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Latin AmericaRegulatory Overview

Marcela SaadPresident & Senior Consultant

MarcM Consulting Canada

mailto:[email protected],[email protected]?subject=RE:%20Latin%20America%20Regulatory%20Overview%20\(Website\)

http://www.marcmconsulting.ca/


PRESENTATION AGENDAPRESENTATION AGENDA INTRODUCTION REGULATORY BUSINESS STRATEGY MERCOSUR / MERCOSUL ENTRY STRATEGY REGULATORY PROCESS ESTABLISHMENT LICENSE TYPES OF PHARMACEUTICAL PRODUCTS REFERENCE PRODUCTS HEALTH REGULATIONS GMP CERTIFICATION STABILITY DATA REGULATORY ENVIRONMENT


IntroductionIntroductionPharmaceutical markets throughout Latin America have some unique characteristics that need to be taken into account. Therefore ...

When a company intends to make a global submission that includes Latin American countries, it is important to perform short and long-term planning that factor in a product strategy, regulatory requirements for product approval and all related investments.

Some analysts refer to this concept as “Regulatory Business Strategy”.


Regulatory Business StrategyRegulatory Business Strategy

Prior to starting product development, some factors should first be reviewed.

Company technical capabilities

Intellectual property (patents)

Local vs. international regulatory environments

Timeline and expected Return On Investment

Partners in target countries

Meet requirements orMeet requirements orneed specialized advice?need specialized advice?

Patent law (yes or no)?Patent law (yes or no)?

Main differencesMain differences

Defined and Defined and evaluatedevaluated

Desired and/orDesired and/or required?required?

MERCOSUR / MERCOSULMERCOSUR / MERCOSUL

Argentina, Brazil, Paraguay and Uruguay have formed “Mercosur” or “Mercosul”, an economic and commercial trading bloc loosely similar to NAFTA. Bolivia, Chile, Ecuador, Peru and Venezuela participate as associate members with Venezuela awaiting full membership pending ratification by Brazil and Paraguay. Mexico participates as an observer.

Mercosur / Mercosul traces its origins back to 1985 but only in 1991 was a harmonization process initiated.

This harmonization process is similar to that of the European Union however full harmonization is still a long way off.



ENTRY STRATEGYENTRY STRATEGY Some important questions must first be answered.

HOW MANYHOW MANYAND AND

WHICH MARKETS?WHICH MARKETS?

WHAT ARE THE WHAT ARE THE

OFFICIAL REQUIREMENTS?OFFICIAL REQUIREMENTS?

LANGUAGE?LANGUAGE? INTERNATIONAL CERTIFICATION? INTERNATIONAL CERTIFICATION? INSPECTION REQUIRED?INSPECTION REQUIRED? LOCAL OR INTERNATIONAL CLINICAL STUDIES?LOCAL OR INTERNATIONAL CLINICAL STUDIES? REFERENCE?REFERENCE? FEES, CHARGES, EXPENSES?FEES, CHARGES, EXPENSES?

Regulatory ProcessRegulatory Process

Site Licenses Site Inspection Pre-market Product Development

Pilot Batches Bio-studies (Pre-clinical, Clinical trials or Bio-equivalence) Regulatory Submission

Market Approval (direct or conditional)

Post Market Changes


Unique RequirementsUnique Requirements

Through an established pharmaceutical company Through a distributor, importer or other


Established in the countryEstablished in the country

Properly documented resident for legal mattersProperly documented resident for legal matters

Properly documented resident for technical mattersProperly documented resident for technical matters

Pharmaceuticals - PharmacistPharmaceuticals - Pharmacist

In addition to obtaining a business license – for pharmaceuticals – must be approved and licensed by the health authority.

Site license for each different type of companySpecial license for controlled drugsLicence from Federal PoliceLicense from Fire DepartmentFederal and State/Municipal licenses


Site/Establishment LicenseSite/Establishment License

Company categorization:

Industry/ManufacturerDistributor ImporterPharmacies/Retail


Site/Establishment LicenseSite/Establishment License

Each company category differs:

Industry/ManufacturerIndustry/Manufacturer: Production, storage and delivery areas, QA ... production and/or packaging are permitted

DistributorDistributor: Storage and delivery areas, QC no product processing allowed - only sales

ImporterImporter: Similar to distributor allowed to import, store and deliver no product processing allowed - only importation and sales

Pharmacies/RetailPharmacies/Retail: Storage and dispensing area no product processing allowed - exception for compounding pharmacies (allowed to work under prescription)



Types of Pharmaceutical ProductsTypes of Pharmaceutical Products

INNOVATIVE, REFERENCE ORORIGINAL DRUGS

SIMILAR

GENERICSRECOGNIZED /

CERTIFIED

OTC

NATURAL PRODUCTS

PRODUCTS DESCRIBED IN THE LOCALPHARMACOPOEIAS (OFICINAIS/ OFICINALES) (I.E. WATER FOR INJECTION)

In this session ... In this session ...

We will not be speaking about Natural Products, OTC Products or “Oficinais”.

Rather, we will be considering only Innovative Products, Generics and Similar Products.


Argentina, Cuba, …Argentina, Cuba, … Innovative drugs (original)Innovative drugs (original)Similar drugs (copies): Similar drugs (copies):

Same active ingredients, concentrations, pharmaceutical forms and dosages

Used for the same indications as the innovative products Pharmaceutical equivalent to innovative products but may

differ in size, shape, packaging and period of activity (expiration date)

May use brand names


Argentina, CubaArgentina, Cuba (continued) (continued)

Generic drugs: Generic drugs: Bio-equivalent to the innovative drugs Off-patent International non-proprietary (generic) names


BrazilBrazil Innovative or reference drugsInnovative or reference drugsSimilar drugs: Similar drugs:

Same active ingredients, concentrations, dosages and pharmaceutical forms as the reference drugs

Used for the same indications Equivalent to reference drugs but may have different size,

colour, shape, packaging and excipients Bio-availability studies required Must be identified by brand names


Brazil Brazil (continued)(continued)

Generic drugs: Generic drugs: Interchangeable with reference drugs by retail pharmacists Same efficacy, security and quality (proved by bio-equivalence

and/or pharmaceutical equivalence) Produced after patent expiration Identified with generic denomination or Brazilian non-

proprietary names (DCB)


MexicoMexico Innovative or reference drugsInnovative or reference drugsSimilar drugs: Similar drugs:

Same active ingredients as reference drugs May be identified with brand names or international non-

proprietary names (INN)Generic interchangeables (Genericos Intercambiables - GI): Generic interchangeables (Genericos Intercambiables - GI):

Interchangeable with reference products as certified by the Health Secretariat

Off-patent and identified by INN


Bolivia, Chile, Colombia, Costa Rica, Bolivia, Chile, Colombia, Costa Rica, Ecuador, Nicaragua, Peru, Uruguay ...Ecuador, Nicaragua, Peru, Uruguay ...

Branded drugs: Branded drugs: Proprietary (innovative) drugs Similar or copy drugs

Generic drugs: Generic drugs: Use INN or other internationally recognized names Off-patent


Innovative drugs (as referenced by the other presentations at this session): Innovative drugs (as referenced by the other presentations at this session): Pre-clinical and Clinical StudiesPre-clinical and Clinical Studies

Phase I and II Original studies with translations of the outcomes are usually accepted

Phase III Some countries accept original studies, others ask for a local Phase III

Phase IV Following product market launch (as Phase III)

Generic drugs:Generic drugs: Therapeutic Equivalence (pharmaceutical equivalence and bio-equivalence) DMF (not complete)

Similar drugs:Similar drugs: Pharmaceutical Equivalence Bioavailability Study DMF (not complete)


Reference drugs - normally innovative products launched in the specific market.

Present results of their pre-clinical and clinical Phase I, II and III studies.

Some countries such as Argentina, Brazil, Mexico and others publish lists of the reference products.


REFERENCE DRUGSREFERENCE DRUGS

Health RegulationsHealth Regulations Countries “sanitary surveillance” (health safety) regulations are

generally based on WHO expert committee suggestions.

Health regulations include sanitary aspects and are known variously as:

“Ley General de Salud” (i.e. Argentina, Mexico, Peru, Nicaragua, Dominican Republic ...)

Brazil: ”Lei de Vigilância Sanitária” 6360/76 Chile: “Codigo Sanitario” Colombia: “Ley 100 de 1993” Venezuela: “Ley Organica de Salud” and others


Specific regulations are variously known as:

Norms (i.e. in Mexico: NOM = Norma Oficial Mexicana; in Colombia: Normatividad)

Resolutions (i.e. in Argentina, Brazil, Colombia, Dominican Republic ...)

Decrees (i.e. in Argentina, Brazil, Colombia, others)Portarias (i.e. Brazil)Lineamientos (i.e. Mexico)and so on


HarmonizationHarmonization World Health Organization (WHO) is currently working towards the harmonization of the regulations, requirements and glossary.

Working groups contain government and industry representatives from all of the countries within the Americas.


Some countries accept GMP certification from FDA-USA and/or WHO to prove GMP compliance. Others accept the Country of Origin Certificate.

The following countries do not inspect foreign producers Bolivia, Chile, Dominican Republic, Guatemala, Peru …


CertificationsCertifications

Good Manufacturing Practices (GMP): Good Manufacturing Practices (GMP):

GMP is one of the most important issues depending on which market a company wants to enter.

Approach varies substantially from country to countrySignificant difference from product to productDifferent understanding from regulator to regulator


Good Manufacturing Practices (GMP): Good Manufacturing Practices (GMP): According to WHO, licensed pharmaceutical products should be manufactured only by licensed manufacturers (holders of a manufacturing authorization) whose activities are regularly inspected by competent national authorities.

The majority of Latin American countries follow the World Health Organization's GMP reports and have incorporated them into their own regulations.


Argentina, Brazil, Colombia and Mexico enforce their own inspection and GMP certification regimes (including international inspections).

Peru, Bolivia, Nicaragua, Costa Rica, Puerto Rico, Chile and others accept GMP certification from the producer.

Some exceptions are applied by trade agreements.


GMPGMPCERTIFICATIONCERTIFICATION

The Quality Assurance System must include:

GMP Manual Quality Control Sanitation and Hygiene Validation Revalidation Self Inspection



The Quality Assurance System (continuation):

Quality audits Complaints Product Recall Contracts Personnel



Further additional considerations:

Premises Equipment Materials Documentation (essential QA component)



Stability Data Stability Data The majority of South American countries require stability data in Zone IV or Tropical (i.e. Brazil large country with huge temperature and humidity diversity).

WHO created a new category, Zone IV “b” (30oC and 75%RH) to comply with a request from Brazil. Many Asian countries have chosen to adopt these limits as well.

Central America and the Caribbean accept stability data in Zone II (similar to North America and Europe).


Regulatory EnvironmentRegulatory Environment

Generally specific application forms are required:

Each country has defined its own format. Some formats are more detailed than others (usually the

applications include company information, formulations, details, pharmaceutical form and presentation).

Technical reports that specify indication, drug action, adverse reactions, precautions and other technical data required by the regulators.


Regulatory EnvironmentRegulatory Environment (continued) (continued)

Text for Labels, Inserts, Packaging

In several Latin American countries, pharmacies/retailers have commercial procedures completely unlike those of North America.

Product presentation is defined by manufacturers according to the indication.



Packages normally include: box + blister pack/bottle/tube + insert.

Inserts usually contain all technical information in simple language so that patients can comprehend.

Some countries (i.e. Brazil) are very strict with texts for labels, packages, blister packs, tubes and inserts. It is necessary to submit all texts for approval as part of the registration dossier.



Advertisements (including material to present to doctors, magazines, newspapers, television and radio) usually need to be submitted for approval.

Some countries (i.e. Brazil, Costa Rica) are more strict than others.

In Brazil, a specific resolution defines what and how the information can be advertised.



In which languages should documents be presented?

Each country has its own language specification(s).

As a partial overview of some of the languages in which documents must be submitted …


Regulatory Environment Regulatory Environment Official LanguagesOfficial Languages

Spanish Argentina, Bolivia, Chile, Colombia, Costa Rica, Dominican Republic, Guatemala, Mexico, Paraguay, Peru, Uruguay, Venezuela ...

Portuguese Brazil


Regulatory EnvironmentRegulatory EnvironmentFees/ChargesFees/Charges

Fee forms are generally payable in local currency. Each country has established its own specific amounts. There is no harmonization of the amounts and how they are charged.

Product registration always has a country defined fee.


SummarySummary In most markets, individual regulatory authorities are responsible for determining entry requirements and it is not uncommon to find different approaches from country to country.

It is important to keep in mind that regulatory authorities with different areas of responsibility are free to define their own requirements without taking into account the policies of other regulatory bodies, even within the same market.


ConclusionConclusionThe final decision remains at all times with a particular regulatory authority and manufacturers should always determine the requirements manufacturers should always determine the requirements of the target marketof the target market before trying to obtain entry for their products.

Proper preparation in advance of any market entry will work to make the process easier, less time-consuming and less costly. Latin America is no exception.


Thank You!Thank You!


For more information, please contact:

Marcela SaadPresident & Senior Consultant

MarcM Consulting Canadawww.marcmconsulting.ca

[email protected]


http://www.marcmconsulting.ca/

mailto:[email protected],[email protected]?subject=RE:%20Latin%20America%20Regulatory%20Overview%20\(Website\)

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