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 ManufacturersBelgrade, March 27-29, 2012

Dr. Ruben G. Carbonell BTEC Director

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BTEC’s unique focus• High-quality hands-on experiences

• Industry-ready workforce training

• Professional development courses

• Process development and analytical services

• 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)

Facility highlights

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!

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Country Institution Fundamentals Adv.

Upstream

Adv.

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

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

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,control

Evaluation of BTEC practices (2)

4. Facilities and utilities (8)

Process flows, HVAC BTEC tour and evaluation (2)

5. Upstream processing (32)

Egg- and cell-, single and multi-usetechnology

CIP/SIP, cell banking, growth kinetics (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, virusseeds, safety and efficacy

Course total = 70 hours

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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

Course total = 70 hours7

Assessment tools used in the program

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Tool Purpose Notes

Registration system

Gather participant information

� Online form connected to database

Course Assessment Tool (CAT)

Measure overall learning during training

� Identical pre-/post-test before & after course

� Computer-based� 2 hours allowed to submit

End-of-module quizzes

Measure participants’ mastery of content

� 30 minutes allowed to complete

End-of-course evaluation

Gather feedback on content, instruction & program logistics

� 20 minutes allowed to complete

Follow-up survey

Gauge transfer of learning to the workplace

� Administered 8 weeks after course ends

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

10© Novartis AG

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

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Policy

QualityManual

Company Standard

Global Practice

Standard Operating Procedures

(SOP)

Quality

Management

Systems –

Documentation

The company’s policy regarding Quality

Describes the Quality system of an organization

Documents define “Who, What, When”

Describe the “How to”

Outlines the minimum regulatory & businessrequirements for Q system

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Online course: Quality and Regulatory Systems

for Vaccine Manufacturing

Module Description

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• Course Introduction and Medical Products• Product Life Cycle• U.S. Food & Drug Administration (FDA)• Other Regulatory Agencies

2 • Quality Systems• Risk Management• Product Design/Process Development

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• Clinical Trials, CTM Manufacturing• Facilities• Utilities• Outsourcing• Equipment Life Cycle, Commissioning

4• Facility and Equipment Qualification• Process Validation• Cleaning Validation

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Online course: Quality and Regulatory Systems

for Vaccine Manufacturing (continued)

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Module Description

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• Components• Production Systems, PAT• Documentation• Training

6• Quality Control, Stability• Failure Investigations• CAPA, Change Control

7• Batch Release• Auditing and Evaluation• Regulatory Approvals

8• Board of Health Inspections• Post-Marketing Surveillance

For additional information, contact:

Dr. Jennifer Ruizjennifer_ruiz@ncsu.edu

919-515-0215

Dr. Ruben Carbonellruben@ncsu.edu

919-513-2000

www.btec.ncsu.edu

For information about BTEC programs, visit:

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