Quality Assurance & Quality Control: Module 6 Pharmchem 4
Quality Assurance & Quality Control: Module 6 Pharmchem 4
Quality Assurance & Quality Control: Module 6 Pharmchem 4
Sample Statistics
Upper warning line
3. Quality Assurance (QA)
Target
Totality of the organized arrangements made with the Lower warning line
objective of ensuring that products are of the quality Lower control line
required for their intended use 1 2 3 4 5
Wide ranging concept that covers all matters individually or Sample Number
collectively influence
Types:
4. Current Good Manufacturing Practice (CGMP) 1. p-Chart proportion of defectives
Part of quality assurance which ensures that products are 2. np-Chart non-proportion (number of defectives)
consistently produced and controlled to the quality 3. X Bar Chart used for measurable characteristics
standards appropriate for their intended use
Warning limit alerts the operator to closely monitor the process
5. Quality Control Action limit alerts the operator to stop the process and do
Part of CGMP concerned with sampling, specifications, corrective action
testing, organization, documentation and release
procedures (PIC/S Guidelines QA CGMP QC) F. VALIDATION AND QUALIFICATION
6. Product Quality Review (PQR) 1. Validation the action of proving and documenting that any
Regular periodic quality reviews of all registered drug process, procedure or method actually leads to the expected results
products to verify consistency of the existing process and to
identify product and process improvements 2. Qualification the action of proving that premises, systems or
equipment work correctly and actually lead to expected results.
7. Quality risk Management (QRM)
A systematic process for the assessment, control, G. PRODUCT DEFECTS
communication, and review of risks to the quality of the
product Non-conformance to a standard or requirement
2. Standard Operating Procedure (SOP) Removal of product from the market because it is either
Step-by-step instruction for doing a particular task or activity defective or potentially harmful
2. Instrumental Methods
Spectroscopy
Chromatography
3. Expiration Date C. ASSAY
Time or date prior to which a product is expected to remain
stable and after which it must not be used To determine the amount of API or biologic activity
Calculated using this formula
Methods:
4. Stability Studies 1. Chemical Assay
Used to estimate the shelf-life of a drug product Titrimetry
Evaluated over time in the same container-closure system in Instrumental methods
which the drug product is marketed
Based on ASEAN Guidelines on Stability Studies 2. Biologic Assay
Climatic zone Animal Assay
Microbial Assay
Climatic Zone Type of Climate Temperature Humidity
Zone I Temperate 21 2 45 5% Animal Assay
(Canada,
Drug Animal used Drug Animal Used
Germany, Russia)
Zone II Mediterranean/ 25 2 60 5% Digitalis Pigeon Chorionic Female Rat
(USA, Japan, Subtropical Gonadotropin
Italy, France, Tubocurarine Rabbit Vasopressin Male Rat
Australia) Insulin Rabbit Oxytocin Chicken
Zone III Hot and dry 30 2 35 5% Glucagon Cat PTH Dog
(Iraq, Jordan) Corticoprin Rat Heparin Sheep
Zone IVA Hot and humid 30 2 65 5% Cod Liver Oil Rachitic Rat Protamine SO4 Sheep
(UAE, Saudi
Arabia) Microbial Assay
Zone IVB Hot and very humid 30 2 75 5% Methods:
(Philippines
and other Asian
Cylinder Plate Method
countries)
Uses a cylinder or paper disc impregnated with sample,
placed on a solidified nutrient medium in a Petri dish
Types of stability Studies
Based on the diameter of the zone of inhibition
a. Long-term Studies
Turbidimetric Method
Conducted under normal conditions
Uses a test tube filled with fluid nutrient medium, where the
Testing period: 0, 3, 6, 9, 12, 15, 18, 24, 36
test organism is inoculated
Based on measurement of transmittance
1.2 Sieving
Adv: fastest True/ Particle volume (Vp)
Limitation: Granule volumes (Vg) = Vp + Intraparticle spaces
At least 25g of sample Bulk volume (Vb) = Vg + Interparticle spaces
Not for oily cohesive material
Density
Porosity (E)
Endpoint for Tapped Density (V500 V1250 = ?) Ability to withstand mechanical shocks from handling in
V1250 = tapped volume manufacturing, packaging and shipping
> 2mL Affects dissolution, and disintegration, BA
Adjustments:
3. powder flow Too hard (may not disintegrate in the required time period)
Too soft (will noy withstand handling)
3.1 Angle of repose ( )
Measure of flowability Hardness Tester
Maximum angle possible between the surface of the pile of Rule of thumb Crude method/ sharp snap (acceptable)
powder and the horizontal plane Stokes (Monsato) Spring
3D angle assumes by a cone-like pile of material Strong cobb Air pump/ hydraulic pressure
Pfizer Pliers (like)
Apparatus: Erweka Suspend motor-driven weight
Fixed funnel; fixed cone (constant diameter), Free standing Schleungier/ Heberlein Motor-driven anvil crushes tablet horizontally;
most widely used (eliminates operator
cone (constant ht.), Tilting box, Revolving cylinder variability)
Acceptance Criteria:
Experimental considerations:
Conventional and ordinary coated tablet: min 4 kg (4-10 kg)
Base must be standardized flat surface without vibration
SL, chewable: 2-3 kg
Funnel must be at least 2-4cm above the cone to avoid
Buccal: 7/8-10 kg
deformation
MR tablets: >10 kg
2. Tablet Thickness
h = height of the powder cone
Importance:
r = radius of the powder cone
Identical appearance
Facilitate packaging
Accuracy for tablet counting machines
measure of compressibility
Apparatus:
Micrometer or Vernier caliper/ thickness gauge
*Same formula as bulk porosity
Acceptance Criteria: 5% of the set standard thickness
dosage unit
Sample: 20 uncoated compressed tablets
2.1 Bacterial endotoxin/ Limulus Amebocyte Lysate test (in 2. Media fill (process simulation testing)
vitro) Evaluates the environment along with the process, operators
LAL source: Horseshoe crab (Limulus polyphemus) and equipment
Detect and quantify endotoxin from gram-negative bacteria Sterile trypticase soy broth is filled into at least 3000 sterile
3 techniques: -25°C
Gel-clot for bacterial growth
Turbidimetric Acceptance Criteria: nmt 0.1% of units is (+) for growth
Chromogenic
3. Electronic/ automated particle counter
2.3 Rabbit test (in vivo) Determines particle size by means of shadow casted by
Rabbit Test particles as it passes through a high intensity beam
Prior test - Samples: 3 healthy, mature rabbits (37 2 °C) Disadv: nonspecific
- Apparatus: Depyrogenated at 250°C
During test - Inj. 10mL/kg TS in the ear vein, completing inj. Within
10mins after start of administration
Counter counter Electrical resistance
- After 1 hour, record the rectal temperature (30 mins/ Gelman counter Tyndall effect
1-hour intervals for 3 hours) Hiac/ Royco = Light blockage
AC (Non- Sum rise:
Pyrogenic) - AC 1: <1.5°C for 3 rabbits (provided NO individual 4. Membrane filtration technique
°C + 5 rabbits Collects particles size greater than the membrane pore size
- °C for 8 rabbits (provided NMT 3 rabbits Disadv: saturable, slow counting
°C
HEPA filter
Example: the ff data were obtained on pyrogen test in 8 rabbits
Rabbit # Temp rise (°C)
Efficiency tests:
1 02
DOP (dioctyl phthalate) test
2 0.6
3 0.3
Test HC (Henkel corp) emery test
4 0.5
5 0.1
6 0.2
7 0.2
8 0.4
Sum rise = 2.5°C
a. Did the individual temp rise of each rabbit comply with the
requirement? Yes °C)
b. Did the temp rise comply with the requirement? Yes (Sum
)
4. Clarity Test
Visual inspection; inverted to see heavy particles (can be
done @ 100% or product
discrimination
5. Particulate matter
Emboli phlebitis
Must be carried out in laminar airflow hood