biosciences’ technology allows for a linear increase in concentration to therapeutic levels, followed by a steady-state, sustained release for desired length of time. The goal is to reduce the number of injections and improve patient compliance.
"All four subcontracts have been executed, and all four research sites have started collecting the data," states Halpern.
- Singh S, Darroch JE. Adding it up. Costs and benefits of contraceptive services. Estimates for 2012. New York: Guttmacher Institute; accessed at http://bit.ly/LD9jMT.