Post on 25-Sep-2020
Current Biologics Regulatory Scenario in Brazil
Carolina Damas Rocha Zarate Blades, PhDOffice of Biological ProductsBrazilian Health Regulatory Agency – ANVISA
Brazil, March/2019
LATAM CMC Strategy Forum 2019
Outline
Biological products
Regulatory framework
Regulatory updates
International Cooperation
Perspectives2
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
Regulatory framework
RDC 55/2010Marketing Authorization
RDC 46/2000Blood products
RDC 323/2003Probiotics
RDC 50/2011Stability
RDC 47/2009RDC 60/2012 Package insert
RDC 71/2009RDC 61/2012
Labelling
RDC 17/2010GMP
RDC 194/2017Allergenics
RDC 187/2017Hyperimmune Sera
Law 6.360/1976Decree 8.077/2013
RDC 234/2005Quality control
RDC 49/2011Post-approval
changes
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Regulatory framework
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Resolution 55/2010
Marketing authorization of Biological Products in Brazil
Biosimilars
Regulatory framework
Stand alone approach
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Resolution 55/2010 Marketing authorization of Biological Products in Brazil
Regulatory requirements for the license of biological products in Brazil
New Biological Products
Biological Products (not new)
Comparability Stand Alone
CMC Needed Comparative Needed
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
Regulatory framework
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Resolution 49/2011 Stablishes requirements and procedures for post‐approval changes of Biological Products
Resolution 50/2011Stablishes requirements and procedures for stability studies of Biological Products
Regulatory framework
Under review
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Regulatory updates
Law 13.411/2016
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.
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Resolution 204/2017:
Stablishes prioritization criteria for:
I. Marketing authorization
II. Post‐approval changes
III. IND submission
Regulatory updates
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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.
Regulatory updates
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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 Immunization Program;
• 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.
Regulatory updates
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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.
Regulatory updates
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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
Regulatory updates
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Resolution 205/2017: Art.18. The following procedures must be followed for the purpose of registration of newdrug for a rare disease:[….]IV ‐ assessment of the request for registration of drug by Anvisa within sixty days aftersubmission, with the emission of the notification requirement or conclusive opinion;[….]VI – Compliance of the requirements, by the interested party, within thirty days after readingthe notification; andVII ‐ assessment of requirements’ compliance, by Anvisa within forty‐five days after thesubmission at the agency.
Regulatory updates
Anvisa has up to 105 days to provide a conclusive opinion (or ask for additional clarification)
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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.
Regulatory updates
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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.
Regulatory updates
OS n. 45, February of 2018 (Orientation of Service)
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Resolution 219/2017For 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.
Regulatory updates
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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 – 1st L Multiple myeloma and pembrolizumab +chemotherapy – 1st L NSCLC) were approved by ANVISA before FDA and EMA in April/18 andJune/18. One indication was approved before EMA (nivolumab + ipilimumab for 1st L Renalcarcinoma cell in Oct/18).
Regulatory updates
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Backlog reduction
Regulatory updates
Marketing authorizaton
Year Average time (days)
2016 247
2017 157
2018 91
Post‐approval
Year Average time (days)
2016 372
2017 245
2018 108
Post‐approval (minor complexity)
Year Average time (days)
2016 1452017 1172018 82
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Marketing authorization ‐ Time for approval – 2018 (average time)
Regulatory updates
Status Backlog (days)
Assessment (days)
MAH (days) Backlog + Assessment
(days)
Total Time for approval
(days)
Priority 21 113 45 134 179
Ordinary 153 214 156 367 523
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Public Assessment Reports on website:http://www.anvisa.gov.br/datavisa/Fila_de_analise/index.asp
Technical basis for the approval or the refusal of marketing authorization of medicinal products
Regulatory updates
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Note of clarification on procedural instruction :http:http://portal.anvisa.gov.br/documents/33836/4095801/Nota+de+esclarecimento+004+de+2017+‐+Medicamentos+Biol%C3%B3gicos/36e8ac57‐64e7‐4e7d‐86b5‐9d4e2f7ebeda
Marketing authorization and Post‐approval changes for Biological Products;
Mandatory documents; Complementary applications.
Regulatory updates
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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).
International Cooperation
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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
Thank you!
Carolina Damas Rocha Zarate Bladesprodutos.biologicos@anvisa.gov.br
Agência Nacional de Vigilância Sanitária ‐ AnvisaSIA Trecho 5 ‐ Área especial 57 ‐ Lote 200
CEP: 71205‐050Brasília ‐ DF
www.anvisa.gov.brwww.twitter.com/anvisa_oficial
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