Equipment Cleaning Validation For Active Pharmaceutical Ingredients

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· Stability of material(s) being cleaned under the proposed cleaning conditions;
· Suitability of the cleaning agent(s) for the materials of construction of the
equipment;
· Equipment surface finish (e.g., stainless steel, glass, polypropylene);
· Rationales for decisions on which materials to test, the limits for testing, and the method
of verification (see Table 1); and
· Evaluation of campaign length.
2.
Equipment with the Same Design and Operating Principle may be grouped for the
purpose of validation. These groupings should be documented and justified. The
documentation should be approved by Site Quality Team and Production
Team. If equipment grouping is used, cleaning validation should be performed
using three executions of the same cleaning procedure using any combination of
equipment within a group.
3.
Where Equipment is Used to Produce Only Early Intermediates (i.e., intermediates
produced prior to the introduction of the API starting materials), cleaning verification
is required. Validation of the cleaning procedures for these cases is not required (see
Table 1).
4.
Selection of The Most Difficult To Clean Product or Process requires consideration
of, at least, the following:
• Solubility of residues in cleaning agents (including cleaning and rinse solvents);
• Potential for polymers, or other side products to form during or prior to the
cleaning operations;
• The Residue Acceptability Limit (RAL) required for cleaning;
• Processing Parameters (e.g., high temperature, use of carbon); and
• Cleaning history.
Selection of the most difficult to clean product or process should be documented in
the validation protocol or a Cleaning Evaluation Report.
5.
Rinsate Method - if a rinsate method is used as the sampling method, a measured
volume of solvent used for the final rinse should thoroughly wet all product contact
surfaces, and should be circulated through all product contact lines before the rinsate
is tested in the laboratory for residues.
6.
Swabbing Method - if swabbing is used as the sampling method, swabbing of
product contact surfaces should be performed in locations from which there is a
likelihood of transfer of residue to a subsequent product and from most difficult to
clean areas (i.e., dead-legs, bottom valves, overheads, tank domes and inlets).