Korean and APEC Perspectives: Recent trends in the regulation of biotherapeutics

Transcription

1 Korean and APEC Perspectives: Recent trends in the regulation of biotherapeutics Jeewon Joung Ministry of Food and Drug Safety Republic of Korea

2 Outline I. Korean Regulatory updates for Biotherapeutics II. Updates on APEC RHSC Biotherapeutics Roadmap III.Conclusion 2

3 Korean Regulatory updates for Biotherapeutics I. Implementation of RMP II. Implementation of patent and exclusivity into drug approval III. Harmonization of comparability data (Stability) IV. Majungmool Project V. Updates for biosimilar products 3

4 Risk Management Plan in Korea History Running pilot program with scope as REMS (2011~2014) 7 products are voluntarily run REMS Expanding the scope and establishment of legislative basis for RMP(Aug. 2014) Enforcement of Pharmaceutical Affairs Act, Article 4. Section 11 Publication of Guideline for RMP assessment (May 2015) Implementation of RMP as of 1 st July 2015

5 US(REMS) EU Japan Korea From Subjects Status of RMP in Korea -Comparison with critical NRAs- Components New drug Biological product Generic(if necessary) On demand from FDA On demand from sponsor Medication Guide Relevant document, communication plan Training program for healthcare professionals Registered pharmacists/ doctors/nurses Patient monitoring Patient registry New drug Biological product Generic(if necessary) New drug Biological product New drug Orphan drug Subject of re-examination Significant amendment Generic(if necessary) On demand from MFDS (Eg. new indication, new If safety signal detected (biological product only) dose regimen..) during post marketing If safety signal detected On demand from EEA On demand from sponsor period during post marketing period On demand from sponsor Risk Minimization Medication Guide Relevant documents Training program Patients alert cards Prospective registry study Prospective epidemiology study Additional data analysis Prescription survey Non-interventional study for off-label use Risk minimization plan - Routine risk minimization measures Risk mitigation measures - Patients guide - Safety measures (E.g. Training - Additional measures program) (Patient guide, Product - Healthcare professionals guide information guide) - Relevant document Additional pharmacovigillance Safety monitoring plan - Routine, Additional Efficacy investigation plan Surveillance measures -Passive(voluntary report)) -Active -Cohort study -Observational study Efficacy investigation plan

6 Implementation of patent and exclusivity into drug approval Background MFDS is taking consideration of patent certification before marketing authorization from March If product of interest is under the court for patent argument, drug approval will be postponed until resolution. Task process 1. Patent listing (by original company or patent holder) called Green list 2. Notification of MA submission(by follow-on company to original company or patent holder) 3. Request of marketing ban (by original company or patent holder); in case that patent infringement, original company can request for marketing ban to MFDS after lawsuit 4. Marketing authorization of first generic (MFDS); If follow-on company wins the patent lawsuit, the first generic can have exclusive marketing protection for 9 months.

7 Implementation of patent and exclusivity into drug approval What are changed in terms of drug approval MFDS should hold authorization for follow-on product during the request for marketing ban period (usually for 65 days) from submission. MFDS review period for generic product(if GMP included): 90 days Conditional approval MFDS should authorize a generic with Marketing ban condition for 9 months MFDS should authorize a subsequent product to first generic product with Marketing ban condition for 9 months

8 Biological products in the Green list Category Products Substance Vaccine 13 9 Blood products 1 1 Toxin 1 1 Recombinant products Cell therapy products 2 2 Total

9 Harmonization of comparability data Stability data requirement for manufacturing changes BEFORE March 2015 As part of comparability data, company should submit 3 commercial batch, 6 month real-time stability data for drug product in almost any cases (MFDS guideline for comparability data requirement for biological product) AFTER March commercial batch, 6 month real-time stability data for drug product is no longer necessary in case for manufacturing changes of drug substances. This update had been concluded as the outcome of APEC biotherapeutics Workshop discussion

10 Majungmool project Mahungmool (=Priming water) project Project to support academia, small scale enterprise, which develop vaccine, antibody, cell & gene therapy product to facilitate the product authorization Target/Hit&lead identification Nonclinical Phase 1 Phase 2 Phase 3 M A Distrib ution Majungmool project Strengthen regulatory advice Building infrastructure 1. Customized regulatory support 2. Early phase scientific advice 3. Basic regulatory training for R&D scientist 4. Fostering non-clinical study center specific for cell & gene therapy product Providing regulatory guidelines in proactive manner

11 Majungmool project Program Products in 2014 Products in 2015 Customized regulatory support (Inc. Early phase scientific advice) Cell therapy 2 products/2companies 4 products/4companies Antibodies 5 products/5companies 7 products/7companies Vaccines 9 products/5companies 28 products/7companies Basic training Cell therapy 10.6~10.7 (123 attendee) 1 st : 2.26~27 (195) 2 nd : 9.3~4 for R&D scientist Antibodies - 1 st : 5.21 (76) 2 nd : Open MFDS day 16 products/ 7 meetings 15 products/ 7 meetings Non-clinical study center for cell & gene therapy product - Designation of 2 centers

12 Updates for biosmilar products 1. Biosimilar updates Category total Product authorized Under clinical study Local Foreign Total Proportion of local development 63% 80% 59% 2. Authorized products Remsima (Infliximab), Herzuma (Trastuzumab), Davictrel (Etanercept), Brensys (Etanercept), Scitropin A (somatropin), ** Imported 12

13 3. Under clinical study 26 biosimilar candidates with 43 protocols (as of ) No of IND Biosimilar Candidates Total Korea

14 Developmental status by product class Total Korean 14

15 Updates on APEC RHSC Biotherapeutics Roadmap I. Outcomes of 2015 APEC Harmonization Center Biotherapeutics Workshop II. Biotherapeutics Center of Excellence 15

16 Plans for APEC Biotherapeutics Roadmap Step ~2014 Assessment of regulatory environment and gaps between APEC members through gap analysis and workshop Step 2 Step ~2016 Training & Workshop Develop training curriculum and conduct training and workshop We are here! Step ~2018 Assessment & training/workshop Analyze steps 1, 2 Review postimplementation of international guidelines Revise training plans and continue trainings to foster experts Step ~2020 Training/workshop Recommendations for regulatory convergence Establish concrete training system Build up collaborative system and information sharing network High regulatory convergence 16

17 2015 AHC Biotherapeutics Workshop Title : 2015 APEC Biotherpeutics Workshop Date : July 1 st -2 nd, 2015 Venue : Songdo Conventia, Incheon, Korea Participation : 157(16 economies), industry(76)-government(53, 30 regulators) Program: 5 Sessions and Post-meeting - Session 1 : Introduction: significant Gaps, CoE - Session 2 : Manufacturing Changes - Session 3 : Similarity Assessment for Biosimilars - Session 4 : Biosimilar Updates: EMA, US FDA, COFEPRIS, CFDA, WHO - Session 5: Biotherapeutics CoE and its consideration - Post-meeting : Topics, Structure, Pilot programe of CoE 17

18 18

19 2015 AHC Biotherapeutics Workshop Outcomes To prioritize identified gap areas for CoE (contours & structures) - Implemented in phase 3 of the roadmap To delve into unique differences(biotherapeutics vs chemicals) & highlight the importance of science based approval pathway - To promote harmonization of regulatory STD for Biotherapeutics & trade among APEC economies - To update on implementation of guidelines for biotherapeutics in various countries & to provide overview/update on WHO or /ICH guidelines - In depth discussion of two areas which are unique to biotherapeutics: Comparability & Biosimilarity 19

20 2015 AHC Biotherapeutics Workshop Outcomes [Post-meeting] Target audience - CMC expert & clinical evaluators Structure - On-line & face-to-face - Two &1/2 days: 1 st day theoretical; the rest with case studies - Two options for RHSC considerations: 1) 2 pilots, sequentially or separately 2) Merged as 1 with parallel tracks - Potentially include partnering with CASSS(non-profit organization) as well as academic partners? 20

21 2015 AHC Biotherapeutics Workshop Outcomes Curriculum topic areas 1) Introduction to biotherapeutics: theoretical aspects(on-line modules) 2) Comparability throughout product lifecycle management : Principles of ICH Q5E(components of comparability) : Case studies for post approval variation 3) Clinical considerations for assessing biosimilarity : Clinical trial design, clinical pharmacology(pk assay), immunogenicity, methodology for assay, analytical comparability - Can run in parallel in the same CoE or network of CoEs(two separate pilots in different CoE s) 21

22 Biotherapeutics CoE: Area of Regulatory Convergence Basic Different levels of regulatory expertise Needs to be basic modules: terms, unique natures (structures, function, development, non-clinical and clinical issues, regulatory considerations) Comparability Fundamental basis for the assessment of biosimialrs Important to differentiate the analytical comparability for biosimilars(who SBP guidance) from it for changes for product s life cycle Biosimilarity Considered as an integrated & essential part of the biosimilars assessment, unique in the biotherapeutic space 22

23 Biotherapeutics CoE: Recommendation for 2016 & beyond WHO (target audience) WHAT (curriculum) APEC member economies with demonstrated interest in harmonization (vs those with systems that are already harmonized or those in early stage of learning) Regulators (CMC experts and clinical evaluators) 1) Comparability assessment of biotherapeutics throughout the product life cycle 2) Clinical considerations of biosimilars WHERE (location) WHEN (2016pilot) Numerous options (one CoE to cover both topics/network of collaborating CoEs) Driven by availability of interested academic partners with relevant expertise Seoul Natl Univ, Northeastern Univ, etc Preferably, in first half of 2016 HOW (Logistics) Online(e-learning) + Face-to-face Theoretical + case studies + hands on Certification or recognition of attendance to be granted 23

24 Biotherapeutics CoE: Next Steps(Operating Plan) Topics Regulatory Gaps between economies Lessons learned of past AHC Biotherapeutics workshop( 13~ 15) Curriculum Development Research(existing referential workshops, symposium, training course) Extra survey may be needed to identify national priority focusing on middle and low economic members Identification of CoE partners Academia: Training experience, resources, geography RHSC, program committee Pilot CoE Operation (in 2016) In 2016 CoE Operation and (2017~, phase3) Feedback from Pilot CoE outcomes Consideration of linking to other CoEs(PV, Clinical trial) 24

25 Tel: Fax: