Process Validation

Summary of Critical Quality Attributes (CQAs) and Critical Process Parameters

(CPPs)
Below notes are a general overview for common Critical Quality Attributes (CQAs) and relevant
Critical Process Parameters (CPPs) of different processes to be considered during process
validation. Specific CQAs and CPPs may vary depending on the formulation and manufacturing
process.

TABLET MANUFACTURING

MANUFACTURING CRITICAL QUALITY RELEVANT CRITICAL

STEP ATTRIBUTES (CQAS) PROCESS PARAMETERS
(CPPS)
1. WEIGHING AND - Accurate drug substance and - Proper calibration of weighing
DISPENSING excipient weights balances
- Homogeneous blend - Consistent material handling
procedures
2. BLENDING - Uniform blend of drug - Mixing time and speed
substance and excipients - Proper blending equipment
- Blend potency and content setup
uniformity
3. GRANULATION - Granule size distribution - Granulation time and speed
- Granule moisture content - Addition rate of granulation
- Granule potency liquid
- Granulator operating parameters
4. DRYING - Moisture content of dried - Drying temperature and duration
granules - Airflow rate in the drying
- Granule particle size and chamber
flowability - Granule bed depth and
uniformity
5. MILLING AND - Particle size distribution of - Milling speed and screen size
SIZING milled granules - Proper mill maintenance and
- Granule potency calibration
6. BLENDING (FINAL - Uniform blend of milled - Mixing time and speed
BLEND) granules and lubricants - Proper blending equipment
- Blend potency and content setup
uniformity
7. COMPRESSION - Tablet weight and thickness - Compression force and speed
- Tablet hardness and - Die and punch specifications
friability - Lubrication process and quantity
- Tablet content uniformity
8. COATING (IF - Film coating thickness and - Coating solution properties
APPLICABLE) uniformity (viscosity, spray rate)
- Tablet appearance - Coating pan parameters
(temperature, rotation speed)
9. PACKAGING - Proper sealing and integrity - Packaging line speed and
of blister or bottle efficiency
- Accurate tablet count per - Proper calibration of packaging
package equipment

SYRUP AND SUSPENSION PREPARATION

MANUFACTURING CRITICAL QUALITY RELEVANT CRITICAL

STEP ATTRIBUTES (CQAS) PROCESS PARAMETERS
(CPPS)
1. WEIGHING AND - Accurate measurement of - Proper calibration of weighing
DISPENSING ingredients balances
- Homogeneous blend - Consistent material handling
procedures
2. MIXING - Uniform distribution of - Mixing time and speed
active ingredients and - Proper mixing vessel setup
excipients and cleaning
- Blend potency and content
uniformity
3. FILTRATION (IF - Removal of particulate - Selection of appropriate filter
APPLICABLE) matter - Clarity of the medium
solution - Filtration pressure and
temperature
4. PH ADJUSTMENT - Target pH value - Addition of acid or base
- Acid-base balance solution
- pH measurement and
adjustment control
5. STERILIZATION (IF - Microbial load reduction - Selection of appropriate
APPLICABLE) - Sterility assurance sterilization method (e.g., heat,
filtration)
- Sterilization temperature and
duration
6. FILLING - Accurate volume and - Filling speed and accuracy
dosage per container - Capping or sealing process
- Proper sealing and closure parameters
integrity
7. LABELING AND - Accurate labeling - Labeling accuracy and
PACKAGING information legibility
- Proper packaging integrity
 - Packaging line speed and
efficiency

SEMI-SOLID PRODUCT MANUFACTURING

MANUFACTURING STEP CRITICAL QUALITY RELEVANT CRITICAL

ATTRIBUTES (CQAS) PROCESS
PARAMETERS (CPPS)
1. WEIGHING AND - Accurate measurement of - Proper calibration of
DISPENSING ingredients weighing balances
- Homogeneous blend - Consistent material
handling procedures
2. MIXING - Uniform distribution of - Mixing time and speed
active ingredients and - Proper mixing vessel setup
excipients and cleaning
- Blend potency and content
uniformity
3. HEATING AND - Uniform heating and melting - Heating temperature and
MELTING of ingredients duration
- Melting temperature range - Selection of appropriate
melting equipment
4. COOLING - Proper solidification or - Cooling rate and
gelation temperature control
- Consistency and texture - Cooling vessel design and
setup
5. HOMOGENIZATION - Uniform distribution of - Homogenization time,
(IF APPLICABLE) particles or droplets - speed, and pressure
Homogeneity of the product - Selection of appropriate
homogenization equipment
6. FILLING OR - Accurate volume or weight - Filling speed and accuracy
PACKAGING per container - Proper - Packaging line speed and
packaging integrity efficiency
- Proper sealing or closure
process
STERILE VIAL AND AMPOULE MANUFACTURING

MANUFACTURING CRITICAL QUALITY RELEVANT CRITICAL

STEP ATTRIBUTES (CQAS) PROCESS PARAMETERS
(CPPS)
1. GLASS VIAL OR - Removal of particles and - Washing temperature and
AMPOULE WASHING contaminants from the duration
glass surface - Selection of appropriate washing
- Residual detergent or solution
cleaning agent levels - Proper rinsing and drying process
2. STERILIZATION - Sterility assurance - Selection of appropriate
- Absence of pyrogens sterilization method (e.g.,
autoclave, depyrogenation tunnel)
- Sterilization temperature and
duration
- Validation of sterilization process
3. FILLING - Accurate volume per - Filling speed and accuracy
container - Vial or ampoule handling and
- Proper sealing and positioning
closure integrity - Capping or sealing process
parameters
4. LYOPHILIZATION - Preservation of product - Freezing temperature and
(IF APPLICABLE) integrity and stability duration
- Residual moisture - Drying temperature and duration
content - Vacuum level and drying
chamber pressure
5. STOPPERING OR - Proper closure integrity - - Stopper or cap placement and
SEALING Prevention of crimping force
contamination - Sealing equipment setup and
validation
6. VISUAL INSPECTION - Absence of visible - Inspection criteria and acceptance
particles or defects limits - Visual inspection
- Container integrity equipment calibration and
validation
7. LABELING AND - Accurate labeling - Labeling accuracy and legibility
PACKAGING information - Packaging line speed and
- Proper packaging efficiency
integrity - Container labeling and packaging
material selection
LYOPHILIZED PRODUCT MANUFACTURING

MANUFACTURING CRITICAL QUALITY RELEVANT CRITICAL

STEP ATTRIBUTES (CQAS) PROCESS PARAMETERS
(CPPS)
1. FORMULATION - Homogeneous blend of - Mixing time and speed
PREPARATION active ingredients and - Proper mixing vessel setup and
excipients cleaning
- pH and osmolality of the - pH adjustment and control
formulation
2. STERILIZATION (IF - Sterility assurance - Selection of appropriate
APPLICABLE) - Absence of pyrogens sterilization method (e.g.,
autoclave, sterile filtration)
- Sterilization temperature and
duration
3. FILLING IN VIALS OR - Accurate volume per - Filling speed and accuracy
AMPOULES container - Vial or ampoule handling and
- Proper sealing and closure positioning
integrity - Capping or sealing process
parameters e.g. machine speed,
temperature, etc...
4. FREEZING - Controlled freezing rate - Freezing temperature and
- Prevention of crystal duration
formation or damage to the - Cooling rate control
product - Selection of appropriate
freezing equipment
5. PRIMARY DRYING - Removal of ice crystals - Drying temperature and
(SUBLIMATION) without collapse of the duration
product structure - Vacuum level and chamber
- Residual moisture content pressure
- Shelf temperature control
6. SECONDARY DRYING - Removal of bound - Drying temperature and
(DESORPTION) moisture duration
- Residual moisture content - Vacuum level and chamber
pressure
- Selection of appropriate drying
equipment
7. STOPPERING OR - Proper closure integrity - - Stopper or cap placement and
SEALING Prevention of contamination crimping force
- Sealing equipment setup and
validation
8. VISUAL INSPECTION - Absence of visible - Inspection criteria and
particles or defects acceptance limits
- Container integrity - Visual inspection equipment
calibration and validation
 9. LABELING AND - Accurate labeling - Labeling accuracy and
PACKAGING information - Proper legibility
packaging integrity - Packaging line speed and
efficiency
- Container labeling and
packaging material selection

Please note that these tables provide an extensive list of CQAs and CPPs, and the specific attributes
and parameters may vary based on the formulation, equipment, and process details. It is crucial to
conduct a thorough risk assessment, process characterization to determine the most critical quality
attributes and associated process parameters for your specific manufacturing processes.

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