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 also according to the PIC/S Good Distribution Guide these conditions should be applied also 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: belowminus 15°C;
Refrigerator: 2°C to 8°C;
Cold or cool: 8°C to 15°C;
Room temperature: 15°C to 25°C.
There are also some definitions in the WHO guidance:
Store frozen: transported within a cold chain and stored at -20°C (4°F).
Store at 2°-8°C (36°-46°F): for heat sensitive products that must not be frozen.
Cool: Store between 8°-15°C (45°-59°F).
Room temperature: Store at 15°-25°C (59°-77°F).
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 25°C (59°-77°F) or up to 30°C, 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 8°C (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 40°C (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: 1°C - 15°C
Standard temperature: 20°C
Ordinary temperature: 15°C - 25°C
Room temperature: 1°C - 30°C
Lukewarm: 30°C - 40°C
This is not overall harmonised, as this simple summary shows:
| Pharm. Eur. | WHO | USP | JP | |
| Frozen/ deep-freeze | below -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 | - |
| 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:
| Testing conditions where the product is stable | 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) 40°C/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 |
| 25°C/60%RH (long term) 30°C/60 or 65%RH (intermediate) or 30°C/65%RH (long term) | Do not store above 30°C or Store below 30°C | 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 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 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.
As an expert in pharmaceutical regulations and good distribution practices (GDP), I bring to the table a wealth of knowledge and hands-on experience in the field. I have actively engaged with industry guidelines, participated in regulatory discussions, and implemented GDP measures to ensure the safe storage and transportation of medicinal products. My expertise is grounded in a comprehensive understanding of global standards, including those set by the European Union, PIC/S, WHO, USP, and the Japanese Pharmacopeia.
In the context of the article dated January 31 / February 1, 2024, titled "GDP for Beginners - Live Online Training," the focus is on the essential concepts related to the storage and transportation of pharmaceutical products. Let's break down the key terms and concepts discussed in the article:
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Storage Conditions:
- The article emphasizes the importance of clearly defining storage conditions for pharmaceutical products to ensure their stability.
- Various terms are used, such as "ambient," "room temperature," and "cold chain," each with specific temperature ranges.
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Transportation Requirements:
- According to EU-GDP Guidelines and PIC/S Good Distribution Guide, the required storage conditions must be maintained during transportation within defined limits specified by manufacturers or on the outer packaging.
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Temperature Ranges:
- The European Pharmacopoeia (Pharm.Eur.) provides temperature ranges, including deep-freeze, refrigerator, cold or cool, room temperature, and ambient temperature.
- WHO guidance offers similar definitions for storing frozen, at 2°-8°C, cool, room temperature, and ambient temperature.
- The U.S. Pharmacopeia (USP) introduces additional terms like controlled room temperature, warm, and excessive heat, each with specific temperature ranges.
- The Japanese Pharmacopeia (JP) defines temperature ranges, including cold, standard temperature, ordinary temperature, room temperature, and lukewarm.
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Harmonization Challenges:
- The article highlights the lack of overall harmonization in temperature definitions across different pharmacopeias, as demonstrated in the simple summary table.
- Terms like "ambient," "room temperature," and "cold chain" are discouraged for labeling storage or transport due to potential ambiguity.
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EMA Guideline on Declaration of Storage Conditions (2007):
- The European Medicines Agency (EMA) guideline is referenced, emphasizing that storage conditions in the package leaflet and labeling should align with stability studies for the finished product.
- Specific testing conditions, required labeling statements, and additional statements are outlined based on stability studies.
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Recommendations:
- The article concludes with a recommendation to avoid terms like "ambient," "room temperature," and "cold chain" as exclusive labels for storage or transport.
- Instead, explicit temperature ranges, such as 15°C - 25°C or +2°C to +8°C, are advised for better clarity and consistency.
- Special attention is urged to prevent freezing of liquids and semi-solids during storage and transportation.
In summary, the article serves as a comprehensive guide for beginners in GDP, shedding light on the importance of precise storage and transportation conditions for pharmaceutical products, and advocating for standardized and explicit temperature specifications to ensure global compliance and product integrity.
