Final Protocol - Diasulin N 100IU

PROCESS VALIDATION PROTOCOL
Diasulin N 100IU/ml SC Injection

(Insulin Human USP 100IU per ml)
PACK: 10 mL Multidose Vial
BATCH SIZE: 30L
PRODUCT CODE:IJ94
Protocol No.: VLD-PQ-Pr-120C

Supersedes: None
ACI Limited
7, Hajeegonj Road, Godnyl
Narayangonj – 1400
Bangladesh
Department: Title: Protocol No. VLD-PQ-Pr-120C
Product PROCESS VALIDATION PROTOCOL
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Product: Diasulin N 100IU/ml SC Injection
Table of Contents
Sr. Contents Page No.
No.
1. Protocol Approval 3
2. Objective, Scope, Responsibilities 4-5
3. Reference, Cleanliness Zone Requirements 6
4. Qualification and training of personnel 7
5. List of analytical equipments qualification summary 7
6. Batch details, Validation Strategy 8
7. Reason for Validation, Prerequisite for process validation ,Abbreviation 8
8. Qualification of Active Materials 9
9. Details of Working standard, Details of Reference document 10
10. Manufacturing Procedure details:
A) Unit formula 11
B) Manufacturing formula 12-15
C) List of manufacturing equipments 16
D) Manufacturing Procedure & flow Chart 17-18
E) General Instructions, Manufacturing Precaution 19
F) process parameters 19-24
11. Sampling Plan and acceptance Criteria 25-26
12. Deviation Summary 27
13. Details of analytical Data Sheet 28
14. Details of Process Sheet 28
15. Validation Report Summary 29
16. Certificate of Approval 30
This is confidential property of ACI Limited, do not disclose without prior consent from Authorized person of Quality Assurance Department of ACI Limited, 7
Hajeegonj Road, Godnyl, Narayangonj, Ph: 880-7630496, Fax: 880-9884784, web: www.aci-bd.com
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1. PROTOCOL APPROVAL
Process validation protocol for Diasulin N 100IU/ml SC Injection(Insulin Human USP 100IU per
ml),10 mL vial of batch size 30 L has been prepared, reviewed, and approved for execution by
personnel from the following functional departments.
Approval:-
Functional Area Name Signature Date
Prepared By
Product Towfika Islam
Development- Product Development Officer
Validation
Checked & Agreed by By
Quality Control Md.Lutfor Rahman Sarker

Asst. QC Manager
Product Mir Motaher Hossain

Development Product Development Manager
G.M. Faruqe Hossain

Quality Compliance Quality Compliance & Validation Manager
& Validation
Niaz Mohammad Sohel
Production Production Manager (Unit-I)
Reviewed By
Quality Assurance A.B.M. Mahfuz ul Alam

Quality Assurance Manager
Approved By
Production Imam Ahmed Istiak
General Manager Operations
Priyatosh Datta
Quality Assurance Director, Quality Assurance
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2. OBJECTIVE
To outline the procedure to be followed to evaluate and qualify the acceptability of manufacturing process
of Diasulin N 100IU/ml SC Injection (Insulin Human USP 100IU per ml), 10 ml multidose vial of batch size
30 L.
Protocol describes Concurrent process validation to establish documented evidence that the
manufacturing process for Diasulin N 100IU/ml SC Injection (Insulin Human USP 100IU per ml), 10 ml
multidose vial of batch size 30L will consistently produce a product which meets predetermined
specifications and quality attributes.
To compile and review the results of process validation to define the process parameters for future
batches. To define procedure and rationale of this validation.
2. SCOPE
The scope of this document is applicable for the concurrent process validation of three batches using
same set of equipments / aids and process for Diasulin N 100IU/ml SC Injection(Insulin Human USP
100IU per ml), 10 ml multidose vial of batch size 30L manufactured in Narayangonj Pharma Factory at
Insulin Project as that of WOCKHARDT, INDIA.
Also applicable for the critical parameters that could either directly or indirectly impact on quality of the
product being manufactured.
2. RESPONSIBILITIES:
In accordance with this protocol, following functional departments are responsible for the preparation and
execution of this validation protocol.
QUALITY ASSURANCE
Executive / designee shall follow the following responsibilities;
 Shall prepare process the validation protocol and report.
 Shall do and ensure the sampling as per the sampling plan.
 Shall check, review and compile the Process Validation Protocol and report.
 Shall review the completed batch records.
 Shall ensure stability studies are conducted as per approved stability protocol.
 Shall investigate , the OOS results.(if any)
 Shall ensure that the personnel involved in the critical operations are trained.
 Shall ensure that cGMP practices are followed during the validation.
 Shall monitor the critical parameters during the process.
Quality Compliance & Validation Manager/ designee shall follow the following responsibilities;
 Shall ensure that the equipment and the supporting system for manufacturing of this product are
qualified and within validated status.
 Shall review process validation protocol and report.
 Quality Assurance Manager shall review the process validation protocol and report.
 Director Quality Assurance shall approve the process validation protocol and report.
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PRODUCTION
Production Manager / designee shall follow the following responsibilities;
 Shall record/inform any deviation from the process.
 Shall train the personnel involved in the process.
 Shall ensure, with the help of Engineering & validation that all necessary equipments/instruments
for the manufacture of this product is available and qualified/validated or calibrated for use.
 Shall fill batch records online.
 Shall provide support for investigation of OOS result (if any)
 Shall check & agreed the process validation protocol and report.
QUALITY CONTROL
Asst. Quality Control Manager / designee shall follow the following responsibilities;
 Shall analyse the sample as per the approved STPs/specifications
 Prepare the In-process and finished product analysis report
 Shall initiate investigation for any out of specification result.
 Shall review the process validation protocol and report.
PRODUCT DEVELOPMENT
Manager Product Development/ designee shall follow the following responsibilities;
 Shall execute the batch manufacture record.

 Shall execute the process validation protocol.
 Shall train the personnel involved in the process.
 Shall fill batch records online.
 Shall review the Process Validation Protocol and report.
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3. REFERENCE:
GUIDELINES:
 Guidance for Industry, USFDA: Sterile Drug Products Produced by Aseptic
Processing-Current Good Manufacturing.
DOCUMENTS:
 Validation master Plan: -ACI/VMP/006
 Process Sheet : 7-10-220-00
 Specification & STP No. (In process): QA/IPC-Insulin001/00
 Specification & STP No. (Finished): SN-5610/2
 Active Air Sampling (SOP: SMM-37) & Settle Plate (SOP: 8-03-15-11)
 Observations of operator practices/room condition (SOP: 7-10-259-00)
 Environmental monitoring of aseptic area for temperature , humidity & pressure
differential(SOP: 7-10-167-00) & Surfaces Monitoring (SOP: SMM-09)
 Microbiological review of aseptic manufacturing (SOP: 8-03-15-00)
 Water Sampling (SOP: SMM-64) & Personnel Monitoring (SOP: SMM-09)
 Nonviable particle Monitoring (SOP: SMM-05)
 Entry into & exit SOPs (SOP: 7-10-259-00)
3. CLEANLINESS ZONE REQUIREMENTS:

Activity Zone Area
Dispensing Under class 100 surrounded by class 10,000
Manufacturing & Filtration In class 1000

Filling and sealing
Class 100 surrounded by class 1000.
Corridor
In class 1000
Packaging Un-classified area
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Batch No:
4. QUALIFICATION AND TRAINING OF PERSONNEL:
Personnel engaged in the Validation project must have adequate qualification and should be trained in the
basic principles of validation and should be thoroughly briefed about the manufacturing process Diasulin
N 100IU/ml SC Injection and the detailed methodology to be adopted for the Performance Qualification of
the process.
A list of the personnel with the qualification and training details should be prepared as per the following
format.
Name Designation Department Trained Signature Signature of

(QA/PD/ on of Trainee Trainer
Production)
5. CALIBRATION & QUALIFICATION STATUS OF EQUIPMENT:
Sr. Equipment Name Code/ Calibrated On Next Due

No Identification Date
No.
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6. TYPE & BATCH DETAILS OF VALIDATION BATCHES:

A minimum three batch shall be planned for the Concurrent validation project.
The batch details of validation batches shall be planned well in advance.
6. VALIDATION STRATEGY:
For the purpose of validation, it is proposed to run three batches of Diasulin N 100 IU/mL SC Injection;
batch size 30L. All the three batches shall be compared to demonstrate the consistency of the process to
produce the product meeting the pre determined specifications and quality attributes.
7. REASON FOR VALIDATION: New Product
7. PREREQUISITE FOR PROCESS VALIDATION:

1. Facility including the major equipment/instruments & the utilities are qualified.
2. All the raw & Packaging materials are tested as per approved specifications (STP) before use.
3. All measuring devices are calibrated.
4. The area is clean & Complies as per the environmental monitoring SOP & its acceptance Criteria.
5. The process sheet & the approved process validation protocol are available.
7. ABBREVIATIONS
SOP: Standard Operating Procedure.
STP: Standard Test Procedure.
OOS: Out of Specifications
WFI: Water for Injection.
BET: Bacterial Endotoxin Test.
SIP: Steam In Place.
CIP: Clean In Place.
RM: Raw Material.
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8. QUALIFICATION OF ACTIVE MATERIALS:
Batch No.:
All the raw materials proposed to be used for the manufacture of validation batches shall have the
following qualification.
1) They must comply with the relevant pharmacopoial & in-house specifications.
2) Preferably the same batch number active principle shall be used for all the validation batches
A list of the personnel with the qualification and training details should be prepared as per the following
format.
Name of Materials Name of Manufacturer Specification # GRN# Release Remarks

status
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Batch No. :
9. DETAILS OF REFERENCE MATERIALS / WORKING STANDARDS:
Sl Name of materials Code No. Manufacturer GRN NO.

No.
Sl Name Batch No. Strength Exp.Date

No.
9. DETAILS OF REFERENCE DOCUMENTS:
Sl Title Doc. No. Revision Effective Date

No. No.
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10. MANUFACTURING PROCEDURE DETAILS:
A) UNIT FORMULA :
Materials Name of materials with Code No. Quantity/ml Overage (%)

Required compendia ref. & code no. (mg)
For
Insulin Human USP 1109002 2

(Recombinant) 3.7091*
Zn (as Zinc Oxide) USP 1126001 NA

0.0275**
Protamine Sulphate USP 1116003 NA
0.37
Disodium Hydrogen USP 1104002 NA
Phosphate 2.08
Anhydrous
Raw Metacresol USP 1113002 NA
1.60
Materials (Distilled)
Glycerine USP 1107004 NA
16.32
Phenol (Distilled) USP 1116002 NA
0.65
Sodium Hydroxide 1119003 NA
USP NF q.s to adjust pH
(1N)
Hydrochloric Acid 1108002 NA
USP NF q.s to adjust pH
(1N)
Water For Injection BP 1123001 NA
q.s to 30 L
* based on minimum USP limit (27.50 IU/mg) for Insulin Human; 3060000 IU is the total Insulin
Human with 2% overage per batch.
** Calculated qty for total Zinc Ion required for the batch
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B) MANUFACTURING FORMULA :
Source: Batch Manufacturing Record Formulation No. FDN-5710

Batch Size: 30.0 Litres, Batch Qty: 2,857 Vials; Batch No. :
Materials Name of materials with Code No. Standard weight Actual weight
Required compendia ref. & code no. (g) (g)
For
Insulin Human USP 1109002
(Recombinant) 111.273*
Zn (as Zinc Oxide) USP 1126001

0.826**
Protamine Sulphate USP 1116003 11.10
Disodium Hydrogen USP 1104002
Phosphate 62.40
Anhydrous
Raw Metacresol USP 1113002
48.00
Materials (Distilled)
Glycerine USP 1107004
489.60
Phenol (Distilled) USP 1116002
19.50
Sodium Hydroxide 1119003
USPNF q.s to adjust pH
(1N)
Hydrochloric Acid 1108002
USPNF q.s to adjust pH
(1N)
Water For Injection BP 1123001
q.s to 30.00 L
* based on minimum USP limit (27.50 IU/mg) for Insulin Human; 3060000 IU is the total Insulin
Human with 2% overage per batch.
** Calculated qty for total Zinc Ion required for the batch
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CALCULATIONS:
Sl Insulin Glargine API details Potency (IU/mg)

No. Ref: As per COA Ref: In house As it is basis As dried basis
Sl Zinc Content Potency : as Zinc (%w/w)

No. Ref: As per COA Ref: In house As it is basis As dried basis
1. Required quantity of Insulin Human with 2% overage per batch as follows:

a) For Calculation of single lot/1st lot:
111.273 × 27.50
W 1= g = g 27.50 IU/mg is the minimum
A1 USP limit for Insulin Human;
Total Insulin required/Batch:
Where 'A1' is the potency of Insulin Human in 3060000 IU eqv to
IU/mg of 1st lot as it is basis. 3060000/27.5/1000=111.273 g
Quantity from the single lot/1st lot = g
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b) For Calculation of another lot, the following box is to Applicable Not Applicable
be used:
(W1–1st Lot Qty) x A1

W2= g = g =
A2
Where 'A2' is the potency of Insulin Human in IU/mg of 2nd lot as it is basis.
Quantity from the 2nd lot = g
Total qty(W)= (1st Lot Qty +2nd lot Qty) g = ( + )g = g
1. Required quantity of Zinc Ion per batch as follows(0.00027 mg required for

each IU of Insulin):
0.00027 × 3060000 3060000 IU is the total Insulin

Total Zinc ion required = g = 0.826 g
1000 Human per batch
(Cal:1) × B ‘B’ is the Zinc ion content as

Endogenous Zinc ion = g = g
100 %w/w in Insulin Human
Exogenous Zinc ion req.= (Total Zinc ion required – Endogenous Zinc ion ) g = g
1% of Zinc Solution to be added = (Exogenous Zinc ion X 100) ml = ml
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1. Required quantity of Protamine Sulphate per batch as follows (0.296 mg Protamine

Base/100 IU):
LOD (%) of Protamine Sulphate = ______________ Sulphate content (%) of Protamine sulphate
= _____
For Protamine Base Content -
[(100 - %LOD) /100] X [(100 - % Sulphate) / 100] = Protamine Base Content ----- (a)
= = ------- (a)
So, required quantity of Protamine Sulphate per batch will be =
[0.296 X batch size in L = _0.296 x 30 _____ g

(a)
= ________________ g of Protamine Sulphate.
Protamine Sulphate required = g
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C. LIST OF MANUFACTURING EQUIPMENT:
Equipment Qualification
Sr. No Equipment Name
Number No.
1. Laminar Air Flow Unit
2. Manufacturing vessel with stirrer-100 L capacity
3. Manufacturing vessel with stirrer-50 L capacity
4. Weighing Balance
5. 20 L Churn vessel – 1 pcs
6. Filter assembly
7. 0.2 micron cartridge filters
8. Autoclave
9. SS bucket 10 liters – 2 pcs
10. Micropipettes 1.0 ml,
11. Spatulas - 5 Nos.
12. Cold Storage Area/Room
13. pH meter
14. Storage vessel – 100 L
15. Storage/ collection vessel for WFI ( 5 – 15) 0 C
16. LAF movable trolley
17. SS Funnel – 02 Nos
18. Pipettes – 5 ml, 10 ml, 20 ml
19. Cold storage Area / Room
20. Glass beaker – 500 ml, 1 L, 2 L.
21. Measuring cylinder – 500 ml , 1 L , 2 L.
22. Silicon Tubing
23. Magnetic stirrer
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24. Freezer & Refrigerator – 01 each in the

dispensing room / area
D. MANUFACTURING PROCEDURE AND FLOW DIAGRAM:

Dispensing of Raw Materials and
primary packing materials under LAF.
CIP & SIP of manufacturing tank &

Sterilization of manufacturing
accessories.
Verification of Raw Materials before

manufacturing
Part I
 Distillation of m-Cresol & Phenol
 Collection & chilling of WFI to 5 to 15° C.
 Addition of fresh m-Cresol, Phenol & glycerine to WFI under
stirring.
 Protamine sulphate preparation & addition
 Complete wetting of Insulin API with cold WFI (5-15 ° C)
Sampling
 Preparation & addition of Zinc oxide solution
before filtration
 pH adjustment to 2.96 to 3.40 at 10ºC to 15ºC
 Volume make up
Filtration
Part II
 Distillation of m-Cresol & Phenol
 Collection & chilling of WFI to 5 to 15° C.
Sampling  Addition of fresh m-Cresol, Phenol & glycerine to WFI under
before filtration stirring.
 Addition & dissolution of Disodium Hydrogen Phosphate
anhydrous.
 ofpH
This is confidential property adjustment
ACI Limited, to 7.70
do not disclose toprior
without 7.90 at 5°C
consent to 15°C
from Authorized person of Quality Assurance Department of ACI Limited, 7
 Volume make up
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Filtration
Mixing of Part I, II
Sampling after 20
hrs for crystal check, Holding of mixer solution (Part I, II) for 24 hrs. for
Appearance, Assay, crystallization
& pH.
Decartoning & pre inspection of Vials
Vial washing
Vial washing Machine
Vial depyrogenation Tunnel Sterilizer

(Temperature & conveyor
speed monitoring)
Sterilisation of rubber stoppers
Vial filling machine.

Filling and Sealing of Vials
Fill volume Checking
Sampling of 100 %Visual Inspection of filled

semi finished /sealed units & packing
product
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E) GENERAL INSTRUCTIONS:
1. Keep all containers of raw materials contained in small containers in cleaned material staging
room.
2. Weigh and keep the required quantities of different raw materials with proper labeling into
separate clean polyethylene bags/clean and dried S.S. Container and record the material
reference no. properly on the process sheet.
3. Swab the raw materials container with 70% IMS.
4. Transfer the swabbed raw materials containers to the aseptic manufacturing area on the day
before manufacturing through pass box.
5. The solution must be manufactured, filled and sterilized on the same day. If this is impossible for
technical reason, sterile filtration must be done within 8 hours of manufacture.
6. Process sheet should be used in the non-sterile office room.
7. Only freshly prepared water for injection will be used after QA Release.
8. Ensure that manufacturing, filtration & filling accessories are cleaned & sterilized.
E) MANUFACTURING PRECAUTIONS:
The product will manufacturing &filling with special precautions.
F) PROCESS PARAMETERS:
STAGE 1: DISPENSING
CHECK BEFORE USE –
1. Room to be used: Insulin Manufacturing Area

2. Previous Product: ___________________________ Batch no. ____________________
3. Room cleaned / not cleaned (put tick) □ Cleaned □ Not Cleaned
4. Balance to be used:
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i) ID # ______________ a) Calibration □ OK □ Not OK
b) Daily Performance Check □ Ok □ Not OK
ii) ID # ______________ a) Calibration □ OK □ Not OK
b) Daily Performance Check □ OK □ Not OK
5. Scoops are cleaned □ OK □ Not OK

6. Absence of any other material in the dispensing room ensured □ OK □ Not OK
(Dispensed or not dispensed)
7. Check the labels on all raw materials container and ensure that right raw materials are there.
□ Ok □ Not OK
8. Exhaust System □ Off □ On

9. Ensure that manufacturing, filtration & filling accessories are cleaned & sterilized.
□ Ok □ Not OK
STAGE 2: MANUFACTURING PROCESS
CHECK BEFORE MANUFACTURING –
1. Room to be used: Insulin Manufacturing Area
2. Previous Product: ___________________________Batch no. _______________________
3. Check & ensure that Manufacturing, Filtration & Filling Accessories are cleaned & sterilized.
□ OK □ Not OK
4. Check and ensure that right raw materials are there. □ OK □ Not OK
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5. Check Primary Packing materials before autoclave and before filling. □ OK □ Not OK
6. Check No of dresses autoclaved before starting operation □ OK □ Not OK
7. Check contact parts after autoclave but before filling □ OK □ Not OK
FOLLOWING IS THE BRIEF PROCESS DESCRIPTION WITH CRITICAL PROCESS

PARAMETERS:
Batch No. :
MANUFACTURING PROCEDURE
Procedure Process Results Limits
Step-I (Buffer Preparation of Buffer Process (5-15)°C

part) solution Temperature
Mixing Time 10mins
pH 7.70-7.90
Step-II Preparation of Process (60-80)°C
(Insulin part) Protamine Sulphate Temperature
Solution
Mixing Time 5-10mins
Preparation of Process (5-15)°C

Preservative Solution Temperature
Mixing Time 5-10mins
Preparation of Insulin Mixing Time 5-10 mins
Paste
Mixing of insulin part Process (10-15)°C

into preservative Temperature
part/Protamine
Mixing Time 15mins
sulphate part
pH 2.96-3.40
Step-III Mix Step II with Step I Mixing Speed Slow

Solution as 1:1 ratio
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(Trial Mixing) pH 7.20-7.45
Step- IV Filtration Prefilter Millipore, pore

(Sterilization by diameter 1.20 µm,
filtration & Mixing of Hydrolyzed PVDF
insulin & Buffer)
Filter Millipore, pore
diameter 0.20 µm,
Hydrolyzed PVDF
Mixing of Insulin & Mixing Time 15mins

Buffer part
Mixing Speed Slow
Step- V crystallization crystal Crystal size and

(crystallization;
shape: Rod shaped
After 20 Hours)
crystals majority with
maximum dimensions
greater than 1 µm but
rarely exceeding 60
µm and free from
large aggregates.
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GLASS VIAL & FLIP OFF SEAL WASHING & STERILIZATION:

Clear Glass Vial Sterilizing 250°C

washing & Sterilization Oven Temperature
Time 1 hour
Flip Off Seal Autoclave Temperature 121°C

washing & Sterilization
Time 15mins
FILL THE VIAL ACCORDING TO THE FOLLOWING SPECIFICATION:
Process Results Specifications
Machine Vial Auto Filling & Sealing machine
Fill Volume NLT 10.50 ml

(10.50-10.70ml)
Vials 10 ml clear glass vial (Code: 180011)
Rubber Stopper 13mm Bromobutyl Rubber

stopper(Code: 140005)
Flip off seal 13mm (Green-3768) flip-off seal

(Code:190003)
Relative Humidity 50%-60%
Room Temperature 21°C-25°C

Nitrogen gas Beforehand filling
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VISUAL INSPECTION:
Process Results Limits
Satisfactory appearance
Faulty filling and sealing 100% vials should pass

this tests
Adequate volume
Seal integrity and leakage
YIELD:
Yield Results
Theoretical yield
Actual yield
Yield percentage
Actual Yield x 100

= ----------------------------- %
Theoretical Yield
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11. SAMPLING & TESTING PLAN, ACCEPTANCE CRITERIA:-
Batch No. :
Sl. Stage Tests Responsibility Results Acceptance Criteria

No.
1 Manufacturing – Appearance QA Clear colour less solution
Insulin solution
(Part I) pH 2.96-3.40
Assay 195 IU/mL to 220 IU/mL
Manufacturing – Appearance QA Clear colourless solution

Buffer solution
(Part II) pH 7.70 – 7.90
2. Bulk sample Appearance QA White milky suspension.

(mixing of
Insulin solution
(Part I) & Buffer pH 7.0-7.5
solution
(Part II)
Assay 90 % to 110 %
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Sl. Stage Tests Responsibility Results Acceptance Criteria

No.
After holding of Appearance White milky suspension.
20 hrs.
pH 7.0-7.5
Assay 90% to 110 %
Crystal Crystal size and shape: Rod

check
shaped crystals majority with
maximum dimensions greater
than 1 µm but rarely exceeding
60 µm and free from large
aggregates.
6. Finished product For QA As per current STP and FPS.

complete
sampling(Top,
analysis.
Middle, Bottom)
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12. DEVIATION SUMMARY:

After careful study of all results a deviation report shall be prepared and documented in the following
format:
PERFORMANCE ACI Limited
QUALIFICATION Narayanganj
DEVIATION
Product : Batch No.:
Process :
Reference:
ANALYTICAL &/OR PROCESS DEVIATION
Problem :
Investigation :
Conclusion :
Prepared by:
Product Development Officer Signature:________________

Date : ________________
Checked by:
Asst. Product Development Manager Signature:________________
Date : ________________
Checked by:
Signature:________________
Quality Assurance Manager Date :________________
Approved by:
Signature:________________
Head, Quality Assurance Date :________________
cc: Head, Production
cc: Product Development
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13. DETAILS OF ANALYTICAL DATA SHEET:
All the supporting data shall be attached.
14. DETAILS OF PROCESS SHEET:
Process sheet shall be attached
15. VALIDATION REPORT SUMMARY:

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Summary & Discussion and Conclusion & Recommendation as a result of validation study
shall be prepared and documented in the following format:
Batch No.:
Reference:
Summary &Discussion:
Conclusion & Recommendation:
Prepared by:
Product Development Officer Signature:________________
Date : ________________
Product Development Manager Signature:________________

Date : ________________
Quality Assurance Manager Signature:________________

Date :________________
Approved by:
Head, Quality Assurance Signature:________________

Date :________________

16. CERTIFICATE OF APPROVAL:
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A certificate of approval after review of report shall be prepared and documented in the
following format.
PERFORMANCE ACI Limited

QUALIFICATION Narayanganj
CERTIFICATE OF APPROVAL
Product : Batch No.:
Process :
Reference :
Remarks: Based on all of the study as per the validation protocol no # -------- as per process
sheet # ------------ is considered □ Validated □ Not Validated
Prepared by: Signature:________________

Product Development Officer Date : ________________
Checked by: Signature:________________

Asst.Quality Control Manager Date : ________________
Checked by: Signature:________________

Product Development Manager Date : ________________
Signature:________________
Checked by: Date : ________________
Quality Compliance & Validation Manager
Signature:________________
Checked by: Date : ________________
Production Manager
Reviewed by: Signature:________________
Quality Assurance Manager Date :________________
Approved by: Signature:________________

Head, Quality Assurance Date :________________

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1.
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QUALITY ASSURACNE, ACI LIMITED,
7, HAJEEGONJ ROAD, GODNYL, NARAYANGONJ-1400
Depar Title: Protocol No.

tment:
Formul PROCESS VALIDATION PROTOCOL
Supersedes: None
ation II
Page No. 48 of 52
Human Insulin Isophane Suspension And Human
Prod
Insulin Injection USP (r-DNA), 100 IU/ml, 10 ML
uct:
Multidose Vial.
Department: Title: Protocol No.

Formulation II
Supersedes: None
Page No. 49 of 52
Product: Insulin Injection USP (r-DNA), 100 IU/ml, 10 ML
Multidose Vial.

Formulation II
Supersedes: None
Page No. 50 of 52
Multidose Vial.
Formulation II
Supersedes: None
Page No. 51 of 52
Multidose Vial.
This is confidential property of ACI Limited, do not disclose without prior consent from Authorized person of Quality Assurance Department of
ACI Limited, 7 Hajeegonj Road, Godnyl, Narayangonj, Ph: 880-7630496, Fax: 880-9884784, web: www.aci-bd.com

Formulation II
Supersedes: None
Page No. 52 of 52
Multidose Vial.

Final Protocol - Diasulin N 100IU

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Final Protocol - Diasulin N 100IU

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PROCESS VALIDATION PROTOCOL

Diasulin N 100IU/ml SC Injection

PACK: 10 mL Multidose Vial

BATCH SIZE: 30L

Protocol No.: VLD-PQ-Pr-120C

2. Objective, Scope, Responsibilities 4-5

3. Reference, Cleanliness Zone Requirements 6

4. Qualification and training of personnel 7

5. List of analytical equipments qualification summary 7

6. Batch details, Validation Strategy 8

7. Reason for Validation, Prerequisite for process validation ,Abbreviation 8

8. Qualification of Active Materials 9

9. Details of Working standard, Details of Reference document 10

10. Manufacturing Procedure details:

B) Manufacturing formula 12-15

C) List of manufacturing equipments 16

D) Manufacturing Procedure & flow Chart 17-18

E) General Instructions, Manufacturing Precaution 19

F) process parameters 19-24

11. Sampling Plan and acceptance Criteria 25-26

12. Deviation Summary 27

13. Details of analytical Data Sheet 28

14. Details of Process Sheet 28

15. Validation Report Summary 29

16. Certificate of Approval 30

Functional Area Name Signature Date

Quality Control Md.Lutfor Rahman Sarker

Product Mir Motaher Hossain

G.M. Faruqe Hossain

Quality Assurance A.B.M. Mahfuz ul Alam

 Shall execute the batch manufacture record.

3. CLEANLINESS ZONE REQUIREMENTS:

Dispensing Under class 100 surrounded by class 10,000

Manufacturing & Filtration In class 1000

Packaging Un-classified area

4. QUALIFICATION AND TRAINING OF PERSONNEL:

Name Designation Department Trained Signature Signature of

5. CALIBRATION & QUALIFICATION STATUS OF EQUIPMENT:

Sr. Equipment Name Code/ Calibrated On Next Due

6. TYPE & BATCH DETAILS OF VALIDATION BATCHES:

7. REASON FOR VALIDATION: New Product

7. PREREQUISITE FOR PROCESS VALIDATION:

8. QUALIFICATION OF ACTIVE MATERIALS:

Name of Materials Name of Manufacturer Specification # GRN# Release Remarks

9. DETAILS OF REFERENCE MATERIALS / WORKING STANDARDS:

Sl Name of materials Code No. Manufacturer GRN NO.

Sl Name Batch No. Strength Exp.Date

9. DETAILS OF REFERENCE DOCUMENTS:

Sl Title Doc. No. Revision Effective Date

10. MANUFACTURING PROCEDURE DETAILS:

Materials Name of materials with Code No. Quantity/ml Overage (%)

Insulin Human USP 1109002 2

Zn (as Zinc Oxide) USP 1126001 NA

Source: Batch Manufacturing Record Formulation No. FDN-5710

Zn (as Zinc Oxide) USP 1126001

Sl Insulin Glargine API details Potency (IU/mg)

Sl Zinc Content Potency : as Zinc (%w/w)

1. Required quantity of Insulin Human with 2% overage per batch as follows:

Quantity from the single lot/1st lot = g

(W1–1st Lot Qty) x A1

Quantity from the 2nd lot = g

Total qty(W)= (1st Lot Qty +2nd lot Qty) g = ( + )g = g

1. Required quantity of Zinc Ion per batch as follows(0.00027 mg required for

2. Previous Product: _____Batch no. _