GDP: Is Temperature Control required for each Transport?

The EU Good Distribution Practice (GDP) Guidelines (2013/C 343/01) revised in 2013 reflect the requirements and expectations of the authorities during the transport and distribution of medicinal products in a very detailed way. Nevertheless, there are still questions and insecurities.

Especially questions on temperature control during transport are recurring. This question is examined in detail in a corresponding questions and answers paper of the German ZLG (Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten/ Central Authority of the German Federal Länder for Health Protection Regarding Medicinal Products and Medical Devices) (in German language).

Here, it is stated that a temperature control is not required for each transport:

"If no constant monitoring of temperature is carried out during the transport of medicinal products a risk assessment must be made of the transportation routes. This includes especially the travel duration including special aspects of the route, the time of year and day, including the weather forecast, the vehicles used and their equipment. The results of this risk assessment have to be part of the transportation planning."

But at the same time this means that monitoring has to be done if no risk assessment was carried out or if the risk assessment led to the result that a temperature control is necessary.

According to the ZLG document a lot of things have to be considered when carrying out the risk assessment:

• The mean kinetic temperature (MKT) cannot be used. The reason is that it does not take into consideration effects "that may lead to irreversible quality defects even when certain temperature limits that are established during stability studies in connection with the marketing authorisation are exceeded only for a short time. And it does not take into consideration the possible formation of fissures in the glass of ampoules and injection bottles at temperatures around the freezing point. Furthermore, calculation of the MKT requires that the temperature profiles of all transports are known that have been carried out previously. But usually this data is not available ...." 
• In order to assess deviations "appropriate procedures" must be established. 
• Storage conditions must generally be respected also during transportation. "Only in cases that according to the packaging or the confirmed written information given by the manufacturer, the pharmaceutical entrepreneur or the marketing authorisation holder. a transport within the aforementioned temperature range will not reduce the quality" this temperature range can be handled more generously. It has been demonstrated for example "in connection with the marketing authorisation of medicinal products on the labelling of which only storage between +2 and +8 °C is indicated that they remain sufficiently stable even if the temperature rises up to +25 °C for a short time."