biosimilars/biotechnology - drug information association · 2011-05-05 ·...

DIA Latin American Regulatory ConferenceDIA Latin American Regulatory ConferencePanama City, Panama

April, 12-15, 2011

Biosimilars/BiotechnologyBiosimilars/BiotechnologyBiosimilars/Biotechnology

Marcelo Mario Matos MoreiraCoordinator – Office of Biological ProductsCoordinator Office of Biological ProductsThe Brazilian Health Surveillance Agency

(ANVISA)

Agência Nacionalde Vigilância Sanitária

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What do we mean by biological/ biotechnology products?gy p

• Biotechnology products include complexBiotechnology products include complexmolecules produced using living organisms fortherapeutic use. Biotech drugtherapeutic use. Biotech drug

Small molecule drug


What is a Biosimilar or Follow-on Biologic?g

• A Biosimilar medicinal product• A Biosimilar medicinal productis a successor to a biologicalmedicinal product for whichmedicinal product for whichpatent protection no longerappliespp

• Manufactured by recombinant DNA technology(i ti f i t th h t ll t d th(insertion of gene into the host cell to produce theprotein)


What is a Biosimilar or Follow-on Biologic?g

• Comparable with the selected• Comparable with the selectedreference product (the alreadylicensed biological medicinallicensed biological medicinalproduct) in terms of quality,safety and efficacyy y

• The Biosimilar product can be approved for thei di ti th f d t isame indications as the reference product given

that they share the same mode of actions


Different names for the same product

BIOSIMILARFOLLOW ON BIOSIMILAR BIOLOGICS (FOB)

•GenericBiological

BIOSIMILAR

SIMILAR BIOTHERAPEUTICPRODUCTS MEDICAMENTO

BIOLÓGICO SIMILAR

Biological•Biogenerics

FOLLOW-ON PROTEIN SUBSEQUENT

(BIOSIMILAR)

BIOLOGICALPRODUCT (FOPPs)FOLLOW ON BIOLOGICS (FOB)

SUBSEQUENT ENTRY BIOLOGICSPRODUCT


A biosimilar is not a generic

- Biosimilars usually do not meet all thediti t b id d iconditions to be considered as a generic

product mainly due to

• manufacturing process characteristics

• raw materials used

• molecular characteristics

• therapeutic modes of action


Biosimilar development

- The development of a Biosimilar medicine requires• a complete product and process development PLUS• a complete product and process development PLUS• a comparative testing at all stages of development in order to obtain approval by competent authoritiesorder to obtain approval by competent authorities

Reference product

Comparative Comparative

Target Complete Characterization

Physico-chemical and

Biological Comparability

Comparative Preclinical

Studies

Comparative Clinical Studies

Risk Management

Plan

Biopharmaceuticals approved as biosimilar medicines


Quality

- Elucidation of structure and other characteristics

• primary and higher-orderstructure• post-translationalmodifications• biological activity• purity• impurities• product-related substances

i h i l ti9www.diahome.orgDrug Information Association

• immunochemical properties

Quality

- Comparability of a product claimed to be similar toanother biological product already marketedcannot be made on gross physico-chemical andbi h i l t lbiochemical aspects alone.

Pre clinical and clinical studies will be necessary• Pre-clinical and clinical studies will be necessary.


Quality

- Key points to be considered:

• Characterisation studiesCharacterisation studies

• Manufacturing process

• Stability data


Quality

- The manufacturer will not have access to all theinformation that would allow comparison in terms ofinformation that would allow comparison in terms ofquality of the marketed product:

• Expression/vector system

• Production and purification details

• Analytical techniquesAnalytical techniques


Quality

- General principles:

• Address pharmaco-toxicologicalt f th Bi i ilassessment of the Biosimilar

• Should be conducted with the finalformulation intended for clinical use

• Minimum: head-to-head comparativetoxicology studiesAdditi l N Cli i l d t d d f th• Additional Non-Clinical data depend of thespecificities of a product


Non-clinical Evaluation

- In vitro studies

•Methodology: Receptor-binding studies, cell-based assays, etcP t bli h bilit f Bi l i l/•Purpose: establish comparability of Biological/

Pharmacodynamic activity of the Biosimilar and Reference



- In vitro studies

• General principlesComparative in natureComparative in naturePerformed in relevant species Employ state of the art technologyp y gy



• In vivo studies

- Endpoints • Biological/pharmacodynamic activity relevant

to the clinical application• Non-clinical toxicity as determined in at least• Non-clinical toxicity as determined in at least

one repeat dose toxicity study in a relevantspecies and including toxicokineticmeasurementsmeasurements


Clinical Evaluation

• Designed to demonstrate comparable safety andefficacy of the Biosimilar to the Referenceefficacy of the Biosimilar to the Reference

• Clinical comparability exercise: stepwise procedure;• Clinical comparability exercise: stepwise procedure;PK and PD studies followed by the pivotal clinicaltrials


Clinical Evaluation

- Efficacy studies

• No dose-finding studiesD t t i d t l d• Demonstrate in adequately powered,randomized, and parallel group clinical trial

• Equivalence or non-inferiority studies may beEquivalence or non inferiority studies may beacceptable for the comparison of efficacy andsafety of the Biosimilar to the Reference;equivalence/non inferiority margins have to beequivalence/non-inferiority margins have to bepre-specified and justified


Clinical Evaluation

- Safety

• Usually, safety data obtained from the efficacytrials will be sufficienttrials will be sufficient

• Comparison with the Reference should includetype, frequency and severity of Adverse Events


Pharmacovigilance

• Close monitoring of the clinical safety: focus on(rare) serious Adverse Events in all approved(rare) serious Adverse Events in all approvedindications

• Pharmacovigilance plan should describe planned• Pharmacovigilance plan should describe plannedactivities and methods based on the safetyspecification

• Risk minimization measures may enhance safe useof Biosimilar


Implementation in Brazil

• RDC 55/2010 – current normative landmark

Route of development by comparability

The regulatory route that can be used by a biologicalprod ct to obtain registration from the reg latorproduct to obtain registration from the regulatoryauthority, in which the exercise of comparability interms of quality, efficacy and safety was used,b t th d l d d t t b blbetween the developed product to be comparableand the comparer biological product.


Further information and contactThe Brazilian Health and Surveillance Agency

Agência Nacional de Vigilância Sanitária

ANVISA

produtos biologicos@anvisa gov [email protected]

Th k ! M h G iThank you! Muchas Gracias!22www.diahome.orgDrug Information Association

biosimilars/biotechnology - drug information association · 2011-05-05 ·...

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