N.44 – Environmental Microbial Data interpretation in aseptic processing.

TRIO

We report what USP 38 – USP Pharmacopeial Conventions says at page1199 in the Chapter “Further considerations about data interpretation” of the document “Overall Management of a microbiological control program”.

ZERO CONTAMINATION

“In the high quality environments required for aseptic processing, detection frequency typically is low. As can be seen from the rates recommended in the enclosed table,

Room classification Active Air Sample
(%)
Settle Plate (9 cm) 4H Exposure (%) Contact Plate or Swab (%) Glove or Garment (%)
Isolator/Closed RABS
(ISO 5 or better)
<0.1 <0.1 <0.1 <0.1
ISO 5 <1 <1 <1 <1
ISO 6 <3 <3 <3 <3
ISO 7 <5 <5 <5 <5
ISO 8 <10 <10 <10 <10

the majority of samples taken in an aseptic processing area will yield a recovery of zero contamination. In the most critical areas within an aseptic  processing operation, it is expected that less than 1% of the samples will yield any recoverably contamination. In the most advanced of modern aseptic operations that use separative technologies such as isolators or closed RABS, the recovery rate will approach zero at all times.

STERILITY ASSURANCE

The microbiologist responsible  for environmental control should not take this to mean that the environmental quality approaches sterility. The sensitivity of any microbial sampling system  in absolute terms is not known. In environmental monitoring, a result of zero means only that the result is below the limit of detection of the analytical system. A false sense of security should not be derived from the infrequency of contamination recovery in aseptic processing.

HUMAN BORNE CONTAMINATION

Sterility assurance is best accomplished by a focus on human borne contamination and the facility design features that best mitigate risk from this contamination. Greatest risk mitigation can be attained by reducing or eliminating human interventions through proper equipment design and by providing sufficient air exchange per hour for the intended personnel population of the facility. Other risk mitigation factors include effective personnel  and material movement and the proper control of temperature and humidity.

Secondary factors for risk mitigation include cleaning and sanitization. Risk analysis models that analyze processes prospectively to reduce human borne contamination risk by minimizing operator intervention are more powerful tools for sterility assurance than monitoring. Environmental monitoring cannot prove or disprove in absolute terms the sterility of a lot of product. Environmental monitoring  can only assure those responsible for a process that a production system is in a consistent validated state of control. Care should be taken to avoid drawing inappropriate conclusions from monitoring results.

REFERENCE

USP 38 –  USP Pharmacopeial Conventions – page1199  – Chapter “Further considerations about data interpretation” – “Overall Management of a microbiological control program.