SURGE Laboratories Private Limited
Semi-basic Manufacturing Area
Title:
Product Master Formula
SMP
Subject:
Standard Manufacturing Procedure (SMP)
Product:
Ciprofloxacin 200mg/100ml IV Infusion
Revision No.: 0
Date: 01-05-2009
Drug
Product Code
Batch #
Batch Size
Pack Size
Page #
Registrat
420 Litres
ion #
CPI
CPI
4000 Vials
1s X 100ml
Page 1 of 1
Shelf Life
Mfg. Date
Exp. Date
Expected Batch
Yield
95 105%
2 Years
Actual Batch Yield
Prepared By
Reviewed By
Approved By
Authorized By
Manager P & D
Manager Production
Manager QA
G.M Plant & Production
DAILY cGMP / IN-PROCESS CHECKS
1.
2.
3.
4.
5.
6.
7.
8.
All activities are performed under the direct supervision of qualified person.
Wear Sterile Specified Uniforms and surgical gloves during all manufacturing and filling activities.
Check all the equipments / Utensils for proper cleanliness.
Check the Graphs of Sterilizers or PLC system graphs to verify the sterilization and pressure differential.
Check the temperature.
Check all the pipes, joints & filters for proper fitting.
Expose the settle plates during filling for 2 hours.
Check Q.C. approval before start of filling.
9. Ensure Line Clearance as per Line Clearance Certificate during all Production activities as per SOP08-QA-004.
10.
Carry out In-process Checks as per SOP-08-QA-005 & record it in Line Inspection Sheet.
11.
Always take out the terminally sterilized vials from ampoule sterilizer after sterilization.
STANDARD MANUFACTURING PROCEDURE (SMP)
A.
WASHING
Sr. #
PROCEDURE STEPS
1. Proceed all the washing activities in GRADE D (ISO-8)
or Class 100,000 environment.
Wash the vials by using Vial Washing Machine (Inv. Code
2.
#: 04-VW-01) or Rotary Washing Machine (Inv. Code #:
04-VW-73).
3.
Wash the vials and machine parts as per SOP-04-005.
4. Get issue of vials as per BMO from Inventory Control one
Operator
Pharmacist
IPQA
Date
SURGE Laboratories Private Limited
Semi-basic Manufacturing Area
Title:
Product Master Formula
SMP
Subject:
Standard Manufacturing Procedure (SMP)
Product:
Ciprofloxacin 200mg/100ml IV Infusion
Revision No.: 0
Date: 01-05-2009
Drug
Product Code
Batch #
Batch Size
Pack Size
Page #
Registrat
420 Litres
ion #
CPI
CPI
4000 Vials
1s X 100ml
Page 2 of 1
Shelf Life
Mfg. Date
Exp. Date
2 Years
Expected Batch
Yield
95 105%
Actual Batch Yield
day before start of manufacturing process.
B.
STERILIZATION
Sr. #
PROCEDURE STEPS
Operator
Pharmacist
IPQA
Date
Operator
Pharmacist
IPQA
Date
Sterilize the washed vials in Dry Oven Sterilizer (Inv.
Code #: 04-OA-08) at 190oC for 2 hours as per SOP-041.
005.
Machine:
Ampoules Sterilizer
Inv. Code. 04 AS 52.
Sterilize the machine parts & filter, stainless steel holding
2. vessels, silicon tubing, gloves, dusters etc in Ampoule
Sterilizer (Inv. Code #: 04-AS-52) at 121o C for 30
minutes as per SOP-04-009.
C.
Sr. #
COMPOUNDING
PROCEDURE STEPS
1. Proceed all the compounding activities in GRADE C
(ISO-7) or Class 10,000 environment.
2. Proceed the compounding process in Compounding
vessel (Inv. Code #: ) or Holding Vessel (Inv. Code #: )
3. Take issue of weighed active and in-active ingredients
from Inventory Control one day in advance as per BMO.
4. Check the name of ingredients, Batch No. and quantities
as per BMO.
5. Clean & Sanitize the compounding vessel as per SOP04-016.
Mop the outer side of Ingredient bags & containers with
6.
70% IPA & shift in Pass through & keep it under ultra
violet light for 10 15 minutes.
Collect the Water for Injection (W.F.I) and submit sample
7.
to QC for complete analysis. Proceed further after QC
approval.
8. Take (70% of total volume) Water for Injection in
compounding vessel and nitrogenate it for 10-15 minutes.
kg at step
9. Add & dissolve Dextrose Anhydrous
# 8 until clear solution is Obtained.
10. Add Ciprofloxacin powder
kg at Step # 9 and
SURGE Laboratories Private Limited
Semi-basic Manufacturing Area
Title:
Product Master Formula
SMP
Subject:
Standard Manufacturing Procedure (SMP)
Product:
Ciprofloxacin 200mg/100ml IV Infusion
Revision No.: 0
Date: 01-05-2009
Drug
Product Code
Batch #
Batch Size
Pack Size
Page #
Registrat
420 Litres
ion #
CPI
CPI
4000 Vials
1s X 100ml
Page 3 of 1
Shelf Life
Mfg. Date
Exp. Date
Expected Batch
Yield
95 105%
2 Years
Actual Batch Yield
stir for 5-10 minutes.
11. Add 1M Lactic Acid Solution till ciprofloxacin powder is
completely dissolved.
Check pH of Solution and adjust if required with 10%
Hydrochloric Acid or 10% Sodium Hydroxide Solution.
12.
pH Range
3.5 4.6
Target pH
4.05
Actual pH
Quantity of 10% HCl solution used
ml
Quantity of 10% NaOH solution used :
ml
Make up the Final Volume of Batch with Water for
Injection.
13.
D.
Theoretical Volume
Actual Volume
420
Litres
Litres
IN-PROCESS QUALITY CONTROL TESTING
Sr. #
PROCEDURE STEPS
Operator
Pharmacist
IPQA
Date
Operator
Pharmacist
IPQA
Date
Send an Intimation Slip (F-08-001) of Ciprofloxacin
1.
solution to Quality Control Department for sampling &
complete Quality Control testing.
2. Ensure the Quality Control Release of Ciprofloxacin
Solution before start of filtration process.
E.
Sr. #
FILTRATION
PROCEDURE STEPS
1. Proceed filtration activity in GRADE C (ISO-7) or Class
10,000 environment.
2. Proceed the filtration process by using Membrane Filter
Assembly (Inv. Code #: 04-MF-41)
3. Perform the bubble point test before and after filtration as
per SOP-04-022 to check the integrity of filter. If test fails,
SURGE Laboratories Private Limited
Semi-basic Manufacturing Area
Title:
Product Master Formula
SMP
Subject:
Standard Manufacturing Procedure (SMP)
Product:
Ciprofloxacin 200mg/100ml IV Infusion
Revision No.: 0
Date: 01-05-2009
Drug
Product Code
Batch #
Batch Size
Pack Size
Page #
Registrat
420 Litres
ion #
CPI
CPI
4000 Vials
1s X 100ml
Page 4 of 1
Shelf Life
Mfg. Date
Exp. Date
2 Years
Expected Batch
Yield
95 105%
Actual Batch Yield
then repeat the filtration with new filter (as and when
required).
4. Connect the silicon tubing with sterilized stainless steel
holding vessel in vial filling room as per SOP-04-016.
After Quality Control Release, filter the solution by
Nitrogen Pressurizing fibre-glass pre-filter and membrane
final filter (0.2 Micron or 142 mm) & transfer the filtered
5.
F.
Sr. #
solution into stainless steel holding Vessel in filling room it
as per SOP-04-016.
Actual N2 Pressure
Filtration Time
VIAL FILLING & SEALING
STAGES / STEPS
Operator
Pharmacist
IPQA
Date
Operator
Pharmacist
IPQA
Date
1. Proceed all the filling activities in GRADE A (ISO-5) or
Class 100 environment.
2. Proceed the filling process by using Vial Filling Machine
(Inv. Code #: ).
3. Wash and sterilize the machine parts & utensils as per
SOP-04-009.
Assemble
the sterilized machine parts, silicon tubing as
4.
per SOP-04-009.
5. Adjust the required volume and then start regular filling
under prevailed aseptic conditions as per SOP-04-003.
Check periodically the volume of vial & record in volume
control sheet (F-04-14) as per SOP-04-026.
6.
G.
Sr. #
Target Fill Volume
105 ml
Minimum Fill Volume
100 ml
Maximum Fill Volume
110 ml
TERMINAL STERILIZATION
STAGES / STEPS
SURGE Laboratories Private Limited
Semi-basic Manufacturing Area
Title:
Product Master Formula
SMP
Subject:
Standard Manufacturing Procedure (SMP)
Product:
Ciprofloxacin 200mg/100ml IV Infusion
Revision No.: 0
Date: 01-05-2009
Drug
Product Code
Batch #
Batch Size
Pack Size
Page #
Registrat
420 Litres
ion #
CPI
CPI
4000 Vials
1s X 100ml
Page 5 of 1
Shelf Life
Mfg. Date
Exp. Date
2 Years
Expected Batch
Yield
95 105%
Actual Batch Yield
Carry out the process of terminal sterilization of filled vials
1. in Ampoule Sterilizer (Inv. Code #: 04-AS-52) at 8 psi /
55Kpa / 0.056 Mpa (110oC) for 30 minutes as Per
SOP-04-009.
H.
PREPARATION & MOPPING OF FILLING AREA FOR NEXT DAY
Sr. #
STAGES / STEPS
Operator
Pharmacist
IPQA
Date
Operator
Pharmacist
IPQA
Date
Operator
Pharmacist
IPQA
Date
Operator
Pharmacist
IPQA
Date
1. Clean & mop the aseptic filling area as per SOP-04-001
for next day.
2. Fumigate the aseptic filling area as per SOP-04-002 as
and when required.
I.
LEAKAGE TEST
Sr. #
STAGES / STEPS
Perform the vacuum leakage test on filled vials in
Ampoule Sterilizer (Inv. Code #: 04-AS-52) using
1.
J.
Methylene Blue dye (1% solution) as per SOP-04-006.
Leakage Pressure
NLT 80 KPa
Time
NLT 120 Seconds
OPTICAL INSPECTION
Sr. #
STAGES / STEPS
Carry out the optical inspection (Manual) of every vial for
1.
low & high volumes, glass piece, black particles, foreign
matter and fibers under light as per SOP-04-030.
2. Carry out periodic line inspection and record observation
in form F-04-12.
Label the vial containers for Product Name, Batch No. &
3. Mfg. Date and store in Quarantine Area and submit
sample to Quality Control Department for complete
analysis.
K.
Sr. #
IN-PROCESS QUALITY CONTROL TESTING
PROCEDURE STEPS
SURGE Laboratories Private Limited
Semi-basic Manufacturing Area
Title:
Product Master Formula
SMP
Subject:
Standard Manufacturing Procedure (SMP)
Product:
Ciprofloxacin 200mg/100ml IV Infusion
Revision No.: 0
Date: 01-05-2009
Drug
Product Code
Batch #
Batch Size
Pack Size
Page #
Registrat
420 Litres
ion #
CPI
CPI
4000 Vials
1s X 100ml
Page 6 of 1
Shelf Life
Mfg. Date
Exp. Date
Expected Batch
Yield
95 105%
2 Years
Actual Batch Yield
Send an Intimation Slip (F-08-001) of Ciprofloxacin filled
1.
& sterilized vials to Quality Control Department for
sampling & complete Quality Control testing.
2. Ensure the Quality Control Release of Ciprofloxacin
Solution before start of coding & packing process.
L.
CODING
Sr. #
1.
STAGES / STEPS
Operator
Pharmacist
IPQA
Date
Operator
Pharmacist
IPQA
Date
Pharmacist
IPQA
Date
Coding of labels and cartons is done manually.
Take the issue of Packaging components as per Batch
2.
Packaging Order (BPO) & code the cartons & labels as
per SOP-04-015.
3. QA Department will paste a Green Release Sticker on
Product Label after review of Batch History Record.
M.
PACKAGING
Sr. #
STAGES / STEPS
1. Packaging of Ciprofloxacin Vials is done manually as per
SOP-04-013.
Paste the sticker labels on Ciprofloxacin vials, pack the
2.
Vials in carton & finally in corrugated shipper & label
them.
3. Carry out periodically In-process checking and line clearance
as per SOP-04-025.
YIELD CALCULATION
Sr. #
STAGES / STEPS
1.
o
Theoretical Yield = ____________4000 Vials______
Actual Yield
Percentage Yield = __________________________
Actual Yield Limit = _________95 105%________
Sample for QC (Solution) = ___________________
Sample for QC (Filled Vials) = _________________
Sample for QC (Packed Vials) = ________________
= __________________________
Operator
SURGE Laboratories Private Limited
Semi-basic Manufacturing Area
Title:
Product Master Formula
SMP
Subject:
Standard Manufacturing Procedure (SMP)
Product:
Ciprofloxacin 200mg/100ml IV Infusion
Revision No.: 0
Date: 01-05-2009
Drug
Product Code
Batch #
Batch Size
Pack Size
Page #
Registrat
420 Litres
ion #
CPI
CPI
4000 Vials
1s X 100ml
Page 7 of 1
Shelf Life
Mfg. Date
Exp. Date
2 Years
o
Retained Sample for QA (Packed Vials) = ________
__________________________________________
__________________________________________
Expected Batch
Yield
95 105%
Actual Batch Yield
DEVIATIONS (If any)
Sr. #
Detail of Deviation
Operator
Pharmacist
IPQA
Date
1.
2.
3.
Remarks (if any):
Officer Production
Manager P&D
Manager QA
DOCUMENTS REVIEW & COMPLETION
All the documents related to manufacturing of the product have been reviewed and found complete in all
respect.
Remarks (if any):
Manager Quality Assurance
