Frequently Asked Queries

Does pharmacy require GMP to dispense an AAV gene therapy product?

Gene therapy manufacturing sites / facilities require Good Manufacturing Practice (GMP) licensing, certification or clearance. A pharmacy dispensing a gene therapy product that has already been manufactured under a GMP license or certificate or clearance would generally not be required to have its own GMP license, certification or clearance (unless the pharmacy is also the manufacturer of the product or no legislated exemption from the requirement for GMP applies).

However, pharmacies are required to adhere to GMP principles and guidelines applicable to their role, as described in the PIC/S Guide to Good Practices for the Preparation (GPP) of Medicinal Products in Healthcare Establishments, and in the PIC/S GMP Guide as adopted in their jurisdiction. For example, in Australia, TGA guidance on Compounded Medicines and GMP and GMP information for manufacturers of compounded medicines and DAAs includes guidance on GMP and dispensing.  

The TGA has produced a step-by-step guide on Australian manufacturing licences and overseas GMP certification and a guide on Determining whether licensing or certification is required. Local State requirements can also apply, for example in NSW the NSW Health Policy Directive on Preparation of pharmaceutical and advanced therapeutic products applies. Also there may be local Pharmacy Board requirements that must be complied with. 

It is important to check your jurisdiction’s specific GMP requirements relevant to pharmacy.

Handling rAAV

In the case of products that are are not yet approved, handling and disposal of gene therapy products for use in clinical trials or under special access schemes should always be in accordance with the sponsor’s Protocol. Where there is a sponsor’s Pharmacy Manual, it should also be followed. The Investigator Brochure gives valuable information on the therapeutic product.

Handling marketing approved gene therapy products should always be in accordance with the sponsor’s Product Information or Package Insert.

Material Safety Data Sheets (MSDS) or Safety Data Sheets (SDS) give information about biosafety risks and methods of decontamination and disposal relevant to gene therapy vectors. 

Examples of Product Information sheets or Package Inserts for AAV gene therapy products approved in a number of jurisdictions include those for Zolgensma (onasemnogene abeparvovec), Hemgenix (etranacogene dezaparvovec-drlb), and Luxturna (voretigene neparvovec).

What are the approval requirements in individual EU countries? 

Authorisation of medicines
In the European Union (EU), there are two main routes for authorising medicines: a centralised route and a national route.  Under the centralised authorisation procedure, pharmaceutical companies submit a single marketing-authorisation application to EMA. This allows the marketing-authorisation holder to market the medicine and make it available to patients and healthcare professionals throughout the EU on the basis of a single marketing authorisation.

However, under EU law EMA has no authority to actually permit marketing in the different EU countries. The European Commission is the authorising body for all centrally authorised product, who takes a legally binding decision based on EMA’s recommendation. This decision is issued within 67 days of receipt of EMA’s recommendation. 

Once granted by the European Commission, the centralised marketing authorisation is valid in all EU Member States as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway.

The centralised procedure is compulsory for (among other things) advanced-therapy medicines (ATMPs),  such as gene-therapy, somatic cell-therapy or tissue-engineered medicines.

Under Regulation (EC) No 726/2004, the centralised procedure for evaluating applications for marketing authorisations
for medicinal products for human use containing or consisting
of genetically modified organisms (GMOs) includes consultation with relevant GMO competent authorities set up under Directive 2001/18/EC

Clinical trials
Medicine developers who wish to conduct clinical trials in the EU need to submit applications to the national competent authorities of the countries where they want to conduct the trials.

EMA does not have a role in the authorisation of clinical trials in the EU; this is the responsibility of the national competent authorities.

However, EMA, in cooperation with the EU Member States, plays a key role in ensuring that medicine developers follow EU and international standards.

For clinical trials national competent authorities need to be consulted. If the trial involves GMOs the national EPA & GMO competent authorities also need to be consulted.