Convergence of Regulatory Expectations Robert Salcedo Biosimilar Solutions

Convergence of Regulatory Expectations Robert Salcedo Biosimilar. Solutions & Biosciences. Corp

Biosciences. Corp & Biosimilar. Solutions • Founded in 2012 • Located in USA, San Ramon, California • • Biosimilar Strategy Biosimilar Portfolio and Capacity Assessment Facility Design, Commissioning & Start-up Cell Line & Process Development Immunogenicity Method and Regulatory Package IND Ready Biosimilars at 50 -100 L Scale FDA and EMEA regulatory support and remediation Contact : • • • Daniel. Chang@biosciencescorp. com Robert. Salcedo@biosciencescorp. com Tel 312 -97205602 or 408 -338 -9339

Outline • Economic Driver(s) • Inspectional Experience • Approaches Taken by Companies • R &D Vs Quality Control • FDA and EMEA New Area of Focus • Balancing GMP and Non-GMP in R &D • Prevailing Trend(s) • Acquisition of Clones • External Method Development • Management Challenges • Strengthening Core

Regulatory Convergence Driven by Economic Forces USA Biotech $400 B by 2019 EU 5 Biotech $200 B by 2022 Biosimilar Market Projected $250 B (EU & US ) by 2022

To Survive Must Think Differently Inside Out Focus on System Data Integrity Fix System One Quality Mindset Deviations Learning Tool Focus On Systematic Solutions Globalize Local Regulations Use Consultant for Short Period Institutionalize Learning CAPA Don’t Solve Problems Right First Time Build Internal Expertise Regulators are your friends Look at the outside Local Regulatory Agencies Aligning Practices With US and EU Expectations

Biosimilar Companies Reaction Create Multinational Leadership Team Own Product Leverage External Experts One Quality Mindset Build Internal Expertise Buy Own Lease Bring in Short term Expert Right First Time Hire Smart People Leverage Local Expertise and Knowledge Strengthening Internal Capabilities & Outsourcing to Reduce Exposure

Regulatory & Quality Focus Regulators Focus on Both End of Development Supply Chain

R & D Heavy Lifting For Biosimilars Scientist Not Used to Thinking c. GMP Regulatory Inspector First Place they will look R&D Process and Methods Primary Part of Biosimilarity Heightened Inspectional Focus on R & D

One Quality System R & D and QC Practices Alignment R&D Product Development Analytical Characterization Quality Target Profile Critical Quality Attributes Critical Process Parameters QC Product Release Process Monitoring Stability CPP tracking Regulators Expect To See One Quality System Across Company

Balancing Act Part of Submission 1: Analytical Characterization Force Degradation Cell Line Characterization Clinical consequences 1 Full Quality System 2 Scientific Understanding 2: Impurity analysis Media Feed studies Purification options Non-GMP Policy and Procedures Defining Practices for c. GMP R & D Activies

Quality and R &D Functions Clear Delineation of Activities QUALITY Clear Definition of what is in/out R&D SOP driven practices to align Speed vs Quality System Alignment Requires Cultural Shift

Rule of Thumb Submission Filing GM P Experiment Not In submission Definition of Experiment Vs Similarity Activities

Successful Companies Embracing Change R & D: 1. 2. 3. 4. 5. 6. Cell Line Purchase Method Development Internal Controls Short term consultants Repatriation Expertise Aligned Quality System Commercial: A B 1. 2. 3. 4. Data Integrity Chain of Custody Process monitoring Investigational expertise 5. Intense audit by external experts Successful Companies Externalizing & Clear Separating Activities

Cell Line Purchase Now Buy Clone and Develop In-House • • • Buy Process with Cell Line Proof CQA required Initial regulatory advise Scale to 25 L with CPP Tech Transfer Clinical Ready process Before Companies Buying Proven Process with Full c. GMP Documentation

Externalize Method Development Develop all methods in-house and outsource a few A B Outsource all methods development Method Outsourcing Follow by Validated Method Transfer

Regulatory Convergence Challenges both Commercial and R& D Systems R&D • • • Define R &D vs c. GMP activities SOP driven practices Leverage external expertise Data Integrity Traceability of data in submissions Commercial • • • Data Integrity Robustness of Quality Systems Investigational practices Independence of Quality Unit Intense audit practices To Be Successful Companies Need to Drive Internal Alignment

One Quality System Inspection Readiness: 1. 2. 3. 4. 5. People Process Technology Systems Data Integrity Stop: ON OFF 1. Focusing on local requirements 2. Separating R &D with Commercial 3. Relying only on local talent Companies Focusing On Global Systems Implementation

Strengthen and Build Internal Expertise Summary Short Term Consultants Repatriate Locals Intensify internal audit Investigational Practices Leverage External Information • Learn from others mistake Focus on data integrity Success Depends Implementing Comprehensive Program Robustness Electronic System Process Monitoring Quality on Floor Statistical Approaches Areas of Focus for Companies with Global Aspirations

Balancing Act Requires Focus Global Expectations One System Focus Local Requirements Executive Leadership Play Key Roles- Process Take Time

Convergence of Regulatory Requirements Questions ? ? ? Robert Salcedo Biosciences. Corp 312 -972 -5602 Robert. Salcedo@biosciencescorp. com