PROTOCOL FOR VALIDATION OF DYNAMIC PASS BOX
EQUIPMENT ID: -----
|
Sr. No. |
Description |
Page No. |
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1.0 |
Protocol
Approval |
3 |
|
2.0 |
Overview |
4 |
|
2.1 |
Objective |
4 |
|
2.2 |
Purpose |
4 |
|
2.3 |
Scope |
4 |
|
2.4 |
Responsibilities and Validation Team |
4
– 5 |
|
3.0 |
Training |
5 |
|
4.0 |
Equipment description |
5 |
|
4.1 |
Equipment Identification
|
5 |
|
4.2 |
Working Principle
|
5 |
|
4.3 |
Brief Machine Description |
5
– 6 |
|
4.4 |
Safety Feature Description |
6 |
|
5.0 |
Validation test procedure and
methodology |
7 |
|
5.1 |
Validation flow chart |
7 |
|
5.2 |
Pre-Validation
Requirement |
8 |
|
5.3 |
Verification of calibration of
gauges |
8 |
|
5.4 |
Preventive Maintenance status |
8 |
|
5.5 |
Testing Procedure |
9 |
|
5.5.1 |
Air Velocity Test |
9 |
|
5.5.2 |
Integrity Test of HEPA filters |
9
- 10 |
|
5.5.3 |
Differential Pressure
Monitoring |
10
|
|
5.5.4 |
Air Flow Pattern Test |
10 |
|
5.5.5 |
Non Viable Particle Count |
10
– 11 |
|
5.5.6 |
Viable Particle Count Test |
11-12 |
|
5.5.7 |
Recovery Test |
12
– 13 |
|
5.5.8 |
Sound Level Test |
13 |
|
6.0 |
Discrepancy and corrective
action report. |
13 |
|
7.0 |
Reference |
14 |
|
8.0 |
Summary |
14 |
|
9.0 |
Conclusions |
14 |
|
10.0 |
Appendix |
14 |
|
11.0 |
Attachments |
15 |
|
12.0 |
Re
Periodic Validation Criteria |
15 |
|
13.0 |
Revision
History |
16 |
1.0 Protocol Approval
|
Signing of this approval page
of protocol indicates agreement with the qualification approach described in
this Document. If any modification in the equipment qualification approach
becomes necessary, a revision through Change control shall be prepared,
checked and approved. This protocol cannot be executed unless approved by
following personnel. |
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Department |
Name |
Designation
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Signature /Date |
Prepared by
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Engineering |
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Quality Assurance |
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Reviewed by
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HOD-Engineering |
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HOD -Microbiology |
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HOD-Production |
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Quality
Assurance |
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Approved
by |
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HOD –
QA |
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2.0 Overview
The Dynamic Pass Box units are designed in accordance with cGMP principles. Dynamic Pass Box units are used for shall be used for material transfer between two areas under different classification. The tests shall be done to evaluate the performance of Dynamic Pass Box that provides a high degree of assurance and reliability to support the process for which the system is intended.
2.1 Objective:
The objective of this protocol is to describe the procedure and plan for validation of Dynamic Pass Box units which are installed in Production-injection.
2.2 Purpose
The purpose of this protocol is to help the operating personnel to plan the validation activities so as to demonstrate the Dynamic Pass Box units shall perform reproducibly and consistently within its full dynamic range of operation according to pre-laid specifications consistently to thus provide a high degree of assurance.
2.3 Scope:
The scope of this protocol is limited to the Dynamic Pass Box units for providing aseptic environment during sterility testing, microbiological testing, culture handling at -------
2.4 Responsibilities and Validation Team
The group comprising of representatives from each of the following departments and they shall be responsible for the overall compliance of this protocol.
Department
|
Responsibility
|
Engineering
|
·
Calibration
of the gauges and instruments ·
Air
velocities from the HEPA filters ·
Integrity
of the installed HEPA Filters ·
Non-Viable
Particulate Matter ·
Differential
Pressure balancing ·
Preparation
of Protocol. |
|
Production |
·
Review
of this protocol. ·
Execution
and collection of the data. |
|
Quality Control |
·
Review
of Validation protocol and report. ·
Performing
air sampling (Active and Passive). ·
Preparation
of Analysis Report and submission to Quality Assurance |
Outside Party
|
·
Participate
and Provide necessary support for the qualification activity to carry out
different test parameters (as applicable). |
Quality
Assurance
|
·
Review
of Protocol and Report ·
Preparation
of Protocol ·
Verifying
the compliance of existing procedures to the outcome of validation ·
Authorization
of the qualification protocol. |
3.0
Training
The
validation team member shall be trained on the protocol execution of validation
activity and report compilation .The training record shall be attached (Format
No.QAGN006/F04)
4.0
Equipment
Description
4.1
Equipment
Identification
|
Name |
Make
/Model |
Pass
Box ID |
Location |
|
Dynamic Pass Box |
Fabtech / FT-DPB-24-24-24 |
PIDPB-01 |
In between Equipment washing
& cooling Zone |
|
Dynamic Pass Box |
Fabtech / FT-DPB-24-24-24 |
PIDPB-02 |
In
between cooling zone & filling room |
|
Dynamic Pass Box |
Fabtech / FT-DPB-24-30-36 |
PIDPB-03 |
In
between external passage & Sealing room |
|
Dynamic Pass Box |
Fabtech / FT-DPB-24-36-36 |
PIDPB-04 |
In
between IRM store & sampling room |
4.2
Working
Principle
The
Dynamic Pass Box units are designed in accordance with cGMP principles. Dynamic
Pass Box units are used for material transfer between two areas under different
classification.
4.3
Brief
Machine Description
The Pass
Boxes units comprises of following parts:
4.3.1
Main
body structure
4.3.1.1
Pre-filter
4.3.1.2
HEPA
filter
4.3.1.3
Motor
blower
4.3.1.4
Side
panels
4.3.1.5
Magnehelic
gauges provided to measure pressure differentials across all filters.
4.3.2
Main Body Structure:
Main body
structure of Dynamic Pass Box
unit provides a platform for fixing the supply filters, motor blower, side
panels, Magnehelic gauges & exhaust filter. Main body structure is
fabricated using SS 304.
4.3.3
Supply Filter
The
function of supply filters is to supply dust free & bacteria free air.
Supply filters consists, pre-filter of 5 micron rating with efficiency of 95%
down to 5 microns and HEPA filter of 0.3 micron rating with efficiency of
99.99% down to 0.3 micron level.
4.3.4
Motor Blower
The motor
blower is situated inside the main body structure. Motor blower is fabricated
by using MS powder coated.
4.3.5
Side Panels
Side
panels are provided to give the support to the main body structure. Side panels
are fabricated by using SS 304.
4.4
Safety Features Description
4.4.1
Earthing Connections
The
Earthing connections are installed to reduce risk of any accident by
overloading, voltage variation or any other electrical fault. MCB should be
provided.
4.4.2
Indicators Switches for
Fluorescent light
The
Indicators should be provided for Fluorescent lights.
4.4.3
Noise Level
The noise
level should not more than 60db of blower motor.
4.4.4
UV Lights
The UV
Lights are effective against a wide variety of microorganisms (bacteria,
viruses)
5.0
Validation Test Procedure and
Methodology
5.2
Pre –Validation
Requirements
Following
instruments shall be required for the Validation of Dynamic Pass Box units
installed in Production Injection
|
S. No. |
Instrument
Name |
Calibration Done
Date |
Calibration Due
Date |
Calibration Certificate
number |
|
1.
|
Digital Vane
Type Anemometer |
|
|
|
|
2.
|
Aerosol
generator |
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|
3.
|
Air borne particulate counter |
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4.
|
Air sampler |
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5.
|
Sound Level Meter |
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5.3
Verification of calibration of
Gauges
It is
necessary to verify and ensure the Calibration status of Gauges before carrying
out validation test. The Calibration status of gauges shall be verified before
validation tests.
|
Instrument |
Magnehelic Gauge I.D. No. |
Location |
Calibrated Date |
Next Due Date |
|
Magnehelic Gauges |
|
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Record
the observation in enclosed Test Data Sheet # 1 for the verification of
calibration of measuring and testing instruments.
5.4
Preventive Maintenance status
This
always necessary to verify and ensure the preventive Maintenance status of
Dynamic Pass Box Units Before carrying out validation activity. The preventive maintenance
status of equipment shall be verified before validation activity.
|
Pass Box Units |
Equipment I.D.
No. |
Location |
Preventive
Maintenance date |
Next Due Date |
|
PIDPB-01 |
In
between Preparation and Sterilization Room & cooling Zone |
|
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|
PIDPB-02 |
In
between cooling zone & Vial Filling and Bunging Room |
|
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|
PIDPB-03 |
In
between external passage & Vial Sealing Room |
|
|
|
|
PIDPB-04 |
In
between IRM Store Room & sampling room |
|
|
Record the observation in enclosed Test Data Sheet #
1 for the verification of preventive Maintenance status.
5.5
Testing Procedures
The
following tests shall be done to evaluate the performance of Dynamic Pass Box
Units.
5.5.1
Air velocity Test
5.5.1.1
Objective:
To
demonstrate that the air system is balanced and capable of delivering required
air volume.
5.5.1.2
Tools required: Calibrated
Anemometer.
5.5.1.3
Procedure
5.5.1.3.1 Measure
the air velocity by the anemometer at a distance of 6” or 152mm from filter
face at five points (four at corners and one at the middle) using calibrated
anemometer.
5.5.1.3.2 Calculate average of the five
reading of the filter. Record the calculation / results in the Test Data Sheet
#2.
5.5.1.3.3 Record the calibration details of
the instrument used for measurement and attach the calibration certificate.
5.5.1.4
Acceptance criteria
5.5.1.5
The
variation among the average velocity across the HEPA filter should be 90 ±20%
feet / minute.
5.5.2
Integrity Test of HEPA Filters
5.5.2.1
Objective
To detect the Leakage or pinhole leak of
HEPA filter.
5.5.2.2
Tools
required: Aerosol generator, Aerosol
Photometer (Calibrated), Poly Alpha Olefin Liquid.
5.5.2.3
Test
procedure
5.5.2.3.1
Position the Aerosol generator and
introduce Aerosol into the upstream air, ahead of the HEPA filters, at the
concentration of 20-80 mg per liter or 20 mg/m3 to 80
mg/m3 of air at the filter’s designed airflow rating and set the
instrument at 100% concentration.
5.5.2.3.2
Scan the downstream side of the filter
with probe at scanning rate not to exceed 5 cm/second or 10FPM. The probe
should be held at a maximum distance of approximately 3 cm from the downstream
filter face.
5.5.2.3.3
During scanning percentage of the PAO
(Poly Alpha Olefin) penetration shown by photometer should be not more than
0.01% through the filter media of 99.99 efficiency HEPA Filters and should be
‘Zero’ through mounting joints.
5.5.2.3.4
Record the
results in the Test Data Sheet #3.
5.5.2.4
Acceptance
criteria
5.5.2.5
There
should not be designated leaks where a reading is greater than 0.01% of the
upstream challenge aerosol concentration
5.5.3
Differential Pressure monitoring
5.5.3.1
Objective
The objective
of this test is to show that the differential pressures across HEPA filters are
within designed values.
5.5.3.2
Tools required: Calibrated Magnehelic Gauge
5.5.3.3
Procedure
Differential
Pressure shall be monitored every 10 minutes for half an hour on Magnehelic
gauges record in the test data sheet#4.
5.5.3.4
Acceptance
criteria:
8-15 mm
of WC
5.5.4
Airflow Pattern Test
5.5.4.1
Objective
The objective of this test is to show
that the direction of the airflow is unidirectional (orderly) i.e. laminar air
flow is observed from filter face to work station where activity is performed.
5.5.4.2
Tools
required: Smoke generator
5.5.4.3
Test procedure
5.5.4.3.1
Take a smoke generator and start it,
generate the smoke, keep the generation point in the place of observation and
check for airflow direction in the Dynamic pass box. It shows laminar air flow
in closed condition.
5.5.4.3.2
Record observations in the Test Data Sheet
#5.
5.5.4.4
Acceptance criteria:
5.5.4.5
The air flow was uniform and
uniformly reaches to the working station form the filter and then it flows
towards the return air filter or Return grill.
5.5.5
Non-viable Particle Count
5.5.5.1
Objective
5.5.5.1.1
To
establish that the area under dynamic pass box meet the requirements for
cleanliness as per EN/ISO 14644-1 & USFDA. Air sample should be taken near
the equipment at working height.
5.5.5.1.2
The
particle counting should be using pre-calibrated particle counter under Dynamic
pass box Units at working height.
5.5.5.2
Tools required: Calibrated Air borne
particulate counter.
5.5.5.3
Test procedure:
5.5.5.3.1
Consider
minimum 3 locations for an area covered under Dynamic pass box (Grade-A) for
non viable particle count.
5.5.5.3.2
Paste
the printouts generated by the particle counter on test data sheet# 10 and
shall be photocopied. Verify the printouts for all calculations and acceptance
criteria as mentioned below. Attach the photocopies of the same to the Test
Data Sheet#6. Attach the calibration certificate of Particle Counter.
5.5.5.4
Sampling:
5.5.5.4.1 Ensure that Dynamic Pass box Unit
shall be in “ON” condition.
5.5.5.4.2 Sampling shall be done at rest
condition and in dynamic condition as pre-determined locations.
5.5.5.4.3
Sample volume shall be collected at working
level by positioning the probe towards airflow.
5.5.5.4.4
Operating personnel put the required
information (For example: Location name/ID, number of samples etc) in the
particle counter.
5.5.5.4.5
Collect and verify the print out from the
particle counter.
5.5.5.4.6
Paste the printouts generated by the particle
counter on Test Data Sheet# 10“Non Viable Particle Count: - Raw Data Attachment
Sheet” and the same shall be signed by the operating
person in “Done by” column and by QA person in “Checked by” column.
5.5.5.4.7
After verification of printouts shall be
photocopied.
5.5.5.4.8 Verify
the printouts for all calculations and acceptance criteria as mentioned below.
5.5.5.4.9 The
details of Test Data Sheet# 6 and Test Data Sheet#.10 should be inline.
5.5.5.4.10 Attach the calibration
certificate of Particle Counter with the report.
5.5.5.5
Acceptance criteria
5.5.5.5.1 All the readings of test should
pass as per the below table:
|
|
Maximum
permitted number of particles per m3equal to or greater than the
tabulated size |
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|
At
Rest (Reference: EN/ISO14644-1) |
At
Operation |
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|
(Reference:
USFDA guide for aseptic preparation) |
(Reference:
EN/ISO14644-1) |
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|
Grade/Class |
0.5
mm |
5.0
mm |
0.5
mm |
5.0
mm |
|
A/Class100 |
3520 |
20 |
3520 |
20 |
5.5.6
Viable particle count test
5.5.6.1
Objective
5.5.6.2
To
ensure that area is properly cleaned to carry out routine aseptic handling of
material / Products and observed viable count is within the defined level.
5.5.6.3
Tools required:
5.5.6.4
Media Plates & Calibrated Air Sampler
5.5.6.5
Test procedure
5.5.6.5.1 The viable monitoring shall be
performed by two methods i.e. Active and Passive sampling
5.5.6.5.2 Follow
the current version of the SOP No. QC-SG-304 “Environmental Monitoring Program
(MEMP) in aseptic Manufacturing Areas”.
5.5.6.5.3 Perform
the Active sampling for at all locations for three working days irrespective of
the routine frequency
5.5.6.5.4 Expose
the media plates for a period of 4 hours at all locations for three working
days irrespective of the routine frequency.
5.5.6.5.5 After
completion of monitoring collect the plates and send to Microbiology lab for
incubation. Result shall be recorded as per SOP No. QC-SG-304 in the respective
format
5.5.6.6
Acceptance
criteria:
The
viable count shall comply as per the current version of the SOP No. QC-SG-304
“Environmental Monitoring Program (MEMP) in aseptic Manufacturing Areas”
5.5.7
Recovery Test
5.5.7.1
Objective:
This
test is performed to determine the ability of the air handing unit, supplying
air to the classified areas to achieve its designed class limit for air borne
particulates within the time limit after contamination of the area up to 100
times more from the initial count of air borne particulates.
5.5.7.2
Tools required:
Air
borne particulate counter, duly calibrated by national / international
traceability.
5.5.7.3
Test procedure:
5.5.7.3.1 Start
the particle counter take the continues reading when result shows the counts
are within the limits
5.5.7.3.2 Generate
particles intensely by aerosol generator or artificial means and observed that
the particle crossed approx.100 times of the initial count for the particles of
0.5 micron.
5.5.7.3.3 After
that stop the activity of generation of particle count by aerosol generator or
artificial means.
5.5.7.3.4 Monitoring
of the particle count shall be continue till the particle counts result shows
the below the initial counts of the rest condition of that area stop the
particle counter.
5.5.7.3.5 Take
all the printed record without tearing pasted the result in the data sheets.
5.5.7.3.6 Calculate
the Recovery time from the time, the particles just exceeded the 100 times of
the initial count to the count that below the initial counts of the rest
condition and record all the observations in Test Data Sheet # 7.
5.5.7.3.7 Attached
printed copy shall the verified and signed after signed take a photocopy of the
same and maintains the record.
5.5.7.4
Acceptance criteria:
Area
should be recovered to its rest state within 15 min
5.5.8
Sound Level Test
5.5.8.1
Objective
The objective of this test is to
prove that the level of sound in Dynamic pass box unit is within acceptable
limits.
5.5.8.2
Tools required: Calibrated
sound level Meter
5.5.8.3
Test
procedure
5.5.8.3.1 Take the reading at 5 locations
(working height) in the pass box area and take the average of the sound level
in the unit of decibel. Record the observations in Test Data Sheet #8.
5.5.8.3.2 Attach the calibration
certificate of sound level Meter.
5.5.8.4
Acceptance
Criteria
The clean room or clean zone
shall meet the acceptance criteria is NMT 60 db.
Note: -
|
Sr.
No. |
If the validation carried out
by the third party (outside party). Then the following points shall be
verified |
|
1 |
Training record of the third party
(outside party) person on the instruments that are used for the validation
activity before the execution of validation activity. |
|
2 |
Training shall be provided to the third
party (outside party) person before execution of the validation activity on
the approved protocol. |
|
3 |
After the execution of tests the raw
data of test performed shall be verified by the QA person. |
|
4 |
The photo copy of the same shall be
shared with the third party (outside party) for the preparation test
certificates. |
|
5 |
At the time of receiving test
certificates and other traceability certificates, the test certificates again
verified with the original raw data. |
|
6 |
After receiving the test certificates
the conclusion and summary shall be written in the report and other
supportive data of third party shall be considered valid. |
6.0
Discrepancy And Corrective Action
Report
Document
any discrepancies observed during the validation of the Dynamic Pass Box Units
in format attached to each Test Data Sheet # 9. Include the corrective actions
of the same. When all the discrepancies are satisfactorily resolved or an
approved action plan is developed which ensures that the discrepancy will be
resolved.
7.0
References
7.1
Validation
Master Plan
7.2
ISO
14644-1 & ISO 14644-3
7.3
US
FDA-Sterile Drug Products
Produced by Aseptic Processing - Current Good Manufacturing Practice.
7.4
EN/ISO
14644-1 - EU Guidelines to Good
Manufacturing Practice Medicinal Products for Human and Veterinary Use.
7.5
Sop
on usage of dynamic pass box PI-SP-023.
7.6
SOP
on environmental monitoring of sterile product manufacturing facility QC-SG-304.
7.7
Sop
on operation of air borne particle counter PI-SP-021.
8.0
Summary
The
validation report shall include a summary of validation activities describing
the following in brief:-
a).
Protocol reference
b).
Dates of validation activities
c).
Pre-validation testes performed
d).
Confirmation of calibration and preventive maintenances status of
e).
Brief on result obtained
9.0
Conclusions
The
validation report shall include statement for conclusion of the validation
activity based on result and observation from the validation activity.
10.0
Appendix
Abbreviations and definitions
|
Abbreviation |
Definitions |
|
HEPA |
High
efficiency Particulate air |
|
SOP |
Standard
Operating Procedure |
|
QA |
Quality
Assurance |
11.0
Attachment
The
following are the attachments which shall be used for collecting and evaluating
the raw-data.
|
Test Data Sheet
No. |
Title |
Pages |
|
Test Data Sheet # 1 |
Calibration and Preventive Maintenance Status |
1 |
|
Test Data Sheet # 2 |
Measurement of Airflow
Velocity |
1 |
|
Test Data Sheet # 3 |
Installed HEPA Filter System Leakages and Integrity Test |
1 |
|
Test Data Sheet # 4 |
Differential Pressure Test |
1 |
|
Test Data Sheet # 5 |
Airflow Direction Test |
1 |
|
Test Data Sheet # 6 |
Non Viable Particle Count Test |
1 |
|
Test Data Sheet # 7 |
Recovery Test |
2 |
|
Test Data Sheet # 8 |
Sound Level
Tests |
1 |
|
Test Data Sheet # 9 |
Discrepancy And Corrective Action Report |
1 |
|
Test Data Sheet #10 |
Non Viable Particle Count:- Raw Data Attachment Sheet |
2 |
|
Attachment – 1 |
Training Record for Executors |
|
|
Attachment – 2 |
Raw data sheet for Particle counter printouts |
|
12.0
Periodic Validation Criteria
|
Sr. No. |
Tests |
Validation Frequency |
|
1.0 |
Air Velocity Measurement |
Six month |
|
2.0 |
Integrity Testing of HEPA Filter |
Six month |
|
3.0 |
Differential pressure Test |
Six month |
|
4.0 |
Air Flow Pattern Test |
Once in Year |
|
5.0 |
Cleanliness Class Verification Non Viable
Particulate count. |
Six month |
|
6.0 |
Recovery Test |
Once in Year |
|
7.0 |
Light level test |
Six month |
|
8.0 |
Sound level test |
Six months |
|
9.0 |
Viable Particulate Monitoring |
Six month |
All these
tests shall be carried out within a grace period of ± 30days.
12.1
Re-validation criteria is as
follows
12.1.1
If
any major changes or modification in the system.
12.1.2
If
any Major changes have been done in the respective room or module, which is
affecting the environmental condition.
12.1.3
If
there is a contamination problem.
12.1.4
At
the time of relocation or Re-qualification
13.0
Revision History
|
S. No |
Points Number |
Details |
|
1.0 |
2.4 |
1.
Responsibility
of the outside party is defined |
|
5.1 |
2.
Addition
of the Sound Level Meter in the Process flow chart |
|
|
5.6.1 to 5.6.8 |
3.
Objective
of each performing test is defined & test procedure is Elaborated |
|
|
5.6.4.4 |
4.
Rectification
of typographical error in acceptance criteria of differential pressure. |
|
|
5.6.4.5 |
5.
Non
Viable Particle Count Acceptance criteria is redefined a)
In
static condition monitoring of non viable particle count for both 0.5μ &
5.0μ particle shall be done as per EN/ISO 14644-1. b)
In
dynamic condition monitoring of non viable particle count for 0.5μ particle
shall be as per USFDA & 5.0μ particle shall be as per EN/ISO 14644-1. |
|
|
5.5.7 |
6.
Addition
of the Recovery Test. |
|
|
Header of the Document |
7.
The
protocol No. is redefined as PRT/PVL/AHS/02/04 as per current version of the
SOP No. QA-GN-002 |
|
Document No. |
Effective Date |
Nature of Change/ Reason for Revision |
|
PRT/PVL/AHS/02/05 |
28-05-2016 |
1.
Removal ID Number of Magnehelic gauge as per
change control no. CCIF-16-QA-027 2.
Table of Revision History change for better
clarity as per change control no. CCIF-16-QA-027. 3.
Removal test data sheet of viable particle count
as per change control no. CCIF-16-QA-027 4.
Change the test data sheet no. of recovery test,
sound level test and Discrepancy And Corrective Action Report from 8,9, 10 to
7,8 and 9 as per change control no. CCIF-16-QA-027. |
|
PRT/PVL/AHS/02/06 |
|
Following change
has been made as per the change control no.CCIF-18-QA-078 1. Updation
in the sampling procedure for Non viable particle count in point no.5.5.5.4.4,
5.5.5.4.5, 5.5.5.4.6, 5.5.5.4.7 and 5.5.5.4.9. 2.
Introduction of Note in page number 13 of 16 if
the validation is done by the third party (outside party). 3.
Preparation
of new Test data sheet#10 “Non Viable Particle Count:- Raw Data Attachment
Sheet”. |
END OF DOCUMENTS
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