QUALITY ASSURANCE - QUALITY CONTROL

 Cooperate with regulatory agencies

TRANS BY: PABALAY, JL
and final authority for product
QUALITY
acceptance or rejection
- totality of characteristics or features  Helps to identify and prepare
of a product that bear on its capacity necessary SOP’s relative to control of
to satisfy stated or implied needs quality
 Audit and quality monitoring
Quality Management
sum total of the organized NOTE:
arrangements made w/ the Audit and quality monitoring
QA object of ensuring that products - to determine if operations have
will be consistently of the quality adequate systems, facilities and
required by their intended. written procedures
Ensure that production
consistently produced &
GMP controlled according to quality
standards & marketing
authorization (from FDA).
- part of GMP concerned with
sampling, specifications & Factors affecting Quality products
testing, & with the organization, (contributing Quality Products)
documentation & release  Personnel  Environment
procedures which ensures that  Procedure  Package
the relevant & necessary tests  Equipment  Starting
QC are intact & in fact carried out &  Premises materials
that  Validate
materials are not released. processes
- mechanisms, processes, Personnel – major source of contaminant
techniques, & activies necessary
to ascertain whether a specific
standard is achieved. QUALITY CONTROL

QUALITY CONTROL
QUALITY ASSURANCE
- part of GMP concerned with
QUALITY ASSURANCE sampling, specifications & testing, &
with the organization,
- sum total of the organized
documentation & release procedures
arrangements made w/ the object of
(methods and procedures in ensuring
ensuring that products will be
the safety of the products)
consistently of the quality required
by their intended. (paperworks) QC Functions

QA Departmental Functions  Testing and acceptance of only highly

quality raw material, representative
 Assures the policies are followed
samples
inept to economic issues associated
 IP tests against criteria
with manufacturing and distribution
 Monitors environmental conditions
of products
 Control packaging components

3 Main Areas of Quality Control

  Raw Material Quality Control (RMQC) - document with the results of all tests
 In Process Quality Control (IPQC) conducted on material to show
 Finished Product Quality Control compliance or non-compliance with
(FPQC) the standard specifications approved
by responsible personnel.

FORMULA

- this is concise and precise statement

of the ingredients that comprise the
product, together with the
percentage and/or weight of each.

RAW MATERIAL SPECIFICATION

- this should enumerate the

characteristics of all the materials
that go into the product and the
permissible range of purity of each
ingredient

STANDARD OPERATING PROCEDURE

- this is a step-by-step method on how

to go about a job

FINISHED PRODUCT SPECIFICATION

- this should cover all characteristics

that affect the proper performance,
purity, safety and stability of the
product

SAMPLE

- finite number of objects selected

from a batch

SPECIFICITY
DEFINITION OF TERMS
- assess unequivocally the analyte in
MONOGRAPH the presence of component that may
be expected to be present.
- a document that specifies all the tests
to be conducted on particular material or ROBUSTNESS
product, the procedure &/or appropriate
- measure of capacity to be unaffected
reference containing the details of the
by small but deliberate variations in
procedure & the expected results
method & provides indication of its
CERTIFICATE OF ANALYSIS reliability during normal usage.
 DEFECTS Major defect

DEFECTS - may affect the function of the object

& therefore, may render the product
- undesirable characteristics of a
useless.
product, failure to conform to
- example: presence of a crack in a
specifications
bottle
DEFECTIVES
Minor defect
- contains one or more defects
- does not endanger life or property
Classification of Defects nor it will affect the function, but
nevertheless remains a defect since it
 According to measurability is outside the prescribe limits.
 According to seriousness or gravity - example: slight variation (deviation)
 According to nature of the color of the label from the
1. According to measurability color standards

3. According to nature
Variable defect

- can be measured directly by Ocular defect

instruments giving dimensions of - a defect that is visible
length, weight, height, thickness, - example: foreign particular
concentration, volume, viscosity, pH, contamination
or size particles
Internal defect
Attribute defect
- not seen although present
- cannot be measured directly by - example: a subpotent drug product
instruments
- it shows mainly the conformance or Performance defect
nonconformance of the material to - defect in function
specifications. - example: a suppository that does not
- this applies to many things that can melt at the body temperature
be judged only by odor or visual
examination like color, clarity, sheer, VARIATION
cleanliness, smoothness, taste, &
Sources of Variation
presence or absence of a
characteristics.  Materials
 Machines
2. According to seriousness or gravity
 Methods
Critical defect  Men

- may endanger life or property & Materials examples:

render the
a. Variation between suppliers of
- product non-functional.
same substance
- example: absence of warning in a
b. Variation between batches from
label for a potent drug
the suppliers
c. Variation within a batch
Machines examples:

a. Variation equipment for the same

process
b. Difference in adjustment of
equipment
c. Aging and improper care

Methods examples:

a. Inexact procedures
b. Inadequate procedures
c. Negligence by chance

Men examples:

a. Improper working conditions

b. Inadequate training, &
understanding
c. Dishonesty, fatigue, and carelessness

ANALYTICAL BALANCES

Class 1.1

- For low capacity (1 to 500 g)

- high sensitivity balances

Class 1 3 Main Areas of Quality Control (Analytical

Test)
- High precision standards for
calibration  Raw Material Quality Control
- for weighing accurate quantities (RMQC)
below 20 mg  In Process Quality Control (IPQC)
Class 2  Finished Product Quality Control
(FPQC)
- may be used to quantity greater than
20 mg RAW MATERIAL QUALITY CONTROL (RMQC)

Class 3 & 4 Adulteration

- used with moderate precision lab - means it contains ingredients (nay

balances sagol ang products)

Class 3 Debasement of article (ADULTERATION)

- for quantity greater than 50 mg Sophistication

Class 4 - “true adulteration”

- addition of inferior material
- for quantity greater than 100 mg
Substitution
 - entirely different from the one d. Optical activity
requested
- angle of optical rotation of a plane
Admixture polarized light
- polarimeter
- add through accident, ignorance,
carelessness e. Boiling point

Spoilage - vapor pressure is equal to

atmospheric pressure
- quality destroyed by microorganism
f. Melting point
Deterioration

- quality impaired due to environment,

insects, etc 3. INSTRUMENTAL

Tests in Raw Material Quality a. IR spec – vibration, compared to standard

Control (RMQC)
b. UV-vis spec – excitation, absorbed and
 Identity Test (ID test)
 Purity Test transmitted light
 Limit Test c. HPLC – retention factor
 Physical Test (Additional)
 Special Test (Additional) d. NMR – amount of magnetic signal/ field
resonance

A. ID TEST (IDENTITY TEST)

1. CHEMICAL (indication)

Examples: (visible reactions)

change in color,
precipitation,
evolution of gas

2. PHYSICAL

a. Specific gravity B. TEST FOR PURITY (PURITY TEST)

- wt of sample/wt of std (water) 1. MONOGRAPH (Assay)

- Pycnometer and Westphal balance
- alcohols at 15.56 C a. chemical – titration
- water at 25 C b. instrumental – HPLC, GC
b. Solubility c. biological
- dissolution of compound at a suitable
solvent

c. Refractive index
C. LIMIT TEST
- bending of light
- Abbe refractometer 1. Gross impurities
 - examples: gross dirt, insoluble matter

2. Biological impurities

- examples: viable microorganism

(aerobic/anaerobic), specific
microbial strains, metabolic IN PROCESS QUALITY CONTROL (IPQC)
products/cell debris
Solid Dosage Forms
3. Chemical impurities
A. GRANULES AND POWDERS
- examples: trace metals (heavy B. TABLETS
metals), ions, degradation products C. NON-STERILE ORAL/TOPICAL
PRODUCTS
Chloride AgNO3 AgCl
Sulphates BaCl2 BaSO4
Arsenic Diethythiocarbamate
(vis-spec 535-45 mm)
A. PRIMARY H. TAPPED DENSITY
Na and Ca Flame spectroscopy MOISTURE CONTENT
Iron Ammonium thiocyanate B. ADEQUACY OF
blood red complex I. CARR INDEX
WETNESS
Heavy metals H2S black C. SHAPE J. HAUSNERS RATIO
Except: D. FINAL MOISTURE K. PARTICLE SIZE
 Zinc (white) CONTENT DISTRIBUTION
 Cadmium (yellow) E. ANGLE OF REPOSE L. THICKNESS
 Tin (orange) F. POROSITY M. HARDNESS
 Manganese (pink) G. BULK DENSITY

IPQC FOR GRANULES AND POWDERS

A. Primary Moisture Content: 31 – 35 %

B. Adequacy of Wetness

C. Shape

D. Final Moisture Content: 0.5 – 1.0 %

Picking (adhere
to punches)
(increase) moisture
Sticking (adhere
to dies)
Capping
Chipping (decrease) moisture
Lamination

E. Angle of Repose
 - is a constant three-dimensional angle
assumed by a cone-like pile of
H. Tapped Density
material.

Methods:
I.
1. Static angle of repose
Carr’s Index
2. Kinetic angle of repose
- is an
1. Static Angle of Repose

Fixed funnel

1. Fixed cone – fixed or constant

diameter
2. Free-standing cone – constant height

Other technique:

1. Tilting box – box with open top is

tilted

2. Kinetic Angle of Repose

indication of the compressibility of a
- Revolving cylinder powder

J. Compressibility Index & Hausner’s Ratio

Interpretation:

Angle of Repose
Flow Property
(degrees)
Excellent 25 – 30
Good 31 – 35
Fair (aid not needed) 36 – 40
Passable – must hang 41 – 45
up
Poor – must agitate,
46 – 55
vibrate
Very poor 56 – 65
Very, very poor >66

K. Particle Size Distribution

F. Porosity
Sieving – most rapid

Mesh # - (#) number linear opening

per square inch
G. Bulk Density Techniques:

a. Sieving
 b. Optical microscopy  Weight variation test
c. Electron microscopy  Content Uniformity test
d. Sedimentation  Disintegration test (U.S.P.)
e. Light Scattering Technique  Dissolution test
f. Adsorption study
g. Electrolytic resistivity
h. Permeameter 1. Weight variation test
i. Coulter counter
j. Light blockage - Weigh 20 tablet selected at random,
each one individually. X1, X2, X3,…Xz
- Determine the average weight. X=
(X1 + X2 = X3, … + Xz) / 20

Limit:

o Upper limit = average weight +

(average weight * %error)
o Lower limit = average weight –
(average weight * % error)
o The individual weights are compared
with the upper and lower limits.
o Not more than two of the tablets
differ from the average weight by
more than the & error listed, and no
tablet differs by more than double
L. Thickness: Vernier Caliper; Micrometer
that percentage.

Weight Variation Tolerances for Uncoated

M. Hardness Tablets

USP XX – NF STANDARDS
Max %
Average wt of
SR NO. difference
tablet
allowed
1 130 or less 10 %
2 130 – 324 7.5 %
3 more than 324 5%
IPQC FOR TABLETS

 Weight variation IP STANDARDS

 Disintegration Max %
 Dissolution Average wt of
SR NO. difference
the tablet
 Drug content allowed
1 84 or less 10 %
2 84 – 250 7.5 %
o HARDNESS 3 more than 250 5%
o FRIABILITY

WEIGHT VARIATION 2. Content Uniformity Test

 Randomly select 30 tablets. 10 of 7.5, KH2 PO4 (phosphate buffer) +
these assayed individually. The tablet pass pancreatic enzyme + NaOH)
the test if 9 of the 10 tablets must contain
not less than 85 % and not more than 115 %
of the labeled drug content and the 10 th
tablet may not contain less than 75 % and
more than 125 % of the labeled content. If
these conditions are not met, remaining 20

tablet assayed individually and none may fall

outside of the 85 to 115 % range.
U.S.P. Method for Uncoated Tablets

o Start the disintegration test for 6

3. Disintegration Test (U.S.P.)
tablets.
o It is the time required for the tablet o If one or two tablets from the 6
to break into particles, the tablets fail disintegrate completely
disintegration test is a measure only with 30 min repeat the same test on
of the time required under a given another 12 tablets (i.e., the whole
set of conditions for a group of test will consume 18 tablets).
tablets to integrate into particles. o Not less than 16 tablets disintegrate
o It is performed to identify the completely within the time.
disintegration of the tablet in o If more than two tablets (from the
particular time period. 18) fail to disintegrate, the batch
o Disintegration test is not performed must be rejected.
for controlled & sustained release
For Coated Tablets
tablets.
o According to the test the tablet must o To remove or dissolve the coat,
disintegrate and all particles must immerse that tablet in distilled water
pass through the 10-mesh screen in for 5 mins.
the time specified. If any of residue o Put the tablet in the apparatus in
remains, it must have a soft mass. water or HCl for 30 mins at 37 C
Disintegration media (according to the U.S.P.). If not
disintegrated, put in intestinal fluid.
o Water o If one or two tablets fail to
o Simulated gastric fluid (pH = 1.2 HCl), disintegrate, repeat on 12 tablets. So
or Simulated intestinal fluid (pH = 16 tablets from the 18 must
 completely disintegrate within the
time, if two or more not
disintegrated the batch is rejected.

U.S.P. and B.P. Method for Enteric Coated

Tablets

o Put in distilled water for five minutes

to dissolve the coat.
o Then put in simulated gastric fluid
(0.1 M HCl) for one hour.
o Then put in simulated intestinal fluid
for two hours.
o If one or two tablets fail to
disintegrate, repeat this test on
another 12 tablets. So, 16 tablets
from 18 should completely
disintegrate. If more than two fail to
disintegrate the batch must be
rejected.

4. Dissolution Test

Dissolution is performed to check

the percentage release from the dosage
forms.

Example: Tablet

Tablet breaks down into small

particles which offers a greater surface area
to the dissolving media.

Disintegration test does not give

assurance that particles will release drug in
solution at an appropriate rate, that’s why
dissolution tests and its specifications
developed for all tablet products.