New Drug Approval Process

550 Pages·2009·13.05 MB·English

by  Richard A. Guarino and Richard Guarino

New Drug
Approval Process
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DRUGS AND THE PHARMACEUTICAL SCIENCES
ASeriesofTextbooksandMonographs
ExecutiveEditor
JamesSwarbrick
PharmaceuTech,Inc.
Pinehurst,NorthCarolina
AdvisoryBoard
LarryL.Augsburger HarryG.Brittain
UniversityofMaryland CenterforPharmaceuticalPhysics
Baltimore,Maryland Milford,NewJersey
JenniferB.Dressman RobertGurny
UniversityofFrankfurtInstituteof UniversitedeGeneve
PharmaceuticalTechnology Geneve,Switzerland
Frankfurt,Germany
JeffreyA.Hughes
AnthonyJ.Hickey UniversityofFloridaCollege
UniversityofNorthCarolina ofPharmacy
SchoolofPharmacy Gainesville,Florida
ChapelHill,NorthCarolina
VincentH.L.Lee
AjazHussain USFDACenterforDrug
Sandoz EvaluationandResearch
Princeton,NewJersey LosAngeles,California
JosephW.Polli KinamPark
GlaxoSmithKline PurdueUniversity
ResearchTrianglePark WestLafayette,Indiana
NorthCarolina
JeromeP.Skelly
StephenG.Schulman Alexandria,Virginia
UniversityofFlorida
Gainesville,Florida ElizabethM.Topp
UniversityofKansas
YuichiSugiyama Lawrence,Kansas
UniversityofTokyo,Tokyo,Japan
PeterYork
GeoffreyT.Tucker UniversityofBradford
UniversityofSheffield SchoolofPharmacy
RoyalHallamshireHospital Bradford,UnitedKingdom
Sheffield,UnitedKingdom
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ForInformationonvolumes1–149intheDrugsandPharmaceuticalScienceSeries,
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150. LaboratoryAuditingforQualityandRegulatoryCompliance,DonaldSinger,
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151. ActivePharmaceuticalIngredients:Development,Manufacturing,andRegulation,
editedbyStanleyNusim
152. PreclinicalDrugDevelopment,editedbyMarkC.RoggeandDavidR.Taft
153. PharmaceuticalStressTesting:PredictingDrugDegradation,editedbyStevenW.
Baertschi
154. HandbookofPharmaceuticalGranulationTechnology:SecondEdition,editedby
DilipM.Parikh
155. PercutaneousAbsorption:Drugs–Cosmetics–Mechanisms–Methodology,Fourth
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156. Pharmacogenomics:SecondEdition,editedbyWernerKalow,UrsA.Meyerand
RachelF.Tyndale
157. PharmaceuticalProcessScale-Up,SecondEdition,editedbyMichaelLevin
158. Microencapsulation:MethodsandIndustrialApplications,SecondEdition,edited
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159. NanoparticleTechnologyforDrugDelivery,editedbyRamB.GuptaandUdayB.
Kompella
160. SpectroscopyofPharmaceuticalSolids,editedbyHarryG.Brittain
161. DoseOptimizationinDrugDevelopment,editedbyRajeshKrishna
162. HerbalSupplements-DrugInteractions:ScientificandRegulatoryPerspectives,
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163. PharmaceuticalPhotostabilityandStabilizationTechnology,editedbyJosephT.
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164. EnvironmentalMonitoringforCleanroomsandControlledEnvironments,editedby
AnneMarieDixon
165. PharmaceuticalProductDevelopment:InVitro-lnVivoCorrelation,editedby
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166. NanoparticulateDrugDeliverySystems,editedbyDeepakThassu,Michel
Deleers,andYashwantPathak
167. Endotoxins:Pyrogens,LALTestingandDepyrogenation,ThirdEdition,editedby
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168. GoodLaboratoryPracticeRegulations,FourthEdition,editedbyAnneSandy
Weinberg
169. GoodManufacturingPracticesforPharmaceuticals,SixthEdition,editedby
JosephD.Nally
170. Oral-LipidBasedFormulations:EnhancingtheBioavailabilityofPoorly
Water-solubleDrugs,editedbyDavidJ.Hauss
171. HandbookofBioequivalenceTesting,editedbySarfarazK.Niazi
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172. AdvancedDrugFormulationDesigntoOptimizeTherapeuticOutcomes,editedby
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173. Clean-in-PlaceforBiopharmaceuticalProcesses,editedbyDaleA.Seiberling
174. FiltrationandPurificationintheBiopharmaceuticalIndustry,SecondEdition,
editedbyMaikW.JornitzandTheodoreH.Meltzer
175. ProteinFormulationandDelivery,SecondEdition,editedbyEugeneJ.McNally
andJayneE.Hastedt
176. AqueousPolymericCoatingsforPharmaceuticalDosageForms,ThirdEdition,
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177. DermalAbsorptionandToxicityAssessment,SecondEdition,editedbyMichaelS.
RobertsandKennethA.Walters
178. PreformulationSolidDosageFormDevelopment,editedbyMojiC.Adeyeyeand
HarryG.Brittain
179. Drug-DrugInteractions,SecondEdition,editedbyA.DavidRodrigues
180. GenericDrugProductDevelopment:BioequivalenceIssues,editedbyIsadore
KanferandLeonShargel
181. PharmaceuticalPre-ApprovalInspections:AGuidetoRegulatorySuccess,
SecondEdition,editedbyMartinD.HynesIII
182. PharmaceuticalProjectManagement,SecondEdition,editedbyAnthonyKennedy
183. ModifiedReleaseDrugDeliveryTechnology,SecondEdition,Volume1,editedby
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184. Modified-ReleaseDrugDeliveryTechnology,SecondEdition,Volume2,editedby
MichaelJ.Rathbone,JonathanHadgraft,MichaelS.Roberts,andMajellaE.Lane
185. ThePharmaceuticalRegulatoryProcess,SecondEdition,editedbyIraR.Berry
andRobertP.Martin
186. HandbookofDrugMetabolism,SecondEdition,editedbyPaulG.Pearsonand
LarryC.Wienkers
187. PreclinicalDrugDevelopment,SecondEdition,editedbyMarkRoggeandDavid
R.Taft
188. ModernPharmaceutics,FifthEdition,Volume1:BasicPrinciplesandSystems,
editedbyAlexanderT.FlorenceandJu¨rgenSiepmann
189. ModernPharmaceutics,FifthEdition,Volume2:ApplicationsandAdvances,
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190. NewDrugApprovalProcess,FifthEditioneditedbyRichardA.Guarino
F iFt h E d i t i o n
New Drug
Approval Process
edited by
Richard A. Guarino, M.D.
Oxford Pharmaceutical Resources, Inc.
Totowa, New Jersey, USA
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ISBN-10:1-4200-8849-1(hardcover:alk.paper)1.Drugapproval–United
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I.Guarino,RichardA.,1935-II.Series:Drugsandthepharmaceuticalsciences;
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[DNLM:1.DrugEvaluation–standards–UnitedStates. 2.ClinicalTrialsas
Topic–standards–UnitedStates. 3.DrugApproval–UnitedStates.
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Preface
Globalregistrationofpharmaceuticaldrug,biologic,anddeviceproductsisnowthe
way pharmaceutical development and marketing are strategically planned. Since
thepublicationofthefourtheditionofNewDrugApprovalProcess,therehavebeen
manychangesintheregulations,requirements,andrecommendationsforinterna-
tionalregistrationandapprovalofnewproducts.
NewDrugApprovalProcess,FifthEditionoffers,indetail,thenecessaryandvital
information on how to develop and submit the research and the documentation
requiredbyworldwideagenciestoobtainnewpharmaceuticalproductapprovals.
The topics include a comprehensive as well as a pragmatic approach in address-
ingallaspectsofclinicalresearchdevelopmentincludingstatisticalmethodologies,
global regulatory requirements for pharmaceutical product applications, and the
mechanicsnecessarytounderstandandimplementGoodClinicalPractices(GCP),
GoodLaboratoryPractices(GLP),andGoodManufacturingPractices(GMP).
Each contributing author is an expert in their respective field and has the
knowledgeandexperiencetoeducatethereadersonthetechnicalaswellasthereg-
ulatoryrequirementsforeachtopicpresented.Inaddition,theyalsogiveapractical
approachtoresolveproblemsthatmightoccurduringproductdevelopment.They
imparttheiryearsofsuccessesandfailuresinawaythatthereaderscantakeadvan-
tage of this information and apply it to their research practices and job descrip-
tions,andcanhaveaclearunderstandingofthescientificandlegalresponsibilities
requiredtobringnewpharmaceuticalproductstomarket.
The approach and format for assembling the specific data necessary to gain
new product approvals globally have drastically changed in the past four years.
The Investigational New Drug (IND) Application is still well accepted by the US
FDAandwillsoonrequireto besubmittedinelectronicform.Thesameinforma-
tion,duetotheimplementationoftheEuropeanDirectives,isnowexpectedinthe
countriesbelongingtotheEuropeanUnionandiscontainedinanInvestigational
MedicinalProductDossier(IMPD).TheNewDrugApplication(NDA)information
is now in the format of the Common Technical Document (CTD) and is submit-
ted to the regulatory agencies electronically termed an eCTD. These submissions
as well as Biologic License Applications (BLAs), Abbreviated New Drug Appli-
cations (ANDAs), Supplemental New Drug Applications (SNDAs), and 505(b)(2)
Applicationsaredetailed.Inaddition,theessentialcomponentsofthenonandpre-
clinicalandclinicaldevelopmentcomprisingthesafetyandefficacyofproductsare
presented and are integrated with the regulatory requirements necessary to expe-
ditenewproductapprovals.TheChemistry,Manufacturing,andControls(CMC),
ix