Biothecnological Products Regulation in Chile and Biosimilarity

CMC Strategy

Forum LATAM 2014

Q.F. Fabiola Muñoz E.

ANAMED-CHILE

Brasilia agosto 2014

Pharmaceutical Products

89.72%8.19%

2.10%10.28%

Productos Farmacéuticos Registrados

Farmaceuticos de síntesis Biologicos Biotecnologicos

Biothecnological products in Chile

BiothecnologicalRegulation

Before december 26, 2011

D.S. 1876/95

Somebiotecnologicals

were approved as biogeneric to the

innovator

Others wereapproved with a

complete or partialdossier

After december 26, 2011

D.S. Nº3/2010 pharmaceutical

regulation

D.S. Nº3/2010 MINSAL

• All Biological products must be considered as new products(53)

• Must submit the complete dossier to demonstrate quality,safety and efficacy (36)

• hormones, Biotechnological, Blood Products, vaccines andothers (12)

• In the case of Biotechnological Products by a Ministry’ sdecree, proposed by ANAMED it shall be established thespecific Biotechnological Norm. This Norm must indicate thebiotechnological products that may present an abbreviateddossier of clinical and preclinical information based on abiotechnological product approved with the complete dossierto demonstrate quality, safety and efficacy ,and it also mustpoint out the biotechnological reference products (42 i)

Considerations in developing Draft

ICH Guidelines

EMA

WHO Recommendationsfor the Evaluation of

Biotherapeutics Products

Similar (PBS). Geneve, WHO, 2009

Norm 140/12 Pharmacovigilance

Quality/ efficacy and

safety

Draft Thecnical Norm

ANAMEDPharmaceutical

Industry and nationaland international

experts

Draft2011 november

Proposal to HealthMinistry

( December 2012)Meeting ANAMED-

Ministry

Juridic DepartamentHealth Ministry

( 2013)

2011 march

Reference Product Selection

1.-Sufficient time comercialization

Clarity regarding its benefit/risk profile

2.-Product approved based on a full dossier

Quality, efficacy and safety

3.-dosage form, dosage, route of administration and indications

of the Biosimilar same as that of de Reference product

4.-A biosimilar should not be considered as Reference product

It distorts the comparison

5.-The same Reference product for exercise comparability

consistent data

Biosimilarity based on concepts of comparability

Quality

preclinical

clinical

Quality requirements

Quality Dossier identical to any biotechnological more comparability exercise with

the reference

Quality requirements

Manufacturing Process: Description complete fabrication method with emphasis on method of purification and GMP compliance.

Characterization of Reference product and Biosimilar: physicochemical properties Information concerning its biological activity Their immunochemical propertiesInformation on impuritiesProduct specifications, techniques and analytical methodologiesStability studies on product Process validation, reprocesses and analytical methods

Clinical

Studies

Pre-Clinical Studies

Characterization and integral comparison on all quality attributes

between PBR and PBS

Requeriments for Biosimilar

Comparability

Pre-clinical in vitro

Receptor binding studies

Cell-based assay

OBJ establish comparability of biological /PD activity

p

Pre-Clinical in vivo

Relevant animal species

Evaluation of biological/PD activity to the clinical application

Repeated dose toxicity study

Clinical

Phase I: PK and PD

Phase III: Pivotal efficacy and safety

Immunogenicity

The lifetime of the medicinal product

PV and Management Risk Plan

Factors Immunogenicity

Protein

Sequences

Folding

Aggregation

Impurities

Patient

Inmune Status

Co-morbidities

Genetics

Route of administration

Frequency

Dose administered

Immunogenicity

Pharmacovigilance (ICHE2E)

Serious Events Reports

Periodic Safety Information

Management Risk Plan

Traceability

• Brand name

• Name of the active substance (INN or DCI).

• Manufacturer

• Batch Number

• Country

OtherchangesOther manufacturing

sites

QualityAttributes

ICH Q5E

Pre change

Post change

Processemanufacturing

Changes in Manufacturing Process

Demonstration of Comparability

Compared versions pre-change and post-change Biosimilar.

Comparisons with the biotech product reference are not required.

Poor people in developing countries

Wealthy peopleand countries

0

10

20

30

40

50

60

70

80

FONASA ISAPRE Otros

%population covered by insurance

% poblacióncubierta

MIXED HEALTH SYSTEM

Health Explicit Guarantees (GES)Covers the cost of catastrophicdiseases, prevalent disease and thedrugs involved in the treatment

GES

GES

2005

80 diseases

Includesmedicines

PrevalentDiseases

(hypertension)

High cost

VIH

Hepatitis C

Sclerosis

Diseases GES

Biotechnological Medicine Diseases

Insulin Diabetes type IInfliximab juvenile Arthritis Idiopathic

Etanercept juvenile Arthritis Idiopathic

Peginterpheron alfa 2a Hepatitis B and C virus infection

Rituximab End Stage Chronic RenalFailureLymphoma in patients of 15years old or over this ageLeukemia in patients of 15 ormore years old

Interpheron beta 1a Sclerosis

Emperor Penguin Magellanic-CHILE, now designated as "Vulnerable Species"

thank you !!

you think they realize the

differences ????