Learning Objectives Background of Gene Therapy

2007 ASHP Midyear Clinical MeetingLas Vegas, NVBackground of Gene Therapy•Level 1 – nonpathogenic•Examples: Bacillus subtilis, E.coli•Basic requirementshttp://www.cdc.gov/OD/ohs/pdffiles/bsl123.pdfBackground of Gene Therapy•Level 2 – pathogenic if injected,inhaled, or ingested or exposedto mucous membranes•Examples: measles virus,hepatitis B virushttp://www.cdc.gov/OD/ohs/pdffiles/bsl123.pdfBackground of Gene Therapy•Level 3 – pathogenic, withpotential for serious or lethaldisease & potential for aerosoltransmission•Examples: M. tuberculosis,Coxiella burnetiihttp://www.cdc.gov/OD/ohs/pdffiles/bsl123.pdf

2007 ASHP Midyear Clinical MeetingLas Vegas, NVBackground of Gene Therapy•Adenovirus•Advantages•Disadvantages•Biosafetyhttp://files.myweb.med.ucalgary.ca/files/91/files/unprotected/Bio‐Safety_of_Viral_Vectors_for_Gene_Therapy.pdfBackground of Gene Therapy•Adeno‐Associated Virus•Advantages•Disadvantages•Biosafetyhttp://files.myweb.med.ucalgary.ca/files/91/files/unprotected/Bio‐Safety_of_Viral_Vectors_for_Gene_Therapy.pdfIssues with Gene Therapy•Technical limitations•Identification of gene•Manufacturing delivery system•Introducing gene into recipient•Appropriate gene expression insubjectRoth RI & Fleischer NM. JAPhA. 2002;42:692‐8

2007 ASHP Midyear Clinical MeetingLas Vegas, NVIssues with Gene Therapy•Patient safety•Acute toxic responses•Fatalities•Potential interactions betweenintroduced gene and therecipient’s genes•Latent effects of therapyRoth RI & Fleischer NM. JAPhA. 2002;42:692‐8Issues with Gene Therapy•Ethical•How to select recipients•Essential genetic repair versusnon‐ essential geneticimprovement•Consequences of intended orinadvertent germ‐linemodificationsRoth RI & Fleischer NM. JAPhA. 2002;42:692‐8Issues with Gene Therapy•Regulatory•Longer follow up of patientsnecessary•Who pays?Roth RI & Fleischer NM. JAPhA. 2002;42:692‐8

2007 ASHP Midyear Clinical MeetingLas Vegas, NVIssues with Gene Therapy•Pharmacy•Traditional role•Treatment coordinator /communicatorRoth RI & Fleischer NM. JAPhA. 2002;42:692‐8Pharmacy and Gene Therapy•Risk assessment•Majority of gene productsunder investigation will beclassified as a biosafetylevel 2DeCederfelt, et al. AJHP 1997;54:1604‐10Pharmacy and Gene Therapy•Compounding worksheet•Calculations performed prior tomixing•Compounding area designatedas biohazardousDeCederfelt, et al. AJHP 1997;54:1604‐10

2007 ASHP Midyear Clinical MeetingLas Vegas, NVPharmacy and Gene Therapy•Equipment needed• BSC class II, type B• ‐80°C freezer• 10% bleach solution• Autoclave• Ice / ice buckets• Sterile admixture supplies• Surgical gowns• Masks• Hair covers• Vortex‐type mixerDeCederfelt, et al. AJHP 1997;54:1604‐10Pharmacy and Gene Therapy•Transport gene product on ice intomixing area•Swab all surfaces of BSC with 10%bleach solution followed by 70%alcohol•Line empty sharps container with aleakproof biohazard bagDeCederfelt, et al. AJHP 1997;54:1604‐10Pharmacy and Gene Therapy•Compounded product is usuallyvery time sensitive•Decontamination of BSC should berepeated•Everything utilized in the processshould be autoclaved for at least 15minutesDeCederfelt, et al. AJHP 1997;54:1604‐10

2007 ASHP Midyear Clinical MeetingLas Vegas, NVPharmacy and Gene Therapy•Preparation methods•All gene therapy preparationsrequire double check•Supply disposal•Delivery to treatment areaUniv . Of Kentucky Pharmacy Policy PH‐10‐04Pharmacy and Gene Therapy•Decontaminate BSC withcurrent, Infection Controlapproved, anti‐viraldisinfectant prior to & aftereach use•Do not use BSC for 1 hour aftercleaningUniv . Of Kentucky Pharmacy Policy PH‐10‐04Pharmacy and Gene Therapy ‐ UK•Biological safety officer•Task force / working party•Genetic modification safetycommittee•Standard operating proceduresSimpson J. Pharmaceutical Journal 2003;271:127‐30

2007 ASHP Midyear Clinical MeetingLas Vegas, NVPharmacy and Gene Therapy ‐ UK•Handling•Storage•Cleaning•Dispensing•Labelling•Operators•Transport•WasteDisposal•SpillageSimpson J. Pharmaceutical Journal 2003;271:127‐30Pharmacy and Gene Therapy ‐ UK•Questionnaire regarding UKpharmacist knowledge•Majority expressed concernsover safety of gene therapy•Majority wanted pharmacistsinvolved in processYousif S, Gorecki DC. Pharmaceutical Journal 2004;272:159‐162Pharmacy and Gene Therapy ‐ UK•Genetically ModifiedOrganisms (GMO) Regulations•‘Contained Use’•‘Deliberate Release’•Class 1 to Class 4Beaney AM. Quality Assurance of Aseptic Preparation Services.2006

2007 ASHP Midyear Clinical MeetingLas Vegas, NVPharmacy and Gene Therapy ‐ UK•Regulatory requirements•Regulation 17•Regulation 18 and Schedule 8Beaney AM. Quality Assurance of Aseptic Preparation Services. 2006Health & Safety Executive website:http://213.212.77.20/biosafety/gmo/index.htmPharmacy and Gene Therapy ‐ UK•Facilities•Not normally appropriate to handlethese products in cytotoxic facilities•Documentation•Labeling•TrainingBeaney AM. Quality Assurance of Aseptic Preparation Services. 2006Pharmacy and Gene Therapy ‐ UK•Aseptic processing•Cleaning•Storage•Transport•Waste disposal•SpillageBeaney AM. Quality Assurance of Aseptic Preparation Services. 2006

2007 ASHP Midyear Clinical MeetingLas Vegas, NVConclusions•Use of gene therapy products willcontinue to increase over the nextdecade•Laboratory practice guidelines arenot sufficient to meet the needs ofpharmacies working with theseagentsConclusions•Pharmacy guidelines forpreparation of gene therapyproducts are necessary•Vector classification schema•Appropriate training of pharmacistsis criticalQuestions?

2007 ASHP Midyear Clinical MeetingLas Vegas, NVReferences•Smith TJ. Gene therapy: Opportunitiesfor pharmacy in the 21 st century. Am JPharm Education. 1996;60:213‐15•DeCederfelt HJ, et al. Handling ofgene‐transfer products by the NationalInstitutes of Health Clinical Centerpharmacy department. Am J Health‐Syst Pharm. 1997;54:1604‐10References•Center for Biologics and Evaluationand Research. Guidance for HumanSomatic Cell Therapy and GeneTherapy. Bethesda, MD. 1998http://www.fda.gov/cber/gdlns/somgene.pdf•Roth RI and Fleischer NM. Genetherapy: Applications to pharmacypractice. JAPhA. 2002;42(5):692‐98References•Simpson J and Stoner NS. Implicationsof gene therapy for hospitalpharmacists. Pharmaceutical Journal.2003;271:127‐130•Yousif S and Górecki DC. Arepharmacists ready for gene therapy?Pharmaceutical Journal. 2004;272:159‐62

2007 ASHP Midyear Clinical MeetingLas Vegas, NVReferences•University of KentuckyHospital Department ofPharmacy Policy on GeneTherapy 10/26/2005.http://www.hosp.uky.edu/pharmacy/departpolicy/PH10‐04.pdfReferences•Simpson J. Progress in gene therapy –are hospital pharmacies the nextbarrier? Hospital Pharmacist.2006;13:266•Beaney AM. Quality assurance ofaseptic preparation services. 4 thedition. Appendix 6: Gene therapy.London: The Pharmaceutical Press;2006