10/11 November 2021
In 2013, the revised EU Good Distribution Practice (GDP) Guideline was published in the Official Journal. The extensive revision of the Guideline from 1994 has raised a lot of questions with regard to the implementation. Some of the key concerns of stakeholders deal with temperature excursions during transport.
Some expectations from the authority are particularly challenging. The associations of the medicinal products manufacturers BAH, BPI, vfa and Pro Generika and the association of wholesalers PHAGRO have now published a position paper and forwarded it to the regulatory authorities. According to a report from the German Federal Association of Pharmaceutical Manufacturers (BAH) very restrictive regulations - to some extent - concerning temperature-controlled transport have been set by the authorities; particularly on hot days in summer where daytime temperatures exceed 25 degrees.
Beside the presentation of the associations' perception of the issue, the paper should also provide arguments when assessing short-term temperature deviations during the transport of medicinal products. The paper states that results from stability studies show that temperature fluctuations in climate zone I/II (relevant zones in the European Union) do not necessarily lead to quality problems. According to the paper, it can be concluded that it should be allowed to accept temporary temperature excursions (except for refrigerated goods).
In this context, the determination of the mean kinetic temperature (MKT) might be used to support this. The MKT is defined as the kinetic average of all temperatures to which the medicinal product has been exposed during storage and transport within the supply chain.
According to the arguments of the associations, the storage temperature indicated should always be considered in connection with the full shelf-life. If a medicinal product is exposed to a temperature of 25°C for 36 months, this results in the same load as 33 months at 21°C and 3 months at 40°C.
Within the framework of the position paper, it is also referred to the Austrian Codex for the transport of medicinal products in Austria last revised in 2014 (available in German language only). This document has been released by the associations PHAGO and PHARMIG. The document states (translated text - unofficial translation):
"Regarding the storage of medicinal products, a distinction is generally made between room-temperature products and refrigerated ones. The storage rooms are accordingly qualified for these temperature ranges. GDP requires that products are transported in an "acceptable range". This formulation considers that for the distribution of medicinal products so many process steps (e.g. loading, unloading, etc.) are executed. Given this fact- with regard to the use of economically reasonable qualified standard transport systems - it is impossible to keep the storage temperature defined at all times without interruption during the whole transport processes.
It is thus justified to define specific transport acceptance criteria on a risk-based approach for short-term interruptions (up to 12 hours): "(…) By means of a risk analysis, it should be noted that the influence of these short-term deviations (up to 12 hours) due to the transport on the stability and the shelf-life is negligible with regard to maximum allowable degradation of the API over the entire products life. (…)".
To what extent the GMP/GDP monitoring authorities will follow this interpretation will have to be observed. The British Medicines Authority MHRA had published a Question & Answer document on the use of the MKT values - please see our News on MHRA principles with regard to the possibilites and the limits of the use of MKT.