1.
PREPARATION, REVIEW & APPROVAL
·
Following
personnel are involved in various activities like preparation, review &
approval of this Master Manufacturing Formula Record.
|
Name
|
Department
|
Function
|
Designation
|
Specimen
Signature
|
|
|
Production Deptt
|
MFR Preparation
|
Chemist
|
|
|
|
Production Deptt
|
MFR Review
|
Asst. Manager
|
|
|
|
Quality Assurance
|
MFR Review
|
Asst. Manager
|
|
|
|
Quality Assurance
|
MFR Approval
|
Manager
|
|
2.
INDEX
|
S.No.
|
Process
Stage
|
Page
No.
|
|
1
|
Preparation,
Review & Approval
|
1
|
|
2
|
Index
|
2
|
|
3
|
Product
Details
|
3
|
|
4
|
Dispensing
of Raw Material
|
4
|
|
5
|
Bill
of Raw Material
|
5
|
|
6
|
Calculation
Sheet for API
|
6-7
|
|
7
|
Pre Manufacturing Instructions
|
8
|
|
8
|
Equipment
/ Machines Detail for Manufacturing
|
8
|
|
9
|
Manufacturing
Operation
|
9-10
|
|
10
|
Sample
Analysis
|
10
|
|
11
|
Batch
Release
|
10
|
|
12
|
Inprocess
Specifications
|
10
|
|
13
|
Bulk Reconciliation
|
11
|
|
14
|
Revision
History
|
11
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3. PRODUCT DETAILS:
|
Product Name (Brand)
|
:
|
|
|
Generic
Name
|
:
|
Clotrimazole
& Hydrocortisone Acetate Cream BP
|
|
Claim
|
:
|
Composition:
Clotrimazole
BP 1.0 % w/w
Hydrocortisone
Acetate BP 1.0 % w/w
Cream
Base
q.s.
|
|
Standard
Batch Size
|
:
|
400.00
Kgs.
|
|
Pack
Size
|
:
|
1
X 15 g
|
|
Shelf
Life
|
:
|
24
Months
|
|
Mfg.
Lic. No.
|
:
|
|
|
Description
|
:
|
Off White soft Cream packed in collapsible lami tube.
|
|
Storage
Condition
|
:
|
Store
at temperatures below 30 °C, Do not freeze.
|
|
Other
Details (If any)
|
:
|
|
4.
DISPENSING OF RAW MATERIAL:
·
Environmental Monitoring: Temperature and RH shall be recorded at
start, end and at 1-hour interval
during dispensing of Raw material.
·
Environmental should within the specified limits
i.e. Temperature: NMT 27 ℃, RH: NMT 60%
·
Line Clearance: Take line clearance before
starting in activity from QA.
·
During line clearance ensure proper cleaning of
area, equipment, utensils etc.
·
Follow dispensing procedure as defined in the
SOP.
·
Warehouse person shall issue the material and QA
person shall verify the material during dispensing for material AR No., labels, quantity etc.
after receiving material production person shall verify the quantity.
·
Verify AR No. before dispensing of material.
·
Record the detail of each material & put the
label with each material.
·
During dispensing store person & QA person
shall verify material details & weight of each dispensed material.
5. BILL
OF MATERIAL & DISPENSING DETAIL:
|
S. No
|
Ingredients
|
Spec
|
Label Claim
|
Overages
|
Std. Qty
For 400 .00 kg
|
Unit
|
|
1
|
Clotrimazole
|
BP
|
1.0%
|
5%
|
4.200
|
KG
|
|
2
|
Hydrocortisone
Acetate
|
BP
|
1.0%
|
5%
|
4.200
|
KG
|
|
3
|
Propylene
Glycol
|
IP
|
|
|
28.000
|
KG
|
|
4
|
Light Liquid Paraffin
|
IP
|
|
|
72.728
|
LTR
|
|
5
|
Hard Paraffin Wax
|
IP
|
|
|
10.800
|
KG
|
|
6
|
Micro
crystalline Wax
|
IP
|
|
|
10.800
|
KG
|
|
7
|
Cetomacrogol-1000
|
IP
|
|
|
8.400
|
KG
|
|
8
|
Cetostearyl Alcohol
|
IP
|
|
|
33.600
|
KG
|
|
9
|
Methyl Paraben
|
IP
|
|
|
0.400
|
KG
|
|
10
|
Propyl Paraben
|
IP
|
|
|
0.100
|
KG
|
|
11
|
Disodium Edetate
|
IP
|
|
|
0.400
|
KG
|
|
12
|
Butylated hydroxytoluene
|
IP
|
|
|
0.400
|
KG
|
|
13
|
Butylated hydroxyanisole
|
IP
|
|
|
0.400
|
KG
|
|
14
|
Sodium Phosphate
|
IP
|
|
|
0.400
|
KG
|
|
15
|
Sodium Acid Phosphate
|
IP
|
|
|
0.020
|
KG
|
|
16
|
Purified Water
|
IP
|
|
|
q.s.
|
KG
|
·
Use
Clotrimazole on 100% assay basis.
·
Use
Hydrocortisole Acetate on 100% assay basis.
·
5 % Overages added of Clotrimazole included under standard
quantity.
·
5 % Overages added of Hydrocortisole Acetate included under standard quantity.
·
* Make up Volume to required quantity with Purified
Water quantity sufficient (q.s.).
·
Ware house shall dispense material & put an
identification tag in each container.
·
QA shall verify the material & other details at
the time of dispensing.
·
Production shall check the gross weight of each
material container before taking into production.
·
Do not open cable ties in case of discrepancy &
inform to QA immediately.
|
AR No.1-
|
|
|
|
AR No.2-
|
|
|
|
AR No.3-
|
|
|
6. API
CALCULATION
6.1. Clotrimazole:
Calculation
for Required API:
For 400.000 Kg. of batch size, Std. Qty. is 4.200
Kg.
For …….……Kg. of Actual Batch Size, Std. Qty. is
…………… Kg. (In case change in batch size)
Required Batch Qty. (A) For AR1= Std. Qty. x100
Assay (AR1)
(A) = ……………..kg.
In case Qty. of AR1is not
sufficient then.
Required Batch Qty. (A) -
Available Qty. of AR1= (B)
(B)
= ……………..kg.
For AR2 =
Qty.Req. (B) x Assay (AR1)
Assay
(AR2)
(C) = ……………..kg.
Qty. Req. (C) - Available Qty.
of AR2= (D)
(D) = ……………..kg.
For AR3 =
Qty.Req. (D) x Assay (AR2)
Assay (AR3)
(E) = ……………..kg.
Total Dispensed Qty. =…………………………………………………………………
= ……………….Kg.
6.2. Hydrocortisone
Acetate:
|
AR No.1-
|
|
|
|
AR No.2-
|
|
|
|
AR No.3-
|
|
|
Calculation
for Required API:
For 400.000 Kg. of batch size, Std. Qty. is 4.200
Kg.
For …….……Kg. of Actual Batch Size, Std. Qty. is
…………… Kg. (In case change in batch size)
Required Batch Qty. (A) For AR1= Std. Qty. x100
Assay (AR1)
(A) = ……………..kg.
In case Qty. of AR1is not
sufficient then.
Required Batch Qty. (A) - Available
Qty. of AR1= (B)
(B) = ……………..kg.
For AR2 =
Qty.Req. (B) x Assay (AR1)
Assay (AR2)
(C)
= ……………..kg.
Qty. Req. (C) - Available Qty.
of AR2= (D)
(D) =
……………..kg.
For AR3 =
Qty.Req. (D) x Assay (AR2)
Assay (AR3)
(E) = ……………..kg.
Total Dispensed Qty. =…………………………………………………………………
= ……………….Kg.
7.
Pre-Manufacturing Instructions:
·
Read the MFR thoroughly before proceeding with
operation and follow it strictly.
·
Carry
out all the activities related to equipment cleaning and material handling
strictly as per respective standard operating procedures.
·
Label
all the materials of process stages.
·
Label
all equipment and area with status and product label and display prominently.
·
All
Raw Materials labels and Equipment Cleaning status labels to be retained with
the Batch manufacturing Record.
·
Get
line clearance before beginning of every operation from QA.
·
Ensure
that environmental conditions are achieved.
·
Protective
mask, surgical gloves and any other safety provisions must be followed.
·
Any
deviation from the BMR must be done with prior approval of QA.
·
Record
all time in 24 Hrs format & Date DD/MM/YY or DD/MM/YYYY format.
8.
Equipment/Machines details for Manufacturing:
|
S.No.
|
Equipments/Instruments
Name
|
Capacity
|
|
01
|
Manufacturing vessel
|
600.000
Ltr.
|
|
02
|
Oil Heating/ Wax Melting Tank
|
400.000
Ltr.
|
|
03
|
Water Heating Tank
|
400.000
Ltr.
|
|
04
|
Weighing Balance
|
100.000
Kg.
|
|
05
|
Weighing Balance
|
2000.000
Kg.
|
|
06
|
Storage Tank
|
500.000
Ltr.
|
|
|
|
|
|
|
|
9. MANUFACTURING:
9.1.
Environmental Monitoring: Temperature and RH shall be
recorded initially & at an interval of 2 hour, during manufacturing. In mfg. area the materials are holded in the same area
therefore environmental conditions are recorded in routine general format also.
9.2. Line Clearance:
Take line clearance before starting in activity.
9.3.
MANUFACTURING PROCESS (A):
9.3.1. Preparation of Cream -
|
Process Description
|
||||||||||||||||||||||||||||||||||||||||||
|
STEP 1: WAX MELTING TANK (OIL PHASE):
Take all following Raw Materials
together into the wax melting tank having capacity of 400 Ltr. And heat up to
80 to 90 ºC for at least 45 minutes.
Transfer the melted wax phase
into the Jacketed mixing tank by passing through filter # 200 mesh size.
Add
Clotrimazole into melted Wax Phase at continuous Stirring at temperature 80 ℃.
STEP
2: Heat the
purified water up to the temperature 80 ℃. after this, add Sodium Phosphate, Sodium
Acid Phosphate.
STEP
3: Transfer the
step 1 and step 2 into mixing tank at the temperature of 70 ± 2 ℃ of both
phases under vacuum continuous the mixing 30 minutes. After that continue cooling
and mixing till temperature reaches to
50 ℃.
STEP
4: Take
propylene Glycol in a S.S. Container and dissolve methyl Paraben and Propyl
Paraben then transfer into the manufacturing.
STEP 5: Take Propylene Glycol in SS
container and titrate Hydrocortisone Acetate until smooth slurry is formed.
Then transfer the slurry into the manufacturing tank.
*
Keeping approximate 1.0 kg Propylene Glycol aside for rinsing purpose.
|
10. SAMPLE
ANALYSIS:
QA will collect the sample and
send to QC for analysis.
11. BATCH
RELEASE:
On the basis of review of
manufacturing process, in-process checks & analytical data, QA shall
release the batch for further processing.
12. INPROCESS
SPECIFICATIONS:
|
S. No.
|
PARAMETER
|
SPECIFICATION
|
LIMITS
|
FREQUENCY
|
|
1
|
Description
|
White to white off soft mass filled in lamitube
|
2 hrs.
|
|
|
2
|
Average wt. of Net filled
|
15 g
|
91 % to 109%
|
30 min
|
|
3
|
Net wt. filled of 10 Tubes
|
NLT 15 g
|
NLT Label claim
|
2hrs.
|
|
4
|
Leak Test
|
Not Permitted
|
Not permitted
|
2 hrs.
|
|
5
|
Batch Details on Crimp
|
Legible and clear
|
Legible and clear
|
30 min
|
13. BULK RECONCILIATION:
Actual Weight
of Final Bulk
% Yield = --------------------------------------- X 100
Theoretical batch size
(LIMIT: NLT- 99.50 %)
14. REVISION
HISTORY:
|
S.No.
|
Revision Number
|
Reason
|
|
1
|
00
|
New Introduction
|
|
|
|
|
Thanks for sharing this useful Blog! The demand of api manufacturers in India is increasing.
ReplyDeleteGreat insights for pharma contractor
ReplyDeleteGreat Site. INNOVATIVE PHARMA is cosmetics manufacturer in India.
ReplyDelete