Drug quality influences treatment efficacy and safety. Quality depends on correct manufacturing and storage: high-quality drugs are available when using rational buying procedures and when suppliers are reliable. It is also essential to ensure optimum transportation and storage conditions.
Each drug is characterised by particular norms written in pharmacopoeia or files presented by manufacturers and recognised by competent authorities in each country. These norms concern aspects (colour, odour, etc.), physicochemical properties, analysis procedures, shelf life and storage conditions.
Analysis certificates guarantee that products from one batch (products from the same production cycle) conform to official quality standards in the country of manufacture. These certificates are provided for each product by manufacturers.
Every unit (box and bottle) should be clearly labelled; each label should clearly indicate the:
– form and dosage,
– number of units (tablets, ampoule, etc.) or the volume (syrup, etc.),
– name and address of the manufacturer,
– batch number,
– expiry date.
Stability of drugs depends on both environmental factors such as temperature, air, light and humidity, and drug-related factors such as the active ingredient itself, the dosage form (tablet, solution, etc.) and the manufacturing process. It is therefore necessary to respect storage instructions given in this guide or by manufacturers (on notices and labels) if the recommendations are not identical.
The temperature in the store should not be above 25 °C.
Storage temperatures are defined by European pharmacopoeia as follows:
freezer - 15 to 0 °C
refrigerator + 2 to + 8 °C
cool + 8 to + 15 °C
ambient temperature + 15 to + 25 °C
During transit and transportation temperatures may attain 50 to 60 °C inside vehicles, shipping containers or on docks and, in this case, shelf life and expiry dates may no longer be guaranteed.
Freezing may be detrimental, particularly for solutions, leading to the deterioration or precipitation of active ingredients as well as the breaking of ampoules and vials.
Vaccines, immunoglobulins and antisera are products that are sensitive to heat and light. Even though new techniques produce vaccines that are less sensitive to heat (called "thermostable"), they still have to be stored in the refrigerator between 2 °C and 8 °C, and the cold chain must be strictly respected during transport.
The vaccine vials may have a heat-sensitive monitor (VVM). The square on the monitor changes colour when exposed to heat over a period of time: if the square is lighter than the circle, the vaccine can be used. If the square is the same colour or darker than the circle, the vial must be destroyed. The monitor registers cumulative exposure to heat.
Controlled temperature chain (CTC)
In certain mass vaccination campaigns only, certain vaccines licensed for use in a CTC can be transported and used out of the cold chain within a specified time limit.
To qualify for use in a CTC the vaccine must be able, once out of the cold chain (2 °C to 8 °C), to tolerate temperatures of up to 40 °C for at least 3 days. The maximum temperature of 40 °C is monitored by a peak threshold indicator in each vaccine carrier used for transport and vaccination in the field.
Air and humidity
In a store, relative humidity should not be above 65% (there are several devices for humidity measurement).
Air is a factor of deterioration due to its content of oxygen and humidity. All containers should remain closed. In airtight and opaque containers (hospital type), drugs are protected against air and light. Opening containers long before the use of drugs should be avoided.
Patients should be informed that tablets should not be removed from blisters until immediately before administration.
Drugs should be protected from light, particularly solutions. Parenteral forms should be preserved in their packaging. Coloured glass may give illusory protection against light.
It is important to be familiar with the normal aspects of each drug (colour, odour, solubility, consistency) in order to detect changes, which may indicate its deterioration. It is important to know that deterioration does not always lead to a detectable external modification.
The principal consequence of deterioration is a reduction of therapeutic activity, which leads to more or less grave consequences for the individual and/or community.
For example, the use of expired antibacterials does not cure an infection and also favours the emergence of resistant strains.
It is not recommended to compensate for a possible reduction of activity by a random increase in the usual dose, as there is a real danger of overdose when using toxic drugs.
Over time, certain drugs undergo a deterioration leading to the development of substances much more dangerous, thus an increase in toxicity. Tetracycline is the main example: the pale, yellow powder becomes brownish and viscous, its use therefore being dangerous even if before the expiry date.
An increase in allergen strength has been observed in certain drugs such as penicillins and cephalosporins.
Suppositories, pessaries, creams and ointments that have been melted under heat should not be used. The active ingredient is no longer distributed in a homogenous manner.
Oral rehydration salts may be used as long as they keep their aspect of white powder. Humidity transforms them into a compact mass, more or less brownish and insoluble. They are therefore unfit for consumption, whatever their expiry date.
Drugs deteriorate progressively and according to various processes, even if stored in adequate conditions. In most countries, regulations impose an obligation on manufacturers to study the stability of their products in standardised conditions and to guarantee a minimum shelf life period. The expiry date indicated by manufacturers designates the date up to and including which the therapeutic effect remains unchanged (at least 90% of the active ingredient should be present and with no substantial increase in toxicity).
The expiry date indicated on the label is based on the stability of the drug in its original and closed container. Shelf life period currently usually guaranteed is 3 and 5 years. Less stable substances are only guaranteed for 1 or 2 years.
The expiry date should be indicated on the label with storage instructions.
Expiry dates are to be respected due to legal obligations and considerations of therapeutic responsibility
In cases where the only available drugs have expired, a doctor may be led to take on the responsibility of using these drugs.
It is evident that a drug does not become unfit for consumption the day after its expiry date. If a product has been stored in adequate conditions (protected from humidity and light, packaging intact and at a medium temperature) and if modification of aspects or solubility have not been detected, it is often preferable to use the expired drug than to leave a gravely ill patient without treatment.
Expiry dates for drugs that require very precise dosage should be strictly respected due to a risk of under-dosage. This is the case for cardiotonic and antiepilectic drugs, and for drugs that risk becoming toxic, such as cyclines.
Destruction of expired or unusable drugs and material
It is dangerous to throw out expired or unusable drugs or to bury them without precaution. For more information about destruction of drugs and material see Interagency Guidelines For Safe Disposal of Unwanted Pharmaceuticals in and after emergencies, WHO/99.2.