Federal agency for medicines and health products

The Belgian Healthcare landscape unravelled: the FAMHP perspective

Christophe Lahorte Vilvoorde, 2nd March 2018

2

FROM:

The main role of the Agency, in the importance of public health is to

ensure the, quality, safety and efficacy of drug products (human +

veterinary) and health products (eg. medical devices, IVDs and blood,

cells & tissues), in clinical development & on the market.

TO: Mission of famhp as part of the EU regulatory network:

Facilitating the translation of innovative scientific advances into medicinal products meeting adequate standards and accelerate patients’ access to promising therapies fulfilling unmet medical needs without jeopardising the safety of the patients.

based on the law of 20.07.2006 (B.S. 08.09.2006) regarding the installment and functioning of the FAMHP.

Evolving mission of the FAMHP

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FAMHP Organogram

Innovation Office - STA unit

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1: Strategy of famhp (1/2) :

- FAMHP : Mid size agency with full competencies( scientific advice , clinical trials , marketing authorisations , vigilance , inspections for medicinalproducts for human and veterinary use )

- Significant investment in the EU regulatory framework at the regulatory , scientific , policy making level

- 35 delegates at EMA / HMA

- 70 scientific internal experts : multidisciplinary , international

- expanded D-base of 800 external experts

- Special focus on access to innovation

- UMN and link with HTA

- Medical devices, cells and tissues

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1: Strategy of famhp ( 2/2 ) :

- Unmet Medical Need ( @ EU Commission STAMP ; @ HMA Working group access to innovation )

- Clinical trials

- EU CTR coordination group ( EU Commission , EMA , HMA )

- CTFG , Expert group on clinical trials

- EU Network training Centre

- National innovation office ( national STA )

- SAWP ( multi national assessment teams )

- CHMP ( Prime ), PDCO, CAT and PRAC

- Centres of Excellence

- Vaccines

- Early Phase development

- Oncology (paediatric)

2: Focus on early access to innovation : Clinical trials

Approved Trials (2014-2016) per therapeutic area: # trials BE, EU

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Therapeutic area - BE, EU total (# clinical trials)

BE EU total

12 % of the trials in EU are performed in Be

22 % Phase 1 trials

Oncology , CNS , viral diseases

Ratio Approved Trials (2014-2016) per therapeutic

area, BE vs EU and per capita

0,0

5,0

10,0

15,0

20,0

25,0

30,0

35,0

40,0

45,0

50,0

Ratio approved trials, taking into account that Be represents 2.2 % of the EU population (red line)

Trials above the red line mean better than the EU average

Belgium vs. Europe

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25%

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2010 2011 2012 2013 2014 2015 2016

Rel

ativ

e %

Bel

giu

m v

s. E

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pe

Am

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nt

Year

Amount of Vaccine CT: Belgium vs Europe

Belgium

Total EU(vaccine)

%Be (/TotalEU vaccine)

EU-landscape

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60

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100

120

140

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2010 2011 2012 2013 2014 2015 2016

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Total EU (vaccine)

%UK (/Total EUvaccine)

%Belgium (/Total EUvaccine)

%Germany (/Total EUvaccine)

%Netherlands (/TotalEU vaccine)

%France (/Total EUvaccine)

Commercial vs. Non-commercial

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UK Belgium Germany Netherlands France EU

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e %

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Country

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commercial

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3: Focus on early access to innovation: NationalInnovation office

• Scientific & technical/regulatory advice (STA):

• optimising curren procedures (eg. patient involvement)

• scope expansion to: borderline & DDCPs, IVD’s (CoDx), medicaldevices & Blood, cells & tissues

• implementing new services (eg. fast-track STA, iterative STA)

• Specific support to SME’s, start-ups and academic researchcenters / hospitals (eg. project info meetings)

• General innovation support & knowledge management

• EU-IN activities (eg. Horizon scanning)

• open to all innovators involved in R&D (eg. Portfolio meetings, FAQs, Passerelle « Access to Innovation »)

• Integrated life cycle approach

3 Main pillars of core activities:

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National Innovation Offices: as starting point

The typical long route of medicines to patients

Chance of reaching access for a product entering the development phase:0.01-0.1% 5-10% 50-60% 75-90%

Pharmaceutical + nonclinical

(4 – 6 y)

Phase I and II

(2 – 4 y)

Confirmatory phase III

(2 - 5 y)

Assessment and approval

(1 – 2 y)

Reimbursement and launch

(0 – 2 y)

Access

National Scientific Advice

PRIME

EMA/CHMP scientific advice

ITF

National

innovation

office

3: Focus on early access to innovation: National scientific advice

54,55%

27,27%

14,29%

0% 10% 20% 30% 40% 50% 60%

Early phase development

Vaccines

Oncology

Domains of Excellence (2015-2016)

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3: Focus on early access to innovation: national scientific-HTA advice

INPUT joint STA-HTA

files/year

Total STA

files/year

% joint STA-HTA

files vs Total Therapeutic area

2011 (*) 2 36 5,6 oncology

2012 0 30 0,0 NA

2013 1 34 2,9 cardiology

2014 2 37 5,4 Infectio / cardiology

2015 1 38 2,6 oncology

2016 1 35 2,8 oncology

TOTAL 6 210 2,8

(*) one application was withdrawn by the applicant prior to formal submission.

Main Questions:

➢ Regulatory aspects (CUP/MNP)

➢ Unmet medical need

➢ Added therapeutic value

➢ Target population

➢ Product positioning (1st – 2nd line)

➢ Clinical Endpoints

➢ Standard of care

Key features:➢ could be complementary or divergent

from EMA views➢ more targeted to local situation➢ Mainly late stage development

3: Focus on early access to innovation : National scientific advice (vaccine applications 2015-2016 )

3: Focus on early access to innovation: Scientific advice at SAWP

➢ 21 % of all EU advices per year coordinated by BE team

➢ Increased demand for SA (> 10 % increase in 2017)

➢ Involvement in joint SA-HTA, biosimilars, biomarker qualifications, …

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Importance of national/EU SA for applicants

• Facilitation & acceleration of clinical research & regulatorysubmissions in Belgium & EU: pre- and post-MAA stage

• Preventing expensive, time-consuming, unnecessary or unethical clinical research

• Better follow-up of product life cycle•

• Building up robust data

• Constructive guidance prior to formal submissions

• Earlier availability & access of new, innovative drug products to patients

• Faster uptake of innovation by NCA’s/EMA in new guidelines

4: Focus on early access to innovation: PRIME

FAMHP in Top 5

2017: 12 PRIME applications

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4: Marketing authorization: Be rapporteurships

Subject - Datefamhp/entity/Division-Unit-Cell

CHMP•Hexavalent pediatric vaccine

•Pneumococcal vaccine

•Rotavirus vaccine

•Human papilloma virus vaccine

•Influenza vaccines

•Hepatitis B vaccine

•Meningococcal ACWY (RMS)

•Measles Mumps Rubella vaccine (co-rapp)

PRAC•Hexavalent pediatric vaccine

•Hepatitis B vaccine

•Malaria vaccine

•Meningococcal group B vaccine

•Rotavirus vaccine

•HPV vaccine

•Flu vaccine

•Pneumoccocal vaccine (co-rapp)

•Measles Mumps Rubella vaccine (co-rapp)

2012-2017 : 17 applications for vaccines via the centralised procedurereceived @ EMA:Be @ CHMP :7 Rapporteurships , 3 Co-rapporteurships , 5 peer reviews Be @ PRAC : 7 Rapporteurships , 2 Co-rapporteurships

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5: Centre of excellence: Early Phase Development

• Regulatory and scientific advice concerning early phase trials

• Clinical Trial attractiveness: network of well known phase I centers, recruiting healthy volunteers

• Stable number of phase I and FIH clinical trials

• Phase I centers all inspected for GCP and if producing IMP’salso for GMP

• Accreditiation of Phase I centers on voluntary basis

• Also recognised clinical centers recruiting patients into earlyphase clinical trials

• Exploratory clinical trials

• Participation at national and EU level in advices, drafting andtraining (SAWP, drafting group FIH GL at EMA, ANSM CSST Rennes, EU NTC)

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5: Centre of excellence: Vaccines

A Belgian network of 4 core expert activities, each embedded withinan national and international network

•Network of well known vaccine clinical trial centers, including phase 1 and challenge trial unit.

•Ongoing research project to keep Belgium attractiveness

•Leading role at EMA CHMP and PRAC for rapporteurship, including first PRIME vaccin

•Internal regulatory network : presence in national and international committees (EMA Vaccine Working Party, FDA, WHO SAGE, CEPI)

•A point of reference at national and EU level

•Advice on quality –non clinical-clinical aspects

•Network of in-house and external experts (academia, government institutions: PHI-INAMI)

•GMP-GCP-Pharmacovigilance inspections (including third countries)

•Batch release: Close collaboration with Belgian OMLC

•Active vaccinovigilance projet

Post licensure surveillance

Scientific -regulatory

advice

Clinical trialsMarketing

authorization

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5. Centre of excellence: Vaccines

• Point of reference for regulatory and scientific advice at European and national level

• Clinical Trial attractiveness: network of well known vaccine clinicaltrial centers, including human challenge unit

• Leading role at EMA CHMP and PRAC for rapporteurship of new marketing authorization (including first PRIME vaccine evaluation)

• Point of reference for GxP inspections (including third countriesinspection)

• Representation in national and internal committees and workinggroups (EMA Vaccines working party, FDA, WHO Sage , CEPI ..)

• Scientific and regulatory expertise: network of internal and

external expertise (academia, governement institutions)

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6: New orientation in view of EU evolutions:

• Focused activities on Safe and Timely Access to Medicinalproducts

• Optimised EMA processes on conditional MA and acceleratedassessment

• Active engagement of famhp in PRIME

• Repurposing active substances/ medicinal products

• Enhancing joint SA-HTA advices with HTA bodies:

cfr. efforts harmonizing HTA at EU level, involving payers early on

in collaboration with licensing agencies

• EU network of national innovation offices : bridging the gap between research at national level and promising new innovativemedicinal product fulfilling an unmet medical need

• Increased focus on healthcare products: medical devices (eg. m-health), IVDs (eg. CoDx) triggered by MDR, IVDR, GDPR, …

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EU

CTAG

Payers

Commissies voor ethiek

Scientific advice

STA

Joint advices

Clinical Trials

UMN(CU-MNP)

MAA

ETA – ETR CTG

Post-Licensing

CURRENT LYFE CYCLE OF MARKETING AUTHORIS. PROCESS

CHMP

COMP PDCO

Multi-nationaltrials

PRAC

Earlier in time

Lessons learned - feed-back loop

HOW THE PROCESS WILL EVOLVE

PRIME

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Publication of Summary of Results• CTR implementation & CTR pilots (wave 3)

• Info to patients and health care providers on running clinicaltrials in Belgium on the FAMHP website

• Campaign creating awareness towards citizens & generalpractinioners (launched end 2017)

• Patient representation: before & during CTA evaluation

• Incentive: 0 fee for handling of initial CTAs & subst. amendments; national scientific advice prior to CTA

• National database for healthy volunteers

• Facilitating recruitment of patients:

o Cooperation between centres (i.e. paediatric oncology)

o Enhancing and facilitating the role of the generalpracticioner

• Fostering the coöperation of all the concerned stakeholders in order to facilitate the access to innovation in the benefit of the patient.

7: Additional initiatives:

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8. Opportunities & challenges towards the future:

• Brexit

• Federal Redesign:

eg. Passerelle “Access to Innovation”

• CTR, MDR, IVDR, GDPR, Better Regulation (VET), …

• Scientific & Technological evolutions

eg. Digital Health (eg. mHealth), Artificial Intelligence, in silico clinical trials, complex trial designs, 3D printing, personalized medicine, …

• Societal evolutions:

eg. engaging health volunteers & patients,

“uberisation” of healthcare,…

Requiring active, multidisciplinary partnerships between

all healthcare stakeholders

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9. Conclusions:

• Solid EU regulatory network HMA-EMA is key

• Famhp is fully engaged in this structure andphilosophy

• Famhp fully subscribes the necessity to stronglyinteract with eg. both Academia andPharmaceutical/Meddev/IVD Industry (i.e. national-global level)

• Famhp recognises the strengths of the different Agencies (i.e. Centres of Excellence andmultinational teams)

• Famhp will consolidate the impact of Brexit

(additional workload / opportunities)

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Contact

Federal Agency for Medicines and Health Products –FAMHP

Place Victor Horta 40/40

1060 BRUXELLES

tel. + 32 2 528 40 00

e-mail: welcome@fagg-afmps.beinnovationoffice@fagg-afmps.be

http://www.afmps.behttp://www.fagg-afmps.be/en/innovationoffice

Your medicines and health products,our concern

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Back-up slides:

DG organograms &EU activities

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Director-general DG PRE authorisation

R&D Division (human)

Administrative Support

Ethics Committees Collaboration Entity

Clinical Trials Entity

Follow-up Entity

CU-MNP Entity

Marketing Authorisation

Division (human)

Staff Member

CP Entity

MRP/DCP/NP Entity

File Management Team I

File Management Team II

Administrative Support Entity

Homeopathic & Herbal Medicines Entity

Medicines for Veterinary Use

Division

Project Manager BR

AMR Entity

Vaccines & Antiparasitic Medicines Entity

Pharmaceuticals Entity

Assessors Division

Staff Member

MedDev Entity

Preclinical & Clinical Veterinary Entity

Nonclinical Entity

Quality Entity

Clinical Human Entity

National Innovation Office

& Scientific-Technical Advice

Unit

Pharmacopeia/API

Unit

Management Support

Spearheads: Early Phase

Development

Vaccines

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DG PRE authorization: summary of core structure

four divisions : • R&D-human CTA, ADR reporting, CUP/MNP, rapid alerts in CT, GCP

• Marketing Authorisation-human CP, MRP/DCP, NP; Homeo-Phyto NP, ASFM applications, HE for ATMPs

• Medicines for Veterinary Use (MAA, AMR, MRL,)

• AssessorsEvaluation of CTA, PIP, SA, CUP, MNP, MAA and variations; active collaboration in national & EU scientific committees (CHMP, PDCO, COMP, CAT) & WPs (SAWP, SWP, expertise); expertise pool

and three units: • National Innovation Office – WTA unit STA, portfolio & project info meetings, support to innovators, SME- & Academics friendly policy

• Pharmacopeia & Raw Materials unit PhEur, TMF, API authorization for pharmacies, EDQM

• supportive unit

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Director-general DG POST authorisation

Marketing Authorisation Division

(Variations & Renewals)

Administrative Support

Management Support

Call Center Marketing Authorisation Entity

Variations without/with minor impact on MA Entity + EC decisions, EU recommends Entity

Change MAH/Batch Releaser Implementation IA referrals Entity

Cluster Entity

Parallel Import Entity

Vigilance Division (pharmaco, materio, haemo, bio)

Administrative Support

Management Support

Human PhV/File management/ADR Entity

File Management

ADR Coordination

Human PhV/Evaluation Entity Coordination Europe

Veterinary PhV entity

Materiovigilance Entity

Bio/Haemovigilance Entity

Health Products division

Medical Devices Entity

Proper Use Division

Administrative Support

Database of Medicinal Products Entity

Information & Documentation Entity

Advertising Entity

Risk Minimisation Activities Entity

Administrative Support

Management Support

Project Management

ZBB

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DG Post: core activities

• Pharmacovigilance:– Pharmaco (human + vet), materio, hemo, bio– link with DG inspection

• ADR

• EU Coördination activities (eg. PRAC: PASS, PAES, referrals)

• Parallel Import

• Change MAH/Batch Releaser Implementation IA referrals

• Marketing Authorisation (Variations & Renewals)

• Risk Management Plans / Risk Minimisation Activities

• Patient Support Programs (PSP)

• Publicity

• Information & Documentation on authorized medicines

• Authorized Medicines Database

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Director-general DG INSPECTION

Industry Division

Medicines GM(D)P Entity

Medicines GCP Entity

Medicines PhVigEntity

Medical Devices Entity (NBs/fabrication/clinical trials)

Human Tissue Material & Blood Entity

File Management Entity/Persons Recognition

Rapid Alert Entity/Sampling Plan

Distribution Division

Distribution & Publicity Medical

Devices Entity

Distribution & Publicity

Medicines Entity

Detached Inspectors/Contr

ollers Entity

File Management Entity

Dispensing Division

Retail Pharmacies

Entity

Hospital Pharmacies/Medi

cinal Stocks at Healthcare

Professionals Entity

Medicinal Stocks at Veterinarians

Entity

File Management Entity

AuthorisationsDivision

Authorisations, Declarations & Certificates Entity

Recognition Human Tissue Material Entity

Establishment of Pharmacies Entity

Register of Pharmacies Entity

Recognition Clinical Biologists Entity

Specially RegulatedSubstances Entity

Management Support

Administrative Support

Special Investigation Unit

Detection EntityData

Management Entity

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DG Inspection: core activities

Market Surveillance by

• Organising inspections and controls on manufacturing, distribution,

dispensing, promotion of medicines and health products, to ensure from

development to use, the quality of medicines and health products

• Inspection of the operators

• Control of the products

• compliance of products

• plus postmarketing sampling plan

• System of alerts

• Delivering authorisations and certificates related to inspections and

controls (authorisations, certificates, declarations, licenses, agreements,...)

• Organising inquiries to fight illegal practices with medicinal products and health products