Quality information – Module 3
- Physicochemical attributes such as solubility, molecular structure, molecular weight, composition if a mixture, function etc. The parameters described should be relevant to the performance of the finished product
- Characterisation – see below
- Method of manufacture: This should include all critical steps, intermediates and controls, and the name and address of the manufacturer. Starting materials and intermediates should be properly controlled and ideally, the excipient would be manufactured under GMP.
- Specifications should be established and justified. Parameters that are likely to be required are those relevant to ensuring quality of the excipient such as assay/purity, impurities, appearance, etc. If the excipient is to be used for a sterile product, microbial contamination should be controlled. More specific requirements such as XRD spectra, Specific Optical Rotation etc may be required if the compound exhibits properties such as polymorphism, isomerism etc. All impurities should have limits in line with ICH guidelines and all potential metal/catalyst contaminants should be identified. Elemental impurities and nitrosamines risk assessments will be required.
- The analytical methods used to test the excipient should be described and validated.
- Batch analysis should be included on representative batches, and preferably more than one batch, to demonstrate that the excipient is of the required quality.
- Information on the container closure system and stability of the excipient should be presented.
Specific requirements for characterisation of a novel excipient
- Evidence of structure – This should include data obtained through techniques such as elemental analysis, IR, NMR and MS spectra, UV characterisation.
- Key intermediates in the excipient manufacturing process should be characterised.
- Polymorphism – all polymorphs should be identified or evidence should be presented to demonstrate that no polymorphic forms exist.
- Physico-chemical characteristics relevant to the drug product should be defined, for example solubility, pKa and pH for injectable products.
Clinical information- Module 4
- Toxicity profile – This can be taken from literature. Full disclosure of any potentially genotoxic impurities or alerts should be provided, and in silico analysis is likely to be required as a minimum.
- Safety profile – Data obtained using the same route of administration in humans/animals should be presented to demonstrate that the excipient has an acceptable safety profile at the calculated maximum exposure.
- If the novel excipients are used in other applications such as food or cosmetics, this is likely to be considered supportive but will not be sufficient in itself.