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02/03/2017
 

What are the regulatory Definitions for "Ambient", "Room Temperature" and "Cold Chain"?

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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:

  • Deep-freeze: below -15C;
  • Refrigerator: 2C to 8C;
  • Cold or cool: 8C to 15C;
  • Room temperature: 15C to 25C.

There are also some definitions in the WHO Guidance:

  • Store frozen: transported within a cold chain and stored at -20C (4F).
  • Store at 2-8C (36-46F): for heat sensitive products that must not be frozen.
  • Cool: Store between 8-15C (45-59F).
  • Room temperature: Store at 15-25C (59-77F).
  • Ambient temperature: Store at the surrounding temperature. This term is not widely used due to significant variation in ambient temperatures. It means "room temperature" or normal storage conditions, which means storage in a dry, clean, well ventilated area at room temperatures between 15 to 25C (59-77F) or up to 30C, depending on climatic conditions.

And the U.S. Pharmacopeia (USP) has some references.USP <659> "Packaging and Storage Requirements" gives various examples for different storage conditions, for example:

  • Cold: Any temperature not exceeding 8C (46 F).
  • Cool: Any temperature between 8 and 15 (46 and 59 F)
  • Room temperature: The temperature prevailing in a work area.
  • Controlled room temperature: The temperature maintained thermostatically that encompasses at the usual and customary working environment of 20-25 (68-77 F). Excursions between 15 and 30 (59 and 86 F) that are experienced in pharmacies, hospitals, and warehouses, and during shipping are allowed. Provided the mean kinetic temperature does not exceed 25, transient spikes up to 40 are permitted as long as they do not exceed 24 h. Spikes above 40 may be permitted only if the manufacturer so instructs.
  • Warm: Any temperature between 30 and 40C (86 and 104 F).
  • Excessive heat: Any temperature above 40 (104 F).

The Japanese Pharmacopeia (JP) describes temperature for tests or storage as follows:

  • Cold: 1C - 15C
  • Standard temperature: 20C
  • Ordinary temperature: 15C - 25C
  • Room temperature: 1C - 30C
  • Lukewarm: 30C - 40C

This is not overall harmonised, as this simple summary shows:

Pharm. Eur. WHO USP JP
Frozen/ deep-freeze >-15C -20C - -
Refrigerator 2C 8C - - -
Cold 8C 15C 2C 8C <8C 1C 15C
Cool 8C 15C 8C 15C 8C 15C -
Room temperature 15C 25C 15C 25C temperature prevailing in a work area 1C 30C
Controlled room temperature - - 20C 25C
excursions between 15C and 30C are allowed
-
Ambient temperature - 15C 25C or 30C 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:

Testing conditions where the product is stable

Required labelling statement

Additional labelling statement, where relevant

25C/60%RH (long term)

40C/75%RH (accelerated)

or

30C/65%RH (long term)

40C/75%RH (accelerated)

None

(The following PL statement is required:

This medicinal product does not require any special storage conditions.)

Do not refrigerate or freeze

25C/60%RH (long term)

30C/60 or 65%RH (intermediate) or

30C/65%RH (long term)
Do not store above 30C or Store below 30C

Do not refrigerate or freeze

25C/60%RH (long term)

Do not store above 25C or Store below 25C

Do not refrigerate or freeze

5C 3C (long term)

Store in a refrigerator

or

store and transport refrigerated

Do not freeze

Below zero

Store in a freezer

or

store and transport frozen

 

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., 15C -25C or +2C to +8C). Particular attention should be given to avoiding freezing of liquids and semi-solids.


 

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