Roberto Carlos Latini

1. Roberto Carlos Latini

2. COUNTRIES THAT HAVE STRUCTURED REGULATORY AFFAIRS SYSTEM(FOR IVD AND MEDICAL DEVICES) • ARGENTINA • BOLIVIA • BRAZIL • CHILE • COLOMBIA • MEXICO • PARAGUAY • URUGUAY • VENEZUELA

3. LEGAL COMPANY ESTABLISHMENT REGULATORY APPROVAL FOR THE COMPANY GMP CERTIFICATE GETTING STARTED PRODUCT REGISTRATION/ NOTIFICATION

4. WAYS TO GET INTO THE LATIN AMERICA MARKET

5. WAYS TO GET INTO THE LATIN AMERICA MARKET • Establishment of a Subsidiary in Brazil: • Advantages: the company will own the registrations under its name. This way, the company will be free to choose and change distributors any time that may find convenient. • Disadvantage: this process is more time consuming, once the company has to get the state (or city) regulatory license and the federal regulatory authorization, before submit the registration of the products. The time to get the said licenses is about 10 to12 months. The average time to register products varies, as follows: • Medical Devices / IVD: 4~6 months. • Medical Consumables and Disposables: 4~9 months

6. WAYS TO GET INTO THE LATIN AMERICA MARKET • Registration on behalf of Distributor’s name: • Advantages: this option is faster than the establishment of a subsidiary, once the distributor already has the regulatory licenses. The timing of this operation will be only that described below for the registration, considering that all documents were sent to the distributor by the manufacturer: • Medical Devices / IVD: 4~6 months. • Medical consumables and disposables: 4~9 months. • Disadvantage:the main disadvantage is that the distributor will hold the registrations, which (generally) are not transferable, unless in case of incorporation, fusion or separation of companies. If the company decides to change the distributor, then the registrations will need to be re-make by the new distributor. However, various distributors can hold the registration of the same product. In this case, each one will have its own registration number.

7. WAYS TO GET INTO THE LATIN AMERICA MARKET • Registration Using an Authorized Representative (Non Commercial Holder): • Advantages: the two basic advantages of this option are that it is faster than the establishment of a local subsidiary, once the Authorized Representative (AR) company already has the regulatory licenses and the timing of this operation will be only that considered to register the products in the Local Regulatory Agencies. The other important advantage is that the mother company can change the distributor any time, once the holder (AR) of the registrations will allow the distributor to import the products using the AR’s registration number. • Disadvantage: the holder of the registrations will not be the mother company, but another one with a legal agreement to represent it in LATAM, regarding the registration of the products only. • Important: the holder of the product’s registration can authorize another company (local distributors) or final consumer (as Hospitals, Labs and Clinics) to import the products under the registration number of the holder. This is perfectly legal, once the holder continues to be technically and legally responsible for the product itself.

8. COMPANIES APPROVAL

9. SOCIAL CONTRACT TAX ID CARD • ALL NEEDED LOCAL LICENSES BUILDING CONSTRUCTION OR OFFICE RENTAL HIRE TECHNICAL AND LEGAL RESPONSIBLE • BLUE PRINTS 1:100 • DESCRIPTION OF THE ACTIVITIES • BASIC LIST OF PRODUCTS TO BE SOLD PREPARATION & SUBMISSION OF THE BLUE PRINTS + DOSSIER PREPARATION & SUBMISSION OF THE LOCAL LICENSE INSPECTION PREPARATION & SUBMISSION OF THE FEDERAL AUTHORIZATION FINAL APPROVAL COMPANIES APPROVAL IN LATIN AMERICA

10. . MEDICAL DEVICES COMPANIES DOCUMENTS REFERENCE

11. . IVD COMPANY DOCUMENTS REFERENCE

12. PRODUCT REGISTRATION

13. MEDICAL DEVICES REGISTRATION

14. BASIC DOCUMENTS TO REGISTER MEDICAL DEVICES IN LATIN AMERICA • COMPANY’S WORKING PERMIT (LATAM) • FREE SALES CERTIFICATE*(WHEN APPLICABLE) • LETTER OF DISTRIBUTION* (WHEN APPLICABLE) • (*) CONSULARIZATION REQUIRED IN THE CLOSEST EMBASSY/CONSULATE OF THE COUNTRIE WHERE THE PRODUCT WILL BE REGISTERED. • GMP CERTIFICATE (WHEN APPLICABLE) • CERTIFICATE OF CONFORMITY (FOR ELECTROMEDICAL DEVICES ONLY) • INSTRUCTIONS OF USE / INSERTS / USER’S MANUAL • SERVICE / INSTALATION MANUAL • LABELING • PACKING • COMPOSITION OF THE MEDICAL DEVICE • BASIC MANUFACTURING FLOWCHART WITH OPERATIONS MADE IN EACH PHASE • VALIDATION OF STERILIZATION PROTOCOL (WHEN APPLICABLE) • PROOFS OF SAFETY AND EFFECTIVENESS (PUBLISHED PAPERS IN SPECIALIZED MAGAZINES OR POINTS SPECIFICALLY DESCRIBED IN LOCAL LEGISLATION)

15. EXTRA DOCUMENTS TO REGISTER MEDICAL DEVICES IN LATIN AMERICA For ElectromedicalEquipments: • Manufacturing Plant Audit; • Tests performed according to the IEC 60601.1 and IEC 60601.2.X; • If the Brazilian Notified Body has a Memorandum of Understanding (MOU) with the one the certified the product in the country of origin then test report can be accepted instead of new tests performed in Brazil. Condoms and Surgical Gloves: • Require local tests and certification. In Vitro Diagnostic kits: • The following IVD Kits may require local tests and certification: ABO / Rh), Hepatites (B / C), Sífilis (Treponemapallidum), HIV, Doença de Chagas (Trypanosomacruzi) and HTLV.

16. EXTRA DOCUMENTS TO REGISTER MEDICAL DEVICES IN LATIN AMERICA • For Orthopedic Prosthesis: • Risk Analysis of the Manufacturer according with ISO 14971, EN 93/42 EEC; • All tests made to approve the raw materials including the Certificate issued by the supplier when applicable;  • All mechanical tests made according to accepted international standards like ASTM, ISO, etc.. For example: dynamic tests, fatigue, static tests, etc.   • Critical analysis of the efficacy of the Orthopedic Prosthesis (made by the Technical Responsible) comparing the nominal features with those obtained in the tests and the biometrical parameters described in the scientific literature. Everything must be compared with the parameters set up during the design phase;

17. EXTRA DOCUMENTS TO REGISTER MEDICAL DEVICES IN LATIN AMERICA • Technical drawings of all components with the physical dimensions and tolerances; •  Controls used by the manufacturer during the manufacturing phase. •  All Quality Certificates obtained by the Manufacturer like ISO 9001, 13485, CE Mark, 21 CFR FDA etc.; •  All Quality Certificates obtained by the third party companies that work for Manufacturer like ISO 9001, 13485, 21 CFR FDA, etc., when applicable; •  Clinical studies performed with the product itself or similar products to prove the efficacy and safety •  If the prosthesis contain any material originated from cattle then Animal Health Certificates issued by the Veterinary authority of the country of origin of the cattle must be presented to prove that the animals were free from spongiform encephalopathy (mad cow disease).

18. DOCUMENTATION FROM MANUFACTURER CRITICAL ANALISYS PREPARATION OF TECHNICAL DOSSIER IN LOCAL LANGUAGE PAYMENT OF TAXES SUBMISSION IN LOCAL REGULATORY AUTHORITIES ANALISYS BY LOCAL REGULATORY AUTHORITIES FINAL APPROVAL MEDICAL DEVICE REGISTRATION FLOWCHART 30 UP TO 150 DAYS CERTIFICATION or REQUIRED LOCAL TESTS

19. . MEDICAL DEVICES REGISTRATION DOCUMENTS REFERENCE TABLE

20. BASIC STRUCTURE OF MEDICAL DEVICES REGISTRATION DOSSIER • FORMS ACCORDING TO LOCAL LEGISLATION • TAX PAID • LABELLING ACCORDING TO LOCAL LEGISLATION • INSTRUCTIONS OF USE / USER MANUAL ACCORDING TO LOCAL LEGISLATION • TECHNICAL REPORT • CERTIFICATE OF CONFORMITY (FOR ELECTROMEDICAL DEVICES ONLY) • PROOFS OF EFFICACY AND SAFETY • NOTARIZED COPY OF THE FREE SALES CERTIFICATE*(WHEN APPLICABLE) • NOTARIZED COPY OF THE LETTER OF DISTRIBUTION*(WHEN APPLICABLE) • LOCAL (LATAM) GMP CERTIFICATE (*) DOCUMENTS MUST BE CONSULARIZED (IN THE COUNTRIE OF ORIGIN) IN THE CLOSEST CONSULATE OF THE COUNTRIE WHERE THE PRODUCT WILL BE CONSULARIZED

21. IVD REGISTRATION

22. DOCUMENTATION FROM MANUFACTURER 30 UP TO 150 DAYS CRITICAL ANALISYS PREPARATION OF TECHNICAL DOSSIER IN LOCAL LANGUAGE PAYMENT OF TAXES SUBMISSION IN LOCAL REGULATORY AUTHORITIES ANALISYS BY LOCAL REGULATORY AUTHORITIES TEST IN LOCAL LAB FINAL APPROVAL IVD REGISTRATION FLOWCHART

23. BASIC DOCUMENTS TO REGISTER IN-VITRO DIAGNOSTIC (IVD) IN LATIN AMERICA • COMPANY’S WORKING PERMIT (LATAM) • TECHNICAL RESPONSIBILITY CERTIFICATE (LATAM) • FREE SALES CERTIFICATE* • LETTER OF DISTRIBUTION* (*) CONSULARIZATION REQUIRED (IN THE COUNTRIE OF ORIGIN) IN THE CLOSEST EMBASSY/CONSULATE OF THE COUNTRIE WHERE THE PRODUCT WILL BE REGISTERED. • INSTRUCTIONS OF USE / INSERTS • ADITIONAL MATERIALS REQUIRED • LABELLING • PACKING • COMPOSITION / QUALI-QUANTI (CENTESIMAL) FORMULA • BASIC MANUFACTURING FLOWCHART WITH OPERATIONS MADE IN EACH STEP • TEST REPORT FOR CRITICAL ITEMS AS SENSITIVITY, ACCURACY, CALIBRATION CURVES, ETC. (LOCAL TEST MAY BE REQUIRED) • VALIDATION OF STERILIZATION PROTOCOL (WHEN APPLICABLE) • PROOFS OF SAFETY AND EFFECTIVENESS

24. . IVD REGISTRATION DOCUMENTS REFERENCE

25. BASIC STRUCTURE OF AN IVD REGISTRATION DOSSIER • FORMS ACCORDING TO LOCAL LEGISLATION • TAX PAID • CERTIFICATE OF TECHNICAL RESPONSIBILITY • LOCAL WORKING PERMIT • FEDERAL WORKING PERMIT • LABELLING ACCORDING TO LOCAL LEGISLATION • INSTRUCTIONS OF USE / USER MANUAL ACCORDING TO LOCAL LEGISLATION • TECHNICAL REPORT • PROOFS OF EFFICACY AND SAFETY • NOTARIZED COPY OF THE FREE SALES CERTIFICATE* • NOTARIZED COPY OF THE LETTER OF DISTRIBUTION* • QUALI/QUANTI FORMULA ISSUED BY THE MANUFACTURER* (JUST FOR IVD) • LOCAL (LATAM) GMP CERTIFICATE (*) DOCUMENTS MUST BE CONSULARIZED (IN THE COUNTRIE OF ORIGIN) IN THE CLOSEST CONSULATE OF THE COUNTRIE WHERE THE PRODUCT WILL BE CONSULARIZED

26. Technical Concepts Q&A

27. Class of Risk • Class I (low risk) • Class II (medium risk) • Class III (medium/high risk) • Class IV (high risk)

28. DEFINITION OF MEDICAL DEVICE • Product, equipment, device, material, article or system of Medical, Odontological or Laboratorial (Clinical Lab) use or application, used for prevention, diagnostic, therapeutic, rehabilitation or anti-conception that does not use pharmacological, immunological or metabolic methods to perform its main function but may be helped in its functions by these methods.

29. Softwares • In general, softwares are classified as follows: • If they are designed only for images or data filing then they will be considered as Class I products - Low Risk; • If they give to the operator the possibility to alter the image or the collected data, then they will be considered as Class II - Medium Risk. Note: it is important to re-enforce that when a product is to be used with another higher risk class product then the first one has to be considered in the same class of risk of the second one.

30. Softwares • Requires Registration, and the Good Manufacturing Practices (GMP) Certificate issued by ANVISA: • Medical Software, notpre-installed in medical devices/equipments, whichperformsimageprocessing, orsuggestsdiagnostics, orisintendedtobeused in surgical procedures or in ICU (intensivecareunit), ordirectlyinfluencesthefunctioningof medical devices/equipmentswhichrequireregistration.

31. Used Equipment / Materials • It is forbidden by LATAM legislation to sell used products. The equipment must be refurbished by the manufacturer or by some service company duly authorized by the manufacturer. The product must have its registration valid. • Some materials can be re-used if re-processed properly by the hospitals.

32. Spare Parts • Once one product is registered is LATAM all its parts and components are automatically considered as registered also but some accessories that can be sold separately like disposables. It is not necessary to keep the registration alive to import spare parts for servicing but the importer has to prove that the said product was imported during the validity of the registration.

33. Harmonization • Many norms are already harmonized in Mercosur. Nevertheless it was expected to harmonization to be concluded and registrations accepted among the countries since 2003. The harmonization is delayed because of the economic situation of some partners and also because new technologies were introduced in the LATAM market what lead the countries to take he discussion to a totally new different level.

34. After Sales Monitoring (Techno Vigilance) • The LATAM market (specially Mercosur) already adopted the Techno Vigilance system. All recalls and malfunction have to be reported to the local authorities. The Regulatory Authorities also monitor the global market looking for problems with products that can be sold in LATAM countries.

35. What happen when I have these changes? (1) • Change the Manufacturing Address: it is possible to update the registration. • Change of the Manufacturer: it is possible to update the registration but it is strongly suggested that the company applies for a new registration. It is faster and less complicated. • My company wants to add a new manufacturing site: no problem. It is just a matter of updating the registration.

36. What happen when I have these changes? (2) • When I have a major change in my product? The company should report to the RA authorities or submit a new registration. • Can I add new products to the approved registration? Yes, if the new product fits the criteria of registration per family of products.

37. Family of Products • What are the basic criteria for registration as Family of Products? • Same manufacturer; • Same technology; • Same composition; • Same use; • Same side effects, warnings and special care.

38. Is It possible to have more than one company holding the registration of the same product? • Yes, since the manufacturer authorizes each applicant. Then each applicant will have its own registration number.

39. TAKE INTO CONSIDERATION… • REGULATORY SYSTEMS IN LATAM ARE NEW COMPARED TO EUROPE OR FDA. • LOW EXPERIENCE OF THE REGULATORY AUTHORITIES IN SOME ISSUES AND TECHNOLOGIES. • SYSTEM HIGHLY INFLUENCED BY POLITICAL FACTS / ENVIRONMENT. • UNEXPECTED CHANGES MAY OCCOUR IN THE LEGISLATION. • INFLUENCE OF OTHER AUTHORITIES THAN THE REGULATORY ONES (METROLOGY, LABOR, ETC).

40. Technical Notes in the Brazilian Health Surveillance Agency – ANVISA • N° 01/2012/GQUIP/GGTPS/ANVISA: for Fitness and Wellness Products; • N° 02/2012/GQUIP/GGTPS/ANVISA: for Electro-Medical Devices; • N° 03/2012/GQUIP/GGTPS/ANVISA: for Medical and Non Medical Devices Definition List; • 04/2012/GQUIP/GGTPS/ANVISA: Software for Medical Devices.

42. Latini & Associados