(GMP guidelines, §4.18: Before any packaging operation begins, there should be recorded checks that the
equipment and work station are clear of previous products, documents or materials not required for the
planned packaging operations, and that equipment is clean and suitable for use).
The packaging should be performed in such a way as to limit the risk of possible mix-up between the test
and reference product. To this effect:
the test and the reference product should be packaged during separate operations and should not
be available simultaneously in the packaging area;
during these operations not only should the test and reference products be kept separate, but also
all material used for the packaging of each product (containers, labels) and the batch record
documents. Material used for different products should not be available in the packaging area
simultaneously;
reconciliation should be performed for the quantities of IMP units, containers and labels introduced
in the working area, used during the packaging and remaining after these operations, before the
area is cleared and before the packaged IMPs are released;
the working area should be cleared of all IMP, packaging material and documents between the
packaging operations of the test and of the reference product (line clearance). If packaging is
performed for several trials successively line clearance should be ensured between each product
and each trial;
once the packaging has been completed for all products to be packaged for a given trial and the
products have been released, the packaged test and reference products can be taken
simultaneously into the packaging area for further operations (e.g. sorting the containers per
subject number);
critical steps should be controlled in-process by appropriately qualified and trained staff.
In the case of liquid formulations the volume packaged should be measured with appropriate precision
and accuracy. If a reconstitution of the product is needed the instructions provided with the product
should be followed. If a specified volume of fluid is to be used for the reconstitution this volume should
be measured with appropriate precision and accuracy.
At least the following elements should be checked in-process by the operator and independently by a
second person:
line clearance before and after packaging;
information on the labels, labelling of the containers, compliance with the randomisation code;
identity of the product introduced in the working area (name, batch number, formulation),
consistency with the identity mentioned on the labels, compliance with the protocol, consistency
between the physical appearance of the product and the description of the product in the batch
release certificate provided by the sponsor;
for each container, number of IMP units introduced into the container, compliance with the protocol
requirements;
in the case of a liquid formulation: adequate reconstitution of the product if needed, volume
dispensed/packaged into each container;
reconciliation of IMP units, containers, labels.
A standard operating procedure (SOP) should describe the packaging operations step by step, including
the controls to be performed at each step and the responsibilities of each person involved.
These operations should only be performed by authorised personnel, qualified by training and education.
Access to IMPs should be limited to authorised personnel, both before and after packaging. Storage
conditions should conform to the provisions of the protocol (temperature, humidity, protection from light
if and as appropriate).
