Biomanufacturing Training and Education Center (BTEC)’s International Influenza Vaccine Manufacturing Training Program

5th Meeting with International Partners on Prospects for Influenza Vaccine Manufacturing Technology Transfer to Developing Country Vaccine Manufacturers Belgrade, March 27-29, 2012

Dr. Ruben G. Carbonell BTEC Director BTEC’s unique focus • High-quality hands-on experiences • Industry-ready workforce training • Professional development courses • Process development and analytical services Facility highlights • North Carolina State University, Raleigh, NC, USA • 82,500 ft2 (7,665 m2) labs, classrooms and offices • $15 million(USD) in cGMP equipment • 3 scales of operation: bench (2 L), intermediate (30 L) and pilot (300 L) 2 BARDA influenza vaccine manufacturing program offerings – 2012 • Fundamentals of cGMP influenza vaccine manufacturing (2 sessions) – Course taught in 2011 • Advanced upstream processes for influenza vaccine manufacturing (1 session) – New course for 2012! • Advanced downstream processes for influenza vaccine manufacturing (1 session) – New course for 2012!

3 Participants in 2012 program by course (46 places filled, 45 individuals)

Adv. Adv. Country Institution Fundamentals Upstream Downstream Egypt Vacsera 2 1 0 India Serum Institute 2 0 0 Indonesia Biofarma 2 2 1 Kazakhstan RIBSP 3 0 0 Korea Green Cross 1 1 2 Mexico Birmex 2 3 2 Romania Cantacuzino Inst. 1 1 1 Russia IEM 2 0 0 Serbia Torlak Institute 1 0 1 South Africa Biovac Institute 2 1 2 Thailand GPO 2 1 2 Vietnam IVAC 2 2 1 Fundamentals – Course content Modules (Total Hours) Activities and labs (Hours) 1. Introduction (4) Not applicable 2. Regulatory / Quality Systems (12) EMA, FDA, ICH, cGMP Guidelines review (3) 3. Aseptic Practices (8) Contamination mitigation, monitoring, Evaluation of BTEC practices (2) control 4. Facilities and utilities (8) Process flows, HVAC BTEC tour and evaluation (2) 5. Upstream processing (32) Egg- and cell-, single and multi-use CIP/SIP, cell banking, growth kinetics technology (16) 6. Downstream processing (32) Centrifugation, chromatography, UF/DF Monolith vs column chromatography (18) 7. Analytical (24) HCP, DNA, endotoxin, bioburden NA, HA, SRID, SDS-PAGE (14) Course total = 120 hours 5 Advanced Upstream – Course content

Modules (Total Hours) 1. Introduction / influenza virus safety (5) 2. Fundamentals of cell culture (22) Sterility, viability and eukaryotic cell growth 3. Process development and scale-up (25) DoE, range-finding and design space 4. Analytical tools (12) Validation of HA assay 5. Regulatory aspects (6) Cell banks, animal-derived materials, virus seeds, safety and efficacy Course total = 70 hours

6 Advanced Downstream – Course content Modules (Total Hours) 1. Introduction (2) 2. Low-speed centrifugation (7) Ranges for process and performance 3. Ultracentrifugation (7) Density gradient separation optimization and scale-up 4. Analytical methods (16) Host-cell protein/DNA, potency, safety 5. Viral inactivation (8) Review and comparison of industry-standard methods 6. Chromatography (16) Range specification and scale-up 7. Tangential flow filtration (8) Range specification and scale-up 8. Process validation (6) Definitions and challenges 7 Course total = 70 hours Assessment tools used in the program

Tool Purpose Notes Registration Gather participant
Online form connected to system information database Course Measure overall learning
Identical pre-/post-test Assessment during training before & after course Tool (CAT)
Computer-based
2 hours allowed to submit End-of- Measure participants’
30 minutes allowed to module mastery of content complete quizzes End-of- Gather feedback on
20 minutes allowed to course content, instruction & complete evaluation program logistics Follow-up Gauge transfer of
Administered 8 weeks survey learning to the workplace after course ends 8 Instructional strategies • Direct instruction by subject matter experts • Egg- and cell-based production approaches • Regulatory issues focus

• Hands-on laboratory exercises • Use of A/CA/7/09-like (H1N1) or model bacteria phage (source: Novartis) 9 Instructional strategies (continued) • Short seminars from industry experts • Tours of local vaccine manufacturing facilities • Partnership with Novartis to use their suspension-adapted MDCK influenza cell line

© Novartis AG 10 Other vaccine manufacturing offerings available outside of BARDA program • Online training courses – Quality and Regulatory Systems for Vaccine Manufacturing – Fundamentals, Upstream, Downstream Operations • Hybrid training courses – Online lectures + on-site hands-on laboratory activities • Customized courses – Upstream, downstream, analytical, regulatory, facilities Contact us to design special programs to meet specific needs of any DCVM Network participants 11 Quality Management The company’s policy Systems – Policy regarding Quality Documentation Quality Describes the Quality Manual system of an organization

Outlines the minimum Company Standard regulatory & business requirements for Q system

Documents define Global Practice “Who, What, When”

Describe the Standard Operating Procedures “How to” (SOP) 12 Online course: Quality and Regulatory Systems for Vaccine Manufacturing Module Description • Course Introduction and Medical Products • Product Life Cycle 1 • U.S. Food & Drug Administration (FDA) • Other Regulatory Agencies • Quality Systems 2 • Risk Management • Product Design/Process Development • Clinical Trials, CTM Manufacturing • Facilities 3 • Utilities • Outsourcing • Equipment Life Cycle, Commissioning • Facility and Equipment Qualification 4 • Process Validation 13 • Cleaning Validation Online course: Quality and Regulatory Systems for Vaccine Manufacturing (continued)

Module Description • Components • Production Systems, PAT 5 • Documentation • Training • Quality Control, Stability 6 • Failure Investigations • CAPA, Change Control • Batch Release 7 • Auditing and Evaluation • Regulatory Approvals • Board of Health Inspections 8 • Post-Marketing Surveillance

14 For additional information, contact: Dr. Jennifer Ruiz [email protected] 919-515-0215 Dr. Ruben Carbonell [email protected] 919-513-2000

For information about BTEC programs, visit: www.btec.ncsu.edu

15