Existing drug and biologics GMP regulations and guidelines that address particulate quality apply either to the external cleanroom environment or to the finished drug product itself, after filling in its final dosage container. In addition to the inspection of final dosage units for visible particles (e.g., per USP <1> Injections), injectable drug products are also subject to lot sample testing for microscopic particles (e.g., per USP <788> Particulate Matter in Injections) (1, 2). Similar tests exist under the European Pharmacopoeia 2.9.19 and Japan Pharmacopoeia 6.06 (3, 4). For global harmonization, these tests have also been incorporated into International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q4B (5).
In contrast to finished injectable dosage units, process equipment, including single-use systems, is not directly regulated under drug or biologics GMP. Consequently, there are no regulations or guidelines for the particulate quality of final filter effluents, single-use filling equipment fluid paths, final bulk drug containers, or even finished drug product dosage containers prior to filling. By themselves, these components and systems do not fall within the scope of GMP regulations, which focus on finished drug products.However, regulatory authorities recognize the potential influence of the process equipment fluid path when in contact with final bulk drug formulation. For example, US 21 CFR Part 211.65 states, "Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements"(6).
While particulate quality of process equipment is not specified, drug manufacturers must ensure that process equipment does not adversely impact the quality of the final drug product. This requires the single-use system user to establish that reasonable controls are in place to ensure that process equipment does not cause the drug product to fail particulate quality specifications.