Región Suramericana

Dra Alejandra Babini

Potenciales conflictos de interés • Conferencias sobre este tema para :

• SAR Sociedad Argentina de Reumatología

• SUR Sociedad Uruguyaya de Reumatología

• Latin American Forum on Biosimilars - Brasil

• GAfPA Latin American Biologics and Biosimilars Policy Advocacy Summit

• Participación en Advisory Boards / conferencias:

• Pfizer

• Abbvie

• Roche

• Janssen

2

Biosimilars in Latin America: Regulatory State of Play

1. Mexico: NOM 257 and NOM 177; 2. Colombia: Decree 1782 of 2014; 3. http://www.bioworld.com/content/colombia-implement-new-guidelines-regulation-biosimilars-0; 4. Ecuador: Reglamento para la Obtención del Registro Sanitario, Control y Vigilancia de Medicamentos Biológicos para Uso y Consumo Humano issued on May 17, 2013 (Chapter VII); 5. Ecuador: Formulario de requisitos que se deben adjuntar para el registro sanitario de medicamentos biológicos extranjeros en general y por homologación (august 8, 2013); 6. Peru: Reglamento que regula la presentación y contenido de los documentos que opten por la via de la similaridad 579288; 7. Chile: NORMA 170 September 6, 2014; 8. Argentina: Disposición 3397/2012 for biologic products; Disposición 7729/2011 for biosimilar drugs; 9. Panama: Resolución número 045MB-MBT CdeM 2015; 10. Dominican Republic: Reglamento técnico para el registro sanitario de medicamentos biotecnológicos innovadores y no innovadores para uso humano. DIGEMAP-03-15; 11. Guatemala: Norma tecnica 67-2015. Ministerio de Salud y Asistencia Social; 12. Costa Rica: Reglamento Tecnico RTCR 440:2010; 13. Venuzuela: Resolución N° 051 de fecha 17 de Junio de 1992. Gaceta Oficial de la República Bolivariana de Venezuela N° 34.989 de fecha 19 de junio de 1992; 14. Brazil: ANVISA: Resolucao RDC N° 55, de 16 de Decembro de 2010; Diario Oficial da Uniao-Secao 1; N° 241; 15. Teixeira VF, et al. Arg Gastroenterol 2016;53:60–1; 16. Paraguay : Resolución S.G. 003 (January 16, 2015); 17. Uruguay: Registro de Medicamentos Biotecnológicos (January 27, 2015)

Mexico: Regulations finalized 11/2014; sets out requirements

for biologic and biosimilar registration – developing

individual product guidelines1

Colombia: Issued decree in 10/2014 creating “3rd pathway”; now implementing regulations,

including immunogenicity guidelines2,3

Ecuador: No biosimilar specific regulations in place4,5

Peru: Regulations in place since 03/20166

Bolivia: Working on guidance

Chile: Regulations in place as of 9/20147

Argentina: Regulations in place as of 11/2011 and 6/20128

Central America and Caribbean Panama: Purportedly interested in adopting

Colombian style 3rd pathway; no biosimilars specific regulations9

Dominican Republic: Regulations in place since 08/201610

Guatemala: Legislation in place as of 11/201111 Costa Rica: Regulations in place as of 3/201212

Venezuela: Regulation for biological products in place, draft biotherapeutics regulations

have been published for comment, but so far no new regulation has been issued13

Brazil: Regulations in place as of 12/2010; has 3rd/individual

development pathway – approved first biosimilar for infliximab in 201514,15

Paraguay: Regulation in place as of 01/201716

Uruguay: Regulation in place as of 01/201517

Biosimilares aprobados por FDA

4

benepali etanercept Samsung 14/01/2016

inflextra infliximab Pfizer Hospira 05 / 04/ 2016

erelzi etanercept Sandoz 30/ 08/ 2016

amjevita adalimumab Amgen 26/ 09 /2016

renflexis / flixabi Infliximab -abda Samsung 21/04/2017

cyltezo adalimumab

Boehringer Ingelheim

25/08/2017

Biosimilares aprobados por FDA

5

benepali etanercept Samsung 14/01/2016

inflextra infliximab Pfizer Hospira 05 / 04/ 2016

erelzi etanercept Sandoz 30/ 08/ 2016

amjevita adalimumab Amgen 26/ 09 /2016

renflexis / flixabi Infliximab -abda Samsung 21/04/2017

cyltezo adalimumab

Boehringer Ingelheim

25/08/2017

Biosimilares aprobados por EMA

6

inflectra infliximab Hospira 10 / 09/ 2013

remsima infliximab Celltrion 10 / 09/ 2013

benepali etanercept Samsung Bioepis 14 / 01/ 2016

flixabi infliximab Samsung Bioepis 26 / 05/ 2016

truxima rituximab Celltrion 17 / 02/ 2017

amjevita adalimumab Amgen 22/ /03/ 2017

solymbic adalimumab Amgen 22/03/2017

rixaton rituximab Sandoz 19/06/2017

erelzi etanercept Sandoz 27/06/2017

tuxella rituximab Celltrion/Tevas 29/06/2017

imraldi adalimumab

Samsung Bioepis

25/08/2017

Biosimilares aprobados por EMA

7

inflectra infliximab Hospira Pfizer 10 / 09/ 2013

remsima infliximab Celltrion 10 / 09/ 2013

benepali etanercept Samsung Bioepis 14 / 01/ 2016

flixabi infliximab Samsung Bioepis 26 / 05/ 2016

truxima rituximab Celltrion 17 / 02/ 2017

amjevita adalimumab Amgen 22/ /03/ 2017

solymbic adalimumab Amgen 22/03/2017

rixaton rituximab Sandoz 19/06/2017

erelzi etanercept Sandoz 27/06/2017

tuxella rituximab Celltrion/Tevas 29/06/2017

imraldi adalimumab

Samsung Bioepis

25/08/2017

rituximab infliximab etanercept adalimumab

Brasil Remsima 2015

(CT-P13)

Argentina Novex 2013

Remsima 2016

Chile Reditux Kikuzubam

Remsima 2015

Paraguay Novex Tidecron (Reditux)

Uruguay

Recommendations for the regulation of biosimilars and their implementation in Latin America

Generics and Biosimilars Initiative Journal (GaBI Journal). 2014;3(3): 143-8.

Alexis Aceituno Álvarez, PharmD, PhD, Eduardo Mysler, MD, Eva Maria Ruiz de Castilla, MS, MAA, PhD, Francisco Javier Flores-Murrieta, PhD, FCP, Juana Hughes, MSc, Valderilio Feijó Azevedo, MD, PhD, MBA

• A significant issue in Latin America is how to re-evaluate products

that were previously approved but no longer fit the current criteria for a biosimilar. As mentioned above, intended copies of biologicals have been used in Latin American countries for many years and in general there were no criteria for the establishment of similarity between these products and their reference products.

Permanece en la región la presencia en el mercado y en

uso, de intentos de copia previos a las Regulaciones

ajustadas a normas internacionales

Primer “ biosimilar “ aprobado

• Novex (rituximab) Lab Elea

• Mabscience / Libbs

• Para Linfoma y extrapolación a todas las demás indicaciones aprobadas de Mabthera Roche

• ANMAT approval 16 Oct 2013 (Argentina)

Position statement on approval of biosimilars in Latin America Posted 10/02/2017 Gaby Journal

The Fifth Latin American Forum on Biosimilars (FLAB) was held in Brasilia, Brazil in 2015 with the theme of

‘Interchangeability and Automatic Substitution’. Discussions centred on the approval of CT-P13, an infliximab

biosimilar; and RTXM83, a proposed rituximab biosimilar, in both Brazil and Argentina. Following these

discussions, Babini et al. [1] published a FLAB position statement on the approval of these monoclonal

antibody biosimilars in the context of current regulations in these two Latin American countries. Through critical analysis of the biosimilarity exercises carried out on the two products, the authors stated that

CT-P13 is the only monoclonal antibody marketed in Latin America that can be considered a true biosimilar.

CT-P13 underwent clinical trials and demonstrates clinical biosimiliarity to the reference product. Despite this,

Babini et al. noted that biosimilarity does not mean guaranteed interchangeability. The biosimilar was tested in

two disease models (ankylosing spondylitis (AS) and rheumatoid arthritis (RA), and was then extrapolated for

the treatment of inflammatory bowel disease (IBD) in over 50 countries, including Brazil. This approval has

been subject to debate, as it was based on extrapolation which is contrary to regulation in Brazil. FLAB

position statement states, for interchangeability that ensures safe and effective treatment, further trials and

evidence are needed to demonstrate that a biosimilar can produce similar effects to the reference product, for

a given condition, in any given patient. Babini et al. reported that such a study has been proposed for CT-P13

[2]. Although clinical trials are underway, at present there is no clinical data available to demonstrate that

RTXM83 is equivalent to its reference, rituximab. Babini et al. reported that this means that it is not a

true biosimilar product. Despite the lack of clinical evidence and contrary to regulation, RTXM83 was

approved as a biosimilar in Argentina. At present, it has not been approved in Brazil.

Position statement on approval of biosimilars in Latin America

Posted 10/02/2017 Gaby Journal

Babini et al. concluded that, to ensure the success of biosimilars and achieve a reduction in drug expenditure, there must be evidence that they achieve similar clinical results to their reference products. Countries in Latin America need to create well-defined pathways and regulations for the approval, review, and pharmacovigilance of biosimilars. To ensure appropriate approval and usage of biosimilars, governments should also ensure their actions are transparent and consistent with regulations in place.

Regulación en Argentina : ANMAT

• Disposición del 2011 • Regula aprobaciones de

productos biotecnológicos

Regulación en Argentina : ANMAT

• Disposición del 2011 • Regula aprobaciones de

productos biotecnológicos

SUBTITULO UNO

SUBTITULO UNO

Biocad registers rituximab similar biotherapeutic product in Bolivia and Honduras

Posted 14/07/2017

Russian biotechnology company Biocad announced on 6 June 2017 that it had obtained a

marketing authorization for its rituximab ‘similar biotherapeutic product’ in Bolivia and

Honduras under the trade name Usmal. Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found

on the surface of immune system B cells.

The news marks Biocad’s first venture into Latin America, a move which it says ‘is strategically

important for further business development in the markets of the MERCOSUR and other

countries in region’. Biocad expects to start shipping its rituximab similar biotherapeutic product to Bolivia and

Honduras in the third quarter of 2017. There are currently only originator biologicals in the Bolivian and Honduran markets. Therefore,

the launch of the Russian similar biotherapeutic product will, according to Biocad, ‘provide the

patients with an access to affordable and highly effective treatment of cancer, thus improving

their life quality and expectancy’. Biocad’s rituximab non-originator biological was approved in Russia in April 2014 [1].

Puntos a debatir

• La región tiene regulaciones sobre Biosimilares

( aprobación y plan de reducción de riesgos)

• Deben cumplirse tales regulaciones

• Biosimilares correctamente aprobados pueden reducir costos y mejorar el acceso a mas pacientes

• Debatir que hacer con los intentos de copia en plaza antes de las legislaciones hoy vigentes

• Debatir porque se aprueban moléculas que no cumplen con las regulaciones vigentes en la actualidad (intento copia / biomimics)

Gracias

CORDOBA ARGENTINA