0.

0 GENERAL INFORMATION
: Piperacillin & Tazobactam for Injection…..
Product Name
……
: Each vial contains:
Sterile Piperacillin Sodium USP
Composition
Eq. to Piperacillin ………………………mg
Sterile Tazobactam Sodium
Eq. to Tazobactam………………………mg
Shelf Life : Months
Batch No. :
Batch Size : kg Vials
Mfg. Date :
Exp. Date :
Product Code :
Pharmacopoeia Reference : IHS
Mfg. License No. :
Description : ….....ml clear molded glass vials type-……..
Issued By QA
:
(Sign. /Date)
Production Commenced On :
Production Completed On :
Checked By Head – Production
:
(Sign. /Date)
Approved By Head – QA
:
(Sign. /Date)

1.0 TABLE OF CONTENTS

0.0 General Information…………………………………………………………………1
1.0 Table of Contents and BMR review checlist………………………………………. 2
2.0 Raw Material Calculation Sheet…………………………………………………….4
3.0 Raw Material & Primary Packing Requisition with Dispensing Specification…. 5
4.0 General Instructions for Processing & Pre Manufacturing Controls……...….....6
5.0 Washing and Sterilization of Rubber Bungs …………………………….……..…..7
6.0 Filling Assembly, Sterile Garment Washing and Aluminum Seal Sterilization …8

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
PR055/F01/16-00 Page 1 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials
7.0 Washing and Sterilization of Vials ………………………………………..……......10
8.0 Differential Pressure ……………………..……………………….…….…………...12
9.0 Powder Filling, Bunging and Sealing of Vials……………………………………...13
10.0 Reconciliation of Primary Packing Material…………….….……………………...20
11.0 Batch Reconciliation...…...………………………………………………….…….....21
12.0 Batch Deviation Report...……………………………………………………………22

1.1 BMR review Checklist

S. No Checklist particulars Observations Remarks
1 Batch execution sheet attached with BMR
2 API COA attached with BMR
3 Bills of Materials attached with BMR
Washing & Sterilization printout attached with BMR
a. Rubber Bungs
4
b. Garments/Machine parts/ Flip off seal
c. Vials
5 Rinse water sample analysis of Machine parts
6 Rinse water/LOD sample analysis of Rubber Bung
Vial Rejection analysis
a. Decrtoning Stage
7 b. Washing stage
c. Filling Stage
d. Sealing stage
8 In-process activity carried out
9 Reconciliation/% yield
10 EMRN attached with BMR
11 Any deviation observed
12 Any correction in BMR
Checked By Production Verified By IPQA

2.0 RAW MATERIAL CALCULATION SHEET

2.1 Calculation of Piperacillin & Tazobactam is as below
2.1.1 Mfg. Date: …………… Exp. Date: ……………. A.R. No.: …………………....

2.1.2 Available Qty. :( W1) ………….…….. Kg Mfg. By: ……………………………….

Assay of Piperacillin & Tazobactam Anhydrous =
2.1.3 Water % Factor
____________%
2.1.4 Calculate the actual quantity of the Piperacillin & Tazobactam required by the formulation A.R.
No……………..
Target Weight = Label Claim X 100 X 100 X Factor
Assay X (100- Water)
= ……………….X 100 X 100 X = …………mg / vial (T1) = Target Weight
Assay (………….. %) x (100 - ………..)
Batch Size in Vials = W1 x 1000x1000 = …………. x 1000x1000 = V1 .........................Vials
PREPARED BY CHECKED BY APPROVED BY
(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 2 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials
T1 ……………
2.1.5 Required Vials from second A. R. No. V2 = V- V1 = …………… - …………… =…………..Vials

2.1.6 Mfg. Date: …………… Exp. Date: ……………. A.R. No.: …………………....
2.1.7 Available Qty. :(W2) ………….…….. Kg Mfg. By: ……………………………….
Assay of Piperacillin & Tazobactam Anhydrous =
2.1.8 Water % Factor
____________%
Calculate the actual quantity of the Piperacillin & Tazobactam required by the formulation A.R.
No……………..
Target Weight = Label Claim X 100 X 100 X Factor
Assay X (100- Water)
2.1.9
= ……………….X 100 X 100 X = …………mg / vial (T2) = Target Weight
Assay (………….. %) x (100 - ………..)
Required Powder in Kg = V2 x T2 = ……………..x……………..= W3 .........................Vials
1000 x 1000 1000 x 1000
Total Quantity of Piperacillin & Tazobactam (W) = W1 + W3 = …………… + …………… =
2.1.10
………………Kg
2.1.11 Total Batch Size in Vials (V) = V1 + V2 = …………………… Vials
Total Target Weight (T) According to ratio:
V = ………………... = …………… A V = …………………... = ……………B
V1 V2
2.1.12
T1 = ………………… = …………... C T2 = ………………… = …………... D
A B
2.1.13 Total Target Weight= C + D = …………… + ………………….. = ……………….. mg

Done by/On: Verified by/On:

Production Officer IPQA – Officer

3.0 RAW MATERIAL & PRIMARY PACKING REQUISITION WITH DISPENSING

SPECIFICATION:
3.1 General Instructions say (Yes/No)
3.1.1 Check that all the materials to be issued are approved by Quality control department

Check the material name, mfg. date, exp. date & assay written in requisition slip
3.1.2
with the approved label of that respective container.
Do the complete gowning along with mask & gloves while dispensing of raw
3.1.3
materials.
3.1.4 Avoid direct contact with the raw materials.

3.1.5 All the equipment used for dispensing purpose should be cleaned.

3.1.6 Check the following parameter before dispensing the raw materials:

3.1.6.1 Ensure cleaning status of dispensing area Satisfactory.

Ensure temperature and relative humidity of the dispensing area (raw material store)
3.1.6.2
as per prescribed SOP No.

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 3 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

3.1.6.3 Ensure the gowning procedure to dispensing area as per SOP No.

3.1.6.4 Ensure LAF pressure is as per prescribed.

3.1.6.5 Ensure calibration status of balance before starting of weighing.

3.1.6.6 Ensure released label on each container.

3.1.6.7 Weighing of materials (refer BOM for entry of weight checking)

3.1.6.8 Inspection record daily is to be recorded.

3.1.6.9 Check the line clearance asset on dispensing booth.

3.1.6.10 Check that there are no unwanted materials in dispensing booth.

Checked By Production Verified By IPQA

 The shelf life is two years.

 The shelf life of the product will depend upon the availability of shelf life of the raw material
used.
 Attached raw and primary packing material slip.

3.2 Raw material requisition & dispensing sheet

Label Dispensed quantity Dispensing
Ingredients & Req.
Claim UOM A.R. No.
specification Qty Gross Wt Tare Wt. Net Wt. Prod. IPQA
mg/ Vial
Sterile
Piperacillin
Sodium USP
Eq. to ………
Piperacillin & mg/vial kg Attached Bills of Material cum
Sterile Requisition as per format no.
Tazobactam
Sodium
Eq. to
Tazobactam
3.3 Vial requisition and dispensing sheet
Required Dispensed Checked By
Material Description Unit A.R. No.
Quantity quantity Prod. IPQA
…… ml molded
Clear glass vials Nos
type-…….
3.4 Rubber Bung requisition and dispensing sheet
Required Dispensed Checked By
Material Description Unit A.R. No.
Quantity quantity Prod. IPQA
PREPARED BY CHECKED BY APPROVED BY
(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 4 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

20 mm grey/bromo
Nos
butyl rubber bung
3.5 Aluminum Flip off seal cap requisition and dispensing sheet
Required Dispensed Checked By
Material Description Unit A.R. No.
Quantity quantity Prod. IPQA
………………. color
Nos
20 mm Flip off seal
* Quantity of Piperacillin Sodium & Tazobactam is calculated on basis of 100% of its assay.

Checked By Production Verified By IPQA

4.0 GENERAL INSTRUCTIONS FOR PROCESSING & PRE – MANUFACTURING

CONTROLS:
4.1 General Instructions
4.1.1 Use trained and qualified personnel to perform activities.
4.1.2 Ensure status labeling at every stage of processing and filling indicating Product
name, Batch No., Processing status and date.
4.1.3 Ensure that the air, water, nitrogen and vacuum supply is on & with in limit
4.1.4 Proceed only after ensuring wash water analysis clearance during every stage of
processing and filling
4.1.5 QA check during batch change over is optional, whereas mandatory, in case of
product change over.
4.1.6 Affix dispensed and cleaned equipment approved labels of on left side page of
BMR on relevant space.
4.2 PRE – MANUFACTURING CONTROLS:
The following area qualification should be strictly adhered to for air quality at Yes/
4.2.1 different stages of manufacturing No

4.2.1.1 Unit preparation and washing of class 1,00,000

4.2.1.2 Manufacturing area of class 100 with class 1000 background for Filling purpose.
Manufacturing area class 100 with class 10, 000 backgrounds for blending and
4.2.1.3
sealing purpose.
All the equipment and utensils used shall be in clean condition with ‘’CLEANED”
4.2.1.4
label affixed after authorization from supervisor and QA Officer.
4.2.1.5 Restrict personnel movement in aseptic area to minimum in order.
Check the room temperature, humidity, positive pressure of all area and laminar
4.2.1.6
flow.
All the equipments, vessels & containers shall bear proper labels showing the
4.2.1.7
contents & stage of processing.

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 5 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials
All rejection generated at different stages shall bear proper label clearly and
4.2.1.8
prominently.
4.2.1.9 All workers must have to wear dresses as per requirement of respective areas.
4.2.1.1
Line clearance of QA is necessary before commencing any operation as per SOP
0
4.2.1.1 Counter check and record weight, A.R. No., expiry date and assay of the raw
1 materials received from the raw material store as per proper material requisition slip.
4.2.1.1 All equipment of the filling area (sterile area) is properly cleaned and sterilized as
2 per SOP No. respectively.
4.2.1.1
Ensure entry, exit, gowning and de-gowning into sterile area as per SOP No.
3
Checked by Verified by
(Production officer) (IPQA officer)

5.0 WASHING AND STERILIZTION OF RUBBER BUNGS

5.1 Washing & Sterilization of Rubber Bungs
5.1. Use trained and qualified personnel to perform activity.
1
5.1. Identify each machine with status label indicating product name; Batch No.; date and stage.
2
5.1. IPQA check during batch change over is optional, whereas mandatory, in case of product
3 change over.
5.1. Use all equipment with safety wherever necessary.
4
5.2 Checklist before line clearance for Bung Processor cum Steam Sterilizer:
Checked Verified
Sr. No. Parameters to be checked Observation
By By
5.2. 1 Ensure Vacuum Gauge (Limit -0.730 to -0.760 mmHg)
5.2. 2 Ensure Compressed Air (Limit 7.5 to 8.5 kg/cm2)
5.2.3 Ensure that Plant Steam Pressure (Limit 6.5 to 7.5 kg/cm2 )
5.2.4 Ensure Process Air Pressure (Limit 8 to 10 kg/cm2)
5.2.5 Ensure that WFI Pressure (Limit NLT 2.0 kg/cm2)
5.2.6 Ensure that PW Pressure (Limit NLT 2.0 kg/cm2)
5.2.7 Ensure that Pure Steam (Limit 4.0 to 6.0 kg/cm2)
5.2.8 Ensure that Pressure FRL (Limit 6.0 to 8.0 kg/cm2)
5.2.9 Ensure that Pressure Door Gasket NST (Limit 2.5 to 3.5 kg/cm2)
5.2.10 Ensure that Pressure Jacket (Limit 1.0 to 1.1 kg/cm2)
5.2.11 Ensure Pressure of Processed air in FRL (Limit 7.0to 8.0 kg/cm2)
5.2.12 Ensure that Pressure of Chamber (Limit 1.2 to 1.4 kg/cm2)
5.2.13 Ensure that Pressure Door Gasket ST (Limit 2.5 to 3.5 kg/cm2)
PREPARED BY CHECKED BY APPROVED BY
(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 6 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials
5.3 Line & Area clearance for Rubber Bung by IPQA officer. Date:
Date of Checked Verify
Previous Item Load No.
completion By Prod. By IPQA

5.4 Decartoning and Washing of Rubber bung

5.4. De-carton the rubber bungs in the de-cartooning area and Date Don Checked Verified
transfer them to washing room as per SOP No. e By by by
Wash the rubber bungs in bung processor as per SOP No. &
5.4. check in process parameters of Washed rubber bungs as under.
Time from ________hrs to _______hrs &.Sterilize the rubber
bungs in HPHV autoclave system at 121°C, 1.2 bar pressures
for 30 minutes as per SOP No. Time from _______hrs to
5.4. ________hrs.

5.5 Rubber Bung Washing Details. Date:

Washing, Sterilization and Drying of Rubber Bungs Checked by
Quantity Load No. PW Wash WFI wash Sterilization Drying
Prod. IPQA
From To From To From To From To

5.6 In process Checks of Bung During Washing

Material Detail Quantity Date of Sampling Clarity After PW Clarity After WFI Prod. IPQA

5.7 Bung Analysis Report. (Attach QC Report)

Material Detail Quantity Date of Sampling A. R. No. pH PW pH WFI LOD

6.0 FILLING ASSEMBLY, STERILE GARMENT WASHING AND ALUMINIUM FLIP

OFF SEAL STERILIZATION
6.1 Filling Assembly Cleaning Record:
6.1. Clean and prepare filling assembly, hopper, port Wheel, scoop Dat Don Checke Verifie
and forceps as per SOP No. Time from _____hrs to _____hrs. e e By d by d by
Sterilize the assembled filling equipments & assembly in
HPHV
6.1. Autoclave system at 121°C and 1.2 bar pressures for 30 minutes
as per SOP No. Time from ______hrs to _____ hrs.
PREPARED BY CHECKED BY APPROVED BY
(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 7 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

6.2 Rinse Water Report. (Attach QC Report)

Date of Analytical
Equipment for Cleaning Previous product Batch No.
Sampling Report No.
filling assembly, hoppers, port
wheel, forceps and scoop
6.3 Sterile Garments Cleaning Record:
6.3. Clean and prepare sterile garments used by filling personnel as Dat Don Checke Verified
per SOP No.. Time from _____hrs to _____hrs. e e By d by by
Sterilize the sterile garments used by filling personnel in
6.3. HPHV
autoclave system at 121°C, 1.2 bar pressures for 30 minutes as
per
SOP No. Time from _______hrs to ______hrs.

6.4 De – Cartooning of Aluminum Flip off Seal

6.4. De-cartons the Aluminum Flip off Seal in the de-cartooning area Dat Don CheckedVerified
and transfers them to washing room as per SOP No. e e By by by
Transfer the seals to perforated SS drums Time from
6.4. __________hrs to __________hrs.
Sterilize the Aluminum Flip off Seal in HPHV autoclave system
at
6.4. 121°C, 1.2 bar pressures for 30 minutes SOP No. Time from
____________hrs to ____________hrs.

6.5 Filling Accessories, Sterile Garment and Flip Off Seal Sterilization Date:
6.5.1 Load the filling equipments, sterile garments and flip off seal in HPHV autoclave system.
6.5.2 Set the temperature 121°C for 30 minutes at pressure 1.2 bar.
6.5.3 Note down the following parameters and attach the supporting documents of sterilization.
Sterilization Drying
Temp Pressure
Item Load No. Date Fro Fro
°C (Bar) To To
m m

Done by Operator Prod. Checked by Production Officer Verify by IPQA Officer

6.6 Filling Accessories, Sterile Garment and Flip Off Seal Sterilization Date:
Compliance for Cleaning/Sterilization
Sr. No. Equipment/Item
Cleaning (Yes/No) Sterilization (Yes/No)
6.6.1 Filling Wheels I and II
6.6.2 Mesh type Piston (Size………….mm, Nos………….)
6.6.3 Powder Hopper I and II

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 8 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

6.6.4 Powder Collector Trays (4 Nos.)

6.6.5 Scoops (2 Nos.)
6.6.6 Forceps (4 Nos.)
6.6.7 Rubber Stopper Container (2 Nos.)
6.6.8 Bung Bowl (1 Nos.)
6.6.9 Rubber bung Chute (1Nos.)
6.6.10 Lint free Mops (10 Nos.)
6.6.11 SS Container (2 Nos.)
6.6.12 Set of Sterile Garments (…………….Nos.)
6.6.13 Aluminum Flip Off Seal (……………………. Seals)
Checked by/On Production: Verified By/On IPQA:

7.0 WASHING AND STERILIZATION VIALS

7.1 Washing & Sterilization of Vials
7.1.1 Ensure and involve trained and qualified personnel to perform activity.
7.1.2 Affix the status label on each machine with product name; Batch no.; date and stage.
7.1.3 IPQA check is mandatory as per BMR or in case of any change over.
7.1.4 Use all equipment with safety wherever necessary.
7.2 Line & Area clearance for Washing and Sterilization of Vials by IPQA Officer.
Checked By Approved
Date Previous Product Batch No.
Production by (QA)

7.3 Decartoning, Washing and Sterilization of Vials.

7.3.1 De-carton the clear transparent glass vials, in de-cartooning area Date Done CheckedVerified
and transfer them to washing room as per SOP No. By By by
7.3.2 Wash the vials in linear washing machine, as per SOP No. & check
in process parameters of Washed vials.
7.3.3 Sterilize the vials in sterilizing tunnel as per SOP No.
7.3.4 Quarantine the shipper aside which are having any broken vials,
record the details in decartoning log book inspect 100% for glass
piece and glass particle at last.
7.4 Decartoning Operation Date:
Date Start Time Stop Time Issued Qty. Reject Qty. Good Qty Done By Check By

7.5 In-process check for Vial Washing. Frequency: Every hour

Pressure in kg / cm2
Clarity of all
Time NLT 2.0 NLT 1.0 NLT 1.2 NLT 1.2 Checked by Verified By
Nozzle
CA RW PW WFI

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 9 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

CA: Compressed Air, RW: Re-circulated Water, PW: Purified Water, WFI: Water for Injections

7.6 In process set parameters: (Depyrogenation) Frequency every hour and when power
switches over to DG or DG switch over to power.
Drying Sterilization Sterilization Cooling Stabilization Conveyer Conveyer Print
Parameters
Zone Zone Entry Zone Exit Zone Zone Start Speed Interval
Limit→ 100-120
70-120°C 300-350°C 310-350°C 30-110°C 25-35°C 300 60 sec.
Time ↓ mm/min.

Checked By: Verified By:

7.7 In process Syringiblity of Washed Vials. (Frequency Every hour)
Rejection Details Checked by
Time Qty. Good % of Rejection.
Fiber Glass Black Other Prod. Q.A

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 10 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

7.8 Washing Operation

Date Start Time Stop Time Issued Qty. Reject Qty. Good Qty Checked By Verified By

*%age Yield

8.0 DIFFERENTIAL PRESSURE

8.1 Pressure Difference (Pa) Frequency: Every hour
Name of Air Lock- Air Lock Air Lock Air Lock Exit Air Cooling Filling Sealing Blending
Corridor
area I -II -III -IV Lock Zone Room Room Room
Limit→ 25±5 35±5 45±5 45±5 35±5 50±5 55±5 60±5 55±5 55±5
Time ↓ Pressure Difference in (Pascal)

Checked By: Verified By:

8.2 Pressure Difference of the LAF Frequency every hour.

Time ↓ LAF on Vial LAF on Sealing

LAF On Cool Zone LAF on Blender Checked Verified
Limit filling &Bunging M/C
By By
→ 10-20 mm of WC 10-20 mm of WC 10-20 mm of WC 10-20 mm of WC

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 11 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

9.0 POWDER FILLING, BUNGING AND SEALING OF VIALS

9.1 General Filling Instructions
9.1.1 Used trained and qualified personnel for all the operations. Yes/No
9.1.2 Check the Temperature & RH of filling room and ensure that are in respective limit
Ensure that the nitrogen gas supply is ON and flow is proper i.e. 0.5kg/cm 2 to 1.5
9.1.3
kg/cm2
9.1.4 Ensure vacuum supply pressure is in respective limit(500-610 mmHg)
Identify machine with status label indicating product name, batch no.; date and
9.1.5
stage
9.1.6 Transfer the sterile material to hopper.
Fill the Powder of target weight to desire strength to the sterilized vials with pre &
9.1.7
post nitrogen flushing.
QA check during batch change over is optional, whereas mandatory, in case of
9.1.8
product change over.
9.1.9 Rejection in filling should be labeled and kept separately & destroyed.
9.1.10 Use all equipment with safety wherever necessary.
9.2 Line & Area clearance for Filling and sealing by IPQA person.
Checked approved
Date Previous product Batch No.
By (Prod.) by (Q.A)

9.3 Checklist before line clearance for Filling and Sealing

Checked Verified
S. No. Parameter to be check Observation
by by
9.3.1 Ensure Vacuum Gauge Hopper –I (Limit -300 to -500 mmHg)
9.3.2 Ensure Vacuum Gauge Hopper –II (Limit -300 to -500 mmHg)
9.3.3 Ensure Nitrogen Pressure Hopper –I (Limit 0.5 to 2.5 kg/cm2)
9.3.4 Ensure Nitrogen Pressure Hopper –II (Limit 0.5 to 2.5 kg/cm2)
9.3.5 Ensure that Compressed Air Hopper –I (Limit 0.5to 3.0 kg/cm2 )
9.3.6 Ensure that Compressed Air Hopper –II (Limit 0.5to 3.0 kg/cm2 )
9.3.7 Ensure Vacuum Gauge Bung (Limit 0 to -150 mmHg)
9.3.8 Ensure LAF Pressure Filling & Bunging (Limit10 to 20 mm of WC)
9.3.9 Ensure LAF Pressure Sealing (Limit10 to 20 mm of WC)
9.4 Pre set up and in process parameters of filling operation:
Sr. No. Test Limit Frequency
9.4.1 Description White/Off White crystalline powder --
Every Half an
9.4.2 Weight variation Target weight ±…… %
Hour
Every Half an
9.4.3 Vial Sealing Proper Sealing
Hour
9.4.4 Empty Vial Syringiblity Visible particulate matter should be absent At starting
9.4.5 Filled Vial Syringiblity Visible particulate matter should be absent Container wise

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 12 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

9.5 Vial filling / sealing operation

9.5.1 Recheck the gross weight of dispensed raw materials. Date Done Checked Verified
9.5.2 Assemble the vial filling, bunging and sealing machine as by by by
per requirement.
9.5.3 Adjust the weight in each piston (1 to 24) as per the target
weight, depending on the assay of raw material as per
calculation done.
9.5.4 Operate the filling, Bunging and sealing machine as per
SOP No. SLL/PR/034.
9.5.5 Collect the filled and sealed vials outside the area through
the channel in containers.
9.6 Filling and sealing details
9.6.1 Filling started at : Date:
9.6.2 Completed at : Date:
9.6.3 Filling machine ID No.: …………….
9.6.4 LAF pressure ……………… (10-20 mm of WC)
9.6.5 Nitrogen Flushing ………………. (0.5 to 1.5 kg/cm2)
9.6.6 Vacuum Pressure …………..mmHg (limit: -400 to -610 mmHg)
9.6.7 Temperature and RH of room Temp. ……….. (25±2%°C). RH ………. (25±5%)
9.6.8 Filling Room Pressure ……………. Pascal (Limit 55-65 Pascal)
9.6.9 Filling operator
9.6.10 Target filled weight …………………mg and weight variation ±…………. %
9.6.11 Weight variation limit __________ mg to __________mg
9.7 Filling operation details.
Issued Powder Powder Loss Good Powder
Date Start Time Stop Time Checked By Verified By
Qty. in kg Qty. in kg Qty. in kg

*%age Yield
9.8 Reconciliation of filled vials.
Date Start Time Material Details Vials Rubber Bungs Aluminum Seal Checked By Verified By
Received Qty.
End Time Reject Qty.
Good Qty.

9.8.1 Reconstitution Clarity Check

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 13 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials
9.8.2 Initial 12+ 12 empty plugged and sealed vials with numbering.
Vial Vial Vial Vial
Black Glass Fiber Black Glass Fiber Black Glass Fiber Black Glass Fiber
No. No. No. No.
01 07 13 19
02 08 14 20
03 09 15 21
04 10 16 22
05 11 17 23
06 12 18 24
Checked By Production Verified By IPQA
9.8.3 Container No. wise 2 vials from each container.
Container No. 1 Container No. 2 Container No. 3 Container No. 4
Vial Vial Vial Vial
Black Glass Fiber Black Glass Fiber Black Glass Fiber Black Glass Fiber
No. No. No. No.
01 01 01 01
02 02 02 02
Container No. 5 Container No. 6 Container No. 7 Container No. 8
Vial Vial Vial Vial
Black Glass Fiber Black Glass Fiber Black Glass Fiber Black Glass Fiber
No. No. No. No.
01 01 01 01
02 02 02 02
Container No. 9 Container No. 10 Container No. 11 Container No. 12
Vial Vial Vial Vial
Black Glass Fiber Black Glass Fiber Black Glass Fiber Black Glass Fiber
No. No. No. No.
01 01 01 01
02 02 02 02
Checked By Production Verified By IPQA
9.8.4 Initial 12+ 12 filled vials with numbering.
Vial Vial Vial Vial
Black Glass Fiber Black Glass Fiber Black Glass Fiber Black Glass Fiber
No. No. No. No.
01 07 13 19
02 08 14 20
03 09 15 21
04 10 16 22
05 11 17 23
06 12 18 24
Checked By Production Verified By IPQA

9.8.5 Clarity of 4 Filled vials after every hour.

Vial 01 Vial 02 Vial 03 Vial 04
Time
White Black Glass FiberWhite Black Glass Fiber White Black Glass Fiber White Black Glass Fiber

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 14 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

Checked By Production Verified By IPQA

9.8.6 Controls after Sealing by Visual Inspection of vials every hour by production and IPQA
alternatively.
Process Parameters Observations
Total Checked
Time Low High Seal Black Glass Broken Without
Rejection by
Weight Weight Defect Particle Particle Vial Bung

Checked By/Date Production: Verified By/Date IPQA:

9.8.7 Weight Variation Sheet for Hopper-I

9.8.7.1 In process checks of filling and sealing operation.
9.8.7.2 Take the weight of vials after every 60 minutes & record the temperature and humidity. Limit:
Temperature 25±2 °C and Relative Humidity 25±5 %.
Date: - Target Wt: -
s
Hopper 1 t Temp. RH Done
Time Weight variation limit Target Wt±……% Limit = _____ to _______ mg °C % by
01 02 03 04 05 06 07 08 09 10 11 12 Average

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 15 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

st
Average Filled Weight of Vial in Hopper I =…………………..mg/vial
Total vials used in wt. variation = …………………….. Vials
Production Officer: IPQA Officer:
Date Date

nd
9.8.8 Weight Variation Sheet for Hopper-II
9.8.9 In process checks of filling and sealing operation.
9.8.10 Take the weight of vials after every 60 minutes & record the temperature and humidity.
Limit: Temperature 25±2 °C and Relative Humidity 25±5 %.
Date: - Target Wt: -
nd
Hopper-II Temp. RH Done
Time Weight variation limit Target Wt±……% Limit = _____ to _______ mg °C % by
01 02 03 04 05 06 07 08 09 10 11 12 Average

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 16 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

nd
Average Filled Weight in the Vial Hopper II =…………………..mg/vial
nd
Total vials used in wt. variation Hopper II = …………………….. Vials
st nd =
Total average Weight = Hopper I + Hopper II /2 …………..+……………./2 =…………….mg/Vial
st nd
Total vials used = Hopper I + Hopper II =………………..+……………. =………………….Vials
Production Officer: IPQA Officer:
Date Date

9.9 Sealing process

Line clearance for sealing process
Checked By Approved by
Date Previous Product Batch No.
Production QA

Procedure From To Done Checked

by by
1. Check the sealing quality of each head before start the machine.
2. Run the machine.
3. Rejection during sealing

In process Check for Sealing Quality:

Date & Parameter Head 1 Head 2 Head 3 Head 4 Head 5 Head 6 Head 7 Head 8
Time
Sealing Quality

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 17 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials
Leak test
Done by
Checked by

Date & Parameter Head 1 Head 2 Head 3 Head 4 Head 5 Head 6 Head 7 Head 8
Time
Sealing Quality
Leak test
Done by
Checked by

Date & Parameter Head 1 Head 2 Head 3 Head 4 Head 5 Head 6 Head 7 Head 8
Time
Sealing Quality
Leak test
Done by
Checked by

9.10
Handling of rejects as per SOP No.:
9.12.1 Open each Vial and discard the powder during in process checking and seal rejection.
9.12.2 Discard the empty vials of weight variation during in process.
9.12.3 Destroyed the vials of visual rejection.
9.12.4 Total no. of vials destroyed
9.11
Finish product sampling:
For sterility : Collect 5 vials initially and at every 30 minutes interval during
9.13.1
filling operation (total composite samples should be 30 vials)
For chemical test and weight variation: Collect 3 vials and at every 30 minutes interval
9.13.2
during filling operation (total composite samples should be 30 vials)
10.0 RECONCILIATION OF PRIMARY PACKING MATERIAL
Sr.
Title Vials Rubber Bungs Al. Seal
No.
ISSUANCE (A)
10.1 Quantity Issued
10.2 Additional Quantity Drawn
(A) Total Quantity Issued. (1+2)
REJECTIONS (B)
10.3 Quantity rejected during decartoning &washing
10.4 Quantity rejected during weight variation
10.5 Quantity rejected during filling/sealing

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 18 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials
10.6 Quantity rejected during in-process
(B) Total Rejected Quantity (3+4+5+6)
CONSUMPTION (C)
10.7 Quantity Transferred to Packing
10.8 Finished sample and other sample
(C) Total Quantity Consumed (7+8)
RETURNED (D)
Quantity returned if any
10.9
(Mention Return Note No.)
ACCOUNTABILITY (E)
10.10 Total accounted Quantity (E)=(B+C+D)
VARIANCE
Variance (±) (%)= A-E/AX100
10.11
Limit =± 0.2%
Remark, if any :
Reconciliation done by (Prod.) Counter checked by (IPQA)

11.0 BATCH RECONCILIATION :

MANUFACTURING RECONCILIATION
Batch size =……………. kg
Target Wt. =……………. mg
Theoretical B. Size (A) =……………. Vials
IN-PROCESSLOSS
Powder Loss in hopper (C) =……………. kg
Powder Loss during wt. control (D) =……………. kg
Spillage during filling (E) =……………. Kg
% Rejection (C+D+E) =…………….. %
Total powder consumed =……………. kg
Average fill weight =……………. mg
TOTAL FILLED QTY.
Total no. of Filled vials (B) =……………. vials
IPQA Testing
No of vials used in Syringiblity =……………. vials
Q.C SAMPLES
For analysis sample =……………. vials
Actual yield % (B/A x100) =……………. %
Transfer for Packing Dept. =……………. vials
PREPARED BY CHECKED BY APPROVED BY
(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 19 of 20
 PRODUCT NAME: PIPERACILLIN AND TAZOBACTAM FOR BMR No.:
INJECTION DPPL/BMR/
…….………... ………
BATCH No. BATCH SIZE Vials

Done by production officer Checked by Q.A officer

Date Date

12 BATCH DEVIATION REPORT:

12.1 Deviation Observation:

12.2 Corrective Action

12.3 Remarks, if any

Prepared by Production Verified by IPQA

Date Date

Checked By Approved By
Head– Production Head – QA

PREPARED BY CHECKED BY APPROVED BY

(Sr. Executive – Production) (Head – Production) (Head – QA)
Name: Name: Name:
Sign.: Sign.: Sign.:
Date: Date: Date:
Page 20 of 20