Product development: the product development (pd) division leads non-clinical, formulation, manufacturing, chemistry manufacturing and controls (cmc), analytical, and material planning and supply activities for ipm's products. This division is responsible for product supply and associated activities (including product manufacturing, packaging, labeling, distribution, and stability) and the post-use testing of dapivirine rings to support adherence assessments during clinical trials. In 2021, pd's efforts included conducting cmc activities to address feedback received from regulatory agencies, including the questions received from the ema as part of the review process of the monthly dapivirine ring regulatory dossier and as a part of the post-authorization commitments to the ema. Following the positive scientific opinion from the ema for the dvr, the pd team continued efforts related to commercial manufacturing of the dvr. This included completing capacity planning with critical vendors such as ipm's dvr product manufacturing partner, ipm's dapivirine drug substance manufacturing partners, and ipm's silicone manufacturing partner. Additionally, ipm supported the completion of manufacturing scale-up (1x to 5x) process validation. The 5x process validation was completed in 2022 and will be used as the dvr manufacturing scale going forward. Further, the pd team continued developing the three-month dapivirine ring and the dapivirine-contraceptive ring.

Regulatory affairs and quality assurance: ipm's regulatory affairs team oversees the monthly dapivirine ring regulatory process, providing leadership in dossier preparation, filings, and post-approval maintenance in Europe, the United States, south Africa, and other target african countries, where ipm is preparing for the market introduction of the ring. This division also supports all regulatory efforts for other ipm products on the product development pathway; this support includes submission and maintenance of investigational new drug (ind) documentation and conducting regulatory agency interactions related to new protocols for upcoming clinical trials. Importantly, in 2021, the regulatory affairs team managed all post-authorization measures related to the ema's positive scientific opinion of the monthly dvr. Additionally, the team completed the necessary activities to secure world health organization (who) prequalification (pq) and a recommendation from the who as an additional HIV prevention choice for women as part of combination prevention. The monthly dvr is now under regulatory review in african countries. These efforts were then leveraged, and the dvr dossier was submitted to numerous african countries for review and approval. By the end of 2021, the monthly dvr had received approval from 5 african countries. The monthly dvr remains under regulatory review in additional african countries.In partnership with the regulatory affairs team, the quality assurance (qa) team ensures ipm's product development and clinical studies are conducted in compliance with all applicable drug and safety laws. Audits are conducted during clinical trials to assure protocol compliance and compliance with an international conference on harmonization of technical requirements for registration of pharmaceuticals for human use (ich) guidelines, good clinical practices (gcp), and all applicable regulations. Vendor audits are also conducted where ipm's clinical, preclinical, or cmc work is conducted.

Clinical and medical affairs: ipm's clinical affairs department is responsible for quality control and compliance, medical safety, pharmacovigilance, medical affairs, clinical operations, biometrics, public affairs, community public affairs, and socio-behavioral sciences for the clinical trials conducted on ipm's products. Key activities in 2021 included:- continued support of the monthly dapivirine vaginal ring (dvr) clinical trialsipm worked with its clinical trial partner, the United States (us) national institutes of health (nih)-funded microbicide trials network (mtn) on the subsequent clinical trials of the dvr:o mtn-034 (reach): a phase 2a crossover trial evaluating the safety of and adherence to a vaginal matrix ring containing dapivirine and oral emtricitabine/tenofovir disoproxil fumarate in an adolescent and young adult female populationo mtn-042 (deliver): phase 3b, randomized, open-label safety trial of dapivirine vaginal ring (vr) and oral truvada use in pregnancyo mtn-043 (b-protected): phase 3b, open-label, safety and drug detection study of dapivirine vaginal ring and oral truvada in breastfeeding mother-infant pairsfurther, the clinical and medical affairs team supported the regulatory affairs team in developing and completing the clinical modules and post-approval amendments of the dvr dossiers submitted to regulatory authorities. - Clinical trial of ipm's three-month dapivirine ring building on the promise of ipm's monthly dapivirine ring, ipm developed the three-month dapivirine ring, designed to increase convenience and reduce annual costs compared to the monthly dapivirine ring. The clinical affairs team worked across departments and with external partners to develop the protocol for the bridging trial and complete all necessary trial preparations. The bridging trial (ipm 054) was initiated in q3 2022.- Clinical trials of the dapivirine-contraceptive vaginal ring, a multipurpose prevention technology (mpt)the three-month dapivirine-contraceptive ring is designed to provide slow and simultaneous release of the antiretroviral (arv) drug dapivirine to prevent HIV and the contraceptive hormone levonorgestrel to prevent unintended pregnancy. A second phase i clinical trial of the reformulated mpt ring (ipm 056/cctn019b) was in the planning stages throughout 2021 and initiated in mid-2022. This trial will be conducted by the eunice kennedy shriver national institute of child health and human development (nichd).