Validation of raw materials


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Validation of raw materials

  2. 2. INTRODUCTIONSolid Dosage Forms- Asubstance having definite shapeandvolumemanufactured fortheadministration ofactive and/or inertingredient(s). Solids includetablets, capsules, powders, granules andcertainsuppositories.
  3. 3. Disadvantages of Solid Dosage Forms1) Difficult to swallow.2) patients cannot swallow pills.3) Takes longer to absorb in the body.Advantages of Solid Dosage Forms1) More accurate dosing.2) Releases medication over a longer period oftime.
  4. 4. VALIDATIONDEFINITION - : QUALITY ASSURANCE DEPT; API DEFINITION -VALIDATION Validation word derived from ‘valid’which means “can be justified or defended”. Validation is a systematic approach toidentifying, measuring, evaluating ,documenting,&reevaluating a series of critical steps in manufacturingprocess that require control to ensure are produciblefinal product.
  5. 5. Validation is an establisheddocumented evidence whichprovides high degree ofassurance that a specificequipment, process, methodor system will consistentlyproduce results meeting itspredeterminedspecifications and qualitycharacteristics”.
  6. 6. VALIDATION OF RAWMATERIALS1) Validation begins with the rawmaterials, active pharmaceuticalingredients excipients.2) Raw materials, major causes of productvariation or deviation from specification.3) Most uncontrollable component in thecomplete product/process validationscheme because morphology particlesize/surface area not be completely definedthis early.
  7. 7. It includes validation of both activeingredients& excipients.Characteristics - particle size, surfacearea, color, density.Chemical characteristics- water contentresidue on ignition & heavy metals.Variables: Flow, blend uniformity, granulationsolution/binder uptakecompressibility, lubricant efficiency.
  8. 8. Example1) Mg sterate (lubricant). Its actiondepends on particle size.2) dyes (color)variation in material occur dependingupon...a) Method of transportation chosen.b) Exposure of material to undesirableconditions (heat and humidity)
  9. 9. RAW MATERIALS & ITSIMPORTANCE• Chemical characteristics : Drugimpurities can affect the stability.• Physical properties: Drugmorphology, solubility & particle size/surfacearea may affects drug availability.• The particle size, shape , and density canaffect material flow and blend uniformity.• The hygroscopic drug caring in handling thematerial and the reproducibility of themanufacturing process.
  10. 10. STEPS FOR RAWMATERIALS VALIDATION1. Each raw material validated by testing at least 3 batchesfrom primary & alternate supplier ; representing theranges, both high and low.2. Depending on the susceptibilityaging, physical, chemical, and/or microbiological stabilityshould be assessed.3. If under acceptable range, especially for materialssensitive to small changes; then appropriate to useseveral lots of raw material with low and high ends of thespecification.4. The final step of raw material validation should involvean on-site inspection of the vendor’s to review themanufacturing operations, controlling & conforming to
  11. 11. ANALYTICAL METHOD OFVALIDATIONPrior to any validation program analytical criteria must beassessedare-Accuracyofmethod: truevaluePrecisionofmethod:estimatereproducibilitySpecificity: accurately measure a SPECIFIC analyte in thepresenceofothercomponents.•out-of-dayvariation:•operatorvariation•instrumentvariation•laboratoryvariation
  12. 12. NEED OF ANALYTICALMETHODS VALIDATIONAnalytical methods need to be validated, verified, orrevalidatedinthefollowinginstances-1) Before initial use in routine testing.2) When transferred to another laboratory.3) Whenever the conditions or method parametersfor which the method has been validated change(for example, an instrument with differentcharacteristics or samples with a differentmatrix) and the change is outside the originalscope of the method.
  13. 13. DEVELOPMENT OFANALYTICAL METHODCognizant of the laboratory conditionsdevelopment of analytical methodroutinely runensuring the validity & ruggednessif less than optimum or if deficientre- evaluationmethod modified---- high accuracy , greater efficiency &high reproducibilitypreferred if automated--- expertise training
  14. 14. CONTROL OF PROCESSVARIABLESDefinationA process variable, is the current status of aprocessundercontrol.The process variable is a dynamic feature oftheprocess which maychange rapidly.Accuate measurementvof process variableis important for the maintanance of accuracyinaprocess.
  15. 15. • Anexampleofthiswouldbethetemperatureofa furnace.Thecurrenttemperatureis calledtheprocessvariable,whilethedesiredtemperatureisknownas the set-point.
  16. 16. Importance1) Measurementofprocessvariablesareimportantincontrollingaprocess.2) The process variable is a dynamic feature of theprocess which may change rapidly. Accuratemeasurement of process variables is importantforthemaintenanceofaccuracyinaprocess.3) There are four commonly measured variableswhich affect chemical and physicalprocess:pressure,temperature,levelandflow.
  17. 17. Process variables:Isforconsistentproduction;by challenging a process during development todeterminevariablestobecontrolled.(forasqualitymeans&specificationcompliance)Stepsindevelopmentofvalidationprogram-1) Obtaining test data to determine thenumericalrangeofeachparameter.Example-Assess the tablet hardness over aseries batches.
  18. 18. 2) Establishings pecification limits from the test dataderivedforagivenparameter.3) Determine how well the specification limit Indicatesthattheprocessisundercontrol.4) Certifytheeqipmentoperatingcondition.Example- rpm,temp are within specificationlimits.
  19. 19. Process Validation is defined as the collection andevaluation of data, from the process design stagethroughout production, which establishes scientificevidence that a process is capable of consistentlydeliveringqualityproducts.It is an establishing documented evidence whichprovides a high degree of assurance that a specificprocess will consistently produce a productmeeting its predetermined specifications andquality characteristics.”CONTROL OF PROCESSValidationDefination
  20. 20. PARAMETERS FORESTIMATION OF PROCESSVALIDATIONProcess validation is generally done with threeconsecutive batches. All the critical parameters were evaluated for fixingthe optimum process parameters. Every processing step is validated for all the threebatches and the results obtained must be presentwithin the acceptance criteria, such that the productcan be forwarded for the commercial production.All the problems that arise during validation areovercome and the product will be kept ready for thecommercial batch production.
  21. 21. CHANGE CONTROL• Must be a review procedure forvalidated processes• From time to time changes may benecessary• Documented change control procedureneeded• changes do not require re-validation
  22. 22. • Written procedures should be in place todescribe the actions to be taken if a change isproposed to a product component, processequipment, process environment, processingsite, method of production or testing or anyother change that may affect product qualityor support system operations.• All changes must be formallyrequested, documented and accepted by thevalidation team. The likely impact / risk of thechange on the product must be assessed andthe need for the extent of re-validation shouldbe determined.
  23. 23. General view of process validation
  24. 24. Schematic diagram of processing steps andrespective in-process variables during tabletmanufactureCAUSE-AND-EFFECT OR "FISHBONE DIAGRAM
  25. 25. 1)The"fishbone" diagram represents all possible relationshipsand interrelationships that may exist among the variousprocessvariables(possiblecauses)andthesingleresponseorproduct attribute (effect) affected during the manufacture ofatabletdosageform.2)Thecentrallineofthecauseandeffectdiagram isacomposite of all the possible factors that may influence thequalityandconsistencyofdoseuniformityofthetablet.3) Branches off the central line represent the influence of thesixunitoperationsorprocesssteps.4)Theprincipleprocessvariablesforeachprocessstepthatcancause or influence the final outcome are depicted as sub-branchesoffeachofthesixmainbranches.
  26. 26. BENEFITS1) Helpsdeterminerootcauses.2) Encouragesgroupparticipation.3) Uses an orderly, easy-to-read format to diagramcauseandeffectrelationships.4) Indicatespossiblecausesofvariation.5) Increasesknowledgeoftheprocessbyhelpingeveryonetolearnmoreaboutthefactorsatworkandhowtheyrelate.6) Identifiesareasforcollectingdata.
  27. 27. GUIDELINES FORPROCESS VALIDATIONSOLID DOSAGE FORMS (TABLETS):A) TabletComposition:1) Normal properties2) Density3) Particle size distribution4) Surface area5) Flow properties6) Moisture content7) solubility
  28. 28. • B) Process evaluation & selection1) Blending operation2) Determine time of un mixing3) Characteristics of blend Bulk density Particle size distribution4) Color uniformityC) Wet granulation1)Evaluation of binder Binder concentration Solubility in granulating solution2)Evalution of mixed granulation3)Evalution of drying
  29. 29. D)Tablet compression1)Appearance2)Color quality3)Powder flow4)Speed of tablet machineE)Tablet coating1)Evaluate coating procedure in differentsize pans2)Coating speed3)Amount of material required application
  30. 30. D) Equipment evaluation1) Blending equipment2) Granulating equipment3) Tablet equipment4) Tablet coating
  31. 31. Check list of Validation and ControlDocumentationSr. No. Selection of cGMP Validation and control documentation1 Introduction Establishing of QA & PV functions2 Organization and personnel. Establishment and facility installation andqualification3 Buildings and facilities Plant and facility installation qualificationMaintenance and sanitationMicrobial and pest control4 Equipment Installation and qualification cleaning methods.5 Air and water quality Water treatment and steam systems air, heat,and vacuum handling.6 Control of raw material, in-processmaterial, productIncoming componentsManufacturing non-sterile products7 Production and process controls Process control systems (instruments andcomputers)8 Packing and labeling controls Depyrogenation, sterile packing, filling, andclosing.9 Holding and distribution Facilities10 Laboratory controls Analytical methods11 Records and reports Computer systems12 Returned and salvage drug products Batch processing