Transcript Folie 1
Biosimilars in the EU General Regulatory aspects Non-clinical and clinical evaluation
Dr. Gonzalo Calvo and Dr. Sol Ruiz CHMP members, European Medicines Agency (EMA) Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)
EVOLUTION OF MAN … in Europe
Dpt. Administración Dpt. Legal Director Ejecutivo Comunicación Dpt. Inspecciones y QC Med Uso Humano (Pre-Autorización) Med Uso Humano (Post-Autorización) Med Uso Veterinario CHMP
PROCEDIMIENTOS DE REGISTRO EN LA UE
• CENTRALIZADO • DESCENTRALIZADOS
• Reconocimiento mutuo • Descentralizado
EL PROCEDIMIENTO CENTRALIZADO ES OBLIGATORIO....
• • • • Tecnología del ADNr Introducción de una etapa biotecnológica Terapia génica (incluye vectores) Terapia celular • • • • HIV Oncológicos Enfermedades neurodegenerativas Diabetes • • Enf autoinmunitarias Enf. virales 1995 2005 2008
Centralised Procedure
•
Regulatory review Process
• 1 Marketing Authorisation
valid EU
• • 1 Invented name (Tradename) 1 Common Labelling
(22 languages identical)
• Summary of Product Characteristics
(SPC)
• User Package Leaflet &
Package Labelling
• Maximum time limit • 210 days Evaluation ---> Opinion
CHMP
• • • • Chairman (Dr Eric Abadie) & Vice-Chairman (Tomas Salmonson)
1
scientific expert
member
nominated by each MS
and 1 alternate 1
scientific expert
member
from NO and IS
and 1 alternate
(observers)
5 co-opted members
(ES, UK, NL, LU, DE)
CENTRALISED PROCEDURE (new product) 4.
5.
6.
7.
1.
2.
3.
“ Pre-submission meeting ” : Meeting at the EMEA to discuss procedural, regulatory or legal aspects of the submission.
A “ Project Team Leader ” (PTL) is appointed by the EMEA Appointment of Rapporteur/Co-Rapporteur and their assessment teams: 7 months prior to the intended submission date (at the CHMP meeting) Decision of the invented name Submission of the dossier Validation of the application Start of the procedure. Timetable: 270 day
Pre submission Secondary evaluation
Centralised Procedure
Day 0 - 120
Primary evaluation CLOCK STOP
Day 121 – 210
Opinion/ Decision
LAUNCH
Post authorisation Activities
PhVWP CTWP SAWP BPWP GTWP VWP CHMP Other WPs BWP QWP SWP BMWP EWP
eCTD package
Modul e 3 Quality
Mod 1 Regiona l Info Not part of CTD Module 2
NC Overvie w NC Summar y Clinical Overview Clinical Summary
C T D
Module 4
Non clinical
Module 5 clinical
Abridged application – generic (no data exclusivity) Healthy Human Volunteer trials Reference Product Bioequivalence Study
Abridged application – Biosimilar (bio-generic) (No data exclusivity) Non clinical studies Clinica l studies Reference Product
General aspects (1)
• • • •
Centralised procedure Biosimilar: = phrmaceutical form, dosis and route of administration It is ot possible in principle to extrapolate between different routes of administration Reference product must be the same troughought the dossier and be available in the EU
General aspects (2)
• • • •
Comparative “in vitro” e “in vivo” non-clinical studies
• • • •
PK PD Immunogenicity Toxicity Efficacy and safety data ensuring clinical comparability Imunogenicity Risk Management Plan
Defines principles General guidelines Quality / Safety Efficacy Biosimilar References Overarching Guideline (CHMP/437/04).
“Guideline on Similar Biological Medicinal Products” Biotechnology- derived proteins Quality Non clinical Clinical Product class specific data requirements Insulin Non clinical Clinical Somatropin Non clinical Clinical GCSF Non clinical Clinical Epoetin Non clinical Clinical IFN-
Non clinical Clinical LMMH Non clinical Clinical
In principle, the concept of “similar biological medicinal products” applies to any biological medicine. Guideline CPMP/BWP/437/04
Insulin Non clinical Clinical Somatropin Non clinical Clinical GCSF Non clinical Clinical Epoetin Non clinical Clinical IFN-A Non clinical Clinical LMWH Non clinical Clinical B-IFN mAbs More complex
Feasible?
Possible?
Risk – – – RISK MANAGEMENT + Benefit
Sistema de Farmacovigilancia y Plan de Gestión de Riesgos
• • •
Riesgos identificados Riesgos potenciales
• •
De clase Individuales Programa para
• • • •
Detectar Cuantificar Minimizar Evaluar el impacto de las medidas
• •
Efectos de clase Immunogenicidad
• • •
Notificación espontánea Estudios epidemiológicos Registros
•
TRAZABILIDAD!
Factors potnetially influencing the immunogenicity of a particular product Structure
Nature of the protein Glycosilation
Other factors
Assay metods Impurities Formulation Route of adminitration Dose and treatment duration Patients characteristics Concomitant treatments ???
Consequences
Loss of efficacy Neutralisation of native proteins General immunological effects
In summary … • • • • • •
The legal framework in the EU is relatively clear The concept of essential similarity and interchangeability is not applicable, today, in most EU conuntries In general. Therapeutic equivalence in at least the most sensitive indication is the rule Clinical immunogenicity data must be provided pre-marketing A RMP should be provided as for an innovator product Challenging future!
Biosimilar thinking has evolved
How much do we need to know?
Idea: C. Nick How much „similarity“ do we need?
El sentido común es, posiblemente, el elemento más importante a la hora de evaluar y utilizar herramients terapéuticas.
Thank goodness! I got it!