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Regulatory workflow for Registration of Biosimilar
products in Egypt
Biologicals Registration DirectorateCentral Administration for Pharmaceutical Affairs
Presented by: Dr/Mona Saleh
Topics discussed in the presentation
2
Establishment HistoryMandate Legal Frame WorkStructure of regulatory bodiesBiologicals in EgyptSimilar Biological productsDevelopment of a Biosimilar productRegistration of a Biosimilar ProductReference guidelines
Establishment History
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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.
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 4
Structure of regulatory bodies
Minister Assistant for Pharmaceutical Affairs
National Organization for Research & Control of Biological “NORCB”
Central Administration for
Pharmaceutical Affairs “CAPA”
Biological products Inspection Directorate
Biological Products Registration Directorate
Minister of Health
GeneralInspection Directorate
GeneralRegistration Directorate
Biologicals in Egypt
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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
Biologicals in Egypt
Blood derived products Vaccines & Sera Epoetins Interferons Heparins Monoclonal Antibodies Cytokines Hormones Insulins Miscellaneous
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Classes of Biological products
Scope of this presentation is All Biological product Classes other than Blood
Products and their recombinant analogues, Vaccines and Sera
Biosimilars
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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
Development of a similar biological product
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Two approaches for development can be applied
Standalone approachcomplete product development
program (Quality, Preclinical and Clinical)
Excluded from the scope of this guidelines
Biosimilar approachcomplete product CMC
development in addition to:
comparability quality exercise, reduced preclinical and clinical
comparability studiesInorder to demonstrate biosimilarity of the proposed biosimilar product with
the reference biologicalproduct
Reference Vs. Biosimilar
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Clinical
Pre-clinical
Quality(CMC)
Reference Biosimilar
Clinical
Pre-clinica
l
Quality
+ comparabili
ty
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How to develop a biosimilar product
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Reference
selection
Data collectio
n
CMC developme
nt
Preclinical developme
nt
Clinical developme
nt
Step wise Biosimilar development process:
Comparability exercise is part of the development process of the biosimilar product
How to develop a biosimilar product continue
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Data CollectionCollect 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
How to develop a biosimilar product (cont.)
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Reference selection
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
- 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:
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How to develop a biosimilar product (cont.)
Reference selection (cont.)The Reference product should be either licensed in Egypt
OrLicensed and widely Marketed in a reference country for at least 4 years
Registration of a biosimilar product
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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
Final dossier approach (Imported product)
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Final dossier approach (cont.)
Company
Required Docs
CAPABiological
Registeration DirectorateFront Office
DisApprovalApproval
Time Line 15 Working Days
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Final dossier approach (cont.)
Company
Required Docs
CAPAPricing
Committee
Price
Time Line 60 Working Days
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Final dossier approach (cont.)
Company
Complete CTD
CAPABiological
Registeration Directorate
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
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Final dossier approach (cont.)
CAPABiological
Registeration Directorate
(EWP decision, PVR, Stability R, TAR, Analysis report, Insert, Pack)
Technical Committee Submission
Issue Registration license
Time Line 60 Working Days
Stepwise approach (Local products)
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Stepwise approach (Local Products) (Cont.)
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Stepwise approach (Local Products) (Cont.)
Company
Required Docs
CAPABiological
Registeration DirectorateFront Office
DisApprovalApproval
Time Line 15 Working Days
25
Stepwise approach (Local Products) (Cont.)
Company
Required Docs
CAPAPricing
Committee
Price
Time Line 60 Working Days
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Stepwise approach (Local Products) (Cont.)
Company
1- ASMF2- SMF of API
CAPABiological
Registeration Directorate
SMF of APICAPA
Biological Inspection Directorate
ASMFNORCB
Technical Committee Submission
(Finished product manufacturing & Control – perform Stability studies – preclinical
studies)
Time Line 60 Working Days
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Stepwise approach (Local Products) (Cont.)D
uri
ng
Th
e 3
Years Company CMC, Preclinical,
Clinical Protocal
CAPABiological Registeration
Directorate
Stability evaluatio
n (stability committ
ee)
Charact. & Anal. procedure
evaluation at NORCB
(registration analysis
certificate)
M.P & process
validation Evaluation (inspection
department) CAPA
Preclinical
studies evaluatio
n (NORCB)
Clinical protocol
evaluation (Ethics
committee at M.O.H &
NORCB
Performing Clinical trials
Supervising the process by NORCB
Approval
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Stepwise approach (Local Products) (Cont.)
Company
Complete CTD
CAPABiological
Registeration Directorate
Time Line 60 Working Days
M1 evaluation (Front office department)
Clinical studies evaluation (Biologicals evaluation committee)
RMP & DDPS (PV center)
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Stepwise approach (Local Products) (Cont.)
(EWP decision, PVR, Stability R, TAR, Analysis report, Insert, Pack)
Technical Committee Submission
Issue Registration license
Time Line 60 Working Days
CAPABiological
Registeration Directorate
Re-registration
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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 comparab
ility studies depend
on the Pv system
and PSUR
Quality Comparab
ility studies on case by case basis
No PSUR on the previous registration
period(No available data on safety and Efficacy)
Phase IV comparab
ility studies is mandator
y
Quality Comparab
ility studies on case by case basis
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
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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
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Thank You
