Biothecnological Products Regulation in Chile and … · Biothecnological Products Regulation in...
Transcript of Biothecnological Products Regulation in Chile and … · Biothecnological Products Regulation in...
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
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.
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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