Learning about Expanded Access and Potential of the Levonorgestrel Intrauterine System (LEAP LNG-IUS): Regulatory Assessment

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NOTE: This report is accompanied by an appendix tool, the LEAP LNG-IUS Regulatory Matrix. Please find this here

With funding from the Bill & Melinda Gates Foundation, FHI 360 and partners Population Services International (PSI) and WCG Cares are implementing the Learning about Expanded Access and Potential of the LNG-IUS (LEAP LNG-IUS) Initiative. The project is intended to help determine if and how expanded access to the levonorgestrel intrauterine system (LNG-IUS) — a long-acting contraceptive — could increase contraceptive use and continuation rates in sub-Saharan Africa. Activities include research among women and providers in Nigeria and Zambia as well as demand forecasting in Kenya, Nigeria and Zambia. The findings from the project will help stakeholders better understand the potential demand for the LNG-IUS, experiences among users and providers, and continuation rates and cost-effectiveness of the LNG-IUS compared with other long-acting reversible contraceptive (LARC) methods.

In addition, under the LEAP LNG-IUS Initiative, a regulatory assessment was conducted in 2018. The goal of the assessment was to identify potential strategies to expedite national registrations of LNG-IUS product(s) in Family Planning 2020 (FP2020) countries. Results of the assessment are presented here.

This report is intended to provide both strategic analysis and technical guidance to donors, implementing organizations and LNG-IUS suppliers. The primary focus of the assessment was on LNG-IUS products that 1) currently have approval from a Stringent Regulatory Authority (SRA); and 2) are currently offered at an affordable public sector price in FP2020 markets. At this time, only Medicine360’s LNG-IUS product, AVIBELA, meets these criteria, so this assessment will likely be most relevant for Medicines360 as well as donors, implementing partners and/or governments who are considering registering or introducing AVIBELA. However, the findings from this report may also be relevant for suppliers of other SRA-approved LNG-IUS products (e.g., Bayer Healthcare) and/or manufacturers of products that are not currently approved by an SRA (e.g., Pregna, HLL Lifecare, and Meril). In addition to commercial products, the International Contraceptive Access (ICA) Foundation provides donations of a free, unbranded LNG-IUS product in FP2020 countries. (See the Overview of LNG-IUS Suppliers section for more information.)

Several potential regulatory strategies to expedite country-level approvals of LNG-IUS product(s) are outlined in this document:

    1. Pursuing World Health Organization (WHO) prequalification either through:
      • Full WHO prequalification; or
      • Abbreviated WHO prequalification for SRA-approved generic or innovator products
    2. Utilizing one of the WHO-supported collaborative procedures:
      • WHO Collaborative Procedure for fully WHO prequalified products; or
      • Accelerated Collaborative Procedure for SRA-approved products
    3. Leveraging regional harmonization mechanisms
    4. Applying for national registrations on a country-by-country basis

A key finding from this work is that each potential pathway has advantages and disadvantages. For example, WHO prequalification or participation in a WHO-supported collaborative procedure could provide strategic value from a marketing perspective and/or be a quicker route to registration in FP2020 countries. However, there also are various challenges which should be carefully evaluated to determine whether following a WHO pathway would result in significant time or cost savings. Similarly, participation in regional harmonization initiatives may allow manufacturers to take advantage of harmonized guidelines and expedited approval timelines; however, these regional initiatives are at varying levels of maturity and implementation, and none of them currently allow for mutual recognition among countries.

Pursuing national registrations individually on a country-by-country basis would ensure that the applicant is compliant with local requirements, allow for the most flexibility, and could potentially offer a route for expedited review, yet there is wide variation in country-specific requirements and submissions may be subject to extended delay outside of the applicant’s control. Thus, the benefits and limitations inherent in each of these registration pathways must be assessed in conjunction with the applicant’s strategic objectives (time, cost, target number of registrations, and specific priority countries) to identify which pathway is most likely to yield the greatest benefit. Refer to the table below, also included in the Conclusions section, for a summary of the advantages and disadvantages of each pathway.

In addition to strategic guidance about the advantages and disadvantages of the different overall regulatory pathways, this report also includes an assessment of the national regulatory requirements in three countries which may be viewed as priorities for LNG-IUS registration and introduction: Ghana, Ethiopia, and Vietnam. These countries were selected for an in-depth assessment after consultation with stakeholders including donors and service delivery groups. However, it is important to note that a number of other countries were also considered as potential priorities, and inclusion in this assessment does not imply commitment from an LNG-IUS supplier or from donors to pursue registration in those three countries, nor does it imply that other countries are not viewed as a priority moving forward. The national regulatory assessments were conducted using online information from each country’s National Regulatory Authority to identify country-specific requirements for pharmaceutical product registration. In-country stakeholders and regulatory teams were also consulted.

Finally, a summary Regulatory Assessment Matrix with information about each of the FP2020 countries is also included for use as a quick-reference document (see separate Excel file for the matrix). Summary information includes each country’s participation in the WHO collaborative procedure, the level of maturity of its applicable regional harmonization initiative (if any), an assessment of the ease of its local registration processes, information about LARC (implant and IUD) use and expansion rates, and a note about whether the country was considered to be a current priority for LNG-IUS registration by stakeholders that were interviewed as part of this process. Information in this matrix is subject to change and includes subjective assessments, based on our team’s knowledge and experience.