Whenever a new residue or piece of equipment is used, an evaluation needs to be made if it can be added to an existing group or if it represents a new worst case that will require a new validation.Identifying Residue and Selecting a Detection Method Before you start identifying residues, first you have to assemble a list of all the possible residues that could be left on critical manufacturing surfaces as a result of the cleaning process: including cleaners, primary ingredients, excipients, decomposition products, and preservatives.
The worst case is usually based on a variety of factors including: product solubility in cleaner; toxicity of the products or respective degraded products being cleaned; dose sizes and normal therapeutic dose size (smaller may be more critical to validate); hardest-to-clean equipment; and worst interactions with the upcoming batch to be cleaned.
In this regard, a sample is taken of an equilibrated post-final rinse that’s been re-circulated over all surfaces.
Such samples should be correlated to a direct measuring technique like swabbing in order to assure that residues are being adequately detected and not simply sitting on the surface and not being dissolved into the equilibrated rinse water.
Simplify Validation Using a Worst Case Matrix To simplify validations, it is recommended that a matrix of worst case equipment to clean and worst case residues to remove be created.
Start by first assembling an equipment matrix and residue matrix that defines all shared and dedicated equipment with what residues they are exposed to.
Specific methods test for an individual ingredient include high-performance liquid chromatography (HPLC); ion selective electrodes; flame photometry; derivative UV spectroscopy; enzymatic detection; and titration.