9. Gesent Kongress , Bonn Stellenwert der wissenschenschaftlichen Beratung bei BfArM und EMA (und G- BA?) aus Sicht der Industrie

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1 9. Gesent Kongress , Bonn Stellenwert der wissenschenschaftlichen Beratung bei BfArM und EMA (und G- BA?) aus Sicht der Industrie Dr. Anja Langeneckert, Head Drug Regulatory Affairs, Roche Pharma AG, Grenzach 1

2 Agenda Wissenschaftliche Beratung bei BfArM, EMA und G-BA Wie? Warum? Points to consider Fazit und Outlook 2

3 Optionen für FORMALEN Scientific Advice (SA) Europa -EMA oder CHMP SA ( = central SA ) Durch die SAWP= Scientific Advice Working Party Deutschland: Nationaler Scientific Advice bei BfArM oder PEI G-BA Anforderung einer Beratung im Vorfeld einer Antragstellung 3

4 EMA CHMP/SAWP Scientific Advice eral_content_ jsp&mid=wc0b01ac b9 SAWP=Scientific Advice Working Party 40 or 70 day procedure (mit oder ohne Diskussionsmeeting) Aber gesamte Zeitschiene ca. 6 Monate Definierte Start/Einreichungszeiten Klar definierter Prozess Hohe Kosten 4

5 EMEA/267187/2005/ Rev. 1 5

6 BfArM 5AF76A6.1_cid322 Schriftlicher Antrag im BfArM-Antragsformular Beratungsgespräch 1-3 Monate später Briefing Dokument 4 Wochen vor Meeting Mündliche oder Schriftliche Beratung möglich Kosten je nach Aufwand Protokoll wird vom Antragsteller spätestens 1 Woche nach Beratungsgespräch eingereicht und finale Version wird vom BfArM ca 1-4 Wochen später 6

7 7

8 Beratung beim G-BA G-BA Antragsformular Beratungstermin innerhalb von 4-6 Wochen Protokoll ca 4 Wochen (oder länger ) 5 Tage für Kommentare Finales protokoll. 8

9 G-BA Beratung Welche Themen? ZVT (zweckmässige Vergleichstherapie) Endpunkte Studiendesign 9

10 Other types of advices Qualification of novel methodologies/biomarker (EMA) Parallel FDA/EMA advice Paralell Health Authority/Health Technology Assessment Body Advice (EMA) Pharmacogenomics Working Party Briefing meetings (EMA) Innovation Task Force meeting (EMA) Portfolio meetings

11 Parallel scientific advice with health-technology-assessment bodies jsp&mid=wc0b01ac058004d5c1 The Agency also offers parallel scientific advice with health-technology-assessment (HTA) bodies. The aim of this is to allow medicine developers to gain feedback from from regulators and HTA bodies at the same time, early in the development of a medicine. This helps them to establish the evidence that both parties will need to determine a medicine's benefit-risk balance and value. A pilot for parallel scientific advice was launched in July Around 25 procedures had been finalised or were ongoing as of November 2013, covering indications such as diabetes, heart failure, lung cancer, breast cancer, pancreatic cancer, melanoma, mesothelioma, asthma, rheumatoid arthritis, multiresistant infections, food allergies, diabetic gastroparesis, Alzheimer s disease, depression, osteoporosis and three rare conditions. 11

12 Warum wissenschaftliche Beratung I? Ask the experts!! Fragen zu/während der Entwicklung eines Arzneimittels pharmazeutische Qualität, Klinik Präklinik Prozedural Externe Validierung der Entwicklungsprogramme Input, ob Entwicklungsprogramm ausreichend ist Verständnis für hot spots und unterschiedliche Auffassungen Endpunkte Vergleichstherapie Studiendesign (Statistik) gewünschte Indikation 12

13 Warum wissenschaftliche Beratung II? Speziell wichtig, in Gebieten wo es keine oder limitierte offizielle Guidelines gibt: Neue Technologien Neue Therapieansätze Neue Endpunkte (surrogate) Approach outside of guideline Opportunity of dialogue during all stages of the drug development process Optimisation of development strategy Acceleration of patient access to medicines 13

14 Scientific Advice may increase chances of success 14

15 CHMP Scientific advice and Outcome of MAAs Regenstrom, J. et al. Factors associated with success of market authorisation applications for pharmaceutical drugs submitted to the European Medicines Agency. Eur J Clin Pharmacol. 20 Nov 2009 Positive predictors for Positive MAA outcome Company size Compliance with obtained CHMP SA Increase of MAAs with CHMP SA from 22% in 2004 to 47% in 2007 Negative predictor: Orphan drug Status 15

16 ..but cannot take over the development risk for companies.however the CHMP wishes to point out that the current strategy as proposed by the company is somewhat risky. (Quote from Roche SA ) 16

17 Points to consider EMA vs Nationale Beratung NOTE : Nationale Behörden sind auch immer in die EMA-Beratung involviert. 17

18 National Scientific Advice EMA Scientific Advice Specific expertise/interest EIH (Entry-Into-Human) Pre-CTA Rapporteurship Co-ordintorship Input before CHMP SA Or instead if non-divergent views Direct dialogue 1 to several countries Potential Rapporteurship Timelines: 2-4 months Cheaper as central SA or even free Pan European View Critical overall development questions Innovations, Advanced therapies No guideline available or Approach (very) different from guideline Biosimilars, Peads, Adaptive/innovative design Protocol assistance (orphan) Qualification of novel methodologies Discrepancy in national SA feedbacks Binding Possibility for parallel CHMP/FDA advice Very busy procedure, limited dialogue Most conservative advice? Timelines: 4-6 months 18

19 Industry s Challenges Balance expectations in the company Integrate advice into global development program (EU and US feedback) Timing! Too early vs too late Workload 19

20 Trends at Roche Involve regulators earlier in development plans In general, SA is sought for development programs Balance between National and CHMP SA Choice of countries For very specific questions or if relationship/expertise - go to one/several countries For general overall development questions go for central SA. For specifically challenging topics discuss first with one country with expertise and then go for central SA Increase in central SA due to need for pan-european view BUT Less transparent and less direct dialogue possible... always case by case... 20

21 EU vs US vs RoW Globale Entwicklung Zulassungsbehörden HTA-bodies Endpunkte(e) Medical practice Zulassungsstatus Zusatznutzen vs Risk-Benefit Guidelines Studiendesign Versorgungsrealität Vergleichstherapie Fachgesellschaften Patienten Payer 21

22 Fazit und Outlook Ein Beratungsgespräch ist IMMER hilfreich Ein gutes Briefing Document ist key to success Gut durchdachte Fragen und genug Informationen, die der Behörde eine Beantwortung der Fragen erlauben.. Sequentielle Kombination von BfArM und EMA-Advice ist optimal Bereit sein für konstruktives feedback Externe Experten zum Beratungsgespräch einladen? GBA und BfArM joint meeting?? SA might increase the chances of success but will not save a non-efficacious or unsafe drug 22

23 Back-up 23

24 Pre-submission phase Clock start Revision of request Presentation of new request Additional expert appointment EMEA REVIEW of evidence Pre-submission meeting With the coordinators Appointment of 2 coordinators Letter of intent SA Meeting 1 EMEA Validation

25 Pre-submission phase Clock start First reporting First Reports Discussion on First Reports Questions SA Meeting 1 Additional experts SA Meeting 2 EMEA REVIEW of evidence EMEA Validation EMEA QUALITY assurance

26 Pre-submission phase Clock start First reporting Possible Finalisation in 40 Days Final Letter Adoption of Final Letter SA Meeting 1 Additional experts SA Meeting 2 CHMP & COMP EMEA REVIEW of evidence EMEA Validation EMEA QUALITY assurance CHMP SAWP EMEA Peer review

27 Pre-submission phase Clock start First reporting Final report Discussion mtg Final Letter SA Meeting 1 Additional experts SA Meeting 2 Additional experts SA Meeting 3 EMEA REVIEW of evidence EMEA Validation EMEA QUALITY assurance CHMP SAWP EMEA Peer review CHMP & COMP

28 EMA Roadmap p