Transcript Title

Regulatory workflow for
Registration of Biosimilar
products in Egypt
Presented by: Dr/Mona Saleh
Biologicals Registration Directorate
Central Administration for Pharmaceutical Affairs
www.eda.mohealth.gov.eg
[email protected]
Topics discussed in the presentation
 Establishment History
 Mandate Legal Frame Work
 Structure of regulatory bodies
 Biologicals in Egypt
 Similar Biological products
 Development of a Biosimilar product
 Registration of a Biosimilar Product
 Reference guidelines
1
Establishment History
 Presidential decree (398/1995)
For NORCB establishment.
 Presidential Decree (244/2009)
executive aspect for NORCB functions.
 Administrative decree (16/2009)
Establishment of Biological Products Registration Department
 Administrative decree (3/2009)
Establishment of Biological Products Inspection Directorate
 Ministerial Decree (297/2009)
Rules & procedures for Registration of Biological products ,
vaccines, serums & blood derivatives.
2
Mandate Legal Frame work
 Pharmacy Law (127/55)
Specially Article 58 , 59 ,60 ,61.
 Ministerial Decree (95/2005)
Assignment responsibility of approving clinical protocols to the Ethics
committee of clinical research
 Ministerial Decree (297/2009)
Rules & procedures for Registration of Biological products , vaccines, serums
& blood derivatives.
 Ministerial Decree (26/2009)
For the charges(fees) rendered for CAPA services.
 Ministerial Decree (399/2010)
Assignment responsibility of approving protocol & following up the process
of clinical trials to NORCB
 Ministerial Decree (632/2010)
Instruction of evaluation working parties of biological
3
Structure of regulatory bodies
Minister of Health
Minister Assistant for Pharmaceutical
Affairs
Central Administration
for Pharmaceutical
Affairs “CAPA”
General
General
Registration Directorate Inspection Directorate
Biological products
Biological Products
Registration Directorate Inspection Directorate
National Organization for
Research & Control of
Biological “NORCB”
Biologicals in Egypt
Biological products are defined as:
Medicinal products made of substances
extracted from or produced by living sources
whether they are genetically modified living
organisms or Liquids and tissues extracted from
various human or animal sources
5
Biologicals in Egypt
 Blood derived products
 Vaccines & Sera
 Epoetins
 Interferons
 Heparins
 Monoclonal Antibodies
 Cytokines
 Hormones
 Insulins
 Miscellaneous
Scope of this presentation is
All Biological product Classes other than Blood Products
and their recombinant analogues, Vaccines and Sera
6
Biosimilars
Biosmilar product is defined as:
Biological product (other than blood derived
products and their recombinant analogues,
vaccines and sera) having the same active
substance, dosage form, Strength and route of
administration of a reference biological product
and has proven through a comparability program
that its quality, safety and efficacy is equivalent to
a reference biological product when prescribed in
a claimed indication
7
Development of a similar biological product
Two approaches for development can be
applied
Biosimilar approach
Standalone approach
complete product development
program (Quality, Preclinical and
Clinical)
Excluded from the scope of this
guidelines
complete product CMC development in
addition to:
comparability quality exercise,
reduced preclinical and clinical
comparability studies
Inorder to demonstrate biosimilarity of
the proposed biosimilar product with
the reference biologicalproduct
8
Reference Vs. Biosimilar
Clinical
Clinical
Preclinical
Preclinical
Quality
+
Quality
(CMC)
comparability
Reference
Biosimilar
9
10
How to develop a biosimilar product
Reference
selection
Data
collection
CMC
development
Preclinical
development
Clinical
development
Comparability exercise is part of the development
process of the biosimilar product
11
How to develop a biosimilar product
continue
Collect all possible accessible data on the reference product from the
literatures before developing the manufacturing process to understand
the reference product characteristics regarding the quality, safety and
efficacy.
Select different batches of the reference product and document its
data (batch no., expiration date,…) in order to perform extensive
analytical characterization for the reference product, this would
enable the applicant to:
- Detect batch to batch variation within batches of the same reference
product.
- Specify the acceptance criteria for biosimilarity with justification
12
How to develop a biosimilar product (cont.)
-A single reference product must be used for all comparability exercises
during the development process (i.e. quality, safety and efficacy).
-The reference product should be justified by the manufacturer of the
biosimilar product according to the following criteria:
Should be authorized on basis of complete dossier (full Quality,
Preclinical and Clinical data), Therefore an approved biosimilar cannot
be considered as a reference product.
Should have the same dosage form, strength, and route of
administration of the biosimilar product intended to be developed
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How to develop a biosimilar product (cont.)
The Reference product should be either licensed in Egypt
Or
Licensed and widely Marketed in a reference country for at least 4 years
14
Registration of a biosimilar product
Two approaches are applied for biosimilar
product registration
Final dossier approach
(for imported products)
Development process has been
already done under supervision of the
manufacturer country’s health authority
and
only evaluation of the final product is
done
Stepwise approach
(for local products)
Development and registration
processes proceed side by side The
manufacturer evaluate the
development process at phases
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Final dossier approach (Imported product)
Phase 1 (Box Approval)
Phase 2 (Pricing)
Phase 3 (Complete CTD Submission & Evaluation)
M2, M4 & M5
(Biologicals
evaluation
committee))
M3 (NORCB)
SMFs, M.P &
process validation
(inspection
department)
Stability
studies
(stability
committee)
PSUR, RMP
& DDPS
(PVC)
Phase 4 (Reports Collec., review and Tech. Committee subm.)
(EWP decision, PVR, Stability R, TAR, Analysis report, Insert, Pack, Price)
Issue Registration license
16
Final dossier approach (cont.)
Required Docs
Approval
DisApproval
Time Line  15 Working Days
17
Final dossier approach (cont.)
Required Docs
Price
Time Line  60 Working Days
18
Final dossier approach (cont.)
Complete CTD
M2
(Biologicals
evaluation
committee))
M3,M4, M5
(NORCB)
SMFs, M.P &
process validation
(inspection
department)
Stability
studies
(stability
committe)
PSUR, RMP
& DDPS
(PVC)
Time Line  60 Working Days
19
Final dossier approach (cont.)
(EWP decision, PVR, Stability R, TAR, Analysis report, Insert, Pack)
Issue Registration license
Time Line  60 Working Days
20
Stepwise approach (Local products)
Phase 1 (Box Approval)
Phase 2 (Pricing)
Phase 3 (API Evaluation Phase)
ASMF Evaluation
SMF of API Evaluation
Issue Preliminary approval (Valid for 3 Years)
(Finished product manufacturing & Control – perform Stability studies –
preclinical studies)
Phase 4 (CMC, Preclinical studies & Clinical protocol
evaluation phase)
Stability
evaluation
(stability
committee
)CAPA
Charact. & Anal.
procedure
evaluation at
NORCB (registration
analysis certificate)
M.P & process
validation
Evaluation
(inspection
department)
CAPA
Preclinica
l studies
evaluatio
n
(NORCB)
Clinical protocol
evaluation
(Ethics
committee at
M.O.H & NORCB
21
Stepwise approach (Local Products) (Cont.)
Performing Clinical trials (during the 3 years)
Supervising the process by NORCB
Phase 5 (Complete CTD Submission stability approval + analysis report,
M1, Clinical studies & PV system evaluation)
M1 evaluation (Front
office department)
Clinical studies
evaluation (Biologicals
evaluation committee)
RMP & DDPS (PV
center)
Phase 6 (Reports Collection, review and Tech. Committee submission)
(EWP decision, PVR, Stability R, TAR, Analysis report, Insert, Pack, Price)
Issue Registration license
22
Stepwise approach (Local Products) (Cont.)
Required Docs
Approval
DisApproval
Time Line  15 Working Days
23
Stepwise approach (Local Products) (Cont.)
Required Docs
Price
Time Line  60 Working Days
24
Stepwise approach (Local Products) (Cont.)
1- ASMF
2- SMF of API
ASMF
NORCB
SMF of API
CAPA
Biological
Inspection
Directorate
(Finished product manufacturing & Control
– perform Stability studies – preclinical studies)
Time Line  60 Working Days
25
During The 3 Years
Stepwise approach (Local Products) (Cont.)
CMC, Preclinical,
Clinical Protocal
Stability
evaluation
(stability
committee
)
Charact. & Anal.
procedure
evaluation at
NORCB (registration
analysis certificate)
M.P & process
validation
Evaluation
(inspection
department)
CAPA
Preclinical
studies
evaluation
(NORCB)
Clinical
protocol
evaluation
(Ethics
committee at
M.O.H &
NORCB
Performing Clinical trials
Supervising the process by NORCB
26
Stepwise approach (Local Products) (Cont.)
Complete CTD
M1 evaluation (Front
office department)
Clinical studies
evaluation (Biologicals
evaluation committee)
RMP & DDPS (PV
center)
Time Line  60 Working Days
27
Stepwise approach (Local Products) (Cont.)
(EWP decision, PVR, Stability R, TAR, Analysis report, Insert, Pack)
Issue Registration license
Time Line  60 Working Days
28
Re-registration
Re-registration process
for products Registered
before as Generics
(i.e. No clinical studies
performed on the
product)
Well established
PV system that
can prove
safety and
Efficacy
Phase IV
comparability
studies depend
on the Pv system
and PSUR
Quality
Comparability
studies on case
by case basis
No PSUR on the
previous registration
period
(No available data
on safety and
Efficacy)
Phase IV
comparability
studies is
mandatory
Quality
Comparability
studies on case
by case basis
29
Reference guidelines
Global:
• WHO- GUIDELINES ON EVALUATION OF SIMILAR BIOTHERAPEUTIC PRODUCTS
(SBPs)
• ICH guidelines
• ICH - Pre-clinical safety Evaluation of Biotechnology-derived
•
•
•
•
•
•
pharmaceuticals S6
ICH- General consideration for clinical trials E8
ICH- Statistical principles for clinical trials E9
ICH- Quality of Biotechnological products: Stability testing of
Biotechnological/Biological products Q5C
ICH- Derivation and characterization of cell substrates used for production
of Biotechnological/Biological products Q5D
ICH- Viral safety evaluation of Biotechnology products derived from cell
lines of human and Animal origin Q5A
ICH- Development and manufacture of drug substances (chemical
entities and biotechnological/biological entities Q11
30
Reference guidelines
•
•
•
•
•
EMA-Overarching biosimilar guidelines
EMA- Product-specific biosimilar guidelines
EMA- Other guidelines relevant for biosimilars
EMA- Scientific Guidelines on Biological Drug substances
EMA- Scientific Guidelines on Biological Dug Products
• FDA- Quality Considerations in Demonstrating Biosimilarity to a Reference
•
Protein Product
FDA- Scientific Considerations in Demonstrating Biosimilarity to a Reference
Product
• CDSCO- Indian Biosimilars Guidelines
31
Thank You