FAQ - Contagem de partículas em laboratórios farmacêuticos ou de ciências biológicas

Pergunta
Please provide a very brief overview of the supporting information we can use to prove compliance.

Resposta

When one looks at the batch record for a pharmaceutical product (either animal or human dose) there are multiple requirements:

• Formulation and strength of product
• Manufacturing variables, fill volume, weight etc
• Environmental conditions
  • Particles
  • Viable contaminants
  • Air Velocity
  • Differential Pressure
  • T/RH
• Personnel training records
• Gowning requirements
• Filling line log records
• Sterilization of glassware
• Cleaning log, media used and duration of contact
• Finished product tests
  • Sterility tests
  • Particle contaminants
  • TOC
  • Etc

From this list we see that the particles form a small component of the overall record where full compliance is required, a fail in any test or condition would either warrant product to be disposed or reviewed in light of other parameters. Failure of product at a finished product testing level is relatively terminal though.

The particle component is one function of several that show control over the general manufacturing environment. The maintenance of the pressure cascade would show that no particles were brought into the cleanroom from an unknown source. Maintenance of the airflow velocity would show that the air wash efficiency under the laminar flow was meeting specification. Viable contamination sampling would show that the major source of uncontrolled contamination was within specification. One would also use particles to prove the efficacy of one of the other parameters should data from that stream not be available for review. The finished product testing would then confirm that the product was filled within a suitable environment, it is useful to note that the particles tested for at finished product testing is for large amounts of large particles and not reflective of environmental conditions during production.

The issue where a system is operating normally, and I use that phrase reservedly, but data is being sent from the instrument into the PAT system but not being recorded is even more robust than no data. One can prove that the alarm lamp did not flash, nor the siren sound, therefore no alarm occurred. Otherwise a record would be in the audit log of the monitoring system (if available) or a paper log, from within the cleanroom. If one accepts that the operators gowned suitably, the viable samples have returned within specification and other environmental parameters were within specification then the system was in control, the lack of post fill evidence for the particulate burden would need to be countered by one of SOP and activity events within the cleanroom during the fill time. Where the system is dynamically linked to a third party auditing system a review of the event log from that application should show any real time events.