Current Research and Innovations Addressing Oxytocin Quality: April 8th Stakeholders Meeting Deepti Tanuku, MA, MPH UNCoLSC Optimal Procurement of Affordable and Quality-Assured Life-Saving Maternal Health Commodities Uganda, September 10, 2015 On April 8th, 2015, global stakeholders on oxytocin quality convened to discuss the existing research and needed future research to improve the quality of oxytocin, and to develop a collaborative agenda for addressing those challenges. The meeting was organized by Jhpiego’s USAID-funded Accelovate program, in collaboration with Maternal Health Technical Resource Team (MHTRT) of the UN Commission on Lifesaving Commodities for Women and Children (UNCoLSC). Participants came from agencies and organizations in public health, pharmaceuticals, advocacy, international development, and academia. On your thumb drives, the meeting organizers have provided you with a word-document summary of the shared findings – we are also happy to provide the detailed meeting report upon request. I will give you the top-level findings and recommendations now.

Snapshot of current research addressing several aspects of oxytocin quality simultaneously How much poor-quality oxytocin is being used? Country case studies in Ghana, Indonesia Who: US Pharmacopeia, USP-PQM Program How stable is oxytocin under varying temperatures and conditions? Thermal Stability Studies, Stability along Supply Chain Who: Partnership for Supply Chain Management (PFSCM), Path, WHO, Merck for Mothers, Concept Foundation Other shared findings:   Participants noted that oxytocin is particularly prone to chemical degradation when exposed to high temperatures. There are varying recommended storage standards across manufacturers and an absence of accepted international guidelines, which causes confusion about the appropriate transport and storage conditions. Until recently, little data had been available about the extent of the trouble, and how much poor-quality oxytocin is reaching the point of use. In addition, there is still some uncertainty about how much of the problem is caused by poor manufacturing processes, and how much is caused by degradation along the supply chain. While there are some manufacturers that produce good quality oxytocin, others may not. Differences in oxytocin quality come from different API, manufacturing processes, and excipients. Varied in-country policies and procurement processes introduce additional quality complications. Research has indicated that there may be a number of unregistered products for sale in some countries. The price of oxytocin is relatively low, and there are hundreds of producers, which increases competitiveness. Most oxytocin is procured my national governments, and many of them may not yet be aware of problems with oxytocin quality. Fortunately, evidence continues to indicate that high-quality oxytocin is safe and very effective for the prevention and treatment of PPH when manufactured, handled, and stored properly. However, there is also space for continued innovation in the uterotonics market. Many of the challenges across the supply chain are well documented, so these messages can be shared with procurement agencies. Several participants noted the need for clear, practical guidance for oxytocin procurers, to ensure they are procuring the best quality oxytocin, and delivering it in a safe, effective way. Robust advocacy and education efforts from a variety of levels will be necessary to improve the quality of oxytocin. Source: Jhpiego Accelovate Oxytocin Quality Stakeholders Meeting Report, April 2015

What program and policy changes improve oxytocin quality? Snapshot of current research addressing several aspects of oxytocin quality simultaneously What program and policy changes improve oxytocin quality? Integration of oxytocin in EPI cold chain, strategies for PPH reduction Who: MSH, Gynuity Which innovations increase access to high-quality oxytocin and how feasible are they? Prioritizing oxytocin quality solutions and pathway to scale Who: Jhpiego Misoprostol and Oxytocin in Uniject: Examining two strategies for PPH prevention in communities, Gynuity Integration of oxytocin in the EPI cold chain: Mali Case Study, MSH Increasing Access to High-Quality Oxytocin through Innovation, Jhpiego   Participants noted that oxytocin is particularly prone to chemical degradation when exposed to high temperatures. There are varying recommended storage standards across manufacturers and an absence of accepted international guidelines, which causes confusion about the appropriate transport and storage conditions. Until recently, little data had been available about the extent of the trouble, and how much poor-quality oxytocin is reaching the point of use. In addition, there is still some uncertainty about how much of the problem is caused by poor manufacturing processes, and how much is caused by degradation along the supply chain. While there are some manufacturers that produce good quality oxytocin, others may not. Differences in oxytocin quality come from different API, manufacturing processes, and excipients. Varied in-country policies and procurement processes introduce additional quality complications. Research has indicated that there may be a number of unregistered products for sale in some countries. The price of oxytocin is relatively low, and there are hundreds of producers, which increases competitiveness. Most oxytocin is procured my national governments, and many of them may not yet be aware of problems with oxytocin quality. Fortunately, evidence continues to indicate that high-quality oxytocin is safe and very effective for the prevention and treatment of PPH when manufactured, handled, and stored properly. However, there is also space for continued innovation in the uterotonics market. Many of the challenges across the supply chain are well documented, so these messages can be shared with procurement agencies. Several participants noted the need for clear, practical guidance for oxytocin procurers, to ensure they are procuring the best quality oxytocin, and delivering it in a safe, effective way. Robust advocacy and education efforts from a variety of levels will be necessary to improve the quality of oxytocin. Several presentations were also made that highlighted ongoing work on developing and integrating oxytocin quality innovations; participants shared updates regarding promising new and developing technologies and commodities, including: Improving Drug Quality with PharmaChk, Boston University Update on Heat-Stable Carbetocin, Merck for Mothers Update on Sub-Lingual Oxytocin, PATH Inhaled Oxytocin, Monash University Source: Jhpiego Accelovate Oxytocin Quality Stakeholders Meeting Report, April 2015

Recommendations for Oxytocin stakeholders Reviewing oxytocin labeling issues Address interrupted cold chain during supply/storage Emphasize oxytocin procurement decisions on not just cost but value of quality-assured oxytocin Consider feasibility/ acceptability of oxytocin quality solutions and innovations Publish case studies to demonstrate ways to improve quality Improved information sharing among partners Some general recommendations for maternal health and oxytocin stakeholders came from this meeting, including those listed on this slide. These were listed at the global level, it is possible that country governments present today in this workshop have thought through some or all of these

Recommendations for Oxytocin stakeholders, cont’d Incentivizing procurement of quality-assured oxytocin, including pre-qualified formulations Incentivize improved manufacturing standards Development of an oxytocin quality testing protocol for countries Development of recommended standard protocols for drug regulatory authorities to follow Study how market authorization is granted, ensure that only authorized products are in country Some specific recommendations for procurement agencies and ministries of health came from this meeting, including those listed on this slide. These were listed at the global level, it is possible that country governments present today in this workshop have thought through some or all of these