My slides for the Regulatory Affairs in Emerging Markets Informa Conference in Berlin, October 2012

1. María Inés Guaia
October 2012 - Berlin

2. Argentina – an emerging economy
$435.6 billion GDP Services 60%
#27 World
#3 Latin America
Industry 30%
8.8% annual growth rate Agriculture 10%
#12 World
#1 Latin America
40 million people
13 million in Buenos Aires and surroundings
30% below poverty line

3. HealthCare and Pharma in Argentina
Pharma industry revenue: about
8.5% of GDP in HealthCare
$4,000 million / year
Voluntary +
Voluntary Social More than half of the market is taken by local
insurance security pharmaceutical companies
9% 4%
HealthCare Nervous System 15.9
system Cardiovascular system 14.2
Digestive system 13.8
No
coverage Systemic antiinfectious 11.2
38%
Antineoplasic and
Social 11.0
inmunomodulators
Security
48%
Muscle-skeleton
aparatus
7.7 %

4. National Regulatory Authority of
Regional Reference (PAHO/WHO)
The drug agency in Argentina
National Administration of
Drugs, Food and Medical Technology
National Institute Direction of Drug Direction of Planning and
Institutional Relations
of Medicines Product Evaluation
(INAME)
Control of Clinical evaluation Direction for Coordination
sites, processes, activities, technologie and Administration
s:
manufacturing, importation, fractioning
, marketing
Direction of National Institute of
Direction of Legal Affairs
Medical Technology Food

6. Drug registration in Argentina
Decree 150/1992 and modifications
Lists of countries by sanitary trust level
ANNEX I USA France ANNEX II Australia China
High Sanitary Japan United Mexico Luxembourg
Surveillance
Kingdom
Brazil Norway
Sweden Netherlands
Cuba New Zealand
Switzerland Belgium
Chile
Israel Denmark
Finland
Canada Spain
Hungary
Austria Italy
Ireland
Germany

7. Drug registration in Argentina
• Product information - name, formula,
‘Article 3’ products pharmaceutical form, pharmacologic
classification, marketing condition
 DPs manufactured in Argentina or • Technical information - testing
an Annex II country, similar to DPs standard, specifications, shelf life,
already registered in Argentina. manufacturing method, pharmaceutical
equivalence evidence
 DPs manufactured in Argentina,
with marketing authorization in an • Labeling texts (packaging and leaflets)
Annex I country, even if ‘novel’*.
• If manufactured in an Annex II country: CPP
Timeline for of origin
approval: about
12 months * ‘Novel’ products: there are no similar
products registered in Argentina • GMP from Annex I country or Argentina

8. Drug registration in Argentina
‘Article 4’ products
• CPP from Annex I country –
 DPs with marketing authorization Marketed status
in at least one Annex I country.
• Labeling texts (packaging and
leaflets)
Timeline for
approval: • Technical information - only
about 10 upon authority request
months

9. Drug registration in Argentina
= ‘Article 3’ DPs
• Product information
‘Article 5’ products
• Technical information
 ‘Novel’* DPs manufactured in Argentina.
• Labeling texts
 ‘Novel’* DPs manufactured in an Annex II
country. • If manufactured in an Annex II country:
CPP of origin
 DPs manufactured in a non-Annex I, non-
Annex II country, and not authorized in • GMP from Annex I country or Argentina
any Annex I country.
plus
Timeline for approval: not
less than 3 years
Safety and efficacy data

10. Renewal of certificate
Every 5 years Documents
(within 30 days prior to • Written request
certificate expiration date)
• Sworn statement – marketed/non
marketed status
• Evidence of marketing
Relatively simple procedure • Certified copy of original certificate
• Copy of last approved labeling texts

11. •
•
Local manufacturing
Importation of drugs Local QC
‘First Batch Verification’
• New product registration Submit form , manufacturing/QC schedule,
• New concentration of technical information, pay fee
biologic or small-
therapeutic-window APIs ANMAT inspects ANMAT doesn’t inspect
• New pharmaceutical
form Send
• Marketing authorization manufacturing/QC
transfer documents
Positive outcome
Marketing Authorization

12. Variations of regulatory impact
Examples:
• Change of excipients
• Change of manufacturer or Submit documents
manufacturer’s name (only for DP) (very variable requirements)
• Change in labeling texts – leaflets
and packaging – including new
indications Wait for approval
• Shelf life extension
• Change of marketing condition
• Marketing authorization transfer
• New primary packaging material

14. GMP inspections from ANMAT
Application for inspection :
When?
documents
For DP manufacturing sites when • Written request
not in Annex I country, and without • Copy of ANMAT authorization to requestor
certificate from Annex I country. • Information on manufacturer/s
• Site Master File
• DP specific • Site authorization from HA in country in which
it is.
• Agreement with MERCOSUR countries • List of pharmaceutical forms manufactured in
(e.g. ANVISA) 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

16. New OTC labeling regulations
Study: Patients hadof PILs interpreting
the content
trouble
Information in question
format
February 2012 What is…? What is … used for? What
warnings are required before/during
new definitions and the use of…? How should I use…?
What should I do if…?
guidelines for labeling texts in leaflets and
packaging of all OTC drug products Illustrations may be
added for better understanding
• 2 years for submitting updated texts
Only information relevant to
• Immediate application for new registrations,
variations and change of marketing condition the patient in layman’s terms

17. Official and unofficial import restrictions 2010 - 2012
Drug products: ‘Automatic Authorization’… ISSUES
- Implementation – delays
Anticipated Sworn
February 2012 - Commercial balance evaluation
- Similar products manufactured
Statement for Importation locally
form to be submitted electronically before placing purchase order
Less flexibility for the
industry
Three signatures before validation:
Consumers associations
• Federal Administration of Public Income (AFIP) – 72 h Pharmacists associations
• Secretary of Domestic Trade
• ANMAT up to 10 days Shortage of products

18. Orphan Drugs
• Low frequency
disorders (<1/2000)
• Severe diseases (risk
of incapacity or death)
New Orphan Drug Regulation
• Complete information of (at least) early
Previously: only special process for phases of clinical research (preclinical
importation of drugs for compassionate use and phases I and/or II) – adapted trials
Very recently! August 2012 regulation • Evidence of orphan status
‘under
for registration of drugs • Plan of efficacy, efficiency and safety
monitoring (patient register,
special conditions’ •
prescription/distribution scheme)
Periodic reports
 Definitions
• Intensive pharmacovigilance
 Requisites • Informed consent
 Creation of special committee of • Labeling: ‘AUTHORIZED UNDER
evaluation
SPECIAL CONDITIONS’

19. ANMAT ‘Public Opinion’ space
Projects for new regulations
Proposed text
Food, Household Products, Cosmetics, Medical
Devices, Drugs, Dietary Supplements, Others
Feedback form
Open for the general public to
participate
www.opinion_publica.anmat.gov.ar

21. eSubmissions: step by step
2010: ‘depaperization’ project
Goals: better service – efficient administration – lower costs – greater
transparency
Currently:
First steps: • Clinical studies submissions
• Electronic payment • Importation authorization requests for
• Digital signature dietary supplements and medical
devices
• Submissions for registration of
cosmetics

22. • Verónica Casaro • My Bayer GRA
Berlin colleagues
And the rest of my Bayer Argentina colleagues:
• Austin Keeble
• Valeria Wilberger • Rafaela Zunini (my favorite
• José Luis Role • Fernanda Balbi proofreader)
• María Inés Pérez • Silvia Fabrizio
• María Cecilia Díaz • Panchi Domínguez
• Verónica Macías
http://niniguaia.wordpress.com/