martes, 22 de octubre de 2013

DEVICE REGULATION & THE HARMONISATION PROCESS IN LATIN AMERICA

There are 23 countries in Latin America (Argentina, Belize, Bolivia, Brazil, the Caribbean [Antilles], Chile, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay and Venezuela) with a total population of approximately 517 million people. The main language in this region is Spanish, although Brazil – with a consumer market of 100 million people – speaks Portuguese.
Latin America is an important region for the medical devices consumer market, particularly with regard to imported products as there are few local industries working with cutting-edge technology, particularly taking into account the proportion of the population in the region.
With regard to the regulations covering medical devices, Latin America offers certain challenge to companies, particularly foreign corporations wishing to build up a presence in the various countries in this region. This is because there are many different procedures and regulations to be followed when gaining approval for medical devices due to the autonomy of the Latin American nations and the lack of international pacts among them in this sector.
It is worthwhile stressing that a company wishing to sell a medical device in Latin America must obtain marketing authorisation for its product in each country, in compliance with local procedures and documentation. The procedures and documentation for regulating medical devices vary from one country to another. This means that a company wishing to sell medical devices in Latin America should be fully familiar with local laws in order to bring the authorisation procedures for its product to a successful conclusion within a reasonable length of time.
Familiarity with local culture is another important tool for understanding the regulations in a given country. Frequently, gaps in this understanding result in delays in gaining regulatory approval for medical devices in the Latin American countries. This is why special care is urged for companies interested in this region in terms of complying with the laws of each country as well as noting political and cultural aspects. Ideally, the company should build up a regulatory team with local representatives able to respond efficiently to the demand for each country, particularly in terms of dossier preparation.
Experience has shown that many of the problems occurring during the authorisation of medical devices in the Latin American countries are due to a lack of familiarity with local laws. It is not uncommon to see companies submitting their products for registration based on the documentation stipulated by regulatory agencies in other countries such as the US Food and Drug Administration (FDA), almost completely ignoring local requirements established through specific laws.
Product classification criteria are other crucial factors to consider when authorising medical equipment. For instance, one Latin American country may exempt a medical device from registration and consequently not require the presentation of much technical information on the product in order to authorise it. However, another country in the region may handle the same product quite differently as it may lack the same scientific experience or understanding, and may consequently require the product to be registered, backed up by a series of scientific documents on the technology used, in order to ensure its quality, safety and effectiveness. Consequently, a product may be classified differently among the various countries in the region.
Nevertheless, it is noted that even today, many companies are still exporting medical devices to the Latin American countries before gaining authorisation from the local authorities, and are quite unaware of local regulations and specific authorisation requirements. Familiarity with the laws of each country in the region should consequently be rated as a crucial factor for successful sales of medical devices and should in fact form an integral part of corporate business plans, in order to avoid the risk of losses while ensuring success with the business as a whole.

Harmonisation Process
Many of the countries in Latin America have signed the Agreement on the Application of Sanitary and Phytosanitary Measures resulting from the General Agreement on Tariffs and Trade, and prompting massive efforts to harmonise local legislation with that of the other members of the World Trade Organisation (WTO). However, the participation of many of these countries in discussion forums such as the Global Harmonisation Task Force have not resulted in any specific document being signed by the Latin American countries to ensure uniform understanding and reciprocal actions, particularly with regard to a specific single format for the dossier filed to register medical devices in the many different countries in this region.
Accordingly, the process of harmonising regulations and construing procedures has been followed in a far more individual manner by each country in Latin America rather than as a regional bloc, meaning that the results have shown that as international discussions progress in this sector, the trend is for each country to fine-tune its legislation individually, adapting it to understandings that are internationally accepted although without such understandings being reciprocal and uniform with the decisions taken by the countries in the region.
Under the Mercosur [Argentina, Brazil, Uruguay and Paraguay] Southern Cone Market Treaty, some significant technical regulations have been established in the medical devices sector through the following Resolutions:

· GMC No 40/00 (Registration of Medical Products);
· No 04/95 (Good Fabrication Practices for Medical Products);
· No 131/96 (Good Fabrication Practices for Medical Products);
· No 21/02 (Inspection System for the Manufacturers or Importers of Medical Products);
· No 21/98 (Operating Licence for a Company Manufacturing and/or Importing Medical Products);
· No 72/98 (Essential Safety, Security and Efficacy Requirements for Medical Products);
· No 79/96 (Diagnostic Products for In Vitro Use);
· No 65/96 (Good Fabrication and Control Practices for In Vitro Diagnostic Reactive Agents); and
· No 38/98 (Scope of Application for the Mercosur Technical Regulations).

Despite the technical standards established under the aegis of Mercosur, companies must still authorise their medical devices in each member country in compliance with local laws and local documentation requirements.
There is no specific control entity covering the medical devices sold in the Mercosur member countries. This means that, at the Mercosur level, the public health entities controlling medical devices in each country are jointly responsible. In Brazil this is the National Sanitary Surveillance Agency (ANVISA, Agência Nacional de Vigilância Sanitária), in Argentina this is the National Medications, Foods and Medical Technology Administration (ANMAT, Administración Nacional de Medicamentos, Alimentos y Tecnología Médica), in Paraguay, the Ministry of Public Health and Social Wellbeing (Ministerio de Salud Pública y Bienestar Social) and in Uruguay, the Ministry of Public Health (Ministerio de Salud Pública).
Under the aegis of the North American Free Trade Association (NAFTA) pact, no specific document has yet been drawn up for the public health sector, far less for medical devices. It is expected that the NAFTA meetings in this sector will progress as the time draws near for this trade agreement to enter into effect.

Definitions
The successful completion of the authorisation process for medical devices in the Latin American countries tends to be proportional to a solid understanding of some important legal and regulatory concepts for this sector. This understanding consists mainly of correctly identifying the documents required by the local authorities. As a result, in-depth familiarity with the regulatory concepts in a specific country will result in more effective technical and scientific talks and negotiations with local professionals, particularly the authorities in charge of authorising the products.
The first and most fundamental concept that should be borne in mind for authorising medical devices in Latin America is the ‘risk to human health’.
According to Articles 3 and 5 of the Agreement on the Application of Sanitary and Phytosanitary Measures, the WTO member countries will ensure that their measures do not constitute arbitrary or unjustified discrimination, and that they are applied in a manner that does not impose clandestine constraints on international trade. Consequently, all public health measures will be based on a proper assessment of the circumstances and the risks to human, animal or plant health or life, taking into consideration the risk assessment techniques drawn up by international entities, with the members taking the available scientific evidence into consideration when assessing risks.
This means that the concept of public health risk is crucial for the progress of discussions with the sanitary control authorities, particularly in the Latin American countries where outdated laws are very common and have not kept up with modern technological trends.

Brazil
According to Brazilian Law, a ‘healthcare product’ is defined as an equipment, device, material, article or system for medical, dental or laboratory use or application, intended for the purposes of prevention, diagnosis, treatment, rehabilitation or birth control and that does not make use of any pharmacological, immunological or metabolic means to perform its main function in human beings, although it could do so.
Resolution RDC No 185, dated 22 October 2001, lists the current procedures for registration, alteration, revalidation and exemptions of medical products registration. This Resolution is applicable to all medical products defined in item 13 of Annex I to the Technical Regulations and ancillary rules defined in item 01 of Annex I, including parts of these products. A ‘part of a medical product’ is taken as meaning a component manufactured solely for the purpose of integration with the product, without which this product does not function, and that may be separated and handled by the user or operator as indicated in the product’s instructions for use.
This Resolution is also applicable to other products defined as ‘correlated’ by Law No 6, 360/76 and Decree No 79, 094/77, including equipment, devices, materials, articles, systems for use or application in physical education, beauty care or aesthetic correction, but excluding reagents for in vitro diagnosis (reagents for clinical analysis laboratories).

Risk rating
For the purposes of applying the registration procedures stipulated in Resolution RDC No 185/01, in item 3.3 of the Form in Annex III.A of the Technical Regulations, the company should state the classification of its product as low risk (Class I), medium risk (Class II), high risk (Class III) or maximum risk (Class IV), applying the classification rules listed in Annex II to the Technical Regulations.

Documentation
The essential basic documents required from the local agent of the foreign company for the registration of products in Brazil are:

a) Application form obtained from the Brazilian Ministry of Health.
b) Original copy of the machine stamped bank slip, which serves as proof of the registration fee payment.
c) Trade Permit (Alvará de Funcionamento) issued by the State authority to the manufacturer’s distributor.
d) Same type of document (Autorização de Funcionamento), issued by the Federal authority to the manufacturer’s distributor.
e) Document showing the technical responsibility of the distributor/manufacturer, issued by the certification entity.
f) Technical Report on the product providing information on the components of, for example, the design/formulation, instructions, directions and cautions.
g) Label sample, brochures and pertinent information about the products, all translated into Portuguese.
h) For products not clearly specified in Brazilian law, it is mandatory to provide information about their utilisation in order to demonstrate efficacy and safety.
i) Copy of the registration granted to the product in the country of origin (or copy of the Certificate of Free Sale).
j) Copy of legal document by which the manufacturer authorises its distributor to trade and distribute the products.
k) A declaration of Good Manufacturing Practices.
l) In the case of a medical equipment, all documents showing product safety, country of origin, comprehensive details of the equipment’s component parts, and the user manual have to be presented for registration.

Among the above requirements, special attention should be paid to the technical report, which must contain the following information:

a) A complete description of the product’s design/formulation, with all the components specified by their chemical designation, and the quantities of each one of them expressed in the metric system.
b) Information on the function of each component, and its function as an integral part of the healthcare product.
c) Name of the components stated in accordance with Pharmacopoeial Standards, Brazilian and International Compendia, or attached bibliography discussing the component and pertinent literature, including safety rules and efficacy. This information must be translated into Portuguese.

Argentina
According to Argentinian Law, a ‘healthcare product’ is an equipment, device, material, article or system for medical, dental or laboratory use or application intended for prevention, diagnosis, treatment, rehabilitation or birth control and that does not make use of any pharmacological, immunological or metabolic means to perform its main function in human beings, although it may be assisted in its functions through such means.
Pursuant to Provision 1285/2004, medical products are classified into Classes I, II, III or IV by the intrinsic risk that they offer to the health of the consumer, the patient, the operator or third parties involved.
The registration of all medical products is mandatory, except for the following:

· Medical products intended for clinical research, complying with the legal provisions established by the Competent Public Health Authority for these activities, with their sale and/or use for other purposes being forbidden.
· New presentations consisting of a set of registered medical products whose label and/or instructions for use should contain information on the medical products in question.
· An accessory produced by a manufacturer solely for integration with another medical product that is already registered where the technical registration report for this medical product contains information on this accessory. New accessories may be attached to the original registration on provision of detailed descriptions of their functions, actions and content.

In order to apply for registration of medical products classified under Classes I, II, III and IV, manufacturers or importers should present the following documents to the Competent Public Health Authority:

a) Documentary proof of payment of the corresponding fee.
b) Information for identifying the manufacturer or importer and the medical product, declared and signed by the duly accredited legal representative and the technical expert in charge.
c) A copy of the intra- or extra-zone authorisation of the manufacturer or exporter, allowing the importer to sell its medical product in the country receiving the product. When authorised by the exporter, the importer should demonstrate the commercial relationship between the exporter and the manufacturer.
d) For imported medical products, documentary proof of registration or Certificate of Free Sale or equivalent document granted by the Competent Authority in the country where the medical product is manufactured and/or sold.
e) Documentary proof of compliance with the legal provisions stipulated by the technical regulations, pursuant to the law regulating this matter.

Manufacturers or importers requesting the registration of medical products classified into Class I should present the documents listed in items (a), (b) and (e) to the Competent Public Health Authority.
The Public Health Authorities will have a period of no more than 180 days to assess the documentation and respond to the applicant. The registration of medical products will be valid for five years and may be revalidated successively for a similar period. An application should be supported by the following documentation:

Class I products
a) Documentary proof of payment of tax.
b) Information identifying the manufacturer or importer and the medical product described in Annexes III.A, III.B and III.C of Provision 2319/02, declared and signed by the duly accredited legal representative and the technical expert in charge.
c) Documentation proving compliance with the technical standards specific to the product, if any (for example, technical regulations for hypodermic syringes or condoms), in the original or notarised copy.
d) For imported medical products, documentary proof of registration or Certificate of Free Sale or equivalent document granted by the Competent Authority in the country where the medical product is manufactured and/or sold (only for the USA, Canada, Japan, EU and Australia). For products originating in Brazil, a Good Manufacturing Practices (BPF) Certificate issued by the public health authorities (ANVISA) and an electrical safety certificate issued by a laboratory acknowledged by ANMAT, where applicable, are required. For products originating in other countries, the establishment must have a Good Manufacturing Practices (BPF) Certificate issued by ANMAT.

Class II, III and IV products
a) Documentary proof of payment of tax.
b) A copy of the intra- or extra-zone authorisation of the manufacturer or the exporter allowing the importer to sell its medical product in the country receiving the product. When authorised by the exporter, the importer should demonstrate the commercial relationship between the exporter and the manufacturer (original or notarised copy, with the corresponding notarization and translation by a sworn translator, when required).
c) Documentation proving compliance with the technical standards specific to the product, if any (for example, technical regulations for hypodermic syringes or condoms), in the original or notarised copy.
d) For imported medical products, documentary proof of registration or Certificate of Free Sale or equivalent document granted by the Competent Authority in the country where the medical product is manufactured and/or sold (only for the USA, Canada, Japan, EU and Australia). For products originating in Brazil, a Good Manufacturing Practices (BPF) Certificate issued by the public health authorities (ANVISA) and an electrical safety certificate issued by a laboratory acknowledged by ANMAT, where applicable, are required. For products originating in other countries, the establishment must have a Good Manufacturing Practices (BPF) Certificate issued by ANMAT.

Venezuela
All equipment or material used in human medicine should be subject to registration or control by the public authorities in the country of origin, in order to ensure that such equipment or material is ‘safe, secure and effective’.
In Venezuela, the registration and control of medical equipment and materials is regulated by Resolution No DM-001 0-99, dated 21 September 1999 (Government Gazette No 36, 843, dated 3 December 1999).
Article 1 of this Resolution stipulates that ‘[a]ll corporate legal entities legally established in Venezuela and wishing to manufacture, import, sell or render maintenance services for materials and equipment used at the various levels in the healthcare area should be registered in advance on the National Sanitary Register, kept by the Healthcare Professions, Establishments, Equipment and Materials Control Regulation Administration, under the General Sector Administration of the Sanitary Control Bureau’.
In turn, Article 4 stipulates that ‘[t]he materials and equipment used in the human healthcare area should be registered with the corresponding Administration of this Ministry as stipulated in Article 1 of this Resolution’.
Among the items required to obtain such registration, the applicant should present a Quality Certificate issued by an accredited institution (Article 6, f).
In order to comply with this legal requirement, the Venezuelan State has approved certain institutions with specialised staff and infrastructure to handle the procedures that lead to the issue of the required certificate, based on the above-mentioned principle of ‘safety, security and effectiveness’. These institutions include the Simón Bolívar University. The safety and security of medical materials or equipment are subject to the criteria used by the specialist analyst, and where effectiveness may depend on complying with the functions for which they were designed and built, pursuant to the technical specifications issued by the manufacturer (meaning that the equipment functions as intended). These two elements are sufficient to provide new grounds for issuing the Quality Certificate.

Documentation
a) Company registration with the public health authorities.
b) Certificate of Free Sale for the product to be registered, issued by the authorities in the country of origin.
c) Power to import, manufacture or register the product in Venezuela, granted by its proprietor to the company applying for registration with the public health authorities.
d) Certificate of compliance with Good Manufacturing Practices issued by the Competent Authorities in the country of origin.
e) Certificate of analytical trials and/or clinical surveys proving the quality and efficacy of the described characteristics of the product, performed in the country of origin, appending protocols certifying to its quality, stability and/or activity, ensuring the confirmation of the product, as applicable.
f) Quality Certificate and protocol for the analysis, providing satisfactory documentary evidence of the product characteristics, issued by one of the institutions accredited by the Ministry of Health and Social Development.

Mexico
According to Mexican Law, ‘health products’ are devices, accessories and instruments for specific purposes, intended to provide medical care, surgery, exploratory diagnostic treatment and rehabilitation procedures in patients, as well as those intended for biomedical research purposes.
The general purpose of the authorisation process is to grant public health registration to medical devices whose therapeutic efficacy and safety have been proven through scientific methodology acceptable to the international community, and which comply with the requirements stipulated in the General Healthcare Act and other applicable provisions for the benefit of the Mexican people.
Materials are classified by risk for public health registration purposes into Class I, Class II and Class III, pursuant to Article 82 of the Healthcare Input Materials Regulations.
Taking into account the provisions in Article 194 of the General Healthcare Act, it is important to note that the documentation should be submitted prior to forwarding the application for preliminary review and guidance, in order to ensure that the application moves ahead smoothly.
Specific documents and data that should be included or appended to the application are:

a) Scientific and technical information demonstrating that the item is safe, secure and effective.
b) The draft label, written in Spanish, pursuant to the corresponding standard.
c) Instructions for use, if any, or operating manual, written in Spanish.
d) A description of the manufacturing process.
e) A description of the structure, materials, parts and functions of any medical equipment.
f) A declaration of Good Manufacturing Practices.
g) Laboratory evidence to ascertain the specifications of the item.
h) Bibliographical references.
i) Other documentation stipulated by the Bureau in the corresponding standards.

In order to obtain public health registration for items manufactured abroad, in addition to complying with the requirements listed above, an application should be submitted in the official format, attaching the following documentation:

a) Certificate of Free Sale or equivalent issued by the public health authority in the country of origin.
b) A letter of representation issued by the manufacturer if the product is not manufactured by the head offices, plant or laboratory applying for registration in Mexico.
c) Certificate of Good Manufacturing Practices issued by the public health authority in the country of origin.
d) Original analysis certificate issued by the company preparing the product, with its company stamp, signed by the chemist in charge of the foreign company.

Chile
There are no legal registration requirements for medical devices as there are for pharmaceutical products, meaning that they may be sold freely with no authorisation issued by the Public Health Institute, pursuant to Law No 19, 497 and Regulation 825/98.
Companies wishing to assess the details of their products may do so at the Diagnostic Reactive and Medical Devices Sub-Department, on a free and voluntary basis, in order to carry out a conformity check which consists of ascertaining, for example, the composition, planned use, manufacturer quality certificates, FDA certificates or those issued by some other agency showing that the product is a medical device. Finally, the Sub-Department issues the certificate and an annex summarising all the technical information on the device.

by Eliana Silva de Moraes is an attorney specialising in food and drug law for the Latin American region.

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