2. In- process quality control
Purpose:
To insure batch uniformity and integrity of drug product
Procedures for I.P.Q.C. should describe:
• In process controls and their limits
• Tests and examinations to be conducted
• Sampling procedures of each batch
I.P.Q.C.:
• For manufacturing operations
• For packaging operations
3. Scanning/Vectorization
Option
Transfer Verify Data Production Steps
& Convert Completeness In-process QC Inspection
Independent QC Inspection
Verify Image Transform Process Decision Point
& Vector Coordinates Main Process Flow
Quality Interactive QC Loop
Review
Scan/ Transform
Vectorize Statistics
Manuscript
Prep Edits
Identify & Positional Accuracy,
Manuscript Automate Pass/
Correct Completeness and
Verification Maps Fail
Gross Errors Topology testing
Basic Production Flow with
Manual Common Quality Control
Digitizing
Checks
4. Edits
Positional Accuracy,
Pass/ Attribute
Completeness and
Fail Coding
Topology testing
Manual
Attribute
Production Steps
Testing
In-process QC Inspection
Independent QC Inspection
Process Decision Point
Main Process Flow Pass/
Interactive QC Loop Edits
Fail
Edgematch Transformation Coordinate Automated
Edgematch
Verification Verification Transformations QC Checks
Final
Sign-off Basic Production Flow with
Common Quality Control Checks
Delivery
5. Independent Inspection
Will always find errors that
elude the data processor.
In-Process Inspection
Useful for controlling simple
data processing actions.
6. General Guidelines
for Cost-Effective Error Checking
Re-work is always more costly
than doing it right the first time.
Check everything once, and then
concentrate on maintaining data
integrity through the remaining
processes.
Minimize the amount of materials
that have to be handled.
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7. QUALITY MANAGEMENT
Data Quality Control is Process Control
Documentation
Record existence of anomalous conditions
Maintain a complete data dictionary
(including data extraction rules)
Always provide staff (or vendor) with
detailed written procedures plus diagrams
describing graphic decision rules
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8. QUALITY MANAGEMENT
Data Quality Control is Process Control
Communication
Develop formal mechanisms
(i.e., standard symbols/colors for errors)
Conduct frequent coordination and status
meetings
Provide honest opinions and feedback
9. IN-PROCESS EVALUATION
Process parameters should be evaluated
and optimized.
For example : Mixing
Order of addition
Mixing speed
Mixing time
Rate of addition etc.,
10. Chemical weigh sheet
Identify the chemicals
Its quantity
The order of using
The sampling directions
Process specifications
Should be in understandable language
In process and finished product
specifications
Proper documentation required
11. GMP CONSIDERATIONS
Process Validation
Regular process review and
revalidation
Relevant written Standard Operating
Procedures
Equipment Qualification
Regularly scheduled preventive
maintenance
12. Validated cleaning procedures
An orderly arrangement of equipment so as
to ease material flow and prevent cross-
contamination
A well defined technology transfer system
The use of competent, technically qualified
personnel
Adequate provision for training of personnel
13. MATERIAL/POWDER HANDLING
Two primary concerns : Achieving reliable
flow and maintaining blend uniformity.
Segregation leads to poor product uniformity.
Handling system :
- Must deliver the accurate amount of the
ingredient
- Material loss should be less
- There should be no cross contamination
14. Avoiding segregation …..
Modify the powder in a way to reduce its inherent
tendency to segregate
Change the particle size such that the active
segregation mechanism becomes less dominant
Change the cohesiveness of the powder such that
the particles in a bed of powder are less likely to
move independent of each other
Modify the equipment to reduce forces that act to
segregate the powder
Change the equipment to provide remixing
15. DRY BLENDING
Dry blend should take place in
granulation vessel
Larger batch may be dry blended
and then subdivided into multiple
sections for granulation.
All ingredients should be free of
lumps otherwise it causes flow
problems.
Screening and/or milling of the
ingredients prior to blending usually
makes the process more reliable
and reproducible.
16. GRANULATION
• The weight of the material and the
shear forces generated by
granulation equipment.
• The use of multifunctional processors
(significant in terms of space and
manpower requirements).
• Viscosity of the granulating solution.
17. FLUIDISED BED GRANULATIONS
Process inlet air temperature
Atomization Air Pressure
Air Volume
Liquid Spray Rate
Nozzle Position and Number of
Spray Heads
Product and Exhaust Air
Temperature
Filter Porosity
Cleaning Frequency
Bowl Capacity
19. Hot Air Oven
Air flow
Air Temperature
Depth of the granulation on the trays
Monitoring of the drying process by the
use of moisture and temperature probes
Drying times at specified temperatures
and air flow
rates for each product
20. Fluidized Bed Dryer
Optimum Load
Air Flow Rate
Inlet Air Temperature
Humidity of the Incoming Air
21. PARTICLE SIZE REDUCTION
Sizing plays a key role in achieving uniformity.
There are two ways of sizing : Particle size separation
and Particle size reduction.
Major Factor – Feed rate of the material.
As the feed rate is increased so is residence time
with in the chamber of the equipment which in turn
results in finer distribution.
During scale up, overhead feeding equipment is
incorporated to mimic large scale production.
22. BLENDING
Blender loads
Blender size
Mixing speed
Mixing time
Bulk density of the raw material (considered
in selecting blender and in determining
optimum load)
Characteristics of the material
24. Dry Blending and Direct Compression
The order of addition of components to the blender
The blender load
The mixing speed
The mixing time
The use of auxiliary dispersion equipment within the
mixer
The mixing action
Compression force
25. Slugging (Dry Granulation)
Forces used for slugging operation
The diameter of the punches
Subsequent sizing and screening operations
26. GRANULATION HANDLING
AND FEED SYSTEM
Evaluation of vacuum automated
handling systems and mechanical
systems
Segregation : Due to static charges
built up due to vacuum can alter
material flow property
The effect of above system on the
content uniformity of the drug and on
the particle size
27. COMPRESSION
Press speed
Handling and compression characteristics
(in the selection of a tablet press)
Die filling rate
Flow rate of granules
Induced die feed systems (for high speed
machines) – speed of feed paddles
The clearance between the scraper blade
and the die table
Design and condition of the punches
29. Pan and Fluidized Coating
Optimum tablet load
Operating tablet bed temperature
Drying airflow rate and temperature
The solution application rate
The size and shape of the nozzle aperture
(for airless sprayer)
The atomizing air pressure and the liquid
flow rate (for air atomized sprayers)
