Filtration
1)
2)
1) Theory and Applications
Nearly all HVAC systems employ a filtration system. The level of filtration can vary widely. A bird
screen prevents the entry of animals and small objects, low efficiency roughing filters protect the heat
transfer elements and maintain a basic level of cleanliness in the system, and Ultra Low Penetration Air
filters (ULPA) can have efficiencies of 99.999% on 0.3 micron test particles. [1] The level of filtration
selected by the designer is related to the requirements of the process. These requirements are driven by
the need to maintain indoor air quality (IAQ), protect the occupants from airborne hazards and
contaminants, or maintain cleanliness in an occupied zone or production area. The requirements can be
set by the owner�s staff, a health care facilities infections control department, building codes, health care
licensing requirements, industry standards, or Environmental Protection Agency requirements for
effluents. For hazardous exhausts, scrubbers may also be employed in the exhaust stream. (Refer to
Chapter 13: Return Relief, and Exhaust and Chapter 14: Scrubbers, respectively, for a discussion of
hazardous exhaust and scrubbers.)
Most filters use a mechanical process that physically captures the contaminants by adhering to the filter
media. However, there are other technologies employed, including electrostatic attraction and air
washing. The air washing approach often yields other benefits in the HVAC process such as
humidification and cooling on the supply side, and neutralization of hazardous vapors in the scrubber on
the exhaust side. Some systems employ chemical filters that are treated with a catalyst designed to react
with the air stream and remove odors and other gaseous contaminants.
Due to the nature of their construction, some filters are considered flammable. As such, they may require
U.L. classification for application in certain systems depending on the requirements of the local code
authority and the insurance underwriter. In rare instances, fire suppression is required for large filter
banks.
In addition to having a major impact on IAQ, filters can have a significant impact on energy consumption
in the system due to the pressure drops associated with them. Both of these factors make commissioning
the filters and their related framing and monitoring systems critical for ensuring a system�s IAQ
performance and energy efficiency. Proper monitoring and change out procedures combined with creative
approaches to achieving the desired filtration efficiency at low pressure drop can significantly reduce the
operating cost and waste streams associated with the HVAC equipment.
2. Commissioning the Filtration System
The following tables outline the benefits and background information associated with testing filtration
systems. These tables are linked to related information throughout the Guide. For additional functional
testing information, refer to Functional Testing Basics for guidance related to all functional testing
activities, regardless of the component or system being tested.
2.1. Functional Testing Field Tips
Key Commissioning Test Requirements
All filters induce an air pressure drop that is related to the efficiency level of the filter and the design of
the filtration media. Because of this pressure drop, filters create an ongoing energy burden in the air
handling system. By working with the designer, owner, and operator, an informed commissioning
provider can help the operating staff find the right balance between the frequency of filter change-outs
(labor costs) and the filter pressure drop (energy cost). Appendix C.2 contains sample calculations for
the horsepower savings associated with reduced pressure drops as well as the operating cost savings
associated with these pressure drops over the life of the filters. Some filter manufacturers offer software
that can perform this calculation.
Commissioning of the filter pressure drop monitoring system ensures that the filter change-out cycles
are optimized and that excessive pressure drops are not introduced into the fan system.
Most filter functional testing has the following goals:
1 Verify that the filters and frames installation provides the intended level of filtration.
2 Verify that the monitoring and indication systems are in place to allow proper filter maintenance.
3 Verify that the installed system provides the required level of filtration by directly measuring the
performance based on particle counts, air patterns, and effluent analysis.
The commissioning provider can also be an advocate for requiring filtering during the temporary
operation of the air handling systems. See Section 11.4.6: Indoor Air Quality for more information.
The acceptance criteria associated with filter testing will vary with the rigor of the test. For pressure
drop indicator calibrations, the acceptance criteria will be related to the accuracy of the instrument being
calibrated as well as the accuracy of the test instrument. Generally, instruments rated for 5%- 10% of
full-scale accuracy will be sufficient as long as the full-scale pressure drop is matched to the dirty
pressure drop of the filter. An instrument rated for 0 to 1 inches w.c. �0.05 inches w.c. monitoring a
filter with a change-out requirement of 0.9 inches w.c. is adequate. An instrument rated for 1 to 10
inches w.c. �0.5 inches w.c. monitoring this filter would not be satisfactory.
The acceptance criteria for qualification-based testing is usually set by the owner's requirements, by
Health Care Facility Licensing standards, or by environmental or code compliance requirements for the
effluent.
Key Preparations and Cautions
Cautions
Inspection of filter banks in operating machinery requires the cautions normally associated with
working in closed proximity to rotating equipment, exposed wiring, steam injection systems associated
with humidity control systems, active control elements, and hot and cold surfaces. Of particular concern
is the need to pass through doors that will have significant opening and closing forces generated on
them by the static pressure differences between the unit's interior and exterior.
When working down stream of any filter bank, remember that you, the commissioning provider, are
basically a contaminant. The severity of contaminant you represent depends on the level of filtration
upstream of your location. You should not enter any portion of the air handling system that is down
stream of filters with dirty shoes. The further into the system you go, the cleaner your attire needs to be.
You may want to carry disposable booties or a clean pair of shoes for the clean sections of an air
handling system on an active construction site.
Proper attire is critical when working down stream of HEPA or ULPA filters. In many locations, the
owner will require full clean room or surgical garb. Even if the owner does not require this, it is
considered good practice in may situations. Given the high cost of the filters ($300 or more per module)
and the penalties associated with downstream contamination, take these simple steps to ensure
cleanliness. Similar considerations apply when changing out the filters, even when working in the
upstream compartment.
Test Conditions
Some filter commissioning functions are passive, relying primarily on visual inspection and procedural
controls to verify performance. Other functions require that the system be operating at its rated air flow
to allow clean filter pressure drop to be verified and filter to frame, frame to frame, and frame to casing
leakage to be checked. For qualification tests, the air handling and scrubbing equipment will need to be
fully functional.
Instrumentation Required
Instrumentation requirements will vary from test to test, but typically includes the following
instrumentation in addition to the standard tool kit listed in Functional Testing Basics:
1 Inclined manometers, Magnehelics., Shortridge Air Data Multimeters., and other instruments capable
of measuring and documenting low air static and velocity pressures.
2 A Borozine gun or smoke sticks to allow the airflow patterns near the filter holding frames to be
viewed and analyzed.
3 For situations where the areas downstream of a HEPA or ULPA filter must be entered, clean suits
and/or clean room gowns, gloves, boots, hair covers, and masks will be required.
4 For applications where filters or scrubbers must be qualified based on performance, special
equipment including particle generators, particle counters, and chemical analyzers will be required
depending on the test protocol. In many instances, retaining the services of a firm specializing in
this type of work will be desirable. These costs should be taken into consideration when establishing
the commissioning budget for systems with these requirements.
Time Required to Test
Visual inspections and pressure drop monitor calibrations and verifications typically take 15 to 30
minutes per filter bank unless the filter bank is unusually large.
Operating inspections for pressure drop and leakage can take 30-60 minutes depending on the rigor of
the test and the size of the filter bank. Qualification testing will take at least 4 to 8 hours for two people
per filter bank in an air handling unit application, with larger filter banks requiring more effort than
smaller banks.
Qualification testing of ceiling filters serving large areas such as clean rooms and surgeries can take
several days to several weeks for a crew of workers. The length of time required will be a function of
the size of the room, the rigor of the test, and the ceiling height. In addition, working in ultra clean
environments requires special dress and site-specific training which can add to the time required to
perform day-to-day tasks.
Filter Validation
Biopharmaceutical processes are validated processes to assure a reproducible product quality within set
specifications. Equally important is the validation of the filters used within the process, especially the
sterilizing grade filters, which often enough are used before filling or final processing of the drug product.
In its Guideline on General Principles of Process Validation (1985) and Guideline on Sterile Drug Products
Produced by Aseptic Processing (2004), the Food and Drug Administration (FDA) makes plain that the
validation of sterile processes is required by the manufacturers of sterile products. Similar demands can
be found in ISO 13408-2 (2003), EudraLex Vol 4 Annex 1 (2008) and PDA Technical Report #26 (2008),
the later being the most comprehensive in the description of filter validation needs.
Sterilizing grade filters are determined by the bacteria challenge tests. This test is performed under strict
parameters and a defined solution (ASTM F 838-05). Since the ASTM challenge test assesses the filter
only under standard conditions, regulatory authorities require also evidence, that the sterilizing grade
filter will create a sterile filtrate, no matter of the process, fluid or bioburden found. This means that
bacteria challenge tests have to be performed with the actual drug product, bioburden, if different or
known to be smaller than Brevundimonas diminuta and the process parameters. The reason for the
requirement of a product bacteria challenge test is threefold. First of all the influence of the product and
process parameters to the microorganism has to be tested. There may be cases of either shrinkage of
organisms due to a higher osmolarity of the product or prolonged processing times. Secondly the filters
compatibility with the product and the parameters has to be tested. The filter should not show any sign
of degradation due to the product filtered. Additionally rest assurance is required that the filter used will
withstand the process parameters, e.g. pressure pulses, if happening, should not influence the filters
performance. Thirdly, there are two separation mechanisms involved in liquid filtration; sieve retention
and retention by adsorptive sequestration. In sieve retention the smallest particle or organism size is
retained by the biggest pore within the membrane structure. The contaminant will be retained, no matter
of the process parameters. This is the ideal and best retention assurance. Retention by adsorptive
sequestration depends on the filtration conditions. Contaminants smaller than the actual pore size
penetrate such and may be captured by adsorptive attachment to the pore wall or by bridging effects.
This effect is enhanced using highly adsorptive filter materials, for example glass fiber or diatomaceous
earth as a prefilter or Polyamide as a membrane. Nevertheless certain liquid properties, e.g. pH or
surfactant content, can minimize the adsorptive effect, which could mean penetration of organisms.
Whether the fluid has such properties and will lower the effect of adsorptive sequestration and may
eventually cause penetration has to be evaluated in specific product bacteria challenge tests.
Before performing a product bacteria challenge test, it has to be assured that the liquid product does not
have any detrimental, bactericidal or bacteriostatic, effects on the challenge organisms. This is done
utilizing viability tests. The organism is inoculated into the product to be filtered at a certain bioburden
level. At specified times the log value of this bioburden is tested. If the bioburden is reduced due to the
fluid properties different bacteria challenge test mode become applicable. If the reduction is a slow
process the challenge test can be performed with a higher bioburden level, bearing in mind that the
challenge level has to reach 107 per square centimeter filtration area at the end of the processing time. If
the mortality rate is too high the toxic substance is either removed or product properties are changed,
always having the viability results at hand to explain such changes. This challenge fluid is called a
placebo. Another methodology would circulate the fluid product through the filter at the specific process
parameters as long as the actual processing time would be. Afterwards the filter is flushed extensively
with water and the challenge test, as described in ASTM F838-05, performed. Nevertheless such
challenge test procedure would be more or less a filter compatibility test.
Besides the product bacteria challenge test, tests of extractable/leachable substances and/or particulate
releases have to be performed. Extractable measurements and the resulting data are available from filter
manufacturers for the individual filters. Nevertheless depending on the process conditions and the
solvents used, product and process specific extractable tests have to be performed. These tests are
commonly done only with the solvent used with the drug product, but not with the drug ingredients
themselves, because the drug product usually covers any extractables profile during measurement. Such
tests are conducted by the validation services of the filter manufacturers using sophisticated separation
and detection methodologies, as GC-MS, FTIR and RP-HPLC. These methodologies are required due to
the fact that the individual components possibly released from the filter have to be identified and
quantified. Elaborated studies, performed by filter manufacturers showed that there is neither a release
of high quantities of extractables (the range is ppb to max. ppm per 10" element) nor have been toxic
substancesbeenfound.
Particulates are critical in sterile filtration, specifically of injectables. The USP (United States
Pharmacopeia) and BP (British Pharmacopeia) quote specific limits of particulate level contaminations for
defined particle sizes. These limits have to be met. Filters are routinely tested, evaluating the filtrate with
laser particle counters. Such tests are also performed with the actual product under process conditions to
proof that the product, but especially process conditions do not result in an increased level of particulates
withinthefiltrate.
Additionally with certain products loss of yield or product ingredients due to adsorption shall be
determined. For example preservatives, like benzalkoniumchloride or chlorhexadine, can be adsorbed by
specific filter membrane polymers. Such membranes need to be saturated with the preservative to avoid
preservative loss within the actual product. This preservative loss, e.g. in contact lense solutions or nasal
sprays, can be detrimental due to long-term use of such solutions. Similarly problematic would be the
adsorption of required proteins within a biological solution. To optimize the yield of such proteins within
an application, small scale adsorption trials are recommended to find the optimal membrane material and
filterconstruction.
Other routine validation or qualification tests would be flow rate and throughput determination, thermal
and mechanical stability for example during in-line steam sterilization or any pulsations
Filter Validation Objectives
To prove the suitability of the filter for a process, the
following questions must be answered:
Does the product affect the filter?
Does the filter affect the product?
Does the product affect microbial retention by
the filter?
To achieve these objectives, Pall uses a Parametric
Approach to ensure that filter validation is
performed taking into account all critical product
attributes and process parameters. This is in line
with regulatory expectations and the
recommendations of PDA Technical Report 26.
