Modular OT Validation
Modular OT Validation
A. Name of the Tests
7.1 Air Velocity and Number of Air Changes Measurement Test.
7.2 Filter Leak Test.
7.3 Non-Viable Particle Monitoring (At rest)
7.4 Clean Room Recovery Test.
7.5 Air Flow Visualization Study.
7.6 Temperature and RH Mapping.
7.7 Differential Pressure Monitoring.
7.8 Viable Particle (Microbial) Monitoring (Static Condition)
| Sr. No. | Test Name | Scheduled Rational | Revalidation frequency |
| 1. | Air Velocity and Number of Air Changes Measurement Test | 1 Time | Annually ±30 days |
| 2. | Filter Leak Test | 1 Time | Annually ±30 days |
| 3. | Non-Viable Particle Monitoring (At rest) | 1 Days | Annually ±30 days |
| 4. | Clean Room Recovery Test | 1 Time | Annually ±30 days |
| 5. | Air Flow Visualization Study | 1 Time | Annually ±30 days |
| 6. | Temperature and RH Mapping | 1 Time | Annually ±30 days |
| 7. | Differential Pressure Monitoring | 1 Time | Annually ±30 days |
| 8. | Viable Particle (Microbial) Monitoring
(Static Condition) |
3 Days | Annually ±30 days |
B. Methodology for Sampling Plan and Procedure:
7.1 Air Velocity and Number of Air Changes Measurement Test by Using Capture Hood:
7.1.1. Objective
To lay down a procedure for air velocity measurement and calculation of number of air changes
7.1.2. Scope
This scope is applicable for determine the air velocity measurement in clean room, Clean air cabinet and calculation of ACPH in clean room area.
- Equipment: “Capture hood”.
- Ensure that the instrument used is within the valid calibration period. In the event of a contractor carrying out the test then the certificate of calibration should be obtained from the contractor before the test is performed.
- Perform the air flow velocity test as per the procedure given below
7.1.3. Procedure
- Ensure that the Air Handling Unit is in “ON” condition, prior to the start of the test.
- Ensure that the instrument (Capture hood) is calibrated and having a valid calibration certificate.
- Set the Capture hood at the supply air grill area and observe the value in display unit.
- Calculate the total air flow from all the supply grill in the room and add the values to get the total air flow in room (CFM).
- Total air flow volume (CFM)/room = Sum of the air flow volume at each supply grill of the room.
- Calculate the number of air changes in the room as per the formula given below:
- Number of air changes/hour in the room = Total Air Flow (CFM) in the room x 60 Room Volume (Ft3)
7.1.4. Acceptance Criteria
The limit of Air velocity and Air changes per hour in the room Recorded
7.1.5. Air Velocity
Air Velocity and Number of Air Changes Measurement Test by Using Anemometer
7.1.6. Objective
To lay down a procedure for air velocity measurement and calculation of number of air changes.
7.1.7. Scope
- Equipment: “Anemometer”.
- Ensure that the instrument used is within the valid calibration period. In the event of a contractor carrying out the test then the certificate of calibration should be obtained from the contractor before the test is performed.
- Perform the air flow velocity test as per the procedure given in the Procedure and record the observations
7.1.8. Procedure
- Ensure that the Air Handling unit is “ON” prior to the start of the test.
- Ensure that the instrument (Vane or hot wire anemometer or flow hood with flow meter) is calibrated and having a valid calibration certificate.
- Measure the air velocity (FPM) at five different locations of grill/filter at a distance of about 150 to 300 mm (6” to 12 “) as shown below and for laminar air flow units measure the air velocity at working level.
- The measuring time at each location should be at least 30 seconds and average reading should be taken. Record the reading in Air Velocity and ACPH test raw data sheet.
- Check the report of external agency and attach the same.
- Calculate the average velocity of the air coming from the supply grill as per following Formula
| B C
E A D |
Average Air Velocity (FPM) = Reading of (A+B+C+D+E)
- Calculate the air flow volume at each grill as per the following given below
- Air Flow volume (CFM)/Grill = Avg. air velocity (FPM) x Effective grill area (Ft2).
- Calculate the total air flow from all the supply grill in the room and add the values to get the total air flow in room (CFM).
- Total air flow volume (CFM)/room = Sum of the air flow volume at each supply grill of the room.
- Calculate the number of air changes in the room as per the formula given below: Number of air changes/hour in the room = Total Air Flow (CFM) x 60 Room Volume (Ft3)
7.1.9. Acceptance Criteria
The limit of Air velocity and Air changes per hour in the room
| Grade / Class of
Area |
Air Velocity | ACPH |
| D / ISO | Individual velocity shall be ±20% from the average velocity |
7.2 Differential Pressure Monitoring:
7.2.1. Objective
To ensure that differential pressure across the rooms are as per design and consistent
7.2.2. Scope
The differential pressure across all the rooms available in the area shall be monitored for three consecutive days.
7.2.3. Procedure
Ensure that AHU is catering to the area are switched “ON” and operational.
Record the differential pressure across the rooms displayed on the room DP transmitters / DP gauges / External DP gauges.
7.3 HEPA Filter Leak Test:
7.3.1. Objective
To lay down a procedure for HEPA Filter Integrity Test (PAO test).
7.3.2. Scope
This Procedure is applicable for testing of HEPA Filter Integrity.
7.3.3. Procedure
- Before performing PAO testing, ensure that Air Velocity Test if done and observations are meeting the acceptance criteria.
- Ensure that Air Handling Unit is in operational.
- Ensure that the aerosol photometer calibrated and traceability certificate is available.
- The aerosol photometer should have a sampling rate of 28 ± 3 L/ min. (1 CFM) with the sensitivity of 10-3 microgram / liter.
- Add Poly-alpha olefin (PAO) at 20 to 80 micrograms/liter ratio or suitable aerosol material recommended by the supplier to the aerosol generator.
- Keep the aerosol generator near the air grill / riser / fresh air damper of the Air supply unit.
- Provide compressed air or Nitrogen to the aerosol generator at the pressure of about 20 PSI (equivalent to 1.4 Kg/cm2) and visually confirm the generation of aerosol.
- Switch ON the Aerosol photometer and set the upstream concentration to 100 %.
- Once the 100% concentration is established at the upstream side, turn the instrument knob to downstream.
- The photometer probe should scan the entire filter face and frame at a position of about 10 to 15 cm from the face of the filter and should be traversed slowly (at a scan rate ofnotexceeding 5 cm / sec. For square probe and about 15 cm2 /sec for rectangular probe), using slightly overlapping strikes, as shown below (Step-2).
HEPA Filter Mounting:
- After completion of testing, the result shall be entered in the respective format i.e. HEPA filter Integrity Test Raw Data Sheet and attach the same.
- Ensure that the probe travels specifically over the entire downstream face of each filter, the perimeter of filter and seals between the filter frame and grid structure including its joints.
7.3.4. Acceptance Criteria
The leakage should not be more than 0.01 % of the concentration.
7.4 Non-Viable Particle Monitoring (At rest)
7.4.1. Objective
To lay down a procedure for Non-viable particle count monitoring in the Clean room / Clean Cabinet to meet the desired Clean room or clean air or clean zone conditions.
7.4.2. Scope
This Procedure is applicable for Non-viable particle count monitoring in the Clean room / Clean Cabinet.
7.4.3. Procedure
Equipment used:
- Discrete particle counter (DPC).
Pre-checks:
- Ensure that the area is cleaned and Air Handling Unit is in operational.
- Ensure the air borne particle counter is in calibrated state and calibration certificate is available with traceability.
- A sampling probe shall be selected to permit Isokinetic sampling in the area.
- Non-viable particle count shall be carried out in “At rest” condition for consecutive runs for each location.
- Set the particle counter as per desired sampling volume/sampling time and total sampling locations as per the clean room requirements.
- Place the Non-viable particle counter at the predefined monitoring location and start the particle counter.
- Set the sampling probe inlet facing into the predominant direction of the air flow (Unidirectional air flow), in case where sampled air flow is not controlled or predominant (non-unidirectional), the inlet of sampling probe shall be directed vertically upward.
Take the printout, check for the acceptance criteria for particle size of 0.5 µm,1.0 µm and 5.0 µm, sign and record the observations in the format provided. Also take a photocopy of the printout and attach with the report.
7.4.4. ACCEPTACNE CRITERIA
The clean room or clean zone is deemed to have met the specified air cleanliness classification if the averages of the particle concentrations measured at each of the locations do not exceed the concentration limits (for 0.5 ,1 and 5.0 µm) given below:
| ISO Class | Maximum permitted number of particles/m3 equal to or above | ||||
| At Rest | In Operation | ||||
| 0.5 µm | 1.0 µm | 5 µm | 0.5 µm | 5 µm | |
| 8 | 3 520 000 | 832000 | 29 000 | Not Defined | Not Defined |
7.6 Air Flow Visualization Study:
7.6.1. Objective
To lay down a procedure for Air Flow Visualization Test in Clean room / Clean Cabinet to ensure the pressure cascade.
7.6.2. Scope
This procedure is applicable for performing Air Flow Visualization Test in Clean room / Clean Cabinet
7.6.3. Procedure
- Air flow visualization test shall be performed in “At rest” condition.
- Ensure that Air Handling unit is in operational and differential pressure inside the room is maintained and no manufacturing process or material inside the room.
- Introduce the smoke by using Water fogger / Dry ice / glycol.
- Generate the smoke near the supply grill and observed the direction of flow.
- Similarly observe the air flow to the return riser by generating smoke near return riser.
- Also ensure the movement of air form one area to nearby area by generating smoke near the door opening.
7.6.4. Acceptance Criteria
The air shall flow from supply grill in to the room and shall blow out through return grill. Air shall move from high pressure zone to low pressure zone. Refer table for pressure zones (High & Low).
7.5 Clean Room Recovery Test:
7.5.1. OBJECTIVE
To lay down a procedure for Clean room recovery time study in Clean rooms.
7.5.2. SCOPE
This Procedure is applicable for performing Clean up time study.
7.5.3. PROCEDURE
- Place the particle counter at the identified location at working height in the respective clean area.
- Take two readings when the AHU is ON in at rest condition.
- ‘Shut OFF’ the AHU and generate the particles concentration 100 times more than the target cleanliness level(i.e. 2 times higher class) by increasing manual interventions / door opening-closing / using PAO. Start taking reading through particle counter to measurement at each 1 minute interval. Note down the time (t100n) taken to cross the particle.
- Keep the particle count at specified sampling location at working height or approximately 1 m from floor level, and set up the flow rate and select the particle size thresholds in accordance with ISO 14644-1. Set a sampling probe inlet facing into the predominant direction of the airflow, the inlet of sampling probe shall be directed vertically upward. The transit tube from the sample probe inlet to the particle counter sensor should be as short as possible. Take the reading at each minute till the area recovered to the designated cleanliness level.
- Switch ON the AHU, start taking reading note down the time taken to regain and stabilized the initial at rest condition.
- Note the time (tn) taken to return to its original condition (Designated cleanliness level). Hence Recovery time shall be calculated as (tn –t100n).
Recovery test shall be performed in critical areas viz. Dispensing, Granulation, Compression, Coating & Primary Packing where the critical process is being carried out.
7.5.4. ACCEPTANCE CRITERIA
Clean room recovery time shall be not more than 15 minutes
7.7 Temperature and RH Mapping
7.7.1. Objective
To ensure that temperature and %RH conditions in the areas being catered by the Air Handling Unit meeting the room conditions for temperature and %RH.
7.7.2. Scope
Temperature and %RH shall be carried out in for three consecutive days for Temperature and %RH condition can be qualified in “At rest” condition.
7.7.3. Acceptance Criteria
Temperature NMT 23°C and %RH NMT 58.
7.8 Viable Particle (Microbial) Monitoring (At static i.e. rest condition and dynamic i.e. operation condition):
7.8.1. Objective
To ensure that microbial load inside the room is as per design and consistent to meet the Clean room classification requirements of Grade – D / ISO 8.
7.8.2. Scope
The microbial load evaluation shall be carried out in classified rooms with both Settle plate method and Air sampling method for three days.
7.8.3. Procedure
- Ensure that AHU catering to the area is switched “ON” and operational.
- Perform the microbial monitoring study as per SOP Refer Microbial monitoring
- Perform both Settle plate monitoring & Air sampling at the same identified worst-case locations. Locations in the layout are identified for Settle plate monitoring as SP1, SP2….and for Air sampling AS1, AS2… for sample identification. Here SP denotes for settle plate, AS denotes for Air sampling and 1, 2,…. are the serial number for the total location in sequential order.
7.8.4. Acceptance Criteria
Review the results and verify against acceptance criteria. Attach the microbial monitoring reports with the summary report. Acceptance Criteria:
The microbial load in the rooms shall meet following acceptance criteria
| Method | Bacteria |
| Microbial passive air sampling (Settle plate) | NMT 100 cfu / plate (Diam. 90 mm cfu/4hrs.) |
| Microbial active air sampling | NMT 200 cfu / m³ |
Training Record:
The following topics shall be covered during training:
- HVAC Revalidation Procedure.
- Documentation Practices for filling of report
- Strategy and procedure of Re-qualification process.
- General precautions / guidelines to be followed during qualification.
- HVAC Revalidation Procedure.
- Documentation Practices for filling of report
- Strategy and procedure of Re-qualification process.
- General precautions / guidelines to be followed during qualification.
Training shall be imparted before execution of the study.
2.0 ACCEPTANCE CRITERIA
- All the instruments should be identified and calibrated. The standards used for calibrating the measuring instrument(s) shall be calibrated against a standard traceable to other approved standards. Calibration details of standard instrument(s) used are within the validity.
- All the relevant standard operating procedures identified during installation qualification should be available and should be adequate. Persons involved in operation, cleaning and maintenance should be trained on the respective procedures.
