SECOND SECTION MINISTRY OF HEALTH DECLARATIONS

Transcription

1 Tuesday October 26 th, 2010 OFFICIAL JOURNAL (Second Section) SECOND SECTION MINISTRY OF HEALTH AGREEMENT to recognize that the requirements set forth under articles 179 and 180 of the Regulations for Health Supplies, and that the technical assessment procedures carried out by the Federal Commission for the Protection against Sanitary Risk are equivalent to grant the registration for health supplies under Chapter IX, Title 2 of the Regulations for Health Supplies, to the requirements set forth under sections 510 (k) and 514 of the Federal Food, Drug and Cosmetic Act and by Title 21, Chapter 1, Subchapter H of the Code of Federal Regulations of the United States of America, as well as those set forth by the Food and Drug Act and the Medical Devices Regulations of Canada to allow to market medical devices in their territory, and to the tests and inspections carried out by the Food and Drug Administration of the United States of America and by Health Canada of Canada in order to allow to market medical devices in their territory. On the margin a seal with the National Crest, this reads: United Mexican States. - Ministry of Economy.- Ministry of Health. BRUNO FERRARI GARCIA DE ALBA, Secretary of Economy and JOSE ANGEL CORDOVA VILLALOBOS, Secretary of Health, based on the provisions under articles 34 fractions I, II and XXXI and 39 fractions VII, XXI and XXIV of the Organic Law of the Federal Public Administration; 4 and 69-C of the Administrative Procedure Federal Law; 4 fraction III and 5 fraction XIII of the Foreign Trade Law; 3 fraction XXIV, 13 paragraph A fraction II, 17 bis fractions IV and VI, 194, 194 bis, 204 and 376 of the General Health Law; 161 bis of the Regulations for Health Supplies; 5 fraction XVI of the Ministry of Economy Internal Regulations and 7 fraction XVI of the Ministry of Health Internal Regulations, and DECLARATIONS As per articles 4 fraction III and 5 fraction XIII of the Foreign Trade Law, it is the obligation of the Ministry of Economy to establish and modify measures to regulate or restrict the exports or imports of merchandise by means of agreements issued by this Agency, or if appropriate, together with the competent authority, and published on the Federal Official Journal; As per article 17 bis of the General Health Law, the attributes for the regulation, control and sanitary development appertaining to the Ministry of Health as per the General Health Law, the Organic Law for the Federal Public Administration and other applicable ordinances, among which we can find the assessment, issuance or annulment of the sanitary registration for health supplies, are exerted by the Federal Commission for the Protection against Sanitary Risk; As per the provisions under articles 204 and 376 of General Health Law, medications and other health supplies, require for their sale and supply, the corresponding sanitary authorization in the mode of a sanitary registration; It is fundamental to grant Mexican people access to the medical equipment, prosthetics, orthotics, functional aids, diagnostic agents, dental supplies, surgery material, medical supplies, hygiene products and other medical devices, with the world s latest technology in the quickest way possible; A considerable portion of the Medical Devices that are marketed in Mexico obtain their pre-registration in the United States of America and Canada; Article 161 bis of the Regulations for Health Supplies sets forth that the Ministry of Health may issue general provisions with the purpose of recognizing that the requirements, tests, assessment procedures and other requirements requested by foreign sanitary authorities to allow them to sell, distribute and use the supplies under the national regulations for Health Supplies in their corresponding countries, are equivalent to those that the General Health Law, the Regulations for Health Supplies and other applicable provisions request in order to guarantee the quality, safety and efficacy that said supplies must meet to get a sanitary registration in the country; The implementation of a mechanism of recognition of equivalence as per article 161 Bis of the Regulations for Health Supplies, enables the aforementioned supplies to enter the Mexican market in a more expedite manner, with the same level of quality, safety and efficacy granted to the users by the assessment carried out by the Federal Commission for the Protection against Sanitary Risk, of the requirements to obtain

2 (Second Section) OFFICIAL JOURNAL Tuesday October 26 th, 2010 the sanitary registration of these supplies, covered in the General Health Law, the Regulations for Health Supplies and other legal provisions that may be applicable; Article 69-C of the Administrative Procedure Federal Law sets forth that the heads of the agencies of the Federal Public Administration may, by means of general agreements published in the Federal Official Journal, set lower response times within the maximum provided in laws and regulations and not to demand the submittal of data and documents provided in the corresponding provisions, when the said information can be obtained by other means; On September 3 rd, 2010 it was published in the Federal Official Journal, the Agreement where the general provisions are set forth which must be fulfilled by the Ministry of Health in order to issue the administrative agreements for recognizing that the requirements, tests, assessment procedures and other requirements requested by the foreign sanitary authorities, to allow them to sell, distribute and use the health supplies in their corresponding countries as referred to under article 194 Bis of the General Health Law, are equivalent to those that the General Health Law, the Regulations for Health Supplies and other applicable legal and technical provisions request, in order to guarantee the quality, safety and efficacy that said supplies must meet to get a sanitary registration in our country, the extension of their registration or any modification to the conditions in which they were registered; In the case of the Medical Devices that have been approved for their sale in the United States of America and Canada by the Food and Drug Administration (FDA) and by Health Canada (HC) respectively, the sanitary Mexican authorities may have access to the relevant information regarding safety and efficacy of these by means of documents required to the applicants of a sanitary registration who have previously obtained the corresponding authorization in the United States of America and Canada in the terms provided in this Agreement; The Federal Commission for the Protection against Sanitary Risk, numeral second of the Agreement where the general provisions are set forth which must be fulfilled by the Ministry of Health in order to issue the administrative agreements to recognize that the requirements, tests, assessment procedures and other requirements requested by the foreign sanitary authorities to allow them to sell, distribute and use the health supplies in their corresponding countries as referred to under article 194 Bis of the General Health Law, are equivalent to those that the General Health Law, the Regulations for Health Supplies and other applicable legal and technical provisions request, in order to guarantee the quality, safety and efficacy that said supplies must meet to get a sanitary registration in our country, the extension of their registration or any modification to the conditions in which they were registered, published in the Federal Official Journal on September 3 rd, 2010, has carried out the necessary actions to assure that the requirements and controls set forth in the regulations and foreign documents mentioned in the numeral second of this Agreement, adequately comply with the objectives of the Regulations for Health Supplies, as long as they are oriented to manufacturing Medical Devices of good quality, safety and efficacy within the terms provided under article 179 of the Regulations for Health Supplies; due to the following reasons: I. The medical devices in the United States of America are classified in conformance to Annex I of the present Agreement, and in Canada, they are classified in conformance to Annex II of the present Agreement, establishing in both countries, more stringent requirements for its commercialization as they move on from Class I to Class III in the case of the United States of America, and from Class II to Class IV in the case of Canada. II. III. In the United Mexican States the Medical Devices from Class I to Class III are subject to the requirements set forth under articles 179 and 180 of the Regulations for Health Supplies in order to obtain the sanitary registration. In the United States of America the medical devices Class I are subject to the following general controls which guarantee their quality, safety and efficacy in a verifiable manner for the Mexican sanitary authorities: Registration of the establishment, and Medical devices manufacturers quality system requirements.

3 Tuesday October 26 th, 2010 OFFICIAL JOURNAL (Second Section) IV. In the United States of America the Class II medical devices are subject to the following controls, general and special, which guarantee their quality, safety and efficacy in a verifiable manner for the Mexican sanitary authorities: (v) Registration of the establishment Medical device manufacturers quality system requirements. Notification, previous to the Premarket Notification [510 (k)] with information which allows to determine that the design, material, chemical composition, energy source, manufacturing process or destined use of the corresponding medical device, is substantially equivalent to the one of a medical device which is already in the American market and that has also been subjected to an approval prior to its Premarket Approval. Reference to the performance standards issued by the Department of Health and Human Services in conformance with the Federal Food, Drug and Cosmetic Act for every type of medical device, and to any voluntary standard to which it may apply, and adequate information in order to prove that the device fully meets these standards or information to substantiate the deviation of such standards, and Requirements of guides issued by the FDA specifically for every type of medical device. V. In the United States of America the Class III medical devices are subject to the following controls, general and special, which guarantee their quality, safety and efficacy in a verifiable manner for the Mexican sanitary authorities, as well as the requirements and controls for the Premarket Approval: VI. (v) Registration of the establishment Medical device manufacturers quality system requirements. Premarket Approval which includes the following requirements and controls: a) Reports of all the information regarding the research that has been carried out in order to prove that the device is safe and effective, including pre-clinical lab studies and clinical studies carried out on humans, along with its conclusions; b) Detailed description of the components, ingredients, properties, indications for use and operating principles of the device; c) Description of the methods, installation and controls used in the manufacturing, making, packaging and installation of the device; d) Description of alternative practices and procedures to treat the ailment or condition which the device is intended for; e) Reference to a performance standard issued by the Department of Health and Human Services in conformance to the Federal Food, Drug and Cosmetic Act and to any voluntary standard to which it may apply, and adequate information in order to prove that the device fully meets these standards or information to substantiate the deviation of such standards; f) Samples of the device and its components, and g) Any other relevant information regarding the application which the Department of Health and Human Services considers appropriate; Supervision after its commercialization, and Requirements of guidelines issued by the FDA specifically for every type of medical device. In Canada the Class II medical devices are subject to the following controls which guarantee their quality, safety and efficacy in a verifiable manner for the Mexican sanitary authorities: Registration of the manufacturer.

4 (Second Section) OFFICIAL JOURNAL Tuesday October 26 th, 2010 VII. VIII. Description of the conditions, purposes and medical uses for which the device is manufactured. List of standards to meet the safety and efficacy requirements of the medical device which are met in its manufacturing process, and International standards of the quality system in the medical device manufacturing process contained in the norm ISO issued by the International Organization for Standardization (ISO), and which are incorporated in the norm CAN/CSA-ISO 13485:03, Medical Devices -Quality Management Systems- Requirements for Regulatory Objectives, and which become mandatory by reference in the Medical Devices Regulations. In Canada the Class III medical devices are subject to the following controls which guarantee their quality, safety and efficacy in a verifiable manner for the Mexican sanitary authorities: (v) (vi) (vii) Registration of the manufacturer. Description of the device and of the materials used in its making. Description of the features of the device which allow it to be used for the conditions, purposes and medical uses for which the device is manufactured. List of standards to meet the requirements of safety and efficacy of the medical device which are met in its design and making. A summary of all research that has been carried out in order to prove that the device is safe and effective, along with its conclusions. Bibliography of all the research regarding the use, safety and efficacy of the device, and International standards of the quality system in the medical device design and manufacturing process contained in the norm ISO issued by the International Organization for Standardization (ISO), and which are incorporated in the norm CAN/CSA-ISO 13485:03, Medical Devices -Quality Management Systems- Requirements for Regulatory Objectives, and which become mandatory by reference in the Medical Devices Regulations. In Canada the Class IV medical devices are subject to the following controls which guarantee their quality, safety and efficacy in a verifiable manner for the Mexican sanitary authorities: (v) (vi) (vii) (viii) (ix) Registration of the manufacturer. Description of the device and of the materials used in its making. Description of the features of the device which allow it to be used for the conditions, purposes and medical uses for which the device is manufactured. Risk assessment with an analysis and risk assessment and risk reduction measures adopted in order to meet the requirements of safety and efficacy. Quality plan which specifies the quality practices, resources and relevant activity sequence for the device. Specifications of materials used in the making and packaging of the device. The manufacturing process of the device. List of standards to meet the requirements of safety and efficacy of the medical device which are met in its design and making; Detailed information regarding the research on which the manufacturer is supported in order to assure that the device meets the safety and efficacy requirements, including pre-clinical and clinical studies, studies of process validation, written reports and, if applicable, software validation studies;

5 Tuesday October 26 th, 2010 OFFICIAL JOURNAL (Second Section) (x) (xi) (xii) Summary of all the research that have been carried out to prove that the device is safe and efficient, including conclusions; Bibliography of all the research about the use, safety and efficacy of the medical device, and International standards of the quality system for the medical device design and manufacture stated under norm ISO issued by the International Organization for Standardization (ISO), and which are incorporated into norm CAN/CSA-ISO 13485:03, Medical Devices- Quality Management Systems_ Requirements for Regulatory Objectives, which become mandatory because they are mentioned in the Medical Devices Regulations. That the Federal Commission for the Protection against Sanitary Risk, under the terms of numeral second in the AGREEMENT which sets forth the general provisions that should be met by the Ministry of Health for the issuance of administrative agreements to recognize that the requirements, tests, assessment procedures and other requirements requested by foreign sanitary authorities to allow their respective countries to sell, distribute and use health supplies under article 194 Bis of the General Health Law, are equivalent to those required by the General Health Law, the Regulations for Health Supplies and other legal and technical provisions applicable for that matter, to guarantee the quality, safety and efficacy that those supplies must meet in order to get a sanitary registration in our country, the extension of said registration or any other modification to the conditions under which they were registered published in the Federal Official Journal on September 3 rd, 2010, has carried out the necessary actions to ensure that the technical and scientific assessment procedures carried out by the foreign sanitary authorities, in conformance with the regulations and documents mentioned under numeral second herein and its results consisting of the registration of the establishment, the premarket clearance [510(k)] and the premarket approval granted by the FDA in the United States of America, which are substantiated by the certificate to foreign government, as well as by the medical device establishment license and the medical device license issued by the HC Canada, offer a degree of compliance with the quality objectives, safety and efficacy of the Medical Devices stated in the General Health Law and in the Regulations for Health Supplies, equivalent to the technical assessment procedures carried out by the Federal Commission for the Protection against Sanitary Risk to give the sanitary registration to a Medical Device in conformance with the Regulations for Health Supplies, by the following reasons: I. The FDA in the United States of America verifies the compliance of the medical devices class I, II and III, with the regulations and documents mentioned under numeral second herein, through the following actions: The medical devices manufactures are regularly inspected (in terms of 2 to 4 years) by the FDA to check the following aspects: a) Quality systems management/ good manufacturing practices; b) Tracking of sold devices; c) Corrections and recalls from the market; d) Life of the establishment license; e) Good laboratory practices for pre-clinical lab trials; f) Compliance with authority reports for adverse events and devices malfunctioning; g) Organization chart of the company, including the key positions job descriptions and the skills of the individuals in the positions; h) Operating procedures; i) Degree of automation; j) Calibrating procedures; k) Production and control documents, and

6 (Second Section) OFFICIAL JOURNAL Tuesday October 26 th, 2010 l) Analytical capabilities; II. The manufacturers and traders of the medical devices, as well as the clinics and the doctors shall report to the FDA about the adverse events and the devices malfunctioning (medical device reports); The manufacturers and traders of the medical devices shall notify to the FDA about the corrections and recalls of medical devices from the market, and The FDA keeps a system to register the mandatory recalls of medical devices from the market; The FDA in the United States of America verifies the compliance of the medical devices Class II with the requirements and regulations controls, and documents mentioned under numeral second herein, through the actions mentioned under the previous section I, and the post-market surveillance; III. IV. The FDA in the United States of America verifies the compliance of the medical devices Class III with the requirements and regulations controls, and documents mentioned under numeral second herein, through the actions mentioned under the previous sections I and II, as well as the following: Revision by some of the 17 specialized panels of the Medical Devices Advisory Committee, listed in Annex III, of the Premarket Approval mentioned in Paragraph 11, fraction V under Declarations clause herein, including the results of the preclinical lab trials and the clinical trials in humans, and Tests to the samples of the devices carried out by the 17 specialized panels of the Medical Devices Advisory Committee listed under Annex III, HC verifies the compliance of the medical devices class II, III and IV, with the requirements and regulations controls mentioned under numeral second herein, through the following actions: Certificates of compliance of norm CAN/CSA-ISO 13485:03, Medical Devices - Quality Management Systems- Requirements for Regulatory Objectives, issued by third parties authorized by HC; Granting of authorization to issue certificates in a valid manner as per the norm mentioned in the previous paragraph, to the certificated registrars in accordance to norm ISO Conformance Assessment Requirements for suppliers of the registration and management systems certification service, and Frequent inspections to third parties authorized by HC to issue certificates of compliance as per the norm mentioned under the previous paragraph ; and That the technical equivalence analysis in the previous paragraphs, as well as the powers invested in the sanitary authorities in our country to revoke at anytime the sanitary registration for health supplies, as well as to dictate the applicable safety measures provided that there is a health risk, substantiate the recognition of technical equivalence mentioned under numeral second herein, we have decided to issue and dictate the publication in the Federal Official Journal the following: AGREEMENT FIRST. - For the effects of this Agreement the following shall be understood as: General Provisions Agreement: Agreement which sets forth the general provisions that should be met by the Ministry of Health for the issuance of administrative agreements to recognize that the requirements, tests, assessment procedures and other requirements requested by foreign sanitary

7 Tuesday October 26 th, 2010 OFFICIAL JOURNAL (Second Section) authorities to allow their respective countries to sell, distribute and use health supplies under article 194 Bis of the General Health Law, are equivalent to those required by the General Health Law, the Regulations for Health Supplies and other legal and technical provisions applicable for that matter, to guarantee the quality, safety and efficacy that those supplies must meet in order to get a sanitary registration in our country, the extension of said registration or any other modification to the conditions under which they were registered, published in the Federal Official Journal on September 3 rd, Agreement of Formalities: Agreement which sets forth the proceedings and services, as well as the formats used by the Ministry of Health through the Federal Commission for the Protection against Sanitary Risk, registered in the Federal Registry of Formalities and Services of the Federal Regulatory Improvement Commission, published in the Federal Official Journal on June 19 th, COFEPRIS: Federal Commission for the Protection against Sanitary Risk. Medical Devices: The medical equipment, prosthesis, orthotics, functional aids, diagnostic agents, dental supplies, surgical and healing material, and sanitary products, and other medical devices mentioned under Chapter IX, Title two of the Regulations for Health Supplies. FDA: The government agency in the United States of America called Food and Drug Administration. HC: The government agency in Canada called Health Canada. Law: General Health Law PROFECO: Federal Attorney s Office of Consumers. Regulations: Regulations for Health Supplies. SECOND. The requirements set forth under articles 179 and 180 of the Regulations and that the technical assessment procedures carried out by the COFEPRIS are recognized as equivalent in order to grant the sanitary registration for Medical Devices Class I, II and III as per the criteria set forth under article 83 of the Regulations: To the requirements set forth under sections 510 (k) and 514 of the Federal Food, Drug and Cosmetic Act and by Title 21, Chapter 1, Subchapter H of the Code of Federal Regulations of the United States of America, as well as those set forth by the Food and Drug Act and the Medical Devices Regulations of Canada to is allow to market Medical Devices in their territory; and To the tests and inspections carried out by the Food and Drug Administration of the United States of America and by HC of Canada in order to allow marketing Medical Devices in their territory. Regardless the classification of the medical devices as per the regulations and documents mentioned under this numeral, the COFEPRIS shall classify the Medical Devices according to the criteria set forth under article 83 of the Regulations. THIRD. The COFEPRIS shall require from the applicants to the sanitary registration of Medical Devices who choose to submit their application under the terms of this Agreement and who count on the establishment registration or premarket clearance [510(k)] or premarket approval granted by the FDA of the United States of America, or medical device license issued by the HC of Canada, the following information and documentation: I. In conformance with article 153 of the Regulations, the official formats shall be used for the sanitary registration pursuant to the Agreement of Formalities, including the receipt of payment of the corresponding rights, the documentary information stated under articles 179 fractions II and III and 180 Fraction II and IV of the Regulations, a copy of the operation notice of the establishment, a copy of the notice of the individual responsible for sanitary matters and the monograph according to the second paragraph under article 153 of the Regulations, issued by the manufacturer duly signed by the individual responsible for the quality assurance of the medical device, with the following information: Trade name;

8 (Second Section) OFFICIAL JOURNAL Tuesday October 26 th, 2010 II. III. (v) (vi) (vii) (viii) (ix) (x) (xi) (xii) General name (if applicable); Description of the Medical Device and purpose of the same; Layout of the structure, parts, materials and functions if applicable, or, if applicable, qualitative and quantitative formulation indicating the effect of the ingredients of the formulation, of the Medical Device; Specifications of the finished product; Summary of the manufacturing process or flow diagram of the manufacturing process; Sterilization method, if applicable; Summary of atoxicity or biocompatibility, if applicable. Expiration date and summary of the stability study endorsing it, if applicable; Features of the primary and secondary packaging; Presentations, codes or models. Summary of the pre-clinical lab trials and of the clinical trials to humans including conclusions, if applicable, and Bibliography references in case there are some. In order to register Class I Medical Devices as per the classification of the United States of America, the following documentation shall be submitted to the COFEPRIS, in addition to the documentation stated under the previous fraction I, to evidence that the commercialization of such Medical Devices is allowed in the United States of America: Original document and certified copy of the certificate to foreign government issued by the FDA, in force, translated into Spanish pursuant to the terms provided under article 153 of the Regulations; The last establishment inspection report that has been performed to the manufacturer of the medical device, translated into Spanish pursuant to the terms provided under article 153 of the Regulations; and Copy of the document issued by the FDA containing the approval of the Medical Device, including the classification information of the same, translated into Spanish pursuant to the terms provided under article 153 of the Regulations. In order to register Classes II and III Medical Devices as per the classification of the United States of America, the following documentation shall be submitted to the COFEPRIS, in addition to the documentation stated under the previous fraction I, to evidence that the commercialization of such Medical Devices is allowed in the United States of America; and Original document and certified copy of the certificate to foreign government issued by the FDA, in force, translated into Spanish pursuant to the terms provided under article 153 of the Regulations; The last establishment inspection report that has been performed to the manufacturer of the medical device, translated into Spanish pursuant to the terms provided under article 153 of the Regulations; and Summary or document evidencing the last technovigilance or surveillance postmarket report of the product, translated into Spanish pursuant to the terms provided under article 153 of the Regulations; and Copy of the document issued by the FDA containing the approval of the Medical Device, including the classification information of the same, translated into Spanish pursuant to the terms provided under article 153 of the Regulations.

9 Tuesday October 26 th, 2010 OFFICIAL JOURNAL (Second Section) IV. Class I Medical Devices under the classification of Canada are excluded from this Agreement. V. In order to register Classes II, III and IV Medical Devices as per the classification of Canada, the following documentation shall be submitted to the COFEPRIS, in addition to the documentation stated under the previous fraction I, to evidence that the commercialization of such Medical Devices is allowed in Canada: Certified copy of the medical device license in force, issued by the HC to the manufacturer, translated into Spanish pursuant to the terms provided under article 153 of the Regulations; Copy of the valid certificate of compliance to norm CAN/CSA-ISO 13485:03, Medical Devices -Quality Management Systems- Requirements for Regulatory Objectives, translated into Spanish pursuant to the terms provided under article 153 of the Regulations; Copy of the valid certificate of compliance to norm ISO Conformance Assessment Requirements for suppliers of the registration and management systems certification service- by an authorized third party (registrar) who issued the certificate mentioned on the previous paragraph, translated into Spanish pursuant to the terms provided under article 153 of the Regulations; and Certified copy of the valid authorization issued by the HC to the authorized third party (registrar) who issued the certificate mentioned on the previous paragraph, translated into Spanish pursuant to the terms provided under article 153 of the Regulations. FORTH. Except for the cases mentioned in the next paragraph, the COFEPRIS shall not require any additional documentation to that applicable according to the previous article, in order to start working on the sanitary registration application submitted as per this Agreement, regardless of the source country of the Medical Device, whose sanitary registration is being requested. In the case of the medical devices using radiation sources, the applicant shall submit a copy of the corresponding license issued by the Ministry of Energy (National Commission on Nuclear Safety and Safeguards), and in the case of diagnose agents where the COFEPRIS deems necessary to prove the efficacy of the same on the population to which it is being applied, due to genetic matters or other characteristics of the population, as well as in the case of condoms due to the fact that it is a public health matter, it may request a certificate of analysis performed by an authorized third party or by a control laboratory adjuvant to the sanitary regulation of the Ministry of Health, in addition to the applicable documentation as per article third herein. FIFTH. The requests to modify the registration conditions and the registration extension of the Medical Device granted pursuant to this Agreement shall include the documents stated in the applicable legal provisions. SIXTH. The COFEPRIS shall inform if there is legal basis to grant the sanitary registration, and the modification or extension to the registration provided that the registration of the Medical device has been granted pursuant to this Agreement, to the applicant within 30 working days as of the following day when the applicant submits the applicable documentation as per numeral third herein. In case the documentation is not complete, the COFEPRIS shall inform the applicant within a term that will be equivalent to one third of the term given to determine if there is legal basis for the application to proceed, provided that it is an administrative one, and two thirds, when it is a technical one, pursuant to article 156 of the Regulations. In case the COFEPRIS fails to determine if the applications for Class I Medical devices sanitary registration, submitted pursuant to this Agreement, are accepted within a 30 working days term as stated in the previous paragraph, the application shall be deemed as accepted.

10 (Second Section) OFFICIAL JOURNAL Tuesday October 26 th, 2010 SEVENTH. The term stated in the first paragraph under numeral sixth herein shall be suspended when the Ministry requires to the applicant, expressly and in writing, documents, clarifications or missing information and it will be resumed within the next working day of the submittal of information or documents by the applicant or when he/she makes the applicable clarifications. In case the applicant does not provide the documents, clarifications or missing information within the term conferred for such effect, the application shall be deemed as not submitted. In any case, the sanitary registration applicant who has the records, permits, approvals or licenses mentioned under numeral third herein, may choose to undergo the ordinary procedure provided under articles 179 and 180 of the Regulations. EIGHTH. This Agreement does not exempt the goods importers, dealers and traders, who get the sanitary registration of a Medical Device pursuant to this Agreement, from the liabilities to comply with the requirements set forth under article 131 of the Regulations or form any other requirement or specification deemed necessary to keep such sanitary registration, pursuant to the applicable legal provisions, as well as from any requirement additional to the sanitary registration that they are bound to meet in order to market the Medical Device within the Mexican territory in conformance with any applicable law, regulation or other provisions. NINTH. The COFEPRIS may cancel or revoke the sanitary registration for the Medical Devices registered pursuant to this Agreement, in conformance with articles 376 and 380 of the General Health Law and other applicable legal provisions. Likewise, the COFEPRIS, the PROFECO or any other competent authority shall have at anytime the power, pursuant to their capacities, to seize or held the goods registered pursuant to this Agreement, as well as to stop their commercialization and to demand their recall in conformance with the provisions under articles 404 fraction X and 414 of the General Health Law, 25 bis of the Federal Law for Consumer s Protection and other applicable legal provisions. That the holders of the sanitary registrations, as well as the importers and the traders of the Medical Devices registered pursuant to this Agreement, shall inform to the COFEPRIS, the PROFECO and to any other competent authority about the revocation, cancelation or suspension of the registration of the establishment, premarket clearance [510(k)] and premarket approval granted by the FDA of the United States of America, or the medical device license issued by the HC Canada, that they know or should know about, likewise, they shall comply with the provisions under article 38 of the Regulations. The conferment of the sanitary registration pursuant to this Agreement shall not hinder the COFEPRIS from exerting its capacities regarding the sanitary surveillance and sanitary control, in conformance with the applicable legal provisions. TENTH. None of the provisions herein shall be construed as a restriction for the entrance of goods which get the sanitary registration before the COFEPRIS pursuant to this Agreement, for the only reason of having gotten their registration through the recognition of technical equivalence set forth. Both, at the time they enter as well as during their transportation and commercialization within national territory, the Medical Devices registered pursuant to this agreement shall be given the same treatment than that granted to the goods via the ordinary procedure before COFEPRIS. TRANSITORY FIRST. - This Agreement shall become effective within the 30 calendar days following to its publication in the Federal Official Journal. SECOND. - The sanitary registration applications, extensions or any other modification to the conditions under which the Medical Devices were registered, mentioned herein, shall be requested using the official formats pursuant to the Agreement of Formalities, including the receipt of payment of the corresponding rights. THIRD.- The sanitary registration applications, extensions or any other modification to the conditions under which the Medical Devices were registered that have been submitted before the COFEPRIS previous to the effective date of this Agreement, shall undergo the ordinary procedure set forth in the Regulations.

11 Tuesday October 26 th, 2010 OFFICIAL JOURNAL (Second Section) FORTH. - In order to prevent the register duplication, the COFEPRIS shall not receive sanitary registration applications for the Medical Devices subject matter of this Agreement if an application to register the same Medical Device has previously been submitted. FIFTH. - The Medical Devices provided under the applicable legal provisions of the United Mexican States and defined under this Agreement are the only ones that will be deemed as the subject matter of this Agreement. Mexico City, October 20 th, The Secretary of Economy, Bruno Ferrari García de Alba. - Paraph. Mexico City, October 20 th, The Secretary of Health, José Angel Córdova Villalobos. - Paraph.

12 (Second Section) OFFICIAL JOURNAL Tuesday October 26 th, 2010 ANNEX I Medical devices classification in the United States of America Pursuant to the Federal Food, Drug and Cosmetics Act of the United States of America Class I Class II Class III Authorized in sections 501, 502, 510, 516, 518, 519 and 520. Subject to general controls when they are enough to provide reasonable guarantee about the safety and effectiveness of the device; or there is not enough information to determine which special controls are necessary. The device is not lifesustaining or life-supporting or its usage is not substantial to prevent human health deterioration and it does not represent an excessive potential risk of illness or injury. It is subject to special controls due to the fact that the general controls are not enough to provide reasonable guarantee about the safety and effectiveness of the device or there is enough information to determine which special controls are necessary. Special controls include the submittal of performance standards, postmarket surveillance and patent registration. The device seems to be life-sustaining or lifesupporting. The commissioner is the one who examines and identifies the special controls and describes the way in which the latter guarantee safety and effectiveness It is necessary to count on the approval, previous to the commercialization as per section 515 FD&C. There is not enough information to determine which general controls or which special controls are sufficient to provide reasonable guarantee about their safety and effectiveness. Additionally, the device is life-sustaining or life-supporting or ) its usage is substantial to prevent human health deterioration and it does not represent an excessive potential risk of illness or injury.

13 Tuesday October 26 th, 2010 OFFICIAL JOURNAL (Second Section) ANNEX II Medical devices classification in Canada Pursuant to Medical Devices Regulations of Canada Class I Class II Class III Class IV Invasive Devices 1 (1) Subject to sub-rules (2) and (3), all the invasive surgical devices (2) An invasive surgical device designed to be absorbed by the body or to remain within the body at least for 30 consecutive days. (3) An invasive surgical device designed to diagnose, monitor, control or correct a defect in the cardiovascular system or in the central nervous system or in a fetus or in a uterus Invasive Devices 2 (1) Subject to sub-rules (2) and (4), all the invasive surgical devices that penetrate the body through a body orifice or that are in touch with the eye surface (3) A device described in sub-rule (1) typically designed to remain within the body or to be in touch with the eye surface for at least 30 consecutive days (4) A device described in subrule (1) designed to prevent the transmission of infectious agents during sexual activity or at least to reduce the risk Invasive Devices 3 Notwithstanding rules 1 and 2 (a) all dental materials and odontological applications and their accessories, and (c) al latex condoms Non-invasive Devices 4 (1) Subject to sub-rule (2), all noninvasive devices designed to be in touch with skin lesions Non-invasive Devices 5 A non-invasive device designed to channel or store body gases, liquids, tissues or fluids in order to introduce them into the body via an infusion or other administration methods Non-invasive Devices 6 (3) A device described in sub-rule (1) modified through a centrifuge, gravity filtration, gases or heat exchange process (1) Subject to sub-rules (2) and (3), a noninvasive device designed to modify the chemical or biological composition of the blood or other body fluids, or liquids in order to introduce them via an infusion or other administration methods (2) A device described in subrule (1) with such characteristics that the modification process may introduce a foreign substance into the body that is or may be potentially dangerous, due to the nature and quantity of the substance Non-invasive Devices 7 A device described in sub-rule (1) if it is designed to operate as a gage, tester or as a support for quality control connected to an active device classified as Class II, II or IV

14 (Second Section) OFFICIAL JOURNAL Tuesday October 26 th, 2010 Active Devices 8 (2) A device described in sub-rule (1) if it is designed to be used within the X-Ray modality (1) Subject to sub-rules (2) and (3), an active device designed for ions radiation, including any device or software designed to control or monitor such device or to influence directly in tits operation (3) Notwithstanding sub-rule (2), an active device designed to perform mammographies Active Devices 9 (1) Subject to sub-rules (2) and (3), an active therapeutic device including any dedicated software, designed to give or to pull out energy to or from the body (2) If the action of giving or pulling out energy via the device described in sub-rule (1) is potentially hazardous, taking into consideration the nature of the action of giving or pulling out the energy, the intensity of the same and the part of the body in question (3) A device described in subrule 2) designed to control the treatment of the patient s condition via closed systems Active Devices 10 (1) Subject to sub-rule (2), an active diagnostic device, including any software, supplying energy in order to get an optical depiction or to monitor physiological processes (2) A device described in subrule (1) designed to monitor, assess or diagnose a disease, disorder, abnormal physical state or pregnancy in case wrong readings may result in an immediate damage Active Devices 11 (1) Subject to sub-rules (2) and (3), an active device including any software, designed for administration of medications, body fluids or other substances to or from the body (2) If the administration or extraction of a substance via the device described in subrule (1) is potentially hazardous due to the nature of the substance administered and the part of the body in question (3) A device described in subrule (2) designed to control the treatment and condition of a patient via closed systems Active Devices 12 NOT APPLICABLE NOT APPLICABLE NOT APPLICABLE Special Rules 13 (b) Medical devices for disinfection or sterilization A medical device designed to be used to: (a) disinfect or sterilize blood, tissues or organs intended for transfusions and transplants

15 Tuesday October 26 th, 2010 OFFICIAL JOURNAL (Second Section) Special Rules 14 (1) Subject to sub-rule (2), (a) a device manufactured from or that incorporates human or animal cells, tissues or their derivatives (b) a device manufactured from or that incorporates a product manufactured through recombinant DNA technologies Special Rules 15 Any device intended to be sold to a health professional or supplier in order to set or fix a mold to meet the individual s needs is classified within the class of finished devices Any device intended to be sold to a health professional or supplier in order to set or fix a mold to meet the individual s needs is classified within the class of finished devices Any device intended to be sold to a health professional or supplier in order to set or fix a mold to meet the individual s needs is classified within the class of finished devices Special Rules 16 Breast implants and tissue expanders for breast reconstruction or augmentation

16 (Second Section) OFFICIAL JOURNAL Tuesday October 26 th, 2010 ANNEX III Specialty Areas Panels of the Food and Drug Administration Number Name of the Panel 1 Anesthesiology and Respiratory Therapy Panel 2 Circulatory System Devices Panel 3 Clinical Chemistry and Clinical Toxicology Devices Panel 4 Dental Products Panel 5 Ear, Nose and Throat Devices Panel 6 Gastroenterology and Urology Devices Panel 7 General and Plastic Surgery Devices Panel 8 General Hospital and Personal Use Devices Panel 9 Hematology and Pathology Devices Panel 10 Immunology Devices Panel 11 Microbiology Devices Panel 12 Molecular and Clinical Genetics Panel 13 Neurological Devices Panel 14 Obstetrics and Gynecology Devices Panel 15 Ophthalmic Devices Panel 16 Orthopaedic and Rehabilitation Devices Panel 17 Radiological Devices Panel