Technical Note about Biological ProductsOctober 19, 2011Due to the recent end of several patents for innovative biotechnologicalproducts, the interest in producing and selling copies of these products hasbeen growing in Brazil and in the world.In Brazil, domestic producers have great interest in this market and have beeninvesting heavily.Biotechnological products are included in different government programs andsince they are high value added and high cost products, they consume asignificant portion of the health budget. Thus, the Brazilian government hasgreat interest in making biotechnological products increasingly more available inthe market so the access can be expanded, always aware of efficacy and safetyissues.In this sense, since 2009 several issues related to biotechnological products,whether innovative or not, and the increase in domestic production capacity forthem, have been discussed in the Executive Group of the Health IndustrialComplex (GECIS).The diverse needs pointed out in this group include the need for review of theregulatory framework to register the biological products, the category in whichbiotechnological products are classified in Brazil.Thus, since 2009, review of the RDC 315/05, the regulatory framework forregistering biological products in Brazil at the time, began to be discussed withinthe ambit of the GECIS and internally at ANVISA.Based on this study, Public Consultation 49/2010 was published in May 2010with the proposal to review the regulatory framework for registeringbiotechnological products. The Public Consultation process extended toDecember 2010 with broad participation by the national production sector,including holding a technical meeting to discuss the contributions made duringthe public consultation process. The meeting of the Collegiate Board fordeliberating on norm publication also included the presence of representativesfrom the national production sector.RDC no. 55/2010 was published in December 2010. It is currently the regulatoryframework for registering biological products, whether innovative or not.In order to elaborate RDC 55/10, regulatory frameworks and guidelines fromdifferent agencies in the world were considered, such as Health Canada(Canada), EMA (Europe), CECMED (Cuba), KFDA (Korea) and the guideline
published by the World Health Organization (WHO) specifically for registeringsimilar biotherapeutic products (WHO SBP guideline).According to the RDC 55/2010, there are two biological and biotechnologicalproducts in Brazil. The innovative products are called new biological productsand the copies are called biological products.New biological products should be registered through the classical regulatorymanner, with presentation of a complete report, with all production and qualitycontrol data and complete nonclinical and clinical data (Phase I, II and III).For biological products, that is, non-innovative products, there are two possibleregulatory paths for registration: the development copy for comparison path andIndividual development copy path. In these two paths, it is possible to present aregistration report with reduced information.In the individual development path, the product is compared to the biologicalproduct used for comparison (new biological product registered based on acomplete report), including its cellular origin, production process, qualityparameters and nonclinical and clinical studies. In this case, data forcomparison are presented between the biological product intended forregistration and the biological product used for comparison, and based on theresults, the nonclinical and clinical development paths can be simplified. Use ofthe development copy by comparison path also enables extrapolation oftherapeutic indications. The development copy by comparison path permittedinternalizing guidelines found in the WHO SBP Guideline.For non-innovative products, based on already existing and successfulexperiences in Brazil, there is a second regulatory path, the individualdevelopment copy, used in cases where there are differences between thebiological product intended for registration and the biological product forcomparison which do not permit using the classical path for checkingcomparability. In this case, the producer can carry out the technologicaldevelopment of its product with production data, quality control and nonclinicaland clinical Phase I and II studies on a non-comparison basis and theirextension can be increased or decreased according to the molecule’scomplexity and specific characteristics. In the development copy by comparisonpath it will be necessary to conduct a Phase III Study of comparison ofequivalence or non-inferiority with the biological product used for comparisonand the extrapolation of therapeutic indications is not conducted.We believe the new regulation proposed for registering biological products inBrazil, RDC55/10, will provide the legal and scientific guidelines needed fordeveloping copies of biological products in Brazil and will close some previouslyexisting regulatory loopholes since it contains specific regulatory paths forregistering non-innovative biological products.
Throughout 2011, ANVISA’s Biological Product Registration and ClinicalResearch Offices have conducted several meetings with different domesticindustries to monitor nonclinical and clinical development of biological products.Additional regulatory needs were detected during this monitoring program.Thus, in order to improve technical and regulatory frameworks, CPBIH/ANVISAelaborated four specific technical guidelines: GUIDELINE FOR EXERCISINGCOMPARABILITY STUDIES FOR REGISTERING BIOLOGICAL PRODUCTS;GUIDELINE FOR ELABORATING CLINICAL STUDY REPORTS FORREGISTRATION PURPOSES AND/OR FOR POST-REGISTRATIONAMENDMENTS OF BIOLOGICAL PRODUCTS; GUIDELINE FORREGISTERING HEPARINS USING THE COMPARISON PATH; GUIDELINEFOR REGISTERING ALPHA INTERFERON USING THE COMPARISONPATH. The guidelines are available on the ANVISA website, clicking on thebiological products link. Another important action was to provide a completeregulatory framework for registering biological products, including the RDC55/10 registration and RDC 49/2011 post-registration norms, among otherRDCs needed for registration and post-registration of biological products.Publication of the legal bases for registering biological products was conductedin partnership with ABDI and will also be available in electronic format on theANVISA website, on the biological products link.Another important initiative will be the creation of the Technical Chamber forBiological Products (CATEBIO), in accordance with the resolution approved at ameeting of the Anvisa Collegiate Board on October 19, 2011. The resolution willbe published in the Official Federal Gazette. CATEBIO is a collegiate board ofan advisory nature technically tied to the Biological Product and RegistrationOffice (CPBIH), of the Efficacy and Safety Evaluation Office (GESEF) and theGeneral Management of Medications (GGMED), comprised of specialists withrenowned knowledge in the clinical and biotechnological area, free of anyconflict of interest. At CATEBIO, specific themes such as the development andregistration of biological products as well as broader issues such as establishingguidelines and elaborating guidelines by product category will be discussed.Over recent months, Anvisa’s major focus in the biological product area hasbeen to monitor the development of copies of monoclonal antibodies by nationaland international industries. Thus, publication of a specific guideline on thetheme is projected for 2012.