SHORT GUIDANCE ON AREA QUALIFICATION

BY

NIKHIL VERMA
BACHELOR OF PHARMACY

MASTER OF PHARMACY

(PHARMACEUTICS)

Prepared By : Nikhil Verma

AREA QUALIFICATION: Area qualification is define as an action of providing
that the area are properly maintained, non-contaminated , work correctly and
actually leads to the expected results.

Sterile area qualification has the following test:

✓ Air supply capacity

✓ Air velocity
✓ Air changes per hour
✓ Air flow pattern
✓ Filter Integrity
✓ Pressure Test
✓ Particle count
✓ Temperature
✓ Relative humidity(based on dosage form)
✓ Differential Pressure
✓ Microbial count
✓ Recovery Test
✓ Noise level
✓ Vibration Test
✓ Noise level

Prepared By : Nikhil Verma

1.Air supply capacity: The aim of this test to demonsterate that the
air system is balanced and capable of delivering sufficient air
volume to maintain required air changes in the defined area.
The air capacity can be determine by the following procedure:
• Measure airflow in supply and returned duct
• Air volume to meet the designed required

2.Air velocity/Uniformity: The aim of this test to demonstrate that

the air system is balanced and capable of delivering sufficient air
volumes to maintained a minimum cross section velocity under
HEPA terminal filter modules.

This test also meant to verify air velocities before the air encounters
an obstruction.

The air velocity /uniformity will vbe demonstrated by the following

procedure of:

• Measure air velocity at the filter face using a caliberated

anemometer.
• Measure at numerous sites to provide one measurement for
every 0.37 meter square filter area.
• For LAF air flows uniformity to be 0.45 m/sec +- 20%
• The airflow should be laminar.

3.Air Changes per hour:

Cleanroom ISO Class Required air changes per hour
class
100 ISO 5 240-480
(Grade A)
1000 ISO 6 150-240
(Grade B)
10000 ISO 7 60-90

Prepared By : Nikhil Verma

 (Grade 7)
100000 ISO 8 5-48
(Grade D)

More air changes per hour are required to maintain the area where
dust is generated as in granulation and tablet compression areas.In
these areas dust is to be removed in short period , hence more air
changes per hour required.

4. Air Flow Pattern: (Laminar )

To determine the airflow interaction with the machines and

equipments, in the critical areas protected by unidirectional flow
the clean air system in the clean area.

This test can be done by:

• Visualise the air pattern at various points in the room using

smock generate or Titanium Tetrachloride sticks.
• Smock should flow from more clean area to less clean area
quickly and smoothly.
5. Hepa filter integrity test:

This test is done at rest phase by using PAO(Poly alpha Olefin)

aerosols into supply duct to HEPA filter.
Acceptance Limit: Less than 0.01%

6.Pressurisation Test:

Airlock or buffer zones are used to separate production areas from

adjacent rooms or corridors/staging area , non classified areas.

Prepared By : Nikhil Verma

 7. Unidirectional Airflow: The Unidirectional airflow will be
demonstrated by the following test:
• Operate the HVAC system of the sterile area and release
smoke into the unidirectional air stream at selected sites
• Measure the deviation of smoke stream from vertical or
horizontal over 90 cm from the flow path.
• To demonstrate that deviation in parallelism airflow shall not
greater than 14 degree.
8. Particle count:
Maximum particle concenterations(per meter cube)

At rest In operation

Grades More than or More than or More than or More than or

equal to 0.5 equal to 5.0 equal to 0.5 equal to 5.0
micrometer micrometer micrometer micrometer

A 3520 20 3520 20

B 3520 29 352000 2900

C 352000 2900 3520000 29000

D 3520000 29000 nA nA

9. Recovery Test: To determine the capabilities of the system to

recover from internally generated from contamination within
reasonable elapsed time period.

10.Microbiological count:
Grade Air sample Settle plate contact plate Glove print 5 fingers
cfu/m3(it (diameter 90 (diameter 55 mm) cfu/gloves
sucks 1000 mm) cfu/4

Prepared By : Nikhil Verma

 liter) hours cfu/plate

A <1 <1 <1 <1

B 10 5 5 5

C 100 50 25 -

D 200 100 50 -

Percentage for media preparation for settle plate : 4 % i.e. 40 gram media in 1000 gram
solution.

11. Noise level: HVAC system has designed not to generate more
than 70 dBa noises in critical areas during its normal operation.

Noise level will be check by using caliberated Octave Band analyser

or any other similar equipment and measure the noise level at
defined locations to confirm that the noise level is within limits

12.Viberations: Viberation level generate by HVAC system will be

checked by using caliberated accelerometer or any other similar
equipment.

Prepared By : Nikhil Verma