Draft for a New Annex 19 to the EU GMP Guide Published

GMP News No. 438

GMP News
21 July 2004

Draft for a New Annex 19
to the EU GMP Guide Published

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 This applies also to analytical reference materials used in tests which have been superseded."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.  

Would you like to comment on the new Annex 19? We are currently preparing a comment, which we will send to the European Commission. If you see any problems that might arise in the implementation of this annex, please send us an e-mail to info (at) gmp-compliance (dot) org until 30 September 2004.
Dr Gerhard Becker

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