Life Cycle Management of Biotech Products An Industry Perspective. Thomas Schreitmueller

Transcription

1 Life Cycle Management of Biotech Products An Industry Perspective Thomas Schreitmueller Co chair FIFARMA Regulatory WG

2 Vision and Mission Vision To be the regional voice of the innovative pharmaceutical industry, supporting the development of a sustainable and patient centric healthcare system in Latin America. Mission To engage in the development of policies that foster the access to high quality pharmaceutical innovations that prolong, preserve and improve life for patients in Latin America.

3 Global Management of Post Approval Change is Complicated I D RATHER BE CHANGING TIRES

4 Global Management of Post Approval Change is Complicated Same Core data/ information submitted to ~140 countries Guidelines exist in only a few Emerging Market countries, therefore different Health Authority expectations Some countries have no defined PAC procedures Frequently changing procedures, requirements and timelines Differences in administrative documentation & supporting data required to demonstrate that a specific change does not negatively impact Q, S or E Companies concurrently manage multiple reviews of same core information and multiple rounds of responses to questions to Health Authorities Adopted from IFPMA 2017

5 Estimated Global Approval Times for Major Changes Example: New drug product manufacturing site < 6 months 6 12 months months >18 months Variability in review & approval times for the same change across markets Adopted from IFPMA

6 Science is evolving and many promising new modalities and medicines are expected to reach NRAs soon CAR T therapies are T cells that have been genetically modified to allow the T cell to recognize and destroy tumor cells Combination therapies increasing quality and quantity of life by combining targeted cancer treatments to increase their effectiveness Gene therapy helping to replace defective or missing genes in cells through the introduction of DNA for the treatment of genetic diseases Cell therapy insertion of living cells into patients to replace or repair damaged tissue, in order to facilitate improved organ or tissue functionality Antibacterial treatments neutralize highly pathogenic bacterial surface proteins or secreted toxins and activate the immune system to directly kill the bacteria With over 7000 medicines in development, the exciting new wave of medical innovation will play a key role in addressing the challenges faced by patients and healthcare systems Adapted from Health Advances analysis; Adis R&D Insight Database. March 2015, compiled by PhRMA 6

7 Developments may be based on innovative Personalised Healthcare (PHC) approaches Science and technology are shifting the boundaries of what is possible in medical research and patient care Key trends/technologies driving evolution in PHC 7

8 New Clinical Approaches in Drug Development Methodologies Biomarker-guided Clinical Trial Designs Basket trials Umbrella trials Adaptive Designs Major Goals Increase R&D efficiency Increase the number of trial participants getting the best treatment

9 Example of basket trial: BRAF V600 Vemurafenib Objective: Explore the effect of a specific treatment in a biomarker positive subgroup (in different histologies) Hyman et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med, 2015, 373:726 36

10 Innovative drug development approaches require innovative and strong regulatory systems and procedures Consequences Smaller Patient Numbers Faster Development Timelines Tighter (more specific) Clinical Experience Shift of traditional preapproval development activities into the postapproval space Enablers Accelerated Approval Pathways Rolling Submissions Parallel Companion Diagnostics (CD) Evaluation Post-Approval Committments CMC-Flexibility Reliance Options Recognition Verification Abbridged Robust Pharmacovigilance System Efficient Life-Cycle Management

11 Efficient Life Cycle Management Key components of an efficient regulatory system are missing in the regulations of many countries 6. Reliance and mutual recognition Risk based classification system 5. Expedited approvals Common classification system 4. Novel regulatory mechanisms and tools Clear and transparent timelines Adapted from IFPMA presentation at DIA Euro 2018 Page 11

12 Implementation of highly elaborated WHO guidance may easily solve many issues achieving efficient product life cycle management (LCM) The WHO post approval change guidance for biotherapeutic products* (BTPs) has all features that will significantly facilitate the work related to product life cycle both at industry and NRAs It should be implemented in each LATAM country!! *WHO Guidelines on post approval changes for biotherapeutic products Appendix 1

13 Suggestions on expedited review procedures* supporting regulatory systems strengthening efforts The NRA performs an assessment of the decision of the NRA of the licensing country to determine whether reliance of that NRA s decision is appropriate. The submission consists of: a cover letter from the marketing authorization holder informing the NRA about the change; a copy of the approval letter issued by the NRA of the licensing country; assessment reports and relevant correspondence from the NRA of the licensing country (if made available by the NRA); a detailed description of the change; and supporting data submitted as necessary if assessment reports are not available. *WHO Guidelines on post approval changes for biotherapeutic products Appendices 2 and 3

14 Rationale for ICH Q12 Opportunities for flexibility in post approval change management have not been fully realized Different requirements around the world are a disincentive to making improvements to increase process robustness Lack of alignment exists regarding necessary information and level of detail in the regulatory dossier So called regulatory commitments impact on postapproval change management ICH Q12 proposed by the Informal Quality Discussion Group (IQDG) and accepted by the ICH Steering Committee in Minneapolis, June 2014

15 Q12 Element: Post Approval Change Management Protocols (PACMP) A PACMP is a regulatory tool that provides predictability and transparency in terms of the requirements and studies needed to implement a change as the approved protocol provides an agreement between the MAH and the regulatory authority. Concept exists in some regions USA: Comparability Protocols. Europe: Post Approval Change Management Protocols. Key elements agreed Description of a PACMP and how it is used Components of a PACMP Types of PACMPs: Specific change. Broader protocols, e.g., multiproduct and/or multi site

16 FIFARMA s asks for NRAs: While we see encouraging examples and results of regulatory systems strengthening efforts in the region like: establishment and implementation of regulations for biologics CRS as the flagship for collaborative regulatory decision making Implemented and piloting reliance based regulatory pathways e.g. Panama and Brazil In many LATAM countries there is a need for: development and implementation of alternative registration pathways piloting, adopting and executing reliance based procedures in regulatory decision making pharmacovigilance system implementation along WHO Triple S principles alignment and establishment of local regulatory requirements along global PAC standards e.g. WHO postapproval guidances for BTPs and vaccines

17 and a last word Fragmentation, duplication and inefficiency are undermining progress.. So we have choice: we can keep doing what we re doing. But we must accept that the outcomes will be the same. Let me remind you that the definition of insanity is to keep doing the same thing and expect a different result. We must do something different. We need innovation and disruption not just for developing new products, but for developing new ways of delivering those products and new ways of working together to deliver results. Bansal Bhavik, medium.com, reinvent the wheel or not From: Opening speech for the World Health Summit, Dr Tedros Adhanom Ghebreyesus, WHO Director General, Berlin, Germany 16 October 2018