PRESENTATION CONTAINS THE INFORMATION ABOUT STANDARD OPERATING PROCEDURES FOR PARENTERAL DOSAGE FORM PREPARATION FOLLOWED BY PHARMACEUTICAL MANUFACTURING COMPANIES.

1. DEPARTMENT OF PHARMACEUTICAL SCIENCES
Dr. HARISINGH GOUR VISHWAVIDYALAYA, SAGAR (M. P.)
SOP FOR PARENTERALS
PRESENTED BY:
AVIJIT KUMAR BAKSHI
SUPERVISED BY:
Dr. DHARMENDRA JAIN
Mrs. NISHI MODI

2. CONTENT
1. SOP FOR SAMPLING OF RAW MATERIALS
2. SOP FOR SAMPLING AND TESTING SCHEDULE OF WATER FOR INJECTION
3. SOP FOR VALIDATION OF CLEAN AREA AND EQUIPMENTS LYING IN CLEAN AREA
4. SOP FOR MAINTENANCE OF ENVIRONMENTAL CONTROL
5. SOP FOR STERILITY TESTING
6. SOP FOR TESTING, RELEASE OR REJECTION OF FINISHED PRODUCT
7. REFERENCE

3. SOP FOR SAMPLING OF RAW MATERIALS
1.0 OBJECTIVE
To lay down procedure of sampling of raw material in order to get a representative sample of the whole lot for
analysis.
2.0 RESPONSIBILITY
• Doing: Technical Assistant
• Checking: Executive/ Manager
3.0 PROCEDURE
• Before proceeding for sampling ensure cleaned status for the sampling area.
• Open the container for sampling one by one.
• Observe visually for appearance of the material for any gross abnormalities like decolourization, lumps, non-
characteristics odour, foreign matter and physical heterogeneity.
• In case of any abnormalities observed, inform to the store in charge and QC executive/Manager.
• Assign the sampled Container No. as follows. (for active raw material only.) e.g. If 25 containers are received
then give the container no. as 1/25, to 25/25 with Reference to drum number of container sampled.
• Reseal the container after sampling as under and transfer it to UT area.
• Transfer the collected sample to QC laboratory under supervision.

4. CONTINUE
• Ensure the sample containers are closed tightly and labelled properly.
• Handover the samples along with (MRR) Material Receiving Report, stores physical verification report,
sampling checklist and supplier’s (COA)Certificate Of Analysis (IF received) to Q.C. department for analysis.
• Mark ‘SAMPLED’ stamps on containers from which the samples are collected. Cross the original approval label
of the manufacturer on all the containers.
• Affix yellow colour duly filled & signed “UNDER TEST’’ label on each container below white label of the store.
• Prepare sampling record of raw material.
• Make the entry of sampling done in sampler booth log card with respective details.
Name of Material :
Material code No :
Analytical Report. No :
Sampled by :
Date :
Container No : of :
Sampled Quantity :

5. SOP FOR SAMPLING AND TESTING SCHEDULE OF WATER FOR INJECTION
1.0 OBJECTIVE
To define the schedule & frequency for testing, locations for sampling and type of analysis required to be carried
out for the water for injection.
2.0 RESPONSIBILITY
• Doing: Technical Assistant ( Microbiologist)
• Checking: Executive/Manager
3.0 PROCEDURE
• Collection of WFI sample for chemical analysis.
• First collect the sample for chemical analysis.
• Flush water from the tap for 30 seconds.
• Rinse the sampling bottles three times with actual sample before sampling for chemical analysis.
• Collection of WFI sample for Total Organic Carbon (TOC) test.
• Use airtight container for the collection of WFI sample for TOC analysis.
• Wash the container prior to sampling with 2N HCl for 2-3 times.
• Collect about 60-70 ml of sample & close the sample container tightly.
• Collection of WFI sample for Microbiology testing.
• Fill the sample collection container with PW (purified water) & keep the cap tightly.
• Wrap it with wrapping/butter paper
• Sterilize it at 121°C for 30 min.

6. CONTINUE
• Discard the PW filled in sterilized sample container just before collection of WFI sample for analysis.
• Collect about 200ml of WFI sample in sterilized container and close tightly.
• Collection of WFI sample for Bacterial Endotoxin Test (BET)
• Use depyrogenated glass container for collection of WFI sample.
• Collect about 15ml WFI sample for BET.
• Frequency of testing:

7. SOP FOR VALIDATION OF CLEAN AREA AND EQUIPMENT LYING IN CLEAN AREA
1.0 Objective
To describe the procedure for monitoring of clean area and equipment lying in the clean area.
2.0 Responsibility
• Doing: Outside agency/Eng. Dept.
• Checking: Executive / Manager/Eng. Dept.
3.0 Procedure
A. HEPA filter integrity i.e. DOP test
FREQUENCY: Every six month
• The test is performed using DOP aerosol generator, which generates dioctylphthalate (DOP) monodisperse
aerosol with air pressure not less than 1.2 kg/cm2.
• Allow DOP aerosol smoke from upstream of HEPA filter and directed down stream through HEPA filter.
• Ensure that upstream flow have 100% concentration, by using a photometer.
• Ensure any leakage in HEPA filter by the photometer probe transverse through out the filter surface at a
distance not more than 3 inches from filter surface.
• In case of any leakage observed, identify the location of leakage and do the necessary action or inform
the engineering department.
• Acceptance Criteria: There should be at least 99.99% retention of particles above 0.3 μ size.

8. CONTINUE
B AIR VELOCITY:
FREQUENCY: Every six month.
• Measure air velocity through supply diffuser in all LAF unit and at each terminal HEPA in clean area with
mechanical vane type or orifice type anemometer in mtr/min. or ft/min.
• The average of 3 readings at different points should be considered if orifice type anemometer is used.
• Collect the print out of results and attach it with report.
• Acceptance Criteria: For LAF: 90 to 110 feet/min.

9. SOP FOR MAINTENANCE OF ENVIRONMENTAL CONTROL
1.0 PURPOSE:
This document deals with the procedure for maintenance of Environmental Control.
2.0 RESPONSIBILITY:
Form Fill Seal department staff.
3.0 PROCEDURE:
• Check all air handling systems of manufacturing and filling area are ‘ON’.
• Record the air pressures of the sterile area in differential pressure checklist.
• Limit
A) Filling Room FFS - 1.5 - 2.0 mmwc
B) Manufacturing Area - 1.5 - 2.0 mmwc
Frequency: Every Shift.
• Ensure that area sanitization is carried out every shift as per SOP.
• Check fixtures, walls and floors for absences of any damage/crevices. (If required, recondition the same
immediately through engineering department ).
• Clean window glass, doors, S.S. switch panels with a wet duster, followed by a dry duster.
• Frequency: Once in a day.

10. CONTINUE
• Record the temperature and humidity of filling and manufacturing area every shift in temperature and
humidity checklist.
Temperature Limit: 22 ± 4°c Humidity: 50 ± 5 %
NOTE: If readings are beyond limits, report to the engineering department and take Appropriate action on
AHU’s to get within limits.
• Check the microbial count in filling and manufacturing areas as per microbiological method.
• Air sampling should be done at various points in the area as per microbiological method.
• Carry out the fumigation as per SOP on the weekends.

11. SOP FOR STERILITY TESTING
1.0 OBJECTIVE
To ensure the that batch of product is sterile or has been sterilized.
2.0 RESPONSIBILITY
• Doing : Technical Assistant (Microbiologist)/Executive
• Checking : Executive /Manager
3.0 PROCEDURE
• STERILITY TESTING PROCEDURE FOR INSULIN
• For finish product : 20 containers of every batch or every lot.
• Arrange the filtration assembly in LAF and connect it with vacuum line / vacuum pump.
• Place sterile 0.45μ membrane on filter holder with the help of sterile forcep and clamped it properly.
• In another LAF, collect the sample solution from ampoules / vials / bottles in a sterile flask with help
of sterile syringe. For dry powder or lyophilized container, add the sterile water / 0.1% peptone
dissolve and then collect it in sterile flask.
• Filter the collected solution aseptically through 0.45μ membrane filter with help of vacuum.

12. CONTINUE
• Simultaneously perform the sterility test of 0.1% peptone water or any other diluent used for rinsing the
filter.
• After completion of filtration, open the assembly and cut the membrane filter in two equal parts with
sterile cutter.
• Inoculate aseptically one half membrane filter with help of sterile forceps in fluid Thioglycollate medium
and other half membrane filter in Soybean casein digest medium. Keep one tube of each medium without
inoculated as a negative control.
• Transfer the medium tubes to walk in incubator through hatch.
• In case of suspension, dissolve the insulin crystals in sterile 20% ascorbic acid (Approx. 50ml).
• Incubation time & temperature is follow.
• A) Fluid Thioglycollate medium : 30 – 35°C for NLT 14 Days
• B) Soybean casein digest medium : 20 – 25°C for NLT 14 Days
• After completion of incubation period, distribute each medium in three tubes and Inoculate the test
organisms.
• Acceptance criteria : Medium should be respond to growth within its incubation period.

13. SOP FOR TESTING, RELEASE OR REJECTION OF FINISHED PRODUCT
1.0 OBJECTIVE
To lay down the procedure for testing & release/rejection of the finished product.
2.0 RESPONSIBILITY
Quality Control Supervisor
3.0 PROCEDURE
• QA Personnel shall collect the Finished Product Sample and hand it over to QC chemist for analysis as per
Finished Product Specification and the same shall be recorded in control sample register.
• The details of the sample collected shall be entered into the entry register maintained separately for
finished goods.
• A Report of the Test Protocol applied and results obtained shall be maintained in a proper format wherein
the Calculations/ worksheet shall be included.
• If the sample is found to be complying to the test specifications, the same shall be released. If the same
does not comply, the material shall be rejected.
• After Approval of a Batch, Proper Control number for the same shall be allocated by QC department and
the same shall be maintained in the Finished Product Register. “Release” labels shall be given to QA
Personnel.

14. REFERENCE
• Escoe, Adrienne. 1997. Nimble Documentation. The Practical Guide for World-Class Organizations.
Milwaukee, Wisconsin: American Society for Quality, Quality Press.
• Garner, Willa Y. and Maureen S. Barge, editors, "Good Laboratory Practices. An Agrochemical Perspective,"
ACS Symposium Series 369, American Chemical Society.
• https://www.pharmaguideline.com/p/pharma-sops.html

15. THANK YOU