PROVIDED INFORMATION ABOUT COMMON QUALITY CONTROL TESTS FOR PARENTRAL.

1. QC Of Sterile Pharmaceutical Product

2. QC Of Sterile Pharmaceutical Product
SUBMITTED BY
ANIKET J.GHOLAP

3. QC Of Sterile Pharmaceutical Product
QUALITY CONTROL TESTS

4. QC Of Sterile Pharmaceutical Product
QUALITY CONTROL
Quality control is define as a set of activities for
ensuring quality in product. The activities focus on
identifying defects in the actual product produce.

5. QC Of Sterile Pharmaceutical Product
TEST FOR STERILITY
Sterility is defines as freedom from the presence of viable
microorganism
Method A:
Membrane
Filtration
Method B: Direct
Inoculation

6. QC Of Sterile Pharmaceutical Product
Fluid
Thioglycollate
Medium
Soyabean-
casein Digest
Medium

7. QC Of Sterile Pharmaceutical Product
METHOD A:MEMBRANE FILTRATION
Membrane filter (0.45 μ pore size)
Filter test solution
Remove filter
Cut filter into two halves
First halve second halve
(for bacteria) (for fungi)
Transfer to 100mL culture media Transfer to 100mL culture media
(FTM) (SCDM)
Incubate 30-35°C for NLT Incubate 20-25°C for NLT
7days 7days

8. QC Of Sterile Pharmaceutical Product
Aseptically opening each sample container
Using a sterile syringe or needle withdraw the required volume of sample
Aseptically transfer into both culture media
FTM SCDM
Incubate 30-35°C for NLT 14 days Incubate 20-25°C for NLT 14 days
METHOD B:DIRECT INOCULATION
METHOD

9. QC Of Sterile Pharmaceutical Product
Observation &
interpretation of result
No evidences of growth Evidences of growth
Pass sterility test
Retesting performed with same no. of sample
& volume of media is in original test
No evidences of growth Evidences of growth
Pass sterility test
Isolate & identify organism
Second retest with twice no. of sample
No evidences of growth Evidences of growth
Pass sterility test Fail sterility test

10. QC Of Sterile Pharmaceutical Product
TEST FOR PYROGEN
Pyrogen is metabolic by product of living micro-organism/
dead micro-organism themselves.
METOHOD A:
RABBIT TEST
OR SHAM
TEST
METHOD B:
LAL TEST OR
BACTERIAL
ENDOTOXIN
TEST

11. QC Of Sterile Pharmaceutical Product
The test involves measurement of the rise in body temperature of rabbits in
presence of pyrogen introduced by the IV injection of a sterile solution into
ear vein of rabbit.
Use healthy, adult rabbits of either sex, preferably of the same variety.
•Having temp. variation high than 39.8°C.
•Showing temp. variation >0.2°C between 2 successive reading in the
determination of initial temp.
•Animal show temp. increase over 0.6°C should be remove from pyrogen
testing
METOHOD A: RABBIT TEST OR SHAM TEST
Principle
Test animals
Do not use any rabbit

12. QC Of Sterile Pharmaceutical Product
Carry out the test using a group of 3 rabbits.
•Preparation of the sample
Dissolve the substance in or dilute with pyrogen free saline solution.
Warm the liquid to approximately 38.5° before injection.
•Volume of injection NLT 0.5 mL/kg & NMT 10 mL/kg of body weight.
•Clinical thermometer inserted into rectum of rabbit to record body temp.
•Two normal reading or rectal temp. taken prior to test injection at an
interval of half an hr. & it mean is calculated initial temp.
•Test solution injected into ear vein.
•Record temp. of each rabbit in time interval 30 min for 3 hrs.
•Different between initial & maximum temp. record & take as response.
PROCESS

13. QC Of Sterile Pharmaceutical Product
INTERPRETATION OF RESULT
No. of rabbits Individual
temp. rise
( C)⁰
Temp. rise in
groups ( C)⁰
Test
3 Rabbits 0.6 1.4 Passes
If above not
passes
3+5=8 rabbits
0.6 3.7 Passes

14. QC Of Sterile Pharmaceutical Product
Advantages of Rabbit Test
The human and rabbits are equally responsive to threshold
levels of the pyrogens.
Disadvantages of Rabbit test
 Based on animal model
 Time consuming
 Only detect presence of pyrogen not quantify them

15. QC Of Sterile Pharmaceutical Product
Measures the concentration of bacterial endotoxin
 Test is using lysate derived from hemolymph cells or amebocytes of
e.g Limulus polyphemus
 Endotoxin limit calculated by K/M
K maximum no. of endotoxin which receive the
patient without suffering toxic reaction
M maximum dose administered to a patient/kg/hr
horse shoe crab.

16. QC Of Sterile Pharmaceutical Product
Mechanism of LAL Test
The test is based on the primitive blood-clotting mechanism
of the horseshoe crab.

17. QC Of Sterile Pharmaceutical Product
PROCEDURE

18. QC Of Sterile Pharmaceutical Product
Different
Techniques
A
Gel-clot
Technique
B
Turbidimetric
Technique
C
Chromogenic
Technique

19. QC Of Sterile Pharmaceutical Product
A. GEL CLOT TECHNIQUE
 A solid gel is formed in the presence of endotoxins.
 Technique requires positive and negative controls.
Positive
controls
A known concentration of endotoxin added to
the lysate solution
Negative controls Water, free from endotoxins, added to the lysate
solution
 This is based on the measurement of color change which is caused by
the release of the chromogenic chemical.
 E.g. The quantity of the p-nitroanilide (chromogenic chemical)
produced is directly proportional to the endotoxin concentration
B. CHROMOGENIC TECHNIQUE

20. QC Of Sterile Pharmaceutical Product
 The development of turbidity after cleavage of an endogenous substrate.
 The test is based on the measurement of opacity change due to the
formation of insoluble coagulin.
 Opacity is directly proportional to the endotoxin concentration.
 This technique is used for water systems and simple pharmaceutical
products.
C. TURBIDIMETRIC TECHNIQUE

21. QC Of Sterile Pharmaceutical Product
Advantages of LAL test
Alternative to animal model
Greater sensitivity
Less variability
Less time consuming
Detect the pyrogen and also measure the quantity of
pyrogen

22. QC Of Sterile Pharmaceutical Product
PARTICULATE MATTER TEST
Particulate matter refers to the extraneous, mobile, undissolved
particles, other than gas bubbles, unintentionally present in the
solutions.
METHODS
A
Light Obstraction
Particle Count Test
B
Microscopic
Particle Count Test

23. QC Of Sterile Pharmaceutical Product
 Particular count is based upon either light scattering, light obstruction/
direct imaging.
 Light blockage which allows an automatic determination of the size of
particles and the number of particles according to size.
A. LIGHT OBSTRACTION PARTICLE COUNT TEST

24. QC Of Sterile Pharmaceutical Product
TYPE PARTICLE SIZE
LVP Max. 50 Particles/mL ≥ 10 µm
Max 5 Particles/mL ≥ 25 µm
SVP NMT 10,000 Particles/Container ≥ 10 µm
NMT 1,000 Particles/Container ≥ 25 µm
USP LIMIT

25. QC Of Sterile Pharmaceutical Product
LEAKAGE TEST
 Test the package integrity.
 Package integrity reflects its ability to keep
the product in and to keep potential
contamination out.
 Leakage tests are 4 type
 Visual Inspection
 Bubble Test
 Dye Tests
 Vacuum Ionization Test

26. QC Of Sterile Pharmaceutical Product
UNIFORMITY OF WEIGHT
Remove the labels & wash the container & dry
Weigh the container along with content
Empty container completely
Rinse with water & ethanol, dry at 100°C to a constant weight
Cool & weigh
Net weight calculated

27. QC Of Sterile Pharmaceutical Product
 All of the tests which are performed are essential and have its own
importance in sterile production .
 All of these tests ensure that product meet its quality which has been
judged to satisfactory also.
 Each test is unique and provides detailed assessment of quality control for
parenteral products.
CONCLUSION

28. QC Of Sterile Pharmaceutical Product
IP 1996 Appendix 2.1 pg. no. A-24 to 26
Appendix 9.5 pg. no. A-117 to 123
Appendix 10 pg.no. A-125 to 126
Remington. The science and Practice of Pharmacy. 21st
ed. Page no.
1367 to 1374.
Pharmaceutical Quality assurance by M.A. Potdar second edition
Nirali prakashan pg. no. 13.22, 13.23
www.pharmainfo.net/lal-test
AJPTR article Nithin Chilukuri-4055(1).pdf
Parenteral-preparations-draft-QAS12-479-18072018.pdf
www.pharmaguideline.com
REFRENCES

29. QC Of Sterile Pharmaceutical Product