General questions
For all of your general questions, questions relating to the start-up and follow-up of a study, audit/inspections ... you can contact the following mail address or phone number:
Before a study can be started in the hospital pharmacy, an pharmacy application form needs to be submitted. This application can be entered via the UZ Leuven website, under Clinical trials hospital pharmacy - Submit new clinical trial.
For a GGO study there is a specific application for GGO studies. The pharmacy will do a feasibility check for the trial and as soon as the application form has been approved by the hospital pharmacy, an initial site visit can take place.
All deliveries of investigational medicinal product (IMP)/equipment for the clinical study can be sent to the following address:
- UZ Leuven Apotheek magazijn
- Refer to protocol number orf S-number
- ATTN Stefanie Goris (clinical studies)
- Herestraat 49
- 3000 Leuven
The warehouse is open every working day between 8 am and 4 pm.
IMP deliveries to the hospital pharmacy are not allowed before the site initiation visit (SIV) took place in the pharmacy. These deliveries will not be accepted and will not be place in quarantine. The courier will have to take the shipments back.
The hospital pharmacy is only accessible for employees working in the hospital pharmacy. Access is badge-controlled.
If the sponsor were to need the licence number or master number, this can be obtained by sending a request via email to apo_studies@uzleuven.be.
No, only activities in the context of a clinical study that do not require a GMP licence can be executed by the hospital pharmacy (see circular 596).
If pharmacists or pharmacy assistants need to be given access to the I(X)RS system, contact details for requesting this access will only be given during the initiation visit of the study.
The hospital pharmacy provides continuity for the delivery of study medication during the weekend, public holidays and outside opening hours (between 5 pm – 8:30 am) of the clinical studies hospital pharmacy for ongoing patients. During these times, no new patients can be entered. During on-call times, the clinical studies team is not available. The on-call pharmacist will deliver the study medication based on the procedures set by the clinical studies team.
The UZ Leuven pharmacy has internal accountability logs that are used for all studies. To create uniformity and transparence for all studies within the clinical studies pharmacy, no modifications are made to these accountability logs. The patient-specific logs are completed by the study coordinator.
The accountability log includes the following components:
- Working name of the study: this name is set in consultation with study coordinator and is for internal use
- Protocol number, name PI and site number
- Description of the IMP (name, strength and pharmaceutical form), batch nummer and expiry date
- Date of delivery and initials of the receiver
- In the case of kit numbers: Medication number
- Without kit numbers: Amount received / Amount delivered / Balance
- Date of delivery + initials of the delivery person
- Subject number
- Amount that needs to be destroyed/sent back
- Date of return and disposal + initials executor
- Verification by the CRA (initials and date)
- Version history and page numbering
The pharmacy itself can't provide labels. If labels are required, these should be provided and supplied by the sponsor. When a product is considered standard of care (SOC), the product will not be labelled as it goes through the commercial, regular route. The clinical studies pharmacy does not intervene in SOC medication.
Standard of care (SOC) medication is medication generally accepted by the guidelines for the treatment of a certain disease or condition. Supply of this type of medication goes through the regular hospital pharmacy. As the clinical trials pharmacy does not intervene in this supply it is not possible to provide delivery documentation, accountability and labeling for these products. Regular legislation will be observed.
Given the fact that the UZ Leuven hospital pharmacy does not have a GMP licence, the pharmacy can only reconstitute medication for administration to patients in its hospital. The hospital pharmacy is not allowed to prepare placebos/IMP capsules/tablets, … or execute preparations. If this is a requirement part of the research, an external company needs to be contacted.
Given the fact that the UZ Leuven hospital pharmacy does not have a GMP licence, the UZ Leuven pharmacy cannot interfere in the reconstitution for multicentre studies. The pharmacy can only perform reconstitution for its own patients. Neither does the pharmacy have a distribution licence to complete the distribution to other centres. More information on the activities that are allowed without a GMP licence are outlined in the 596 circular.
Site initiation visits (SIV) are mandatory for all studies that require storage of study medication in the pharmacy. This applies to both commercial and academic studies. For transit studies the clinical studies pharmacy will perform a limited number of assignments that are not study-specific. As a result, a site initiation visit (SIV) is not required for a transit study in the pharmacy. If the sponsor requires a site initiation visit in the pharmacy for a transit study, this can be arranged in consulation with the pharmacy. The SIV will be limited to the information required for the activities of the department.
For transit studies the clinical studies pharmacy only performs a limited amount of non study-specific tasks. Other activities are delegated to the study coordinator. These limited tasks include receiving study medication whereby the medication is temporarily stored in the right storage conditions until study staff comes to collect the medication. For transit studies, the pharmacy is not responsible for confirming and registering the deliveries, follow-up of the temperature excursions during transport/storage, keeping track of accountability and executing destructions.
An appointment for a monitoring visit, a close-out visit, site initiation visit or GMO preparation can be booked via the UZ Leuven website under Clinical Studies hospital pharmacy - Make an appointment. The online booking system will allow you to select the type of appointment and time for your appointment.
Visits with a view to an audit cannot be booked online. For this you need to contact the clinical studies department.
If there are no slots available in the required framework for first patient visits, you can contact apo_studies@uzleuven.be.
Immediately contact the clinical studies pharmacy when an audit is announced. Given the fact that UZ Leuven is a large centre with a large number of ongoing studies, timely notification of an audit is necessary.
Pharmacy binders and quickboxes with prescriptions (if any) will be kept at least 25 years after the end of the clinical study. The first couple of years these are stored in the hospital pharmacy warehouse. When storage capacity is exceeded, the oldest files are transferred to the external archiving firm Oasis in Turnhout. Any other documentation unrelated to the pharmacy will be kept separately by the site. The pharmacy binder and the investigator file are not archived together.
Delivery and storage/return
Study medication is delivered to the pharmacy warehouse. Non-refrigerated medication and/or refrigerated medication is placed on a transport trolley after receipt in the warehouse and taken to the pharmacy via internal transport. Refrigerated medication that is not delivered in a cool box is kept in a refrigerator in the warehouse until transport to the pharmacy. Deliveries of dry-shippers with study medication that has to be stored at temperatures of <-80°C, are directly delivered to the pharmacy.
A delivery can only be confirmed when an analysis certificate has been provided as this is a requirement according to GMP annex 13.
For deliveries outside the warehouse's office hours and during the weekend, the courier should report to the pharmacy counter or to the reception desk in the reception hall if the counter is closed. In the latter case, the pharmacist on call is contacted. The on-call pharmacist can receive the study medication, or request to have the study medication delivered at an agreed time.
Medication for a transit study is delivered to the warehouse and delivered to the clinical studies pharmacy via internal transport. If applicable, a member of the clinical studies team performs the initial check of the temperature monitor without turning it off. The study medication is temporarily stored under the correct termperature requirements. A member of the clinical studies team registers the transit delivery in an internal electronic system alerting the trial desk staff that the medication has been delivered at the pharmacy and that it can be picked up with the appropriate document.
All medication supplied for clinical studies is stored separately from commercial medication. The clinical studies pharmacy has storage areas that are completely separate from the regular pharmacy. In case the medication has be be quarantined because of temperature excursions, expiry dates ... this medication will be stored in a quarantine area, separate from the rest of the study medication stock.
No, the pharmacy has its own internal system for temperature monitoring during storage. This is sufficient for the GCP requirements. This also means that the pharmacy will not take into account the use of externally supplied continuous temperature loggers that are permanently present during storage (e.g. Mini-Tag®), or the use of externally supplied tablets or other devices for the follow-up of temperature during storage.
Used and unused study medication can be destroyed locally at the request of the sponsor. The clinical studies pharmacist has a written-out procedure of the destruction process. This procedure is available on request.
As described in our destruction procedure, the pharmacy does not provide a destruction certificate. The company Indaver, which will destroy the medication by burning, will not provide a destruction certificate either. In certain cases, destruction of medication on the ward is also possible (e.g. in case of transit studies), as there is a uniform destruction policy throughout the hospital.
At the request of the sponsor, used and unused study medication can be returned to the sponsor or to a depot. In this case, the sponsor's instructions are followed but the CRA/sponsor is responsible for the administrative steps (e.g. labels, transport, etc.).
Study medication that is returned, whether it is used or unused, can only be returned to the pharmacy for destruction/return on the day of the planned monitoring visit by the CRA or the day before the MOV by the study coordinator in case of unblinded CRA. The pharmacy cannot store study medication that was returned by a patient.
All deliveries for clinical studies have to be done at the hospital pharmacy warehouse. It is not possible for the courier to take the shipping box and the temptale back immediately. The temptale is read by clinical studies team and data is delivered to the sponsor. The shipping box and if appllicable the temptale can be collected the following working day from the hospital pharmacy warehouse, in case the return documents were provided with the shipping box.
Temperature
Study medication can be stored under the following temperature conditions:
- Room temperature: 15°C – 25°C
- Refrigerator/cold store: 2°C- 8°C
- Deep freezer: -15°C tot -25°C
- Ultra freezer: -70°C tot -90°C
Every refrigerator, deep freezer, ultra freezer and room temperature area where study medication is stored, is equipped with an AeroScout Sensor Tag. This is used as the primary reigstration system. Data are registered every 10 minutes.
Every working day, the temperature is checked by a member of the clinical studies team based on the data of the AeroScout Sensor Tags.
The AeroScout Sensor Tags are used as primary system. If there is a problem with an AeroScout Sensor Tag the building management system (GBS) can be consulted. This is used as a back-up system.
If a device (refrigerator, deep freezer ...) breaks down, the technical department will have replacement devices available. Study medication is put into the replacement device as quickly as possible.
The Aeroscout Sensor Tag immediately generates an alarm when the set limit values have been exceeded or have gone below the set limit values.
If a alarm is generated outside office hours, during the weekend or public holidays, the on-call pharmacist will be contacted by phone.
The device is checked visually by whoever received the notification. If the problem can be solved immediately (e.g. the door of the device was open) or if there is no immediate visible cause for the notification (the device is working normally), no further follow-up is required.
For each temperature excursion, study medication from the affected device or room is quarantined, and placed under the required temperature conditions. The sponsor and/or CRA of the study/studies concerned will be notified in writing. A quarantine document will always be filled out.
As soon as the sponsor and/or CRA releases the study medication again, the study medication is returned to the study storage and is available for use again.
AeroScout Sensor Tags (and the building management probes) are calibrated every year by the technical department.
Calibration certificates can only be requested after delivery of the study medication. It's only after delivery that we know in which device the study medication will be stored.
The technical department is responsible for the maintenance of all devices used for storing study medication. Maintenance is scheduled every six months.
Maintenance certificates are available on request via apo_studies@uzleuven.be.
All devices are connected to the emergency power. In case of a power cut, the emergency generator is activated. The technical department is automatically warned and will attempt to solve the problem as soon as possible.
Preparations
Study medication is prepared in biohazard cabinets type II A2. Quality control for the biosafety cabinets is done every 6 months. After every accidental maintenance which can affect the normal functioning of the biosafety cabinet, a new quality control is performed.
Maintenance certificates of these cabinets are available on request via apo_studies@uzleuven.be.
For preparing medication, UZ Leuven templates are used at all times rather than IMP worksheets provided by the sponsor. The use of a template creates uniformity and reduces the chance of errors.
An IMP transfer document will not be completed by the hospital pharmacy because all details of completion and delivery are visible in our electronic system, the KWS (klinisch werkstation - Clinical work station).
For preparations, the pharmacy will provide labels. This will include the following general information:
- Patient name
- Name of the product + Internal working name + S number + dosage
- Solvent and solvent volume
- Method of administration
- Unique number per preparation
- Preparation date + time of preparation
- Shelf-life after preparation
- Reference 'Exclusively for clinical research’
- Date of birth patient
- QR code for scanning
Because the label is limited in size, extra additions (e.g. patient number) are not possible.
The use of closed transfer devices is only allowed for commercial cytostatic drugs that have stability data readily available. Only when explicitly requested by the sponsor will this be allowed for preparations of other study medication.
The availability of specific equipment for preparation can be requested via apo_studies@uzleuven.be
Pharmacy-owned preparation materials are used during reconstitution of study medication. If the sponsor cannot agree to this due to compatibility problems, the sponsor has to provide the alternative equipment himself.