1. Pharma Regulatory Affairs in
Mexico
Maria Ines Guaia - Informa Conference: Regulatory Affairs in Emerging Markets - Prague, October 2013

2. Disclaimer
•
For educational purposes, some tables and graphs have been
borrowed from an informative COFEPRIS presentation. You can find
the complete original presentation in the following link:
http://www.deloitte.com/assets/DcomMexico/Local%20Assets/Documents/mx(esmx)PanoramaMexico_IndustriaCofepris.pdf

3. Mexico: an emerging economy
$1.177 trillion GDP
Services 70%
#14 World
#2 Latin America
Industry 26%
Annual growth rate:
3.9 (2012)
3.5 (exp. 2013)
Agriculture 4%
120 million
people (est. 2012)
46% below poverty line

4. Mexican GDP growth
Source: COFEPRIS

5. Mexican GDP growth
relative to US GDP growth
Source: COFEPRIS

6. Mexican balance of payments
Accounting record of all monetary transactions between a country and the rest
of the world. Indicator of a country's position in the global economy.
Source: COFEPRIS / Data: 2010

7. Mexican fiscal deficit
Difference between public expenditure and income. Indicator of a government’s
budget and dependence on credit.
Source: COFEPRIS / Data: 2011

8. Direct foreign investment
in Mexico
Source: COFEPRIS

9. Public expenditure in drug
products
Source: COFEPRIS

10. Public expenditure in drug
products - global comparison
Source: COFEPRIS

11. Out-of-pocket health
expenditure
as a percentage of total health expenditure
Source: COFEPRIS

12. The pharma industry in Mexico
% of GDP
1.2
% of manufacturing GDP
6.9
Annual exports (millions of USD)
2,200
Total pharma market (billions of
dollars)
13
Direct employment
78,500
Indirect employment
330,000
2nd biggest in LatAm
11th biggest worldwide
Source: COFEPRIS
Steady annual growthrate
2005-2011: average of 4.8%

13. The pharma industry in Mexico
Mainly internal consumption (exports only 14% of production)
Source: COFEPRIS

14. COFEPRIS: the Mexican
Health Authority
Regulates:
• Food and beverages
• Tobacco products
• Healthcare supplies
(including drugs, medical
devices, vaccines, blood
and tissues, etc.)
• Healthcare services
• Other consumer goods
(cosmetics)
• Pesticides, plant nutrients
and toxic substances
• Emergencies
• Occupational health
• Environmental risks
92 billion $ market!
(around 10% of GDP)
Through all the supply chain
• Production
• Distribution
• Commercialization
• Imports
• Exports
• Advertisement
• Sales and supply

15. COFEPRIS: the Mexican
Health Authority
July 2012: COFEPRIS recognized as Health Authority of Regional
Reference
COFEPRIS
Commisionate:
Mikel Arriola
Photo: PAHO
Other ARRs: ANVISA (Brazil), ANMAT (Argentina), INVIMA
(Colombia), CECMED (Cuba)

16. Drug product
Registration in Mexico
General
overview

17. Drug registration in Mexico
Timeline to approval
Registration period: 5 years
officially: 6 months
In reality: very variable and
changing 12 – 24 months
Submission for registration renewal:
at least 6 months before registration
expiry
new entity
Small molecules
Registration
cases
Biotechs
generic
new entity
biocomparable
Vaccines
Orphan drugs
Before submission:
Committee of New
Molecules

18. Dossier structure
for the different registration cases
Vaccines
New Molecules
•
•
•
•
Module I. Legal/Administrative
information
Module II. Quality information
Module III. Preclinical studies
Module IV. Clinical studies
•
•
•
•
Orphan drugs
Generic drugs
•
•
•
Module I. Legal/Administrative
information
Module II. Quality information
Module III. Bioavailability and/or
bioequivalence
Module I. Legal/Administrative
information
Module II. Quality information
Module III. Preclinical studies
Module IV. Clinical studies
•
•
•
•
•
Module I. Legal/Administrative
information
Module II. Quality information
Module III. Justification of ‘orphan drug’
status
Module IV. Preclinical studies
Module V. Clinical studies

19. Dossier structure
content of the modules
Module I. Legal/Administrative information
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Form.
Proof of payment of fee.
Sanitary authorization. (licencia sanitaria) For foreign manufacturing site provide
licence, certificate or other document authorizing the site to manufacture the pharmaceutical
products of interest, issued by country of origin, legalized or apostilled, translated to Spanish
by an official translator (perito traductor).
‘Responsible sanitario’ notice.
Labeling texts (if applicable).
Complete and summarized prescription information.
GMP certificate for manufacturing site of API.
GMP certificate for manufacturing site of finished product.
GMP certificate for manufacturing site of diluent (if applicable).
For drug products manufactured outside of Mexico: Certificate of Pharmaceutical Product
(CPP) of origin, apostilled or legalized, with official translation (perito traductor).
Representation letter, assigning the legal representative of the foreign company in Mexico.
(Reccomended: broad power of representation letter, minimum validity time of 5 years.
Commercial name.
Intellectual property information.
Information on the waiver for the local manufacturing facility requirement.

20. Dossier structure
content of the modules
Module II. Quality information
1. API
1.1. Manufacturing information
1.2. General information
1.3. Quality control
1.3.1. Literature/Pharmacopoeial references. Specifications. Analytical methods.
Validation reports. Certificates of analysis (CoAs).
2. Excipients and additives
2.1. For new additives, usage safety information
2.2. Quality control
2.2.1. Literature/Pharmacopoeial references. Specifications. Analytical methods.
Validation reports. Certificates of analysis (CoAs).

21. Dossier structure
content of the modules
Module II. Quality information (cont.)
3. Finished product
3.1. Pharmaceutical development
3.2. Formula
3.3. Manufacturing information
3.3.1. Manufacturing/packaging order, in-process controls.
3.4. Quality control
3.4.1. Monograph
3.4.2. Specifications
3.4.3. Analytical methods and validation reports (if applicable)
3.4.4 Certificates of analysis (CoAs).
3.5 Stability
3.5.1 Stability protocol
3.5.2. Tabulated stability data
3.5.3 Analytical evidence for first and final testing points.
3.5.4 Conclusions

22. Dossier structure
content of the modules
Module II. Quality information (cont.)
4. Packaging materials
4.1. Description and capacity of primary packaging materials.
4.2. Description and capacity of secondary packaging materials.
4.3. Description, capacity and information of any additional materials or devices.

23. Dossier structure
content of the modules
Module III. Preclinical studies (for new molecules, vaccines, orphan drugs).
1. Preclinical studies
1.1. Pharmacodynamics' studies
1.2. Pharmacokinetic studies
1.3. Toxicology
Module IV. Clinical studies (for new molecules, vaccines, orphan drugs).
1. Clinical studies
1.1. Phase I studies
1.2. Phase II studies
1.3. Phase III studies
1.4. Phase IV studies (if applicable)
1.5. For combination of two or more drugs: risk-benefit assessment.

24. Dossier structure
content of the modules
Module III. Bioavailability and/or bioequivalence (for generic drug products)
1. Type of test
1.1. A
1.2. A (3)
1.3. B
1.4. C

25. Biotech regulations:
Mexico at the vanguard
Late ‘90s
1997
1998
Some legal
adaptations to
include
innovative
biotech drug
products
Modification of
General Health
Law – all biotech
products
Inclusion of some
concepts and
guidelines in Health
Supplies Regulation
2004
2005
USA – EU
EU: First specific
started
guidelines
discussions on
regulations for
SBP
+170 biotech drug products approved
2007
2009
Starts congress
discussion in
Mexico
Modification to
Health
General Law –
general
principles for
SBP
Development of
specific, detailed
regulation
COFEPRIS, industry,
other actors
Oct 2011 –
April 2012
Modification of
General Health
Law
Sep 2012
Operative
guidelines
became
effective

26. Drug registration in Mexico
foreign manufacturers
Until August 2008: local
manufacturing site requirement
the solicitor of a registration had to
own a manufacturing facility in
Mexico
Foreign manufacturer
•
•
License to
manufacture medical
products
GMP certificate
Currently:
Solicitor must hold
license, permit or similar
document issued by the country
of origin authorizing the
manufacturing of medical
products
Legal
representative
Warehouse (storage and
distribution)
Importer (Mexican
company)
Lab of Analysis (Authorized
Third Parties)
Unit of
pharmacovigilanc
e
Sanitary responsible

27. New Molecule Committee
For registration of novel compounds

28. Presentation at the New
Molecule Committee
Cases in which a drug is considered a “New Molecule”
• New drug substances (new in the world or new for Mexico)
• New combinations of drug substances (for Mexico)
• New indications
• Other special cases (e.g. similar biotherapeutic products)
1- Request meeting with the New Molecule Committe. (before
dossier submission)
2- Presentation by company on the product, followed by questions
by the members of the committee.
3- After the meeting, the committee will issue a report thet will be
attached to the dossier for submission.

29. Pre-revision of submission dossiers by
Authorized Third Parties
A solution for eternal approval timelines

30. Pre-revision of dossier
Starting in 2012, the possibility of having submission dossiers pre-revised by
private parties especially authorized by COFEPRIS was introduced.
How does it work? After all the necessary meetings and exchange of information, the ATP
will issue a technical report. If this final report is positive, it can be attached to the submission
package for registration. This submission package will enter the COFEPRIS through a
special fast-track channel and will be revised in a much shorter time than applications going
through the conventional channel.
This option is available for new drug applications, renewal of registration certificate and
variations.
COFEPRIS doesn’t have any inference in the relations and terms of agreement between
clients and ATP.
Main benefits of this new option
• Cut current revision times.
• Avoid unnecessary deficiency letters.
The technical report that the ATP issues does not replace the evaluation
and decision by COFEPRIS.

31. Significant reduction in
processing times!
NEW August 2013: expansion of the Third Authorized Parties’ pre-revision
scheme to include biotech products
Source: COFEPRIS

32. GMP verification and
certification

33. GMP verification by COFEPRIS
GMP Certificates issued by FDA
When?
• For new registration and manufacturing
changes of biologic, biotech and
hemoderivate products.
• For new registration or renewal of drug
products or drug substances of any kind
manufactured in countries not considered as
high sanitary surveillance by COFEPRIS.
Inspection is required
prior to submission
the certificate is an important document to be
annexed to the submission dossier
What?
Manufacturing sites of drug substance
and drug product – DP/DS specific
(USA), ANVISA (Brazil), Health Canada
(Canada), EMA (EU), Pharmaceutical and
Food Safety Bureau (Japan), and Therapeutic
Goods Administration (Australia) are
accepted.
Cooperation within the Pacific Alliance
bloc and with other Sanitary
Authorities of Regional Reference
Request for inspection
• Submit form and required documents
• Propose two inspection dates (production of
DS/DP) and inspection schedule
• Propose hotel and flight options. Cost of visit +
travel expenses: company
• Arrange a Spanish translator
• Timeline to get an inspection: about 3 months

34. Required info and documents
•
Name and general data of the applying company,
authorization
•
Name of DP/DS – use, action, indication
•
Name and address of all sites involved in manufacturing
process, description of process stages
•
Manufacturing process – list and description of other DS/DP
manufactured in same line
•
Person designated by the applicant to be in charge
•
Technical documents:
 Organization charts
 Architectural drawings
 Flowchart of manufacturing process
 General summary of quality system
 Validation master plan
 Two last annual product reports
Payment
•
All documents in
Spanish, or English
with Spanish
translation, verified
and signed by technical
responsible
Documents issued by
foreign authorities:
apostilled or
legalized and
translated by certified
translator
NEW! AUGUST 2013: Open call to private parties to enroll as
inspectors for DS and DP facilities (Authorized Third Parties)

35. Clinical trials in Mexican
population

36. Local Clinical Trials in Mexico
• Why?
Pharmacogenomic studies have shown that
drug
metabolism
in
Mexican-Hispanic
population can be influenced by its genetic
makeup.
• In which cases?
Local clinical studies are required by COFEPRIS
for:
• New molecules
• Biotech and biocomparable products
• Generic drugs that are not commercialized
anywhere else in the world.
• Other cases upon authority request
• When?
• Previous submission and approval of clinical
protocol – Have results before submission for
registration.
• How?
When
clinical
studies
are
multicentric, Mexican population must be
included.
Sample size: not specified in regulations;
to be calculated based on incidence of
disease.
If Mexican patients are not included in the
clinical trials: New Molecule Committee
will request pharmacokinetic studies to
evidence not significant differences in
safety or efficacy in Mexicans.
• Good Clinical Practices guidelines

37. Agreement for innovation
October 2012

38. Agreement for Innovation
Three main tenants
1. Give
strong support for innovation projects proposed by the
national sector: expedition of approval of clinical protocols to be carried out in Mexican
clinical centers, follow-up on the execution of the studies, and expedition of registration
approval timelines for drug products manufactured in Mexico, from the current average of 240
working days to 60.
2. Strengthen
the import of innovative drugs to the Mexican
market: recognition of product registrations in the USA, Canada, Switzerland, Australia
and the EU and expedition in registration approval timeline for drug products being marketed
in any of these countries from a current average of 360 working days to 60.
3. Make
Mexico the first country of commercialization of new
innovative drug products: modification of the Regulations for Healthcare
Supplies: the previously compulsory requirement of providing a CPP of origin offers now the
alternative of being waived if a report of clinical trials on Mexican population is submitted.

39. Agreement for Innovation
Results: reduction in dossier revision times
Source: COFEPRIS

40. Agreement for Innovation
Concrete results
•
88 new innovative drug products have entered the Mexican market,
most of them through the expedited revision process for registration of
innovative imported drugs registered in high-sanitary-surveillance
countries, and including five orphan drugs. Most of the newly approved
drugs target cardiovascular, oncologic or cerebrovascular conditions.
•
Increase of 20% from 2011 to 2013 in applications for clinical trials in
Mexico (current figure: 388 applications), and COFEPRIS is
implementing measures to decentralize the revision of clinical protocols
to the National Institutes of Health in order to reduce evaluation times,
from 90 to 30 days.
•
In January 2013, one new drug was approved in Mexico before any
other country in the world, making Mexico a worldwide pioneer for an
innovative drug product for the first time: Lixisenatide (Sanofi Pasteur),
trade name Lyxumia, the latest pharmaceutical innovation to treat Type
2 Diabetes, a once-daily injectable GLP-1 receptor agonist.

41. Coming soon:
Regulations on personalized
medicine/pharmacogenomics

42. Regulations on personalized
medicine
Guidelines coming soon
•
Guidelines to guarantee safety and effectiveness of personalized
therapies based on pharmacogenomics approach
•
Define specific GMP requirements for pharmacogenomics-based
products.
•
Make Mexico a pioneer in regulation for this kind of product in Latin
America.

43. Thank you! Gracias! Děkuji!
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