development of a harmonized dossier for use across latin america l.
Skip this Video
Loading SlideShow in 5 Seconds..
“Development of a Harmonized Dossier for use Across Latin America” PowerPoint Presentation
Download Presentation
“Development of a Harmonized Dossier for use Across Latin America”

Loading in 2 Seconds...

play fullscreen
1 / 43

“Development of a Harmonized Dossier for use Across Latin America” - PowerPoint PPT Presentation

  • Uploaded on

“Development of a Harmonized Dossier for use Across Latin America” . Maritza Moncayo Manager, Regulatory Affairs, Astellas Pharma CPDG Symposium, April 11, 2008. Promote a brief understanding of the local requirements in the Latin American region

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

PowerPoint Slideshow about '“Development of a Harmonized Dossier for use Across Latin America”' - LionelDale

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
development of a harmonized dossier for use across latin america

“Development of a Harmonized Dossier for use Across Latin America”

Maritza Moncayo

Manager, Regulatory Affairs,

Astellas Pharma

CPDG Symposium, April 11, 2008

Promote a brief understanding of the local requirements in the Latin American region

Help in the understanding of the development of a harmonized dossier that can be used across Latin America

  • Latin America General Overview
  • Requirements for Submission
  • Stability Studies
Latin America

General Overview

latin america overview
Latin America Overview

Language: Primarily Spanish, Portuguese some islands French and English

Population: 561,326,261

Economic performance: a economic growth rate of 5.3% was estimated in 2006, equivalent to a per capita increase of 3.8%

Total Area: 18,376,0202 km

Central America – 7 countries

The Caribbean – 26 countries and territorries

South America – 15 countries

largest pharmaceutical markets worldwide
Largest Pharmaceutical Markets Worldwide

(US$B – 2006)

US $B (2006)









Figures for 2006

Source: IMS Health

latin america market is worth over us 35b
Latin America Market is Worth Over US$ 35B

LA Markets in 2006 (US$B)

* Rank position in Worldwide Sales by Country

Figures for 2006

Source: IMS Health

latin america overview8
Latin America Overview


  • Latin America countries developed legislations for drug registrations, inspection, drug control and life cycle.
  • Legislation and review process varies from country to country
  • Classification of the products varies to the degree of development (new chemical entities, generic, similar etc.)

Source: Paho.Working Group on Drug Registration in Latin America

latin america definition
Latin America Definition

Reference Drug also referred to as a New Molecule Entity (Innovator),

is a unique compound that has been approved by the FDA or any major

Market (EMEA, JP, CANADA) and has patent protection and the efficacy,

Safety and quality has been proven.

Generic drug must contain the same active ingredients as the original

Formulation (innovator). They are assumed to be

identical in dose, strength, route of administration, safety, efficacy, and

intended use. In most cases, generic products are not available until the

Patent protection of the original developer expired.

Similar Drug: Is structurally similar to already known drug which

contains the same API, same concentration, form, administration,

dosing and therapeutic, preventive or diagnostic indication as the

reference product that has already been registered.

latin america overview10
Latin America Overview

Approval conditioned on:

  • Presentation and evaluation of a dossier per local country regulation and requirements
  • Product approval in one of the reference countries or in a country of high development (Japan, Canada, EMEA, USA) presentation of a CPP per WHO (World Health Organization) guideline
  • Approval Time: Varies between 2 to 24 months
latin america overview11
Latin America Overview

General Requirements:

    • Legal Documents (POA, LOA, CPP etc.)
    • Information on Drug Substance
    • Information on Finish Product
    • Clinical Data
    • Packaging Materials (primary & secondary)
    • Package Insert or SPC
  • The difference in requirements in the Americas generated initiatives from international agencies to find mechanisms to harmonize the requirements for drug registration. No specific agreement has been yet finalized.
harmonization efforts
Harmonization Efforts

Groups working on harmonization initiatives:

  • NAFTA – The North American Free Trade Agreement, limited to the exchange of information as an instrument for promoting harmonization. (Canada, Mexico and USA)
  • MERCOSUR - Southern cone Common Market (Brazil, Argentina, Paraguay and Uruguay, Chile and Bolivia participate as observers)
  • CAIS – Central American Integration System (Costa Rica, El Salvador, Honduras, Guatemala and Nicaragua), recently approved mutual recognition of drug registration among Guatemala, El Salvador and Honduras for product manufactured locally.
  • CAN – Andean Community of National (Bolivia, Colombia, Ecuador, Peru and Venezuela)
  • CARICOM – Caribbean Community
  • PAHO/WHO – Pan American Health Organization/World Health Organization


latin america harmonization efforts
  • International Conference of Harmonization ICH and Global Cooperation Group (GCC) – Achieve harmonization initiatives in different parts of the world.
  • Pan American Health Organizacion (PAHO) created a work team to create a proposal for Latin America harmonization on Common Requirements for Drug Registration for Latin America.
paho harmonization efforts
PAHO Harmonization Efforts

A proposal to


requirements for:

Steps under discussion:

  • Implement instruments developed
  • Train region
  • Develop norms, guidelines and proposals
harmonization initiatives
Harmonization Initiatives
  • PAHO working team prepared a survey on LA requirements for drug registration and identified gaps
  • With the survey information a proposal was prepared recommending the countries the necessary and sufficient requirements of a drug product that can be a guarantee to the public health on the safety, efficacy and drug quality as well as the harmonization of the labeling requirements in the region (draft)


latin america overview16
Latin America Overview

Bioequivalence Studies:

  • Is required for most oral generic drug products seeking a marketing authorization in Latin America to prove the product is therapeutically equivalent to the innovator. (Efficacy, Safety and Quality)
  • It may be waived when a product is administered parenterally (IV, IM, SC) or for solutions for oral use: otic or ophthalmic, topical products inhalators or nasal spray products.

Clinical trials:

  • All countries subscribe to the principle of the Declaration of Helsinki and county specific regulations
  • In an effort to avoid duplication of work and acceptance of data from clinical trials from other countries led different regions to harmonize standards for good practice in clinical research.
  • ICH, EMEA, US, Japan, Canada and the World Health Organization, among others, produced guidelines standardizing criteria
  • Within the framework of the ICH there emerged Guidelines for GCP, which set forth a series of guidelines for the design, implementation, auditing, completion, analysis, and reporting of clinical trials in order to ensure their reliability.


ctd dossier in latin america
CTD dossier in Latin America
  • Is NOT a common dossier for all Latin America
  • It does not define the contentof a registration dossier
  • It’s not a road towards common review practices across the region

It is….

  • A tool to ease the location of the information needed in each country
dossier preparation flow

















Local Format




HA Approval



Dossier Preparation Flow

Critical steps

registration requirements paho survey
Registration Requirements (PAHO Survey)

Source: Paho.Working Group on Drug Registration in Latin America

registration requirements paho survey21
Registration Requirements (PAHO Survey)

Source: Paho.Working Group on Drug Registration in Latin America

registration requirements paho survey22
Registration Requirements (PAHO Survey)

Source: Paho.Working Group on Drug Registration in Latin America

registration requirements paho survey23
Registration Requirements (PAHO Survey)

Source: Paho.Working Group on Drug Registration in Latin America

  • Language: Spanish
  • Population:40,301,927
  • Regulatory Authority: under the supervision of Ministry of Health (Minsa).

ANMAT - set in 1992 Argentine National Administration of Drugs, Food & Medical Technology (equivalent to the FDA)

Avenida de Mayo 869 (C1084AAD)

Ciudad Autónoma de Buenos Aires - Argentina –

Tel: 54-11-4340-0800 / 54-11-5252-8200

  • Website:
  • Questions can be sent to:

Regulatory Legal Framework for Imported Product:

Pharmaceutical Law 16.463, ( 04/08/1964), establishes

the scientific and sanitary criteria of approval and

authorization of pharmaceutical products. (API, quality,

efficacy, safety, therapeutic advantages)

  • Decree 150: New Product Registrations implemented in 1992 with updates 1890/92, and 177/93.
  • Controlled Drugs - SEDRONAR - Secretariat of Planning for the Prevention of Drug Addiction and Fight Against Narcotrafficking
  • Time of approval: 90-120 days
  • Product renewal: Every 5 years

* The importer must have a local laboratory facility, quality control release product, be registered with ANMAT, have a Technical Director

  • Products that have been approved and are marketed in the countries indicated in Annex I & II DO NOT require local clinical trials to demonstrate the efficacy and safety of the product.
  • NME that are being developed in Argentina or that will be imported from a country that is not included in Annex I or II MUST provide local Clinical Pharmacological investigation of Phases O, I, II, III (Disposition 5330 GCP, ICH).
  • Annex 1: United States, Japan, Sweden, Israel, Canada, Austria, Germany, France, United Kingdom, Netherlands Belgium, Denmark Spain, Italy.
  • Annex 2: Australia, Mexico, Brazil, Cuba, Chile, Finland, Hungary, Ireland, China, Luxembourg, Norway, New Zealand.
  • After approval and previous to the marketing of the product it’s mandatory that the lots be tested locally and in presence of the authority. Dispositions: 6877/2000

Language: Portuguese

Population: 190,010,647

Regulatory Authority:

ANVISA (National Health Surveillance Agency) established in January 1999 - under the auspices of the Ministry of Health

The Agency is autonomous operating under a special regime.

It’s main purpose is to foster protection of the health of the population by exercising sanitary control over production and marketing of products.

  • Website:
  • Questions to:
  • Regulations can be found at:


Regulatory Legal Framework:

  • Law No. 6360/76 which has been updated on several occasions since its introduction.
  • Resolution No. 136 of 29 May 2003 - This Regulation applies to all new or innovative medicaments except those, which are governed by specific legislation (similar)
  • Resolution No.17 of March 2, 2007–Registration of Similar Product
  • Resolution No. 16 of Marc 2, 2007 – Registration of Generic
  • Resolution No. 1 of July 29, 2005 – Guide for stability studies
  • Time of approval: 6 to 24 months
  • Product renewal: Every 5 years
  • All material included in the product dossier, such as production and quality control reports, information contained in the labels, inserts, and packaging, shall be in Portuguese.
  • Any official documents in a foreign language used for registration, issued by the health authorities shall be accompanied with a certified sworn translation.

Requirements: Resolution No. 136 of 29 May 2003

  • Technical information of the API
  • Pharmacodynamics; Pharmacokinetics
  • Transmissible Spongiform Encephalopathy (TSE)/BSE certificate if applicable
  • Quality control of all raw materials used
  • Quality control of finished product
  • All documents shall be addressed in hard copy signed on the final page and initialed on every page by the technician responsible for the company. Add a copy of all technical reports recorded on diskettes or CD-ROM in doc extension files or in any extension acceptable to ANVISA.
  • Transfer of methodology to execute local product release
  • GMP certificate issued by ANVISA or a copy of the application voucher requesting the inspection by ANVISA of the manufacturing site.
  • Price certificate of the countries where the product is marketed must be submitted in order to obtain final approval, if product is not yet marketed submit a proposed price.
brazil stability
Brazil Stability

Refer to Resolution No. 1 of July 29, 2005 for specific guidance

  • Language: Spanish
  • Population: 108,700,891
  • Regulatory Authority:

Is a decentralized organ of the Department of Health with technical, administrative and operational autonomy

COFEPRIS - Comisión Federal para la Protección contra Riesgos Sanitarios

Monterrey No. 33, Col. Roma, Delegación Cuauhtémoc, C.P. 06700, México, D.F. Tel: 5080 5200

  • Website:
  • Questions can be sent to:
  • Regulations can be found at:

general changes in mexico regulations
General changes in Mexico regulations
  • For new registration Mexico could submit:
    • Clinical trials done in Mexico (finished)
    • 2 types of drugs (reference and generics)
  • Longer times for resolutions/approvals
    • New products registered and sold in the country of origin - 240 working days (in some cases might need a meeting with the new molecules committee of the Health Authority)
    • Generics 180 working days
    • Prior approval variations 180 working days
    • Free sale certificate, GMPc 60 working days
  • In order to register a product in Mexico you must have a “Licencia Sanitaria” authorization of the operation of a manufacturing plant that must conduct ALL the production process



  • Language: Spanish
  • Population:15.116.435
  • Regulatory Authority:

ISP - Instituto de Salud Pública de Chile

Av.Marathon N° 1000 Ñuñoa

Santiago, Chile

Telephone: 56-2- 3507477

  • Website:
  • Regulation and Questions can be found and sent to:
  • Time of approval: 9-12 months
  • Product renewal: Every 5 years
  • Legal Framework: Reglamento del Sístema Nacional de Control de Productos Farmacéuticos, Decreto Supremo 1.876 de 1.995.


  • Formula
  • Manufacture method
  • Control tests of the raw materials, intermediate products and

finished product

  • Stability test of pharmaceutical product (on 3 batches, accelerated and long term)
  • Stability test of drug (*)
  • Pharmacological animal studies (*)
  • Toxicological animal studies (*)
  • Physical-chemical data (*)
  • Pharmacokinetic studies (*)
  • Dissolution test (*)
  • Complete clinical trials (complete papers and summary sheet) (*)
  • Expert reports (*)
  • Samples of finished products: 15
  • Working standard
  • Origin / Manufacturer of drug (raw material) and standard
  • IR, UV, HPLC spectrum or other, of drug (raw material) and standard
  • Storage conditions of finish product, raw material, and standard
  • COA of drug (raw material) and standard
  • Validation (analytical methods and manufacture)
  • (*): If the pharmaceutical product is new in Chile
  • Language: Spanish
  • Population: 44,379,598
  • Regulatory Authority:
  • INVIMA – Instituto Nacional de Vigilancia de Medicamentos y Alimentos Carrera 68 D No. 17 - 11 / 21Bogotá D.C. - ColombiaTelephone: (57)(1) 294 8700
  • Website:
  • Regulation and Questions can be found and sent to:
  • Time of approval: 9-12 months
  • Product renewal: Every 10 years
  • Legal Framework: Decree 2092 of 1986 and Decree 677 of 1995 (additional amendments)
  • Colombian product registrations last ten years, but all medicines with an 'expired' period of data exclusivity are exempt
  • Does not require Good Manufacturing Practice (GMP) compliance for raw materials, nor studies proving bioequivalence for generics
3. Stability Studies

in Latin America

drug substance stability studies
Drug Substance Stability Studies
  • Not required across the region
  • Argentina, Chile follows ICH guidelines
  • Brazil – follow local guidelines
finish product stability studies
Finish Product Stability Studies

Refer to country specific stability guidelines for additional information






El Salvador


Costa Rica





Zone II - 25°C±2°C/60%±5%RH





Zone IVa - Hot and Dry


Zone IVb - Hot and Humid


Zone Classification

The Caribbean Islands





French Guiana


  • When you start investigating a new molecular entity, think it will be registered around the world and will provide a cure to a specific disease, then the main concern is to ensure the finished product reaches the population with approved criteria for QUALITY, EFFICACY and SAFETY
  • Every country has it’s own regulations and approval process THAT MUST BE TAKEN INTO CONSIDERATION