Documentation · Biodecontamination · Cycle Development
Qualification & Validation
Qualification and Validation, Cycle Development (CD) and Cycle Validation (CV)
Manufacturing of high performance pharmaceutical machines and equipment must follow strict guidelines. There is no room for failure; therefore all involved parties must be aware of and follow relevant norms.
Qualification and documentation processes start in the planning phase of a project and continue through manufacturing and the equipment lifecycle. User requirements and equipment functions need to be defined early. The specification shall clearly define CQAs and CPPs, including materials, processes, assembly, surface properties, radii, electrical equipment and automation platform.
Machine manufacturers need a mature and robust quality management system consisting of a norm database and internal SOPs / guidelines. Every step from planning through design, manufacturing and commissioning must be reviewed and documented.
The right sequence of actions guarantees efficient qualification / validation performance
Example for Qualification / Validation tests
URS / FS / HDS / SDS / IQ / OQ / PQ / SMDS / ... What’s that?
| VMP | Validation Masterplan (see also PQP) |
| PQP | Project Qualification Plan |
| URS | User Requirement Specification |
| RTM | Requirement Traceability Matrix |
| FS | Functional Specification |
| HDS / SDS | Hardware Design Specification / Software Design Specification |
| SMDS | Software Module Design Specification |
| ICD | Internal Checkout Documentation |
| IQ | Installation Qualification |
| CAL | Calibration |
| OQ | Operational Qualification |
| PQ | Performance Qualification |
| CD/CV | Cycle Development / Cycle Validation |
| DQ | Design Qualification |
| RA | Risk Analyses |
| (c)FAT | (customized) Factory Acceptance Test |
| DR | Disaster Recovery |
| AFT | Alarm & Function Testing |
| (c)SAT | (customized) Site Acceptance Test |
D-Value determination
Cycle Development for H2O2 Biodecontamination
Cycle Development includes:
- OQ studies
- Tests with chemical indicators (CI)
- Tests with biological indicators (BI), stainless steel coupons inoculated with 6 log of the most resistant viable spores of Geobacillus stearothermophilus.
- BI wrapped in Tyvek became an industrial standard to ease handling and to challenge the biological test system.
Cycle Development is designed to determine process parameters, worst-case BI positions and process limits needed for successful H2O2 distribution during biodecontamination. Critical factors include temperature, humidity, amount of H2O2 required to reach a defined concentration, and the peroxide injection rate needed for a 6-log reduction.
Before starting CD/CV, every BI lot should be verified / tested in the user’s own laboratory to ensure it meets the expected quality standards. Each BI lot varies slightly in population, resistance and survival time.
Acceptance criteria:
- No significant difference from expected resistance (D-value < 1.5 min).
- No single late survivor has to be present.
After a biodecontamination cycle, the BIs are transferred from the isolator into nutrient broth and incubated at 55°C for seven days. Once Cycle Development is finished, Cycle Validation follows. Statistical interpretation of results is performed according to ISO 14161.
