VALIDATION OF VIAL WASHING MACHINE
Table of Contents
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Sr. No. |
Section Title |
Page No. |
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1.0 |
Protocol approval |
3 |
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2.0 |
Overview |
4 |
|
2.1 |
Objective |
4 |
|
2.2 |
Purpose |
4 |
|
2.3 |
Scope |
4 |
|
3.0 |
Validation team |
4 |
|
4.0 |
Training |
5 |
|
5.0 |
Equipment details |
5 |
|
6.0 |
Validation test procedure |
8 |
|
6.1 |
Flow chart |
8 |
|
6.2 |
Pre- validation requirement |
9 |
|
6.3 |
Verification of calibration of instrument |
9 |
|
6.4 |
Verification of preventive maintenance status |
9 |
|
6.5 |
Validation procedure |
10 |
|
7.0 |
Sampling Plan
and Acceptance Criteria |
14 |
|
8.0 |
Discrepancy and Corrective Action Report |
15 |
|
9.0 |
References |
15 |
|
10.0 |
Summary |
15 |
|
11.0 |
Conclusion |
15 |
|
12.0 |
Attachment |
15 |
|
13.0 |
Periodic validation schedule |
16 |
|
14.0 |
Revalidation schedule |
16 |
1.0
Protocol Approval
Signing of this periodic validation protocol approval page indicates
agreement with the validation approach described in this document. If
modifications to the validation become necessary, an addendum or revised
version will be prepared and approved.
This protocol has been reviewed for adequacy and accuracy and approved
by the following personnel
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Department |
Name |
Designation |
Sign & Date |
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Prepared by
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Production-Injection |
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Quality Assurance |
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Reviewed by
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HOD – Production |
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HOD-Microbiology |
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HOD- Engineering |
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Quality Assurance |
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Approved by |
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HOD – QA |
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The
container closer component of a sterile drug product is required to be washed.
The washing of different sizes of glass vials comprises of eight different
washing stages which includes treatment of re-circulated water, water for
injection and compressed air. Washing efficacy is monitored by spiking by
endotoxin, and by observing particulates residues. This process of washing of
different sizes of glass vials in different washing stages are required to be
validated as per GMP requirement.
2.1
Objective:
The objective
of this protocol is to be described the procedure and plan for validation of
washing of different sizes of glass vials using vials washing machine Equipment
ID.PIVWM-01.
2.2
Purpose:
The
purpose of this protocol is to carry out validation of vials washing machine
to-
Ø Demonstrate that
vials washing machine shall perform washing of different sizes of glass vials
which meets the desired meet acceptance criteria in a consistent manner when
operated as per the standard operating procedure.
Ø The validation
shall be tested at extreme and optimum operation condition.
2.3
Scope:
The scope of this validation
is limited to the validation of vial washing process for different sizes of
glass vials used in Nectar Lifesciences Limited unit VI.
3.0
Validation
Team:
Responsibilities: The group comprising of representatives from each of the following departments
and they shall be responsible for the overall compliance with this protocol.
|
DEPARTMENT |
RESPONSIBILITY |
|
Engineering & Utility |
Ø Arranging for
execution of the document and providing facilities Ø Responsible for
review of protocol and report |
|
Production |
Ø Participate and
provide necessary support for validation Ø Responsible for
preparation and review of protocol |
|
Microbiology |
Ø Responsible for
testing of sample involved Ø Responsible for
preparation and review of the protocol |
|
Quality Assurance |
Ø Monitoring the qualification activities.
Data compilation and review of the generated data Ø Preparation of the Qualification report
in consultation with the qualification team Ø Authorization of the qualification
report. |
4.0
Training: The validation team
member shall be trained on the execution of vials washing machine validation
activity and report compilation. The training record shall be attached with final report (Format No.
QAGNOO6/F08).
5.0
Equipment
Details: The vials washing machine shall be used for washing and
Sliconisation of different sizes of glass vials from 10ml to 100 ml in eight
different washing stages which include treatment of re-circulating water,
purified water, water for injection and compressed air with the additional
facility of silicon treatment in 9th and 10th wash.
5.1
Equipment
Description:
|
Equipment Name |
Vials
washing machine |
|
Equipment
I.D |
PIVWM-01 |
|
Location |
Vials
washing and sterilization Room |
|
Manufacturers
Name |
M/s
Ambica Engg. Works, Ahmedabad |
|
Model |
AHLVW-300 |
|
Dimensions |
|
|
Width |
2220
mm |
|
Height |
1675
mm |
|
Length |
3840 |
5.2
Design:
5.2.1
Working Principle:
The Vial Washing Machine
(AHLVW-300) ID. No. PIVWM - 01 is designed to wash vials of different sizes
from 10ml to 100ml. Complete washing of vials will occur in eight different
washing stages comprising of Re-circulated purified water, Purified Water,
Water for Injection and Compressed Air.
The Vial Washing Machine (AHLVW - 300) ID No. PIVWM
- 01 works on the principle of jet washing of the individual vials in inverted
position by a series of jets, 25 pockets are used for washing of 10, 15 and 20
ml vials, 12 Pockets are used for washing of 50 and 100 ml Vials. The maximum rated capacity of the machine is
18000 vials per hour in-case of 25 pockets, and 9000 vials per hour in case of
12 pockets. In feed lifter carries the vials in to the pockets & moving on
a chain horizontal conveyor with vertical up spray nozzles, entering the vials
co-axially and injected re circulated purified water filtered through 10µ
Cartridge filter, purified water filtered through 5µ Cartridge filter, water
for injection filtered through 1µ Cartridge filter & compressed air filtered
through 0.22µ Cartridge filter at specified station.
5.2.2
Brief Instrument Description:
The vial washing machine comprises of the following parts:
·
Vials Infeed zone
·
Vial Washing zone
·
Vial Out feed zone
·
Vial Out feed from conveyor
·
Pump, Tanks, Pipe fitting & Pressure
gauges
·
Filter housing
5.2.2.1
Vial Infeed Zone:
The process of washing begins with loading of pre checked vials on in-feed platform and pushing manually to the conveyor. The conveyor carries the vials on the in-feed lifter by the help of loosening device. The in-feed lifter carries the vials into the pockets.
5.2.2.2
Vial Washing Zone:
The vials set up in to the pockets after feeding.
The index channel of vials carries forward at a time. During each stoppage of
this movement, nozzles manifold raises up and nozzles enters the mouth of each
individual vials. A solenoid valve in the water and air lines is activated and
a jet of air/water hits the inside of the vials to clean it. .An external
cleaning station cycle is also provided to clean the outer surface of the each
vial. Standard washing cycle occurs as per following sequence
The sequence of the internal washing cycle is as
below
|
No. of Wash |
Station Details |
Internal or External |
Wash details |
|
1st Wash |
Station 1 |
Internal Wash |
Compressed
air |
|
2nd
wash |
Station
2 |
External Wash |
Recirculated
water |
|
3rd
wash |
Station
3 |
Internal Wash |
Recirculated
water |
|
4th
wash |
Station
4 |
Internal Wash |
Purified
water |
|
5th
wash |
Station
5 |
External Wash |
Purified
water |
|
6th
wash |
Station
6 |
Internal Wash |
Water
for injection |
|
7th
wash |
Station
7 |
External Wash |
Water
for injection |
|
8th
wash |
Station
8 |
Internal Wash |
Compressed
air |
|
9th
wash |
Station
9 |
Internal Wash |
Spare
for silicone treatment |
|
10th wash |
Station
10 |
Internal Wash |
Spare
for silicone treatment |
5.2.2.3
Out feed Zone:
After washing these washed vials are taken away from the pockets with support of vials guide plate and come out of the out feed lifter. Out feed lifter come down and the pusher pushes the vials on the out feed platform to conveyor.
5.2.2.4
Out feed Conveyor:
The out feed conveyor is chain linked with mesh conveyor made up of stainless steel 316 which conveys the washed vials from the unloading unit to the in feed of sterilizing tunnel. The speed of conveyor is controlled from the control panel of the machine
6.0 Validation
Test Procedure:
6.1 Flow Chart:
|
|
|
6.2 Pre –
Validation Requirements:
Following chemical/equipment shall be required for the
validation of Vial Washing Machine
Ø Sodium Chloride.
Ø Activated Charcoal Powder
Ø Bacterial endotoxin
Ø Liquid Borne Particle Counter
Ø Weighing balance
Ø 10 ml to 100ml moulded glass vials
|
Sr.No. |
Test parameter |
Details |
|
1.0 |
Verification of Calibration |
Ø Before start the validation
activity |
|
2.0 |
Verification of preventive
maintenance status |
Ø Before start the validation
activity |
To qualify this test the equipment should fulfill the acceptance criteria described in the individual test procedure. After completion of the validation tests all the data generated will be compiled together to evaluate the capability of the vials washing machine.
6.3
Verification of
Calibration of Instrument:
The calibration of gauges and instrument shall be carried out
prior to validation activity and record in the table as given below.
|
Instrument |
Range |
ID No. |
Location |
Calibration Date |
Next Due date |
|
PRESSURE GAUGES |
0
to 4 Kg/cm2 |
PIVWPG-01 |
|
|
|
|
0
to 4 Kg/cm2 |
PIVWPG-02 |
|
|
|
|
|
0
to 4 Kg/cm2 |
PIVWPG-03 |
|
|
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0
to 4 Kg/cm2 |
PIVWPG-04 |
|
|
|
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0
to 4 Kg/cm2 |
PIVWPG-05 |
|
|
|
6.4
Verification of
Preventive Maintenance Status:
The preventive maintenance of vials washing and the support
system shall be carried out before the validation activity and record as per
the table given below.
|
Equipment |
ID No. |
Location |
Preventive Maintenance Date |
Next Due date |
|
Vials
washing machine |
|
|
|
|
|
Water
for injection |
|
|
|
|
|
Compressed
air |
|
|
|
|
|
Purified
water |
|
|
|
|
6.5
Validation
Procedure:
The following tests shall be carried out to establish the
validation of Vial Washing Machine (PIVWM-01):
Ø Chemical
decontamination study (By spiking with Sodium chloride)
Ø Particulate
decontamination study (by spiking with Charcoal powder).
Ø Endotoxin
decontamination study (By spiking with Endotoxin).
6.6 Chemical soluble matter Decontamination
Study:
The following tests shall be carried out to establish the
efficiency of vial washing machine to removed chemical matter.
6.6.1
Preparation of
sodium chloride solution:
6.6.1.1
Weigh 40 gm of sodium chloride & dissolve in purified
water to make up the volume
200 ml (20% w/V).
6.6.2
Spiking of vials
with chemical:
6.6.2.1
Spiked the no. of vials as per the table 3 for test.
6.6.2.2
Dispense 1.0 ml of the sodium chloride solution to vial to be
spiked.
6.6.2.3
Swirl the vial so that the solution is distributed throughout
the vial.
6.6.2.4
Mark the vials with permanent marker resistant to washing.
6.6.2.5
Dry the vials at 60°C till no water traces are
observed in the vial.
6.6.2.6
Initial chemical
concentration determination (Positive control):
The initial concentration of NaCl solution shall be
determined by quality control as per the formula described in cleaning
analytical method validation protocol no. PRT/CMV/GSC/00.
6.6.2.7
Chemical soluble Matter
decontamination study:
6.6.2.7.1
Objective
The objective of this test is to determine that the vial
washing machine is capable of removing chemicals matter, if present in the
vials.
6.6.2.7.2 Test Requirements
Ø Sodium chloride
spiked vials, AgNo3 (0.1M) solution, HNO3(2M)
6.6.2.7.3 Test Procedure
The procedure for the chemical decontamination study is
defined below
(a) Load the In-feed
belt of the Vial Washing machine with vials of one of the selected pack size.
(b) Set the vials
washing machine as per SOP PI-SP-006.
(c) Switch “ON” The
Vial Washing Machine and operate as per SOP No. PI-SP-006.
(d) For 10ml to 20 ml
allow the machine to run & place 25 vials of spiked & marked vials in
between the other vials while machine is running as per conditions as defined.
(e) For 50 ml and 100
ml allow the machine to run & place 12 vials of spiked & marked vials in
between the other vials while machine is running as per conditions as defined.
(f) Allow the spiked/
challenge vials to go through washing cycle.
(g) Collect the
washed (spiked) vials after completion of washing cycle.
(h) Transfer the
collected vials to Q.C laboratory for testing.
(i) Fill the vials
with filter water (WFI) as per the quantity defined in table -2 and vortex the
vials for 2-3 minute.
(j) Pool the sample one
by one in to Nessler Cylinder add 1 ml of 0.1(N) AgNo3 and 1 ml of
(2M) HNO3 Mix it view against black back ground.
(k) For positive
control vials shall be checked for the recovery of spiked qty by titration with
0.1(N) AgNo3.
6.6.2.8
Acceptance Criteria
Each test solution for the all spiked vials should be free
from any opalescence or turbidity and shall be not more intense color with
reference of the WFI filled in other Nessler Cylinder.
Positive control shall be recovered more than 90% of the
spiked quantity.
The washing performance shall be not accepted as complies if
any spiked vials show any turbidity or opalescence or more intense color than
WFI reference standard.
6.6.2.9
Results
The result shall be recorded in Text Data sheet # 1.
6.7
Particulate insoluble
Particulate matter decontamination study:
The
following tests shall be carried out to establish the efficiency of vial
washing machine to removed insoluble
particulate matter.
6.8
Preparation of
charcoal solution (6.6 %):
Weigh 19.8 gm of charcoal & dissolve in purified water to
make up the volume 300 ml.
6.9
Spiking of vials
with charcoal:
6.9.1
Spiked the no. of vials as per the table 3 for test.
6.9.2
Dispense 1.0 ml of the charcoal solution to vial to be
spiked.
6.9.3
Swirl the vial so that the solution is distributed throughout
the vial.
6.9.4
Mark the vials with permanent marker resistant to washing.
6.9.5
Dry the vials at 60°C till no water traces are
observed in the vial.
6.9.6
Chemical insoluble
Matter decontamination study:
6.9.6.1
Objective
The objective of this test is to determine that the vial
washing machine is capable of removing chemicals insoluble matter, if present
in the vials.
6.9.6.2
Test Requirements
Ø Charcoal solution
(6.6 %) spiked vials, Liquid Particle counter.
6.9.6.3
Test Procedure:
Following the procedure defined below for
the particulate decontamination study
(a) Load the In-feed
belt of the Vial Washing machine with vials of one of the selected pack size.
(b) Set the vials washing
machine as per SOP PI-SP-006.
(c) Switch “ON” The
Vial Washing Machine and operate as per SOP No. PI-SP-006.
(d) For 10ml to 20 ml allow the machine to run & place 25
vials of spiked & marked vials in between the other vials while machine is
running as per conditions as defined.
(e) For 50 ml and 100
ml allow the machine to run & place 12 vials of spiked & marked vials
in between the other vials while machine is running as per conditions as defined.
(f) Allow the spiked/
challenge vials to go through washing cycle.
(g) Collect the
washed (spiked) vials after completion of washing cycle.
(h) Transfer the
collected vials to Q.C laboratory for testing.
(i) Fill the vials
with filter water (WFI) as per the quantity defined in table -2 and vortex the
vials for 2-3 minute.
(j) Pool the sample
and perform the analysis for spiked vials.
(k) Calculate the
particulate counts in spiked wash vials by subtracting the particles of the
water blank.
6.9.6.4
Acceptance Criteria:
LBPC: For ≥ 10µ: NMT 60 Particles/ml
For ≥ 25µ: NMT 6 Particle/ml
6.9.6.5
Result:
The result shall be recorded in text Data Sheet # 2.
6.10
Endotoxin decontamination
study:
6.10.1
Objective
The objective of this test is to demonstrate
that the vials washing machine is capable of removing endotoxin load up to 3
log reduction if present in vials.
6.10.2
Test Requirements:
(a)
Endotoxin Kit (b) Endotoxin spiked vials
6.10.2.1
For procedure of spiking of vials with endotoxin:
Refer
SOP QC-SP-357 “Handling and maintenance of endotoxin indicators”
6.10.2.2
Acceptance
Criteria
A minimum log reduction of 3
logs should be achieved.
6.10.2.3
Results shall be recorded Test Data sheet # 3.
6.11
For the vial
selection for each time of validation matrix shall be followed as per annexure no.1.
6.12
For the spike of Sodium Chloride solution, Charcoal
solution and BET for each time of validation qty shall be followed as per annexure no.2.
6.13
For the recovery or for the analysis of rinse sample
the rinse water quantity of WFI or Lal reagent water quantity
followed as the quantity as per annexure
no. 3
6.14
For the pressure set
parameters for the Recalculated water PW, WFI, compressed Air and Washing Speed
set parameters shall be followed during all types of vials washing performances
as per annexure No. 4
7.0
Sampling Plan and
Acceptance Criteria:
|
Stage |
Sampling
Criteria |
Test to be
performed |
Sample quantity |
Acceptance
Criteria |
|
|
Before vial
washing |
Recirculated
Water |
Visual Check and
LBPC |
Around 100 ml |
1.
Shall be free from visible particles 2.For
sub visible particles ≥10
µ =NMT 60/ml ≥25
µ NMT 6/ml |
|
|
WFI quality |
Around 100 ml |
||||
|
Compressed air
quality (Bubbling of compressed air in 100 ml water) |
Around 100 ml |
||||
|
After Vial
washing |
Sodium chloride
spiked vials |
Removal of
chemical matter |
Annexure no.-2 |
Absent |
|
|
Charcoal spiked
vials |
Removal of
particulate matter |
1.
Shall be free of visible particles 2.For
sub visible particles ≥10
µ NMT 60/ml ≥25
µ NMT 6/ml |
|||
|
Bacterial
Endotoxin spiked vials |
Endotoxin decontamination study
|
Should show more
than 3 log reduction |
8.0
Discrepancy and Corrective Action Report:
Documentary and discrepancies observed during the validation of the
equipment in format attached to each test data sheet # 4. Include the
corrective action of the same. When all the discrepancies are satisfactory
resolved or an approved action plan is developed which insure that the discrepancies
will be resolved.
9.0
References:
(a)
User operating manual
(b)
USP 30
(c)
SOP of “Handling and maintenance of endotoxin
indicator” SOP No. QC-SP-357.
(d)
SOP of “Operating of vials washing machine. SOP No.
PI-SP-006
10.0
Summary:
The validation report shall include a summary
of validation activities describing the following in brief
(a)
Protocol reference
(b)
Dates of validation activites
(c)
Pre- validation testes performed
(d)
Confirmation of calibration and preventive
maintenance
(e)
Chemical decontamination study
(f)
Removable of insoluble particle matter
(g)
Endotoxin spiking study report of vials
11.0
Conclusion:
The validation report shall include statement
for conclusion of the validation activity based on result and observation from
the validation activity.
12.0
Attachment:
The following are the attachment which shall be used for collection and
evaluating the raw data.
|
Sr.No. |
Test data sheet No. |
Test data sheet Title |
No.
of pages |
|
1.0 |
Test data sheet
# 1 |
Chemical
decontamination study |
03 |
|
2.0 |
Test data sheet # 2 |
Insoluble Particulate matter
decontamination study |
02 |
|
3.0 |
Test data sheet # 3 |
Endotoxin
decontamination study |
07 |
|
4.0 |
Test data sheet # 4 |
Discrepancies
and corrective action |
01 |
13.0
Periodic validation schedule:
|
Sr.No. |
Tests |
Frequency |
|
1.0 |
Chemical
decontamination study |
Once in 6 month |
|
2.0 |
Particulate matter decontamination study |
Once in 6 month |
|
3.0 |
Endotoxin decontamination study |
Once in 6 month |
14.0
Revalidation schedule:
Revalidation shall be carried out in case of
14.1
Major maintenance of critical
parts.
14.2
Change of cycle program, inclusion
of new load.
END OF
THE DOCUMENT
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