s.gurubalaji@gmail.com CMA,CPP,CQA for oral solid dosage form (OSD)Pharmaceutical unit operations: Input material attributes Process parameters (Critical material attribute) (Critical process parameters) (CMA) (CPP) Quality attributes (Critical quality Attibute) (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 Number of revolutions (time and Particle shape speed) Particle size distribution = Bulk/tappeditrue density Agitating bar (o1Voff pattern) Bulk/tappeditrue den: : ee Discharge method ‘Moisture content properties + Electrostatic properties Holding time Flow properties + Maisture content Environment temperature and RH Cohestien/nihtsies properties Powder segregation = Electrostatic piopertiesPharmaceutical unit operations Input material attributes (Critical material attribute) Process parameters (Critical process parameters) (CPP) Quality attributes cal quality Attribute) §eGAy 2, Size reductian/comminution * Ribbon dimensions ibbon density. _ + Ribbon porosity/solid fraction mills + Particle/granuile size + Mill type + Partiele/granule size distr + Electrostatic properties + Speed + Particle/granule shape + Hardness/plasticity * Blade configuration, type, orientation |+ Particle/granule shape factor * Viscoclasticity * Screen size and type e.g. aspect ratio), « Briweness veeding rate * Particle/granule density/Porosity [Fluid energy mill, SSS Bulktappeditrue density form/polymorph + Number of grinding nozzles | Flow properties * Moisture content * Feed rate '* API polymorphic form + Granule porosity/densit + Nozzle pressure * API crystalline morphology « Classifier = Cohesive/adhesive properties ule/ribbon milli ¢ propetties + Mill type * Hardness/Plasticity: + Speed (+ Viscoelasticity + Blade configuration, type, orientation * Brittleness en size and typeThat stevia atributes ical mater (ema Fines Onenire Pari 4 Hn east asi dle til cee oe eee nt Siete eee aePharmaceutical unit operations Fluidized bed Inlet air volume, temperature, dew point Process parameters ‘Quality auribunes: (Critical process parameters) (CPP) (Critical quality Attribute) (CQA) 4. Drying, nue size and distribution ale strength, union Particle shy Cohesive/adhesive properties Product temperature Exhaust air temperature, flow Flow iiviupped/irue density Electrostatic properties Fitter type and orifice size Maisture content Harciness/plasticity Shaking intcrval and duration Residual solvents Viscoclasticity Total drying Gime ‘API polymorphic form ar tansition Brittieness fray Purity profile Elasticity Type of tay dryer ‘Moisture profile fe. product Solid form/palymorgh Moisture content Bed thiekness/tray depth (depth af product per tray) Type of drving tray liner (ez, paper, plastic, Synthetic fiber, cle.) jeimperature vs. LOD) Potency. (Cohesive adhesive properties Quanity cars and ways per chamber Quy of prosiet por ray Electrostatic proper Drying time and temperature Ai flow niet dew paint facuumrvmicroweave Jacket temperature ‘Condenser temperalure Impeller specd Bleed air volume “Vacuum pressure Microwave power Electric field Energy supplicd Product temperature Bowl and lid temperature “Total drying time(CMA) Input material altributes (Critical material attribute) Process parameters (Critical process parameters) (CPP) ‘Quality attributes (Critical quality Attribute) (CQA)} Particle siz . distribution —_& ‘Type of roller compactor Ribbon appearance (edge attrition, Finesloversize Auger (feed screw) typeldesign (horizontal, ling, lamination, color, etc.) Particle shape vertical or angular) Electrostatic properties Hardness/plasticity Bulk/tapped/true densi Viseoelast Cohesive/adhesiveproperties _/ Deaerai n (e.g, Vacuum) F Auger (feed screw) speed |: Roll shape (cylindrical or interlocking). Roll surface design (smooth, knurled, serrated, F pocketed) ‘I : Ribbon thickness Ribbon density(eg. envelop | “fiensity) Ribbon porosity/solid fraction Ribbon tensile strength/breaking force Brittleness. / Roll gap width (e,g., flexible of fixed) } Throughpurrate ‘API polymorphic formand Elasticity b Roll speed rans Solid form/polymomph Roll pressure Roller temperature ‘ines recycled (yes or no, # of eveles)Toput material atiributes (Critical material attribute) (CMA) Pharmaceutical unit operations Process parameters (Critical process parameters) (CPP) 3, Extrusion-Spheronizalion Quality attributes (Critical quality Attribute) (CQA) Particle size distribution “Type of extruder (serew or basket) Extrudate Finesioversize Screw length, piteh, and diameter Density Particle shape Serew channel depth Lengthithickness/diameter (Cohesive/adhesivepropenties Screw blade configuration Moisture content Electrostatic properties }: Number of screws (single/dual) ‘API polymorphic form and transition Hardness/plasicity Die or screen configuration (c.g., radial or axial) + Content uniformin f Bulk/tapped/true density. Dic lengihidiameter ratio Throughput Niscoclasticit Elastic Solid forn/polymomph Roll diameter (mm) Screen opening diameter (mum) Screw speed (rpm) Feoding rate (piminy ellets after spheronization ( Pellets size and distribution tio) Type and scale of spheranizer (+ Bulks/Tapped density. ft Spheronizer load level I: Flow properties Plate geometry and speed (+ Brittleness Plate groove design (spacing and pattem) Elasticity Air flow [+ Mechanical strength Residence time b FriabititPharmaceutical unit operations ibutes Process parameters (Critical process parameters) (CPP) Quality attributes. (Critical quality Attribute) (CQA) 6. Hot melt extrusion Particle size, disiribution Screw design (iwin/single) [ Exarudate density Fines/oversi Screw speed |p Lengih/thickness/diameter F Polymorphic form and | Particle shape Screw opening diameter (mum) ransition ‘Melting point Solid and liquid feed rates f Comtent uniformity ‘Density Feeder type/design Throughput Solid form/polymorph [Feed rate | Moisture content Fe No. of zones / Zone temperatures ‘Chilling rateTnput material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Pharmaccutical unit operations ‘Quality attributes (Critical quality Attribute) (CQA)| 7 Tabletting Particle/gramule size [: Type of press (model, geometry, number of stations) ‘Tablet appearance ippe [+ Hopper design, height, angle, vibration Tablet weight Fines/oversize Feeder mechanism (gravity/forced feed, shape of hwhecis, 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. ensile strength | Electrostatic properties ‘Tooling design (e.g., dimension, score configuration, ‘Thickness/dimensions. Hardness/plasticit Bulk/tapped/true density ality of the metal Maximum punch load ‘Tablet porosity/density/solid fraction Friability Viseoclasti Brittleness. Press speed/dwel Precompression force Tablet defects. Moisture content lasticit [Main compression force jsimegration Solid fornm/palymorph |: Punch penetration depth Dissolution | Moisture [Ejection force + Dwell TimePharmaceutical unit operations Input material attributes (Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) (Critical quality Attribute) KEQA) %. Encapsulation Particle/granule size and } Machine type Capsule appearance | Machine fill speed Weight | Tamping Force Weight uniformity Particte/gramute shape fe No. of tamps Content uniformity Cohesive/adhesive properties + Auger screw design/speed Moisture content Electrostatic properties, |. Powder bed height Slug tensile strength Hardness/plasticity Bulk/tappeditrue density Disintegration Dissolution Viscoclasticity. Brittleness Elasticit Solid fornvpolymorph MoisturePharmaceutical unit operations Tipal maternal attabutes Process parameters ‘Quality altributes (Critical material attribute) (CMA (Critical process parameters) (CPP) (Critical quality Attribute) (CQA) ‘Tablet dimensions ‘Typs of pan coater (conventional or side-vented) ‘Coating efficieney Tablet defects an (ly perro pata pers K.Core tablet weight before and after Hardness/plasticliy Density. Pan load level Porosity Pan rutaon speed Moisture conten 6 weight gain Fi thickness flow rate, volume, temperature, dew point Product temperature Individual nozale spray rate Toul spray rate ‘Alomizaion air pressure Moisture (gain/loss) during overall Pattern ait pressure [process Exhaust ait emperature, air flow: Residual solvent(s) ‘Total couting, curing time and drying. time Disintegration Dissolution Tablet defecis Visual attributesInput material attributes {Critical material atsibute) (CMA) Process parameters process parameters) ‘Quality attributes {Critical quality Attriburioy (CQA) Tablet dimensions “Type of fluid bed coator fe Coming efficicncy Tubtet defects. Fluid hed load tevel [Coro tablet weight before and afer Hardness pluctici porosity moisture content Air distribution plate type and size | Enviromental equivalency factor Filter type and oritive size b Cowtes drug product (eg, tablet oF Pilter differential pressure psule) appearance f Fitcr shaking imerval ae doration [Spray nazzie (type. quantity, pattems, configaration) ENozrle part size Tol preheating time bw in lm thickness | Cotins polymer noe J Jor Salons Spray rate per nozzle “Total spray rate Atomization air Inlet air Now rate, volume, temperature, dew point Product temperauure Exhuust air temperature air low J Hardnessibreaking foreeitensile Moisture (gain/lose) during overall | feesidial sofvent(3) Total coating. curing and drying time k Disinre [Tablet defects Visual attributes(Critical material attribute) (CMA) Process parameters (Critical process parameters) (CPP) Quality attributes (Critical quality Attribute) {CQA) HI. Laser drilling Size/dimensions = Polymer type Conveyor type Conveyor speed I Depth membrane thickness Laser power f Shape of the opening Number of pulses | Type(s) of lenstes) * One or two sided + Number of holes