ISO 14644 Cleanroom Validating to ISO Class 8

I recently had a customer ask us some questions about certifying and testing two cleanzone tents in which he wants to validate to ISO 14644 class 8. As he did not have prior experience validating to ISO 14644 standards, he purchased the ISO 14644-1 and ISO 14644-2 books from the IEST. As with most people the first time through, he has struggled to understand exactly what he needs to do in order to validate. Below is a question and answer session that transpired between the customer, myself and Jim Akey from LWS.

Q.Based on the area (in meters) of each room (15’ X 18’), the minimum sample point locations is 5 per room. Using a DPC to determine room particle counts, a sample volume is needed. Based on ISO 14644-1:1999(E) Annex D, and an ISO Class 8 requirement, Cn is very large, and Vs is small (less then 2 liters). Do I just take 28 liters over 1 minute as a standard? Why? If not, how do I determine the sample volume?

A.This is a two part answer:

1. Sample Locations – 14644 states that to determine the minimum number of Sample Locations (B.4.1.1) you take the square root of the Area (in m2). If the room is 15′ x 18′, this equates to 25.08382 square meters. The Square Root of 25.08382 (room area) = 5.0083749 (sample locations).

ISO 14644 states that you must round up, so 5.0083749 = 6 Locations.

2. Sample Volume per Location – Vs = 20/Cn,m x 1000 (ISO 14644 B.4.2.1)
Vs = “is the minimum single sample volume per location expressed in liters (except see B.4.2.2)”
Cn,m = “is the class limit (number of particles per cubic meter) for the largest considered particle size specified for the relevant class”
20 = “is the defined number of particles that could be counted if the particle concentration were at class limit”
For the above room and ISO class (I am using 0.5 microns and greater) the formula would be:
Cn,m = 3,520,000 (number of particles at 0.5 micron and greater that are allowed per cubic meter – this is determined by the chart in the standard)
20 / 3,520,000 = 0.0000056
0.0000056 x 1,000 = 0.0056
0.0056 liters would be the minimum sample volume, except that B.4.2.2 states “The volume sampled at each location shall be at least 2 liters, with a minimum sampling time at each location of 1 min.”
Since 0.0056 liters is less than the 2 liters required in B.4.2.2 – the minimum sample volume at each location would be 2 liters.

Q.How is the number of particles per cubic meter calculated (ISO 14644-1:1999(E) Annex D.1.7)? I need the number of particles per cubic meter to calculate the 95% upper confidence limits since the number of sampling locations is less then 10.

A.The easiest way to see if you are within classification is to compare the particle counts to the chart (Table 1) in the ISO standard. There is a formula to determine this – Section 3.2 of ISO 14644-1

ISO 14644-1 Cleanroom Standards

Particle Size
Class 0.1 µm 0.2 µm 0.3 µm 0.5 µm 1 µm 5 µm
ISO 1 10 2
ISO 2 100 24 10 4
ISO 3 1,000 237 102 35 8
ISO 4 10,000 2,370 1,020 352 83
ISO 5 100,000 23,700 10,200 3,520 832 29
ISO 6 1,000,000 237,000 102,000 35,200 8,320 293
ISO 7 352,000 83,200 2,930
ISO 8 3,520,000 832,000 29,300
ISO 9 35,200,000 8,320,000 293,000

Notes: Number of particles per cubic meter (m 3 )

Q.I would like to assess the air change rate – which I think is “Airflow Volume’ or perhaps ‘Airflow Velocity’? According to ISO 14644-3:2000(E), I think I would reference Annex B.4 Airflow test? What minimum air change rate should I use as the acceptance criteria? I have heard 6 to 20/hour, but have not seen the number in print any where. Is there a formula? Can you provide me a reference? Is Airflow Velocity the same as Airflow Volume?

A.Air Velocity is not addressed in sections one or two. I would suggest you purchase the ISO 14644-3 standard which specifies test methods for characterizing the performance of cleanrooms and clean zones. If you are only interested in calculating air exchanges per hour, the formula is very simple. Calculate total volume of air (cubic feet) by multiplying length, width and height of the room. The resulting number is your volume of air in cubic feet. Divide your cubic footage by 60, the resulting number is the amount of cubic feet per minute required for one complete air exchange. Divide this number into the amount of CFM your air handler is delivering, the resulting number is your air exchanges per hour!

L X W X H = Cf
Cf/60 = X
CFM/X = air exchanges per hour
Q.I am also proposing to perform:

a. A filter leakage test to verify filter integrity;
b. Airflow direction test and visualization (in the operational state only) to verify the required airflow pattern; and
c. Containment leakage to verify non-cross contamination.

Are all three of these tests applicable to the ‘clean zones’ we have, and is this overkill for ISO Class 8?

A. The more testing done, the better. When Validating a clean room all of the tests mentioned should be performed. However, once the room has been validated, doing these tests on a weekly basis is overkill. The standard tells you how often these tests need to be performed.

I hope that if anyone else has these types of issues, this blog will help provide some direction. If you have other questions or comments about validating and testing to ISO 14644 standards, we are available to answer your questions. There are 3 ways you can get assistance:

1. Click on the comments button below and ask your question(s)
2. email info@particlecounters.org
3. call toll free 1-800-531-4889

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25 Comments »

  1. Jeff Bush Said,

    June 15, 2006 @ 6:57 pm

    When calculating sample volume per location, as demonstrated above, why did you choose the smallest particle size listed in the table (0.5um) for a class 8 cleanroom. The ISO standard as you quoted it above says to use the “largest considered particle size specified for the relevant class”?

    Shouldn’t you have used 5um which would give a sampling volume of 0.68 liters?

    This wouldn’t change the sampling volume pf 2 liters for the person above but it would for my company which is trying to validate a ISO Class 6 cleanroom.

  2. Jim Akey Said,

    June 16, 2006 @ 11:20 am

    Jeff:

    Sorry for the confusion – I was using the 0.5 micron size as an example. When validating a clean room with a 6-channel particle counter, you will need to determine the minimum sampling volume for each channel size (Lighthouse Particle Counters have the clean room standards built in to assist in these calculations). As a general rule, the larger the particle size, the more air (volume) you will have to sample. This is especially true in the lower (cleaner) classifications.

    Once these minimum sample volumes have been determined and recorded, we are ready to proceed. For validation purposes, it is best to “test” for as many particle sizes as possible. For ISO Class 8 – sample for 0.5, 1.0, and 5.0 microns. Remember, you will need to sample for the largest “minimum sample volume” as figured using the equasion above. If you do not meet the largest sample volume, you will fail the test!!

    You mentioned ISO Class 6 – for this classification, I would sample for the 0.3, 0.5, 1.0, and 5.0 microns. Again, make sure you meet the specified minimum sample volumes for each particle size.

    Once the clean room has been validated – you will be performing regularly scheduled “spot checks” to ensure that you are still within classification. For this, you can choose one or two particle sizes to check for. generally, most people check the 0.5 and / or 5.0 micron channels.

  3. Barry Kitchener Said,

    June 16, 2006 @ 4:48 pm

    First, confirm that you are referring to an area certification, not validation. typically validation refers to the pharmaceutical industry and is a procedure that is set by the company and then strictly adherred to.

    When certfying a clean area there are a set number of samples and locations that must be taken based upon the intended room classification. Classifications are either ISO 14644-1 or Fed Std 209E. Depending on the class, size of room and room condition(as built, at rest, at operation) will determine the amount of air that must be sampled. Lighthouse Solair particle counters have these report calculations built-in and make it simple for the operator to make the correct decisions.

  4. Gerry Guardiola Said,

    April 30, 2007 @ 6:55 pm

    Hi :
    Is there any written restriction about the use of powder paint in the ISO clean room standards? let’s say Class 8. We use hardcoat anodizing in the covers & bases of our industrial RF catheter welding equipment, but we can easily damage the surface (dings, dents) when the product is silkscreend by our suppliers, assembled in the production lines or even when it’s tested in the quality areas. Is it specifically called out as a contaminant source or it’s a hoax?
    Gerry

  5. alberto michelini Said,

    May 6, 2007 @ 3:41 am

    B.4.2.2
    It is easy to found a number of sample locations, I use the square root of the area. My question is about a point B.4.2.2
    If I use a particle counters equipment that aspire 0.1 cfm = 2.83 liters/min my sample for locations should be 1 minute. But if I use a particle counters equipments that aspire 1 cfm = 28.3 liters/min my sample can to be less 1 min.(20 sec for exemple) ?
    Thanks for your attention.

  6. Alex Zurawlev Said,

    June 1, 2007 @ 9:31 am

    I need to test a Clean Room for pressurization.
    I believe ISO 14644-2 states this but of course I dont have a copy.’
    I was just wondering the best method ie equipment used to dothis.
    Thanks for your help
    Alex

  7. v jithendra kumar Said,

    June 29, 2007 @ 1:37 am

    sir i want information about clean room validation

  8. Sheikh Rahman Said,

    July 26, 2007 @ 7:09 am

    Hi,
    How do I know about the celanroom class required for different pharmaceutical practices?
    For example, which class to be maintained for tablet coating, syrup filling, cephalosporin production, injectable production, sterile production, sterile wash room, quarentine etc?
    Thanks
    Asif

  9. jigendra Said,

    July 27, 2007 @ 3:07 am

    We are validation class D = Class 8 (ISO) for our oral solid dosage manufacturing facility

    During qualification for Microbial quality sampled quantity of Air is 1000 lit (equal to one cubic meter of Air) from each sampling point. It takes 10 minutes for sampling activity.

    Pl. advise whether this is acceptable from Regulatory point of view.

    Jigendra
    QA Professional.

  10. ksvrrao Said,

    October 10, 2007 @ 7:08 am

    I would like to qualify a clean room at ISO5. if I choose 0.5 and 5.0 micron size particles as reference particle sizes for qualifcation, what should be the sample volume for 5 micron particles? i think as per ISO, we have to sample greater than 28.3 liters in one minute for 5 micron particles. I have a particle counter that can sample at a flow rate of 1 CFM. Can we really sample 1CFM and yet meet the ISO Classification for 5.0 micron particles? The limit for 5 micron in this case would be ’0′

  11. kashif Said,

    October 25, 2007 @ 7:18 am

    Hi,

    Could you please help us to know, that what should be the average particle counts in any operation theater? If particle counts range between 80000 – 100000 with >3 micron per litre air,in an Operation theater how would you read that.

    Best Regards

    Kashif Saleem

  12. Tony Wood Said,

    November 1, 2007 @ 11:59 am

    You discribed how to calculate the air exchange rate that the equipment could perform given dimensions for the clean room area, but didn not mention the minimum rate of exchange for any of the classes. Does anyone know where this info is? Cheers all.

  13. c.k.chang Said,

    February 24, 2008 @ 11:35 pm

    Hi,
    Just to check with you, how to calculate the airflow needed for a room that requires positive pressure by 15Pa relative to corridor? Thank you. The room dimension is 25 x 20 x 10 ft (H). It is a laboratory.

  14. D.Poon Said,

    March 10, 2008 @ 7:00 pm

    If I were to validate a clean room to ISO class 7 and a gowning room to ISO class 8, do I require ACH for both rooms or just for the clean room? There is differential pressure monitoring with positve pressure from clean room to gowning room to hallway.

  15. A. L.V.PRASAD Said,

    March 30, 2008 @ 11:34 am

    what is difference between hepa filter integrity and efficiency?

  16. Dave Said,

    April 11, 2008 @ 9:25 am

    Hi Prasad,

    The short answer is that integrity refers to how well the filter is sealed for leaks, and efficiency refers to how well it filters particle concentrations at a certain size micron. To elaborate… A true medical grade HEPA is rated at 99.97% efficiency for particles that are 0.3 µm and above. The integrity of the filter will determine how much of the incoming air stream will pass through the filtration. A filter that is poorly constructed may have leaks which allow airflow to pass through the leaks in the filter, rather than go through the filtration element, as airflow always tends to take the least torturous path. Therefore, if the filter has poor integrity, the overall efficiency of the system will be lower, as the poorly constructed filter allows more contaminated air to pass through it.

    Another issue deals with the construction of the air cleaners themselves…manufacturers who cut corners when designing the air cleaner are more prone to leave gaps around the filter frame, allowing for airflow to seep around the filter altogether. A well constructed unit will provide an air-tight seal between the filter frame and the filter track, usually with a gasket material such as felt, ensuring that 100% of the air moving through the air cleaner is forced through the filter media.

    One way a HEPA filter manufacturer can prevent leaks in the filter media is to have the filter material warm rolled…this prevents the filter media from cracking as it’s pleated and compressed into the filter frame. A cheaply made filter may be folded, like an accordion, to compress it enough to fit the frame – this method makes the filter more prone to cracking.

    I hope this answers your questions. Please let me know if you have any other questions, or need additional information.

  17. Rod Said,

    April 11, 2008 @ 10:55 am

    Hello Kumar,

    To answer your question, there is a big difference between validation and certification. Certification information can be found in the ISO 14644-1 manual, available from IEST.org–Proving continued compliance, is a completely different procedure, which is outlined in the ISO 14644-2, also available through the IEST. Validation usually refers to a procedure that outlines the functions and features of a particle counter.

    As far as particle counters go… For “certifying” a cleanroom you want to use a 1CFM particle counter. The room will need to be tested in all three states (as built, at rest and at operation). Sampling points are determined by the square root of the square meters of the room. Particle counters such as the Lighthouse 3100+ have built in “cleanroom calculators” that can calculate your minimum sample volume requirements as well as the number of sampling points and generate a pass/fail report with a printed receipt via the built-in thermal printer. For proving continued compliance (ISO 14644-2), verifying, spot checking or, what some people refer to as “validating” you can use a 0.1 cfm handheld particle counter to perform spot checks. Most of my customers use handhelds to test any area critical to the process, at frequent intervals.

    The wording “validating” actually refers to FDA validation documents, which is the process that FDA regulated pharmaceutical companies have to complete. The validation documents basically list and verify all of the functions and features of a particle counter as well as particle counter software. We have validation manuals available for all Lighthouse products.

    An example of the terminology as used in the U.S.:

    You certify a cleanroom. You verify that a cleanroom is still within certification specifications. You validate a particle counter.

    I hope this answers your questions and points you in the right direction. If you have any questions, send me an email or give me a call.

  18. Dan Milholland Said,

    April 14, 2008 @ 11:01 am

    Jigendra ,

    Class D Air is defined in Volume 4, EU Guidelines to GMP, Annex 1. Section 19 “Recommended limits for microbiological monitoring of clean spaces during operation” states Class D should average no more than 200 cfu/cubic meter if using an air sampler and 100 cfu/4 hours on 90 mm diameter settling plates.” If the sample rate of your air sampler is 100 lpm, then you would have sampled 1,000 l or 1 cu meter in 10 minutes. That should meet or exceed the regulatory requirements.

  19. gbelezos Said,

    May 19, 2008 @ 3:20 pm

    Hello. I have been tasked to re-implement air particle checks in our class 1, class 10, and class 10000 cleanrooms. I have climet 400 particle counter which seems to work well. What would you recommend for monitoring the fab, in terms of settings (1 or .1 cubic feet, .3 or .5 um, #readings at each point) and frequency. I am new to this and have no guidance at my small company. Thanks.

  20. formula for air exchanges per hour Said,

    June 11, 2008 @ 11:21 pm

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  21. qin Said,

    January 20, 2009 @ 1:00 am

    Hi,
    May I know how to calculate the CFU per cubic meter from the number of colony units formed on the agar plate?

    Thanks.

  22. tricon Said,

    March 30, 2009 @ 9:38 am

    Hi,
    I am looking to scource information on ISO 14644 class 8 standards with particular emphasis on how this standard impacts on a machine builder. Is there a particular website or literature that may be of use to me. One of the criteria required for the machine is that it will be installed in – “Operating environment: ISO 14644 Class 8″

    Thank’s

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