2017

WHO GMP
COMPLIANCE IN
LATAM REGION

Prepared for
 TABLE OF CONTENTS
1. LIST OF ABBREVIATIONS ................................................................................................ 2
2. EXECUTIVE SUMMARY ................................................................................................... 4
3. GLOSSARY....................................................................................................................... 5
4. INTRODUCTION .............................................................................................................. 6
5. REGULATORY STATUS OF WHO- GMP IN LATAM COUNTRIES ..................................... 7
6. REGIONAL GMP REQUIREMENTS FOR COUNTRIES WITH PARTIAL WHO COMPLIANCE
8
6.1 Nicaragua and Guatemala ................................................................................... 8
6.2 Panama................................................................................................................ 9
6.3 Mexico ................................................................................................................. 9
6.3.1 Manufacturing Master File .............................................................................. 9
6.3.2 Packaging ......................................................................................................... 9
6.3.3 Manufacturing Record................................................................................... 10
6.3.4 Miscellaneous ................................................................................................ 10
7. MARKET INTELLIGENCE REPORT FOR LATAM REGION ................................................ 12
8. INFERENCE ................................................................................................................... 13
9. REFERENCES ................................................................................................................. 14

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1. LIST OF ABBREVIATIONS

Agência Nacional de Vigilância Sanitária (National Health

ANVISA
Surveillance Agency)

Comisión Federal para la Protección contra Riesgos Sanitarios

COFEPRIS
(Federal Commission for the Protection against Sanitary Risk)

GMP Good Manufacturing Practices

HEPA High Efficiency Particulate Air

HVAC Heating, Ventilation and Air Conditioning

TRS Technical Report Series

WHO World Health Organization

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 LIST OF TABLES
Table 1: WHO- LATAM GMP Compliance

Table 2: Market Data for LATAM Region

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2. EXECUTIVE SUMMARY
Eris is planning to market its generic products in LATAM region for which it is looking
for a careful comprehension of pertinent regulations to empower promotion and sale of its
products.

In this regard, Eris has approached Freyr for support in:

• Identifying the countries that require drug manufacturer’s adherence to World

Health Organization (WHO) Good Manufacturing Practice (GMP) guidelines only;
• Also, those countries that require adherence to WHO GMP guidelines as well as
regional guidelines as part of the manufacturing process.

Freyr has deployed multiple methodologies for collation of WHO GMP guidelines and the
GMP guidelines of all the LATAM countries. The strategy includes extensive search in
multiple global regulatory databases, Fryer’s in-house knowledge repositories, mapping
GMP requirements of each LATAM country with those of WHO Technical Report Series
(TRS) No. 961, as well as an in-depth analysis of the obtained information.

Through this report, Freyr has attempted to answer key inquiries regarding GMP
requirements of WHO and the LATAM countries. The report might be reconsidered in
view of the inputs, remarks and queries from the Eris team.

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3. GLOSSARY
GMP: It is a system for ensuring that products are consistently produced and controlled
according to quality standards. It is designed to minimize the risks involved in any
pharmaceutical production that cannot be eliminated through testing the final product.1

WHO: WHO is a specialised agency of the United Nations that is aimed at building a
better, healthier future for people all over the world. WHO staff work side by side with
regional governments and other partners to ensure the highest attainable level of health for
all people.2

WHO Certification Scheme: It is a Scheme developed by WHO in response to the

request of WHO Member States to facilitate international trade in pharmaceutical products
between Member States and it gives guidance to the issuing as well as requesting health
authorities.3

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4. INTRODUCTION
Licensed pharmaceutical products should be manufactured only by licensed manufacturers
whose activities are regularly inspected by competent national authorities. GMP guide
shall be used as a standard to justify GMP status, which constitutes one of the elements of
the WHO Certification Scheme on the quality of pharmaceutical products moving in
international commerce, through the assessment of applications for manufacturing
authorizations and as a basis for the inspection of manufacturing facilities.

Latin America is one of the top emerging markets in the pharmaceutical industry. This
region shows a great deal of diversity in its approach to pharmaceutical products because
of differences in economics, resources, access to care, and definition of regulatory
requirements by country. Seeking regulatory harmonization, LATAM countries have
begun implementing common GMP guidelines of WHO.4

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5. REGULATORY STATUS OF WHO- GMP IN LATAM COUNTRIES 5

Countries with 100% WHO- Countries with over 75% WHO- Countries with 75% WHO-
GMP compliance GMP compliance GMP compliance

Argentina 6 Nicaragua 17 Mexico 20

Bolivia 7 Guatemala 18
Brazil 8 Panama 19
Costa Rica 9
Chile 10
Cuba 11
Dominican Republic 12
Ecuador 13
Haiti 14
Peru 15
Venezuela 16
Table 1: WHO- LATAM GMP Compliance

In Suriname, Guyana, Honduras and Trinidad & Tobago, legal provisions exist requiring
manufacturers to be licensed, but there are no regulations requiring manufacturers to
comply with GMP. Regulations for GMP in these countries are not published by their
governments.21

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6. REGIONAL GMP REQUIREMENTS FOR COUNTRIES WITH PARTIAL WHO
COMPLIANCE
6.1 Nicaragua and Guatemala

In addition to the requirements framed by WHO, manufacturers of pharmaceuticals in

Nicaragua should comply with the following concerns:

• Manufacturers must at least have the updated drawings and diagrams of:
o Construction plans and remodelling;
o Plan of distribution of areas;
o Flow diagram of personnel;
o Flow diagram of materials;
o Process flow diagram;
o Service plan (air conditioning, compressed air, drainage water, sewage
water, electricity, steam, pure steam and gases);
o Plan for the evacuation of personnel in case of emergency and location plan
for emergency exits; and
o Diagram of the water treatment system for production.
• Equipment cleaning must be recorded with a label stating the name of the
personnel involved in cleaning, cleaned date, name and batch number of the last
manufactured product, name and batch number of the product to be manufactured.
This should be signed by the personnel who is involved in cleaning and also the
operator who verified it.
• All pharmaceutical plants must have a water treatment system which allows
obtaining quality water as per the specifications for production. The system should
be subjected to planned maintenance and monitoring.
• Tanks and cisterns for water storage must have written procedures for cleaning,
sanitization and control. Frequency of actions and sampling points must be
registered. Storage pharmaceutical grade water should not exceed 24 hours or else
they should be recirculated.
• The air treatment system must have written procedures and instructions covering
precautions for handling and there must be a documented preventive maintenance
program, covering the periodic air system controls supplied to different areas of
production.

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 • There should be written procedures for destruction of waste and air filters used in
the system of ingestion and extraction of air.
• Microbiological tests should be conducted according to the scheduled procedures
to ensure quality of air.17 18

6.2 Panama

Labels of products manufactured by contract in abroad, should contain a statement

“Packaged in Panama by....”.19

6.3 Mexico

Mexico is a well-regulated country which holds the second largest pharma market share in
the LATAM region. The pharmaceutical industries planning to market their products in
Mexico are required to undergo thorough scrutiny in terms of overall quality compliance.
Even though the Mexican standards correspond to WHO GMP requirements, the
manufacturers should also meet the local mandates recommended by Federal Commission
for the Protection against Sanitary Risk (COFEPRIS). The following are the additional
Mexican GMP requirements:

6.3.1 Manufacturing Master File

The updates of the manufacturing master file shall be made known to COFEPRIS by
means of free writing.

• Major Changes to manufacturing master file:

o Change of the Health Officer, the person responsible for the production unit
and / or responsible for the quality unit.
o Changes in critical systems
o Inclusion of new drugs that require new cleaning validation
• If there are minor changes, the manufacturing master file should be updated at least
every two years and notified to COFEPRIS.

6.3.2 Packaging

The graphical representations of the packaging should be included in the SOPs for
packaging.

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 6.3.3 Manufacturing Record

The manufacturing record of each batch should be preserved for at least one year after its
expiration date and for the case where the date of reanalysis is assigned, the records shall
be retained for at least three years after the batch is completely distributed.

6.3.4 Miscellaneous

• The manufacturing areas that are classified should comply with the criteria
established in Appendix A- Classification of manufacturing areas of the
Standard: Mexican Official NOM-164-SSA1-2015, Good Manufacturing
Practice drug;
• Pipes must be identified, according to the code of NOM-026-STPS-2008.
• The Heating, Ventilation and Air Conditioning (HVAC) system must be
designed and shaped according to the minimum considerations set out in in
Appendix A of the Standard: Mexican Official NOM-164-SSA1-2015, Good
Manufacturing Practice drug;
• If due to the characteristics or nature of the product or process the temperature
and / or RH is other than those set out in the Regulatory Appendix A of the
standard, it must be justified in the related technical documentation;
• An identification system must be established to show the cleaning status of the
equipment;
• Acceptance levels of product traces or their intermediates, cleaning agents,
should be defined through validation studies;
• The purification system and distribution of water for the manufacture of
pharmaceuticals, where applicable, must be designed, built and maintained to
ensure the required water quality, according to the Mexican Pharmacopeia;
• Drinking water must comply with the provisions of Mexican Pharmacopeia
and current NOM-127-SSA1 standards;
• Air systems shall be designed, constructed and maintained in accordance with
Mexican Pharmacopoeia;
• The HVAC system shall be rated in accordance with the Mexican
Pharmacopoeia taking into account at least the following parameters:
temperature and relative humidity of the areas it feeds, air injection volume,
pressure differentials between areas, number of air changes, Particle count,

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 airflow, cleaning levels, flow rate, and High Efficiency Particulate Air (HEPA)
filter integrity tests;
• The qualification of water systems for pharmaceutical use must be made in
accordance with Mexican pharmacopoeia and its supplements;
• The aseptic processes should be validated.20

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7. MARKET INTELLIGENCE REPORT FOR LATAM REGION

Countries Pharma Market Generic Market Hypertension Market Diabetes Market

Brazil USD 35.13 Bn USD 11.6 Bn USD 2.5 Bn USD 3.5 Bn

Venezuela USD 13.4 Bn USD 5.36 Bn USD 350** Mn USD 412 Mn

Mexico USD 13.2 Bn USD 11.08 Bn USD 350** Mn USD 1.22 Bn

Guatemala USD 12.9 Bn USD 7.74 Bn USD 300** Mn USD 1.29* Bn

Argentina USD 6.9 Bn USD 4.5 Bn USD 200** Mn USD 0.7* Bn

Columbia USD 5 Bn USD 1.6 Bn USD 130** Mn USD 2.7 Mn

Chile USD 2.89 Bn USD 1.7 Bn USD 40 Mn

USD 0.04 Bn
Peru USD 2 Bn USD 340 Mn USD 54** Mn USD 200 Mn

Ecuador USD 1.33 Bn USD 390 Mn USD 35** Mn USD 133* Mn

Dominican
USD 607 Mn USD 360 Mn USD 16** Mn USD 60* Mn
Republic

Costa Rica USD 530 Mn USD 160 Mn USD 14** Mn USD 53* Mn

Panama USD 307 Mn USD 180 Mn USD 8**Mn USD 30.7* Mn

Nicaragua USD 297 Mn USD 178Mn USD 8** Mn USD 30* Mn

Cuba USD 444 Mn USD 266 Mn USD 12** Mn USD 44.4*Mn

Bolivia USD 390 Mn USD 234 Mn USD 10.5** Mn USD 39* Mn

Table 2: Market Data for LATAM Region

*Approximate value obtained by taking share of global diabetes market over global
pharma market. Actual figures may vary slightly.
** Approximate value obtained by taking share of global hypertension market over total
global pharma market. Actual figures may vary slightly.
Note: In LATAM countries average generic market share is 65%. For few countries,
generic market size has been calculated from this data.
References from 22 to 50 refer to market intelligence report.

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8. INFERENCE
It is advisable for the companies entering the LATAM market to begin with acquiring the
Brazilian (ANVISA) GMP certificate, this will help in bypassing the subsequent GMP
audit visits from the other countries as it is acceptable in most of the other LATAM
countries.

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9. REFERENCES

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