HEALTH SERVICES FRAMEWORK AND COMPETENT AUTHORITIES
1 Describe the bodies and their responsibilities (public and private sector) concerned with the delivery of healthcare and appropriate products for treatment.
The Mexican healthcare system comprises public (social security institutions) and private sectors.
The private sector comprises private institutions, insurers and independent professionals, the users of which are not restricted. Individuals and private insurers fund this sector. Private health insurance generally covers professional, executive and higher levels of the private sector. Enrolment in private health insurance has increased considerably over the years. According to official figures, up to 50 per cent of annual health spending in Mexico comes from out-of-pocket payments related to private doctors, insurance and drug acquisitions.
The public sector comprises:
- social security institutions exclusively directed to formal workers, in which the funding comes from contributions by the federal government, the employer and the employee, such as the:
- Mexican Institute of Social Security;
- Institute of Social Security for State Workers;
- specialised public institutions for members of the military and navy force; and
- PEMEX Medical Services, for Mexican petroleum workers; and
- public institutions exclusively directed to attend people not covered by social security, in which the funding comes from the federal government, states and patients, such as:
- the Wellness and Health Institute; and
- state health institutions.
In the public sector, social security and public institutions provide medicines. However, if the medicine is not available when required, some public insurers allow private registered pharmacies to supply prescribed medicines and to request a refund for these.
Competent authorities for authorisation
2 Identify the competent authorities for approval of the marketing of medicinal products and medical devices. What rules apply to deciding whether a product falls into either category or other regulated categories?
The Mexican authority responsible for enforcing the regulatory framework relating to medical products is the Federal Commission for Protection against Sanitary Risk (COFEPRIS), which is part of the Ministry of Health. Within it is the New Molecules Committee and the Subcommittee on Biotech Products, which assess biological medicinal products.
The regulatory framework is set out in the following federal laws:
- the General Health Law;
- the General Health Law Regulations for Healthcare Products;
- the Official Mexican Standards (NOMs);
- the Mexican Pharmacopoeia; and
- COFEPRIS's Rules listing healthcare products that do not require a marketing authorisation in view of its low risk to human health.
Products are classified according to the definitions provided in this legal framework.
3 Describe the general legislative and regulatory framework for approval of marketing of medicinal products and medical devices.
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 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.
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.
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.
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 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.
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.
4 What legislation controls and which rules apply to ethics committee approval and performance of clinical trials in your territory for medicinal products and medical devices?
Further to international guidelines – such as the Nuremberg Code, the Declaration of Helsinki, the World Health Organization guidelines and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines – the General Health Law and its Regulations for Health Research (RLGSMIS) and the Official Mexican Standard (NOM) for Health Research in Human Beings (NOM-012-SSA3-2012) regulate ethics committee approval and performance of clinical trials in Mexico.
Moreover, Mexican health authorities have issued guidelines for ethics committees (the 'Agreement establishing the general provisions for integration and operation of research ethics committees and hospital units that should have them, in accordance with the criteria established by the National Bioethics Commission'). According to these guidelines, committees must be integrated from different specialties and must include professionals from different areas, such as psychology, nursing, social work, sociology, anthropology, philosophy and law.
The Federal Commission for Protection against Sanitary Risk (COFEPRIS) approves ethics committees pursuant to the regulatory framework.
5 What requirements exist for reporting the commencement of a trial and its results to the competent authorities or the public?
Any research on human beings must be approved by COFEPRIS. This research may include testing new medicinal products or new uses, dosages or administration routes for already approved medicinal products. Essentially, the main requirements for an application for authorisation from COFEPRIS are:
- approval by an independent ethics committee registered with the Ministry of Health;
- approval by the medical institution or institutions where the clinical trials will be conducted. These institutions must be approved by COFEPRIS to conduct clinical trials;
- clinical trial protocol (including the schedule and the approximate number of medicinal products to be imported);
- written informed consent templates;
- preclinical and clinical data that justifies conducting the research;
- description of available resources to conduct the research and to address emergencies (including a statement of sponsorship); and
- a written letter by the qualified investigator acknowledging his or her responsibilities, and data from the investigator and his or her staff.
Applications should include details of the time frame of the protocol, indicating the possible dates of commencement and conclusion. The principal researcher must compile a final technical report for the clinical trial. When clinical trials last longer than one year, annual technical reports for the health authorities must be compiled. Medical assistance and financial indemnification for damage caused by the clinical trial must be provided to research participants.
Preclinical data must be collected to justify whether clinical trials can be conducted. The RLGSMIS requires measures to ensure that the investigator does not have conflict of interest to:
- protect the rights of research participants;
- maintain accurate results; and
- allocate resources.
The principal researcher must compile a final technical report for the clinical trial. When clinical trials last longer than one year, annual technical reports for the health authorities must be compiled. Accordingly, the following NOMs apply:
- Medicinal Products Labelling (NOM-072-SSA1-2012);
- Pharmacovigilance (NOM-220-SSA1-2016);
- Interchangeability and Biocomparability Tests (NOM-177-SSA1-2013);
- Biological Products (NOM-257-SSA1-2014);
- Good Manufacturing Practices for Medicinal Products (NOM-059-SSA1- 2015); and
- Good Manufacturing Practices for Active Ingredients (NOM-164-SSA1- 2015).
Consent and insurance
6 Are there mandatory rules for obtaining trial subjects' consent to participate? Must sponsors arrange personal injury insurance to a particular limit?
Investigators must obtain informed consent from the research participants in a formal written document, which must also be signed by two witnesses. In simple terms, the validity requirements for consent are that a participant grants it on a voluntary basis, with capacity to do so and sufficient information (knowing the potential risks and benefits). Participants maintain the right to withdraw from the study at any time. Investigators must ensure post-care for them until it is clarified that no damage arises from the research.
According to NOM-012-SSA3-2012, in relation to clinical trials in human beings, the clinical trial budget should include compensation to which the subject of investigation will be legally entitled in the case of damage directly related to the clinical trial. Where appropriate, this financial fund may be covered by study insurance.
Originally published by Lexology.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.