Marketing authorisation

Time frame

How long does it take, in general, to obtain an authorisation from application to grant, what fees are payable and what is the normal period of validity of the authorisation?

Requirements and time frames vary among new molecules, biologicals and follow-on products. Article 166 of the Health Law Regulations sets out the following approval time frames:

  • 180 calendar days for medicines that include an active pharmaceutical ingredient or therapeutic indication already approved in Mexico;
  • 240 calendar days for medicines approved abroad but not in Mexico; and
  • 180 calendar days for new drugs (a meeting with the New Molecules Committee is required).

 

The approval time frame for biologicals and biosimilars is 180 calendar days (articles 177 and 177-bis(4) of the Health Law Regulations).

These time frames may vary in practice but can be reduced if the application has been pre-examined by a third examiner (private company) approved by the Federal Commission for Protection against Sanitary Risk (COFEPRIS) to do so.

Government fees for analysing marketing authorisation applications are as follows:

  • new molecules and biologicals: around US$8,600; and
  • generics and biosimilars: around US$4,800.

 

Drug manufacturers must renew their licence every five years, subject to the relevant tests, including submission of a certificate of good manufacturing practices (GMP) in force.

Protecting research data

What protection or exclusivities apply to the data submitted by originators to gain initial approval and, on variation or new application, to add indications or pharmaceutical forms?

There is no specific body of local legislation for data protection exclusivity (RDP) in Mexico. In 2012, COFEPRIS issued internal guidelines to provide a five-year term of protection that only covers new chemical entities. However, the reliability of these guidelines is still uncertain.

Some cases are brought before the federal courts, which decide whether the health authorities have to observe RDP in respect of the product of interest for a five-year period set forth by the North American Free Trade Agreement (NAFTA) and the United States-Mexico-Canada Agreement (USMCA). Within the corresponding cases, preliminary injunctions are requested so that COFEPRIS observes the requested RDP until the merits of the case are decided. The granting of these injunctions is subject to the criterion and discretion of the court handling the case.

Based on the interpretation of international treaties, RPD for at least five years for new chemical entities, formulations, new indications, and orphan drugs has been obtained through litigation.

Concerning biologics, longer periods of RDP have been requested based on NAFTA (which provides that this protection should be at least five years) and international comparative law; however, the analysis in this regard is done on a case-by-case basis.

The new USMCA entered into force on 1 July 2020. This treaty will have an impact on the current situation concerning RDP in Mexico. 

The USMCA used to describe the periods of protection more clearly than the current NAFTA; however, the amendments to the USMCA completed on December 2019 eliminated the provisions for new formulations or combinations, and new method of administration: at least three years, at least 10 years for biologics, and at least five years for new chemical molecules, with a transition period of five years.

Without those specific provisions, and with no domestic law, uncertainty among the generic and innovative pharmaceutical industries continues. To obtain this protection, litigation would still arise against the eventual refusals of COFEPRIS to recognise regulatory protection for more than five years for biologics and at least three years for new indications.

The amendments to the USMCA will not necessarily result in adverse decisions since the wording of NAFTA ‘establishing at least five years of protection’ remains the same as it has been since 1994 with NAFTA.

Moreover, there are favourable precedents with the NAFTA wording, obtaining more than five years of RDP for biologics. Therefore, the main grounds for a legal action trying to obtain more than five years RDP for biologics also remain. 

The Agreement on Trade-Related Aspects of Intellectual Property Rights is still in force and is implemented through the Code of Commerce. In addition, the internal guidelines issued by COFEPRIS and several favourable legal precedents in this regard remain.

Other international treaties will be in force, including the treaty between Mexico and the European Union that binds the parties to recognise at least six years of RDP for both small molecules and biologics, although this treaty is not yet in full force.

Finally, the RDP provisions of the Comprehensive and Progressive Agreement for Trans-Pacific Partnership have been suspended.

Freedom of information

To what extent and when can third parties make freedom of information applications for copies of research data submitted by applicants for authorisation to market medicinal products or medical devices?

According to the General Law of Access to Public Data, personal data and all data of applications under assessment are classified. Thus, health authorities usually reject freedom of information applications for data contained in marketing authorisation applications for medicinal products and medical devices. However, in some cases, they may allow release of certain information that is considered public information.

Regulation of specific medicinal products

Are there specific rules for approval, and rewards or incentives for approval, of particular types of medicinal products, such as traditional herbal and homeopathic products, biologicals and biosimilars, controlled drugs, orphan drugs and those for paediatric use?

Pharmaceutical productsNew molecules

Applicants for marketing authorisations must prove the safety and efficacy of their products through standard clinical trials, according to the rules set out by the General Health Law, its regulations and the Official Mexican Standards (NOMs) of good manufacturing of medicines and active ingredients, as well as the approval of their products as new molecules from the New Molecules Committee.

 

Generics

Applicants for marketing authorisations must prove that their products are bioequivalent to the innovator product. The NOM setting the test to prove that a generic drug is interchangeable with a reference drug was updated in recent years (NOM–177–SSA1–2013).

There is a linkage system between COFEPRIS and the Mexican Institute of Industrial Property, which aims to prevent the granting of marketing authorisations in violation of patent rights.

 

Biologics

Further to legal and administrative information, the essential dossier submission requirements for innovative products manufactured in Mexico are preclinical and clinical trials, certificates of good manufacturing practices (GMP) of the active pharmaceutical ingredient and the medicinal product, analytical methods, summaries, the manufacturing licence, prescription information, the label and a pharmacovigilance programme.

For innovative products manufactured abroad, additional requirements apply, in particular, a certificate for export, a letter of representation with apostille and a legal representative with an address in Mexico. In cases where the GMP certificates are not issued by an agency recognised by COFEPRIS, such as the US Federal Drug Administration or the European Medicines Agency, an inspection in situ will be required.

 

Biocomparables (follow-ons)

The essential dossier submission requirements for biocomparables are almost the same as those for innovative biotech products, except for the requirements to prove safety, efficacy and quality.

For these purposes, biocomparable applicants must submit:

  • in vitro studies or comparative non-clinical studies;
  • a report of a comparative test of pharmacokinetics, if determined by the Ministry of Health, to show pharmacokinetic comparability on key parameters between both the follow-on and the product of reference;
  • pharmacodynamics test reports; and
  • comparative efficacy and safety clinical tests to show similarity between both the follow-on and the product of reference.

 

Once approved, close pharmacovigilance should be followed.

 

Orphan drugs 

Orphan drugs were introduced into the General Health Law and the Mexican Pharmacopeia some years ago. In practice, they are approved by a particular procedure, following rules for new molecules when applicable and appropriate; however, specific rules would be welcomed.

 

Medical devices

Marketing authorisation requirements for medical devices depend on the level of risk involved in their use, according to a threefold classification:

  • Class I: products that are well known in medical practice and for which safety and efficacy have been proven. They are not usually introduced into a patient’s body;
  • Class II: products that are well known in medical practice, but may have material or strength modifications. If introduced, they remain in a patient’s body for less than 30 days; and
  • Class III: products either recently accepted in medical practice or that remain in a patient’s body for more than 30 days.

 

COFEPRIS analyses all medical devices and, if applicable, the software that enables them to work. Mobile medical applications are a new area that COFEPRIS may address in the future with particular regulations, especially if they present health risks.

Post-marketing surveillance of safety

What pharmacovigilance or device vigilance obligations apply to the holder of a relevant authorisation once the product is placed on the market?

The NOM for pharmacovigilance, NOM-220-SSA1-2016 (NOM-220), establishes mandatory provisions regarding pharmacovigilance that apply to all medicines.

NOM-220 requires marketing authorisation holders to have a pharmacovigilance plan, which must include provisions for monitoring adverse effects in patients caused by the product at every stage of treatment.

The notice of adverse effects (grade 2) must detail the product’s international non-proprietary name, distinctive name, batch number and manufacturer’s name.

The National Commission for Pharmacovigilance should verify the plan to manage risks and, if applicable, require the implementation of an intensive pharmacovigilance plan.

Regarding medical devices, the marketing authorisation holder is required to have registered a technovigilance unit before COFEPRIS. The unit should have manuals and standard operating procedures. A qualified person, who should receive, sort and report adverse effects, should be in charge of the unit.

Other authorisations

What authorisations are required to manufacture, import, export or conduct wholesale distribution and storage of medicinal products and medical devices? What type of information needs to be provided to the authorities with an application, what are the fees, and what is the normal period of validity?

Companies manufacturing medicinal products in Mexico must be approved by COFEPRIS through a manufacturing licence or authorisation. Manufacturers must renew their licence every five years, subject to the relevant tests, particularly regarding GMP.

Any import of drugs, health products or raw materials for drugs must be approved by COFEPRIS. A marketing authorisation is needed unless an exemption applies. The import of a minimal quantity of products without a marketing authorisation can be approved in certain circumstances (eg, for clinical trials and orphan drugs).

Foreign marketing authorisations are not valid in Mexico. However, COFEPRIS has developed a special procedure for drugs requiring first-time approval in Mexico but that have been approved by equivalent regulatory authorities abroad. In this procedure, the approval requirements of the foreign agencies are recognised as equivalent to those in Mexico.

Sanctions

What civil, administrative or criminal sanctions can authorities impose on entities or their directors and officers for breach of the requirements concerning controlled activities?

COFEPRIS can request reports from marketing authorisation holders and make on-site inspection visits of the manufacturing, distribution or storage facilities.

COFEPRIS can initiate ex officio legal proceedings to sanction non-compliance. Ultimately, these legal proceedings can result in the revocation of authorisations. COFEPRIS is also entitled to implement measures on behalf of public health, such as the seizure of products and ordering partial or total suspension of activities, services or advertisements. Under certain conditions, COFEPRIS has statutory authority to revoke any manufacturing approval or impose sanctions, ranging from a fine of up to 16,000 times the minimum wage to the closure of the corresponding establishment or facility.

The imposition of administrative sanctions does not exclude civil and criminal liability. Administrative infringers can incur penalties ranging from a fine of up to 20,000 times the minimum wage to final closure of the establishment. Repeated infringement is also considered to be a criminal offence.

COFEPRIS has broad jurisdiction to seize counterfeit or illegal medicines. The General Health Law classifies the manufacturing and sale of counterfeit or falsified medicine as a crime. In addition, COFEPRIS commonly enters into collaboration agreements with the General Attorney and the Customs Office to investigate and prevent counterfeit and illegal medicine activities.

Exemptions

What, if any, manufacture and supply of medicinal products is exempt from the requirement to obtain an approval to market?

No medicinal product is exempt from requiring marketing authorisation in Mexico unless it is a magistral formula, which is a medicine compounded in a local pharmacy to fit the unique need of a patient according to a detailed facultative prescription of a physician, under certain conditions and requirements, such as the requirement that the pharmacy needs regulatory approval to do so.

Parallel trade

Are imports allowed into your jurisdiction of finished products already authorised in another jurisdiction, without the importer having to provide the full particulars normally required to obtain an authorisation to market? What are the requirements?

The import of medicinal products requires a marketing authorisation, unless an exemption applies. These exemptions for medicines are essentially for lab tests, clinical trials, raw materials for assembly processes for export, special treatments for illnesses with low prevalence and social interest, personal use and donations.

Regarding medical devices, the exceptions are essentially lab tests, clinical trials, personal use, physician use, donations and used devices.

In January 2020, the Ministry of Health published a decree in the Official Gazette whereby the government allows the importation of medicinal products already authorised in another jurisdiction (the United States, Canada, Switzerland and the European Union). Certain requirements must be complied with before importation.