It is a part of good manufacturing practice that a product should meet qualitative and quantitative specifications and quantitative label claims for all ingredients throughout the productʼs shelf-life, and companies generally label products with a date by which they should be used by consumers. For supplements, assurance of product stability is related to the quality of the product and consumer confidence, and product safety is a relatively minor concern.
Some common ingredients in supplements, or their declared constituents, are inherently unstable. When a shelf-life date is provided on labelling, the product manufacturer is responsible for ensuring its accuracy, based on a realistic assessment of relevant data obtained under conditions similar to those under which the product is likely to be distributed, stored and used.
The ideal way a shelf-life can be confidently estimated is to conduct a ʻreal-timeʼ study exceeding the time of the required shelf-life at a temperature and humidity simulating the conditions to which the product is likely to be exposed. In most cases, however, real-time studies before a product launch are not commercially viable, and shorter studies are utilised. These are commonly designated ʻaccelerated studiesʼ.
Accelerated studies utilise the fact that, in general, the rate of a chemical reaction doubles with every 10°C rise in temperature. Therefore, accelerated studies involve storage of the product at temperatures considerably above the expected ambient storage in the market place. Thus, if the ambient average temperature is 30°C, the accelerated storage must be at temperatures of 40°C and above. The accelerated studies should be carried out at two or more elevated temperature points, particularly where extended shelf-life is required. A study where there is only one temperature point at 10ºC above the ambient may in some cases only give confidence of 2 x accelerated storage time. That is, if the accelerated storage time for certain products is 6 months, the confidence for the shelf-life is only 12 months.
The accuracy of both real-time and accelerated shelf-life studies depends on the selection of representative product ingredients or constituents, or specific product attributes, that can be examined qualitatively or tested quantitatively in relation to the product matrix.
Well-characterised quantitative test methods are available from the literature and various compendia for all the vitamins and many other supplement ingredients. For botanical products that do not declare specific levels of naturally-occurring constituents, qualitative review of such attributes of taste, odour, and colour may be appropriate to review product stability. On the other hand, when a botanical constituent is declared, a significant amount of analytical work may be needed on the product before a stability study can commence if scientifically valid methods are not readily available. It is expected that this analytical work would be undertaken prior to manufacturing and packaging to ensure label accuracy.
For products containing two or more ingredients, different ingredients may degrade at different rates so reliance cannot necessarily be placed on one single ingredient or constituent; instead multiple assays may be needed. For such products, a single accelerated study may only be able to give a rough approximation of the shelf-life and should be accompanied by real-time studies and/or other data whenever possible. Other data can consist of real-time experience on similar products or other information on the stability of the ingredients and constituents. In other words, undue reliance should not be placed on an accelerated study alone.
2. Objectives of Stability Testing
Stability studies can be carried out for two purposes:
- To estimate the chemical and physical stability of the product and to ensure that the claimed levels of ingredients are retained during the intended shelf-life of the product.
- To confirm packaging protection and integrity. This is to ensure that the packaging is suitable for the product for the intended shelf-life and that it is not permeable to oxygen, moisture and ultra-violet light.
These objectives are inter-related as any deficiencies in packaging integrity can have a detrimental effect on the product stability. A product can be more stable in one package than in another.
It is recommended that consideration is given to the suitability of the packaging before a product stability study is undertaken.
3. Regulatory Approaches to Stability
In most countries across the world where the labelling of a shelf-life date for supplements is required by law there is either a specific or implied requirement for stability data. In the countries or regions where supplements are legally defined as foods (for example, USA, European Union), the requirement for stability data on a product can be implied in legislation or regulation but is not always specified. However, use of a shelf-life date, whether voluntary or required, should be based on data that supports and justifies the chosen date. This will not only ensure the accuracy of the shelf-life date, but will provide the manufacturer with reasonable justification to demonstrate to regulatory authorities that there is sound reasoning behind the determination of the shelf-life of the product. The evidence for the justification can be based on:
- data from an appropriate stability study on the specific product;
- extrapolation of data from stability studies on similar products (similar products are those with similar matrices and containing the same or very similar combinations of ingredients);
- bibliographical references from scientific literature relating to the stability of the ingredients;
- combinations of the above.
Flexibility is needed when determining the shelf-life for products containing two or more ingredients, so that all available and relevant data can be used to indicate the stability of such products.