drug registration in mexico

ASSESING THE REGULATORY ENVIRONMENT IN MEXICO

CASE STUDY

María Inés GuaiaOctober 2012 - Berlin

Mexico: an emerging economy

112 million people

44% below poverty line

Services 70%

Industry 26%

Agriculture 4%

$1.231 trillion GDP#14 World#2 Latin America

3,9% annual growth rate

Mexico and the pharma businessMexican pharmaceutical market worth around• Epidemiological

transition

• Strong brand loyalty

• Black market, low-cost medicines

• 2/3 of the population under the social security system

Public sector (generic drugs –

tender)Private sector

% Value 20 80

% Volume 80 20

Aim: universal healthcare

#10 World#2 Latin America

$13 billion

The drug agency in MexicoComisión Federal para la Protección contra Riesgos Sanitarios

Federal Commission for Protection against Sanitary Risks

July 2012: PAHO/WHO designated COFEPRIS National

Regulatory Authority of Regional Reference

New Molecules Committee

• New drug substances (new in the world or new for Mexico)

• New combinations of drug substances• New indications• Other special cases (e.g. similar biotherapeutic products)

REPORT registration process

Support in evaluation of quality, efficacy and security information

Understanding pharmaceutical registration in Mexico

General Panorama

Drug registration in Mexico

small molecules

new entitylocal manufacturing

import

genericlocal manufacturing

import

biotechsnew entity

local manufacturingimport

biocomparablelocal manufacturing

import

Timeline to approval official: 6 months real: very variable 12 – 24 months

NEW 2012! Authorized third parties review dossiers (cost) and generate report –include in submission – COFEPRIS response in 30 days! (no experience yet)

Registration period: 5 yearsRenewal submission: at least 6 months before registration expiry

Registration cases

Small molecules, new entities

• Form• Stability studies• Efficacy and safety information (publications,

studies)• Labeling texts• Patent or licensing documents• Origin identification and GMP certificate for

DS+DP• Technical information for raw materials.• Technical information for finished product.• Technical information for packaging materials.

If not manufactured in MexicoAdditionally:• CPP of origin• DS+DP GMP certification

of origin by a recognized country (apostilled/legalized)

• Authenticated representation letter, if solicitor is not affiliate or headquarter of manufacturing company

Before submission for registration New molecule Committee

Small molecules, generic

• Form• Stability studies• Interchangeability evidence• Labeling texts• Patent or licensing documents• Origin identification and GMP certificate for

DS+DP• Technical information for raw materials.• Technical information for finished product.• Technical information for packaging materials.

If not manufactured in MexicoAdditionally:• DS+DP GMP certification

of origin by a recognized country (apostilled/legalized)


Biotechs, new entity

•Form •Patent or licensing documents•Labeling texts •Risk management plan

•Clinical studies•Origin identification and GMP certificate for DS+DP+diluent•Copy of sanitary license and technical responsible designation for solicitor, manufacturing, packaging, storage and distribution sites

•Drug substance: technical documents, manufacturing information, origin and history of biologic raw materials.

•Additives/excipients: technical documents.

•Drug product: technical documents, manufacturing information.

•Diluent: technical documents.

•Packaging: technical documents.

Before submission for registration New molecule Committee

Biotech Products Evaluation Subcommittee

If not manufactured in MexicoAdditionally:• CPP of origin• DS+DP+diluent GMP

certification of origin by a recognized country (apostilled/legalized)


• Document accrediting a legal representative as resident in Mexico.

Biotechs, biocomparable•Form •Patent or licensing documents•Labeling texts •Risk management plan

•Biocomparability studies•Origin identification and GMP certificate for DS+DP+diluent•Copy of sanitary license and technical responsible designation for solicitor, manufacturing, packaging, storage and distribution sites

•Drug substance: technical documents, manufacturing information, origin and history of biologic raw materials.

•Additives/excipients: technical documents.

•Drug product: technical documents, manufacturing information.

•Diluent: technical documents.

•Packaging: technical documents.

If not manufactured in MexicoAdditionally:• CPP of origin• DS+DP+diluent GMP

certification of origin by a recognized country (apostilled/legalized)


• Document accrediting a legal representative as resident in Mexico.

Overview of the local clinical trials requirement

Local Clinical Trials in Mexico•Why? Pharmacogenomic studies have shown that drug metabolism in Mexican-Hispanic population can be influenced by its genetic makeup.

•In which cases? Local clinical studies are required by COFEPRIS for: •New molecules •Biotech and biocomparable products•Generic drugs that are not commercialized anywhere else in the world.

•Other cases upon authority request

•When? •Previous submission and approval of clinical protocol – Have results before submission for registration.

•How? When clinical studies are multicentric, Mexican population must be included.

Sample size: not specified in regulations; to be calculated based on incidence of disease.

If Mexican patients are not included in the clinical trials: New Molecule Committee will request pharmacokinetic studies to evidence not significant differences in safety or efficacy in Mexicans.

•Good Clinical Practices guidelines

New regulation for biotech products

Critical update

Infectious diseases

Epidemiological transition

Chronic and degenerative diseases

Biotech drug products

• Cancer• Diabetes• Rheumatoid

Arthritis

New challenges for evaluation and regulation!

Innovative drugs

Novel small molecules New biotech products

Subsequent entry drugs

Generic drugs (bioequivalent)

Similar Biotherapeutic Product (SBP)

The need for updated regulations

Structural and functional complexity

‘The product is the process’

Mexico

Apr 2012

Regulation became effective

Late ‘90s

Some legal adaptations to

include innovative biotech drug

products

1997

Modification of General Health Law – all biotech products

1998

Inclusion of some concepts and

guidelines in Health Supplies Regulation

+170 biotech drug products approved

2004

USA – EU started discussions on

regulations for SBP

2005

EU: First specific guidelines

2007

Starts congress discussion in Mexico

2009

Modification to Health General Law – general principles for

SBP

Development of specific, detailed regulation

COFEPRIS, industry, other actors

Biotech regulations: Mexico at the vanguard

Oct 2011

New biotech regulation

Summary of new regulations• Definition of biocomparability

• Preclinical and clinical studies to evidence comparability

• 12 years from submission of patent of reference - request authorization to start studies and tests

• New Drug Committee: Biotech Products Evaluation Subcommittee

• Labeling: MB (Medicamento Biotecnológico) or MBB. (Medicamento Biotecnológico Biocomparable) + INN

• Prescriptions: INN mandatory, proprietary name optional

• Pharmacovigilance

• Local clinical studies (innovative or biocomparable) might be requested

• Inmunogenigity studies and adverse effects reports – in the case of biocomparables, to evidence comparability

• For biocomparable products: toxicology tests in animals, characteristics of pharmacodynamic studies and minimum requisites of comparative clinical studies are detailed

• Specific requirements set on a ‘case by case’ basis, and then defined for INN

• The better characterization and physic-chemical comparability evidence, the less clinical evidence will be required

Regulatory aspects

Assessing the GMP inspection process by COFEPRIS

GMP verification by COFEPRISWhen?

• For new registration and manufacturing changes of biologic, biotech and hemoderivate products.

• For new registration or renewal of drug products or drug substances of any kind manufactured in countries not considered as high sanitary surveillance by COFEPRIS.

Inspection is required prior to submission

the certificate is an important document to be annexed to the submission dossier

What?

Manufacturing sites of drug substance and drug product – DP/DS specific

GMP Certificates issued by FDA (USA),

ANVISA (Brazil), Health Canada

(Canada), EMA (EU), Pharmaceutical

and Food Safety Bureau (Japan), and Therapeutic Goods Administration

(Australia) are accepted.

Request for inspection

• Submit form and required documents

• Propose two inspection dates (production of DS/DP) and inspection schedule

• Propose hotel and flight options. Cost of visit + travel expenses: company

• Arrange a Spanish translator

• 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

• Name and address of all sites involved in manufacturing process, description of process stages

• Manufacturing process – list and description of other DS/DP manufactured in same line

• Person designated by the applicant to be in charge

• Technical documents: Organization charts Architectural drawings Flowchart of manufacturing process General summary of quality system Validation master plan Two last annual product reports

• Payment

All documents in Spanish, or English with Spanish translation, verified and signed by technical responsible

Documents issued by foreign authorities: apostilled or legalized and translated by certified translator

• Erika Aguilar• Luis Joaquín Serrano• Esther Domínguez• Omar Cruz• María del Carmen García Floriano• Austin Keeble• former Bayer colleagues

Thank you! Gracias!

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