Current Biologics Regulatory Scenario in Brazil

Transcription

1 LATAM CMC Strategy Forum 2019 Current Biologics Regulatory Scenario in Brazil Carolina Damas Rocha Zarate Blades, PhD Office of Biological Products Brazilian Health Regulatory Agency ANVISA Brazil, March/2019

2 Outline Biological products Regulatory framework Regulatory updates International Cooperation Perspectives 2

3 Biological Products Vaccines; Hyperimmune sera; Blood products; Biomedicines classified as: a) medicines obtained from biological fluids or animal originated tissue; b) medicines obtained through biotechnological procedures. Monoclonal antibodies; Medicines containing live, attenuated or dead microorganisms; Probiotics; Allergens. 3

4 Regulatory framework RDC 47/2009 RDC 60/2012 Package insert RDC 71/2009 RDC 61/2012 Labelling RDC 234/2005 Quality control Law 6.360/1976 Decree 8.077/2013 RDC 55/2010 Marketing Authorization RDC 46/2000 Blood products RDC 194/2017 Allergenics RDC 323/2003 Probiotics RDC 17/2010 GMP RDC 49/2011 Post-approval changes RDC 50/2011 Stability RDC 187/2017 Hyperimmune Sera 4

5 Regulatory framework 5

6 Regulatory framework Resolution 55/2010 Marketing authorization of Biological Products in Brazil Stand alone approach Biosimilars 6

7 Regulatory framework Regulatory requirements for the license of biological products in Brazil New Biological Products Comparability Biological Products (not new) Stand Alone CMC Needed Comparative Needed Resolution 55/2010 Marketing authorization of Biological Products in Brazil Pre-clinical Needed Comparative May be reduced Clinical 1 and 2 Needed Comparative When needed, may not be comparative Clinical 3 Needed Comparative Comparative with exceptions Immunogenicity Needed Comparative Needed Same comparator Not applicable Yes Not applicable Risk management plan Needed Needed Needed Extrapolation Not applicable Possible Not possible 7

8 Regulatory framework Resolution 49/2011 Stablishes requirements and procedures for post approval changes of Biological Products Resolution 50/2011 Stablishes requirements and procedures for stability studies of Biological Products Under review 8

9 Law /2016 Establishes new deadlines for the conclusion of the drug applications. Marketing authorization: Ordinary category: 365 days* (487 days) Priority category: 120 days* (160 days) Post approval changes: Ordinary category: 180 days* (240 days) Priority category: 60 days* (80 days) * An extension of 1/3 of the time can be granted, under justification. Categories will be defined according to technical complexity, clinical, social and economic relevance. 9

10 Resolution 204/2017: Stablishes prioritization criteria for: I. Marketing authorization II. Post approval changes III. IND submission 10

11 Prioritization criteria (Biological Products) Marketing authorization Drugs for neglected, rare or emerging diseases; public health emergencies; or serious debilitating diseases, in situations where there is no therapeutic alternative available, or when there is a significant improvement in the safety, efficacy; New drugs intended to pediatric population; Vaccines or hyperimmune sera to be incorporated into the National Immunization Program; Drugs that are part of the strategic product list, under the Brazilian National Health System (SUS) and object of a Productive Development Partnership (PDP), e.g. biosimilars. 11

12 Prioritization criteria (Biological Products) Post approval changes New indication or extended use for neglected, rare or emerging diseases; when there is a significant improvement in the safety, efficacy; or for serious debilitating diseases, in situations where there is no therapeutic alternative available; New indication or extended use for pediatric population; Vaccines or hyperimmune sera incorporated into the National ImmunizationProgram; Applications related to the process of internalization of the production of drugs that are part of the strategic product list, under the Brazilian National Health System (SUS) and object of a Productive Development Partnership (PDP), e.g. biosimilars. 12

13 Prioritization criteria (Biological Products) In addition to the previous criteria, Anvisa may classify as priority applications for marketing authorization and post approval changes of drugs (under medical prescription), when there is a risk of market shortage with public health impact. 13

14 Resolution 205/2017: Establishes a special procedure for the consent of clinical trials, certification for good manufacturing practices and registration of new drugs for treatment, diagnosis or prevention of rare diseases*. * one that affects up to sixty five people in every one hundred thousand individuals 14

15 Resolution 205/2017: Art.18. The following procedures must be followed for the purpose of registration of new drug for a rare disease: [.] IV assessment of the request for registration of drug by Anvisa within sixty days after submission, with the emission of the notification requirement or conclusive opinion; [.] VI Compliance of the requirements, by the interested party, within thirty days after reading the notification; and VII assessment of requirements compliance, by Anvisa within forty five days after the submission at the agency. Anvisa has up to 105 days to provide a conclusive opinion (or ask for additional clarification) 15

16 OS n. 45, February of 2018 (Orientation of Service) Reliance Pilot Project (duration: 1,5 year in progress); Establishes an optimized review pathway for the assessment of Biologics (for Marketing Authorization and Post approval changes applications); Eligibility Criteria: approved in the US FDA and EMA; Approval reports should be provided by the applicants. Page 16 16

17 OS n. 45, February of 2018 (Orientation of Service) Marketing authorization: US FDA and EMA approval; Detailed approval letters and/or assessment reports Post approval changes: US FDA and/or EMA approval; Detailed approval letters and/or assessment reports Complete information required by Brazilian legislation must be presented; Quality changes: same specifications, shelf life; Efficacy and safety changes: same labelling content, including indications, dosage, warnings and precautions, ARs; Any differences must be justified. 17

18 Resolution 219/2017 For some post approval applications, if Anvisa has not started the assessment within 180 days, the post registration change shall be deemed acceptable. Demands that marketing authorization holders submit additional documents to the original application (risk assessment, statement); Does not apply for efficacy and safety changes and changes to the drug substance of biological products. 18

19 Backlog Reduction New strategies which enable to considerably reduce the timelines for assessing the applications Timelines were accomplished in most cases for biologics. Approval before FDA and EMA in 2 cases and before EMA in 1 case (variations of new therapeutic indication). Two of the new indications (daratumumab 1 st L Multiple myeloma and pembrolizumab + chemotherapy 1 st L NSCLC) were approved by ANVISA before FDA and EMA in April/18 and June/18. One indication was approved before EMA (nivolumab + ipilimumab for 1 st LRenal carcinoma cell in Oct/18). 19

20 Backlog reduction Marketing authorizaton Year Average time (days) Post approval Year Average time (days) Post approval (minor complexity) Year Average time (days)

21 Marketing authorization Time for approval 2018 (average time) Status Backlog (days) Assessment (days) MAH (days) Backlog + Assessment (days) Total Time for approval (days) Priority Ordinary

22 Public Assessment Reports on website: Technical basis for the approval or the refusal of marketing authorization of medicinal products 22

23 Note of clarification on procedural instruction : +Medicamentos+Biol%C3%B3gicos/36e8ac57 64e7 4e7d 86b5 9d4e2f7ebeda Marketing authorization and Post approval changes for Biological Products; Mandatory documents; Complementary applications. 23

24 International Cooperation Strengthen International Cooperation MoU with Danish Health and Medicines Authority Workshop in November 2018: Brazilian Legislation X European Legislation; Quality, safety and efficacy requirements for Biological Products; Case studies (biosimilars). 24

25 Perspectives Anvisa CTD guideline; Resolution on less complex Biologicals (draft concluded, available for PC soon); Resolution on Stability (draft in progress); Resolution on Post registration changes (draft in progress); Implementation of Quality System for Biological Products in accordance with Good Revision Practices; Improvement of the Biological Products webpage: Hot site for biosimilars; General information about vaccines. 25

26 Thank you! Carolina Damas Rocha Zarate Blades Agência Nacional de Vigilância Sanitária Anvisa SIA Trecho 5 Área especial 57 Lote 200 CEP: Brasília DF