Gene Replacement Therapy: A Primer for the Health-system Pharmacist

Abstract

Purpose: Comprehensive review of gene replacement therapy with guidance and expert opinion on handling and administration for pharmacists.

Summary: There are currently ∼2600 gene therapy clinical trials worldwide and 4 Food and Drug Administration (FDA)-approved gene therapy products available in the United States. Gene therapy and its handling are different from other drugs; however, there is a lack of guidance from the National Institutes of Health (NIH), FDA, Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and professional associations regarding their pharmaceutical application. Although the NIH stratifies the backbone biologicals of viral vectors in gene therapies into risk groups, incomplete information regarding minimization of exposure and reduction of risk exists. In the absence of defined guidance, individual institutions develop their own policies and procedures, which often differ and are often outdated. This review provides expert opinion on the role of pharmacists in institutional preparedness, as well as gene therapy handling and administration. A suggested infrastructural model for gene replacement therapy handling is described, including requisite equipment acquisition and standard operating procedure development. Personnel, patient, and caregiver education and training are discussed.

Conclusion: Pharmacists have a key role in the proper handling and general management of gene replacement therapies, identifying risk level, establishing infrastructure, and developing adequate policies and protocols, particularly in the absence of consensus guidelines for the handling and transport of gene replacement therapies.

Keywords: biosafety; gene therapy; hospital pharmacy services.

Figure 1.

Risk identification for gene therapy products based on replication competency status, ability to integrate into the genome, and toxicity of transgene. The flow chart tool emphasizes the gene therapy safety attributes that should primarily be considered when deciding BSL handling and procedures. If a gene therapy product has the ability to replicate or can integrate into the genome or contains a toxic transgene, it is recommended that a more detailed risk evaluation by an institutional committee will be conducted to determine safety handling processes. *BSL-1 classification is recommended provided that the gene therapy product was manufactured without using adenovirus or any other helper virus of human origin. BSL1, biosafety level 1.