A PROCESS VALIDATION GUIDE FOR COLD CHAIN LOGISTICS: ENSURING COMPLIANCE GLOBALLY

Transcription

1 A PROCESS VALIDATION GUIDE FOR COLD CHAIN LOGISTICS: ENSURING COMPLIANCE GLOBALLY Presented by: Gary Hutchinson, President, Modality Solutions 8 th BSMA Conference Preparing the Biotech Supply Chain for 2025 October 15th, 2015

2 Supporting Your Distribution Processes Requires an Integrated Approach Stability Studies Process Validation Packaging Qualification

3 The Growth in Biologics Requires a New Supply Chain Design The biopharmaceutical industry typically takes 10 to 15 years and an average of more than $1.2 billion to develop a new therapy A UPS survey found the majority of biopharmaceutical companies (74%) cite temperature-sensitive concerns as the top regulatory challenge in the supply chain The growth of novel biological therapies including monoclonal antibodies, is setting the scene for tomorrow's cold chain These novel therapies are particularly susceptible to injury from extremes in temperature, shock, vibration, pressure, and humidity

4 Increasing Complex Molecules Are Changing Biopharmaceutical Logistics 7 times 20 times 4 times Small molecule (0.3 kda) Insulin (5.8 kda) Recombinant DNA ( ~22 kda) Monoclonal Antibody (~150 kda)

5 Integrate Your Cold Chain Management Systems with Your Process Validation Approach Quality Systems Risk Management Assessment Product Stability Mitigation Planning Qualify/Verify Monitoring and Controls Partners NCs and exceptions CAPA and Change Control Management Review Cold Chain Integrity Storage (chemical stability) vs. Distribution (physical stability) Stability Testing for Logistics Stability Budgeting Excursion Management Validation Master Planning Thermal Profiles Transport Lanes Active Refrigeration Cold Chain Process Validation Quality Agreements Key Performance Indicators Audits and Inspections Subcontractors

6 Modern Quality Management Systems for Cold Chain Rely on Three Basic Tools Quality Systems NCs and exceptions CAPA and Change Control Management Review Risk Management Product Stability Qualify/Verify Partners Modern Quality System Tools Trending of Non-Conformances in Cold Chain Continuous Improvement and Effectiveness Monitoring Critical-to-Quality Attributes to Increase Quality System Maturity

7 Risk Management Approaches Are Necessary Quality Systems Risk Management Assessment Mitigation Planning Monitoring and Controls Cold Chain Integrity Product Stability Qualify/Verify Partners Mitigate Anticipate Evaluate

8 Product Stability Studies Should Reflect the Realities of Distribution of Biologics Quality Systems Risk Management Product Stability Storage vs. Distribution Stability Testing for Logistics Stability Budgeting Excursion Management Qualify/Verify Partners Study ICH Guidelines Distribution Storage 5 C through shelf life 25 C to point of failure Accelerated Either 25 C/60% RH or 30 C/65% RH for 6 months -20 C ± 5 C for 1 week and 37 C ± 2 C for 1 week

9 A Validation Master Plan for Your Cold Chain Organizes your Qualification Approach Quality Systems Risk Management Product Stability Qualify/Verify Master Validation Plan Performance Qualification Operational Qualification (containers AND product) Installation/Component Qualification (Product, Primary Container, Insulated Shippers, Secondary Packaging, Devices) Testing Standards (Profiles) Validation Master Planning Thermal Profiles Transport Lanes Active Refrigeration Cold Chain Process Validation Partners

10 Managing Your Partners in Your Cold Chain is Required for Your Success Quality Systems Risk Management Product Stability Qualify/Verify Partners Enforceable Relevant Scrutinized Quality Agreements Key Performance Indicators Audits and Inspections Subcontractors

11 STABILITY STUDIES DESIGNED TO SUPPORT DISTRIBUTION

12 Successful Supply Chain Design Requires a Well Documented Approach to Validating Your Supply Chain Outline your approach in a validation master plan Define how to determine allowable temperatures outside labeled storage conditions with stability data Include the data in your regulatory filing Be prepared to explain your approach and data during an inspection Elements of Validation Master Plan Category Minimum Best in Class Product characterization Packaging qualification Process validation Stability testing to ICH guidelines Vendor s test data Representative transport lanes Dynamic studies to end of shelf testing ISTA Standard 20 data Actual transport lanes

13 Dynamic Stability Studies Show Product Quality and Efficacy During Distribution Complex biologics and their containers are susceptible to hazards other than temperature Additional assessments should be made after exposure to temperature, shock, vibration, pressure, and humidity Issues could range from cosmetic defects to chemical or physical change drug product Hazard Extremes Issue Temperature Shock Vibration Pressure -20 C to 37 C 36 drops or approx. 50Gs Resonant frequency 9.6 psia or 12,000 feet Chemical or physical change Visible particulates Subvisible particulates Container closure integrity Humidity 90% RH Cosmetic and legibility Evaluation Should Continue Through End of Shelf Life

14 Dynamic Stability Studies Require a Testing Methodology The test methods give you confidence that the end result meets all requirements The test methods have be science based with data to support your claim Test profiles replicate known and anticipated environmental conditions in the distribution network Testing profiles allow real world conditions to be tested in the lab

15 Dynamic Stability Studies Should Be Conducted in Parallel to Registration Stability Studies Present data and draw conclusions of risks to exposures outside of labeled storage conditions in marketing application Prepare Stability Budget for exposures during manufacturing and distribution Alternatively, Test Expired Commercial Product to Help Determine Impact at End of Shelf Life

16 PACKAGING QUALIFICATION

17 Your Packaging Qualification Approach is Key to Maintaining Product Quality and Minimizing Risk Outline your approach in a validation master plan Determine how much you will rely on your vendor s test data ISTA standard is best in class At a minimum, you should expect to do performance qualification on your shippers Elements of Validation Master Plan Category Minimum Best in Class Product characterization Packaging qualification Process validation Stability testing to ICH guidelines Vendor s test data Representative transport lanes Dynamic studies to end of shelf testing ISTA Standard 20 data Actual transport lanes

18 Public Standard for Packaging Qualification Process Flow is Published International Safe Transit Association (ISTA) has published Standard 20 for packaging qualification ISTA recommends the use of their hot and cold profile (7E which supersedes 7D) Any profile can be used for Standard 20

19 Testing Profiles Should Simulate Environmental Conditions in Global Logistics Network Testing profiles: Replicate known and anticipated environmental conditions in a global distribution network Are based on established industry standards Enable innovators to test packaging in the laboratory with consistency, reliability, and confidence

20 Physical Qualification Tests Shipper Integrity Drop testing for small parcel shippers ASTM D Standard Test Method for Drop Test of Loaded Containers by Free Fall

21 Physical Qualification Tests Shipper Integrity Slide Impact for pallet shippers ASTM D Standard Test Method for Impact Testing for Shipper Containers and Systems

22 Verification Shipments Demonstrate a Reproducible Process

23 Pack Out Instructions Summarize Qualification Testing in Usable Format Materials required Minimum and maximum load volumes How many qualified hours within a specified temperature range Temperature monitoring requirements and placement Valid modes of transportation

24 REAL WORLD VERSUS SIMULATION TESTING

25 The Global Transportation System is Increasing Complex

26 Risks to Drug Product During Transport are Real Simulation Exercises Allow Rapid Testing of Multiple Formulations Individual Environment Hazards Can Be Isolated or Tested Concurrently Affects on Visible Particulate, Sub-Visible Particulates, and % Main Peak Can Be Identified and Mitigated

27 Develop a Test Sequence to Simulate Extreme Conditions During Transport Temperature with.. Pressure Shock/Drop Humidity

28 Transport Simulation for Dynamic Stability Studies Allow Greater Process Understanding Controlled versus uncontrolled environment Reduce risks of false positives and false negatives in testing Technical Assessments and data can be presented in a pre-approval and biennial inspections Real Transport Failures Cannot Be Assigned a Root Cause

29 DEVELOPING A STABILITY BUDGET

30 Your Stability Budget Has to Cover the Entire Supply Chain Drug product may experience exposures outside of storage conditions during distribution and use Some temperature conditions are unacceptable regardless of time of exposure

31 What is a Stability Budget? Operation Duration (Hrs) Formulation 8 Filling 8 Packaging 48 Shipping Preparation 2 SOP Reference Time out of storage (TOS) controlled and documented in batch record Shipment to DC 72 Quality Agreement with Carrier Finished Goods Receipt 2 Pick/Pack Operations 4 Shipment to 1 st Customer 72 Quality Agreement with Wholesaler End Use Budget 48 Regulatory Filing/ Package Insert Total Exposure Time 264 Total Remaining Time 456 Reserved for Patient Stability budgets are a strategy to assure drug quality throughout the entire supply chain Help determine how long drug can spend outside the labeled storage temperature range Just like the money in your checking account, you can only spend what you have in the bank

32 Patient Use Must Be a Key Consideration Operation Duration (Hrs) Formulation 8 Filling 8 Packaging 48 Shipping Preparation 2 SOP Reference Time out of storage (TOS) controlled and documented in batch record Shipment to DC 72 Quality Agreement with Carrier Finished Goods Receipt 2 Pick/Pack Operations 4 Shipment to 1 st Customer 72 Quality Agreement with Wholesaler End Use Budget 48 Regulatory Filing/ Package Insert Total Exposure Time 264 Delineate acceptable time out of storage conditions by process steps in the supply chain Manufacturing steps are included in batch manufacturing record Quality agreements with carriers and wholesalers are important control Total Remaining Time 456 Reserved for Patient

33 The Correct Stability Program Design to Support Distribution Will Drive Success Real World vs. Simulation Testing Prepare Stability Budget Stability Studies for Distribution Dynamic Stability Studies Show Product Quality and Efficacy During Distribution The Benefits to Simulated Transport Testing Can Be Significant Your Stability Budget Has to Cover the Entire Supply Chain

34 CONTACT INFORMATION Gary Hutchinson President, Modality Solutions