458.46 MEDICINES AUTHORITY (FEES) REGULATIONS LEGAL NOTICE 315 of 2006, asamended by Legal Notices 427 of 2007, 228 and 444 of 2012, and305 of 2014. LEGAL NOTICE 315 of 2006, asamended by Legal Notices 427 of 2007, 228 and 444 of 2012, and305 of 2014. 1. Citation. Thetitle of the se regulations is the Medicines Authority (Fees) Regulations. Interpretation. Amendedby: L.N.228 of 2012; L.N.444 of 2012. 2. Forthe purposes of the seregulations- "active pharmace uticaling redient" (API) meansany substanceor mixture of substances intended tobeused in themanufacture ofmedicinal product andthat, whenused inthe production ofmedicinalproduct, becomesanactive ingredient of thesaid product. The sesubstance sare inten ded tofurnishpharmacologicalactivityorotherdirect effectin the diagnosis, cure, mitigation, treatment or prevention ofdise ase or toaffectthestructure and function of thebody; "APImanufacturer" meansaperson, groupofpersonsorcompany involved in themanufacture ofactive pharmaceuticaling redients; "certificate ofapharmaceuticalproduct (CPP) "or"export certificate " or "ex portcertificate "meansacertificate, complying with the formatspecified by World Health Organisation, providing detailsaboutsinglenamedmedicinalproduct, whichmay belicense dorunlicensedin Malta. Itprovides detailsabout the product anditsmanufacture including, but not limitedto, themarketing authorisation (MA) holder, where applicable, the active ing redients andexcipients, themanufacturing and packaging sites and whe therornot the productisplacedonthe marketin Malta; "concerned Member State " mean sa Member Stateor States whichmutualrecognition is soughtin the mutualrecognition and decentralised procedures; " Directive 2001/83/EC" means Directive 2001/83/EC2004/27/E Cand Directive 2004/24/ECmeans Directive 2001/83/ECof European Parliament and of the Councilof 6 November 2001 on the Communityco de relating tomedicinal products forhumanuse, anditsamendment sasamendedby Directive; "extensionofamarketing authorisation "or "extension " meansvariation whichis listedin Annex Iof Regulation 1234/2008/E Cand fulfilsthe conditions laiddowntherein; "follow-upinspections " refers toinspection s other thanthosereferredtoasmajorins pections; "GMPcertificate " meansacertificateis sued bythe Medicines Authorityfor the purpose ofconfirming toaman ufactureroverallconclusion ofan inspection w ithrespecttocompliancegoodmanufacturing practice; "goodclinical practice inspection " meansan inspection per formed toassessthest andards forthe design, conduct, performance, monitoring, auditing, recording, analysis andreporting ofclinicaltrials soastoprovide as surance that the data andreportedre sultsarecredible an daccurate, andthattherights, integrity and confidentiality oftrial subjectsareprovided; "herbalmedicinal product" meansanymedicinal product, exclusivelycontain ing as active ingredientsone or moreherbalpreparations, orone ormore suchherbalsubstances incombination withoneormore suchherbalpreparations; "importer " meansany personorgroupofpersonsorcompany involved inthe importation of Medicinal productsobtained fromsourceoutsidethe European Union or the European Economic Area; " importing activity" istheaction bywhichmedicinal products sourced fromoutsidethe European Union or the European Economic Are aare obtained, storedand distributed; "majorinspection " referstoinspections carrie doutfor the firsttimeina particularareaorsite, orinspectionstoalready existing sites thathad major variation soralterations; "marketingauthorisation transfer" iswhenamarket ing authorisationistrans ferred from the existing market ing authorisationholdertoanotherus ingatrans ferprocedure. Atrans fermay occureither during orafteris sue ofamarketing authorisation andentailschange in legalentity; "parti almanufacturing " hasthesamemeaningas "assembly" the Medicines Act; "periodicsafetyupdatereport "or"PSUR" referstoperiodicalre portscontaining the recordsreferredto in regulation 32 of the Pharmacovigilance Regulations; "pharmacovigilance inspection " meansan inspection carrie douttoassess the pharmacovigilance programmeofamarket authorizationholderduring which the followingareassessed: (a) monitoring ofadversedrugreactionsendorsed bycompany foritslicensed products; (b) the assessment ofriskandbenefits ofmedicine susedtodeterminewhataction shouldbetakentoim provetheir safeuse; (c) supplyof informationtooptimise safe and effectiveuse ofmedicines; (d) monitorimpactofanyactiontakenbythe company; "post-authorisationsafetystudy "or"PASS" meansanystudy relating toanauthorised medicinal productcon ducted with the aimofidentifying, characteris ing orquantifyingasafetyhazard, confirming the safety profile of the medicinal product, orofmeasuring effectivenessofriskmanagement measures; "reference Member State " meansthe Member State, whichhas produced the assessment re portforagivenmedicinalproduct, whichservesas the basis for the mutualre cognition and decentralised procedures; "tradition alherbalmedicinal product" isaherbalmedicinal substancethat ful fils the conditions laiddown inthe Herbal Medicinal Products Regulations; S.L.458.44 "urgentsafetyrestriction " meansan interimchange inthetermsof themarketing authorisation duetonew informationhavingabearing on the safeuse of the medicinalproduct; "variation relating toapharmaceuticalactivity" meansanychangepertaining tothe relate d activitythatmayormaynotrequire anins pection. Variations notrequiring an ins pectionare thosechanges in the administrative details appearingonlicence, suchaschanges inname ofcompanyorchange innames ofkeypersonnel. Variations thatrequire an ins pectionarechanges thatcanhave an effecton thequalitysystemof the companyand, oron thequality of the productdirectlyor indirectly whichhencerequires anins pection, suchasinachangeina particularstage of themanufacturing proces sor ins tallationofnewequipment; "variationtothetermsofamarketing authorisation " meansanamendment tothecontents of the particulars and documents referredto in regulations 5 to8 of the Medicines (Marketing Authorisation) Regulations, Article 6(2) of Regulation (EC) No 726/2004, point (a) of Article 7(1) and Article 34(1) of Regulation (EC) No 1901/2006 of the European Parliament and of the Counciland Articles 7and 14(1) of Regulation (EC) No 1394/2007 of European Parliament and of the Councilin thecase ofmedicinal products forhumanuse: S.L.458.34 (1) " Minorvariationoftype IA "meansavariation whichhasonlyaminimalimpactornoimpactatall, onquality, safetyorefficacy of themedicinal productconcerned; (2) " Minorvariationoftype IB "meansavariation whichis neithe raminorvariation oftypeI Anoramajor variation oftypeI Inoranextension; (3) " Majorvariationoftype II"meansavariation whichis notanextension and whichmayhaveasignificantimpacton thequality, safetyorefficacy ofmedicinal productconcerned. Majortype IIvariationsmaybesimpleor complex; (4) " Type IIComplex variation "meansavariation, itfalls withinone ormore of the following des criptions: (a) the application relatestothe re sults ofclinicaltrialsorotherdata (including pharmacologicaland toxicologicaltestsas wella sextensiveevidence frompostmarketing experienceor publications) thatneedtobenewlyassessed; (b) the application is supported by substantialamount sofdata, thathavenot previous lybeenassessed; (c) the application relatestochangesin indications foruseinathe rapeuticare aforwhich productwasnot previous ly indicated foruse; (d) the application relatestochangesin indications foruse inrespectofanorgan, orany otherpart, of thehuman bodyforwhich the productwasnot previous ly indicated foruse; (e) the application is supported by datawhichcomprisesorincludes the re sults ofclinicaltrialsorphysico-chemical, microbiologicalor pharmacologicalandtoxicologicaltests; (f) the application relatestoan increase in maximumdose; (g) the application relatestoanewdosageregimen; (h) the application relates toachange in the method ofsaleor supplyofanactive ingredient prescription on lytopharmacysale; (i) the application relates toachange inconditions ofprescribing; (j) the application relatestotheremoval of contra-indication; (k) the application relatestoan increasedduration oftreatment; (l) the application relates toachange in the route ofadministration of thesamedosageform; (m) the application relates toanewroute ofsyn thesisthathas notprevious lybeenassessedanda European Pharmacopoeia Certificate of Suitability is notavailable for the active in g redient; (n) the application relatestoanew methodofsterilisation of the product; (o) the application relatestoanew containermaterials forasterileproduct; (p) the application relatestoanew active ing redientmanufacturernot previous ly approvedmanufacture the active ingredientconcernedandwhodoes notholda European Pharmacopoeia Certificate of Suitabilityforthe substanceconcerned; (q) the application relatestoamajor formulationchangewhichaffects morethanonesection Module 3 of thedossierand, orrequiresare-evaluation of thesafetyorefficacy ofproduct, suchas- (i) achange in morethanone excipient, exceptforachangeinakeyexcipient (suchasapreservative, release-controlling excipient, orstabiliser); (ii) whenachange in the keyexcipientalonewill be regar de dasamajor formulationchange; (iii) the inclusion for the firsttime ofanovelexcipient notused beforeinany product; (iv) achangewhichrequiresan in-vivobioa vailabilitystudytobecarriedout; (v) achangewhichresultsinachangetothe rapeuticcharacteristics of the product; (r) the application relatestochange in the method ofmanufacture of the active ing redient whichintroducesnewimpurities orchanges thelevelofimpurities and whichrequires fur therqualification insafetystudies; (s) the application relates toanychange insourcematerials, methodofmanufacture oranalytical procedures fora productofbiologicalorbiotechnologicalorigin whichmightsignificantly affect thequality of the product; (t) the application relates toachange inqualitative composition of the immediate packaging ofasterile product, whe recontainermaterialhas notbeen previous ly approved forsuchuse; (u) the application relatestothe introductionofnovelmethodofanalysis; (v) the application relatestoanewmanufactureror processforafluvaccine; (5) " Groupedvariations "are variations thatcan be submittedinone application form; grouping mustbeinline Annex IIIof Regulation 1234/2008 andoffici algroupingguidelines; "wholesaledealer " meansany personorgroupofpersonsorcompany involvedin thewholesale dealing activity; "wholesale dealing activity " hasthesamemeaningas "wholesale distribution "inthe Medicines Act. Cap. 458. Cap. 458. 3. (1) Thereshall bepaid tothe Medicines Authority, respectofmarketing authorisation activities whe re Maltais Reference Member State, the feesspecified in the Schedules theseregulations. (2) Validationof applications will notstartunless the relevant feesare paid. (3) Suchfees shallnotinclude any feescharged byothercompetent authorities in relation toany documentation, reports, orservices required bythe Medicines Authorityforfinalis sue ofauthorisations andlicences, wherethe searerequired. (4) Any additional expenses incurredbythe Medicines Authorityshallbechargedseparately. (5) Inexception alcircumstances and at the discretion of Chief Executive Officer of the Medicines Authority, inconsultation with the designated Minister, waivers forfees due under the seregulationsmaybegranted. 4. Product sonderogati on list. Forthe purposeof theseregulations, products whichwe re on the derogation listand we re grante damarketing authorisation through the transition al PMA/MAprocesspriorto 31 st December, 2006 and theirline extensions, willbecharged feesas applicable the mutualrecognition procedure (Malta Concerned Member State), provided that the authorisation requested wouldhave alreadybeen approvedinatle astoneother Member State. Alternatively, national feesshallapply.