IDRAC 28906

HOW TO MARKET ORPHAN DRUGS

(Mexico)

Recent Document Updates Date Updated Sections

Minor Edit* Aug-2016
* Minor Edit = grammar edit or minor wording change including updated IDRAC-links

1. Introduction

There is no official procedure for obtaining registration of orphan drugs in Mexico. Art. 224 bis of the
General Law of Health (IDRAC 28639) includes the following definition: Orphan medicinal products
aimed at the prevention, diagnosis or treatment of rare diseases, are those that have a prevalence of
not more than 5 people by each 10 thousand inhabitants.

In 2010 an agreement was signed between the representatives of the Pharmaceutical Industry and the
COFEPRIS, with the purpose of establishing the requirements for granting the orphan product status,
but the regulation has not changed yet further to the agreement.

A document called Letter of recognition (Oficio de reconocimiento) for the orphan product is currently
issued (different to a Marketing Authorization). With this document, the Holder will be able to apply for
the import application. This solution is an emergent measure till the modification to the Regulation of
Health Sector Products (IDRAC 28983) is published.

2. Procedure

2.1. Request of Orphan status

To obtain the Letter of recognition for orphan products the applicant has to present:
- a written request (Escrito libre),
- the Operating Notification (Aviso de funcionamiento) and/or Sanitary license (Licencia Sanitaria)
of the marketing authorization holder and/or distributor,
- the technical responsible notification (Aviso de responsable sanitario) for all the establishments
involved in the product commercialization,
- Free sales certificate (FSC) / CPP,
- GMP certificate of the API manufacturer,
- GMP certificate of the final product manufacturer,
- Letter of representation in case the applicant is not a subsidiary of the parent company in the
country of origin,
- Patent,
- Information related to the API,
- Quali-quantitative product formula signed by the technical responsible,
- Summary and flow diagram of the manufacturing process, with a description of the controls,
- Certificate of analysis,
- Description, specifications and analysis certificate of the primary packaging,
- Summary of the stability studies,
- Draft of the labeling, SPC and patient leaflet, with the artworks and labeling used in the country
of origin,

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- Information related to the prevalence of the cases reported for the disease/deaths in the orphan
population, information from international databases related to the recognition of the orphan
status by other National Regulatory Agencies (such as EMA, FDA),
- Preclinical and clinical information.

Requirement New product Orphan product

Legal Reference Yes No
Sanitary register Yes No
Administrative and legal documents Yes Yes
Chemical information and evaluation Yes Yes
Medical evaluation Yes Yes (from the country of origin)
Sample of labeling and packaging Yes - for import purposes, the labeling
material, SPC and patient leaflet of the country of origin will be accepted
for evaluation purposes, but will not be
authorized for commercialization
Recognition for orphan product No Yes
status issued by a recognized
authority (FDA, EMA among others)
2.2. Content of the dossier

Cofepris is now asking for orphan products, the same documentation as for Marketing Authorization
requests. The Table of Contents of the Application Dossier for Orphan Drug Status (IDRAC 167799)
presents the content of an application for the registration of these products.
The information to be presented is classified in five Modules:

Module I: Legal and Administrative Information

1. Written request (Escrito libre), letter asking for the recognition of the orphan product status,
2. Sanitary License (Licencia Sanitaria),
3. Operating notification (Aviso de Funcionamiento) from the warehouse,
4. Operating notification (Aviso de Funcionamiento) from the distribution site,
5. Technical responsible notification (Aviso de responsable sanitario) for the warehouse,
distributor and holder of the orphan status,
6. Labeling, according to the norm NOM-072-SSA1-2012 (IDRAC 154428) (2 copies for each
presentation/concentration of product, according to the Written request),
7. Artworks from the country of origin,
8. Instructions for use (according to the norm NOM-072-SSA1-1993 (IDRAC 154428))
9. Package insert from the country of origin,
10. SPC (Informacin para prescriber amplia), please refer to Product Information: Summary of
Product Characteristics (SmPC) / Information for Healthcare Professionals (IDRAC 30939),
11. Patient leaflet, including in the Warnings section: This medicine can only be administered by
specialists. Please refer to Product Information: Package Insert / Package Leaflet / Patient
Information (IDRAC 30938),
12. GMP certificate of the manufacturer(s) of API(s),
13. GMP certificate of the manufacturer(s) of finished product,
14. Free sales certificate (FSC) or product certificate,
15. Letter of representation (if applicable),
16. Commercial name,
17. Information about the patent of the API.

Module II: Quality Information

1. API
1.1 Obtained from Chemical Synthesis.
1.1.1. Manufacturing information: name and address of the manufacturing site, route of
synthesis

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1.1.2. General information:

-Chemical Name
- Structural definition of the API
- Solvents used and probable impurities obtained during the synthesis
1.1.3. Controls of the API: Specifications, methods, with bibliographic references and analytical
certificates.
1.1.4. Stability (protocols, summarized tables of the parameters evaluated under accelerated
conditions or long term studies), and conclusions.

1.2 Biologic API

1.2.1. Manufacturing information;
- Name of manufacturing site;
- Flow chart of the process including in process controls,
- Inform if during the process a sterilization process or lyophilization is made,
- In case that either of these two processes are done, the full information of how they are done
has to be presented,
- Information of the construction of the system.

1.2.2. General Information:

- Chemical name, International Common Denomination (DCI), generic denomination,
- Physical description: white powder, molecular weight, solubility
- Description of the chemical structure and molecular formula;
- Characterization of the product (made by a structural analysis),

1.2.3. Analytical Controls, specifications with the justification for each analysis, analytical
methods used. One to three CoAs.

1.2.4 Stability tests: Protocol, summary of evaluated parameters, accelerated and long term
from one to three batches, conclusions. The foreign stability tests are accepted.

2. Finished Product
2.1.Description of the product: Quali-quantitative formula, pharmaceutical form, use.
2.2.Manufacturing process:
- Description of the manufacturing process with correspondent flow charts, in process
controls. If a sterilization process is included, submit the whole information. It is
recommended to submit manufacturing and packaging orders of batches used for
stability tests.
2.3. Controls of the finished product: specifications of the medicinal product and corresponding
justifications, description of the analytical methods, and corresponding CoAs.
2.4.Stability test (for one to three batches): stability protocol (in case that the orphan product
is added to a solution for its application, the stability test of the final solution has to be
presented also).
- If the applicant has different container-closure systems, stability tests for each system
have to be done.
2.5. Container-closure system: description and capacity of the primary and secondary
packing material, specifications, analysis methods, results of the hermetical proof (if
applicable).

3. Blood products
3.1.Starting materials: certificate of analysis of the plasma,
3.2.Manufacturing process
3.3.For the finished product: specifications, analytical methods, stability tests.

Module III: Information supporting the orphan status of the product

Information on the prevalence of the reported cases of the disease in the population (5 patients by
each 10 000 inhabitants).

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Orphan status recognition: information of the international data base of other National Regulatory
Agencies, like EMA, FDA, etc.
If possible give information of cases diagnosed in Mexico, especially for the products other
countries do not recognize as orphans. The accepted information is the one generated by
recognized Health Institutions (in Mexico: Instituto Mexicano del Seguro Social (IMSS), Instituto de
Seguridad y Servicio Social de los Trabajadores del Estado (ISSSTE)).

Module IV: Preclinical studies

Summary of Pharmaco-dynamic studies;

Summary of Pharmacokinetic studies;
Summary of Toxicology studies.

Module V: Clinical studies

Summaries of clinical studies, Phase I, II and III.

3. Import of orphan drugs

The application (Form: Application for Authorisations, Certifications and Inspections (IDRAC 119714))
to import orphan drugs should state the following number (see Instructions (IDRAC 119720)):
Homoclave COFEPRIS-01-010-D (Modalidad D: Sanitary permit to import medicaments that are not or
do not contain psychotropics for personal use, and are not registered in Mexico).

A medical prescription that includes the official recognition number (Cdula Profesional) of the
physician that shows the name of the product and the quantity should be annexed to the application
(This document is not required for medication sold over the counter).

Source: Art. 196, Point III of the Regulation of Health Sector Products (IDRAC 28983) [Reglamento de
Insumos para la Salud (RIS)].

For more information refer to the section: Temporary Use Authorisation (IDRAC 29100).

Source: Ch.B. (Independent Consultant)

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