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defined guidance, individual institutions develop their own policies and procedures, which often differ and are often outdated.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.

Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges

“…8 The National Institutes of Health (NIH) Recombinant DNA Guidelines and the World Health Organization (WHO) Laboratory Biosafety Manual categorize infectious agents into risk groups for laboratory research (Risk Groups 1-4). 23 The risk group informs about the level of containment needed to minimize risk during the handling of these infectious agents as designated by its biosafety level. 23 The Centers for Disease Control and Prevention (CDC), WHO, and NIH have published recommendations for work at different biosafety levels (BSL-1 to BSL-4) for wild-type virus and viral vector handling in a laboratory research setting.…”

“…23 The risk group informs about the level of containment needed to minimize risk during the handling of these infectious agents as designated by its biosafety level. 23 The Centers for Disease Control and Prevention (CDC), WHO, and NIH have published recommendations for work at different biosafety levels (BSL-1 to BSL-4) for wild-type virus and viral vector handling in a laboratory research setting. When viral vector systems are used in gene therapy experiments in a clinical setting, these recommendations are adapted to do a comprehensive risk assessment and for developing a mitigation plan.…”

“…When viral vector systems are used in gene therapy experiments in a clinical setting, these recommendations are adapted to do a comprehensive risk assessment and for developing a mitigation plan. 19,23 As with risk group classification, biosafety levels differ by viral vector systems. Historically, IBCs have been responsible for reviewing any risks associated with viral shedding and insertional mutagenesis during the protocol review process.…”

“…2,20,21 As of 2019, almost 2600 gene therapy clinical trial studies have been completed, are ongoing, or have been approved worldwide. 22,23 Furthermore, 232 gene and cell therapy trials have been approved worldwide, and 4 gene therapy products that were approved by the Food and Drug Administration (FDA) are available in the United States. 15,22,23 The majority of these gene therapy trials, almost 70%, are based on viral vectors.…”

“…22,23 Furthermore, 232 gene and cell therapy trials have been approved worldwide, and 4 gene therapy products that were approved by the Food and Drug Administration (FDA) are available in the United States. 15,22,23 The majority of these gene therapy trials, almost 70%, are based on viral vectors. 15,24 Although transfer of genetic material into cells may be accompanied through nonviral vector-based delivery systems, we will be evaluating only the most common biosafety issues associated with viral-based vector systems in this review.…”