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P218: Pharmacist Training for Advanced Therapeutic use in a First in Human Study (FIH): Delivery of AAV9 CRISPR/Cas9 in Aviremic HIV Participants

Poster Presenter

Samantha Seepersad

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Excision Biotherapeutics
United States

Objectives

This case study is to provide Lessons Learned and Best Practices for pharmacy training strategies in a FIH study of a novel therapeutic where changes in administration occur as new information develops with real-world examples in a AVV9 containing CRISPR/Cas9 HIV trial.

Method

This study in HIV participants is conducted at 3 US sites. The product is an AAV9 viral vector delivering CRISPR/Cas9 via a single IV dose. Dose delivery system was developed cross-departmentally based upon compatibility studies and training provided to the sites in person and remotely.

Results

Dosing in this study is an AAV9 containing CRISPR/Cas9 viral vector-based product, a novel therapeutic agent delivered via a single IV dose administration. The product is supplied in multiples vials needing to be pooled, mixed, and diluted on site by the pharmacist in a type A2, class 2 biosafety cabinet. A variety of factors must be taken into consideration for preparation and administration of this novel therapeutic including prevention of potential shearing of the AAV9 vector during the preparation, stability timeframe from preparation to administration, IV flushing prior to administration, use of the specified infusion pump and individual pharmacy and site capabilities. Cross-department development of two protocols for compatibility studies occurred to ensure suitability of all components prior to the start of each dosing cohort and included the feasibility of administration at each site. After dosing the first cohort, revisions to the preparation process were required based upon feedback from the pharmacists, viewing the in-clinic preparation, and the increased dosage between cohorts a second compatibility study was conducted and site re-training occurred. The revisions to the process included adding different components to the supplies for preparation, additional steps in pipetting and pooling the product to ensure the correct dose will be administered. Site retraining was conducted in-person and remotely utilizing a variety of training tools including the pharmacy manual, dosing worksheets, videotaped demonstrations, power point slide review and on-site observation at each site prior to dosing. Training was developed cross departmentally requiring collaboration of CMC, Clinical Operations, QA, Supply Chain and Translational Medicine to find solutions that worked for each individual site.

Conclusion

Dosing novel therapeutics in FIH study requires careful planning by cross-departments to ensure product integrity and appropriate dose administration occurs for each participant across sites. A well-planned compatibility study is required prior to finalization of the pharmacy manual to mimic the real-life administration for accurate dosing. Site selection is critical to ensure capabilities including access to the appropriate biosafety cabinet, infusion pumps and experience with gene therapy products and administration. Site staff training including pharmacy and infusion nurses needs to be consistent for accurately dosing all participants. With cross-department collaboration among CMC, Clinical Operations, QA, Supply Chain and Translational Medicine, the development of manuals and training materials the product was administered consistently across sites and within sites with no dosing errors. The Lessons Learned and Best Practices resulted in multiple compatibility studies and retraining of the sites. Using a variety of training methods and ensuring continuous line of communication between the sponsor and sites, a consistent and reliable product administration process was developed. Authors include RoseAnn Branca, Samantha Seepersad-Nayee, Panos Argiras, Qin Xiang, William Dexter Kennedy, MD