master formula records of hydroxy progesterone caproate injection
NAME OF PRODUCT : hydroxy progesterone caproate injection
COMPOSITION : Each ml Contains:
Hydroxy progesterone Caproate I.P. 250.0 mg
Ethyl Oleate I.P. q.s.
BATCH SIZE : 100 Litres
SELF LIFE : 3 Years
PACKAGING : 1 ml White ampoule
MANUFACTURING FORMULA :
|Sr. No.||Raw Material||Qty Per ml||Overages||Total qty per ml||Quantity per batch|
|01.||Hyroxy progetrone Caproate||250.0mg||–||250.0mg||25.00kg|
|04.||Benzyl Alcohol||4.0 %||–||4.0 %||4.0.kg|
CALCULATION : Hydroxy progesterone Caproate I.P.250.0mg
— For each ml
— _____________ x 250 mg x 100 Litres
— (Assay – Water)
— ( Assay according to Quality Control Report )
EQUIPMENT USED :
PROCESS STEGE EQUIPMENT AND VESSELS
1) DISPENSING (a) Weighing Machine
2) BULK MANUFACTURING (a) 50 Litre S.S.Tank with lid and sterrer.
(b) 100 Litre S.S.Tank with lid and sterrer.
(c) 142 mm/293 mm filter assembly.
3) FILTERATION (a) Bubble point Apparatus
(b) Filtration Assembly – 142 mm /293 mm
(c) 20 litres/50 litres receivingVessels / filling tank
(d) Autoclave .
4) FILLING & SEALING (a) Automatic Ampoule filling and sealing machine
(b) S.S.Container / Tray
5) AMPOULE WASHING (a) Ampoule washing machine
(b) S.S.Boxes / Tray
(c) Dry Heat Sterilization (D.H.S.)
6) LEAK TESTING (a) Vaccum Pump
7) OPTICAL TESTING (a) Optical testing tables.
8) BATCH PRINTING (a) Batch printing machine
9) LABELLING & PACKING (a) Labelling machine
(b) Taping machine
(c) Strepping machine
GENERAL DISPENSING PROCEDURES :
THE MAIN STEPS IN DISPENSING AREA :
Transaction with Raw Material Store :
Depending upon the production programme and availability of raw materials,bulk requisitions duly authorized by
Production Manager / Mfg . Chemist , must be given to store , 2 hour’s in advance . While receiving the materials
should be checked by concerned Supervisor for the following :-
- a) Label
- b) A.R. Number from Q.C.
- c) Quantity
- d) Checking of weight in the weighing room
- e) Physical damage if any.
On receiving the raw materials requisition, the materials are dispensed in the following manner.
Materials contained in polythene bags are first depacked into s.s.container and duly labeled . Materials
received in fibre drums and carbous need not be depacked, only external cleaning with a clean dry cloth is sufficient.
The materials are dispensed as per the requisition duly authorized by Production Manager / Mfg.Chemist received
from the production department. The materials are weighed on electronic balance. All the materials dispensed are
weighed by on Supervisor and counter checked by another Supervisor.
BULK MANUFACTURING :
- Clean all the equipment /containers required for bulk manufacturing with (teepol/liquid soap) rinse it with tape water and D.M.Water.
- In the bulk manufacturing area rinsed twice all the above mentioned items with fresh distilled water.and total equipment ,
- tank dry to dry heat sterilization.
- Collect 80 litres Ethyl Oleate in the tank heat it to 120°c. keep it axide for cooling in sterile area. Take Ethanol
- in s.s. container 10th add in to it Benzyl Benzoate add Benzyl alchohol .
- Then add Hydoxy progestone caproate by small quantity into the main solution .Till complete solution
- with continuous stirring.
- Make-up the volume up to 100 litres with Ethyl oleate.
PREPARATION OF FILTER ASSEMBLY :
To be done under controlled environment , use 142 mm / 293 mm filter assembly . Before using , dismantle
all parts of the assembly like plates, lower plate, upper plate, clamps, nozzles , distributors, gasket , distributing net etc .
wash them with teepol , raw water and then washed with hot distilled water .cool them for better handling.
Mounting is done as follows:
1) Put lower plate on legs.
2) Put distributing net on lower plate on that the sieve is kept.
3) Put membrane filter on sieve, do not touch the paper on any surface. Put some distilled water on
the paper so it get soaked. Put the pre filter on it,
4) Put the upper plate with gasket properly fitted.
5) Clamp the filter assembly. Tighten the opposite clamps at a time to avoid any leakages.
6) Fix latex tubing.
7) Perform bubble point test at 40 pound pressure. If it passes the bubble point then sterilize it.
If it fails then mount the filter paper again . Filter assembly should not be fully airtight while sterilizing.
Sterilization of filter assembly is done at 117 0 C for 30 minutes. After sterilization, filter the prepared batch
filtered the solution in sterilized S. S. receiving vessels. Bubble point test perform before and after the filtration.
AMPOULE WASHING :
1) Decarton the ampoules in clean plastic creates in aseptic area.
2) Transfer the creates in washing room.
3) Arrange these ampoules in S.S. trays.
4) Load tray in ampoules washing machine.
5) Put on the cycle.
6) Ampoules are washed through unit with 5 micron filtered D.M. water with alternate the flushing with filtered compressed air.
7) Unload the machine and arrange.
8) The ampoules into S.S. tray for dry heat sterilizations.
To be sterilized at minimum 200° C for 1 hour.
STERILIZATION OF SOLUTION :
The product is aseptically filled . Sterilization is achieved by filtering through a membrane filter. Filteration is
done through a 142 mm/293 mm membrane filter of 0.22 micron size. Prefilter1.5micron used is 142 mm/293 mm.
1) FILLING UNIT :
It consist, of S.S. syringes, holders, filling needles, gassing needles, silicone tubing etc.
The above should be first cleaned carefully with teepol, raw water and then washed with hot distilled water.
After cleaning. Syringes deeped in distilled water and kept in S.S. tank which are then invaded into
the autoclave for sterilizing. The sterilization cycle is 117 0 C for 30 minutes.
2) RECEIVING VESSELS :
Vessels which are used to collect the filtered solution have to be first washed with teepol solution steamed,
then washed with hot distilled water and taken into the unit preparation area. Here they are rinsed twice
with fresh distilled water . The opening of vessals are then sterilized at 117 0 C for 30 minutes.
3. GARMENTS :
Garments that are used in the sterile filling area are first checked if they are torn . Torn garments are rejected.
Clean garments are then folded property and two sets are put into one sterilization box open loaded into
the autoclave for sterilization . The sterilization cycle is 117 o C for 30 minutes . After sterilization the
perforation are closed . The garments are taken to the air lock and are hanged on to hangers.
4. GLOVES :
New gloves are washed thoroughly with DM water and then with distilled water. The gloves are also checked
for any tearing and if found any, rejected . These gloves are then put into s.s. unit boxes with the perforation
open and sterilized at 1170 C for 30 minutes.
FILING OPERATION :
Filling of ampoules with sterile solution is done in sterile area. Ampoules filling is done on four head
ampoule filling and sealing machine.
Filling capacity of the machine is 80 ampoules per minute . During filling, the production supervisor has
to conduct creation in process control test at regular interval.
In process Test Frequency
a. Fill volume 1.0 to 1.15 ml 30 minutes
b. Nitrogen gassing is proper or not every one hour
c. Optical checking every one hour
write filing is going on movement should be restrained and there should be less talking. The machine should be kept clean.
During lunch break the full area should be cleaned , spraying of antiseptic solution should be taken up at regular intervals.
The arranged ampoules on the jolley are sterilized by dry heat sterilization at 115 0 C for 30 minutes. After the
cycle is completed the ampoules are allowed to cool in the sterilizers. After some time the ampoules are taken
out and are kept in hold area and precaution were taken to avoid any accident . After they are completely cooled
taken out to quarantine . In the sterilization area special precautions are taken for the worker because temperature
is variate in these areas there to avoid any type of accidents.
VISUAL INSPECTION :
Next day sterilized ampoules are taken for visual inspection. Visual inspection is done on inspection table.
The inspection is fitted with a source of illumination such as tube light . The screen has half the area painted with white and half the area painted in black. The front of the light is covered so that the direct light does not fall on the a separate table . The ampoules are checked by swirling its contacts by wrist movement and observe for any particle or foreign matters . There should be a gap of 5 to 10 minutes after one hour of working. Trained operators should only be allowed.
Type of rejection :
1. Black particles
2. White particles
4. Glass particles
5. Shining matters
6. Sealing rejection
7. Less / high volume