GMP expectations of Non Traditional APIs

Where dosage form manufacturers are using as active substances materials that are not true APIs and where there is difficulty in getting the manufacturer of these starting materials to comply fully with Part II of the GMP Guide (usually due to the scale of production by the starting material manufacturer and the purchasing power of the dosage form manufacturer) the following should be considered and appropriate elements applied: 1. There should be a clear specification for the material being purchased, detailing both chemical and physical attributes as appropriate. This should be agreed between the supplier and purchaser. The key processing parameters which are required to be controlled to give product that meets the specification should be identified. The starting materials manufacturer should undertake to operate to the key processing parameters and there should be a system of change control with notification being given to the dosage form manufacturer if the process changes. An agreement/contract between the starting material manufacturer and the dosage form manufacturer (and any other intermediaries) should be available. This should clearly document the above. The dosage form manufacturer should perform audits of the starting material manufacturer (these should preferably be on site, but if access is not allowed then a paper audit will need to be performed). The audits should be against the requirements of Part II of the GMP Guide with the main focus upon control of the key parameters and conformance to specification. The dosage form manufacturer should conduct a risk assessment and document his rationale for the approach that has been adopted, and be in a position to defend this during inspection. The material should be fully tested on receipt by the dosage form manufacturer. It may be possible to scale down testing based on knowledge suppliers systems and history of supply.

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