Empty hard gelatin capsules are provided as an excipient for the development and manufacturing of pharmaceutical products. Drug product manufacturers undertake alternative capsule source projects for a number of reasons like cost savings; addition of supplementary and/or alternative suppliers; an existing supplier may no longer be able to supply; and, reduction of risk due to relying on a single source.
In the United States, drug product manufacturers who want to supplement or change their hard gelatin capsule supplier(s) must file the change in a regulatory submission to the Food and Drug Administration (FDA). To be successful as an alternative source of capsules, new suppliers should be prepared to: provide the required documentation to support the regulatory submission; comply with appropriate Good Manufacturing Practice (GMP) regulations; and, satisfy any other requirements of drug product manufacturers.
For empty hard gelatin capsules used in drug products marketed in the US, the addition of a new capsule supplier is an annual reportable change (which is a notification to the FDA stating the change has been implemented to the drug product), provided there are no changes to capsule composition or appearance which includes changes to size, color or dye; the information to be provided in the annual report is provided in the FDA’s Manual of Policies and Procedures 5016.6. Changes in capsule composition, appearance, or a change from gelatin to non-gelatin alternative are categorized as a prior approval supplement (PAS) requiring additional data to show equivalency and approval by the FDA before the change can be implemented.
Therefore, when sourcing capsules from new suppliers, drug product manufacturers would want to see that the addition of capsules from the new source is simply an annual reportable change so that they wouldn’t need to generate additional data and wait for agency approval for marketing the drug product made with capsules from the new supplier.
Once a prospective alternative supplier is identified, the drug product manufacturer begins the supplier qualification process with an assessment to determine the potential risks due to source, origin and use of the capsule ingredients. Following this step, an audit is conducted to verify that the capsules are produced in a manufacturing facility that follows appropriate GMPs, and samples from representative lots are tested to determine conformance to applicable specifications. Once compliance with GMPs and conformation to specifications have been demonstrated, the drug product manufacturer will request and review the information required for regulatory submission for the addition of capsules from the new supplier.
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The next steps in the supplier qualification process
Performing trials to confirm the capsules from the new supplier have no machinability issues, and
testing the drug products made with these capsules to verify that they meet specifications and are equivalent to the drug product made with the capsules from the primary supplier.
The drug product manufacturer also requires documentation from the new supplier to verify process capability and to confirm the safety of the capsules (i.e. BSE/TSE, residual solvents and elemental impurities).
