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COFEPRIS:
Regulatory actions to improve access to
medicines and health
Mario Alanís Garza
IX Annual meeting
2014 ICORD Conference
Ede, Netherlands
October, 2014
• The Federal Commission for the Protection Against Sanitary Risks (COFEPRIS) is the Mexican
institution responsible to guard and preserve the citizen´s constitutional right to Health through
sanitary vigilance, regulation, and outreach.
• COFEPRIS was conceived by law as a macro sanitary regulator compared to other international
sanitary agencies which regulate specific industries individually.
Regulated Sectors
1.
2.
3.
4.
5.
Food and Beverages
Health Supplies
Health Services
Cosmetics and beauty products
Pesticides, Vegetable nutrients
and Toxic substances
6. Emergencies
7. Labor Safety and Health
8. Environmental Risks
The value of the products regulated by COFEPRIS represents
9.8% of
Mexican GDP.
Industries Regulated by COFEPRIS
Miles de millones
(2009 last available year)
700
624
600
500
400
237
300
151
200
139
100
24
10
Industria Alimentaria
Industria Tabaco y
Bebidas
Industria Farmacéutica
Industria química
Fabricación de
Fertilizantes, pesticidas
y otro agroquímicos
Fabricación Material
Desechable de uso
médico, dental,
oftálmico
3
• México tiene el lugar 11 dentro de los quince principales mercados internacionales.
Valor 15 mercados nacionales principales
(2009)
(Miles de millones de dólares)
250.00
200.00
150.00
100.00
50.00
E.U
Japón Alemania China
Fuente: IMS Health (2010).
Francia Canadá
Brasil
Italia
España
Reino
Unido
México
India
Corea Australia Turquía
del Sur
•
The trade balance of pharmaceutical products in Mexico shows a deficit. During 2012, imports of pharmaceutical
products totaled 4 billion 985 million USD. Exports on the other hand reached 1,874 million USD. The deficit
was close to 3 billion 111 million USD.
•
In reference to the medical devices, the trade balance showed a surplus. During 2012, exports of medical
devices reached 6 billion 343 million USD while imports totalled 3 billion USD. The trade balance surplus
excedeed 3 billion USD.
Exports and Imports of Medical Devices,
México (2008-2012)
Exports and Imports of Pharmaceutical
Products, México (2008-2012)
Exportaciones
6,000
Importaciones
4,985
Millones de dólares
4,063
4,000
4,325
3,881
3,000
2,000
1,305
1,268
1,458
1,774
1,874
1,000
5,000
Importaciones
6,072
6,000
4,540
Millones de dólares
5,000
Exportaciones
7,000
5,453
4,758
4,804
4,000
3,000
6,343
2,092
2,160
2008
2009
3,032
3,188
2011
2012
2,411
2,000
1,000
0
2008
2009
2010
Fuente: Estadísticas del Comercio Exterior, INEGI (2013).
2011
2012
0
2010
5
Evolution of the Mexican Pharmaceutical Regulation
1. The legal requirement of
bioequivalence is
During this period the sanitary
implemented.
registrations for medicines had indefinite 2. A network of laboratories is
created to perform
duration and without the legal obligation
to be bioequivalent.
bioequivalence tests
through Authorized Third
Parties.
2009
1920
First Saniitary
Registration issued
in Mexico
2001
July 5
COFEPRIS is
created
2005
Reform to the Enactment of
National Health the Biologic
Law
Drugs Act
2010
Domestic market with
only two types of
medicines:
1. Innovative Drugs
2. Generics
2011
2012
PAHO
2014
Implementation
WHO
recognizes
of National
declares
COFEPRIS
as
Secondary
Healh Law
COFEPRIS
Regulations NRA of
Reform on
a Functional
for Biologic Regional
renewal of
NRA
Drugs
Reference
Sanitary
Registrations
PAHO Recognition
•
On June 2012, COFEPRIS achieved international recognition as a Regulatory National Agency of
regional reference in matter of drugs and vaccines by PAHO.
•
COFEPRIS is the first regulatory agency of Level IV for drugs and vaccines.
– The first sanitary agency to score 100% in its evaluation.
– The first sanitary agency to be recognized by PAHO for drugs and vaccines.
•
In Latin America only 5 out of 45 (10%) national sanitary regulatory agencies have been
recognized by PAHO with level 4 which is the highest level possible.
•
This measure is triggering significant benefits to the health systems, and is increasing investment
opportunities and the foreign trade for the pharmaceutical sector.
Recognition by the WHO of COFEPRIS for vaccines
• COFEPRIS completed the process of recognition to the World Health Organization
on vacciones.
• As a result of the evaluation process done by WHO, COFEPRIS was declared
FUNCTIONAL on vaccines for the period from June 2014 to June 2017.
• Thus, Mexico joined the elite group of 28 countries in health regulation. This is, only
14% of health agencies in the world hold the classification of functionality.
• Due to the above, WHO will support Mexico at implementing a roadmap for the
Prequalification of Biologic Products seeking to enter the Vaccine Revolving Fund,
which value is $6 billion a year.
• Finally, Mexico will participate as a leader in the experts panel for consultation, in
order to generate a evaluation tool globally harmonized in drugs and vaccines
evaluation.
• The first meeting will be held in December 2014, in Geneva.
Characteristics of pharmaceutical policy
– Rests on four fundamental pillars
– The pillars are aligned with the 3 priorities of health policy established by the Federal
Government.
– Its main objective is to improve access of the population to a well-supplied drug market that
offers innovative and generic medicines at the best prices.
Pillars of Pharmaceutical Policy
Government’s Health Policy Priorities
A regulatory agency that guarantees the
safety, quality and eficacy of all drugs.
A reliable scheme to authorize sanitary
registrations.
Removal of barriers to market entry for
products that are safe and of high quality.
Harmonization of the sanitary agency with best
international practices.
1. Effective Access
2. Service quality
3. Prevention
Pharmaceutical Innovation
Innovation in Health provides better treatments for patients, reduces hospital days and
recovery periods, avoids expensive surgeries, improves quality of life and life expectancy,
and increases productivity.
With an enabling environment for pharmaceutical innovation, Mexico can:
1. Be an example in offering innovative treatments and drugs for its population.
2. Increase the dynamism in the market for clinical research.
3. Be the first country to market innovative medicines.
4. Generate savings in public and private health expenditures.
5. Attract more domestic and foreign investment.
6. Encourage greater economic growth.
• Through the fostering of pharmaceutical innovation, there are more incentives for
manufacturers to invest in Research and Development (R+D).
• Approximately, 50% of global spending in pharmaceutical R+D is done in the United States.
• The main countries that invest in pharmaceutical R+D are the United States, United Kingdom,
Switzerland, France, Germany, Japan and Denmark.
• Investment in pharmaceutical R+D in Mexico is close to 262 million dollars.
Spending in Pharmaceutical Research and Development
in different Countries, 2010
Millions of dollars
(by main pharmaceutical companies of each country*)
45,000
40,000
35,000
30,000
25,000
20,000
15,000
10,000
5,000
0
39,289
11,150
United States
Germany
8,785
United
Kingdom
8,763
Switzerland
4,569
3,453
2,252
262
France
Denmark
Japan
Mexico
Source: COFEPRIS (2013) with information from IMS Health (2010) and The Association of the British Pharmaceutical Industry.
* Pharmaceutical countries considered represent 61% of the world pharmaceutical market.
Pharmaceutical Products Discovery, Development and Approval Process
•
•
•
Developing a new medicine takes an average of 10-15 years
For every 5000-10,000 compounds, only about 1 is approved
Research and development of new medicines entails a complex, risky, and costly process
involving several actors along three phases: basic research, pre-clinical trials and clinical
trials.
Development of pharmaceutical products
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Granting of
sanitary
registrations
Generation of Clinical Data
Pre-Clinic
Phase
Phase
I
Phase
II
Safety
Phase
III
Efficacy
Phase
IV
Market entry and
Pharmacovigilance
Market entry of new medicines
Agreement for the Promotion of Innovation
• In the past, new molecules in Mexico took an average of 360 days to
enter the pharmaceutical market.
• The agreement on new molecules represented an effort to strengthen
the access of Mexican families to medicines, reduce health care costs
and encourage innovation in three key areas:
1. Foster projects of innovation in Mexico.
2. Strengthen the entry of molecules from other countries to the
Mexican market.
3. Mexico becoming a first country to market an innovative drug.
13
Innovation Policy
Days to Grant Registration for Innovative Drugs
400
360
300
300
290
270
220
200
203
180
180
150
120
120
100
90
60
México (con acuerdos)
Brasil
India
Argentina
Reino Unido
Estados Unidos
China
Australia
España
Singapur
Arabia Saudita
0
Canadá
•
México (antes)
•
Mexico implemented equivalence with the USA, Canada, Europe, and Australia and became the fastest country
to authorize the marketing for new molecules while, at the same time, ensure efficacy, safety, and quality of
medicines.
Mexico also substituted the requirement of a foreign free sale certificate with a report of clinical studies in Mexican
population.
Two new molecules have entered the Mexican market as a global launch pad: Lixisenatide used to treat Type 2
Diabetes and Fluticasone/Vilanterol used to treat Chronic Obstructive Pulmonary Disease (COPD).
Number of Days
•
14
Agreement for the
Promotion of Innovation
• The opportunity cost associated with the days a file is processed has
decreased in approximately 40 million dollars (500 million pesos). This cost was
estimated in 45 million dollars (570 million pesos).*
• Further, with the equivalence agreement on new molecules, the regulatory
burden for each file decreases in 82%.
Benefits of the agreement on new molecules
45 million dollars
Before the agreement
With the agreement
Decrease in opportunity cost of 40
million dollars (500 million pesos).
7 million dollars
Reduction in regulatory burden
of 82%.
100%
18%
Oportunity Cost (in million dollars)
Regulatory Burden (%)
* Calculation of the opportunity cost consists of the daily administrative cost to process registrations for new molecules multiplied by the
number of days requeried to grant authorization.
15
Incentives for New Molecules
• Pharmaceutical innovation directly benefits consumers through: 1) lower drug prices; 2) reductions
in hospital stay days; and 3) increases in the quality of life and life expectancy.
• During 2011 and 2014, COFEPRIS issued 133 sanitary registrations for innovative drugs for the
treatment of cardiovascular diseases, oncological diseases, and other medical conditions. This
represents an increase of 4,333% relative to 2010.
Sanitary Registrations issued to innovative medicines
35
Entry into force of the Agreement for the
Promotion of Innovation
30
25
20
32
15
25
10
15
5
0
18
18
13
12
3
2010
First Semester
Second
2011
Semester 2011
First Semester
Second
2012
Semester 2012
First Semester
Second
Second
2013
Semester 2013 Semester 2014
Removal of the requirement to have a manufacturing plant on national soil
 In 2011 the Mexican Government removed the requisite to have a manufacturing plant in
Mexico to market a medicine.
 Approval of the first 303 registrations in this category which had been requested more than 10
months before.
Impact:
BENEFITS:
• Increase the supply of pharmaceuticals.
• Availability of new molecules for research and
development.
Investment above 100 million dollars
in the next five years.
100% increase in the workforce of the
firms involved.
Actions to facilitate access of Orphan Medicines
18
ORPHAN Medicines
Background
•
•
•
•
•
•
•
Before 2010 Mexico did not officially recognized the existence of orphan medicines
and consequently and no sanitary authorization was identified.
During 2010, COFEPRIS reached an Agreement Pharmaceutical Industry by which
the holder of the authorization could request the import permit .
The authorization of an Orphan drug would result of the authority evaluation and
classification.
The authority issues an authorization not an official registration.
The official authorization of orphan drug entered as an emergency measure to
facilitate entry while the RIS modification is published and is a free process.
The Mexican Health Law recognized orphan medicines in March 2012 defining as
that which affects no more than 5% of the population.
The new regulation are currently under discussion.
• The Certification is an official document, allowing to import .
• Allows population to utilize the medicine .
Comparison of drug evaluation requirements
Requirement
Generics
New molecule
Orphan drugs
Legal Framework
Yes
Yes
No
Sanitary Authorization
Yes
Yes
No
Certification
No
No
Yes
Guidelines for obtaining recognition
No
No
Yes
Administrative - Legal
Yes
Yes
No
New Molecules Committee
No
Yes
No
Chemical Evaluation
Yes
Yes
Yes
Medical Evaluation
Yes
Yes
Yes (original country)
Interchangeability Test
Yes
No
No
Labels and Prescribing information
Yes
Yes
Yes (origin labels)
Sanitary Authorizations for Orphan Drugs
Year
Applications
Number of
Recognitions
Granted
2010
21
14
2011
11
07
2012
12
13
2013
11
07
2014
07
07
Total
62
48
Other regulatory reforms that increase access
22
Health Supplies
Simplified
Vaccine
Liberation
• The guidelines for the scheme were published in
the Official Gazette of the Federation (DOF) on
June 1st, 2011.
• The new scheme implies a 2-month waiting
time reduction.
• The maximum allowed response time was
reduced from three to only one month.
• During 2013, a total of 40.5 million doses of
vaccine were released.
• Since the new guidelines were published, a total
of 111.8 million doses have been released.
23
Regulation on Biologic Medicines
Comprehensive Legal Framework for
Biologic Medicines
1. 2009. Enactment of the Biologic
Medicines Act.
•
This new biotechnology regulation places Mexico’s
legal framework among the most modern and
forward looking legislation currently operating in the
European Union and the United States.
2. October 18, 2011. Issuance of the
Administrative Regulations regarding
Biologic Medicines by the President.
Enactment on April 16, 2012.
•
In Mexico, 35% of the new applications for
innovative pharmaceutical sanitary registrations are
related to molecules derived from biotechonology
processes, especially in fields related to cancer and
neurological diseases.
3. September 20, 2012. Issuance of
specific requisites to produce and
commercialize biologic medicines by
COFEPRIS.
Benefits of
changes to
legislation
COFEPRIS has issued registrations to 14 biologic
medicines: Axuares, Illaris, Infinitam, Advate, Ryzodeg,
Benlystia, Xgeva, Perjeta, Etart, Tresiba, Arzerra IV, Wetlia,
Kadcyla and Simponi.
These reforms place Mexico among the nations with leading legislation in
biologic medicines.
Comparative Law of Biological Medicines
Country
United
States
European
Union
Mexico
Type of Law
 Classification of biologic medicines into: “Biologics” and “Follow-On Biologics (FOB)”.
1. The applicant must comply with requirements and test which prove eficacy, safey and
quality based on a case by case basis.
2. Generic biological medicines must duplicate the innovative process of the innovator.
It is intended to have an fast aproval process
 Classification of medicines: biologicals and biosimilars
1. The applicant receives a user guide showing the relevant guidelines
2. The biosimilar medicines are approved based on the comparability principles. Studies
must show comparability with innovative biologicals
3. It si not necessary to duplicate the whole process like in the FDA.
 Classification of biological medicines: innovatives and biocomparables
1. The applicant must comply with requirrements and test proving quality, safety and
efficacy (case by case)
2. Once inthe market, there must be farmacovigilance
3. In-vitro” and clinical studies are utilized for biocomparables.
Valid
since
Abril,
1996
Octubre,
2005
Agosto,
2009
The introduction of biologic medicines, innovative drugs and
follow-on biologics increases benefits for the agents participating
in the pharmaceutical market.
• Direct Benefits for the public sector:
– Savings in government expenditures.
– Increases in the capacity to receive more patients and treat complex
diseases.
• Direct Benefits to the consumer:
– Increases in the supply of drugs for complex pathologies.
– Decreases in the price of drugs and increase in accessibility.
Drugs and Medical Devices Specialized Lanes
• In the past and before this strategy was implemented, every document filed before COFEPRIS
was processed through a single authorization lane.
• To expedite the sanitary authorization process, specialized lanes considering a risk-based
approach were implemented:
Lane
Characteristics and Operation
LANE 1
Administrative Paperwork
LANE 2
Pharmaceuticals, Classes I, II, III
Subdivided in 3 production lines:
i)
Extensions
ii)
Modifications
iii) New sanitary registrations
LANE 3
Pharmaceuticals, Class IV
Subdivided in 3 production lines based on a risk point system
Pharmaceuticals, Classes V, VI
Subdivided in 3 production lines:
i)
Extensions
ii)
Modifications
iii) New sanitary registrations
Pre-verification of administrative paperwork
Waiting time was reduced from
1 year to 3 working days for
administrative procedures
COFEPRIS has issued 10,507 sanitary registrations under the simplified
procedure within 3 to 15 working days.
Allopathic Drugs
•
Lane started on June 16th, 2011
•
On average processes 112 files per month, or 4 per day
STATUS
AUTHORIZED
WARNINGS
IN PROCESS
WITHDRAWALS
SUB TOTAL
Medical Devices
•
•
Lane started on August 5th, 2011
On average processes 107 files per month, or 4 files per day
Instructions for Prescriptions
•
•
Started on May 1, 2012
On average processes 37 files per month or 1 per day
AUTHORIZED
WARNINGS
IN PROCESS
SUB TOTAL
AUTHORIZED
WARNINGS
IN PROCESS
SUB TOTAL
TOTAL
NUMBER
4,081
484
298
31
4,894
4,391
10
70
4,471
864
154
124
1,142
10,507
Calls for Authorized Third Parties
Allopathic drugs, medical devices and plants
•
Public calls were published with the objective of reducing the sanitary authorization waiting times by
two thirds, (i.e. going from 2 years to 4 months).
Public Call for
Authorized
Third Parties
1
el registro
modificaciones
Pre-dossier
for y obtaining
registry,a
modifications,
and renewals
of sanitary
condiciones
de registro
de
registrations
for medical
devicesclases
of classes
dispositivos
médicos
I, III,y
II and III.
III.
Publication
DOF
June 30 2011
2
Pre-dossier
for
obtaining
registry,
modifications, and renewals of sanitary
registrations for allopathic drugs, vitamins and
herbal drugs.
Publication
DOF
June 30 2011
3
Verification visits for the certification of good
manufacturing practices
Publication
DOF
July 6 2011
Benefits of Authorized Third Parties
The “Pre-dictamination” of Third Parties allows the authoirity to reduce signifcantly the
processing time of each individual filing. For example, in the case of new registrations the
processing time reduction is approximately reduced by 2 years on average.
Modificación
Prórroga
Registro
Average processing time for filings of drug products (months)
Type of filing
•
Trámite COFEPRIS
30
Trámite con Pre-dictamen
4.5
Trámite COFEPRIS
6
Trámite con Pre-dictamen
3.75
Trámite COFEPRIS
2
Trámite con Pre-dictamen
0.5
0
5
10
15
Months
20
25
30
30
Increasing Access: Savings in medications in both private and public
sectors (2011-2014)
• The average price of medications in drug stores has decreased 62%.
• The average price for public purchases of medications has decreased 60%.
Medicine Prices in Public Sector and Private Sector, Mexico (2013)
$1,800
$1,600
Prices for Private Sector
Prices for Public Sector
$2,073
$1,400
Reduction in prices of
62%
$1,200
$1,000
$788
$800
$809
$600
$400
$200
Reduction in prices of
60 %
$324
$0
Before the delivery of active sustances
Time
After the delivery of active sustances
31
•
In 2010, about 30% of the market value corresponded to generic drugs, while in 2012 this figure
rose to nearly 52%. This represents an increase of 77% in just two years.
•
On the other hand, generic drugs in 2010 represented 54% of the market volume, while for 2012
accounted for 84% of the pharmaceutical market in Mexico. This represents a growth of 56% in
the period 2010-2012.
90
Penetration of Generics in the Mexican Pharmaceutical Market, 2010-2012
80
Market share (%)
70
60
50
84.1
40
30
20
10
51.9
54
2012
2010
29.3
0
2010
Market
(%), (%)
value
Valor deshare
mercado
Source: Funsalud. Analysis with information from IMS Health (2012).
2012
Market share
(%), volume
Volumen
de mercado
(%)
• Mexico gained two positions in pharmaceutical spending as a percentage of total health expenditure,
from 28.3% in 2010 to 27.1% in 2011.
• This development is associated with the access strategy for pharmaceuticals from the Ministry of Health,
which have generated savings of 20 billion pesos in 2 years. This rate will continue decreasing,
according to the 2011 figure.
Spending on Pharmaceuticals in different countries
Gasto
en medicamentos
como
%ofdeltotal
gasto
en salud
Spending
on pharmaceuticals
as a %
healthtotal
expenditure
(left(lado
axis) izq.)
Spending
on pharmaceuticals
as a %
axis)
Gasto
en medicamentos
como
%ofdelGDP
PIB(right
(lado
der.)
3
35
2.5
30
6.8
6.8
8.4
9.4
9.4
9.4
Denmark
Norway
Luxembourg
New Zealand
Netherlands
11.4
0.5
0
Switzerland
United States
Austria
Sweden
Chile
Finland
Germany
Iceland
Australia (2010)
Belgium
France
Italy
OECD
Canada
Spain
Ireland
Portugal
Slovenia
Czech Republic
Korea
Japan (2010)
Estonia
Poland
Mexico (2011)
Mexico (2010)
Slovak Republic
Greece
0
United Kingdom…
11.7
11.7
12.1
12.6
13.2
14.1
15.4
15.4
15.5
15.6
16.2
16.4
16.6
17.4
17.5
5
1
17.9
19.5
20.0
20.2
20.3
21.5
22.5
28.3
27.1
10
27.4
1.5
28.5
15
33.4
20
% of GDP
2
25
Hungary
% of total health expenditure
40
The issuance of 21,874 sanitary registrations from March 2011 to August 2014, represents a market
value greater than 2.4 billion dollars, and has a growth rate of 14,454% relative to 2010. Progress
has been as follows:
25,000
Issuance of 527 sanitary registrations
per month, on average, in the period
March, 2011- August, 2014
20,000
15,000
10,563
11,312
11,618
11,900
13,344
13,700
13,873
14,384 14,657
15,100
15,602
16,017
16,453 16,673
17,394
17,862 18,233
18,745
19,209 19,823
19,977
20,377
22,123
21,678 21,874
20,916 21,292
10,000
7,419
5,000
152
0
• A total of 11,877 sanitary registrations have been issued from June 2012 to August 2014.
This improvement implies an average of 439 monthly registrations. The issuance of
sanitary registrations will continue growing given that COFEPRIS regulates 10% of GDP.
COFEPRIS:
Regulatory actions to improve access to
medicines and health
Mario Alanís Garza
IX Annual meeting
2014 ICORD Conference
Ede, Netherlands
October, 2014