What are the need-to-know characteristics of regulatory, nonclinical and clinical specific to microbiome products? A transnational perspective -Regulatory environment for microbiome products, Differences between USA and EU regulatory requirements; -Microbiome products NC evaluation compared to drugs/ biologics NC evaluation: same objectives but different strategies; - Regulatory NC considerations and approach; -Take-home messages: integrated approach CMC / nonclinical / clinical

1. 1
Cécile Rousseau
Director
rousseau@voisinconsulting.com
Peri Aghadiuno
EU Medical Director
aghadiuno@voisinconsulting.com
Clara Desvignes
Senior Regulatory Scientist
desvignes@voisinconsulting.com
MICROBIOME:
What are the need-to-know characteristics of regulatory,
nonclinical (NC) and clinical specific to microbiome products? A
translational perspective
March 27, 2019
BioEurope Spring & Microbiome Therapeutics EU

2. 2
Agenda
1 Introduction
2 Regulatory: Positioning and regulatory pathway
3 Case studies, discussion and Q&As
4 Nonclinical
5 Clinical
6 Case studies, discussion and Q&As
7 Regulatory: Interactions with agencies
8 Wrap-up & conclusions

3. 3
The collection of microbes that inhabit an environment, creating a “mini ecosystem”.
100 thousand billion
(1014) bacteria
> 3 million bacterial genes
1-2 kg of bacteria
(30% caloric intake)
Introduction
Gastro-Intestinal upsets & GI-
related complications
Brain health
Cardiovascular system
Immune system
Diabetes
Obesity
Skin health
Infectious
Skin health
Infectious
Cover several therapeutic areas

4. 4
Introduction
Unbalanced
diet
Probiotics
DiseasePrebiotics
AntibioticsFMT*
Health
Disease
Healthy microbiome
Dysbiosis
*Fecal Microbiota Transplant
Maintain health Prevent disease
Restore health / Manage the
disease
Common Foods, Fortified
Foods, Dietary Supplements
Drugs (incl. Biologics), Medical
Devices
Drugs (incl. Biologics), Medical
Devices, Medical Foods

5. 5
Regulatory development challenges: Legal basis
• Product classification: What actually is the product / new development?
• Applicable product positioning in key global markets
Regulatory pathway has impact on cost & time to market and life cycle
o Dietary supplement
o Foods with categorized Health claims
o Medical Food
o Drug / Biological product / Live
Biotherapeutic Products (LBP)
o Food supplement
o Functional foods/Foods with Health claims
o Food for Special Medical Purposes
o Biological product / Medicinal product

6. 6
Agenda
1 Introduction
2 Regulatory: Positioning and Regulatory pathway
3 Case studies, discussion and Q&As
4 Nonclinical
5 Clinical
6 Case studies, discussion and Q&As
7 Regulatory: Interactions with agencies
8 Wrap-up & conclusions

7. Drug positioning and its pathways

8. Microbiome therapeutic products positioning and registration

9. 9
EU – Regulatory definitions
Medicinal product
- According to Directive 2001/83/EC : “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 or
administered to human beings either with a to restoring, correcting or modifying
physiological functions by exerting a pharmacological, immunological or metabolic
action, or to making a medical diagnosis.”
Biological medicinal product
- According to Directive 2003/63/EC: “A biological medicinal product is a product,
the active substance of which is a biological substance”, i.e. “a substance that is
produced by or extracted from a biological source and that needs for its
characterization and the determination of its quality a combination of physico-
chemical-biological testing, together with the production process and its control. ”

10. 10
Product type
Competent
Authority
Dossier Process
Medicinal
products (small
molecules,
herbals…)
National
Drug
Competent
authorities
(Member
states –
MS)
CTD format
National procedure
 Application made to 1 national Competent Authority
 Time for review: 210 days (except clock stops)
Mutual Recognition Procedure (MRP)
 Application made to 1 selected Member State (“Reference Member State
(RMS)”)
 Once MAA approved by the RMS, application to other selected concerned
Member States (CMS) (up to 28 (27) countries)
 Time for review: 90 days, after first MA
Decentralized Procedure (DCP)
 Same principle as MRP, except that applications to RMS and CMS are done at
the same time.
 Time for review: from 210 days
ATMPs
Biotech
products
Blood products
Certain
diseases
EMA
Centralized procedure (Europe-wide marketing authorization issued by the EU
Commission)
 28 (27) countries
 Time for review: 210 days (except clock stops)
EU - Drug product Registration Procedures

11. Fill-out the form to download
the full presentation