The story goes on like this. A group of people do not know how an elephant looks like; in fact, the animal is new to them. So, their eyes are masked and allowed to touch and say, how an elephant looks like? Their interpretation of elephant was funny based on the portion they touched. One said, it looks like a flexible trumpet touching the trunk, next one said as a solid sharp-edged stone touching the tusk, one said as a big fan blade touching the ears, the other one said it looks a pillar touching the legs and for one it was like a wall after touching its body and it looked a slender snake like creature after the feel of the tail.
Likewise, the dark subject in Pharma industry is the shelf-life assessment and the periodic replacement frequency of HEPA [High Efficiency Particulate Filters] filters in Grade-A manufacturing area and in case of tunnel sterilizer [Depyrogenation of glass vials used for the product filling] which remains critical. The periodic replacement frequency is kept arbitrarily based on the numbers rather than performing a complete risk assessment.
Criticality
The HEPA filter in the Grade A area and in the tunnel sterilizer is critical due to the exposure of the product / sterilization of the glass vial. The HEPA filters in the subsequent areas of processing i.e., Grade B, C and D are less critical in the order wise due to the lesser product exposure. So, during the regular HEPA filter integrity test, a failed HEPA is more critical in Grade A where the product gets exposed and less critical in Grade B, C and D areas where the there is no product is exposed. Risk to the product is more in Grade A. So periodic replacement frequency gains importance in Grade A HEPA filters of the critical area and in the tunnel sterilizer.
Zones in Tunnel sterilizer
Requirement of filter integrity testing
The HEPA filters of Grade A are integrity tested at a frequency of once in every 6 months as per the regulatory guidance requirements.
General replacement criteria
1.Failed integrity test of HEPA filter.
2.Airflow test failure.
3.Previously repaired filter.
HEPA filter Manufacturer’s recommendations
The manufacturer of HEPA filters in use recommend replacement based on either failed particle counts or when the resistance to airflow reaches double its clean pressure drop.
Guidance
There is no regulatory guidance referring to the periodic replacement of the HEPA filters. It is very difficult to fix a replacement frequency since the application varies and the environment, design, practice play an important role in the shelf life. Few Pharmaceutical manufacturers of dry powder observe frequent choking of the filter due to the fine particles that get generated. So, a uniform approach is completely ruled out.
Other references
The Department of Energy Technical Standard DOE HDK-1169-2003 [“Nuclear Air Cleaning Handbook”], Appendix C, recommends establishing a 5-year HEPA filter life for wet ventilation systems and 10-year HEPA filter life for dry ventilation systems.
Risk assessment
Instead of relying on guidances and references, truly a complete and a detailed risk assessment needs to be done for fixing the periodic replacement of the HEPA filters. The risk assessment should include the trend as applicable, address the product risk mitigation controls in place in case of filter integrity failure and taking into the account of the following parameters and not limited to:
1.Choosing the right and high quality HEPA filters. In case of tunnel sterilizer, the filters which can withstand the higher dry heat.
2.Storage of the HEPA filters.
3.HEPA filter integrity testing.
4.Continuous non-viable particle monitoring in the Grade A area.
5.Continuous viable particle monitoring in the Grade A area.
6.The contaminant level of the upstream air of the HEPA filter is controlled by prefilters in the supply air unit and make up air unit. The increased preventive maintenance regime for inspection and replacement of the pre filters.
7.Checking the differential pressure across the final HEPA filters-this becomes more important in the assessment of the shelf life of the HEPA filters as any drift would be a vital indicative parameter.
8.Robust viable environmental monitoring.
9.To avoid physical damage of the HEPA filters during the routine operations.
Note-The images given for representation in this blog are taken from Google Images. Many thanks for Google.