Dry Powder Injection (DPI) products (e.g., sterile powders in vials for reconstitution) require controls for sterility assurance, dose accuracy, powder performance, and container–closure integrity. Typical tests & checks span raw materials, in-process controls, and finished product testing.
Incoming / raw material checks
- API and excipients: identity, assay, impurities, particle size distribution, moisture (LOD/KF), microbial limits (where applicable), and compatibility.
- Primary packaging (vials, stoppers, seals): dimensional checks, extractables/leachables qualification, siliconization (if used), and sterilization certificates.
In-process controls (during filling and closing)
- Environmental monitoring in Grade A/B areas: viable and non-viable counts, differential pressure, temperature/RH.
- Sieve/particle control (if required): prevent lumps, foreign matter.
- Blend uniformity (for powder blends): sampling plan + assay/marker.
- Fill weight / net content: frequent checks with defined alert/action limits.
- Stopper placement and crimping: visual and torque/crimp integrity checks.
- Inert gas purge (if applicable): oxygen level verification.
- Line clearance & reconciliation: printed components, vial counts, rejects.
Finished product tests (common)
Chemical / physical
- Appearance (color, caking, visible particles)
- Assay and related substances
- Uniformity of dosage units (mass variation/content uniformity as applicable)
- Moisture content (critical for stability and flow)
- Reconstitution time and clarity after reconstitution
- pH (after reconstitution)
- Particulate matter testing for reconstituted solution (USP <788> / <789> as applicable)
- Extractable volume (deliverable volume after reconstitution)
Microbiological
- Sterility test (USP <71>)
- Bacterial endotoxins test (LAL; USP <85>)
- Bioburden (pre-sterilization, where applicable)
Container–closure integrity
- CCI testing (deterministic methods like HVLD, helium leak, vacuum decay, etc., based on strategy) plus dye ingress where justified.
Stability and Shipping
- ICH stability (assay, impurities, moisture, appearance, reconstitution behavior, sterility/endotoxin where relevant) and transport validation (vibration/temperature excursions).
These checks collectively ensure the DPI remains sterile, potent, easily reconstituted, and safe through shelf life.