Performance Qualification Protocol for Vial Filling Machine

Performance Qualification Protocol for Vial Filling Machine

  • OBJECTIVE
  • To establish documented evidence which will provide a High degree of assurance and reliability about the performance of the Vial Filling Machine.
  • To Demonstrate that the equipment / system is performing reproducibly and consistently within its operating range of operation and fill weight according to manufacturer’s specifications.
  • SCOPE
  • The scope of this protocol is limited to carry out the performance Qualification of Vial Filling Machine located in the Vial Filling Room.
  • To be performed after the completion and authorization of Operational Qualification.
  • To be performed at the time of relocation or Requalification.
  • Abbreviations and definitions
Abbreviation Definitions
PQP Performance Qualification Protocol
SOP Standard Operating Procedure
NA Not Applicable
No. Number
ºC Degree Centigrade
% Percentage
Mg Milli gram
  • EQUIPMENT DESCRIPTION
  • Vial filling machine is installed in vial filling room.
  • Automatic single Head Injectable Powder Filling Machine is a compact versatile machine. The Machine is precision built on sturdy welded frame of S.S. 304 completely enclosed in stainless steel sheet. This machine can be used to fill sterile powder in vials received from the Sterilizing tunnel.  Then vial will be transferred to the next operation of Rubber Stoppering and transferred to sealing.  This Machine will handle glass vials ranging from 5 ml to 20 ml
  • Powder Filling Unit: 
  • Powder from the powder hopper, will be sucked by the powder wheel, which is located just below the powder hopper. The powder wheel will be having a continuous vacuum suction, which sucks the powder from the powder hopper to the predetermined level of the piston length and then the doctor blade inside the powder hopper will doctor off excess powder. During the indexing movement of the powder wheel powder will be held by the vacuum till powder-filling port comes just above the vial. The vial sensor will sense the vial and it passes the signal to the solenoid valve and vacuum will get off and the compressed gas will flush the powder into the vial. During the filling operation vial will be held to the position by the vial separators. To achieve filling into 5ml to 20ml vials. If required single vial can also be filled with multiple doses to get the desired fill weight. Then vial further moves on conveyor for rubber stoppering operation.
  • Media Filling Unit:
  • Media filling unit is required for process simulation study, which works on the basic principal of simple piston mechanism. Media will be sucked from the liquid media holding tank with the aid of the syringe during the down ward movement of the piston. And it delivers the liquid media during its upward movement into the vial. The bottom end of the syringe is fitted with eccentric shaft. The provided mechanical setting will vary its volume. The volume of the deliverable media will be from 4ml to 80ml.
  • Rubber Stoppering Unit:
  • The filled vials will be held with the aid of gripper belts at rubber-stoppering station. The rubber stoppers from the vibratory bowl will be dispensed through chute. and places stopper on the vials. No rubber stopper – machine stop and no vial -no rubber stopper – machine stop, mechanism will ensure perfect closing of the vial on – line.
  • Pre And Post Gassing Mechanism:
  • The filling machine will be provided with appropriate pre and post gassing mechanism to provide inert environment in the empty vial as well as in the powder filled vial to avoid degradation as per the product requirement.
  • RESPONSIBILITIES AND IDENTIFICATION OF EXECUTION TEAM
  • Responsibilities: The group comprising of representatives from each of the following departments shall be responsible for the overall compliance with this protocol.
Department Responsibility
Production Execute the validation activity & provide necessary support.
Engineering & Utility Participate & provide necessary support for the validation activity
Quality Assurance Monitoring, sampling & reviewing the validation activities.
  • Identification of Executors: The personnel involved in the execution of this protocol shall be recorded- Name, Designation, Signature and Date.
  • TEST PROCEDURES
  • Following test procedures are followed to qualify the equipment for its performance.
  • Qualification Matrix
  • Six fill weights are selected ranging from minimum to maximum based on the product list proposed (used in production) to evaluate the performance range of the filling machine. Fill weight, Fill volume, Vial size and Rubber stoppers are mentioned in the table below.
Vial Size Target

Fill Weight in mg

Machine Speed Rubber stopper
5 ml 125 Minimum 20 mm

Bromo Butyl

Medium
Maximum
250 Minimum
Medium
Maximum
10 ml 500 Minimum
Medium
Maximum
1000 Minimum
Medium
Maximum
20 ml 2000 Minimum
Medium
Maximum
3000 Minimum
Medium
Maximum
  • The drug considered for filling machine performance qualification is Calcium Carbonate.
  • Before Tap density 0.43gm/cc
  • After Tap density 0.55gm/cc
  • It is worthy that the other Cephalosporins, which will be filled by machine, would also be in the similar range of Bulk Density.
  • Verification Of The Impact Of Machine Speed On The Fill Weight
  • Tools required: Change parts, Analytical balance.
  • Material required: Calcium Carbonate, Vials & Rubber stoppers as required.
  • Test procedure:
  • Required machine parts are assembled on the vial filling and stoppering machine.
  • The rubber stoppers (suitable to vial size) are obtained from the Steam steriliser are charged into the respective hopper.
  • Indent and receive the Calcium Carbonate and charged into the respective hopper.
  • The sterilized and depyrogenated vials (as required) are obtained on the scrambler of the vial-filling machine from the sterilizing tunnel.
  • The Calcium Carbonate is filled into the vials as per the fill weight criteria (Refer qualification matrix).
  • Operate the machine as per the SOP and adjust the Vacuum and Nitrogen gas pressures as required.
  • For each fill weight, machine shall be operated at three different speeds i.e minimum, medium and maximum and at each speed for a period of 10 minutes.
  • Collect 20 vials at initial, middle and at the end of the filling operation of the particular speed and test for physical parameters such as Appearance, Weight variation, Average weight and Rubber stopper fixing.
  • Follow the above procedure for each vial size as per the qualification matrix.
  • Verification Of The Impact Of Powder Level In The Hopper On Fill Weight.
  • Tools required: Change parts, Analytical balance.
  • Material required: Calcium Carbonate, Vials & Rubber stoppers as required.
  • Test procedure:
  • This study can be performed during above trials by checking the powder level in the hopper. Or
  • Filling will be carried out at three different levels i.e Full, Half and 1/4th level of powder in the hopper at normal operating range (i.e 80 – 100 vials/minute).
  • Collect 3 sets of vials at each level and test for physical parameters such as Appearance, Weight variation, Average weight and Rubber stopper fixing.
  • Follow the above procedure for each vial size as per the qualification matrix.
  • Acceptance criteria
  • Powder spillage should not be found during filling.
  • No vial should damage.
  • Weight variation :± 5% of target fill weight
  • Average weight :± 2% of target fill weight
  • Rubber stoppers should be fixed properly to the vials.
  • RECORDING OF OBSERVATIONS
  • Record the observations of after execution of each test procedures, in the annexure –1 (Recording of Observations For Performance Qualification).
  • DISCREPANCY AND CORRECTIVE ACTION REPORT
  • Document any discrepancies observed during the Performance qualification of the equipment in annexure -1. 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.
  • COMPILATION, REVIEW AND SUMMARY REPORT
  • Compile and review that all test functions have been completed, reconciled and attached to this protocol. Verify that the approvals for deviations have been taken and are resolved appropriately to the satisfaction.
  • Performance Qualification shall be considered acceptable when all the conditions specified in the test procedures have been met.
  • Prepare the summary report in the annexure –2 (Performance Qualification Report) and submit this for review, approval and authorisation to Validation Core Team.
  • References
  • Annexure – 1 (Recording Of Observations For Performance Qualification)

Annexure – 1 (Recording Of Observations For Performance Qualification)

Details Of Operational Qualification Report
Report No. Date Of Authorisation

 

Identification Of The Executors

 

S. No. Name Designation & Department Sign & Date Training Details

 Comments:

Reviewed by: Date:

Verification Of The Impact Of Machine Speed On The Fill Weight.

 

EQUIPMENT OPERATION DETAILS
Vial size 5 ml Date of Vial Filling & Stoppering
Type & Size of Rubber stopper used Target Fill Weight 125 mg
Number of Vials sealed / minute at Minimum, Medium and Maximum speed. Minimum speed  (________________) Medium speed  (________________) Maximum speed  (________________)
Filling & Stoppering From
To
Done by PD

Sign & Date

Checked by PD

Sign & Date

Verified by IPQA

 Sign & Date

 

INSPECTION OF FILLED & STOPPERED VIALS FOR DEFECTS
Speed Defects
Spillages Cracks /

Vial damages

Any other defects
Minimum speed  (______________________)
Medium speed  (______________________)
Maximum speed

(______________________)

Inspected by PD

Sign & Date

Verified by IPQA

Sign & Date

  • Comments:
  • Reviewed by:Date:

 

Vial Size 5 ml Target Fill weight 125 mg
Acceptance Criteria: 1. Uniformity of Weight ± 5 % of average weight

2. Average weight ± 2 % of target fill weight (122.5 – 127.5 mg)

WEIGHT VARIATION
Vial No. Weight in mg
Minimum Speed Medium Speed Maximum Speed
Initial Middle End Initial Middle End Initial Middle End
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production:                                   Verified By IPQA
  • Sign & Date  Sign & Date
  • Comments:

 

  • Reviewed by:  Date:
EQUIPMENT OPERATION DETAILS
Vial size 5 ml Date of Vial Filling & Stoppering
Type & Size of Rubber stopper used Target Fill Weight 250 mg
Number of Vials sealed / minute at Minimum, Medium and Maximum speed. Minimum speed  (________________) Medium speed  (________________) Maximum speed  (________________)
Filling & Stoppering From
To
Done by PD

Sign & Date

Checked by PD

Sign & Date

Verified by IPQA

 Sign & Date

 

INSPECTION OF FILLED & STOPPERED VIALS FOR DEFECTS
Speed Defects
Spillages Cracks /

Vial damages

Any other defects
Minimum speed  (______________________)
Medium speed  (______________________)
Maximum speed

(______________________)

Inspected by PD

Sign & Date

Verified by IPQA

Sign & Date

  • Comments:
  • Reviewed by:  Date:
Vial Size 5 ml Target Fill weight 250 mg
Acceptance Criteria 1. Uniformity of Weight ± 5 % of average weight

2.  Average weight ± 2 % of target fill weight (245.00 – 255 mg).

WEIGHT VARIATION
Vial No. Weight in mg
Minimum Speed Medium Speed Maximum Speed
Initial Middle End Initial Middle End Initial Middle End
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production: Verified By IPQA
  • Sign & Date  Sign & Date
  • Comments: 
  • Reviewed by: Date:
EQUIPMENT OPERATION DETAILS
Vial size 10 ml Date of Vial Filling & Stoppering
Type & Size of Rubber stopper used Target Fill Weight 500 mg
Number of Vials sealed / minute at Minimum, Medium and Maximum speed. Minimum speed  (________________) Medium speed  (________________) Maximum speed  (________________)
Filling & Stoppering From
To
Done by PDSign & Date
Checked by PD Sign & Date
Verified by IPQA Sign & Date

 

INSPECTION OF FILLED & STOPPERED VIALS FOR DEFECTS
Speed Defects
Spillages Cracks /

Vial damages

Any other defects
Minimum speed  (______________________)
Medium speed  (______________________)
Maximum speed

(______________________)

Inspected by PD

Sign & Date

Verified by IPQA

Sign & Date

  • Comments:
  • Reviewed by:  Date:
Vial Size 10 ml Target Fill weight 500 mg
Acceptance Criteria 1. Uniformity of Weight ± 5 % of average weight

2. Average weight ± 2 % of target fill weight (490.00 – 510.00 mg).

WEIGHT VARIATION
Vial No. Weight in mg
Minimum Speed Medium Speed Maximum Speed
Initial Middle End Initial Middle End Initial Middle End
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production: Verified By IPQA
  • Sign & Date  Sign & Date
  • Comments:
  • Reviewed by:  Date:
EQUIPMENT OPERATION DETAILS
Vial size 10 ml Date of Vial Filling & Stoppering
Type & Size of Rubber stopper used Target Fill Weight 1000 mg
Number of Vials sealed / minute at Minimum, Medium and Maximum speed. Minimum speed  (________________) Medium speed  (________________) Maximum speed  (________________)
Filling & Stoppering From
To
Done by PD

Sign & Date

Checked by PD

Sign & Date

Verified by IPQA

 Sign & Date

 

INSPECTION OF FILLED & STOPPERED VIALS FOR DEFECTS
Speed Defects
Spillages Cracks /

Vial damages

Any other defects
Minimum speed  (______________________)
Medium speed  (______________________)
Maximum speed

(______________________)

Inspected by PD

Sign & Date

Verified by IPQA

Sign & Date

  • Comments:
  • Reviewed by:  Date:
Vial Size 10 ml Target Fill weight 1000 mg
Acceptance Criteria 1.  Uniformity of Weight ± 5 % of average weight

2. Average weight ± 2 % of target fill weight (980.00 – 1020.00 mg).

WEIGHT VARIATION
Vial No. Weight in mg
Minimum Speed Medium Speed Maximum Speed
Initial Middle End Initial Middle End Initial Middle End
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production: Verified By IPQA
  • Sign & Date  Sign & Date
  • Comments:
  •  Reviewed by: Date:
EQUIPMENT OPERATION DETAILS
Vial size 20 ml Date of Vial Filling & Stoppering
Type & Size of Rubber stopper used Target Fill Weight 2000 mg
Number of Vials sealed / minute at Minimum, Medium and Maximum speed. Minimum speed  (________________) Medium speed  (________________) Maximum speed  (________________)
Filling & Stoppering From
To
Done by PD

Sign & Date

Checked by PD

Sign & Date

Verified by IPQA

 Sign & Date

 

INSPECTION OF FILLED & STOPPERED VIALS FOR DEFECTS
Speed Defects
Spillages Cracks /

Vial damages

Any other defects
Minimum speed  (______________________)
Medium speed  (______________________)
Maximum speed

(______________________)

Inspected by PD

Sign & Date

Verified by IPQA

Sign & Date

  • Comments:
  • Reviewed by:  Date:
Vial Size 20 ml Target Fill weight 2000 mg
Acceptance Criteria 1.Uniformity of Weight ± 5 % of average weight

2. Average weight ± 2 % of target fill weight (1960.00 –  2040.00 mg)

WEIGHT VARIATION
Vial No. Weight in mg
Minimum Speed Medium Speed Maximum Speed
Initial Middle End Initial Middle End Initial Middle End
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production: Verified By IPQA
  • Sign & Date  Sign & Date
  • Comments: 
  • Reviewed by:  Date:
EQUIPMENT OPERATION DETAILS
Vial size 20 ml Date of Vial Filling & Stoppering
Type & Size of Rubber stopper used Target Fill Weight 3000 mg
Number of Vials sealed / minute at Minimum, Medium and Maximum speed. Minimum speed  (________________) Medium speed  (________________) Maximum speed  (________________)
Filling & Stoppering From
To
Done by PD

Sign & Date

Checked by PD

Sign & Date

Verified by IPQA

 Sign & Date

 

INSPECTION OF FILLED & STOPPERED VIALS FOR DEFECTS
Speed Defects
Spillages Cracks /

Vial damages

Any other defects
Minimum speed  (______________________)
Medium speed  (______________________)
Maximum speed

(______________________)

Inspected by PD

Sign & Date

Verified by IPQA

Sign & Date

  • Comments:
  • Reviewed by:  Date:
Vial Size 20 ml Target Fill weight 3000 mg
Acceptance Criteria 1.Uniformity of Weight ± 5 % of average weight

2. Average weight ± 2 % of target fill weight (2940.00 – 3060.00 mg)

WEIGHT VARIATION
Vial No. Weight in mg
Minimum Speed Medium Speed Maximum Speed
Initial Middle End Initial Middle End Initial Middle End
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production: Verified By IPQA
  • Sign & Date  Sign & Date
  • Comments:
  • Reviewed by:   Date:
Verification Of The Impact Of Powder Level In The Hopper On Fill Weight

 

Vial Size 5 ml Target Fill weight 125 mg Speed:
Acceptance Criteria 1. Uniformity of Weight ± 5 % of average weight

2. Average weigh ± 2 % of target fill weight (122.5 – 127.5 mg)

WEIGHT VARIATION
Vial No. Weight in mg
Hopper Full Hopper Half Hopper 1/4th
Set 1 Set 2 Set 3 Set 1 Set 2 Set 3 Set 1 Set 2 Set 3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  •  Performed By Production: Verified By IPQA:
  • Sign & Date  Sign & Date
Vial Size 5 ml Target Fill weight 250 mg Speed:
Acceptance Criteria 1.  Uniformity of Weight ± 5 % of average weight

2.  Average weight ± 2 % of target fill weight (245.00 – 255 mg).

WEIGHT VARIATION
Vial No. Weight in mg
Hopper Full Hopper Half Hopper 1/4th
Set 1 Set 2 Set 3 Set 1 Set 2 Set 3 Set 1 Set 2 Set 3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production:  Verified By IPQA:
  • Sign & Date  Sign & Date
Vial Size 10 ml Target Fill weight 500 mg Speed:
Acceptance Criteria 1.    Uniformity of Weight ± 5 % of average weight

2.    Average weight ± 2 % of target fill weight (490.00 – 510.00 mg).

WEIGHT VARIATION
Vial No. Weight in mg
Hopper Full Hopper Half Hopper 1/4th
Set 1 Set 2 Set 3 Set 1 Set 2 Set 3 Set 1 Set 2 Set 3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  •  Performed By Production: Verified By IPQA:
  • Sign & Date  Sign & Date
Vial Size 10 ml Target Fill weight 1000 mg Speed:
Acceptance Criteria 1.    Uniformity of Weight ± 5 % of average weight

2.    Average weight ± 2 % of target fill weight (980.00 – 1020.00 mg).

WEIGHT VARIATION
Vial No. Weight in mg
Hopper Full Hopper Half Hopper 1/4th
Set 1 Set 2 Set 3 Set 1 Set 2 Set 3 Set 1 Set 2 Set 3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production: Verified By IPQA:
  • Sign & Date  Sign & Date
Vial Size 20 ml Target Fill weight 2000 mg Speed:
Acceptance Criteria 1.    Uniformity of Weight ± 5 % of average weight

2.    Average weight ± 2 % of target fill weight (1960.00 – 2040.00 mg)

WEIGHT VARIATION
Vial No. Weight in mg
Hopper Full Hopper Half Hopper 1/4th
Set 1 Set 2 Set 3 Set 1 Set 2 Set 3 Set 1 Set 2 Set 3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  • Performed By Production:  Verified By IPQA:
  • Sign & Date Sign & Date
Vial Size 20 ml Target Fill weight 3000 mg Speed:
Acceptance Criteria 1. Uniformity of Weight ± 5 % of average weight

2. Average weight ± 2 % of target fill weight (2940.00 – 3060.00 mg)

WEIGHT VARIATION
Vial No. Weight in mg
Hopper Full Hopper Half Hopper 1/4th
Set 1 Set 2 Set 3 Set 1 Set 2 Set 3 Set 1 Set 2 Set 3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Minimum
Maximum
Average
  •  Performed By Production: Verified By IPQA:
  • Sign & Date  Sign & Date
Discrepancy And Corrective Action Report
Reference :

Discrepancy :

Corrective Action :

Satisfactorily completed? [Yes / No]:

Checked by / date:  Reviewed and approved by / date:

Reference :

Discrepancy :

Corrective Action :

Satisfactorily completed? [Yes / No]:

Checked by / date:  Reviewed and approved by / date:

Reference :

Discrepancy :

Corrective Action :

Satisfactorily completed? [Yes / No]:

Checked by / date:  Reviewed and approved by / date

  • REQUALIFICATION CRITERIA
  • Requalification criteria is as follows
  • If the machine is subjected for any major maintenance, up-gradation and/or modification that could directly or indirectly affect fill weight and equipment performance.
  • Any change in the fill weight range , vial and rubber stopper specification
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