Pharma Regulatory Affairs in ArgentinaSteady regulations in a turbulent environment María Inés Guaia

October 2013 - Prague

40 million people

13 million in Buenos Aires and surroundings

30% below poverty line

Services 60%

Industry 30%

Agriculture 10%

$435.6 billion GDP#27 World#3 Latin America

8.8% annual growth rate

#12 World#1 Latin America

Argentina: an emerging economy

HealthCare and Pharma in Argentina

8.5% of GDP in HealthCare

No coverage38%

Social Security 48%

Voluntary insurance

9%

Voluntary + Social security

4%

HealthCare system

Pharma industry revenue: about

$4,000 million / year

More than half of the market is taken by local pharmaceutical companies

Nervous System

Cardiovascular system

Digestive system

Systemic antiinfectious

Antineoplasic and inmunomodulators

Muscle-skeleton aparatus

15.9

14.2

13.8

11.2

11.0

7.7 %

The drug agency in Argentina

National Administration of Drugs, Food and Medical Technology

National Institute of Medicines

(INAME)

National Institute of Food

Direction of Drug Product Evaluation

Direction of Medical Technology

Direction of Planning and Institutional Relations

Direction for Coordination and Administration

Direction of Legal Affairs

Control of sites, processes, activities, technologies: manufacturing, importation, fractioning, marketing

Clinical evaluation

National Regulatory Authority of Regional Reference (PAHO/WHO)

Structuring the submission dossierDifferent cases

Drug registration in Argentina

Lists of countries by sanitary trust level

ANNEX I USA France

Japan United Kingdom

Sweden Netherlands

Switzerland Belgium

Israel Denmark

Canada Spain

Austria Italy

Germany

ANNEX II Australia China

Mexico Luxembourg

Brazil Norway

Cuba New Zealand

Chile

Finland

Hungary

Ireland

High Sanitary Surveillance

Decree 150/1992 and modifications

Drug registration in Argentina

• Product information - name, formula, pharmaceutical form, pharmacologic classification, marketing condition

• Technical information - testing standard, specifications, shelf life, manufacturing method, pharmaceutical equivalençce evidence

• Labeling texts (packaging and leaflets)

• If manufactured in an Annex II country: CPP of origin (marketed)

• GMP from Annex I country or Argentina

DPs manufactured in Argentina or an Annex II country, similar to DPs already registered in Argentina.

DPs manufactured in Argentina, with marketing authorization in an Annex I country, even if ‘novel’*.

‘Article 3’ products

* ‘Novel’ products: there are no similar products registered in Argentina

Timeline for approval: about 12 months

Drug registration in Argentina

• CPP from Annex I country – Marketed status

• Labeling texts (packaging and leaflets)

• Technical information - only upon authority request

DPs with marketing authorization in at least one Annex I country.

‘Article 4’ products

Timeline for approval: about 10 months

= ‘Article 3’ DPs

Drug registration in Argentina

• Product information

• Technical information

• Labeling texts

• If manufactured in an Annex II country: CPP of origin (marketed)

• GMP from Annex I country or Argentina

‘Article 5’ products ‘Novel’* DPs manufactured in Argentina.

‘Novel’* DPs manufactured in an Annex II country.

DPs manufactured in a non-Annex I, non-Annex II country, and not authorized in any Annex I country.

Safety and efficacy data

plusTimeline for approval: not less than 3 years

Biotech registration in Argentina

Regulation: October 2011

• Hemoderivatives• Products obtained with recombinant DNA techniques• Monoclonal antibodies• Biological drugs produced from animal tissues or biologic fluids• Other biological products

Biosimilar/biocomparable drugs

GMP inspections from ANMAT

When?

For DP manufacturing sites when not in Annex I country, and without certificate from Annex I country.

• DP specific

• Agreement with MERCOSUR countries (e.g. ANVISA)

Application for inspection: documents

• Written request• Copy of ANMAT authorization to requestor • Information on manufacturer/s• Site Master File• Site authorization from HA in country in

which it is.• List of pharmaceutical forms manufactured

in site• List of DS manipulated in site• List of pharmaceutical forms by DS to import • Information and documents on third parties

involved in manufacturing or control• Fees

Post-submission actions and life-cycle management

‘First Batch Verification’• Local manufacturing• Importation of drugs Local QC

• New product registration• New concentration of

biologic or small-therapeutic-window APIs

• New pharmaceutical form• Marketing authorization

transfer

Submit form , manufacturing/QC schedule, technical information, pay fee

Marketing Authorization

Positive outcome

ANMAT inspects ANMAT doesn’t inspect

Send manufacturing/QC documents

Renewal of certificate

Documents

• Written request

• Sworn statement – marketed/non marketed status

• Evidence of marketing

• Certified copy of original certificate

• Copy of last approved labeling texts

Every 5 years(within 30 days prior to certificate

expiration date)

Relatively simple procedure

Variations of regulatory impact

Examples:

• Change of excipients• Change of manufacturer or

manufacturer’s name (only for DP)• Change in labeling texts – leaflets

and packaging – including new indications

• Shelf life extension• Change of marketing condition• Marketing authorization transfer• New primary packaging material

Submit documents (very variable requirements)

Wait for approval

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New Opportunities and Challenges

eSubmissions: step by step

2010: ‘depaperization’ projectGoals: better service – efficient administration – lower costs – greater transparency

Currently:• Electronic payment• Digital signature• Clinical studies submissions• Importation authorization requests for dietary

supplements and medical devices• Submissions for registration of cosmetics• NEW! JULY 2013: Adverse reactions

reports (pharmacovigilance)

New OTC labeling regulations

new definitions and guidelines for labeling texts in leaflets and packaging of all OTC drug products

• 2 years for submitting updated texts

• Immediate application for new registrations, variations and change of marketing condition

Information in question formatWhat is…? What is … used for? What warnings are required before/during the use of…? How should I use…? What should I do if…?

Illustrations may be added

for better understanding

Only information relevant to the patient in layman’s terms

Study: Patients had trouble interpreting the content of PILs

February 2012

More new labeling regulations!

new requirement of information on gluten content in leaflets and labeling texts of all drug products

Active lobbying by celiac disease association

May 2013

‘This drug product is gluten-free’

or

‘This drug product contains gluten’

+ analyses to show that products are gluten-free+ GMP certificates to proof no contamination

1 year (from 2nd May 2013) for all oral-dose products to comply

Orphan Drug Regulations

Previously: only special process for importation of drugs for compassionate use

August 2012 regulation for registration of

drugs ‘under special conditions’ Definitions

Requirements

Creation of special committee of evaluation

Orphan Drugs• Low frequency disorders

(<1/2000)• Severe diseases (risk of

incapacity or death)

• Complete information of (at least) early phases of clinical research (preclinical and phases I and/or II) – adapted trials

• Evidence of orphan status

• Plan of efficacy, efficiency and safety monitoring (patient register, prescription/distribution scheme)

• Periodic reports

• Intensive pharmacovigilance

• Informed consent

• Labeling: ‘AUTHORIZED UNDER SPECIAL CONDITIONS’

Thank you! Muchas gracias!

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