It is now 50 years since modern hormonal contraception became available, nevertheless, it remains a challenge to provide products of assured quality at an affordable price to people throughout the world. This issue is a particular priority for those directly involved in access to contraception and in trying to meet the targets of Millennium Development Goal 5 (see Access to drugs for maternal health)

Since its inception, Concept has been actively involved in efforts to achieve equitable access to quality assured hormonal contraceptive methods, something, we believe, which is essential as part of overall efforts to reduce maternal mortality and morbidity.  
Concept is currently engaged in ensuring access to low-cost generic contraception of assure quality; and in expanding the availability of the once-a-month injectable, Cyclofem®.

 

Working with generic hormonal contraceptive manufacturers

In recent years, generic contraceptive companies have gained significant market share in the oral contraceptive market of both developed and developing countries. As such, several of the traditional manufacturers of hormonal contraceptives have withdrawn from this market leaving just two major multinational players. In addition there has been a shift of focus to high-value implants, steroid-releasing intra-uterine devices, vaginal rings and patches.. For these reasons, as well as cost, major procurement agencies have begun to access products from the generic pharmaceutical industry in lower and middle income countries. Their requirement has been to obtain products of internationally assured and verifiable quality at an affordable price, something that, at least with regard to assured quality, remains elusive.

Concept has, and continues to play a leading role in this area as the manufacturing environment goes through a process of unprecedented change, as companies address the more stringent manufacturing requirements being progressively implemented in many countries. Concept is building on the instrumental role it played in the introduction of dedicated emergency contraception, beginning in 1994 as a founder member of what became the International Consortium for Emergency Contraception (ICEC), through to our current activities to ensure quality manufacturing and access to products from the developing country generic pharmaceutical industry. In 2007, we published the most authoritative report on the subject to date.

We remain actively engaged in a number of important activities directly supporting improved access to affordable hormonal contraception. One important activity, supported by the Innovations Fund of the Reproductive Health Supplies Coalition is allowing us to build on findings of the earlier report. We are engaged in reviewing the current situation in terms of the current capabilities of a leading group of generic contraceptive manufacturers and determining the technical, quality and other challenges facing these companies, particularly in the manufacture of products of assured quality. A critical component is to assist companies in understanding the requirements of WHO’s Prequalification of Medicines Programme for reproductive health and what is necessary to get specific products prequalified.

We continue to provide technical inputs, through Health Concepts International, with our licensees engaged in the manufacture and marketing of the once-a-month injectable contraceptive, Cyclofem®; as well as supporting other manufacturers around the world with technical consultancy and laboratory services.

 

Cyclofem®

The once-a-month injectable contraceptive, Cyclofem®, was licensed  to Concept Foundation under its collaborative agreement with WHO. Since its introduction in the early ‘90s, Cyclofem® has become well-used in a number of developing countries, particularly in Indonesia (which was the first country in which it was registered) and in Latin America. It provides an additional safe and effective choice to women, particularly younger women at the beginning of their contraceptive lifecycle and an estimated 2.5 million women are now regular users of the method. In 2007, medroxyprogesterone acetate, 25mg + estradiol cypionate, 5 mg (Cyclofem®) was included as an injectable hormonal contraceptive in WHO’s Model list of Essential Medicines.

Cyclofem® is the most studied monthly injectable contraceptive.  Studies have included: pharmacokinetic/ pharmacodynamic studies, which resulted in the selection of the dose, 25 mg medroxyprogesterone acetate + 5mg estradiol cypionate; metabolic and other safety studies, which showed insignificant or no effects on lipid metabolism, coagulation and fibrinolysis, glucose metabolism and prolactin;  Phase III and introductory trials. In these and subsequent studies, more than 140,000 woman-months of use were studied. No serious adverse events were observed and only 10 pregnancies occurred, giving a remarkable efficacy of one pregnancy every 1,200 years of use.  This is the highest efficacy seen with any non-permanent method of contraception. These studies also showed more regular bleeding patterns than progestogen-only injectables; no effect on blood pressure; and a rapid return to fertility (Hall, 1998).

It is now recognized that estradiol (or its precursor esters, such as estradiol cypionate), has favourable effects on lipid metabolism and cardiovascular function. Estrogen also has an important role in bone mass accumulation and retention and studies on the use of 5mg of estradiol cypionate monthly (i.e., the same dose as in Cyclofem) have shown a favourable effect on bone in DMPA users. A recent review has concluded that in relation to liver function, the natural estradiol ester is even safer than ethinyl estradiol, found in combined oral contraceptives.

Cyclofem® can make a major contribution to contraceptive choice in developing countries, and Concept is increasing its efforts, with its pharmaceutical partners, to further expand the geographical availability of the product, with a particular focus on Africa and South Asia.

For further information about Concept’s work on generic hormonal contraceptives or Cyclofem®, please contact lester.chinery@conceptfoundation.org.