On 15 July, the EU Commission published the draft for a new Annex to the
EU GMP Guide for commenting by the industry. The document is titled "Reference Samples and Retention Samples"
and defines the handling of reference and retention samples of starting
materials, packaging materials, and finished drug products.
The need for a common regulation within
the EU might have resulted from the fact that there have been problems
with follow-up stability of medicinal products in different EU Member
States. Moreover, the difficulties connected with storage and transport
become increasingly the focus of GMP attention of the authorities.
This Annex aims at a Europe-wide harmonisation, in the first place, of
course, with regard to the handling of reference and retention samples,
but also concerning a consistent use of the technical terms. The
introductory note already says "The
Annex provides definitions of the terms 'reference sample' and 'retention
sample', which are often incorrectly considered as synonyms." The
linguistic distinction is then clarified through the following
definitions:
Reference sample: a sample of a batch of starting material,
packaging material or finished product which is stored for the purpose of
being analysed…
Retention sample: a sample of a fully packaged unit from a batch of
finished product. It is stored for identification purposes. …
The following chapters of this document describe in detail the
handling of reference and retention samples with regard to:
- duration of storage
- sample size
- storage conditions
- written agreements on the responsibility for the samples
- written agreements with manufacturers from third countries with or
without MRA
- responsibility for the samples in case of parallel import/parallel
distribution
- responsibility for the samples after the closedown of a production
site or the withdrawal of the manufacturing authorisation
One detail in this document deserves increased attention. Section 4.4
says:
"It should be ensured that all necessary analytical materials and
equipment are still available, or are readily obtainable, in order to
carry out all tests given in the specification until one year after expiry
of the last batch manufactured. This applies also to analytical reference
materials used in tests which have been superseded."
This means that not only reference
samples of manufactured batches and starting
materials have to be stored for the required period, but also everything
else that is necessary for a future analysis, like reference standards and
analytical equipment. Thus, those responsible have to make sure that -
e.g. when the dosage form is changed - parts of the equipment that are not
used in routine analysis any more are not discarded too early. The same
goes for reference standards.
You can download the draft for Annex 19 by clicking here.
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