Informal risk mitigation brought about the technology advances seen in aseptic processing. Confidence in aseptic processing is not derived from monitoring or testing; it is the result of attention to detail in aseptic processing design. With newer technologies the emphasis must shift even farther from monitoring & testing.
Aseptic Processing Definition
“Handling sterile materials in a controlled environment, in which the air supply, facility, materials, equipment and personnel are regulated to control microbial and particulate contamination to acceptable levels.”
PDA, TR# 22, 2011 revision
Sterility & Sterility Assurance – 1
• Sterility is an absolute concept, and cannot be directly measured.
• Sterility assurance is easy to define, but no easier to quantify:
• In sterilization, it is estimated using a PNSU (or SAL) for each process. Actual sterilization process performance is much better than the minimum expectation of 1×10-6.
• In aseptic processing, process simulation demonstrates a maximum contamination rate from a point-in-time evaluation.
• Neither sterility nor sterility assurance can be accurately quantified!
Sterility & Sterility Assurance – 2
• There are no direct means to measure sterility assurance in aseptic processing.
• Sterility testing is severely limited by sample size and microbial recovery.
• Environmental monitoring suffers from inadequate recovery and limited sample size. In addition it’s not looking at the production materials.
• Process simulation demonstrates maximum contamination rates in an individual exercise.
• All are means for testing ‘sterility into the product’! They are unacceptable as ‘proof’ of anything, let alone something as important as patient safety.
Sterility Testing, Environmental Monitoring & Media Fills cannot assure Product Sterility
• Sterility testing is so severely limited statistically it could be renamed “the test for gross microbial contamination”.
• The sterility test was introduced in the 1930’s when lot sizes were smaller, processing was manual and contamination rates were likely much higher. Advances in process capability have made it more of a ceremonial regulatory exercise, than an effective means of process control.
- author: Mascherpa Vittorio