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Drug registration in Mexico
CASE STUDYASSESING THEREGULATORYENVIRONMENT INMEXICO María Inés Guaia October 2012 - Berlin
Mexico: an emerging economy $1.231 trillion GDP Services 70% #14 World #2 Latin America Industry 26% 3,9% annual growth rate Agriculture 4% 112 million people 44% below poverty line
Mexico and the pharma business Mexican pharmaceutical market• Epidemiological transition worth around• Strong brand loyalty $13 billion• Black market, low-cost #10 World medicines #2 Latin America• 2/3 of the population under the social Public sector security system (generic drugs – Private sector tender) Aim: universal % Value 20 80 healthcare % Volume 80 20
The drug agency in Mexico Comisión Federal para la Protección contra Riesgos Sanitarios July 2012: PAHO/WHO designatedFederal Commission for COFEPRIS NationalProtection against Sanitary Regulatory Authority ofRisks Regional ReferenceNew Molecules Committee Support in evaluation of quality, efficacy and• New drug substances (new in the world or new for Mexico) security information• New combinations of drug substances• New indications REPORT registration• Other special cases (e.g. similar biotherapeutic products) process
Understandingpharmaceuticalregistration in MexicoGeneral Panorama
Drug registration in Mexico Timeline to approval NEW 2012! Authorized official: 6 months third parties review dossiers real: very variable 12 – 24 months (cost) and generate report –Registration period: 5 years include in submission –Renewal submission: at least 6 months COFEPRIS response in 30before registration expiry days! (no experience yet) local manufacturing new entity small import molecules local manufacturing genericRegistration import local manufacturingcases new entity import biotechs local manufacturing biocomparable import
Small molecules, new entities Before submission for registration New molecule Committee• Form If not manufactured in• Stability studies Mexico• Efficacy and safety information (publications, Additionally: studies) • CPP of origin• Labeling texts • DS+DP GMP certification of origin by a recognized• Patent or licensing documents country• Origin identification and GMP certificate for (apostilled/legalized) • Authenticated DS+DP representation letter, if• Technical information for raw materials. solicitor is not affiliate or headquarter of• Technical information for finished product. manufacturing company• Technical information for packaging materials.
Small molecules, generic• Form If not manufactured in• Stability studies Mexico• Interchangeability evidence Additionally: • DS+DP GMP certification• Labeling texts of origin by a recognized• Patent or licensing documents country (apostilled/legalized)• Origin identification and GMP certificate for • Authenticated DS+DP representation letter, if• Technical information for raw materials. solicitor is not affiliate or headquarter of• Technical information for finished product. manufacturing company• Technical information for packaging materials.
Biotechs, new entity Before submission for registration New molecule Committee Biotech Products Evaluation• Form Subcommittee• Patent or licensing documents• Labeling texts If not manufactured in• Risk management plan Mexico Additionally:• Clinical studies • CPP of origin• Origin identification and GMP certificate for DS+DP+diluent • DS+DP+diluent GMP• Copy of sanitary license and technical responsible designation for certification of origin by a solicitor, manufacturing, packaging, storage and distribution sites recognized country (apostilled/legalized)• Drug substance: technical documents, manufacturing • Authenticated information, origin and history of biologic raw materials. representation letter, if solicitor is not affiliate or• Additives/excipients: technical documents. headquarter of• Drug product: technical documents, manufacturing information. • manufacturing company Document accrediting a• Diluent: technical documents. legal representative as resident in Mexico.• Packaging: technical documents.
Biotechs, biocomparable• Form• Patent or licensing documents If not manufactured in• Labeling texts Mexico• Risk management plan Additionally: • CPP of origin• Biocomparability studies • DS+DP+diluent GMP• Origin identification and GMP certificate for DS+DP+diluent certification of origin by a• Copy of sanitary license and technical responsible designation recognized country (apostilled/legalized) for solicitor, manufacturing, packaging, storage and distribution • Authenticated sites representation letter, if• Drug substance: technical documents, manufacturing solicitor is not affiliate or headquarter of information, origin and history of biologic raw materials. manufacturing company• Additives/excipients: technical documents. • Document accrediting a legal representative as• Drug product: technical documents, manufacturing resident in Mexico. information.• Diluent: technical documents.• Packaging: technical documents.
Overview of thelocal clinical trialsrequirement
Local Clinical Trials in Mexico• Why?Pharmacogenomic studies have shown that drug • How?metabolism in Mexican-Hispanic population can When clinical studies arebe influenced by its genetic makeup. multicentric, Mexican population must be included.• In which cases?Local clinical studies are required by COFEPRIS Sample size: not specified in regulations;for: to be calculated based on incidence of• New molecules disease.• Biotech and biocomparable products• Generic drugs that are not commercialized If Mexican patients are not included in the anywhere else in the world. clinical trials: New Molecule Committee• Other cases upon authority request will request pharmacokinetic studies to evidence not significant differences in• When? safety or efficacy in Mexicans.• Previous submission and approval of clinical • Good Clinical Practices guidelines protocol – Have results before submission for registration.
New regulation forbiotech products Critical update
The need for updated regulations Chronic and Mexico degenerative Epidemiological Infectious transition diseases diseases • Cancer • Diabetes Biotech drug • Rheumatoid Arthritis products Structural and functional complexity Innovative Novel small ‘The product is the New biotech products drugs molecules process’ SimilarSubsequent Generic drugsentry drugs (bioequivalent) Biotherapeutic New challenges Product (SBP) for evaluation and regulation!
Biotech regulations: Mexico at the vanguard Late ‘90s 1997 1998 2004 2005 Some legal Modification of Inclusion of some USA – EU started EU: First specific adaptations to General Health Law – concepts and discussions on guidelinesinclude innovative all biotech products guidelines in Health regulations for SBP biotech drug Supplies Regulation products +170 biotech drug products approved Development of specific, detailed regulation Oct 2011 2007 2009 Apr 2012 COFEPRIS, industry, Starts congress Modification to other actors New biotechdiscussion in Mexico Health General Regulation Law – general regulation principles for became SBP effective
Summary of new regulations• Definition of biocomparability • Local clinical studies (innovative or biocomparable) might be requested• Preclinical and clinical studies to evidence comparability • Inmunogenigity studies and adverse effects reports – in the case of• 12 years from submission of patent of biocomparables, to evidence comparability reference - request authorization to start studies and tests • For biocomparable products: toxicology tests in animals, characteristics of• New Drug Committee: Biotech Products pharmacodynamic studies and minimum Evaluation Subcommittee requisites of comparative clinical studies are detailed• Labeling: MB (Medicamento Biotecnológico) or MBB. (Medicamento Biotecnológico • Specific requirements set on a ‘case by Biocomparable) + INN case’ basis, and then defined for INN• Prescriptions: INN mandatory, proprietary • The better characterization and physic- name optional chemical comparability evidence, the less clinical evidence will be required• Pharmacovigilance
Assessing the GMPinspection process byCOFEPRIS Regulatory aspects
GMP verification by COFEPRIS When? GMP Certificates issued by FDA (USA), ANVISA (Brazil), Health Canada• For new registration and manufacturing changesof biologic, biotech and hemoderivate products. (Canada), EMA (EU), Pharmaceutical and Food Safety Bureau (Japan), and• For new registration or renewal of drug products Therapeutic Goods Administrationor drug substances of any kind manufactured in (Australia) are accepted.countries not considered as high sanitarysurveillance by COFEPRIS. Request for inspectionInspection is required prior • Submit form and required documents to submissionthe certificate is an important document to be annexed to • Propose two inspection dates (production ofthe submission dossier DS/DP) and inspection schedule • Propose hotel and flight options. Cost of visit What? + travel expenses: companyManufacturing sites of drug substance and • Arrange a Spanish translatordrug product – DP/DS specific • Timeline to get an inspection: about 3 months
Required information and documents• Name and general data of the applying company, authorization• Name of DP/DS – use, action, indication All documents in• Name and address of all sites involved in manufacturing Spanish, or English process, description of process stages with Spanish translation, verified• Manufacturing process – list and description of other DS/DP and signed by technical manufactured in same line responsible• Person designated by the applicant to be in charge• Technical documents: Documents issued by Organization charts foreign authorities: Architectural drawings apostilled or Flowchart of manufacturing process General summary of quality system legalized and Validation master plan translated by certified Two last annual product reports translator• Payment
Thank you! Gracias!• Erika Aguilar• Luis Joaquín Serrano• Esther Domínguez• Omar Cruz• María del Carmen García Floriano• Austin Keeble• former Bayer colleagueshttp://niniguaia.wordpress.com/