On the outer packaging of pharmaceutical products one often finds labels with storage requirements like, for example, "ambient", "room temperature" and "cold chain". But what do they exactly mean? And do these conditions also apply during transport?
The second question is easy to answer: "The required storage conditions for medicinal products should be maintained during transportation within the defined limits as described by the manufacturers or on the outer packaging." (EU GDP Guidelines). But according to the PIC/S Good Distribution Guide these conditions should also be applied for transportation (see section 9.2.1).
With the first question, it is more difficult. Here, different definitions can be found.
The European Pharmacopoeia (Pharm.Eur.) gives some hints in chapter 1.2 (Other provisions applying to general chapters and monographs) with referring to analytical procedures:
There are also some definitions in the WHO Guidance:
And the U.S. Pharmacopeia (USP) has some references.USP <659> "Packaging and Storage Requirements" gives various examples for different storage conditions, for example:
The Japanese Pharmacopeia (JP) describes temperature for tests or storage as follows:
This is not overall harmonised, as this simple summary shows:
Pharm. Eur. WHO USP JP Frozen/ deep-freeze >-15°C -20°C - - Refrigerator 2°C – 8°C - - - Cold 8°C – 15°C 2°C – 8°C <8°C 1°C – 15°C Cool 8°C – 15°C 8°C – 15°C 8°C – 15°C - Room temperature 15°C – 25°C 15°C – 25°C temperature prevailing in a work area 1°C – 30°C Controlled room temperature - - 20°C – 25°C
excursions between 15°C and 30°C are allowed- Ambient temperature - 15°C – 25°C or 30°C depending on climatic conditions - -
And then there is the EMA GUIDELINE on DECLARATION OF STORAGE CONDITIONS from 2007, requiring that the storage conditions given in the package leaflet (PL) and the labelling of medicinal products should refer to the stability studies made for the finished product:
Required labelling statement Additional labelling statement, where relevant 25°C/60%RH (long term) 40°C/75%RH (accelerated) or 30°C/65%RH (long term) None (The following PL statement is required: Do not refrigerate or freeze 25°C/60%RH (long term) 30°C/60 or 65%RH (intermediate) or Do not refrigerate or freeze 25°C/60%RH (long term) Do not store above 25°C or Store below 25°C Do not refrigerate or freeze 5°C ± 3°C (long term) Store in a refrigerator or Do not freeze Below zero Store in a freezer or store and transport frozen Testing conditions where the product is stable Do not store above 30°C or Store below 30°C
So, as a resume, terms like "ambient", "room temperature" and "cold chain" should be avoided as the only labelling for storage or transport boxes and containers because they are not always clear and might have different meanings in other parts of the world. Storage conditions are always better explicitly specified in terms of a defined temperature range (e.g., 15°C -25°C or +2°C to +8°C). Particular attention should be given to avoiding freezing of liquids and semi-solids.