Performance qualification.
HVAC system PQ begins only after OQ has been completed successfully. Because airborne viable and nonviable particulate levels,
room bioburden, and temperature/relative humidity control rely on a system operating as designed, the transition to PQ must
occur only after OQ is complete and all deviations are resolved.
Like IQ and OQ, the test procedures for HVAC system PQ are now well defined. Standard PQ acceptance criteria are published
by organizations such as the European Commission (EC), International Organization for Standardization (ISO), and FDA.
Currently, the definitive standard for multinational companies is the EC Guide to Good Manufacturing Practice, Revision to Annex 1, Manufacture of Sterile Medicinal Products (9). This document provides supplementary guidance on the principles and guidelines of GMP as applicable to sterile products
such as LVPs. One section in Annex 1 is specific to clean environments used for aseptic manufacturing. Annex 1 divides manufacturing
areas into letter grades (A, B, C, D) that closely correspond to the older Class 100, 10,000, and 100,000 conditions contained
in Federal Standard 109 (now cancelled). One notable difference from previous standards is that air-sampling volumes have
now increased to 1 m3, a change from the historical 1-ft3 sample size specified in the LVPs. As expected, upward adjustments have been made to particle limits because air-sample
volumes have now increased by approximately 35 times.
ISO 14644-1, "Cleanrooms and Associated Controlled Environments—Part 1: Classification of Air Cleanliness," should be consulted
when qualifying HVAC systems other than those supporting aseptic production. ISO 14664-1 assigns nine particulate classifications
to manufacturing areas, with Class 1 the most demanding and Class 9 the least restrictive (10). ISO classes 5–9 are appropriate
for all pharmaceutical facilities. In solid-dosage facilities where airborne dusts are expected, it often makes little sense
to monitor particulate levels while operations are in progress. However, baseline (static) information is often useful, as
this may provide a sign of HEPA filter failure or other indication of unwanted particulation.
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