Reference samples are retained to fulfil two purposes; firstly to provide a sample for analytical testing and secondly to provide a specimen of the fully finished product. They serve as a record of the batch of finished product or starting material and can be assessed in the event of, for example, a dosage form quality complaint, a query relating to compliance with the marketing authorisation, a labelling/packaging query or a pharmacovigilance report.
Samples may therefore fall into two categories:
Reference sample: a sample of a batch of starting material, packaging material or finished product which is stored for the purpose of being analysed should the need arise during the shelf life of the batch concerned. Where stability permits, reference samples from critical intermediate stages (e.g. those requiring analytical testing and release) or intermediates, that are transported outside of the manufacturer’s control, should be kept.
Retention sample: a sample of a fully packaged unit from a batch of finished product. It is stored for identification purposes. For example, presentation, packaging, labelling, patient information leaflet, batch number, expiry date should the need arise during the shelf life of the batch concerned.
For finished products, in many instances the reference and retention samples will be presented identically, i.e. as fully packaged units. In such circumstances, reference and retention samples may be regarded as interchangeable.
It is necessary for the manufacturer, importer or site of batch release, to keep reference and/or retention samples
from each batch of finished product and, for the manufacturer to keep a reference sample from a batch of starting material and/or intermediate product. Each packaging site should keep reference samples of each batch of primary and printed packaging materials.
Records of traceability of samples should be maintained and be available for review by competent authorities.
Duration of Storage
Reference and retention samples from each batch of finished product should be retained for at least one year after the expiry date.
The reference sample should be of sufficient size to permit the carrying out, on, at least, two occasions, of the full analytical controls on the batch in accordance with the Marketing Authorisation File which has been assessed and approved by the relevant Competent Authority / Authorities.
Storage of reference samples of finished products and active substances should be in accordance with the labelling requirements and should be in accordance with the marketing authorisation (e.g. refrigerated storage where relevant). (Note for Guidance on Declaration of Storage Conditions for Medicinal Products and Active Substances)