According to EU Directive 2002/46/EC, a food supplement is a product marketed in dose form.1 In other words, it is a product that contains a substance or substances that have an intended nutritional or physiological effect, together with other ‘non-active’ components that enable the formulation to be delivered and function properly (known in the pharmaceutical industry as excipients). These non-active components may have a very simple role in the formulated product, such as a tablet filler or a capsule shell. However, they may have a more complex role, such as controlling the bioavailability of the main component. An example would be a one-a-day time release vitamin C product in which the non-active ingredient controls the slow release of the vitamin itself.
Ingredient Synergies
The selection of appropriate components for a food supplement product is a vital part of the overall formulation process. The non-active components can contribute greatly to the characteristics — and hence customer quality perception — of the marketed product. A customer would certainly not make a repeat purchase of a tablet that is so soft that it falls apart when removed from a blister pack. Hence, the use of suitable materials, which allow the production of a robust product, is essential. As well as functional characteristics, the non-active components can have an effect on the properties of the food supplement product, such as the ease with which a tablet or capsule can be swallowed, or to provide taste masking properties for odorous products such as those containing fish oils.
The non-active components can contribute greatly to the characteristics of the marketed product
There is an obvious overlap between the substances used as non-active components of food supplement products and the excipients used in the pharmaceutical industry. Manufacturing companies in many cases will use some materials interchangeably between products for these two sectors. This is not surprising; the technologies used to formulate tablets, capsules or liquid products for both industries have a great deal in common, although different regulatory environments and cost structures may apply.
Regulatory Insight
For a material to be suitable for use as a non-active supplement component in the EU, it must be either a food ingredient in its own right or an approved food additive with a permitted use in the appropriate food category; that is, Category 17, food supplements as defined by Commission Regulation 1333/2008.2 For example, if lactose is used as a component of a supplement product, because it is classed as a food ingredient, it needs to be ‘food grade’. However, if hydroxypropyl methylcellulose (HPMC) is used as a component, as a food additive, it needs to meet the purity requirements for E464 as given in Commission Regulation 231/2012.3
HPMC also has a monograph in the European Pharmacopoeia, which prescribes its purity criteria for use in pharmaceutical applications. Although there are some overlaps, there are significant differences (see Table 1). It would not be valid to say that either requirement is more demanding; however, it is important to understand that they are different.
| Table 1: Purity Requirements for HPMC | ||
| Test | Regulation 231/2012 E464 | European Pharmacopoeia 8.0 (0348) |
| Assay | 19–30% methoxy groups | 16.5–30% methoxy groups |
| 3–12% hydroxyl-propoxyl groups | 04–32% hydroxyl-propoxyl groups dependent) | |
| pH | 5–8 (1% solution) | 5–8 (2% solution) |
| Loss on drying | Max. 10% (105 °C, 3 h) | Max. 5% (105 °C. 1 h) |
| Sulphated ash | 1.5% or 3% (type dependent) | 1.5% |
| Propylene chlorohydrins | Max. 0.1 mg/kg | No requirement |
| Arsenic | Max. 3 mg/kg | No requirements for specific metals |
| Lead | Max. 2 mg/kg | Total heavy metals = Max. 20 ppm |
| Mercury | Max. 1 mg/kg | Elemental impurities will be addressed shortly by new guidance |
| Cadmium | Max. 1 mg/kg | |
| Molecular weight | 13,000–200,000 | Specified by viscosity of solution |
Colour Additives: Common Ground
One area in which there is close alignment between the food supplement and pharmaceutical sectors is that of food colours. All the colour additives permitted for food products are also permitted for the colouring of medicinal products. Indeed, the pharmaceutical legislation merely cross-references that from the food industry. The only divergence is that materials used to colour medicine must be an approved food colour, which means that materials such as food extracts with colouring properties may not be used in conjunction with medicines.
Importance of the Supply Chain
It is essential that companies that manufacture food supplement products have a thorough understanding of the supply chain for all the ingredients
It is essential that companies that manufacture food supplement products have a thorough understanding of the supply chain for all the ingredients in their finished products, including the non-active components. It is important to be fully aware of the provenance of these ingredients, even when purchased from third parties such as distributors and brokers.
Without this full knowledge, it is impossible to evaluate any changes in the supply chain and any subsequent effect on the finished product. A change by the component manufacturer may result in only a minor physical or chemical change to the material, but this could create bigger issues for the final product or its manufacturing process.
In summary, a manufacturer of food supplement products needs to select all product components diligently, including the non-active ingredients. They need to select sources that have transparent supply chain traceability, right back to the actual ingredient manufacturer. Owing to synergies with the pharmaceutical sector, there are benefits in dealing with suppliers that are familiar with both industries.
References
1. OJ L 183, 12.7.2002, p51
2. OJ L 354, 31.12.2008, p16
3. OJ L 83, 22.03.2012, p1
For more information
Carl Mroz is Director of Global Regulatory Affairs at Colorcon and has more than 25 years of experience in the pharmaceutical and food supplement industry. Colorcon is the global market leader in the supply of excipients for solid oral dosage forms for use in both the pharmaceutical and supplement sectors.