1. IN PROCESS QUALITY
CONTROL FOR VARIOUS
Prepared By:- Priyanka Yadav
M.PHARM (QA) 1st SEM
Guided By:- Mr Hiren Kadikar
Arihant school of Pharmacy & BRI
IN PROCESS QUALITY
Carried out during production in order to monitor & it is
necessary to adjust the process to ensure that the product
conforms to its specification.
The control of environment or equipment is also regarded
as part of IPQC.
Whenever any production process is going on, it is
necessary to see that the process is going on as desired.
This is required to avoid less of efforts And if the process
has not proceeded as desired ,then the whole processed
material may be required to reprocessed or rejected.
Identify the type of formulation you are manufacturing or going
to manufacture, e.g. tablets, liquid, injectables, ointment etc….
Identify which are the critical steps in the manufacturing of the
product where it will be necessary to check certain parameters
to confirm that the process is in control.
Identify the limits of parameters which will confirm that the
parameters are within the control. Define the frequency of
checking for each parameter.
Create monitoring & control records for all IPQC process.
IPQC procedure should available in the form of SOP which is
duly written approved & authorized for use.
In the designing of IPQC system following steps should
IPQC FOR TABLET:
Essential for consumer acceptance.
The control of general appearance of tablet involves no. of
attributes such as tablet size, Shape, color, taste, surface
texture, any identifying markings.
The thickness of the tablet is only dimensional variable.
At constant compressive load, tablet thickness changes with
change in die fill, with particle size distribution
While with constant die fill thickness will vary with change in
Thickness measured in micrometer-gives idea about
variation in individual tablet, another is sliding caliper scale-
uses 4-5 tablet for the measurement.
Thickness should be controlled within ±5% variation of
The color of a product must be uniform within a single
tablet, from tablet to tablet & lot to lot.
Usually color comparison requires that sample to be
compare against the standard color.
Color evaluation is done by-
TRISTIMULUS COLORIMETRIC MEASUREMENT
MICRO REFLECTANCE PHOTOMETER.
Tablet required certain amount of strength or hardness &
resistance to withstand mechanical shocks of handling in
manufacture, packaging & shipping.
Historically strength of tablet is determined by breaking it
between the 2nd & 3rd finger with thumb as fulcrum.
The Monsanto tester,
The Erweka tester,
The Pfizer tester,
The strong cob tester,
The Schleuniger tester.
As the pier's handle are squeezed, the tablet is
compressed between a holding anvil & piton is connected
to a direct force reading gauge.
The dial indicator remains at the reading where the
tablet Breaks & return to zero by depressing a reset
For this ROCHE FRIABILATOR is used, in which no. of
tablet subject to combined effect of abrasion & shock by
utilizing a plastic chamber that revolves at 25 rpm, dropping
the tablets from a distance of 6 inch with each revolution.
Pre weighed tablet is placed in chamber which is then
operated for 100 revolutions.
The tablets are then deducted & reweighed.
Limit -0.5 to 1%
High loss occurs in effervescent & chewable tablet & may
be due to use of deep concave punches, due to low moisture
Rough handling test —vibration test, drop test, incline plane
CONTENT UNIFORMITY OF ACTIVE INGTREDIENT:
Small variation between individual preparations is accepted.
For tablets two tests:-Uniformity of weight ,
Uniformity of API.
For the test of uniformity of weight in practice, sample of 10
tablets are taken & weight throughout the compression
The composite weight divided 10 but contains the usual
problems of average value.
The USP/NF provides limit for the permissible variation in the
weights of individual tablet which is expressed as a % of avg.
Wt. of the sample.
For those 20 tablets are weights individually, then avg. wt. is
calculated, and compare individual wt. to avg. wt.
Tablet complies if NMT 2 is outside the % limit.
•Weight variation tolerance for uncoated tablets :
•According to USP:
•According to IP:
Average wt( mg) Maximum % difference
130 or less 10
More than 324 5
Average wt( mg) Maximum % difference
85 or less 10
More than 250 5
The drug release process from immediate release include
step at which the tablet disintegrates into small fragments.
The test is carried out by agitating a given number of tablets
in an aqueous medium at defined temperature & time to reach
the end pint of the test is recorded.
Preparation complies with test if the time to reach this end
point of test is point at which all visible parts of the tablets
have been eliminated from a set of tubes in which tablets have
been held during agitation.
The tubes are closed at the lower end by a screen & the
tablet fragments formed during the disintegration are
eliminated from the tubes by passing the screen opening.
APPARATUS USED FOR DISSOLUTION TEST:
Single tablet is placed in a small wire mash basket fastened to
the bottom the shaft connected to variable speed motor.
The basket is immersed in the dissolution medium contained in
The flask is maintained at 37˚c+ 0.5˚c by a constant temperature
Samples are withdrawn at interval to determine the amount of
drug in solution.
Basket is replaced by paddle –formed from a blade & shaft.
The test tolerance is expressed as a % of labeled amount of drug
dissolved in the time limit.
e.g. Methyldopa tablet –medium: 900ml 0.1N HCL.
Apparatus -2 at 50 rpm with time limit of 20 min.
Amount dissolved in 20 min. is NLT 80%of labeled amount.
IPQC FOR CAPSULE:
DISOLUTION & DISINTEGRATION TEST
WEIGHT VARIATION TEST FOR HGC &SGC
MOISTURE PERMEATION TEST:
The degree & rate of moisture penetration
determined by the packing the dosage unit together with color
–revealing desiccant pellet, exposing the packaged unit to
known relative humidity over a specified time observing the
desiccant pellet for color change—due to absorption &
comparing pre test & post test wt. of packaging unit.
IPQC FOR LIQUID ORALS:
The purified water used for manufacturing purpose must
meet the standards
Raw materials used for manufacturing purpose are all
approved labels fix on it
Physical characteristics of raw material like color, odor
and consistency should be checked before compounding.
Raw materials having factor of moisture should be
considered if required as per BMR before use.
Weighed raw materials by store officer should be counter
checked by pharmacist, if any difference is noted it should
be immediately brought to the notice of factory manager.
pH of the product should be checked before & after filtration.
Physical description of the final product should meet the
Equipment & machinery used for filling & capping should be
thoroughly checked & adjusted as per required specification.
•Intermittently filled volume is checked at 30 min. interval.
IPQC FOR OINTMENTS:
Various experiments are done for 3 different functions:--
•PENETRATION OF THE BASE THROUGH SKIN:
Fixed quantity of base –x gm. Rubbed on fixed area for
fixed time. Unabsorbed base was collected –y gm.(x-y)
difference give penetration.
Biopsy is taken to check penetration after rubbing on skin,
Liquid paraffin-slow, almond oil-fast.
•TEST FOR PERMEATION:
Fixed amount of drug rubbed on fixed area for fixed
time. Then concentration of drug is measured in urine.
E.g. methyl salicylate. Radioactive Nacl used as drug.
•RATE OF RELEASE OF DRUGS:
Na –fluorescence in as a drug mix with base ----rubbed ---
stain produced---more pigmentation----more release.
•Agar cup-plate method: bacteriostatic drug is used ----
zone of inhibition is measured.
•Bandelin: release of Nacl in water can be detected at
IPQC FOR PARENTRALS (STERILE):
It involves two stages:
A. Inspection of manufacturing facility.
B. Product testing.
A. INSPECTION OF MANUFATURING FACILITY:
Facility including walls, ceiling, equipments, work surface
should be periodically monitored for contamination .for this
the object are swabbed & incubated on sterile nutrient
media to observe microbial growth.
B. PRODUCT TESTING:
There are 5 Tests: 1. Sterility testing
2. Clarity testing
3. Leak test
4. Pyrogen test
1) STERILITY TESTING:
All the parentral preparation which are supplied in sterile
form must confirm the test for sterility
The sterility testing is carried out under aseptic condition.
The test for sterility is done for detecting the presence of
viable forms of bacteria, fungi, and yeast in parentral
All glassware require for the test should be sterile. Culture
media should be prepared as per pharmacopoeia.
The test samples of parental preparation are transferred
into test tube containing sterile culture media.
These test tubes are incubated for specific period of time
into incubator at favorable condition.
The presence of turbidity in culture media indicates the
growth of microorganism & sample fails to comply the test.
This can be confirmed by repeating the test. Thus the test
for sterility is the most reliable method for determining
whether or not particular lot of material is sterile.
The test is based on the principle that if bacteria or fungi
are placed in a medium which provides nutritive material &
water & kept at a favorable temperature. The organism will
grow & their presence can be detected by turbidity in clear
STEPS INVOVLED IN STERILITY TESTING:
•Selection of the sample size
•Selection of the quantity of the product to be used.
•Method of testing.
•Observation & results.
SELECTION OF SAMPLE SIZE:
•Sample is representative of whole of bulk material
•Mixing is required when taking the sample.
•The random sampling should be carried out.
•As per IP minimum number of no. of items are
recommended to be tested.
SELECTION OF THE QUANTITY OF PRODUCT:
For injection— minimum no. of items
X<100 4 container whichever is grater
100< X<500 10 container
X > 500 20 container
•X <1ml whole content
•1ml < X <4ml half content
•4ml < X <20ml 2ml
•20ml < X <100ml 10%
•X > 100 not less then half quantity
METHOD OF TESTING OF STERILITY:
I. MEMBRANE FILTERATION METHOD:
This method is preferred for oily preparation & ointment,
soluble liquid, powder& liquid product where the volume is
more then 100ml.
It involves filtration of sample through a membrane filter with
a porosity of 0.45 micron diameter approximately 47 mm.
After the filtration membrane is removed aseptically from the
metallic holder & divided in two halves –1st half & 2nd half.
1st half is transferred into 100ml of culture media meant
for fungi. (Soya-bean casein digest medium for anaerobic
Then it is incubated for 20°-25°c for NLT 7 days.
2nd half is transferred in 100 ml of fluid thioglycolate media
then it is incubated at 30°-35°c for NLT 7days.
For both of them observed the media for growth.
FLUID THIOGLYCOLATE MEDIA:
Yeast extracts 5gm
Pancreatic digest of casein 15gm
Na- thioglycolate 0.5gm
METHOD OF PREPARATION:
Mix all the ingredient except Na-thioglycolate & Resazurin in
a mortar, add hot water.
Transfer into the flask. add remaining water. heat on water
bath till clear solution.
Add Na-thioglycolate adjust the pH between 7.1-7.3 with 1N
Reheat the solution .filter it add Resazurin solution transfer
into final container sterilized by autoclaving for 20 min. at
121°c & cool at 25°c.
Stored at 20°-30°c.during storage if more then 30% of upper
portion of media has change to pinkish color it is suitable for
SOYA-BEAN CASEIN DIGEST MEDIUM: FORMULA-
Pancreatic digest of casein 17gm
Dibasic potassium phosphate 2.5gm
Peptic digest of Soya-bean 3gm
METHOD OF PREPARATION:
Dissolve all ingredients into water. Make clear by warming
cool it to room temperature.
Adjust the pH to 7.1-7.5 by 0.1 N NaoH. Transfer in a
suitable container sterilized by autoclave 121°c for 15 min.
II. DIRECT INNOCULATION METHOD:
•In this method the specified quantity of sample is taken
aseptically from the container & transfers it to vessel of
•Mix the liquid with the medium and incubate for NLT 14
days .observe the growth of microorganism in the media.
OBSERVATION & RESULT:
If there is a evidence of growth then retest. If no growth then
pass it for further process. Retest with same no. of container.
No growth Presence of growth
Pass Repeat --1
Growth No growth
Repeat test --2 No growth then pass
Identify & isolate the organism ,if distinguish the
microorganism then retest is carried out & if not
distinguished then it Fail the test.
2) LEAK TEST:
•Ampoules are used to provide a hermetically sealed
container for a single dose of product so there should not be
any interchange between the content of sealed ampoule & its
•If any capillary pores or tiny cracks is present so
microorganism or any other contaminant may enter the
ampoules or the content may leak outside or spoil.
•Change in temp. During storage occur will cause expansion
or contraction of ampoules & content so completely ampoule
• Leaker test is used to detect the incompletely sealed
ampoules for its discardation.
•In addition small crakes may occur around seal or at base of
ampoule as a result of improper handling.
Leaker are detected by producing a –ve pressure within
an incompletely sealed ampoule, in vacuum chamber while
the ampoule is entirely submerged in deep color solution of
dye. E.g. Methylene blue.
Due to atmospheric pressure dye tries to penetrate the
opening visible after washing ampoule.
Leaker detection is more effective when ampoules are
immersed in bath of dye during autoclaving cycle. In this
test both Leaker test & sterilization is done in the one step.
Capillary, bottles, & vials are not subjected to this test
because rubber closure is not rigid.
3) CLARITY TEST:
•USP states that good pharmaceutical practice required that all
containers be visually inspected & that any with visible particle
Q.C. responsibility is to discard individual container of
product that the user will consider to be unclean.
In any lot of product there may be few container having
visible particle this must be detected by visual inspection &
Suspension, emulsion or dry solids in addition to solution
should be compounded & processed under clear condition to
minimize the presence of foreign matter.
The visual inspection of product container is done by human
inspection of each container under a good light against
reflection into eyes & against a black & white background.
4) PYROGEN TEST:
•The amount of pyrogen substance in preparation is
determined by qualitative biological test on response of rabbits
because rabbit show same response as in human being.
•If pyrogenic substance is injected to rabbit vein, an elevation
of temperature within period of 3 hours. For this test it is
difficult to obtained consistent result with rabbit because use of
rectal thermometer so, replaced by thermocouples which
eliminate the handling of rabbit for individual temp. reading.
•In vitro test for pyrogen detected by using the gelling property
of limulus amebocyte lysate. In presence of pyrogen endotoxin
from gm-ve bacteria a firm gel is formed within 60 min. when
incubated at 37 °c
5) ASSAY: content of API is determined by different methods
like UV, TITRATION. Assay method is different for different
38. STANDARD OPERATING PROCEDURE:
A written authorized procedure which gives instruction for
performing operations. E.G.: Equipment, sampling, cleaning,
In order to ensure that the best possible medicine be made
available to the consumer, it is imperative that it fulfills three
Therefore to ensure the highest standards for his drug
products, that have to be ultimately consumed by the patient,
standard operating procedures (SOPs) need to be laid down.
39. SOPs are tool to ensure that good manufacturing practices
(GMP) are being followed wherever applicable.
They contain the relevant information about any activity or
procedure (cleaning, operation, calibration, validation,
maintenance, training etc.) to be performed.
REASONS FOR SOP:
For some time now, especially during the last ten years,
there has been an over what are available in the market.
It was increasingly being felt that in addition to clinical
safety of a drug, that is established by the inventor before
introducing a product in the market, other factors also
affect the quality of drug products.
This means that if an activity is to be performed, there should
be documentary evidence to prove that the activity was done,
it was done by a predefined person , it was done by the required
procedure and this was checked/verified by a predefined person.
40. CONTENT OF SOP:
Objective of SOP
Procedure to be followed
Person responsible for doing the activity
Person responsible for checking
It should contain –name of company, SOP number,
PRECAUTION FOR PREPARING SOPS:
It should be written in a clean language.
Record must be kept.
41. PREPARATION OF SOP:
The SOP should be written by a supervisor who is
supervising the actual performance who is actually involved
with the activity in the respective department.
All SOPs must be written in the following format .
•Section1 - OBJECTIVE
•Section2 - RESPONSIBILITY
•Section3 - ACCOUNTABILITY
•Section4 - PROCEDURE.
42. SOP FOR CLEANING
Clean environment and clean operation is the
heart of pharmaceutical activities.
Cleaning directly related to – Purity & Safety.
Cleaning SOP - cleaning equipment, cleaning agent,
frequency of cleaning records of work performed.
43. CLEANING OF DISPENSING EQUIPMENTS:
LIKE SCOOPS, SPATULAS ETC.
CLEANING AGENTS:- 2% TEEPOL SOLUTION , 70%IPA
For every drug substance, dedicated Equipments are used.
Immediately after completing the dispensing operation
dispensing equipments are removed from the dispensing area
& taken up for cleaning.
The operator should wear rubber gloves.
After rinsing under running tap water Equipment is scrubbed
with 2% teepol solution , and rinsed with D-water.
44. To remove the sticky substance the equipments are rinsed
with hot water & scrubbed with 2% Teepol solution.
1st rinses by tap water, 2nd rinses by D-water & the equipment
is spray with 70% IPA & dried with hand held dryer.
This clean & dry equipment is wrapped in AL- foil.
A label is affixed having details like Name of dry substance,
date of cleaning, clause ‘I AM CLEAN’.
45. CLEANING OF RAW,PAKAGING & FINISHED
In the process of receiving, issuing, dispensing lot of dust is
created which settles & contaminates the whole area around
the dispensing table or the entire store.
The dust settles in the bulk container that may cause cross
So, care should be taken in cleaning the whole area.
Collect the settled powder over tables, floors, containers etc.
by using vacuum cleaner.
Vacant the empty containers from the areas or from the racks
& wipe the dust with a cotton cloth.
Use the wet mop for cleaning of floors. Use liquid soap
(100ml in 10 lit water) for wet mopping followed by swabbing by
fresh tap water.
46. CLEANING OF DISPENSING TABLE:
Clean the surface of the container & dispensing table with a
Take only one item at a time for dispensing.
Collect the spoiled powder over & around the dispensing table
with a duster.
Wipe the dust from dispensing area and clean with dry cloth.
Clean the dispensing area with a wet cloth and repeat it for
Apply IPA 70% to avoid contamination & for cleaning.
47. WEAKLY CLEANING PROCEDURE:
Collect the dust settled over the office equipments, furniture
& walls by using vacuum cleaner.
Wipe the dust with dry duster.
Sweep the floor thoroughly & use wet mop for cleaning the floor.
CLEANING ONCE IN THREE MONTHS:
Clean the ceiling of whole area of stores including racks, walls.
wipe the racks & walls with dry cloth duster.
Sweep the floor, Add 100gm caustic soda to 10 liter of tap water
for cleaning the floor, mop the floor with this solution.
Wipe the floor with 1% Teepol solution.
Apply pest control insecticide inside the stores.
49. SOP FOR FILLING
LIQUID ORAL FILLING:
Before starting liquid or suspension filling its necessary
to ensure that , the bulk container having
released label for filling.
The filling machine is assured to determine required
volume to fill in washed bottles & cleaned caps are used.
Filling volume record is to be maintained as per
Suspension is filled under the constant stirring operation
& care should be taken during suspension filling that there
should be no air entrapment.
50. ASEPTIC FILLING:
For aseptic filling pre sterilized vials, ampoules, filling
assemblies, sterile filtered solution & class 100 Area are
check all steam sterilized materials have indicator &
expiration date, also check all assemblies.
open the sterilized bin contains filling assemblies and tubing
on LAF bench.
Connect two silicon tubing to the two outlets of sterile solution
fix the housing of filling assembly to the filling machine.
Insert the piston in to syringe to the piston holder to the
Attach one tubing to the inlet of filling nozzle and
attach the free end to outlet of syringe.
Connect the other end of tube, attach to tank to the inlet
of filling assembly. And also connect the nitrogen overlay in
Vent the holding tank with a sterilized vent filter.
Adjust the required flow rate of nitrogen and check alarm
Pump the solution in filling tubing up to the filling nozzle.
Remove Any air Bubble in the tubing.
Wipe the vials feeding ampoule filling hopper with sterile
70% Isopropyl Alcohol.
Fill few vials/ampoules and check fill volume. Reject the
first few filled vials/ampoules.
53. SOP FOR DRYING
DRYING USING FLUID BED DRYER:
Load the bowl with material to be dried.
Spread the material uniformly in bowl to avoid lumps.
Move the product bowl below the retarding chamber & keep
the window in viewing position.
Position the bowl lift the bottom of FBD by moving jack handle
to the opposite side & seal the trolley to the retarding chamber.
Now, check & ensure that there is no leakage.
Set the timer & switch on the heating, maintaining the desired
inlet air temperature.
Put off the heater & bring timer to ‘0’. When drying is complete
put off the main switch. Lock & withdraw the bowl.
54. DRYING USING TRAY DRYER:
Load about 2-3 kg of material on each tray.
Place the tray in tray chamber & load them to top rack to
After completion of loading close the chamber door.
Set drying temperature by coarse setting
knob & the fine setting knob.
Start the dryer & Adjust time and alarm knob.
Label on door identifying name, batch no. of product.
When required temperature is reached, note down time of
At the end of required drying cycle time bring down the set
temp. to zero by knob. So, that cooling of product is faster.
Then open the door of drier.
Unload each tray of material into container with poly bags.
Close bag & label it. Replace each unloading tray back to dryer
& closed & place to be cleaned tag on it.
55. SOP FOR COMPRESSION
◊During compression of tablets it is advisable to check the
of tablets in order to ensure that the tablet will comply with
Tablet is placed between two anvils & pressure is applied.The
pressure which is required to crush the tablet is measure in
56. PFIZER TESTER:
As the pier's handle is squeezed, the tablet is compressed
between a holding anvil & piton, which is connected to a direct
force reading gauge.
The dial indicator remains at the reading where the tablet
Breaks & return to zero by depressing a reset button.
Determined by VERNIER CALIPER.
This is measured at 15 min. interval.
It should be clean & whole unit is remove from glass beaker.
It contains 6 cylindrical tubes, from each disc is removed &
tablet is placed then disc is placed.
In the glass beaker add medium & temperature should be
37˚+ 2˚ c. now this assembly is place in glass beaker in such
a way that it will remain below 2.5 cm from the surface of
medium & above the 2.5 cm from the bottom of the beaker.
The motor is driven with frequency of 28-32 cycle/min.
time required for tablet to pass from the mesh is recorded &
compare with ideal.
58. SOP FOR COATING
OPERATION OF CONVENTIONAL COATING PAN:
•Loading of uncoated tablets in the coating pan
3.Hot air blower
•Ensure the working and effectiveness of exhaust system &
hot air blowers.
•Arrange the position of hot air blowers & exhaust pipes.
•Carryout the coating operation as per the SOP laid down in the
Following parameters are strictly controlled:
•Compressed air pressure. 58
59. •After completion of coating, check laid down physical
parameters of coated tablets as per procedure.
•Remove coated tablets /pellets/granules from the pan into
double polybags in an Al-container.
STOPPING THE OPERATION IN COATING SECTION:
• conventional coating pan (when coating is continue)
Switch off the mains of pan, hot air blowers & exhaust
Close the main compressed air inlet valve.
Close the pressure regulator valve of feed vessel.
Remove the spray gun stand.
Switch off the lights of the department.
60. •Conventional coating pan (when loading/unloading is continue)
Fix the lid of the pan tie the unloaded drums & Label them.
Keep the unloaded drums on pallet.
Switch of the lights of the department.
• At the end of the shift:
In automatic pan close the main compressed air valves.
Close the door of the pan.
If loading is going on then keep empty drums on the pallet.
Put the used polybags in dustbin.
Cover the mouth of pan with polybag.
Switch off the lights of the department.
At the weekend unload the tablets from pan.
61. SOP FOR STERILIZATION
Sterilization is process of eliminating or killing all the
microbes by heating, irradiation, etc.
It is also the method by which all contaminations are
Certain pharmaceutical products must be sterile
injections, ophthalmic preparations, irrigations
solutions, haemodialysis solutions
Two categories of
Those that can be
sterilized in final
Those that cannot
sterilized and must
What is the definition of “sterile”?
Free from microorganisms
In practice no such absolute statement regarding
absence of microorganisms can be proven
Defined as the probability of 1 in a million of a
container being contaminated (10-6)
This referred to as the Sterility Assurance Level (SAL)
Organisms are killed in an exponential fashion
SOP FOR HOT AIR OVEN
1. Inspect the Oven.
electric power connections are made correctly
the area around the oven is clear.
Inspect the inside of the oven to make sure that no one has
left their specimen.
2. Oven in Use Notification
List any special precautions or comments
3. Turning on the Thermal Ovens
Turn on the oven by pressing the main power switch.
When oven is at desired temperature, prepare to load the
4. Loading the ovens
5. Removing samples from oven
Before you start to take anything out of the oven make
sure you have everything you are going to need.
6. Finishing Up
Turn off the oven
SOP FOR AUTOCLAVE
1. Autoclaving time and temperature depends on the
composition and nature of the items being autoclaved
15 minutes at 2500 F (1210 C) or 5 minutes at 2700 F
2. Items to be sterilized are loaded into the autoclave in
a manner so that nothing touches the inside of the
3. Make sure that the water reservoir is filled
(approximately 1” from top),with Distilled Water.
4. Items to be sterilized should be placed into the
autoclave so that steam can uniformly flow between
items and so that no air pockets are formed.
5. Small items to be autoclaved should be bagged or
wrapped in heat-resistant plastic, paper, or cloth.
6. Set appropriate temperature for the cycle.
Turn the autoclave to FILL and wait until the water in
the bottom of the autoclave covers the fill plate.
Turn the autoclave to STERILIZE and load autoclave
When cycle is complete, turn autoclave to VENT and
remain there until pressure drops.
7. Sterilized supplies must be labeled with date
8. Sterilization indicator strips (e.g., autoclave tape, steam
indicator strips) should be used.
9. When autoclaving Biohazardous waste:
Bags/containers should not be overfilled, half to three
quarters full is recommended.
Add water (e.g., approximately 1 cup) to the biohazard
bag/container prior to sealing the container so that steam
10.When the autoclave cycle is complete and the pressure
returns to zero the door may be opened
Turn the autoclave to POWER OFF.
11.Before opening the door, staff members
should have heat-resistant autoclave gloves.
Open door slowly and once opened, walk away from the
direct line of the steam.
12.The bottles and the water will remain very hot for a
long while. It is recommended that the bottles not be
used until the next day.
13. Staff members encountering malfunctions, should
report it immediately to the supervisor, and not attempt to
fix it themselves.
SOP FOR DISINFECTANTS
Disinfectants are substances that are applied to
non-living objects to destroy microorganism that are living
on the objects.
Disinfection does not necessarily kill all microorganisms,
especially non resistant bacterial spores; it is less
effective than sterilization which is an extreme physical
and / or chemical process that kills all types of life.
• Destroy microorganisms
within the body
• Destroy microorganisms on
• Intended to destroy all forms
of life, not just
Disinfectant (Mode of action)
Denature protein and lipid:
• Acid/ Basic
Release chemical bond: Aldehydes , Enzymes
Increase positive ion (Oxidant): Halogens, H2O2,
Gowning: The process of wearing special garments in order to
control particulate contamination.
Clean room: A controlled environment area with special HVAC
and architectural features to control airborne particulate
Disposable or launder able smocks
Isopropyl 70% wipes or liquid
Isopropyl 70% foaming hand cleaner
Tacky floor mats
Enter gown room and step on tacky mat with both feet.
Put on hair cover
Put on smock
Sit on bench and put on shoe covers one foot at a time.
Place covered foot on clean side of bench.
80. Put on gloves if product contact anticipated.
Clean hands with foaming alcohol before entering
main clean room.
Items entering clean room must be wiped down
with Isopropyl and wipes if they may be dirty or
No corrugated cardboard, pencils, or fiber
shedding materials allowed in the clean room.
81. Do not exit clean room while gowned.
Remove gowning items in reverse order of
Replace gowning weekly or if dirty.
Replace hair covers and shoe covers daily or as
Remove sheet on tacky mat daily or as needed.
♥ STERILITY TESTING:
♠ The test for sterility is applied to pharmacopoeial
articles that are required according to the
Pharmacopoeia to be sterile.
♠ However, a satisfactory result only indicates that no
contaminating viable micro-organisms have been
SOP FOR MEMBRANE FILTRATION
♠ The test must be carried out under aseptic
conditions designed to avoid accidental
contamination of the product during testing.
♠ For achieving these conditions, a grade A laminar
airflow cabinet or an isolator is recommended.
♠ The working conditions in which the tests are carried
out should be monitored regularly by appropriate
sampling of the air.
♠ Method A is to be preferred where the
♠ An oil
♠ An ointment that can be put into solution
♠ A non-bacteriostatic solid not readily soluble in
the culture medium
♠ A soluble powder or a liquid that possesses
Method A: MEMBRANE
♠ The method calls for the routine use of positive and
negative controls. A suitable positive control is the
occasional use of known contaminated solution
containing a few microorganisms of different types.
(approximately 10 CFU in the total volumes employed).
♠ A suitable unit consists of a closed reservoir and a
receptacle between which a properly supported
membrane of appropriate porosity is placed.
♠ A membrane suitable for sterility testing has a diameter
of approximately 50 mm.
Dissolve 1 g of peptic digest
of animal tissue (such as
bacteriological peptone) or its
equivalent in water to make 1
Filter or centrifuge to clarify,
adjust to pH 7.1 ± 0.2,
Dispense into flask and
sterilize at 121º for 20
If the test sample contains
lecithin or oil,
use fluid A to each liter of
which has been added 1 ml of
Adjust to pH 7.1 ± 0.2,
dispense into flasks and
sterilize at 121º for 20
♥Procedure For Aqueous
♠ Prepare each membrane by aseptically transferring a small
quantity of fluid A on to the membrane and filter it.
♠ For each medium to be used, transfer aseptically into two
separate membrane filter funnels.
♠ Alternatively, transfer aseptically the combined quantities of
the preparation under examination prescribed in the two
media onto one membrane.
♠ If the solution under examination has antimicrobial
properties, wash the membrane by filtering through it not
less than three successive quantities each of 100 ml, of
sterile fluid A.
♠ The quantities of fluid used should be sufficient to allow
growth of a small inoculums of organisms.
♠ After filtration, remove the membrane from the holder,
transfer the whole membrane or cut it aseptically into
2 equal parts.
♠ Transfer one half to each of two suitable media.
♠ Alternatively, transfer the medium onto the membrane in
the apparatus. Incubate the media for not less than 14 days.
♠ If the test specimen is positive before 14 days of
incubation, further incubation is not necessary.
♠ For products terminally sterilized by a validated moist heat
process, incubate the test specimen for not less than 7 days.
♥Procedure For oils and oily solutions:
♠ Filter oils or oily solutions of sufficiently low viscosity
without dilution through a dry membrane.
♠ Dilute viscous oils as necessary with a suitable sterile
diluents such as isopropyl myristate that has been
shown not to have antimicrobial properties under the
conditions of the test.
♠ Allow the oil to penetrate the membrane and filter by
applying pressure or by suction, gradually.
♠ Wash the membrane by filtering through it at least three
successive quantities, each of approximately 100 ml, of
sterile fluid B or any other suitable sterile diluents.
♠ Complete the test described under For aqueous solutions
from AFTER FILTRATION.
♥Procedure for Ointments & Creams:
♠ Dilute ointments in a fatty base and emulsions of the water-
in-oil type to give a fluid concentration of 1 per cent w/v,
with a suitable sterile diluent such as isopropyl myristate
previously rendered sterile by filtration.
♠ through a 0.22 ì m membrane filter that has been shown
not to have antimicrobial properties under the conditions of
♠ Filter as rapidly as possible
♠ Complete the test as described under For oils and oily
solutions, from WASH THE MEMBRANE.
Indian Pharmacopoeia 2007 Vol-1 ,56-70
Pharmaceutical Microbiology by N.K.Jain
D.H.Shah, SOP guidelines, Business horizons pharmaceutical
Manohar A. Potdar(2008) CGMP for pharmaceuticals, Pharmamed
Leon Lachmann(1990)the theory & practice of industrial pharmacy,
3rd edition ;296
Howard C. Ansel(2007) Angel’s pharmaceutical dosage forms &
drug delivery systems, 8th edition, By Wolters Kluwer health Pvt.
Ltd. New Delhi;218
M.E.Aulton(2002) Pharmaceutics the science of dosage form
design, 2nd edition; 417.