A marketing authorization submission represents a major effort for the pharmaceutical industry, and requires a large team as well as detailed planning of all steps that will be part of this process.

In addition to the development of preclinical, clinical, and chemical manufacturing and control (CMC) documentation, which should be supported by the Regulatory Affairs department to define requirements in all territories to which registration will be submitted, the department should also define the requirements for Good Manufacturing Practice certification (cGMP) for the involved plants.

Globally, there is a harmonization movement for the optimization of inspections by authorities for the certification of pharmaceutical manufacturing plants, represented by the Pharmaceutical Inspection Co-Operation Scheme (PIC/S).

In Latin America, there is a wide range of cGMP related requirements, ranging from acceptance of certifications issued by foreign authorities to the need for inspection by the local authority for issuing the certification. There is also variation in the need to present certification for only the drug product (finished product), or also for intermediates and even for the active pharmaceutical ingredient (API).

Given this diversity of scenarios, when submitting in several countries in Latin America, it should be noted that it may be necessary to consider a period of time in project timelines for certification by local authorities, for issuing and legalizing documents by foreign authorities or other scenarios that may require some time for regularization.

Below we present the requirements to present cGMP in drug products marketing authorization submissions in major countries in the region.

Argentina

ANMAT requires the submission of cGMP to drug products manufacturing plants issued by the authority itself, upon inspection, or by other authorities considered as a reference for sites located in their respective countries.

Authorities recognized by regulation are from the following countries: United States of America, Japan, Sweden, Switzerland, Israel, Canada, Austria, Germany, France, United Kingdom, the Netherlands, Belgium, Denmark, Spain and Italy.

For manufacturintg sites located in MERCOSUR, ANMAT recognizes the reports issued by the authorities of these countries, and it is necessary that  ANMAT itself issues the certificate based on these reports.

It is important to point out that ANMAT is also a member of PIC/S.

Brazil

For approval of drug products MA in Brazil, ANVISA requires the presentation of the cGMP issued by the agency itself for the drug product manufacturing site; it is possible to present only the cGMP application for the initial MA submission.

For initial certification, ANVISA performs the inspection in the product manufacturing site. For re-certifications, ANVISA carries out a risk assessment to define the need for a new inspection.

Therefore, consideration should be given to the time Anvisa will take to perform the inspection and issue certification on the project schedule.

Currently, the new API regulation is under public consultation, and it is expected that upon the official publication of the regulation, certification will be required for all APIs. See more details in our post (http://bit.ly/2N1Utcg).

ANVISA is currently working to be a member of PIC/S and has completed one of the necessary steps for this association with the publication, in August 2019, of new regulations establishing drug GMP requirements in line with the PIC/S guidelines.

Colombia

INVIMA requires cGMP from the drug product manufacturing site, as well as Good Laboratory Practice certification (cGLP) for the laboratory that performs quality control for product release, issued by INVIMA itself. For both, inspection by the authority is required. It also accepts the cGMP issued by the authorities recognized by them as reference.

These authorities are the ones from the following countries: United States of America, Canada, Germany, Switzerland, France, England, Denmark, the Netherlands, Sweden, Japan, and Norway.

Mexico

On March 18th, 2021, three of COFEPRIS’ Guidelines were revoked for irregularities in their publication procedures. Among them was the Guideline Establishing Criteria for cGMP.

Thus, in this moment, the Guideline is suspended and the subject is not regulated. (updated on March 29th, 2021).

Even though the Guideline remains suspended, on May 6th, 2021, COFEPRIS published a communication in their website informing that they will begin to recognize decisions on medicines cGMP from Level IV PAHO Agencies and WHO’s Strict Agencies. (updated on May 18th, 2021)

According to the previous version of the Guideline, from March 16th, 2020 COFEPRIS required cGMP from all sites involved in the drug product manufacturing chain, including the API manufacturers. The certification must have been issued by COFEPRIS itself after inspection or by authorities recognized by them as a reference.

In January 2018, COFEPRIS formally became a member of PIC/S. In this way, in August 2018, the recognized authorities ceased to be those previously listed and are now the PIC/S members.

In the update to the Guideline issued in March 2020, the list of recognized authorities was reduced. The authorities now recognized are TGA (Australia), Health Canada (Canada), US FDA (United States of America), MHLW (Japan), MFDS (Korea), MHRA (United Kingdom), Swissmedic (Switzerland) and EMA (Europe). (updated 30th April)

It is important to mention that ANVISA was considered as a reference authority before the update from August 2018, and the GMPc issued by this authority are no longer recognized by COFEPRIS. (updated 30th April)

New certificates must have been presented in all new MA submissions and, in the case of products already approved, at the next renewal of the marketing authorization.

The matter must now go through the entire procedure under Mexico’s Administrative Procedure Law, before it can be regulated. (Updated on March 29th, 2021).

Vita published on its blog the detailed version of GMP certification for Mexico, available through the link: https://bit.ly/2Pd9RWX.

Peru

DIGEMID requires the cGMP from the drug product manufacturing plant issued by DIGEMID itself, upon inspection, or by authorities recognized by them as reference.

DIGEMID recognizes GMPc issued by authorities considered by them as being of high surveillance, as defined by regulation, from the following countries: France, the Netherlands, United Kingdom, United States of America, Canada, Japan, Switzerland, Germany, Spain, Italy, Belgium, Sweden, Norway, Australia, Denmark, Portugal, Republic of Korea, Ireland, Hungary, and Austria.

Bolivia

AGEMED requires the presentation of cGMP for the drug product and accepts the document issued by the authority of the country where the manufacturing site is located.

It is provided by local regulations that the authority may request the inspection of the sites in question if they deem necessary, or may request additional information or the inspection report from the authority of the country of origin or from the applicant.

Venezuela

INH-RR requires the presentation of cGMP for the drug product and accepts the document issued by the authority of the country where the manufacturing site is located.

Considering local experience, although not defined in the requirements checklist, API cGMP presentation was required for a new molecule in the country.

Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama (signatory countries of the Central American Technical Regulation – RTCA)

The authorities of each country follow the requirements set by the harmonized RTCA regulation for drug product MA submissions. Each of them requires the submission of the cGMP for the drug product and accepts the document issued by the authority of the country where the manufacturing site is located.

It is provided by the RTCA that the local authorities may inspect the plants in question if they deem necessary, or recognize the certification of authorities considered to be of high surveillance by the World Health Organization (WHO).

Chile and Cuba

Local authorities in these countries require the submission of cGMP for the drug product and accept the document issued by the authority of the country where the manufacturing site is located.

For more information on the main health authorities in Latin America, check out our post at: https://bit.ly/2kqrnYp.

Count on Vita to assist your company in developing drug products registration and post-registration projects in Latin America.

Contact us: info@vitaraconsulting.com.