Overview of New Drugs Registration in Mexico

Esperanza Olivares Lopez

Table of Contents Mexico’s Health Authority

Definition

Classification of Drugs in Mexico

Different Steps of Drugs Registration in Mexico

Content of Registration Dossier

Cofepris GMP Inspection

Consultation Meeting with Cofepris

Registration Fees & timelines

References

The Federal Commission for Protection against Health Risks(COFEPRIS) is a decentralized body of the Ministry of Health, thatis, it has technical, administrative and operational autonomy, itspurpose is to protect the health of the population.

COFEPRIS through the Sanitary Authorization Commission (CAS) is the one who in charge of decide the sanitary registration of drugs in Mexico.

New Molecule Committee of COFEPRIS requests and technical meetings are through the Center for Integrated Services (Centro Integral de Servicios, CIS).

Mexico’s Health Authority

Cofepris

CAS

CCAyAC

CGJC

SG

CIS

CEMAR

CGSFS

COS

*Abbreviation• CFS- Comisión de Fomento Sanitario.• COS- Comisión de Operación Sanitaria• CCAyAC- Comisión de Control Analítico y Ampliación de

Cobertura• CAS- Comisión de Autorización Sanitaria• CEMAR- Comisión de Evidencia y Manejo de Riesgo• CGSFS- Coordinación General del Sistema Federal

Sanitario• CGJC- Coordinación General Jurídica y Consultiva• CIS-Centro Integral de Servicios

Definition

Cofepris defines a drug as:

“Any substance or mixture of substances of natural or synthetic origin that has a therapeutic,

preventive or rehabilitative effect, that is presented in a pharmaceutical form and is identified as

such by its pharmacological activity, physical, chemical and biological characteristics. When a

product contains nutrients, it will be considered a medicine, as long as it is a preparation that

contains individually or in association: vitamins, minerals, electrolytes, amino acids or fatty

acids, in concentrations higher than those of natural foods and it is also present in some defined

pharmaceutical form and the indication of use contemplates therapeutic, preventive or

rehabilitative effects.”

-Article 221, Section I of the General Health Law

Classification of Drugs in Mexico

Mode of Preparation

Origin of their Materials

Mode of Delivery

Domestic or Foreign

In Mexico Drugs can be classified in different categories based on the following criteria:

Drugs Classification Based on their Mode of Preparation

Classification Definitions

Magisterial drugs They are prepared according to the formula prescribed by a doctor

Officinal drugs They are prepared according to the rules of Mexican Pharmacopoeia

Pharmaceutical Specialties

They are prepared with formulas authorized by the Ministry of Health, in establishments of the pharmaceutical industry.

Classifications Based on Origin

Classification Definitions

AllopathicAny substance or mixture of substances of natural or synthetic origin that has a therapeutic, preventive or rehabilitative effect, that is presented in a pharmaceutical form 'and is identified as such by its pharmacological activity, physical, chemical and biological characteristics, and is registered in the Pharmacopoeia of the United Mexican States for allopathic medicines

HomeopathicAny substance or mixture of substances of natural or synthetic origin that has a therapeutic, preventive or rehabilitative effect and that is prepared in accordance with the manufacturing procedures described in the Homeopathic Pharmacopoeia of the United Mexican States, in those of other countries or other national and international sources of scientific information

HerbalProducts made from plant material or a derivative thereof, whose main ingredient is the aerial or underground part of a plant or extracts and tinctures, as well as juices, resins, fatty and essential oils, presented in pharmaceutical form, whose therapeutic efficacy and security has been scientifically confirmed in national or international literature.

Classification Based on Mode of Delivery

Categories Definitions

I Medicines that can only be purchased with a prescription or special permission, issued by the Ministry of Health

II

Medicines that require a medical prescription for their acquisition that must be kept at the pharmacy that supplies it and be recorded in the control books that are kept for this purpose. The treating physician may prescribe a maximum of two presentations of the same product, specifying its content. This prescription will be valid for thirty days from the date of preparation of the same.

III

Medicines that can only be obtained with a prescription that can be filled up to three times, which must be sealed and recorded each time in the control books kept for this purpose. This prescription must be retained by the establishment that supplies it on the third occasion; the treating doctor will determine the number of presentations of the same product and their content that can be purchased each time.

IV Medications that require a prescription to be purchased, but can be refilled as many times as prescribed by the prescribing physician

V Non-prescription drugs, authorized for sale exclusively in pharmacies

VI Medicines that do not require a prescription to be purchased and that can be sold in establishments other than pharmacies. Medicines or other health supplies may not be sold in semi-fixed stalls or mobile modules.

New Molecule Registration Steps

Step 1• Consultation Meeting with Cofepris New Molecules

Committee

Step 2• Request GMP inspection from Cofepris

Step 3• Prepare and Submit registration dossier to third party

or directly to Cofepris for review and approval

STEP 1. Consultation Meeting with New Molecule Committee

Supporting documents must be submitted in a USB drive.

Documents must beTranslated into Spanish.

The applicant must identify the applicable evaluation route for the product registration.

A consultation meeting is mandatory before submitting the registration dossier to the New Molecule Committee (NMC) at Cofepris

1A meeting request must be submitted to NMC with the associated documentation.

2NMC reviews application and notifies applicant of meeting request decision within 60 days.

3NMC will notify the applicant of the scheduled meeting day 20 business days in advance.

4Applicant must Confirm scheduled meeting date with the NMC

5A presentation must be sent to NMC 5 days prior to the confirmed meeting date

6NMC will issue a *Technical Opinion 20 business days after the meeting.

7The applicant can submit the Technical Opinion and the complete Technical dossier to Cofepris

Document Considerations

* A good technical opinion must be obtained in order to continue to Step 7 - Cofepris submission. If a technical opinion obtained advises the applicant for further revision the applicant must update their application and begin the application process to the NMC all over again.

STEP 2. Request for Cofepris GMP Inspection

Mexico has its own Good Manufacturing Practices requirements. Manufacturer must request COFEPRIS for GMP inspection before submitting the

registration dossier. Manufacturer with GMP certificate from reference countries are exempt from Cofepris

GMP inspection. GMP certification must be obtained for all applicable manufacturing sites. ( drug

substance and finished products).

2. Content of Application for GMP Inspection• Name and general information of the requesting establishment

• Name of the drug or medicine for which you are requesting verification of GMP

• Name and full address of the establishment(s) involved in each stage of manufacturing

• Description of the process that is carried out in each of the establishments involved

• The manufacturing process for which verification of GMP is requested

• A list and description of products that are made.

• Name of the legal representative, health officer or person designated by the establishment to attend the diligence

• Organization charts (general, of the production and quality departments, indicating the reporting lines)

• Plans of the establishment and production areas

• Block diagram of the manufacturing process

• General summary of the quality system including validation and qualification

• Information from the last two annual review reports, specifically indicating: manufactured lots, rejected lots (indicating reasons), released lots that were subject to investigation, conclusion and actions carried out, number of reprocessed batches, complaints, returns and withdrawal of products from the market, as well as conclusions of the report.

STEP 3. Prepare and Submit Registration Dossier

List of Requirements New molecules

Module I. Legal/ administration information X

Module II. Quality information X

Module III. Preclinical studies X

Module IV. Clinical Studies X

3. Content of Registration DossierModule No Content

Module I. Legal administrative

information

• Application Form• Proof of Payment of fee• Sanitary authorization• Responsible Sanitario notice• Labeling and prescribing information• GMP certificate API and FP manufacturing sites• CPP • Commercial name• Patent certificate

Module II. Quality information

API• Manufacturing information• Quality control• Excipients and additives, literatureFinished product• Pharmaceutical development• Formulation• Manufacturing information, in process controls• Quality control• Monographs specifications• Analytical methods certificates of analysis • Stability studies and stability data• Packaging materials (description and capacity)

3. Content of Registration Dossier

Module No Content

Module III. Preclinical

studies

Preclinical studies• Pharmacology studies• Pharmacokinetic studies• Toxicology

Module IV. Clinical studies

Clinical studies• Phase 1 studies• Phase II studies• Phase III studies• Phase IV studies

Registration Process for Foreign Manufacturer

Foreign manufacturer

Prior registration in

reference country

No Prior registration in

reference country

Request GMP

certificate in the country of

origin

Make clinical studies in Mexican

population.

Request meeting with

the COFEPRIS New Molecules

Committee

Use 3rd partyto evaluate

technical file

3rd Party issues

evaluated report to

Manufacturer/ Mexican

AuthorizedHolder

Submit registration request to

COFEPRIS

*3rd Party known as "notified bodies. A notified body is an organization designated by Cofepris to assess the conformity of certain products before being placed on the market. These bodies carry out tasks related to conformity assessment procedures set out in the applicable

legislation.

*Reference countries: USA FDA, Canada’s Health Canada, Switzerland’s Swissmedic,

European Medicines Agengy (EMA) and Australia’s TGA

Registration Fees & Timelines

Classification Time of response ( Natural Days) Fees ( Mexican Pesos)

Generic 180 Days $82,011.99

New molecule 180 Days $146,641.88

Additional Fees Time of response (Business Days) Fees ( Mexican Pesos)

GMP InspectionTimelines Vary $96,666.39

Request meeting with the COFEPRIS New Molecules

Committee60 Days NA

Receive New molecule Committee conclusions after

meeting20-40 Days NA

*Fees for Notified Bodies Vary

References Ley General de Salud. Diario Oficial de la Federacion. Mexico

Health Secretary NOM-059-SSA1-2015, Good Manufacturing Practices for Medicines. Published September 9th 2015. Consulted April 8th 2020. Available at http://dof.gob.mx/nota_detalle.php?codigo=5424575&fecha=05/02/2016

Health Secretary NOM-072-SSA1-2012, Labeling of Medicines and Herbal Remedies. Published February 9th 2012. Consulted April 8th 2020. Available at https://www.dof.gob.mx/nota_detalle.php?codigo=5278341&fecha=21/11/2012

Health Secretary NOM-073-SSA1-2015, Stability of drugs and medicines, as well as herbal remedies. Published February 26th 2015. Consulted April 8th 2020. Available at http://www.dof.gob.mx/nota_detalle_popup.php?codigo=5440183

Health Secretary NOM-177-SSA1-2013, That establishes the tests and procedures to demonstrate that a drug is interchangeable. Requirements to which the Authorized Third Parties that carry out the interchangeability tests must comply. Requirements to carry out the biocomparability studies. Requirements to which the Authorized Third Parties, Research Centers or Hospital Institutions that carry out the biocomparability tests must comply. Published May 6 th 2013. Consulted April 8th 2020. Available at http://www.dof.gob.mx/nota_detalle.php?codigo=5314833&fecha=20/09/2013

Health Secretary NOM-220-SSA1-2016, Installation and Operation of Pharmacovigilance. Published September 23rd 2016 . Consulted April 8th 2020. Available at http://dof.gob.mx/nota_detalle.php?codigo=5490830&fecha=19/07/2017

Reglamento de Insumos para la Salud. Diario Oficial de la Federacion. Mexico.

Suplemento para establecimientos dedicados a la venta y suministro de medicamentos y demás insumos para la salud. Sextaedición, México 2018.