The Importance of Developing a Global Regulatory Strategy towards the Goal of Registration - Carlos Langezaal, Eisai Inc

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Carlos Langezaal - Eisai Inc, Speaker at the marcus evans Discovery Summit Fall 2011, delivers his presentation on The Importance of Developing a Global Regulatory Strategy towards the Goal of Registration

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The Importance of Developing a Global Regulatory Strategy towards the Goal of Registration - Carlos Langezaal, Eisai Inc

  1. 1. The Importance of Developing a Global Regulatory Strategy Towards the Goal of Registration Carlos Langezaal, PhD Director, Global Regulatory Affairs Eisai, Inc.
  2. 2. From Compound to Drug 10 - 12 Years $7500-3000M 1 DRUG 10 GO INTO MAN 100 INTO DEVELOPMENT 1000 SCREENED FOR ACTIVITY 10000 COMPOUNDS
  3. 3. New Drug Development Process and Strategy Pre-Clinical Research Synthesis and Purification IND / CTA NDA / MAA Clinical Research Post- Marketing Animal Testing Phase 1 Phase 2 Phase 3 Accelerated Approval Potential Regulatory Meetings Phase 4 PMRs REMS / PSUR
  4. 4. Regulatory Affairs and the Product Life Cycle Renewal Pharmacovigilance Advice on Product Development Variations Advertising Approval / Cleared Submit MAA /NDA Regulatory Questions MAA/ NDA Approval CTA/IND Extensions/Updates CTA/IND
  5. 5. Regulatory Input into Development Life- cycle manage-ment File & Launch Phase III PoC to commit to Phase III FTIH to PoC Candidate selection to FTIH Lead to Candidate Target to Lead Gene - Function - Target Association Disease selection Target family selection Prior to First Time in Human What do the animal data tell us? Do we need to amend our target group on the basis of toxicity findings? Initial Product Profile What studies will be needed? What are the issues we need to discuss with regulatory authorities? Prior to Large Scale Clinical Trials Have we agreed our development plan with Regulators? Does the trial design meet regulatory/clinical end points? Prior to Submission Does the data support the proposed labeling? What can we learn from competitor’s experiences? How do we maximize life cycle management? Following Initial Opportunity Assessment What lessons can we learn from previous development projects?
  6. 6. Three phases of regulating products <ul><li>IND / CTA phase </li></ul><ul><li>Licensure phase </li></ul><ul><li>Post licensure phase </li></ul>
  7. 7. Regulation of Clinical Research in the US IND Start Clinical Program Clinical Hold 30 Days <ul><li>Other considerations: </li></ul><ul><li>Pre-IND meeting </li></ul>
  8. 8. IND Format and Content <ul><li>Provide technical information for adequate evaluation to support proposed clinical investigation </li></ul><ul><ul><li>Cover letter, introduction, agreements </li></ul></ul><ul><ul><li>CMC information </li></ul></ul><ul><ul><li>General Investigational Plan, IB and Protocol </li></ul></ul><ul><ul><li>Pharmacology and Toxicology data </li></ul></ul><ul><ul><li>Any previous human experience </li></ul></ul><ul><li>Provide information on proposed clinical program </li></ul><ul><li>CTD format vs “old” format </li></ul>
  9. 9. Regulation of Clinical Research in Europe <ul><li>Includes all clinical trials in the EU </li></ul><ul><li>Describes a single harmonized process across all EU member states – Clinical Trial Directive </li></ul><ul><ul><li>Individual member states can implement the Directive slightly differently </li></ul></ul>
  10. 10. Timelines <ul><li>CTA approvals: </li></ul><ul><ul><li>allowed up to 60 days with one clock stop – as a notification </li></ul></ul><ul><ul><li>requires written approval for biotech (60 days) </li></ul></ul><ul><li>In practice timings vary considerably e.g.: </li></ul><ul><ul><li>Belgium 28 days </li></ul></ul><ul><ul><li>France, Ireland, Sweden, UK 30 days </li></ul></ul><ul><ul><li>Netherlands 49 days </li></ul></ul><ul><li>Phase I Studies </li></ul><ul><ul><li>Belgium 15 days, France 14 days, Germany 20 days, Netherlands 21 days, UK 14 – 21 days </li></ul></ul>
  11. 11. CTAs – Format of Applications (1/2) <ul><li>Eudract Number </li></ul><ul><li>Application Form </li></ul><ul><li>Clinical Protocol </li></ul><ul><ul><li>Describing in detail the objectives of the trial and how it will be conducted </li></ul></ul><ul><li>Investigators Brochure (IB) </li></ul><ul><ul><li>Information on the drug that is critical to the Investigator (e.g. results of previous studies, marketing status) </li></ul></ul>
  12. 12. CTAs – Format of Applications (2/2) <ul><li>Investigational Medicinal Product Dossier (IMPD) </li></ul><ul><ul><li>Summary of Quality – information on trial material and how it is manufactured and controlled </li></ul></ul><ul><ul><li>Summary of Safety – information on safety studies undertaken on the trial product </li></ul></ul><ul><ul><li>Efficacy – summary of human studies to date </li></ul></ul><ul><li>Manufacturer’s Authorization for Investigational Medicinal Products (GMP) </li></ul><ul><ul><li>Manufacture outside EU - must be released by EU QP </li></ul></ul><ul><li>Examples of labeling </li></ul>
  13. 13. CTA End of Trial Notifications and Reports <ul><li>End of trial notifications – national and global reports are required within 90 days of last patient visit </li></ul><ul><li>End of trial reports required within 1 year of completion </li></ul>
  14. 14. The Application <ul><li>US: New Drug Application (NDA) </li></ul><ul><li>EU: Marketing Authorisation Application (MAA) </li></ul><ul><li>Japan: JNDA </li></ul><ul><li>Format </li></ul><ul><ul><li>(e)CTD format in 3 ICH regions </li></ul></ul><ul><ul><li>Other regions: national (e)CTD derivatives </li></ul></ul>
  15. 15. NDA / MAA / JNDA <ul><li>The application includes </li></ul><ul><li>Regional documentation (CTD Module 1) </li></ul><ul><li>Summaries of CMC, non-clinical and clinical (Module 2) </li></ul><ul><li>The drug's test results (Modules 3, 4 & 5) </li></ul><ul><ul><li>CMC (CTD Module 3) includes Manufacturing information to demonstrate proper manufacture of the drug </li></ul></ul><ul><ul><li>non-clinical (CTD Module 4) </li></ul></ul><ul><ul><li>clinical (CTD Module 5) </li></ul></ul><ul><li>Proposed label. The label provides: </li></ul><ul><ul><li>necessary information about the drug, including uses for which it has been shown to be effective, possible risks, and how to use it </li></ul></ul>
  16. 16. US Approval Routes <ul><li>NDA </li></ul><ul><ul><li>505(b)(1) Traditional </li></ul></ul><ul><ul><li>505(b)(2) New route/form. for patented drug </li></ul></ul><ul><ul><li>ANDA Generic </li></ul></ul><ul><li>BLA (NDA for biologics) </li></ul><ul><li>DEVICES </li></ul><ul><ul><li>PMA (NDA equivalent) </li></ul></ul><ul><ul><li>510(k) Based on predicates (features approved) and </li></ul></ul><ul><ul><li>NSUR (No Significant Use Risk) </li></ul></ul>
  17. 17. US Timelines and speeding access to important new therapies <ul><li>Standard Review – 10 Months (PDUFA) </li></ul><ul><li>Priority Review – 6 Months (given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists) </li></ul><ul><li>Fast track - process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and fill an unmet medical need </li></ul><ul><ul><li>includes eligibility for Accelerated Approval and Rolling Review </li></ul></ul><ul><li>Accelerated Approval regulation - allowing earlier approval of drugs to treat serious diseases, and that fill an unmet medical need based on a surrogate endpoint . Condition that post marketing clinical trials verify the anticipated clinical benefit </li></ul>
  18. 18. EU Application Procedures <ul><li>3 European Procedures </li></ul><ul><li>Centralised </li></ul><ul><ul><li>one application to the central EMA allows marketing everywhere in the EU </li></ul></ul><ul><li>Mutual Recognition </li></ul><ul><ul><li>an approval in one country is ‘mutually recognised’ in a number of other EU member states </li></ul></ul><ul><li>Decentralised Procedure </li></ul><ul><ul><li>an assessment is carried out by one country – this is discussed and agreed by a number of other EU member states </li></ul></ul><ul><li>Need for agreed PIP prior to EU MAA submission </li></ul><ul><li>National Procedures in individual countries </li></ul>
  19. 19. Centralised Procedure Key Points <ul><li>One Dossier for the whole EU </li></ul><ul><li>Submitted to EMA and the CHMP members </li></ul><ul><li>Appointment of Rapporteur/Co-Rapporteur </li></ul><ul><ul><li>CHMP members from 2 countries to perform “lead assessment” </li></ul></ul><ul><li>One evaluation period leading to a one EU-wide MA in 27 MS (+ linking National Licences in Norway/Iceland) </li></ul><ul><li>Application review and maintenance all handled by the EMA </li></ul><ul><li>National Agencies through CHMP members have opportunity to ask questions/comment on application </li></ul>
  20. 20. Centralised Procedure - Applicability <ul><li>Compulsory for </li></ul><ul><ul><li>Biotechnology products </li></ul></ul><ul><ul><li>designated Orphan Medicinal Products </li></ul></ul><ul><ul><li>drugs for treatment of AIDS </li></ul></ul><ul><ul><li>Cancer </li></ul></ul><ul><ul><li>Neuro-degenerative disorders </li></ul></ul><ul><ul><li>Diabetes </li></ul></ul><ul><ul><li>Auto Immune diseases </li></ul></ul><ul><ul><li>Viral diseases </li></ul></ul><ul><li>Optional </li></ul><ul><ul><li>New Active Substance </li></ul></ul><ul><ul><li>Significant therapeutic, scientific or technical innovation or that the granting of authorisation is in the interest of patients </li></ul></ul><ul><ul><li>Generics / Hybrids of Centrally Authorised products </li></ul></ul><ul><ul><li>Duplicate licences of Centrally Authorised products </li></ul></ul>
  21. 21. Submission of MAA <ul><li>Date of submission agreed between applicant and EMA in relation to published Target submission dates ( www.ema.eu.int/ ) </li></ul><ul><li>Explicit guidelines, but get confirmation in pre-submission meeting(s) </li></ul><ul><ul><li>1 Jan 10: e-CTD MAAs mandatory </li></ul></ul><ul><li>Dossier to be submitted in parallel to Rap/Co-Rap </li></ul>
  22. 22. Deciding your filing strategy <ul><li>Elegibility/compulsory Centralized Procedure </li></ul><ul><li>Commercial Considerations, market accessibility </li></ul><ul><li>One centralized license vs individual licenses (Filing only in certain countries) </li></ul><ul><li>Data protection </li></ul>
  23. 23. EU Timelines and speeding access to important new therapies <ul><li>Review: 210 days (+3 months Commission decision) </li></ul><ul><li>Accelerated evaluation: 150 days </li></ul><ul><li>Guidance: EMEA/419127/2005 </li></ul><ul><li>Scientific Advice </li></ul><ul><li>Guidance: EMEA/4260/01 </li></ul><ul><li>Orphan designation </li></ul><ul><li>Regulation (EC) No 141/2000 </li></ul>
  24. 24. Post Authorization Activities <ul><li>Post Licensing commitments (US & EU) </li></ul><ul><li>Amendments to Marketing Authorisations (MAs) (EU)/ Amendments to NDA / Supplements to NDA (US) </li></ul><ul><li>Renewals (EU) </li></ul><ul><li>Annual Reports (US) </li></ul><ul><li>PSURs (EU) </li></ul><ul><li>RMP / REMS </li></ul>
  25. 25. Develop Regulatory Strategy <ul><li>Think Globally </li></ul><ul><li>Start early and fine tune during development </li></ul>

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