How to Keep a HEPA Happy

by the HVAC COP

Recently there has been a bit of discussion on the COP regarding HEPA filters. The
Engineering Roundtable also did a bit of informal benchmarking around filters recently,
so we thought it may be a good opportunity to summarize some of these discussions –
adding some comments – always hard to resist!

Test Frequency
There are no specific GMP regulations (US or European) on the test frequency for HEPA
filters, but the FDA “Guidance for Industry Sterile Drug Products Produced by Aseptic
Processing – Current Good manufacturing Practice” D 2 suggests a frequency of 6
months for the Aseptic filling room. CEN 14644 part 2 Annex A suggests that the
frequency of leak testing should not exceed 24 months, provided there is routine
monitoring of the system performance.

Industry practice seems to be developing into:

6 monthly for grade A & B areas
Annually for other areas

Test Methods
The use of a PAO test seems almost universal, although there are some potential
benefits to using the ambient particle counter based approach – for example no oil
residue left on the filters potentially prolonging their life. A full face scan is the most
commonly adopted test method of the options presented in ISO 14644-3.

When to Change Filters

Filter manufacturers do not state a usable life for their products, recommending a
change based on the pressure drop. This is the approach generally adopted, with the
proviso that in the event of a repair, the filter will be changed once the repair length
exceeds certain dimensions – IEST –RP CC006.2 Testing Cleanrooms states that
“HEPA or ULPA filters may be repaired providing;
1) the size of the repair or repairs does not block or restrict more than 3% of the
filters face area (not including the frame) and
2) The lesser dimension of any repair does not exceed 3.8 cm (1.5”) or as otherwise
agreed upon by the buyer and seller.”
The benchmarking survey showed an interesting result – where terminal HEPA filters
are preceded by a main HEPA as a pre-filter, not only do they last longer, the failure
rates appear to be lower – there’s an interesting project for someone to investigate!

Stage 1 and Stage 2 non-HEPA Air Filters

Stage 1 and Stage 2 non-HEPA air filters can keep the HEPA filters cleaner and more
operational over large time periods. Especially, if installed to prevent microbial
contamination and growth through patterns in the HEPAs. Prevention of microbial
contamination using anti-microbials impregnated in Stage 1 and Stage 2 air filters before
the HEPAs can help the lifecycle and longevity of the HEPAs. Additionally, Stage 1 and
Stage 2 air filtration media, when chosen correctly, can eliminate 1-5 micron and, in
many cases, submicron particulates enhancing the longevity of the downstream HEPA
filtration.
What to Do if a Test Fails….
The actions taken in the event of a test failure will be dictated by the site Quality unit,
and to a certain extent depend on the location of the filter; but would typically include a
review of the environmental data for the area since the last satisfactory leak test. The
engineer can help by providing technical data for Quality to consider – for example, if
there is a HEPA pre-filter (AHU mounted for example), then the effect in terms of air
quality of a leak could be relatively minor – consider the air quality after the prefilter, and
the damaged area, versus the area of all the filter material. Even without a HEPA
prefilter, the room counts may not have changed significantly.

HEPA Repairs
Most people have a common approach to filter repair – though personal past experience
has shown that some locations are more likely to require repairs that others – probably
due to the location being near a door, so the media may have been flexed/stressed more
often. A repaired filter would not last as long as the original – the theory developed was
that the greater weight of the repair created an area of stress concentration on the
media. There are some companies in Europe who do not repair filters if they are used in
the aseptic filling area.

Gel Seals
Gel seals solve a lot of edge seal leakage problems but may have their own problems as
well. When they were first used certain gels degraded after a few filter tests, but in
general these problems appear to have been solved, though this is something to be
aware of.

High Temperature HEPA filters

A whole new topic, these filters are used in depyrogenation ovens and tunnels and have
yet another set of problems. These online discussions continue, so we’ll summarize
them in a future E-Letter.

For more information, or to get an answer for a specific problem, take a look at the ISPE
HVAC COP website.

Thanks to Thomas Spearman of Eli Lilly for the benchmarking data.