Navigating Regulatory Expectations in Biosimilar Solutions and Biosciences Corp

Convergence of Regulatory Expectations Robert Salcedo BiosimilarSolutions & BiosciencesCorp

BiosciencesCorp & BiosimilarSolutions 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 50-100L 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 EU5 Biotech $200B by 2022 USA Biotech $400B by 2019 Biosimilar Market Projected $250B (EU & US ) by 2022

To Survive Must Think Differently One Quality Mindset Regulators are your friends Look at the outside Inside Out Fix System Focus Use Consultant for Short Period Globalize Local Regulations Deviations Learning Tool Focus on System On Systematic Solutions Build Internal Expertise Right First Time Data Integrity Don t Institutionalize Learning CAPA Solve Problems Local Regulatory Agencies Aligning Practices With US and EU Expectations

Biosimilar Companies Reaction 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 cGMP R&D Process and Methods Primary Part of Biosimilarity Regulatory Inspector First Place they will look Heightened Inspectional Focus on R & D

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

Balancing Act Part of Submission 1: Analytical Characterization Force Degradation Cell Line Characterization Clinical consequences Scientific Understanding 2: Impurity analysis Media Feed studies Purification options Full Quality System Non-GMP Policy and Procedures Defining Practices for cGMP 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 Quality System Alignment Requires Cultural Shift

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

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

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

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

Regulatory Convergence Challenges both Commercial and R& D Systems R & D Commercial Define R &D vs cGMP activities SOP driven practices Leverage external expertise Data Integrity Traceability of data in submissions 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: Stop: 1. People 2. Process 3. Technology 4. Systems 5. Data Integrity 1. Focusing on local requirements 2. Separating R &D with Commercial 3. Relying only on local talent ON OFF Companies Focusing On Global Systems Implementation

Strengthen and Build Internal Expertise Summary Short Term Consultants Focus on data integrity Repatriate Locals Robustness Electronic System Success Depends Implementing Comprehensive Program Intensify internal audit Process Monitoring Investigational Practices Quality on Floor Leverage External Information Learn from others mistake 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 BiosciencesCorp 312-972-5602 Robert.Salcedo@biosciencescorp.com