BTEC’s International

Influenza Vaccine Manufacturing

Training Program –

Challenges and Lessons Learned

Dr. Ruben Carbonell

BTEC Director

November 2011

BTEC’s unique niche • High-quality hands-on education

• Educate and place students in

workforce

• Professional development courses

• Process development and analytical services

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• NC State University’s Centennial Campus

• 82,500 ft2 (7,665 m2) labs, classrooms,

offices

• $15 million (USD) in cGMP equipment

• 3 scales of operation:

bench (2 L), intermediate (30 L), and pilot (300 L)

Facility highlights

Country Institution #

Egypt Vacsera 3

India Serum Institute

of India

2

Indonesia Biofarma 4

Korea Green Cross 1

Mexico Birmex 3

Romania Cantacuzino

Institute

4

Russia IEM 3

Serbia Torlak Institute 3

Thailand GPO

Thai FDA

5

2

Vietnam IVAC 5

Fundamentals of cGMP Influenza Vaccine Manufacturing (BARDA)

Countries/institutions participating in 2011

Tools created for 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 pretest/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 ended

• 13 questions

Instructional strategies

• Direct instruction by

subject matter experts

• Presentation of both

egg- and cell-based

production approaches

• Hands-on laboratory

exercises (43 hours total)

• 3 weeks, 5 days/week,

8 hours/day (120 hours)

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Instructional strategies (continued)

• Short seminars

– Use of disposable equipment by Sartorius Stedim

– Novartis’s response to 2009 pandemic

• Tours of local vaccine manufacturing facilities

(Novartis and Pfizer, 8 hours total)

6 © Novartis AG

Generalized influenza vaccine process

Upstream

processing

Downstream

processing

Formulation

Fill / Finish

Final

characterization

Release

Eggs

Cells

LAIV

Whole virus

Subunit

Split

Centrifugation

Chromatography

UF / DF

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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-use

technology

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 8

Challenges and keys to success

Challenges Solutions

Conducting a

large project within

limited time frame

Use a project

management approach

Training a

heterogeneous

group

• Present fundamental

principles and

practices

• Provide opportunities

for hands-on training

• Encourage peer

learning

• React quickly to

feedback

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Challenges and keys to success

Challenges Solutions

Recruiting and

ensuring logistical

support for a

heterogeneous

group

Partner with NC State’s

Global Training Initiative

(GTI)

Provide an

industry-relevant

course with

significant

hands-on training

in a safe manner

• Create a team of

subject matter

experts

• Develop a

generalized process

for influenza vaccine

production

• Utilize cell- and egg-

based technologies

Lessons learned • Language barriers

– Use clear, simple language in instruction, quizzes

– Maximize hands-on activities; limit lecture

• Heterogeneous group

– Assess participants’ competencies prior to their arrival

– Implement pre-arrival survey

– Adjust instruction accordingly

• Safety concerns

– Use models instead of actual influenza virus in

some modules

• Live viruses should be used in next round

– Novartis cell line

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The 2012 program • Emphasize process

development, scale up and

validation

• Create 2 new courses

– Advanced Upstream

Processes for Influenza

Vaccine Manufacturing

– Advanced Downstream

Processes for Influenza

Vaccine Manufacturing

– June 2012: back-to-back

course offerings

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• Develop an in-house, cell-based,

industrially representative,

influenza vaccine production process

• Continue

offering the

Fundamentals

of cGMP

Influenza

Vaccine

Manufacturing

course

• Extend the project by

investigating institutions’

training needs

– March workshop at BTEC

– Visits to some facilities

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