CMA-CPP-CQA for oral solid dosageform

CMA-CPP-CQA for oral solid dosageform

1. CMA,CPP,CQA for oral solid dosage form (OSD) CMA : Critical material attributes CPP : Critical process parameters CQA : Critical quality attributes OSD : Oral solid dosage forms [email protected]

2. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) ( CPP) Quality attributes (Critical quality Attribute) (CQA) 1. Blending/mixing Particle size Type and geometry of mixer Blend uniformity Particle size distribution Mixer load level Potency Fines/oversize Order of addition Particle size Particle shape Number of revolutions (time and speed) Particle size distribution Bulk/tapped/true density Agitating bar (on/off pattern) Bulk/tapped/true density Cohesive/adhesive properties Discharge method Moisture content Electrostatic properties Holding time Flow properties Moisture content Environment temperature and RH Cohesive/adhesive properties     Powder segregation     Electrostatic properties

3. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA) 2. Size reduction/comminution • Particle/granule size Ribbon milling   • Particle/granule size distribution • Ribbon dimensions   • Fines • Ribbon density   • Particle/granule shape • Ribbon porosity/solid fraction   • Bulk/tapped/true density Impact/cutting/screening mills • Particle/granule size • Adhesive properties • Mill type • Particle/granule size d istribution • Electrostatic properties • Speed • Particle/granule shape • Hardness/plasticity • Blade configuration, type, orientation • Particle/granule shape factor (e.g., aspect ratio) • Viscoelasticity • Screen size and type • Brittleness • Feeding rate • Particle/granule density/Porosity • Elasticity Fluid energy mill • Bulk/tapped/true density • Solid form/polymorph • Number of grinding nozzles • Flow properties • Moisture content • Feed rate • API polymorphic form • Granule porosity/density • Nozzle pressure • API crystalline morphology   • Classifier • Cohesive/adhesive properties   Granule/ribbon milling • Electrostatic properties   • Mill type • Hardness/Plasticity   • Speed • Viscoelasticity   • Blade configuration, type, orientation • Brittleness   • Screen size and type • Elasticity   • Feeding rate  

4. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA) 3. Wet granulation ( High/low shear granulation ) • Particle size distribution • Type of granulator (High/low shear, top/bottom drive) • End point measurement (e.g., power cons, tor,.) • Fines/Oversize • Fill level • Blend uniformity • Particle shape • Pregranulation mix time • Potency • Bulk/tapped/true density • Granulating liquid or solvent quantity • Flow • Cohesive/adhesive properties • Impeller speed, tip speed, configuration, location, power consumption/torque • Moisture content • Electrostatic properties • Chopper speed, configuration, location, power consumption • Particle size and distribution • Hardness/plasticity • Spray nozzle type and location • Granule size and distribution • Viscoelasticity • Method of binder excipient addition (dry/wet) • Granule strength and uniformity • Brittleness • Method of granulating liquid addition (spray or pump) • Bulk/tapped/true density • Elasticity • granulating liquid temperature • API polymorphic form • Solid form/polymorph • granulating liquid addition rate and time • Cohesive/adhesive properties • Moisture content • Wet massing time (post-granulation mix time) • Electrostatic properties   • Bowl temperature(jacket temperature) • Granule brittleness   • Product temperature • Granule elasticity   • Post mixing time • Solid form/polymorph   • Pump Type: Peristaltic, Gear type     • Granulating liquid vessel (e.g., pressurized, heated)     Fluid bed granulation     • Type of fluid bed     • Inlet air distribution plate     • Spray nozzle (tip size, type/quantity/ pattern/configuration/position)     • Filter type and orifice size     • Fill level     • Bottom screen size and type     • Preheating temperature/time     • Method of binder excipient addition (dry/wet)     • Granulating liquid temperature     • Granulating liquid quantity     • Granulating liquid concentration/viscosity     • Granulating liquid holding time     • Granulating liquid delivery method     • Granulating liquid spray rate     • Inlet air, volume, temperature, dew point     • Atomization air pressure     • Product and filter pressure differentials     • Product temperature     • Exhaust air temperature, flow     • Filter shaking interval and duration  

5. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA) 4. Drying • Particle size, distribution Fluidized bed • Granule size and distribution • Fines/oversize • Inlet air volume, temperature, dew point • Granule strength, uniformity • Particle shape • Product temperature • Flow • Cohesive/adhesive properties • Exhaust air temperature, flow • Bulk/tapped/true density • Electrostatic properties • Filter type and orifice size • Moisture content • Hardness/plasticity • Shaking interval and duration • Residual solvents • Viscoelasticity • Total drying time • API polymorphic form or transition • Brittleness Tray • Purity profile • Elasticity • Type of tray dryer • Moisture profile (e.g. product • Solid form/polymorph • Bed thickness/tray depth (depth of product per tray) temperature vs. LOD) • Moisture content • Type of drying tray liner (e.g., paper, plastic, • Potency   synthetic fiber, etc.) • Cohesive/adhesive properties   • Quantity carts and trays per chamber • Electrostatic properties   • Quantity of product per tray     • Drying time and temperature     • Air flow     • Inlet dew point     Vacuum/microwave     • Jacket temperature     • Condenser temperature     • Impeller speed     • Bleed air volume     • Vacuum pressure     • Microwave power     • Electric field     • Energy supplied     • Product temperature     • Bowl and lid temperature     • Total drying time  

6. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA)   Roller compaction/ chilsonation   Particle size, distribution Type of roller compactor Ribbon appearance (edge attrition, • Fines/oversize • Auger (feed screw) type/design (horizontal, splitting, lamination, color, etc.) • Particle shape vertical or angular) • Ribbon thickness • Cohesive/ adhesiveproperties • Deaeration (e.g., vacuum) • Ribbon density (e.g., envelop • Electrostatic properties • Auger (feed screw) speed density) • Hardness/plasticity • Roll shape (cylindrical or interlocking). • Ribbon porosity/solid fraction • Bulk/tapped/true density • Roll surface design (smooth, knurled, serrated, or pocketed) • Ribbon tensile strength/breaking • Viscoelasticity force • Brittleness • Roll gap width (e.g., flexible or fixed) • Throughput rate • Elasticity • Roll speed • API polymorphic formand transition • Solid form/polymorph • Roll pressure     • Roller temperature     • Fines recycled (yes or no, # of cycles)  

7. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA) 5. Extrusion–Spheronization • Particle size distribution • Type of extruder (screw or basket) • Extrudate • Fines/oversize • Screw length, pitch, and diameter • Density • Particle shape • Screw channel depth • Length/thickness/diameter • Cohesive/ adhesiveproperties • Screw blade configuration • Moisture content • Electrostatic properties • Number of screws (single/dual) • API polymorphic form and transition • Hardness/plasticity • Die or screen configuration (e.g., radial or axial) • Content uniformity • Bulk/tapped/true density • Die length/diameter ratio • Throughput • Viscoelasticity • Roll diameter (mm) • Pellets after spheronization • Brittleness • Screen opening diameter (mm) • Pellets size and distribution • Elasticity • Screw speed (rpm) • Pellets shape factor (e.g. aspect • Solid form/polymorph • Feeding rate (g/min) ratio)   • Type and scale of spheronizer • Bulk/Tapped density   • Spheronizer load level • Flow properties   • Plate geometry and speed • Brittleness   • Plate groove design (spacing and pattern) • Elasticity   • Air flow • Mechanical strength   • Residence time • Friability

8. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA) 6. Hot melt extrusion • Particle size, distribution • Screw design (twin/single) • Extrudate density • Fines/oversize • Screw speed • Length/thickness/diameter • Particle shape • Screw opening diameter (mm) • Polymorphic form and transition • Melting point • Solid and liquid feed rates • Content uniformity • Density • Feeder type/design • Throughput • Solid form/polymorph • Feed rate   • Moisture content • No. of zones     • Zone temperatures     • Chilling rate  

9. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA) 7. Tabletting • Particle/granule size • Type of press (model, geometry, number of stations) • Tablet appearance and distribution • Hopper design, height, angle, vibration • Tablet weight • Fines/oversize • Feeder mechanism (gravity/forced feed, shape of wheels, • Weight uniformity • Particle/granule shape direction of rotation, number of bars) • Content uniformity • Cohesive/adhesive • Feed frame type and speed • Hardness/tablet breaking force/ properties • Feeder fill depth tensile strength • Electrostatic properties • Tooling design (e.g., dimension, score configuration, • Thickness/dimensions • Hardness/plasticity quality of the metal) • Tablet porosity/density/solid fraction • Bulk/tapped/true density • Maximum punch load • Friability • Viscoelasticity • Press speed/dwell time • Tablet defects • Brittleness • Precompression force • Moisture content • Elasticity • Main compression force • Disintegration • Solid form/polymorph • Punch penetration depth • Dissolution • Moisture • Ejection force     • Dwell Time  

10. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA) 8. Encapsulation • Particle/granule size and distribution • Machine type • Capsule appearance   • Machine fill speed • Weight • Fines/oversize • Tamping Force • Weight uniformity • Particle/granule shape • No. of tamps • Content uniformity • Cohesive/adhesive properties • Auger screw design/speed • Moisture content • Electrostatic properties • Powder bed height • Slug tensile strength • Hardness/plasticity   • Disintegration • Bulk/tapped/true density   • Dissolution • Viscoelasticity     • Brittleness     • Elasticity     • Solid form/polymorph     • Moisture    

11. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) (CQA) 9. Pan coating • Tablet dimensions • Type of pan coater (conventional or side-vented) • Coating efficiency • Tablet defects • Pan (fully perforated or partial perforated) • Core tablet weight before and after • Hardness/plasticity • Baffle (design, number, location) preheating • Density • Pan load level • Moisture (gain/loss) during • Porosity • Pan rotation speed preheating • Moisture content • Spray nozzle (type, quantity, pattern, configuration, • Environmental equivalency factor   spray pattern) • Coated drug product (e.g., tablet or   • Nozzle to bed distance capsule) appearance   • Distance between nozzles • % weight gain   • Nozzle orientation • Film thickness   • Total preheating time • Coating (polymer and /or color)   • Inlet air flow rate, volume, temperature, dew point uniformity   • Product temperature • Hardness/breaking force/Tensile   • Individual nozzle spray rate strength   • Total spray rate • Friability   • Atomization air pressure • Moisture (gain/loss) during overall   • Pattern air pressure process   • Exhaust air temperature, air flow • Residual solvent(s)   • Total coating, curing time and drying time • Disintegration     • Dissolution     • Tablet defects     • Visual attributes

12. Pharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) ( CPP) Quality attributes (Critical quality Attribute) (CQA) 10. Fluid bed coating • Tablet dimensions • Type of fluid bed coater • Coating efficiency • Tablet defects • Fluid bed load level • Core tablet weight before and after • Hardness/plasticity • Partition column diameter preheating • Density/porosity moisture content   • Partition column height • Moisture (gain/loss) during preheating • Number of partition columns   • Air distribution plate type and size • Environmental equivalency factor   • Filter type and orifice size • Coated drug product (e.g., tablet or   • Filter differential pressure capsule) appearance   • Filter shaking interval and duration • % weight gain   • Spray nozzle (type, quantity, pattern, configuration) • Film thickness   • Nozzle port size • Coating (polymer and /or color)   • Total preheating time uniformity   • Spray rate per nozzle • Hardness/breaking force/tensile   • Total spray rate strength   • Atomization air pressure • Friability   • Inlet air flow rate, volume, temperature, dew point • Moisture (gain/loss) during overall   • Product temperature process   • Exhaust air temperature, air flow • Residual solvent(s)   • Total coating, curing and drying time • Disintegration     • Dissolution     • Tablet defects     • Visual attributes

13. Pharmaceutical unit operations Input material attributes (Critical material attribute) ( CMA) Process parameters (Critical process parameters) ( CPP) Quality attributes (Critical quality Attribute) ( CQA) 11. Laser drilling Size/dimensions • Conveyor type • Opening diameter ( internal and external) Polymer type • Conveyor speed • Depth membrane thickness • Laser power • Shape of the opening   • Number of pulses   • Type(s) of lens(es)     • One or two sided     • Number of holes