Sterilizing filtration is a high-risk sterilization method, and quality management should begin with controlling risks at the source.
Source risk control for sterilizing filters imposes quality requirements on the manufacturer.
Filter manufacturers should typically qualify the filters according to appropriate pharmacopoeia methods and make the results public to ensure their suitability for pharmaceutical production. This qualification documentation can be part of the user's process validation but does not replace it. PDA Technical Report No. 26 details the corresponding qualification and validation work that manufacturers and users should perform on filter membranes and filter devices, respectively.
Qualification and Validation Recommendations
L = Batch Release Criteria
Q = Qualification
V = Process-Specific Validation
V* = Can be tested using membrane discs or filters
E = Evaluate if testing is necessary
Source: Translated from PDA Technical Report No. 26
Bacterial Retention Test
After the manufacturer performs qualification in saline lactose broth, water, or other appropriate liquids, the filter user should re-confirm it under their specific process conditions. This is because the former uses standard solutions and conditions, which cannot simulate actual process conditions.
Chemical Compatibility
The manufacturer can qualify the chemical compatibility between the filter and the product, but the user must confirm the compatibility of the process fluid and the filter under specific operating conditions. This is typically confirmed by methods such as integrity testing, flow rate, and visual inspection.
Extractables
The manufacturer tests using model solvents and specific experimental conditions. The user can also perform additional confirmation based on the specific product and process.
Potential Leachables
Typically related to the specific product and process conditions, the user should qualify and evaluate them to ensure they do not pose a hazard to the product.
Safety Tests (e.g., Biological Reactivity)
Usually completed by the manufacturer, as they test the inherent safety of the filter material itself, which is independent of the usage process. Therefore, the user does not need to repeat the confirmation.
Sterilization
The manufacturer will qualify the filter's sterilization tolerance and conditions, which may not represent actual process conditions. Therefore, the user should validate the sterilization method under specific process conditions.
Particulate matter, fiber shedding, oxidants, TOC, conductivity, and flow rate are typically qualified by the manufacturer, while the user should evaluate whether additional testing is needed based on specific process conditions.
If a validation or test item is related to specific process conditions, the user should evaluate or re-validate it.