An Introduction to Process and Cleaning Validation in the Biologics Industry

Transcription

1 An Introduction to Process and Cleaning Validation in the Biologics Industry Michelle Lombardo, Scientist II MS&T-FLS Presentation for Center for Excellence in Education, Bite of Science-Frederick 02Nov17

2 Who is Michelle Lombardo? 2

3 My Career Path

4 AstraZeneca Global, science-led biopharmaceutical company Develops, manufactures and markets medicines to prevent or treat illness Biologics Manufacturing Center in Frederick Largest biologics manufacturing facility in AstraZeneca Manufacture medicines for the treatment of cancer, respiratory and autoimmune conditions Careers: Manufacturing, Quality Assurance, Quality Control, Science & Technology, Facilities & Engineering, Supply Chain 4 We push the boundaries of science to deliver life-changing medicines

5 Campus Orientation Occupied Sq. ft. Use of Space Building ,200 Manufacturing Science & Technology space includes reserve multi-product bulk manufacturing capacity 4 x 2.5KL bioreactors Building 660 Occupied Sq. ft. 60,000 Use of Space laboratories and administrative functions 5 Building 633 Occupied Sq. ft. 367,100 Use of Space bulk cell culture production suites, laboratories, warehouse, and administrative space 4 x 15K L bioreactors Occupied Sq. ft. Use of Space Building ,000 Distributed Material Ctr. Finished Product Storage (-40 )

6 Two Types of Medicines: Small Molecules and Biologics Small Molecules Low molecular weight (< 900 Da) Synthesized through chemical reactions Example: Aspirin C 9 H 8 O 4 Biologics (Large Molecules) Can be 150 kda Produced by living cells Example: Durvalumab (monoclonal antibody) 6

7 Small Molecule Drug Compared to Biologic 7 Aspirin (acetylsalicylic acid) 180 Daltons Human IgG1 (e.g. palivizumab (Synagis ) ~150,000 Daltons

8 Biologics Process Flow 8

9 Many different roles in pharma and biotech companies are needed to develop drugs Research & Development MS&T Supply Chain Quality Facilities & Engineering Manufacturing & Operations Finance, Human Resources, SHE 9

10 Research & Development MS&T DELIVERS EFFICIENT BIOPROCESSES Manufacturing Sciences & Technology Supports ongoing manufacturing operations and leads cell culture process monitoring, troubleshooting and optimization for products manufactured on site 10

11 MS&T Career Ladder Technical Ladder Managerial Ladder Distinguished Fellow Senior Fellow Fellow Principle Scientist Vice President Senior Director Director Associate Director Senior Scientist Scientist II Scientist I** Senior Manager Manager Associate Scientist II / Associate Engineer II* Associate Scientist I / Associate Engineer I* ** No title distinction between Scientist or Engineer title since both disciplines must be understood at this level and above. Manufacturing Technology Associate II Manufacturing Technology Associate I *Associate Scientist or Engineer title is based on college major

12 Job Scope for MS&T Scientist Project Management Manufacturing Support Industry Knowledge Leadership Plans, designs, and executes multiple simultaneous projects that are complex and technically demanding within a specific area/field. Initiates, implements, plans, directs, and executes investigations to resolve deviations, understand process trends, and/or improve process performance. Typically conducts more than one significant project at a time. Responsible for meeting project goals within time and budget constraints. Responsible for balancing day-to-day technical support for manufacturing and longer term projects and investigations. Develops investigation findings and makes recommendations. Makes detailed observations, analyzes data, and interprets results. Utilizes forward-looking perspective to contribute to go/no go decisions. Effectively presents results at internal meetings and external scientific meetings. Responsible for maintaining technical expertise on an entire section of the manufacturing process (either upstream or downstream). May make recommendations on outside technologies for company to pursue. Works under general supervision of higher-level scientist or manager. May supervise lower-level scientists and associates 12

13 A Day in the Life 13

14 What is Validation? Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stages. In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results. Validation is a requirement of food, drug and pharmaceutical regulating agencies such as the US FDA. Since a wide variety of procedures, processes, and activities need to be validated, the field of validation is divided into a number of subsections. 14 IVT Network

15 What is Cleaning Validation? CIP Supply The process of providing Documented evidence that the cleaning methods employed within a facility consistently controls potential carryover of product, cleaning agents and extraneous material into subsequent product to a level which is below predetermined acceptance criteria. CIP Return PG 15 CIP Return Pump

16 Background of Clean-In-Place (CIP) Up to the 1940s, closed systems were disassembled and cleaned manually Brushes, buckets, hoses Staff entered large vessels to clean the interior. CIP originated as a manual practice in the dairy industry. Basis of CIP technology is largely derived empirically; rules of thumb from early dairy applications. Basic Law of CIP: If you can get it wet, you can get it clean. Dale Seiberling In early 1980 s, CIP entered BioPharm Industry The advent of automated/ semi-automated CIP was a boon to industries that needed frequent internal cleaning of their equipment Pharmaceutical, Food & Beverage, Cosmetics 16

17 Process Flow for Bringing in New Soilants FactoryTalk

18 Fundamental Design of CIP: Cleaning Process Rinse, Clean, Rinse, Verify Initial water rinse (cold) Cleaning agents Final WFI rinse (hot) Swab worst-case locations Dirty Equipment Removal of most of product Removal of any remaining residual Cleaning agents/ residuals Removed Cleanliness verified 18

19 What is Process Validation? 19

20 Process Validation Elements of Evaluation Population Doubling Level 20 GE Healthcare, biomerieux, Grainger

21 What is Continued Process Verification (CPV)? You can t manage what you don t measure W. Edwards Deming Developed by Walter Shewhart (Bell Labs ~1924) 21 W. Edwards Demingbecame the foremost champion and proponent of Shewhart's work.

22 Process Capability 22

23 HOW CAN YOU PREPARE FOR A CAREER IN THIS INDUSTRY? POSSIBLE SUBJECTS TO STUDY IN SCHOOL Sciences Chemistry Physics Biology Communications Economics Engineering Intellectual Property Law Computer Sciences Math & Statistics Technical Writing PRACTICAL EXPERIENCE Internships Job shadowing Presentations Science camps Science clubs Science fairs 23

24 WHAT TRAITS AND SKILLS HELP PEOPLE SUCCEED? Creativity Accept advice Curiosity Be a gracious winner/ loser Honesty Check your work Persistence Follow rules Respect for others Teamwork Learn from mistakes Practice Good Communication 24

25 References MedImmune Annual Report Marketing Research Bureau PALL Pharmaceutical Online VWR IVT Network Acknowledgements Center for Excellence in Education Scott Rosenthal Michelle Michael Edward Wyman 25