Post on 30-Apr-2018
An introduction to the regulatory framework
of Biotechnology
Business Economics of Biotechnology
8 November 2012
Marc Martens
2© Bird & Bird LLP/LSTS 2012
Section 1 – Introduction
Section 2 – Biotechnological medicinal products
Sub-Section 1 – Medicinal productsmarketing authorisation
abridged proceduresRegulatory Data
Protection
Sub-Section 2 – Biological medicinal products, biosimilars
Sub-Section 3 – Cells tissues ATMPs
Section 3 - GMOs
Section 4 - Conclusion
Table of contents
4© Bird & Bird LLP/LSTS 2012
Biotechnology
Biotechnology is the use of living organisms, or products of living organisms, for human benefit, to make a product or solve a problem
● Scope is extraordinarily broad, as to origins and technologies involved
Applications historically used for ages, and still used today
● Selective breeding, fermentation, …
5© Bird & Bird LLP/LSTS 2012
Types of biotechnology : helicopter view (1)
Different types of biotechnology
● Microbial
● Agricultural• Genetically modified cultures
• Molecular pharming
● Animal• Transgenic animals as sources of antibodies (bioreactors)
• Aquaculture
● Forensic (DNA Fingerprinting)
● Bioremediation (e.g. oil degrading bacteria)
● Medical
All types are interdependent (>same scientific sources)
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Types of biotechnology : helicopter view (2)
● WHITE biotechnology• Industry
● RED biotechnology• Medicine
● GREEN biotechnology• Agriculture
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Genetic engineering through molecular
biology and Analysisthrough
bioinformatics
Environmentaland aquaticapplications
Drug development
Agricultural biotechnology
Detection
Pharmaceuticals and Healthcare
Regulatoryapproval / Oversight
Schematic view
Physiology (human, animal, plant)
MathematicsMolecular and
cell biologyImmunology
Statistics MicrobiologyBiochemistry
PhysicsChemical
engineering
Computer Science
Genetics
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8© Bird & Bird LLP/LSTS 2012
Physiology (human, animal, plant)
MathematicsMolecular and
cell biologyImmunology
Statistics MicrobiologyBiochemistry
PhysicsChemical
engineering
Computer Science
Genetics
Genetic engineering through molecular
biology and Analysisthrough
bioinformatics
Schematic viewPharmaceuticals and Healthcare
Detection
Regulatoryapproval / Oversight
Agricultural biotechnology
Drug development
Privacy/ Data protection/
Criminal law
Pharmaceutical law/Social security law /
Patients’ rights
Public bodies (EU: EMA, EFSA, etc.
National: FAHMP, FASFC, ethics
committees etc.)
GMO regulations / consumer protection
Pharmaceutical law / Clinical
trials
GMO regulations / consumer protection
Environmentaland aquaticapplications
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Depending on the product, the intended application, or finality, different regulatory frameworks can apply
● crucial to consider those aspects in the earliest stages of product development
Some areas subject to Health, Environmental as well as Ethicalconcerns
Some areas of biotechnology are highly regulated
10© Bird & Bird LLP/LSTS 2012
Phyto-pharmaceutical
product
Importance of product qualification
Medical device
e.g. Directives90/385/CEE
and 93/42/CEE
Foodstuff(possibly GMO)
Numerousregulations
and directives
Cosmetics
e.g. Directive 76/768/EEC
Food additive
e.g. Directive 89/107/CEE
Chemicalproduct
e.g. Regulation1907/2006,
Directive 67/548/EEC
Medicinalproduct
e.g. Directive 2001/83/EC,
Regulation 726/2004
Product
e.g. Directive 91/414/EEC
12© Bird & Bird LLP/LSTS 2012
Section 1 – Introduction
Section 2 – Biotechnological medicinal products
Sub-Section 1 – Medicinal productsmarketing authorisation
abridged proceduresRegulatory Data
Protection
Sub-Section 2 – Biological medicinal products, biosimilars
Sub-Section 3 – Cells tissues ATMPs
Section 3 - GMOs
Section 4 - Conclusion
Table of contents
13© Bird & Bird LLP/LSTS 2012
Sub-Section 1 – Medicinal productsmarketing authorisation
abridged proceduresRegulatory Data
Protection
14© Bird & Bird LLP/LSTS 2012
Definition of “medicinal product”:“Any substance or combination of substances presented as having properties for treating or
preventing disease in human beings; or
Any substance or combination of substances which may be used in or administered to human
beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic
action, or to making a medical diagnosis.”
(Directive 2001/83/EC)
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Brief introduction on medicinal productsWhat is a medicinal product ?
Broad, twofold definition● presentation criterion
● application criterion
Case law● Medicinal product / Food
• Vitamin preparations can be medicinal products
• Herbal tea can be a medicinal product
● Medicinal product / Cosmetics
• A hair growth product is a cosmetic, but can be presented as a medicinal product
• Eye lotions can be medicinal products
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Brief introduction on medicinal productsThe legal framework
EU law
● Community Code on medicinal products = Directive 2001/83/EC• Supplemented by other sources
- Regulations (a.o., Regulation 726/2004)
- Guidelines (EMEA)
- Court of Justice/General Court case law
Belgian law
● Implementation of Directive 2001/83/EC• Act of 25 March 1964
• Royal Decreee of 14 December 2006
● Key role of the competent authority : Federal Agency for Medicinesand Health Products (FAHMP)
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Brief introduction on medicinal productsThe Marketing Authorisation (MA)
Basic rule : all medicinal products are subject to a MA
MA dossier intended for the assessment of :● Quality● Safety● Efficacy
MA procedures for medicinal products● Centralised● Decentralised procedure (DCP)
and mutual recognition procedures (MRP)● National procedure
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Key role of the ReferenceMember State
Application in one MemberState (e.g. Belgium)
Dossier filed at the FAHMP (Federal Agency for Healthand Medicinal Products)Competent authority : Ministry of Public Health
MA only valid in Belgium MA valid throughout the EUNational MAs
Dossier filed at the EMEA (London)Competent authority : European Commission
Dossier filed in one or several Member States (simultaneously or not) -MA may be extended to other Member States
Centralised procedureMutual recognition
procedureDecentralised procedure
Overview of MA procedures under EU law
19© Bird & Bird LLP/LSTS 2012
Timeline of a medicinal product
10 25201550
Life cycle IP
SPC
2 1RDP 8
Patent Application
Pharmacology
Chronical toxicity
Acute toxicity
Clinical Trials IPhase II
Phase III
Marketing authorization
Price
Reimbursement
Pharmacovigilance
SPC
Basic Patent SPC
R&D Clinical trials Placing on the market
20© Bird & Bird LLP/LSTS 2012
Information to provideThe full dossier
Bio-pharmaceutical StudiesStudies Pertinent to Pharmaco-kinetics Using Human Bio-materialsHuman Pharmaco-kineticHuman Pharmaco-dynamicEfficacy and Safety StudiesPost-marketing Experience
Clinical study reports
PharmacologyPharmaco-kineticsToxicologyOther Toxicity Studies
Non-clinical reports
Summary of product characteristics, labelling and package leaflet, etc.
Administrative information
See Annex I of Directive 2001/83 and Notice to Applicants
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Types of abridged procedures
« without prejudice to IP rights », the applicant will not have to provide the results of pre-clinical tests and clinical trials under:
● Bibliographic procedure
● Two abridged procedures
● Hybrid abridged procedure
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Generics : abridged procedure
Medicine
Compared to the reference product :
● Same qualitative and quantitative composition in active substances
● Same pharmaceutical form
● Bioequivalence (demonstrated by bioavailability studies)
Article 10.1 Directive 2001/83● the applicant is not required to provide the results of pre-clinical
tests and of clinical trials if he can demonstrate that the medicinal product is a generic of a reference medicinal product which is or has been authorized under Article 6 for not less than eight years in a Member Stateor in the Community
● Right of reference
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Regulatory Data Protection / Exclusivity
For pioneer applicant (innovator):● Right to prevent during a certain period of time the regulatory authorities
from relying on the preclinical and clinical trials results of the princeps(reference medicinal product) when considering the approval of a second application (for a generic)
For second applicant (usually a generic):● Right to apply for MA according to an abridged MA procedure and thus to
rely on the original data submitted by the pioneer applicant when the data exclusivity period has expired
Means a generic has to provide his own clinical data while RDP is in force● But that a generic can rely on data filed by innovator after expiry of RDP
RDP rules have evolved over time● Mainly to encourage generic competition and reduce drug prices
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Duration of RDP: the “8+2+1” rule
Data exclusivity period for all reference medicinal products (MRP, CP, DP)No reference can be made to the results of the tests/trials conducted for the reference product
Marketing exclusivity for all reference medicinal products Generic cannot be put on the market but generic applicant can seek a MAby referring to the data of the reference product (abridged procedure)
Extension (see hereafter)
8 years
2 years
1 year
+
+
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8+2+1 RDP for new indications: new NCE’s
Directive 2001/83, article 10.1, al 4
New therapeutic indications have to bring a significant clinical benefit in comparison with existing therapies
Application for a new indication for a well-established substance
Non-cumulative period of 1 year of data exclusivity
Data exclusivity period refers exclusively to the data concerning the new indications
Once the well-established character is demonstrated, the additional 1 year exclusivity can be obtained without time limit
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Active Substance
What is meant by active substance?• The different salts, esters, ethers, isomers, mixtures of isomers, complexes
or derivatives of an active substance = same active substance - art. 10.2 (a) Directive 2001/83 and SmithKline Beecham decision
• Unless they differ significantly in properties with regard to safety and/or efficacy - in such cases, additional information providing proof of the safety
and/or efficacy of the various salts, esters or derivatives of an authorized active substance must be supplied by the applicant
What is meant by pharmaceutical form?• The various immediate-release oral pharmaceutical forms = one and same
pharmaceutical form
Only a medicinal product authorized on the basis of a complete dossier (quality, safety, efficacy, with non-clinical tests and clinical trials) can be used as reference
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Is there any additionnal period for RDP for new strenghths, pharmaceutical forms,…
“Global MA” concept
● No further period of RDP
● “When a medicinal product has been granted an initial marketing authorization in accordance with the first subparagraph, any additional strengths, pharmaceutical forms, administration routes, presentations, as well as any variations and extensions shall also be granted an authorization in accordance with the first subparagraph or be included in the initial marketing authorization. All these marketing authorizations shall be considered as belonging to the same global marketing authorization, in particular for the purpose of the application of Article 10(1)”, see Art. 6 (1), al. 2 of Directive 2001/83
● Meaning no additional RDP for line extensions (other than new indications)
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Global MA - issues
Meaning of the « same MA holder »?● = applicants belonging to the same mother company or group of companies,
as well as applicants which have concluded agreements (e.g. licensees) or which exercises concerted practices concerning the placing on the market of the relevant medicinal product
● see NTA, Chap. 2, para 3.2.1. & Commission Communication on the Community MA procedures for medicinal products, OJ C 229
What if a subsequent MA (i.e. for a new pharmacological form) isgranted centrally?● « Where a product is initially authorized nationally and subsequently, an
additional strength, pharmaceutical form, administration route or presentation is authorized through the centralized procedure, this shall also be part of the global marketing authorization » (see NTA, Chap. 1 , para.2.3)
What about « multiple applications »?● covered by the “Global MA” concept (see NTA, Chap. 1, para 2.3)
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Main Changes in EU RDP Regulation (1)
Previous rules
Line Extension
Duration
Current rules (nov. 2005)Directive 2001/83 as modified
by Directive 2004/27
• MRP: 6 – 10 yearsCP: 10 yearsEx-concertation: 10 years in all MS
• Limitation to patent expiry
• MRP: 6 – 10 yearsCP: 10 yearsEx-concertation: 10 years in all MS
• Limitation to patent expiry
No supplementary RDP (art. 6), except +1 year when:- new therapeutic indication- new indication for well-established substance
No supplementary RDP (art. 6), except +1 year when:- new therapeutic indication- new indication for well-established substance
No supplementary RDPNo supplementary RDP
Change ofclassification +1 year RDP+1 year RDPNo supplementary RDPNo supplementary RDP
• 8 years
+ 2 (marketing exclusivity)
+ 1 (see hereunder)
• No limitation to patent expiry
• 8 years
+ 2 (marketing exclusivity)
+ 1 (see hereunder)
• No limitation to patent expiry
30© Bird & Bird LLP/LSTS 2012
Main Changes in RDP Regulation (2)
Characteristic of considered
product
« Generic » medicine(SmithKline Beecham, Novartis)
« Generic » medicine(SmithKline Beecham, Novartis)
• Medicine « essentially similar » to the reference product
• Concept not defined in legislation• Conditions: Notice to Applicants + case law
• Medicine « essentially similar » to the reference product
• Concept not defined in legislation• Conditions: Notice to Applicants + case law
Bioequivalence Unclear situation : see Generics, NovartisUnclear situation : see Generics, Novartis Must be demonstrated by appropriate bioavailability studies
Must be demonstrated by appropriate bioavailability studies
Previous rulesCurrent rules
Directive 2001/83 as modified by Directive 2004/27
ReferenceProduct
• « is or has been authorized »• European reference product,
must not be authorized in the MS where the protection is sought
• Global MA: one and unique application for a product line
• « is or has been authorized »• European reference product,
must not be authorized in the MS where the protection is sought
• Global MA: one and unique application for a product line
• Must be « marketed », = authorized• In the country where generic
authorization is sought• Authorization of generic even if
MA of reference product is withdrawn (AstraZeneca)
• Must be « marketed », = authorized• In the country where generic
authorization is sought• Authorization of generic even if
MA of reference product is withdrawn (AstraZeneca)
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Definition of “Biological medicinal product”
Means that the active ingredient is a biological substance derived from living cells
“Biological substance”● Substance produced or extracted from a biological source● Combination of physico-chemical-biological testing, production process and its
control are needed for its characterization and determination of quality
Examples of biological medicines:● Immunological medicinal products and medicinal products derived from blood
and human plasma (article 1.4 et 1.10 of Directive 2001/83)● Medicinal products developed by recombinant DNA technology, controlled
expression of genes coding for biologically active proteins from a cell culture, hybridoma and monoclonal antibody methods
● ATMP
Biologicals are among best-selling/fastest growing drugs in the world● Epogen/Procrit®, Enbrel®, Humira®, Remicade®, Herceptin®, Avastin®
See Annex 1 of Directive 2001/83, Part I; point 3.2.1.1 (b))
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Centralised procedure
Annex to Regulation 726/2004 (centralised procedure for MA) considerstwo types of ‘biotechnological’ medicinal products :
● Medicinal products developed by means of certain biotechnological processes:
• recombinant DNA technology,• controlled expression of genes coding for biologically active proteins in
prokaryotes and eukaryotes including transformed mammalian cells,• hybridoma and monoclonal antibody methods
● Advanced Therapies (Advanced Therapy Medicinal Products) –a more recent addition, through Regulation 1394/2007
Those products have to be authorized through the centralisedprocedure
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Centralised procedure
Characteristics
● Single application
● Single evaluation
● Single decision for the whole EU territory (+ Iceland, Liechtenstein and Norway)
Application procedure can take up to 2-3 years
The dossier requirements are extensive, expensive and take a lot of time to prepare
www.ema.europa.eu
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Adoption of CHMP Opinion + CHMP Assessment Report. Adoption of a timetable for the provision of product information translations
Final draft of English SPC, labelling and package leaflet sent by applicant to theRapporteur and Co-Rapporteur, EMEA and other CHMP members.
Restart of the clock and oral explanation (if needed).
CHMP discussion and decision on the need for adoption of a list of “outstanding issues” and/or an oral explanation by the applicant. If an oral explanation is needed, the clock is stopped to allow the Applicant to prepare the oral explanation. Submission of final inspection report to the EMEA, Rapporteur and Co-Rapporteur by the inspection team (at the latest by day 180).
Deadline for comments from CHMP Members to Rapporteur and Co-Rapporteur, EMEA and other CHMP members
Joint Response Assessment Report from Rapporteur and Co-Rapporteur received by CHMP members and the EMEA. EMEA sends this joint Assessment Report to the applicant making clear that it is sent for information only and does not yet represent the position of the CHMP. Where applicable inspection to be carried out. EMEA/QRD sub-group meeting for the review of English product Information with participation of the applicant (optional) around day 165.
Submission of the responses, including revised SPC, labelling and package leaflet texts in English.Restart of the clock
CHMP adopts the LoQ as well as the overall conclusions and review of the scientific data to be sent to the Applicant by the EMEA.Clock stop. At the latest by Day 120, adoption by CHMP of request for GMP/GLP/GCP inspection, if necessary (Inspection procedure starts).
Receipt of draft list of questions (including the CHMP recommendation and scientific discussions), from Rapporteur and Co-Rapporteur, as discussed with the peer reviewers, by CHMP members and EMEA
Rapporteur, Co-Rapporteur, other CHMP members and EMEA receive comments from Members of the CHMP (including peer reviewers).
Receipt of the Assessment Report(s) or critique from Rapporteur and Co- Rapporteur(s) by CHMP members (which includes the peer reviewers) and EMEA. EMEA sends Rapporteur and Co-Rapporteur Assessment Report/critique to the applicant making it clear that it only sets out their preliminary conclusions and that it is sent for information only and does not yet represent the position of the CHMP.
Start of the procedure
ACTION
* Target dates for the submission of the responses are published on the EMEA Website
Source : EMEA, EMEA Pre-submission procedural advice for users of the centralised procedure, May 2008
Timetable for the evaluation of the MA Application
150
By 210
181 > 210
181
180
170
121*
120
115
100
80
1*
DAY
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Follow-up of the CHMP Opinion
Dossier to EMEA
CHMP Opinion
210 days(clock stop possible)
unfavourable favourable
Applicantannounces
appeal
Applicant doesnot appeal
15 days
60 daysto submit
CHMP reconsiders
or not60 days
CHMP Opinion
30 days
15 days
Transmission of Opinion (+annexes) to Commission, Member States, Applicant
Draft Commission decision
ApplicantMember States
Commission decision
Appeal(CFI)
ECJ
37© Bird & Bird LLP/LSTS 2012
Timeline of a medicinal product
10 25201550
Life cycle IP
SPC
2 1RDP 8
Patent Application
Pharmacology
Chronical toxicity
Acute toxicity
Clinical Trials IPhase II
Phase III
Marketing authorization
Price
Reimbursement
Pharmacovigilance
SPC
Basic Patent SPC
R&D Clinical trials Placing on the market
38© Bird & Bird LLP/LSTS 2012
What is a biosimilar?
According to article 10.4 of Directive 2001/83
● Where a biological medicinal product which is similar to a reference biological product does not meet the definition of generic medicinal products, owing to, in particular, differences relating to raw materials or manufacturing processes, the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided.
● Type and quantity of supplementary data provided must comply with • relevant criteria stated in the Annex; and • related detailed guidelines.
● The results of other tests and trials from the reference medicinal product's dossier shall not be provided.
Consequence: a biosimilar is defined by what is accepted or not by the EMEA (or other competent authorities)● No a priori definition of the acceptable differences between a biosimilar
and the reference product
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Active substance for biological medicinalproducts
“Biosimilar”
● “similar” product made according to a different process
• For example different construct, host, cell line, protocol or purification steps
• In practice: impossible to know without access to original process
• But developers of biosimilars have normally no direct access to originator’s data
- Have to reverse engineer
● (i.e. made using different process): additional pre-clinical tests or clinical trials required to show similarity
40© Bird & Bird LLP/LSTS 2012
Same active substance (NTA for biological medicinal products) =
• Same molecular structure
• Same nature of source material
• Manufacturing process
“Biogeneric” and biosimilar● same product made according to the same process
• In practice: impossible to do without access to original process
● no additional tests or trials required
• But requires the same process to be used (usually not accessible to generic)
Active substance for biological medicinalproducts
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Which approval route for biosimilars?
Centralized procedure for MA is compulsory for the following biotechnological processes (EU Regulation 729/2004)
● recombinant DNA technology
● controlled expression of genes coding for biologically active proteins from a cell culture
● hybridoma and monoclonal antibody methods
Biosimilars: mainly follow the central route
But could fall outside
● if developed according to other biotechnological processes
● non-biotech
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Biosimilars’s specific route for approval: EU Legislative Framework
+
Article 10.4
Biosimilars ≠ Generics
Supplementary data to be provided
Refers to Annex I and Guidelines
re. the type and quantityof data
Annex 1 +Directive 2001/83 Also
General Principles Practical Requirements
Part II, Section 4
Type and quantity of supplementary data
is determined on a case-by-case basis
→ Specific Guidelines
Applicable general principles in a guideline
→ Overarching Guideline
Other relevant Guidelines
GMP’s: Directive 2003/94
+ Guide
Regulation 726/2004
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Overarching GuidelineDefines basic principles, philosophy + « User guide »
General Guidelines
General principles for assessing quality,
non-clinical, clinical aspects
Product Specific Guidelines
Annexes to General Guideline on (non-) clinical issues
Address specific pre-clinical andclinical issues re. specific products
Guidelines on biosimilars
Somatropin
Insulin
Granulocyte-colony Erythropoietins
IFN-alpha
LMW heparin, etc.
Quality issues
(Non-) Clinicalissues
Apply to all
biosimilars
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Specific nature of biosimilars and consequences
Generics Biosimilars
Simple SmallStable
ComplexLarge
Less stable
Easy to characterize
Chemical process
Easy to reproduce
Identical copies
Biological substancesExtremely complex biological process :
not easy to reproduceSimilar copies
Difficult to characterize
Characteristics
Characterization
ManufacturingProcess
Bioequivalence Comparability studiesto demonstrate
similarity
Abridged Procedure for MA
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Source : Cecil Nich, BSC, Future opportunities for biosimilar mAB, 2010
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Information required for a biosimilar’s MA
Quality dataComplete self-standing quality dossier
+ Comparability exercise
Non-clinical data
Clinical data
Pharmacovigilance
Case-by-case basisAbridged programs (in vitro/in vivo)+ Comparability exercise
Abridged programs but most of the time: extensive trials are requiredAll results must be submitted ( + and -)
+ Comparability exercise
Monitoring = necessary, as for all other medicinesPharmacovigilance SystemsRMP
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Comparability of different processes?
“The product is the process”: marketing authorisation is granted for the product (defined by INN name) made according to a specific process
● The development of a biosimilar requires a complete independent product and process development
● Plus comparative testing at all stages in order to obtain approval
● Biological product is defined by the way it is manufactured● Process determines structure of product (e.g. glycosylation) and of impurities (e.g. isomers)
which may influence either affinity or potency
● Any change in the process inevitably affects the final product
Reference product
Target Qualityby Design
Quality Module 3
Physico-Chemical and
BiologicalComparability
Comparative Preclinical
Studies
Comparative clinical studies
RiskManagement
Plan
Comparative Comparative
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Experience so far:Overview of EU authorized biosimilars
Somatropin
INN Biosimilar
Epoetin alfa
Epoetin zeta
Filgastrim
Omnitrope® (Sandoz)
Valtropin® (BioPartners)
Binocrit® (Sandoz)
Epoetin alfa Hexal®
Abseamed® (MAP)
Silapo® (Stade Arzneimittel)
Retacrit® (Hospira)
Biogastim® (CT Arzneimittel)Filgastrim Ratiopharm®, Ratiogastrim®, Tevagrastim®
Reference Product
Genotropin® (Pfizer)
Humatrope® (Eli Lilly)
Eprex®/ Erypo® (J&J)
Neupogen® (Amgen)
Filgastrim Hexal®, Zarzio® (Sandoz)
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Experience so far:Refusal/Withdrawals of biosimilars
Interferon alfa
INN Biosimilar
Human insulin
Alpheon (Biopartners)
Insulin Marvel short
Insulin Marvel Intermediate
Insulin Marvel long
Status
Refused in June 2006
Withdrawn
Not all biosimilar applications have been successful
50© Bird & Bird LLP/LSTS 2012
Acceptable differences between biosimilarsand reference product
Different host cells
Quality differences between biosimilars and reference drug products
Different levels of impurities
Different formulation
Different glycosylation
ValtropinAbseamed, Binocrit,Epoetin alfa Hexal
Retacrit and Silap
Source: H. Schellekens & E. Moors, « Clinical comparability and European biosimilar regulations », in Nature Biotechnology January 2010, nr. 1, vol. 28, p. 29
Zarzio and Filgastrim Hexal
Biograstim, Filgrastim,
Ratiopharm, Ratiograstim
and Tevagrastim
Abseamed, Binocrit,Epoetin alfa Hexal
Retacrit and Silap
Zarzio and Filgastrim Hexal
51© Bird & Bird LLP/LSTS 2012
Acceptable differences between biosimilarsand reference product
These variations can have a potential major effect on a productsafety and efficacy
So far: clinical studies show no negative effect
● The differences have not compromise the efficacy or increasedthe level of adverse effects
• compared with the reference product
● Raise the question of the relevance of the comparison exercice• Comparison of quality characteristics between biosimilar and
reference product will always show differences (« product is the process »)
• Clinical data are mandatory
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Strategic Issues (1)
Merits / added value of comparability exercises are put into question● Often lack in the dossier or are incomplete, sometimes
even show that biosimilar lacks (clinical) comparability● May be a barrier for development of biosimilars of
complex biologics● Drop it?
Which degree of discretion for the competent authority?
General wording of the Guidelines● « appropriate comparability exercise », « deviation has
to be justified or, if necessary, demonstrated »« normally comparative clinical trials are required »…
● Large margin of appreciationRole of the industry in the development of guidelines
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Strategic Issues (2)
Do biosimilars get all indications ?
INN
Clear labelling
No substitution
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Cells and tissuesIntroduction
Example : uses of Mesenchymal Adult Stem Cells© stemcell-bridge.com
There are many types of cells and tissues, from embryonic stem cells to adult organs
The source of cells and tissues can behuman or animal
Cells and tissues can be used for various applications, e.g.
Scientific research
Autologous or allogeneicgrafts
Medicinal products
In vitro Diagnostics
…
57© Bird & Bird LLP/LSTS 2012
Cells and tissuesInternational Framework (examples)
•Universal texts● International
• Universal Declaration of human rights of 10 December 1948• International Covenant on Economic, Social and Cultural Rights (1966)• Universal Declaration on Bioethics and Human Rights of 19 October 2005• UN Declaration on the Rights of Indigenous Peoples in 2007• (…)
● General EU texts• Convention for the Protection of Human Rights and Fundamental Freedoms of 4 November 1950• Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of
Biology and Medicine: Convention on Human Rights and Biomedicine, Oviedo, 4 April 1997, (not ratified by Belgium)• Charter of Fundamental Rights of the European Union of 12 December 2007
•Specific texts● Patient rights
• Declaration of Lisbon on the rights of the patient (2005)• UN Political Declaration on HIV/AIDS• Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals
with regard to the processing of personal data and on the free movement of such data• Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code
relating to medicinal products for human use● Experiments
• Nuremberg Code (1947) • WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects (1964)• Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws,
regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use
• Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Biomedical Research(2005)
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Cells and tissuesEuropean Directives
Directive 2004/23 of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells
Directive 2001/83 Community code relating to medicinal products for human use
● Directive 2002/98 of the European Parliament and of the Council of 27 January 2003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC
● Directive 2004/33 of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components
● Regulation 1394/2007 on Advanced Therapy Medicinal Products
Directive 98/79/EC : in vitro diagnostics (IVD)
● Genetic testing with medical purpose
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Transversal principles of healthcare law
● Respect for human dignity
● Right to respect of privacy
● Right to body integrity
● Unavailability of the human body
● Non-commerciality of the body and the biological material
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Directive 2004/23/ECScope, objective and main principles
● Scope• Human tissues and cells intended for human application
● Objective• Standards of quality and safety on EU scale
● Main principles• Donation : voluntary and unpaid
- compensation for the donors strictly limited to the expenses and inconveniences related to the donation
- Informed consent• Procurement :
- carried out on a non-profit basis, - by persons who have successfully completed a training programme,- in a tissue establishment authorised for procurement or in a procurement
organisation• Traceability of the tissues and cells• Basic requirements for import and export
- Imports from third countries must comply with standards equivalent to those laid down in the Directive
- Exports to third countries must comply with the requirements of the Directive
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Use of human cells and tissuesDifferent finalities
● Grafts (no substantial manipulation before graft)• Autologous (donor = receiver)• Allogeneic (donor is not the receiver)
● Scientific research• With human application• Without human application
● Substantial manipulation(s)• Tissues and cells can become a medicinal product
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Advanced therapy medicinal products
Medicaldevices
Legislation
Science
Medicaldevices
Tissueengineering
Celltherapy
Gene therapy
Biotechex : insulin
Medicinalproducts
ex: aspirin
« Advanced therapies »
Source : P. Selis, 1st EMEA Workshop on ATMP, 3/4/2009
CHMP expertise
CAT (new)Committee for Advanced
Therapies – Scientificexpertise
ATMP Medicinal products
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Regulation 1394/2007 : objectives & scopeLex specialis which introduces additional provisions to those laid down in Directive 2001/83/EC● Lays down specific rules for ATMPs
Principles of existing legislation on medicines apply to advancedtherapies● Centralised procedure for MA
● Demonstration of Quality, Safety & Efficacy
● Post-authorisation vigilance
ATMPs may contain human or animal cells
Regulation is directly applicable (but a transitional period is provided for)
Directive 2001/83 Regulation1394/2007
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Ruled by Directive 2004/23 except in the case of manufactured products covered by other Community legislation (e.g. Regulation 1394/2007)
Always ruled by Directive 2004/23 insofar as the human tissues and cellsare intended for human applications
● Donation
● Procurement
● Testing
● Processing
● Preservation
● Storage
● Distribution
Interaction Directive 2004/23 and Regulation 1394/2007
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The Belgian legislation on the procurement and use of human biological material
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Several drafts have been discussed in Parliament
Long debates in Senate Commission
Purpose● Initially : confusion around the umbilical cord blood storage (ethical)
issues● Implementation of Directives 2004/23, 2006/17 and 2006/86● Creation of a legal framework for the activities implying the use of human
biological material
Now : Act of 19 December 2008 on the procurement and use of human biological material for human medical applications and scientific research● Entered into force since 1 December 2009● Exception : biobanks regime (art. 22)
Law on human biological materialNew Belgian legal framework (1)
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Law on human biological materialScope
Human applications
- Transplantation
- Manufactured products
Scientific research
Implying a human application or not
Human cells and tissues, including- Gametes- Embryos- Foetuses- Substances extracted thereof
Blood, organs, hair (exceptfollicles), nails, urine, breastmilk, faeces, tears and sweat.
In scope
Not in scope
Product finalityProduct
Donation and operationscarried out for exclusivelydiagnostical purpose, collection and operations in the framework of a single intervention
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Law on human biological materialBasic principles
● Donation and collection : informed consent
● Data protection, privacy and patients’ rights
● Unpaid donation
● No advertising
● Informed consent • Written
• Subject and purpose defined
• Always revocable (until first use after procurement)
• Donor must be informed of possibility of second use / opposition to it
● Collection on deceased persons : articles 10 to 14 of the Law of 13 June 1986 on transplantation apply
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Law on human biological materialNew Belgian legal framework (2)Numerous provisions of the Law required implementing measures, laid down in Royal Decrees
5 Royals Decrees of 28 September 2009
2 Ministerial decrees : price of human biological material + appointmentof Minister’s delegate
No RD yet (maybeamendments to Law
Biobanks
Regime applicable to gametes, gonades, fragments of gonades, embryosand fœtal human corporal material
Notification of serious adverse reactions and events
Standards for hospitals
Quality and safety standards for the operations performed on humancorporal material 1 December 2009
(Publication 23 October 2009)
General requirements for banks for human corporal material, intermediary structures and production establishments
entry into force
01.12.2012 (withretroactive effect on samples collected as
from 01.02.2012
Cord blood storageNEWNEW
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Scope of the Law vs. Scope of Directive 2004/23
In scope as far as the cells and/or tissues are meant for humanapplication
Always in scope
• Tissue establishments• Procurement organisation
• Banks for human biologicalmaterial• Intermediary structures• Production establishments • Biobanks
Only applies to the donation, procurement and testing of the cells and tissues intended for the manufacturing of products ruled by other Community legislations.
Autologous : standards of qualityand safety only related to (7, §4, 2) donation, procurement and testing.
Human cells and tissuesHuman biological material
Scientific research
Accreditedstructure(s)
Manufacturedproducts
Concerned material
Directive 2004/23Law
Allogeneic : standards of qualityand safety related to all phases/operations
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Law on human biological materialFour different structures
Bank for human biological material (BHM)
Intermediary structure (IS)
Production establishment (PE)
Biobanks (BB)
All structures must be accredited
BHM, IS and PE are subject to common requirements
BB are subject to a specific regime
Humanapplications
Scientificresearch
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StructuresOperations subject to accreditation
**
Imp
ortation
and
exporation
collection
**
*
distribu
tion
***Intermediary structures
Human corporal banks
***Biobanks
********Production establishments
Hu
man
app
lication
storage
preservation
processin
g
testing
procu
remen
t
Human corporal material
Ruled by the provisions of the lawand/or its implementing provisions
Must be performed in a hospital
* : in cooperation with a bank** : only for the production of autologous ATMPs*** : also makes the material available. Only for
scientific research without human application
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Law on human biological materialBank for human biological material (BHM)May be accredited to perform any operation
Managed by accredited hospital (Act of 7 August 1987)or National Defence Hospitalor Medical Science Faculty with Academic Hospital
Distinct legal entity
Not for profit organisation
Open issue : type of control on the structure : managed by hospitalonly? Public/private partnership possible ?
Depots Article 20 RD « standards »
● subdivision of a BHM that stores human biological material intended for human applications on the hospital site
● The BHM remains responsible for the compliance of the stored material
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Law on human biological materialIntermediary structures (IS)
Public/private entity
May be accredited to perform the processing, preservation, storage and distribution
Compulsory cooperation with a bank (agreement required)
Structure can be used to produce allogeneic ATMPs
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Law on human biological materialProduction establishment (PE)
Public/private entity
May be accredited to perform any operation (except testing) in the framework of the industrial manufacturing of autologousATMP
Not allogeneic ATMPs
Biological material can be transmitted directly to the PE aftercollection, without intervention of a BHM
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Law on human biological materialRequirements common to BHM, IS and PE
Accreditation
● Prior inspection by the Agency
● Validity : maximum 4 years (+ inspection every 2 years)
● Procedure
● Dossier requirements
● EC opinion (EC as defined in the Law on experiments on humans)
Accreditation specifies type of material, type of operation(s) and for the PE : type(s) of ATMP
Manager needs to be a doctor with a special training
The same legal entity can be accredited as IS and PE
● Activites and management of both structures must however be distinct
Register
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Law on human biological materialSecond use
Principle : donor must consent to any second use
● Explicit written consent to the person responsible in the establishment (not the doctor who made the collection)
Any kind of second use : advice Ethical Committee
Exceptions
● Scientific research : informed consent considered as given if no prior explicit opposition to second use (implied IC)
● Biobanks : EC opinion not required• EC opinion given in the framework of BB accreditation is sufficient
• Limit : second use must form part of the activities and finalities for which BB has been accredited
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Law on human biological materialQuality standards for the operations performedon human biological material and traceability
QualityQuality system based on good practices and kept up-to-date, including atleast standard operating procedures, guidelines, handbooks, reportingforms, donor records and information on the final destination of the biological material
Quality standards in principle applicable to all operations
Specific to PE : human biological material intended for the preparation of medicinalproducts (vaccines, medical devices, ATMP,…) : standards are onlyapplicable to donation, collection, procurement and testing
TraceabilityUnivocal donor identification system (unique code allocatedto every donation)
Traceability must remain possible during 30 years (and maximum 50 years)
See also upcoming RD implementing Directive 2009/120
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Law on human biological materialQuality and safety standards for the operationsperformed on human biological material
Collection of the human biological material
Performed by doctors, pharmacists, dental surgeons, nurses, midwives, labtechnicians, graduates in biological, chemical or biomedical sciences who have attended a specific training
Procedures and criteria are laid down for :Donor selection
Biological testing of the material
Procedure for the collection, procurement and reception of the material
Quality standards forManagement, equipment, buildings, documentation of the establishments
Processing of the material
Storage
The establishments are responsible for the quality of the material during the distribution of it
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Biobanks and scientific research
● Public/private entity
● May be accredited to store human biological material and to make it available exclusively for scientific research withouthuman application
● Subject to a specific regime still to be defined• Initially a Royal Decree would define it
• It seems the specific regime will be included in the Law itself (by end 2012 or mid 2013)
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Biobanks and scientific research
● Any research activity (with or without human application) implying human biological material is subject to the provisions of the Law
● Legal restrictions applicable to scientific research:• Prohibition of any use of the material without a prior favourable
opinion of an EC unless the intended use is part of the activitieswherefore the biobank had been approved by an EC (part of the « notification/accreditation » process
• Import and export of human biological material by a biobank : prohibited if biobank has not been notified on beforehand, and approved for such activities
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Hot topics
Different regime for allogeneic and autologous ATMP● PE are independent from BHM whereas IS are not● Manufacturing autologous ATMP can take place without intervention of a
BHM : direct transfer of biological material to the PE after collection● Manufacturing allogeneic ATMP subject to a heavier burden, a.o. prior
agreement with BHM● Ethical issues and interest of public research
Article 7, § 4 of the Law provides that the quality standards withwhich PE must comply only concern the donation, collection, testingand procurement of the human biological material● The same rule does not apply to IS● This means IS are subject to the quality standards laid down by application
of the Law for every operation
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Extent and scope of the informed consent when material collectedfor diagnostical/treatment purposes is further used for scientificresearch
● There is an « implicit consent » provided for the second use of residual material collected in compliance with the law
• Residual material is the part of the human biological material that has been collected for diagnostical or treatment purposes for the donor and that, after a sufficient and relevant part has been preservedfor the diagnostic itself or the treatment as such on grounds of new scientific data, is redundant as to these objectives, and couldtherefore be destroyed.
Hot topics
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GMOs
Genetic modification is also known as "genetic engineering” or “recombinant-DNA technology”
● Purpose : introduce novel traits to micro-organisms, plants and animals
GMOs = organisms in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating or natural recombination.
● Most common types of GMOs that have been developed and commercialised= genetically modified crop plant species
Highly regulated : a GMO or a GM food or feed product can only be put on the market in the EU after it has been authorised on the basis of a detailed procedure, based on a scientific assessment of the risks to health and the environment
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Use of GMOs
GMOs can serve various purposes● Feed, Food, Textile industry, …
Some areas subject to Health, Environmental as well as Ethicalconcerns
Where GMOs are used for food or feed, specific rules apply thataim at ensuring● high level of protection of human life and health
• safety assessment
● promoting the right of consumers to information • specific labelling requirements
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Examples
Examples of genetically modified crop plant species
● Genetically modified maize, soybean, oil-seed rape and cotton varieties
Examples of purpose of genetic modification
● Resistance to certain insect pests
● Tolerance to herbicides
● Modifications of taste, shape or color
● Better yield
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Deliberate release(experimental)
The timeline of a GM crop species : an overview
Containeduse
R&D
Directive 2009/41/EC Directive 2001/18/EC Regulations 1829/2003
and 1830/2003Directive 2001/18/EC
Authorization atnational level +information to
EU Commission and other MS
Authorization atnational level +
reinforcedinformation to
EU Commission and other MS
Application with national authorities,
then EFSA (assessment) + EU
Commission (authorisation + risk
management
Authorization atnational level +
reinforcedinformation to
EU Commission and other MS
Phase
Decisionlevel
Relevant EU legislation
1 2 3 4Deliberate release Marketing
Exposure/ risk level
LowHigher
Higher
Highest
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First phase : « Contained use » (1)
Contained use = any activity in which micro-organisms are genetically modified or in which such GMMs are cultured, stored, transported, destroyed, disposed of or used in any other way, and for which specific containment measures are used to limit their contact with, and to provide a high level of safety for, the general population and the environment (Directive 2009/41/EC).
Also applies to GMOs in general, although Directive 2009/41/EC only refers to GMMs explicitly
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First phase : « Contained use » (2)
First step of the R&D process (research phase, in laboratories)
Risk of contamination is low, except in case of « accident » (as defined in Directive 2009/41/EC)
Regulatory requirements relatively flexible but some obligations must be complied with:
● User of GMO evaluates the contained use as to the risksinvolved > classes 1 to 4 : level of containment
● Evaluation dossier is submitted to (national) competentauthority
● An emergency plan must be put in place by the user
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Second and third phases : « Deliberate release » (1)
« any intentional introduction into the environment of a GMO or a combination of GMOs for which no specific containment measures are used to limit their contact with and to provide a high level of safety for the general population and the environment »
● For any other purpose than for placing on the market
● Experimental or not
Subject to an authorization procedure
● Standard procedure (directive 2001/18/EC, article 6)
● Differentiated procedures (directive 2001/18/EC, article 7)
● Simplified procedures (commission decision 94/730/EC)
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Second and third phases : « Deliberate release » (2)
Standard procedure : notification including: ● Technical dossier (contents : Annex III of Directive 2001/18/EC)
providing notably:• general information including information on personnel and training,• information relating to the GMO(s),• information relating to the conditions of release and the potential receiving
environment,• information on the interactions between the GMO(s) and the environment,• a plan for monitoring in accordance with the relevant parts of Annex III in order to
identify effects of the GMO(s) on human health or the environment,• information on control, remediation methods, waste treatment and emergency
response plans,• a summary of the dossier;
● Environmental risk assessment and the conclusions required in Annex II, section D + any bibliographic reference and indications of the methods used
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Second and third phases : « Deliberate release » (3)Follow-up of standard procedure
● Decision within 90 days –can be suspended:• if missing info (suspension until provision of missing info –no
deadline)
• if public inquiry or consultation (maximum extension: 30 days)
● Exchange of info between competent authorities, through the Commission – observations from other MS
● Written decision allowing or rejecting the release, possiblysetting specific conditions
● Continued update of info by notifier, during and/or afterdecision
● After completion of release : reporting by notifier
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Second and third phases : « Deliberate release » (4)
Differentiated procedures
● Two conditions :• sufficient experience has been obtained of releases of certain
GMOs in certain ecosystems
• concerned GMOs meet the criteria set out in Annex V of Directive 2001/18/EC
● If both conditions are met : reasoned proposal for the application of differentiated procedures from the competentnational authority to the Commission
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Second and third phases : « Deliberate release » (5)Follow-up of differentiated procedures
● 30 days after receipt of proposal, Commission :• Transmits proposal to other competent authorities > observations
• Make the proposal available to the public > comments
• Consults Scientific committee > opinion
● Decision on the proposal within 90 days (same possibilities of suspension
as in standard procedure) (in accordance with article 30, § 2 of Directive 2001/18/EC)
• establishes the minimum amount of technical information from Annex III necessary for evaluating any foreseeable risks from the release, in particular:
- information relating to the GMO(s);
- information relating to the conditions of release and the potential receiving environment;
- information on the interactions between the GMO(s) and the environment;
- the environmental risk assessment.
● Written decision allowing or rejecting the release, possibly setting specificconditions
● Continued update of info by notifier, during and/or after decision
● After completion of release : reporting by notifier
Reaction (if any) within 60 days
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Second and third phases : « Deliberate release » (6)
Simplified procedures (Commission Decision of 4 November 1994 establishing simplified procedures concerning the deliberate release into the environment of genetically modified plants pursuant to Article 6.5 of Council Directive 90/220/EEC)
● Simplified procedure = single notification dossier to be submitted for more than one release of GM plants which have resulted from the same recipient crop plant species but which may differ in any of the inserted/deleted sequences or have the same inserted/deleted sequence but differ in phenotypes.
● Notifier can submit in a single notification information on several releases of GM crop plants, to be released on several different sites, on conditions described in Annex to Decision 94/730
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Fourth phase:« Placing on the market » (1)“placing on the market" = holding of food or feed for the purpose of sale, including offering for sale, or any other form of transfer, whether free of charge or not, and the sale, distribution and other forms of transfer themselves.
Regulation 1829/2003 provides for a single authorisation procedure for food products containing GMOs:
- application in accordance with the Regulation for all food products containing GMOs that comply with the provisions provided for by Directive 2001/18
- single application for food and feed uses and for cultivation : a GMO which is authorised can be used not only in food and animal feed but also for cultivation or deliberate release into the environment.
MA is renewable for 10-year periods
The granting of authorisation does not lessen the general civil and criminal liability of any food operator in respect of the food concerned
Authorisation procedure in a nutshell : Application
with national authorities
EFSAassessment
6 monthsEU Commission draft decision
Standing Committeeon the Food Chain and Animal Health
Approval draft decision
Rejection draft decision Council of Ministers3 months
decision
no decision
3 months
Final decision by Commission
Final decision by Commission
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Deliberate release(experimental)
The timeline of a GM food product : an overview
Containeduse
R&D
Directive 2009/41/EC Directive 2001/18/EC Directive 2001/18/EC
+ Regulations 1829/2003and 1830/2003
Directive 2001/18/EC + Regulations 1829/2003
and 1830/2003
Authorization atnational level +information to
EU Commission and other MS
Authorization atnational level +
reinforcedinformation to
EU Commission and other MS
Authorization atEU level (EFSA)
Authorization atEU level (EFSA)
Phase
Decisionlevel
Relevant EU legislation
1 2 3 4Deliberate release Marketing
Exposure/ risk level
LowHigher
Higher
Highest
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Specificities of the framework applicableto GM food (1)GM foods can only be authorised in the EU if they have passed a rigorous safety assessment.
Procedures for evaluation and authorisation of GM foods
● Regulation 1829/2003 on GM food and feed
● Directive 2001/18/EC on the release of GMOs into the environment
Authorisation is applied for in the MS, and granted by the European Commission, with the support of the EFSA
GMO Panel of the EFSA carries out assessments
● Panel composed of independent scientific experts supported by a number of specialised Working Groups drawing on a pool of more than 40 external experts in fields such as allergenicity, ecology, microbiology, toxicology, plant physiology and molecular genetics
● Independence of the experts guaranteed through policy on declaration of interests (experts have to declare any potential conflicting interests in advance of each meeting)
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Specificities of the framework applicableto GM food (2)
EFSA GMO Panel assessment
● are based on scientific dossiers presented by applicants and any other relevant scientific information;
● aims to ensure its evaluations meet the highest scientific standards, which is reflected in the GMO Panel guidance, which describes the data applicants must include in their application dossiers, including all the necessary studies on human and animal safety and on environmental impact (http://www.efsa.europa.eu/en/gmo/gmoguidance.htm)
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Specificities of the framework applicableto GM food (4) - Labelling requirements (articles 12 to 14 of Regulation 1829/2003)Specific labelling requirements (in addition to the other requirements of Community law concerning the labelling of foodstuffs):● if list of ingredients:
• more than one ingredient : words ‘genetically modified’ or ‘produced from genetically modified (name of the ingredient)’ in parentheses immediately following the ingredient concerned;
• ingredient designated by the name of a category: words ‘contains genetically modified (name of organism)’ or ‘contains (name of ingredient) produced from genetically modified (name of organism)’;
• the indications may appear in a footnote to the list of ingredients, if printed in a font of at least the same size as the list of ingredients.;
● if no list of ingredients : words ‘genetically modified’ or ‘produced from genetically modified (name of organism)’ on the labelling;
● Special rule : food offered for sale to the final consumer as non-pre-packaged food, or as pre-packaged food in small containers of which the largest surface has an area of less than 10 cm2: the information required must be displayed either on the food display or immediately next to it, or on the packaging material, in a font sufficiently large for it to be easily identified and read.
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Specificities of the framework applicableto GM food (4) - Labelling requirements (articles 12 to 14 of Regulation 1829/2003)
In specific cases, labelling must also mention any characteristic or property, as specified in the authorisation :● where a food is different from its conventional counterpart as regards
composition, nutritional value or nutritional effects, intended use of the food and/or implications for the health of certain sections of the population;
● where a food may give rise to ethical or religious concerns.
Labelling of foods which do not have a conventional counterpartmust contain appropriate information about the nature and the characteristics of the foods concerned.
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Currently authorised GMOs
EU Register of GM food and feed : http://ec.europa.eu/food/dyna/gm_register/index_en.cfm
Currently around 50 authorised GM food and/or feed :
● 26 types of GM maize,
● 8 types of GM cotton,
● 7 types of GM soybeans,
● 2 types of GM oilseed rape,
● 1 type of GM starch potato,
● 1 type of GM sugar beet.
● 1 type of Swede-rape (koolzaad)
● 2 microorganisms (bacterial proteins and yeast)
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Controversy and scientific criticism towardsGMO: the recent case of Biologist Seralini● Pictures of rats with impressive
tumors have gone around the world in no time
● Study published in "Food and Chemical Toxicology“, August 2012
● Publication of a study denouncing long term toxicity of Roundup (herbicide) and a GM type of maize (Roundup tolerant)
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Controversy and scientific criticism towardsGMO: the recent case of Biologist Seralini
● Controversy grew as no scientific consensus can be found around the methodology of the Biologist
• choice of the rats species
• attitude towards press : sensationalism, search for immediate release of the (shocking) information, study immediately communicated to mass media, etc.
● Difficulty to evaluate the ethics and independence of the Biologist(well-known for anti GMo positions) vs. powerful lobby from GM producers
• Industry also carries out tests and uses them to support inocuity of GMO
• precautionary principle vs. profit?
Thank youMarc Martens
Avenue Louise 235 /1 Louizalaan
1050 Brussels
marc.martens@twobirds.com
Bird & Bird is an international legal practice comprising Bird & Bird LLP and its affiliated businesses. www.twobirds.com