Generic Drug Product Development: International Regulatory Requirements for Bioequivalence

330 Pages·2010·3.426 MB·English

by  Isadore Kanfer (ed.), Leon Shargel (ed.)

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Generic Drug
Product Development
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Generic Drug
Product Development
International Regulatory Requirements
for Bioequivalence
Editedby
Isadore Kanfer
RhodesUniversity
Grahamstown,SouthAfrica
Leon Shargel
AppliedBiopharmaceutics,LLC
Raleigh,NorthCarolina,USA
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Preface
HISTORYOFTHISSERIESOFBOOKSONGENERICDRUGPRODUCT
DEVELOPMENT
Thefirstbookinthisseries,GenericDrugProductDevelopment:SolidOralDosage
Forms,waspublishedin2005byMarcelDekker,Inc.,NewYork,aspartoftheir
series in drugs and the pharmaceutical sciences. The objective of the first book
wastodescribe,fromconcepttomarketapproval,thedevelopmentoftherapeu-
ticequivalentgenericdrugproducts,includingregulatoryandlegalchallenges.
Thesecondvolume,GenericDrugProductDevelopment:BioequivalenceIssues,was
publishedin2008byInformaHealthcareUSA,Inc.,NewYork,andfocusedon
problemsconcerningthescientificdemonstrationofbioequivalence(BE)oftwo
drugproducts:atest(T)andareference(R)product.
ABOUTTHISBOOK
Thisbook,thethirdinthisseriesonGenericDrugProductDevelopment,provides
informationontheregulatoryrequirementsforbioequivalenceinseveraldiffer-
entcountriesaroundtheworld.
The advent and application of bioequivalence testing has had a signif-
icant impact on the process of drug product development both for innova-
tor/brandpharmaceuticalmanufacturersandalsoforthegenericdrugindustry.
Intheformerinstance,innovator/brandcompanies’useBEduringtheirformu-
lationdevelopmentofproductspriortoembarkingonclinicalstudiesonsafety
andefficacyandsubsequentlytofacilitatepostapprovalchangesinformulation.
Generic drug manufacturers, on the other hand, are able to circumvent clinical
trialsinpatientsbyusingBEtoobtainmarketapprovalfortheirproducts.
Although the underlying scientific principles of BE have been well-
established and many drug regulatory agencies around the world have largely
adopted standard methodology and acceptance criteria, some differences exist
intheapplicationofthemethodologyandinterpretationoftheoutcomesamong
differentcountries.HencetheobjectiveofthisbookistooutlinethespecificBE
requirements of each of the included countries where such information will be
useful to prospective generic drug manufacturers intending to obtain market
approvalinaspecificcountry.
CONTENTS
Thebioequivalenceregulationsandrequirementsofthefollowingcountriesand
theirassociatedregulatoryagenciesareincludedinthisbook:
vii
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viii Preface
(cid:2)
Australasia—TherapeuticGoodsAdministrationofAustraliaandMedsafe,a
businessunitoftheNewZealandMinistryofHealth
(cid:2)
Brazil—The National Agency for Sanitary Surveillance (Agencia Nacional
deVigilanciaSanitaria,ANVISA),GeneralManagementofGenericProducts
(GereˆnciaGeraldeMedicamentosGene´ricos,GGMED)
(cid:2)
Canada—Health Products and Food Branch (HPFB), Therapeutic Products
Directorate(TPD), HealthCanada
(cid:2)
European Union—European Medicines Agency (EMEA), Committee for
MedicinalProductsforHumanUse(CHMP)
(cid:2)
India—Central Drugs Standard Control Organization (CDSCO) under the
Government of India having certain powers vested in them and each State
hasitsowndrugregulatorysystemhavingcertainpowers
(cid:2)
Japan—TheMinistry ofHealth,LabourandWelfare(MHLW)inaccordance
withthePharmaceuticalAffairsLaw
(cid:2)
South America—In accordance with guidelines of PAHO (Pan American
Health Organization) through PANDRH (Pan American Network for Drug
RegulatoryHarmonization)
(cid:2)
SouthAfrica—MedicinesControlCouncil(MCC),DepartmentofHealth
(cid:2)
Taiwan—TheBureauofPharmaceuticalAffairs(BPA),DepartmentofHealth
(DOH)
(cid:2)
Turkey—TheGeneralDirectorateofDrugandPharmacy(GDDP,Ministryof
Health(MoH)
(cid:2)
UnitedStatesofAmerica—FoodandDrugAdministration
(cid:2)
WorldHealthOrganization(WHO)
The chapters include background information and history of the devel-
opment of rules, regulations, and guidelines in a specific country along with
patentinformationandnationalrequirementsforinterchangeabilitywheresuch
requirementsexist. Thisisfollowedbybioequivalencerequirementsincluding
thechoiceofreferenceproduct,bioequivalencemetricsused,andacceptancecri-
teriaaswellasstudydesigns forimmediate-releaseandcontrolled-/modified-
release products for oral administration. Sections also include information on
therequirementsfortheassessmentoffoodeffects,metabolitesandchiraldrugs,
useof“add-on”andsteady-statestudies,conditionsforbiowaivers,bioanalyti-
calandstatisticalrequirements.Mostoftheguidelinesalsoincluderecommen-
dations for the assessment of drug products not intended for absorption into
the systemiccirculation such as topicalproducts for local/regional action(e.g.,
dermatological corticosteroid products and other creams, gels, ointments, and
lotions as well as nasal sprays/aerosols and oral inhalation products). In addi-
tion, the bioequivalence requirements for postapproval formulation changes,
biowaivers for additional strengths of the same product, and the use of disso-
lutiondataforbiowaiversarealsoincluded.
Bioequivalence has been acknowledged as a valuable tool and has been
used as a surrogate measure to assess the safety and efficacy of generic
medicines, also termed multisource products. However, as mentioned previ-
ously, in general, the methods used and the bioequivalence requirements of
most regulatory agencies have much in common, but in some countries spe-
cificissuesandapproachesdiffer.Thisvolumeprovidesrelativelydetailedinfor-
mationrequiredbytheregulatoryauthoritiesofseveraldifferentcountriesand
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Preface ix
the implications of their different requirements and approaches for the market
approval of a generic product, particularly with respect to it’s declaration of
interchangeability/switchability.
A list of definitions, abbreviations and symbols has been included where
manyofthetermsarecommonlyusedinmostcountries.
IsadoreKanfer
LeonShargel
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Acknowledgments
Theeditorswishtoexpresstheirgratitudetoalltheauthorswhohavegivenso
generouslyoftheirtimeandexpertisetoprovidethesetextsandtotheorganiza-
tions,forwhichtheywork,whichhavegraciouslyallowedthemtodoso.

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