Development of a harmonized dossier for use across latin america
Download
1 / 43

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


  • 607 Views
  • 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

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
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 l.jpg

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

Maritza Moncayo

Manager, Regulatory Affairs,

Astellas Pharma

CPDG Symposium, April 11, 2008


Objectives l.jpg

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

Objectives


Agenda l.jpg
Agenda: the Latin American region

  • Latin America General Overview

  • Requirements for Submission

  • Stability Studies


Slide4 l.jpg


Latin america overview l.jpg
Latin America Overview the Latin American region

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 l.jpg
Largest Pharmaceutical Markets Worldwide the Latin American region

(US$B – 2006)

US $B (2006)

254

30

20

40

60

10

50

254

Figures for 2006

Source: IMS Health


Latin america market is worth over us 35b l.jpg
Latin America Market is Worth Over the Latin American regionUS$ 35B

LA Markets in 2006 (US$B)

* Rank position in Worldwide Sales by Country

Figures for 2006

Source: IMS Health


Latin america overview8 l.jpg
Latin America Overview the Latin American region

Background:

  • 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 l.jpg
Latin America Definition the Latin American region

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 l.jpg
Latin America Overview the Latin American region

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 l.jpg
Latin America Overview the Latin American region

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 l.jpg
    Harmonization Efforts the Latin American region

    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

    Source: Paho.org


    Latin america harmonization efforts l.jpg
    LATIN AMERICA HARMONIZATION EFFORTS the Latin American region

    • 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. http://www.paho.org/search/DbSReturn.asp


    Paho harmonization efforts l.jpg
    PAHO Harmonization Efforts the Latin American region

    A proposal to

    harmonized

    requirements for:

    Steps under discussion:

    • Implement instruments developed

    • Train region

    • Develop norms, guidelines and proposals


    Harmonization initiatives l.jpg
    Harmonization Initiatives the Latin American region

    • 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)

    Source: Paho.org


    Latin america overview16 l.jpg
    Latin America Overview the Latin American region

    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.

    Source: Paho.org


    Slide17 l.jpg

    2. Requirements for Submission the Latin American region


    Ctd dossier in latin america l.jpg
    CTD dossier in Latin America the Latin American region

    • 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 l.jpg

    Sections the Latin American region

    Edited

    reduce

    EU, CA,

    US, JP

    Dossier

    Translate

    Local

    Language

    (Spanish-

    Portuguese)

    Country

    Affiliate

    Agent

    Legal

    Docs

    Local Format

    Country

    HA

    Review

    HA Approval

    Questions

    Feedback

    Dossier Preparation Flow

    Critical steps


    Registration requirements paho survey l.jpg
    Registration Requirements (PAHO Survey) the Latin American region

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


    Registration requirements paho survey21 l.jpg
    Registration Requirements (PAHO Survey) the Latin American region

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


    Registration requirements paho survey22 l.jpg
    Registration Requirements (PAHO Survey) the Latin American region

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


    Registration requirements paho survey23 l.jpg
    Registration Requirements (PAHO Survey) the Latin American region

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


    Argentina l.jpg
    Argentina the Latin American region

    • 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: anmat.org.ar

    • Questions can be sent to: [email protected]


    Argentina25 l.jpg
    Argentina the Latin American region

    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


    Argentina26 l.jpg
    Argentina the Latin American region

    • 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


    Brazil l.jpg
    Brazil the Latin American region

    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: www.anvisa.gov.br

    • Questions to: https://www.anvisa.gov.br/institucional/faleconosco/opcao2.asp#

    • Regulations can be found at:

      http://www.anvisa.gov.br/medicamentos/registro/index.htm


    Brazil28 l.jpg
    Brazil the Latin American region

    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.


    Brazil29 l.jpg
    Brazil the Latin American region

    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 l.jpg
    Brazil Stability the Latin American region

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


    Mexico l.jpg
    Mexico the Latin American region

    • 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: http://www.cofepris.gob.mx/index.htm

    • Questions can be sent to: [email protected]

    • Regulations can be found at:

      http://www.cofepris.gob.mx/bv/noms.htm


    General changes in mexico regulations l.jpg
    General changes in Mexico regulations the Latin American region

    • 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

    REGULATIONS

    STABILITY


    Chile l.jpg
    Chile the Latin American region

    • 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: http://www.ispch.cl/

    • Regulation and Questions can be found and sent to: http://www.ispch.cl/oirs/

    • 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.


    Chile34 l.jpg
    Chile the Latin American region

    CHEMICAL AND PHARMACEUTICAL DOCUMENTS

    • 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


    Colombia l.jpg
    Colombia the Latin American region

    • 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: http://www.invima.gov.co/Invima/index.jsp

    • Regulation and Questions can be found and sent to: http://www.invima.gov.co/Invima//normatividad/medicamentos.jsp?codigo=182

    • 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


    Country general information l.jpg
    Country General Information the Latin American region


    Central america general information l.jpg
    Central America General Information the Latin American region


    Slide38 l.jpg

    3. Stability Studies the Latin American region

    in Latin America


    Drug substance stability studies l.jpg
    Drug Substance Stability Studies the Latin American region

    • Not required across the region

    • Argentina, Chile follows ICH guidelines

    • Brazil – follow local guidelines


    Finish product stability studies l.jpg
    Finish Product Stability Studies the Latin American region

    Refer to country specific stability guidelines for additional information


    Slide41 l.jpg

    Mexico the Latin American region

    Belize

    Guatemala

    Honduras

    El Salvador

    Nicaragua

    Costa Rica

    Colombia

    Peru

    Brazil

    Bolivia

    Zone II - 25°C±2°C/60%±5%RH

    Paraguay

    Chile

    Argentina

    Uruguay

    Zone IVa - Hot and Dry

    30°C±2°C/65%±5%RH

    Zone IVb - Hot and Humid

    30°C±2°C/75%±5%RH

    Zone Classification

    The Caribbean Islands

    Panama

    Guyana

    Venezuela

    Suriname

    French Guiana

    Ecuador


    Conclusion l.jpg
    Conclusion the Latin American region

    • 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


    Slide43 l.jpg

    Thank you, the Latin American region

    ?


    ad