Demystifying ISO-1464420th Nov 2016

Cleanroom concepts

ISO 14644/2015 what are the changes in ISO 14644 -2015.?What would be the impact on the industry?How to correlate with WHO TRS 961 annex 6

-2011 and Federal 209 E guidelines.What are the other nomenclatures prevalent

in the industry with respect to area classification.

FAQsCase study.Conclusion.

Classification of the latest ISO guidelines.S

no:Guideline Subject

01 ISO-14644-1 Air cleanliness by particle concentration.

02 ISO-14644-9 Surface cleanliness by particle concentration.

03 ISO-14644-8 Air cleanliness by chemical concentration.

04 ISO-14644-10 Surface cleanliness by chemical concentration.

05 ISO-14644-12 Air cleanliness by nano particle concentration. (less than 0.1 Micron).

06 ISO-14698-9 Air and surface cleanliness by viable counts.

Difference between Federal 209E & ISO.?Basic difference is with the terminology and the

specifications. Fed-209E guideline and ISO both the guidelines use the enumeration of the 0.5 micron particles but the basic difference between 209 E and ISO is the sampling requirements. The area sampled as per FED 209 guidelines is 1 cubic feet whereas as per the ISO guidelines the area a 1 cubic meter. S

no:FED 209 E guideline ISO14644

1 Class 100,000 ISO class 82 Class 10,000 ISO class 73 Class 1000 ISO class 64 Class 100 ISO class 5

How small is 1 micron?

One micron is one millionth of a meter and 1/25000th of

an inch.

Focus on ISO-14644-1The area of interest is ISO 14644 guideline as

it covers particle counts and has been changed recently.

So what are the changes??1) Name changed from classification of air

cleanliness to classification of air cleanliness by particle concentration.

2) The number of sampling locations are now fixed for area less than 1000 square meters. For area greater than 1000 square meters the following formula would be applicable.

Number of sampling points required as per the area.

Area in meter square

Minimum Sampling

locations to be tested.

Area in meter square

Minimum Sampling

locations to be tested.

2 1 52 104 2 56 116 3 64 128 4 68 1310 5 72 1424 6 76 1528 7 104 1632 8 108 1736 9 116 18

Number of sampling points required as per the area.

Area in meter square

Minimum Sampling

locations to be tested.

148 19156 20192 21232 22276 23352 24436 25500 261000 27

Focus on ISO-14644-1Formula:N= 27x (Area)/1000 where “N” is the number

of sampling points.Air particulate counts using LSAPC techniques at

rest conditions.WHO Grade ISO Class 0.5 µm 5.0 µm

A 5 3,520 29 Abolished

B 6 35,200 293

C 7 352,000 2,930

D 8 3,520,000 29,300

Focus on ISO-14644-1Air particulate counts using LSAPC techniques

in operation conditions.

The major impact will be on the documentation changes and the SOPs for area qualification should be revised.

WHO Grade ISO Class 0.5 µm 5.0 µmA 5 3,520 29

AbolishedB 6 3,52,000 2900C 7 3,520,000 29,000D 8 Not Defined Not Defined

Classification using viable counts.

Ref: WHO-TRS-961-Annexure 6 & TRS 902. can be used as a reference for the viable microbial counts. Instead of the ISO 14698-9 guideline which is more generalized.

Grade Air sample (CFU/m

3)

Settle plates (diameter 90 mm) (CFU/4

hrs )

Contact plates

(diameter 55 mm)

(CFU/plate)

Glove print

(5 fingers)(CFU/glove)

A <1 <1 <1 <1B 10 5 5 5C 100 50 25 -D 200 100 50 -

Other Noticeable Changes :There is no need to calculate the UCL for the

observations of all measuring points each individual point has to meet the specifications.

The length of the tubing used in particular counter should be less than 1 meter.

The classification number, the air sample volumes, measuring times as well as the cancellation criterion is not changed and remains the same to the version ISO14644-1:1999.

FAQsHow much should be the sampling volume

??The sampling volume for grade A is as per

the exact volume of air contained in one cubic meter of space. That is equivalent to 1000 ltrs, for other grades 20 to 30 ltr can be sampled from each location and then extrapolated to find the exact number of particles in one cubic meter.

Frequency of tests: Air Particulate Count.Classification Maximum time

intervalTest method

≤ ISO class 5

6 Months Annex B in ISO 14644-1:1999

> ISO class 5

12 Months Annex B in ISO 14644-1:1999

Note: Particle count tests will normally be performed in the operational state, but may also be performed in the at rest state in accordance with the designated ISO classification.

Frequency of tests:Classification Maximum

time intervalTest method

Airflow volume or airflow velocity

12 months ISO 14644-3:-clause B.4

Air pressure difference

12 months ISO 14644-3:-clause B.4

The above mentioned test s and the frequency is for all the classes and measured at rest and in operation conditions

Frequency of tests:

Test parameter

Classification Maximum time interval

Test method

Installed filter leakage

All Classes 12 Months ISO-14644/WHO

Airflow visualization

All Classes 12 Months ISO-14644/WHO

Recovery All Classes 12 Months ISO-14644/WHO

Containment Leakage

All Classes 12 Months ISO-14644/WHO

Filter Integrity All Classes 6 Months ISO-14644/WHO

Instruments and techniques used in carrying out the various tests in the qualification and requalification of the area required for the manufacturing of pharmaceuticals for human and veterinary use.

Anemometer

HEPA Filter

DO’s & Don'ts The use of titanium tetra-chloride for air flow

pattern has been banned and instead dry ice i.e. solid carbon dioxide is being used as an alternate.

The DOP test has been replaced with PAO- poly alpha olefins.

Formaldehyde has been banned from use as a fumigating agent. The material of choice now is VIROSIL & Minncare solution. It’s a combination of hydrogen peroxide and acetic acid.

Case study: If a site has a new facility 1500 square meters how many sampling points would be required?

Conclusion: The new guideline has been simplified and all other remaining the same as the previous 1999 guideline.

Questions ?? & Suggestions are welcome on my e mail address manojfromumbai@gmail.com.