Carmina Más Arcas
Specialist in Hospital
Doctor of Pharmacy
Chief of the Pharmacy Service
Valenciano de Oncología
In the first article of this series we looked at the different areas of disease management in which gene therapy is showing promise. In this article we look at the role of the hospital pharmacy in gene therapy research.
The main problems associated with gene therapy for hospital pharmacy departments are related to:
- The nature of the product.
- The vehicle.
Vectors are considered the most appropriate vehicles to get genetic material to the cell or organ involved. The nature and properties of vectors may vary. The characteristics of the ideal vector are set out in Table 1,(1) and the differences between viral and nonviral vectors are shown in Table 2.
Although all vectors share the capacity to insert genetic material so that it may be expressed later at a suitable and effective level, the choice of vector will depend on the specific objectives to be achieved and the strategy to be used to attain them. This may affect the success of a specific clinical trial, bearing in mind that there is no gene therapy product on the market as yet and we are not absolutely sure what the optimum vector will be.
Pharmacokinetics and pharmacodynamics
Gene therapy is directed neither by the principles of absorption, distribution, metabolism and excretion, nor by parameters such as half-life.
It is expressed in plaque-forming units per volume – pfu/ml – a unit not habitually used by pharmacy departments and on medical prescriptions.
The legal framework
Gene therapy is classed as a biotechnology as it alters the genome of a cell in order to obtain some benefit for medicine, arable and livestock farming, industry and so on. However, it is important to recognise that biotechnology comprises other applications that are not gene therapy. Action within the legal framework is complicated as there is legislation on biotechnology that is not always applicable to gene therapy, and furthermore, gene therapy still does not have a single substance classification, since it may be considered to be a medicine as well as a biological product, reagent, etc.
EC regulations of relevance to gene therapy research are as follows:
- Regulations 2309/93 EEC: establishment of the European Drug Agency.
- Directives 90/219/EEC and 90/220/EEC transposed in Spain in Act 15/94.
- Council of Europe Bioethics Convention or Human Rights Convention 1997: primacy of the human being over society or science.
- Council of Europe Resolution: ResAP (2001)(2): considers the hazards of gene therapy and offers recommendations on good practice in conjunction with the set of professionals involved, with compulsory notification at stages of research, production and use of pharmaceutical products obtained by genetic engineering.
- Directive 2001/20/EC: harmonisation of legal provisions on the application of good clinical practice in clinical trials.
Gene therapy products should be handled in class II vertical laminar flow biological safety cabinets. It is preferable for these cabinets to be contained in rooms with pressure cascade control, to prevent any possibility of contamination between rooms, so that the product, the worker and the environment are all protected.(2) In addition, a standard procedure for working, cleaning maintenance, and so on, should be followed.
In gene therapy preparation, the following factors need to be taken into account:
- The type of cleaning products, such as 10% bleach and 70% alcohol.
- A sterile preparation technique.
- Use of automatic, not manual, pipettes.
- Samples should be handled using sealed transfer systems, such as that shown in Figure 2.
- If dispensing by syringe, fit with an airtight cap.
- Use of sterile double gown, mask, hat and shoes.
- Dispensing and handling inside the hospital should take place in airtight transparent containers, suitably labelled and identified.
- Administer with the stability time indicated in the protocol.
- Never refreeze.
- All material used should be disposed of in the airtight container, which should later be included in the biohazardous waste destruction system.
- Monitor preparation personnel exposure time.
Gene therapy products should be stored in freezers with graphic temperature controls and a temperature range of –70 to –80°C for stability of products containing gene p53.
The movement of samples should be recorded and monitored, detailing their receipt in carbon dioxide snow, their storage should be as mentioned above, and an administrative report made on their use, patient, dose, date, etc.
Coordination of the services involved
The development of gene therapy at our hospital involves the coordination of the departments listed in Table 3.
Gene therapy is a great challenge for pharmacy departments, which have to ensure the safety of these products, as well as other drugs, when they are manipulated before administration to a particular patient. Hospital pharmacists may also be involved in:
- Reviewing protocols and putting forward suggestions for their design with regard to the safety of the professionals involved in the process.
- Logistic support decisions.
- Compliance with standards of good clinical practice in the receipt, inspection, recording, storage, safety (freezer under lock and key and graphic temperature control), preparation, labelling, dispensing and follow-up of the samples for the trial.
The tasks and responsibilities of every person involved in the multidisciplinary process have to be laid down before starting the clinical trial at a centre. Only duly trained and authorised persons familiar with the nature and hazards of gene therapy may have access to the product.
Every effort should be made to protect the patient, preparer, administrator, product and environment at all times.
- Fominaya J. Vectores de transferencia génica. In: 3er Curso de biotecnología para farmacéuticos de hospital. Madrid: CIEMAT,Ministerio de Ciencia y Tecnología,CNB; 2002.
- Más Arcas C,Diaz de Brito L. Condiciones generales y comprobaciones de puesta en marcha. Manual misterium. Instituto Valenciano de Oncología (IVO). Valencia: Grifols Engineering; 2002.