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 batchI.P.Q.C.: • For manufacturing operations • For packaging operations
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 StatisticsManuscript Prep Edits Identify & Positional Accuracy,Manuscript Automate Pass/ Correct Completeness andVerification Maps Fail Gross Errors Topology testing Basic Production Flow with Manual Common Quality Control Digitizing Checks
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 FailEdgematch Transformation Coordinate Automated EdgematchVerification Verification Transformations QC Checks Final Sign-off Basic Production Flow with Common Quality Control Checks Delivery
Independent Inspection Will always find errors that elude the data processor.In-Process Inspection Useful for controlling simple data processing actions.
General Guidelinesfor 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.6
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 rules7
QUALITY MANAGEMENTData Quality Control is Process ControlCommunication Develop formal mechanisms (i.e., standard symbols/colors for errors) Conduct frequent coordination and status meetings Provide honest opinions and feedback
IN-PROCESS EVALUATION Process parameters should be evaluated and optimized. For example : Mixing Order of addition Mixing speed Mixing time Rate of addition etc.,
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
GMP CONSIDERATIONSProcess ValidationRegular process review andrevalidationRelevant written Standard OperatingProceduresEquipment QualificationRegularly scheduled preventivemaintenance
Validated cleaning proceduresAn orderly arrangement of equipment so asto ease material flow and prevent cross-contaminationA well defined technology transfer systemThe use of competent, technically qualifiedpersonnelAdequate provision for training of personnel
MATERIAL/POWDER HANDLINGTwo primary concerns : Achieving reliableflow 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
Avoiding segregation …..Modify the powder in a way to reduce its inherenttendency to segregateChange the particle size such that the activesegregation mechanism becomes less dominantChange the cohesiveness of the powder such thatthe particles in a bed of powder are less likely tomove independent of each otherModify the equipment to reduce forces that act tosegregate the powderChange the equipment to provide remixing
DRY BLENDINGDry blend should take place ingranulation vesselLarger batch may be dry blendedand then subdivided into multiplesections for granulation.All ingredients should be free oflumps otherwise it causes flowproblems.Screening and/or milling of theingredients prior to blending usuallymakes the process more reliableand reproducible.
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.
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
Hot Air OvenAir flowAir TemperatureDepth of the granulation on the traysMonitoring of the drying process by theuse of moisture and temperature probesDrying times at specified temperaturesand air flow rates for each product
Fluidized Bed Dryer Optimum Load Air Flow Rate Inlet Air Temperature Humidity of the Incoming Air
PARTICLE SIZE REDUCTIONSizing plays a key role in achieving uniformity.There are two ways of sizing : Particle size separationand Particle size reduction.Major Factor – Feed rate of the material.As the feed rate is increased so is residence timewith in the chamber of the equipment which in turnresults in finer distribution.During scale up, overhead feeding equipment isincorporated to mimic large scale production.
BLENDINGBlender loadsBlender sizeMixing speedMixing timeBulk density of the raw material (consideredin selecting blender and in determiningoptimum load)Characteristics of the material
SPECIALISED GRANULATIONPROCEDURES• Dry Blending and Direct Compression • Slugging (Dry Granulation)
Dry Blending and Direct CompressionThe order of addition of components to the blenderThe blender loadThe mixing speedThe mixing timeThe use of auxiliary dispersion equipment within themixerThe mixing actionCompression force
Slugging (Dry Granulation)Forces used for slugging operationThe diameter of the punchesSubsequent sizing and screening operations
GRANULATION HANDLING AND FEED SYSTEMEvaluation of vacuum automatedhandling systems and mechanicalsystemsSegregation : Due to static chargesbuilt up due to vacuum can altermaterial flow propertyThe effect of above system on thecontent uniformity of the drug and onthe particle size
COMPRESSIONPress speedHandling and compression characteristics(in the selection of a tablet press)Die filling rateFlow rate of granulesInduced die feed systems (for high speedmachines) – speed of feed paddlesThe clearance between the scraper bladeand the die tableDesign and condition of the punches
TABLET COATING (FILM COATING) Pan Coating Fluidized Bed Coating
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)
Fluidized Bed CoatingBatch sizeDrying/fluidizing airvolumesSpray nozzle dynamicsSpray evaporation rate