“It’s all in a decade’s work”: A Ten-Year Retrospective Report on the IMPT
Plan deliberately and early

To ensure efficient and effective research and development, researchers and developers must use systematic evaluation and rigorous product-development planning and implementation processes. As the product-development cycle progresses […] development plans should be refined to incorporate emerging information. –Excerpt from “Saving Lives” brief, 2010

A key role of the IMPT is to advance a larger fieldwide strategy to ensure effective and efficient MPT R&D. As such, the IMPT network–led by the Secretariat–works to continuously assess the status of the MPT field, identify priority areas, and accelerate action around those areas through objective guidance and tools, as well as convene technical experts. Over the past decade this effort has been iterative, enabling the IMPT to adapt as the MPT field evolves. A wide range of tools and guidance have been developed in collaboration with experts within the IMPT network to inform the strategic direction of the MPT field. These include:

Early stage assessments to clarify product role and intended context.

In the early years of the IMPT, the SAWG worked to critically examine scientific and technical issues facing the development of MPTs (see section one). Outcomes from the “Global Forum on MPTs” helped shape the agenda of the SAWG as they tapped into multidisciplinary experts from across the globe. As part of this early work, the IMPT initiated an MPT product prioritization and gap analysis exercise to clarify objectives and lay a firm foundation for the strategic development of MPTs, including which indications to prioritize. Recommendations were vetted at the Product Prioritization Stakeholder Meeting, held in October 2012, which brought together technical experts to review preliminary recommendations, including those on product profile, priority candidates, and gaps.

The resulting meeting report summarized key recommendations and suggestions in three priority areas:

      1) Active Pharmaceutical Ingredients (APIs);
      2) Formulation and Delivery; and
      3) Coordination and Process.

Overall, the expert group noted a few key takeaways: The need for “good basic science” that can inform MPT R&D; the inclusion of young women aged 14-17 in research studies; the incorporation of “deliverability” and “access” planning as key factors guiding MPT prioritization and investment; continued exploration of approaches to working across HIV, STI, and family planning programming; as well as planning ahead for anticipated complex regulatory processes for MPT R&D; and finally, meeting participants recommended that MPT development must balance advancing products with the most near-term potential, while also continuing to work toward concepts and products that best meet the parameters specified in the prioritization exercises. As noted in the meeting report, “Those working on MPTs should ‘dream big’ rather than only settling for working on and refining what is already in the near-term pipeline.” Seven years later, despite the MPT field’s advancement toward specific recommendations from the 2012 Product Prioritization Stakeholder Meeting, many of the ‘takeaways’ described above remain at the core of the IMPT’s efforts.

Clear go/no go decisions for safety, efficacy, acceptability, and cost-effectiveness parameters.

In the two years following the October 2012 meeting that worked to define general target attributes for MPT products, the IMPT also worked to inform standard-setting in MPT product development. In 2014, the MPT Product Prioritization and Gap Analysis exercise was released–a summary of survey findings intended to inform network efforts to support strategic focus on MPT priority product development strategies among funders and product developers. This exercise provided a basis for target product profile (TPP) development, described below, among other efforts such as better understanding social-behavioral and commercialization issues relevant to achieving high-impact MPT products.

In this way, two years after the 2012 Product Prioritization Stakeholder Meeting, the IMPT had evolved beyond simply prioritizing specific MPT product dosage forms and general MPT product attributes to the development of more specific TPPs focused on each type of prioritized product dosage form. These dosage-form specific TPPs, published in 2014, worked to define the necessary attributes and required supporting data for the successful development of impactful MPT products. At the time, two TPPs with dosage-form specifics were published. One on the MPT Intravaginal Ring, the second on the MPT Long-Acting Injectable.

Building off of this work, in 2015 the IMPT determined that a Strategic Evaluation Framework (SEF) would be a useful tool for funding agencies to work with their product developers and other implementing partner grantees to help fill identified research gaps and break from the limitations of the current clinical research paradigm. The brief entitled, “Laying the Groundwork for a Strategic Evaluation Framework (SEF) for HIV Prevention and MPT Product Development,” outlined the three key components of an SEF: the Target Market Profile (TMP), the Strategic Target Profile (STP), and the Target Product Profile (TPP). With the TPPs having already been completed, in 2015, the IMPT led research to support the development of a generalized TMP and STP for ARV-based prevention and MPT products. The eventual SEF for MPT development–published in 2016–aimed to inform design and development decisions in a way that maximize market success and impact of potential products aligned with the market drivers for MPT target populations.

More recently, an emergent key challenge for MPT R&D is that investment in the MPT field stems primarily from the US Government, including NIH and USAID, as well as smaller non-profit and for-profit entities that often do not have resources for end-user research–not to mention the capacity and expertise for manufacturing, and scale-up. Large scale pharmaceutical companies typically boast the necessary infrastructure for end-user and other ‘end stage’ considerations into their early stage R&D investment decisions, for example. But this is not the scenario for how current MPTs in the pipeline are funded and developed.

With this in mind, in order to help guide decisions for prioritizing investments and integrating end-user research early and throughout the biomedical HIV prevention product development process, the IMPT, in close collaboration with USAID’s Office of HIV/AIDS (OHA), developed a framework designed to inform investment decisions that integrate user perspectives at various stages of product development for USAID’s Microbicide Program. The content of this framework was generated through consultations with experts representing global pharmaceutical organizations with experience in standard R&D as well as public-private partnerships, smaller biotechnology companies, and non-profit product developers.

Highlighted in this framework is the importance of end-user considerations being recognized as a critical part of the HIV prevention product development process, as well as guidance on what type of user and market data to incorporate at which stage (from R&D to launch) that would increase the potential success of new biomedical HIV prevention products in the highest risk populations. The final published framework will be available in available soon.

Reviews of feasibility, sources of supply, and manufacturability to identify issues that will affect MPT product specifications.

The complexity of developing MPT products includes numerous factors beyond combining indications. As such, the IMPT has taken a closer look at a number of areas identified as critical gaps or key research areas. Following the 2015 Priority Issues Identification Exercise, the IMPT Secretariat convened three technical meetings examining the challenges of combining hormonal contraceptives (HCs) with antiretrovirals (ARVs) in MPTs and also hosted a summary webinar on the topic. The work around this topic also resulted in the peer-reviewed publication of a Strategic Action Framework on HC MPTs.

Also in 2016, the IMPT hosted a two-day workshop focused on clinical trial evaluation for MPTs with the goal of informing an overall strategy for the successful clinical evaluation of MPTs. Meeting participants outlined strategies for successfully addressing challenges and risks, and identified critical market issues that can be addressed through clinical evaluations of MPTs, or through the study of intended target populations. Similarly, in 2017, the IMPT hosted a webinar on bioavailability and bioequivalence strategies–a key issue for MPT R&D that emerged from the network. Other IMPT-hosted technical webinars under this topic area include the discussion of: manufacturing issues for MPTs; opportunities and challenges in developing long-acting MPTs; and the development of MPTs to address STIs.

Building off of findings from the HC MPT workstream, in 2018 the IMPT initiated a new work stream activity focused on novel female-initiated non-hormonal contraceptive (non-HC) approaches, including approaches that may be combined with agents that prevent STIs, including HIV, that can help advance the development of non-HC MPTs. To identify priorities and gaps that can inform product development and investment decisions in this area, in 2019 the IMPT conducted an extensive literature review of work conducted in the area of non-HC over the past forty years, as well as conducted interviews with technical experts working on male and female non-HCs. Outcomes from this activity will be a white paper outlining recommended action areas to advance this area of MPTs to be vetted as part of the annual Contraceptive Development Meeting hosted by the Contraception Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in November 2019. This meeting is inclusive of all NICHD's Contraceptive Development Branch awardees that are developing new and improved methods of non-hormonal contraception, including MPTs. Stay tuned!

Evaluations to ensure that the needs of end-users, health care providers, and other stakeholders are incorporated throughout the development process.

The IMPT has long recognized that developing a successful and impactful MPT depends on factors beyond success in the lab. A key focus of the IMPT has been on activities that are critical to ensuring that MPTs in development are not only efficacious in clinical trials, but also desired, acceptable, and accessible once commercially available. Toward this end, the IMPT collaborated with experts from across the field for several years–first starting in 2016–to develop a Market Access Framework, which serves as a roadmap for user evaluations.

Similar to MPT investment tracking, a task of the IMPT Secretariat is to annually track end-user research within the MPT field. To better understand this landscape, the IMPT has conducted a methods analysis looking at different types of research in this space and released a report comparing socio-behavioral research with human-centered design (HCD) and convened two technical webinars on the topic–also described in section one. The first highlighted new research exploring the acceptability of and preference between potential MPT product types, drivers of future product use, and other important end-user considerations. The second engaged new stakeholders in the end-user space by bringing together experts for a dynamic discussion of lessons learned from conducting end-user research in the fields of contraception, HIV, and MPTs to synthesize and share best practices for MPT product development and introduction. Developing MPTs that put women at the center of product R&D was a core premise in the founding of the IMPT, and the network is working to enhance its end-user portfolio as more products move through clinical trial phases and inch closer to reality.

Business and financial analysis plans for sustainability.

In a landscape of limited funding to support product development and introduction, it is necessary to take a close look at financial and market considerations to support the pursuit of products with the best chance to make an impact. To this end, the IMPT developed an online interactive target population mapping tool–launched in 2018–that overlays HIV prevalence and the total addressable market for contraception to illustrate the ‘hot spots’ where an MPT that combines HIV prevention with contraception might have the greatest impact. The contraceptive method mix was also added to the map to further illustrate key factors for consideration when looking at the target population. Previously, the IMPT looked at impact modelling around MPTs–publishing a landscape review report as well as a technical webinar around the topic. This provided the foundation for current work to develop an investment case for MPTs, but certainly more work to help ensure the market success of MPTs is needed. Moreover, the SACC has prioritized public-private partnerships in order to ensure MPT product supply and financing. MPT product developers have worked hard to foster these partnerships–but more work needs to be done to better engage the private sector and help ensure the future of MPT product development and introduction.

With over two dozen products in varying stages of development in the MPT product development pipeline, there has been great progress over the past decade. Still, there is much work to do, including: focused research for pressing questions around MPT market, facilitating public-private partnerships, supporting rigorous and feasible clinical trials, and ensuring a robust manufacturing infrastructure. Further, given limited resources and the high cost of clinical trials, rigorous standards to guide product investment decisions that can help ensure product success are critical. HIV Prevalence Tool