Paul-Ehrlich-Institut

Sub­mis­sion and Mod­i­fi­ca­tion of the Sta­bil­i­ty Pro­to­col

Since coming into force of the German ordinance on GCP in 2004 amendments concerning stability documentation of biological medicinal products and their extension of shelf-life have been considered as substantial amendments that have to be authorized by the competent national authority. After the publication of the "Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials" on 03.05.2012, the Paul-Ehrlich Institut implements the guideline concerning stability documentation as follows:

Initial clinical trial application submitted after 03.05.2012

  1. The submission of a stability protocol for the investigational product as part of an initial clinical trial application is accepted by the approval of the clinical trial. Further extensions of shelf-life are not considered as substantial according to § 10 Absatz 1 Nr. 4 GCP-V as long as the guideline is followed. An information of shelf-life extension as non-substantial amendment is not required.
  2. If there is no stability protocol in an initial clinical trial application, an extension of shelf-life is considered as a substantial amendment according to § 10 Absatz 1 Nr. 4 GCP-V.

Initial clinical trial application before 03.05.2012

  1. If the stability protocol was enclosed in the initial clinical trial application, the applicant should inform the Paul-Ehrlich-Institut once that further extension of shelf-life will be done according to the stability protocol. Thereafter the extension of shelf-life is considered as non-substantial for the remaining period covered by the stability protocol as long as the guideline is followed.
  2. If the stability protocol was not enclosed in the initial clinical trial application, a subsequent submission of the stability protocol for the investigational product as substantial amendment is possible. Further extensions of shelf-life are considered as non-substantial for the remaining period of the clinical trial as long as the guideline is followed.
  3. If there is no subsequent submission of the stability protocol, extensions of shelf-life are considered as a substantial amendment according to § 10 Absatz 1 Nr. 4 GCP-V.

Further extensions

After lapse of time of the stability protocol all further extensions of shelf-life of the medicinal product are considered as substantial amendment that have to be approved by the Paul-Ehrlich-Institut.

Special rules for allergens

Due to special rules for allergens we ask to consider the following:

The requirements for stability data supplied with the IMPD as stated in the "Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials" (EMA/CHMP/BWP/534898/2008) are applicable to clinical trials with allergens.

Where stability data on the whole shelf life or the required stability data for extrapolation of shelf life according to the above mentioned guideline are not available, a shelf life of maximum 12 month may be granted based upon data from an on-going stability study. For this, the batch with which the clinical trial is being performed (IMP batch) should be produced not earlier than 3 months after the production date of the batch which is being used for the on-going stability study presented in the IMPD. In this on-going stability study all relevant data have to be measured every 3 months. A minimum of 3 months stability data must be demonstrated in the IMPD. Thereby real time stability data as requested by the "Guideline on Allergen Products – Production and Quality Issues" (EMEA/CHMP/BWP/304821/2007) is available at any time point for the shelf life of the IMP batch.

Contact

Questions concerning allergens could be directly addressed to pei@pei.de (reference: stability allergens).

For all other investigational products ct@pei.de could be addressed.

Updated: 21.11.2019