- Email: [email protected]
Vaccine production training to develop the workforce of foreign institutions supported by the BARDA influenza vaccine capacity building program
Vaccine 31 (2013) 1646–1649
Contents lists available at SciVerse ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Vaccine production training to develop the workforce of foreign institutions supported by the BARDA influenza vaccine capacity building program E. Bart Tarbet a,∗ , James T. Dorward b , Craig W. Day a , Kamal A. Rashid c a b c
Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA College of Education and Human Services, Utah State University, Logan, UT, USA Center for Integrated BioSystems, Utah State University, Logan, UT, USA
a r t i c l e
i n f o
Article history: Received 10 March 2012 Received in revised form 14 June 2012 Accepted 14 June 2012 Available online 29 June 2012 Keywords: Vaccine Influenza Production capacity Workforce Training
a b s t r a c t In the event of an influenza pandemic, vaccination will be the best method to limit virus spread. However, lack of vaccine biomanufacturing capacity means there will not be enough vaccine for the world’s population. The U.S. Department of Health and Human Services, Biomedical Advanced Research and Development Authority (BARDA) provides support to the World Health Organization to enhance global vaccine production capacity in developing countries. However, developing a trained workforce in some of those countries is necessary. Biomanufacturing is labor-intensive, requiring unique skills not found in traditional academic programs. Employees must understand the scientific basis of biotechnology, operate specialized equipment, and work in an environment regulated by good manufacturing practices (cGMP). Therefore, BARDA supported development of vaccine biomanufacturing training at Utah State University. The training consisted of a three-week industry-focused course for participants from institutions supported by the BARDA and WHO influenza vaccine production capacity building program. The curriculum was divided into six components: (1) biosafety, (2) cell culture and growth of cells in bioreactors, (3) virus assays and inactivation, (4) scale-up strategies, (5) downstream processing, and (6) egg- and cell-based vaccine production and cGMP. Lectures were combined with laboratory exercises to provide a balance of theory and hands-on training. The initial course included sixteen participants from seven countries including: Egypt, Romania, Russia, Serbia, South Korea, Thailand, and Vietnam. The participant’s job responsibilities included: Production, Quality Control, Quality Assurance, and Research; and their education ranged from bachelors to doctoral level. Internal course evaluations utilized descriptive methods including surveys, observation of laboratory activities, and interviews with participants. Generally, participants had appropriate academic backgrounds, but lacked expertise in vaccine production. All participants acknowledged the utility of the training, and many expressed interest in receiving additional support to implement new practices at their home institutions. © 2012 Elsevier Ltd. All rights reserved.
1. Introduction The global manufacturing capacity for seasonal influenza vaccine is only about 300 million doses per year, and the capacity for pandemic influenza vaccine is much less [1,2]. In the event of an influenza pandemic, vaccination would be the best way to prevent infection and save lives. However, the lack of biomanufacturing and vaccine production capacity means that there will not be enough of the necessary vaccine for the world’s population [3]. The Biomedical Advanced Research and Development Authority (BARDA) in collaboration with the World Health Organization (WHO) have
∗ Corresponding author at: Institute for Antiviral Research, 5600 Old Main Hill, Utah State University, Logan, UT 84322-5600, USA. Tel.: +1 435 797 3954; fax: +1 435 797 3959. E-mail address: [email protected] (E.B. Tarbet). 0264-410X/$ – see front matter © 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2012.06.041
supported the development of influenza vaccine production facilities in developing countries [4]. However, major limitations exist in developing a trained workforce in those countries and institutions supported by the BARDA and WHO. Biomanufacturing is a labor-intensive endeavor requiring unique skills that are not readily found in traditional academic programs [5]. Biomanufacturing employees are not only required to have an understanding of the scientific basis of biotechnology, but they must also learn how to operate specialized equipment and work in an environment that is highly regulated by current good manufacturing practices (cGMP). The vaccine biomanufacturing training course developed by Utah State University (USU) was intended to meet the need for hands-on, competency-based training. The training consisted of an intensive 3-week industry-focused biomanufacturing training course for participants originating from institutions supported by the BARDA and WHO international influenza vaccine production capacity building program. Lectures in the morning covered theory
E.B. Tarbet et al. / Vaccine 31 (2013) 1646–1649
1647
Table 1 Education level of participants in vaccine training course. Foreign institution/location
Education
Job function
Torlak Institute of Virology, Vaccines and Sera – Belgrade, Serbia National Institute of Vaccines and Biological Substances (IVAC) – Nha Trang, Vietnam
M.D./Ph.D. Ph.D. B.S. B.A. B.A. M.S. B.Sc. B.Sc. B.Sc. B.S. B.S. B.S. B.S. B.S. B.Sc. M.S.
Director of QA/QC Director of QA/QC/R&D Technical Engineer, Validation Downstream Processing Freeze-Dry Department Production Manager Production Manager Production Specialist Production Manager Scientist, Virology Department Scientist, Biotechnology Scientist, QA Department Scientist, Biotechnology QA Department Chief, Vaccine Production Scientist, Vaccine Production
Green Cross – Korea The Holding Company for Biological Products & Vaccines (VACSERA) – Egypt
Institute of Experimental Medicine, Russian Academy of Medical Sciences – St. Petersburg, Russia Cantacuzino Institute – Bucharest, Romania
The Government Pharmaceutical Organization – Bangkok, Thailand
and recent developments in virology, immunology, biotechnology, and vaccine biomanufacturing. Laboratory exercises in the afternoon provided extensive hands-on practice for participants. Thus, daily coursework was divided into approximately 50% lecture and 50% hands-on training. This pedagogy, mixing theory and hands-on practice with each aspect of the manufacturing process, has been used for 10 years in the biotechnology and bioprocessing training programs at USU and provides a rich and effective learning environment [6].
biomanufacturing processes, critical assays for quality, and critical steps for documentation of a vaccine product. In addition, quality control tests like end-point titration for quantitation of virus, virus inactivation testing, and vaccine potency assays were completed in the laboratory. The training course also covered regulatory aspects of vaccine manufacturing in a cGMP environment and gave participants practice in writing a standard operating procedure.
2. Training course curriculum
The training course was designed for participants from vaccine manufacturers in developing countries. As such, a culturally and academically diverse group of participants were expected. Two potential barriers to participant success in the training course were insufficient English language skills and lack of formal education in the chemical and biological sciences. The educational levels of course participants are listed in Table 1. During the selection process, we sought to identify candidates who were most likely to have difficulties with the intensive nature of the course. In addition, the lecture component of the curriculum was designed to give the scientific background knowledge necessary to understand the hands-on training. One of our selection criteria was an academic degree in the biological sciences or biochemical engineering. The education of participants ranged from bachelors to doctoral level (Table 1).
The curriculum was designed to provide students with the knowledge and skills to understand modern influenza virus vaccine biomanufacturing, along with training in problem-solving skills. The sequence of the curriculum followed a vaccine production “campaign” [5]. For the purpose of our training curriculum, the production campaign was divided into a number of distinct interrelated phases that were taught sequentially. In this manner the students gained an overall perspective of the manufacturing process and could understand the role and importance of each phase. The curriculum was divided into six components: (1) bio-safety pertaining to viral vaccine production; (2) techniques and scaleup strategies for growth of cells in bioreactors; (3) basic virology including viral assays and viral inactivation; (4) scale-up strategies for production of recombinant proteins in 100 L fermenters; (5) downstream processing of vaccines including final product formulation and filling; and (6) egg- and cell-based vaccine production with emphasis on cGMP. During the course, procedures used in manufacture of both an egg-based and a cell-based influenza virus vaccine were completed to illustrate and practice all aspects of the production process including inoculation, incubation, harvesting, centrifugation, filtration/diafiltration, inactivation, detergent splitting, formulation, and sterile filtration. Participants gained experience in critical
3. Participant selection and target organizations
4. Evaluation methods Evaluation of the training course is ongoing and employs an embedded case study research design [7]. The purpose of this study design is to establish a baseline for expectations of participants and developers, provide project staff with regular feedback on course activities, establish participant understanding and conceptual development, and describe how course activities inform overall project operation. Four questions guided the internal
Table 2 Evaluation questions and associated methods. Evaluation questions
Evaluation methods
How do training objectives influence participant knowledge and skills regarding vaccine manufacturing? What knowledge and skills do participants bring to the training?
Pre-training self-assessment of expertise and experience. Observations and interviews with participants and instructors. Daily observations and interviews with project personnel, observation of post-training debriefing sessions. Weekly group responses and surveys, and daily informal interviews during training. Trend analysis of weekly self-assessments and group responses on understanding. Laboratory observation checklist.
How do participants view objectives of the vaccine manufacturing training course? How is communication implemented within the project team and instructors regarding course improvement?
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E.B. Tarbet et al. / Vaccine 31 (2013) 1646–1649
Table 3 Results of training course pre-survey. Training course objectives
Knowledge (1 = novice, 5 = expert)
Experience (1 = little, 5 = extensive)
Principles and techniques used in egg-based vaccine production. Principles and techniques used in culturing animal cells for virus propagation. Cell line characterization and quality assurance in a cell culture laboratory. Principles and techniques used for scaling up animal cells in bioreactors for vaccine production. Basics of recombinant vaccine production utilizing large scale fermentation vessels. Steps involved in separation and purification of viral vaccines. Regulatory aspects of viral vaccine production in a cGMP environment.
Avg. = 2.1 Avg. = 1.9 Avg. = 1.5 Avg. = 1.4 Avg. = 1.4 Avg. = 1.6 Avg. = 2.3
Avg. = 1.5 Avg. = 1.4 Avg. = 1.4 Avg. = 1.2 Avg. = 1.2 Avg. = 1.2 Avg. = 2.0
evaluation and multiple methods were used to derive answers to those questions (Table 2). The internal evaluators sought limited information from other instructors, project staff, or BARDA team members. Data collection was derived from multiple sources, including: the pre-training survey; three end-of-week content and understanding surveys; multiple observations of lecture and laboratory activities; a set of three formal group interviews; and periodic informal interviews with participants and instructors. Results of the Pre-Survey indicate that participants lacked expertise in cell culture and influenza virus vaccine production (Table 3). Initial findings from the external evaluation suggest that the training course increased the capacity of all home institutions by deepening and expanding the participants’ knowledge base about the techniques and technologies related to egg- and cell-based vaccine production. In addition, informal sharing or formal training of colleagues by the participants has increased the knowledge and understanding of other people at the home institutions. All participants expressed an interest in additional training. 5. Analysis and limitations For the purposes of this report, analysis was limited to descriptive statistics of quantitatively oriented data, and thematic interpretation of qualitative information. Given the limited number of participants from any given demographic group or location, cross-tabulations of quantitative results by sub-categories (gender, ethnicity, country of origin) is not warranted. In order to maintain a reasonable level of interpretation, analyses were limited to initial descriptive analysis of quantitative data, identification of potential themes, and subsequent interpretation of qualitative information based on those themes. 6. Outcome and lessons learned The overall goal to increase influenza virus vaccine production in developing countries was fully supported and endorsed by the leadership team. Initial findings include: 1. The training course curriculum was implemented with very few changes and met expectations of course participants. 2. Participants brought limited expertise and experience with influenza virus vaccine production to the training course. However, sufficient emphasis on fundamental concepts and skills, and coordinated lecture topics with same-day laboratory activities enabled participant understanding. 3. Participant selection in several countries was based, to some degree, on English language proficiency. This suggests that consideration should be given to sending experts to regional training workshops in member countries as an option to bringing participants to the United States. 4. All participants acknowledged the utility of the training course. Many participants expressed an interest in extending the course beyond three weeks, or having additional program support as
they extend efforts to implement new knowledge, skills, and technologies at their home institutions. 7. Conclusions and summary On the basis of internal and external evaluation of the vaccine manufacturing training course at USU, the following conclusions can be made: 1. The training course increased the participants’ knowledge base about the techniques and technologies related to egg- and cell-based vaccine production and is expected to increase the capacity of all their home institutions. 2. The greatest benefit from this training in the future will come from continuing and on-going partnerships with a few institutions. 3. Developing a detailed understanding of the priorities and needs of each participating institution before the training course begins would allow customized training. 4. Efforts should be made to enroll participants with strong English skills, who have the support of their home institutions to implement what they learn, and who have the ability to train others. The immediate impact of the course is evident from the positive responses and the desire for additional training by all participants. However, the long term impact is more difficult to evaluate, especially after only one year. Impact evaluations, such as individual job performance and organizational performance can be completed, but a number of factors and partners outside the training component must also be considered. Vaccine manufacturing facilities in the U.S. and Western Europe are for the most part privately owned commercial enterprises. However, vaccine manufacturers in developing countries are either government owned, or receive major government support. Therefore, government policies and available funding can directly impact the direction and outcome of local vaccine manufacturers. In addition, training in vaccine production at an international level could not be completed without a host of collaborations. Therefore, the credit for an increase in global influenza vaccine production must be shared by the partners which have provided the necessary assistance, including: leadership provided by the WHO and the U.S. Department of Health and Human Services, funding for training provided by BARDA, vision provided by the Developing Countries Vaccine Manufacturers’ (DCVM) Network [8,9], support from the governments of countries in which the vaccine manufacturers operate, and the facilitation from management of the respective vaccine manufacturers. With that said, we can describe one instance in which vaccine production training had a direct impact on future vaccine manufacturing capacity. In December 2011, South Africa and the Republic of Kazakhstan were added to the group of nations supported by the BARDA and WHO training programs. Three employees from the Research Institute for Biological Safety Problems in Kazakhstan participated in our training course. After attending training at USU, the participants negotiated with the leadership of their Institute to alter the
E.B. Tarbet et al. / Vaccine 31 (2013) 1646–1649
building plans for the manufacturing facilities for influenza vaccines in Kazakhstan. Prior to training, they had planned to build a facility that would focus on egg-based influenza vaccine production. After attending our training course, they changed their plans to include two production lines; one devoted to egg-based vaccines and another to include cell-based technologies. Establishing a cell-based manufacturing process in Kazakhstan will provide the platform to develop additional vaccines, or biologics, and ensure the sustainability of the vaccine manufacturing process in that region. We are currently developing a short workshop that can be completed on-site at the various DCVMs. This will allow us to adapt the training to the needs of the various organizations and hopefully see an immediate impact on more personnel, and subsequent influenza vaccine production. Acknowledgements This training course was supported by grant 1IDSEP10000601-00 from the HHS/ASPR/BARDA. Conflict of interest: The authors declare no conflicts of interest.
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References [1] World Health Organization. H5N1 Avian influenza – first steps towards development of a human vaccine. Geneva: World Health Organization; 2005. August 12. Available at: http://www.who.int/csr/disease/avian influenza/statement 2005 08 12/en/print.html. [2] Gronvall GK, Borio LL. Removing barriers to global pandemic influenza vaccination. Biosecurity and bioterrorism: biodefense strategy, practice, and science, vol. 4. Mary Ann Liebert, Inc.; 2006. p. 168–75. [3] Fedson DS. Pandemic influenza and the global vaccine supply. Clin Infect Dis 2003;36:1552–61. [4] Perdue ML, Bright RA. United States of America Department of Health and Human Services Support for advancing influenza vaccine manufacturing in the developing world. Vaccine 2011;29(Suppl. 1):A48–50. [5] McKown RL, Coffman GL. Development of biotechnology curriculum for the biomanufacturing industry. Pharm Eng 2002;2(3):1–6. [6] Rashid K, Weimer B. The Role of Academia in Biotechnology and Bioprocess Workforce Development. Bioprocess Int 2005;3(1):16–22. [7] Yin RK. Case study research, design and methods. 3rd ed. Newbury Park: Sage; 2003. [8] Jadhav S, Datla M, Kreeftenberg H, Hendriks J. The developing countries vaccine manufacturers’ network (DCVMN) is a critical constituency to ensure access to vaccines in developing countries. Vaccine 2008;26:1611–5. [9] Jadhav SS, Gautam M, Gairola S. Emerging markets & emerging needs: developing countries vaccine manufacturers’ perspective and its current status. Biologicals 2009;37:165–8.
Contents lists available at SciVerse ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Vaccine production training to develop the workforce of foreign institutions supported by the BARDA influenza vaccine capacity building program E. Bart Tarbet a,∗ , James T. Dorward b , Craig W. Day a , Kamal A. Rashid c a b c
Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA College of Education and Human Services, Utah State University, Logan, UT, USA Center for Integrated BioSystems, Utah State University, Logan, UT, USA
a r t i c l e
i n f o
Article history: Received 10 March 2012 Received in revised form 14 June 2012 Accepted 14 June 2012 Available online 29 June 2012 Keywords: Vaccine Influenza Production capacity Workforce Training
a b s t r a c t In the event of an influenza pandemic, vaccination will be the best method to limit virus spread. However, lack of vaccine biomanufacturing capacity means there will not be enough vaccine for the world’s population. The U.S. Department of Health and Human Services, Biomedical Advanced Research and Development Authority (BARDA) provides support to the World Health Organization to enhance global vaccine production capacity in developing countries. However, developing a trained workforce in some of those countries is necessary. Biomanufacturing is labor-intensive, requiring unique skills not found in traditional academic programs. Employees must understand the scientific basis of biotechnology, operate specialized equipment, and work in an environment regulated by good manufacturing practices (cGMP). Therefore, BARDA supported development of vaccine biomanufacturing training at Utah State University. The training consisted of a three-week industry-focused course for participants from institutions supported by the BARDA and WHO influenza vaccine production capacity building program. The curriculum was divided into six components: (1) biosafety, (2) cell culture and growth of cells in bioreactors, (3) virus assays and inactivation, (4) scale-up strategies, (5) downstream processing, and (6) egg- and cell-based vaccine production and cGMP. Lectures were combined with laboratory exercises to provide a balance of theory and hands-on training. The initial course included sixteen participants from seven countries including: Egypt, Romania, Russia, Serbia, South Korea, Thailand, and Vietnam. The participant’s job responsibilities included: Production, Quality Control, Quality Assurance, and Research; and their education ranged from bachelors to doctoral level. Internal course evaluations utilized descriptive methods including surveys, observation of laboratory activities, and interviews with participants. Generally, participants had appropriate academic backgrounds, but lacked expertise in vaccine production. All participants acknowledged the utility of the training, and many expressed interest in receiving additional support to implement new practices at their home institutions. © 2012 Elsevier Ltd. All rights reserved.
1. Introduction The global manufacturing capacity for seasonal influenza vaccine is only about 300 million doses per year, and the capacity for pandemic influenza vaccine is much less [1,2]. In the event of an influenza pandemic, vaccination would be the best way to prevent infection and save lives. However, the lack of biomanufacturing and vaccine production capacity means that there will not be enough of the necessary vaccine for the world’s population [3]. The Biomedical Advanced Research and Development Authority (BARDA) in collaboration with the World Health Organization (WHO) have
∗ Corresponding author at: Institute for Antiviral Research, 5600 Old Main Hill, Utah State University, Logan, UT 84322-5600, USA. Tel.: +1 435 797 3954; fax: +1 435 797 3959. E-mail address: [email protected] (E.B. Tarbet). 0264-410X/$ – see front matter © 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2012.06.041
supported the development of influenza vaccine production facilities in developing countries [4]. However, major limitations exist in developing a trained workforce in those countries and institutions supported by the BARDA and WHO. Biomanufacturing is a labor-intensive endeavor requiring unique skills that are not readily found in traditional academic programs [5]. Biomanufacturing employees are not only required to have an understanding of the scientific basis of biotechnology, but they must also learn how to operate specialized equipment and work in an environment that is highly regulated by current good manufacturing practices (cGMP). The vaccine biomanufacturing training course developed by Utah State University (USU) was intended to meet the need for hands-on, competency-based training. The training consisted of an intensive 3-week industry-focused biomanufacturing training course for participants originating from institutions supported by the BARDA and WHO international influenza vaccine production capacity building program. Lectures in the morning covered theory
E.B. Tarbet et al. / Vaccine 31 (2013) 1646–1649
1647
Table 1 Education level of participants in vaccine training course. Foreign institution/location
Education
Job function
Torlak Institute of Virology, Vaccines and Sera – Belgrade, Serbia National Institute of Vaccines and Biological Substances (IVAC) – Nha Trang, Vietnam
M.D./Ph.D. Ph.D. B.S. B.A. B.A. M.S. B.Sc. B.Sc. B.Sc. B.S. B.S. B.S. B.S. B.S. B.Sc. M.S.
Director of QA/QC Director of QA/QC/R&D Technical Engineer, Validation Downstream Processing Freeze-Dry Department Production Manager Production Manager Production Specialist Production Manager Scientist, Virology Department Scientist, Biotechnology Scientist, QA Department Scientist, Biotechnology QA Department Chief, Vaccine Production Scientist, Vaccine Production
Green Cross – Korea The Holding Company for Biological Products & Vaccines (VACSERA) – Egypt
Institute of Experimental Medicine, Russian Academy of Medical Sciences – St. Petersburg, Russia Cantacuzino Institute – Bucharest, Romania
The Government Pharmaceutical Organization – Bangkok, Thailand
and recent developments in virology, immunology, biotechnology, and vaccine biomanufacturing. Laboratory exercises in the afternoon provided extensive hands-on practice for participants. Thus, daily coursework was divided into approximately 50% lecture and 50% hands-on training. This pedagogy, mixing theory and hands-on practice with each aspect of the manufacturing process, has been used for 10 years in the biotechnology and bioprocessing training programs at USU and provides a rich and effective learning environment [6].
biomanufacturing processes, critical assays for quality, and critical steps for documentation of a vaccine product. In addition, quality control tests like end-point titration for quantitation of virus, virus inactivation testing, and vaccine potency assays were completed in the laboratory. The training course also covered regulatory aspects of vaccine manufacturing in a cGMP environment and gave participants practice in writing a standard operating procedure.
2. Training course curriculum
The training course was designed for participants from vaccine manufacturers in developing countries. As such, a culturally and academically diverse group of participants were expected. Two potential barriers to participant success in the training course were insufficient English language skills and lack of formal education in the chemical and biological sciences. The educational levels of course participants are listed in Table 1. During the selection process, we sought to identify candidates who were most likely to have difficulties with the intensive nature of the course. In addition, the lecture component of the curriculum was designed to give the scientific background knowledge necessary to understand the hands-on training. One of our selection criteria was an academic degree in the biological sciences or biochemical engineering. The education of participants ranged from bachelors to doctoral level (Table 1).
The curriculum was designed to provide students with the knowledge and skills to understand modern influenza virus vaccine biomanufacturing, along with training in problem-solving skills. The sequence of the curriculum followed a vaccine production “campaign” [5]. For the purpose of our training curriculum, the production campaign was divided into a number of distinct interrelated phases that were taught sequentially. In this manner the students gained an overall perspective of the manufacturing process and could understand the role and importance of each phase. The curriculum was divided into six components: (1) bio-safety pertaining to viral vaccine production; (2) techniques and scaleup strategies for growth of cells in bioreactors; (3) basic virology including viral assays and viral inactivation; (4) scale-up strategies for production of recombinant proteins in 100 L fermenters; (5) downstream processing of vaccines including final product formulation and filling; and (6) egg- and cell-based vaccine production with emphasis on cGMP. During the course, procedures used in manufacture of both an egg-based and a cell-based influenza virus vaccine were completed to illustrate and practice all aspects of the production process including inoculation, incubation, harvesting, centrifugation, filtration/diafiltration, inactivation, detergent splitting, formulation, and sterile filtration. Participants gained experience in critical
3. Participant selection and target organizations
4. Evaluation methods Evaluation of the training course is ongoing and employs an embedded case study research design [7]. The purpose of this study design is to establish a baseline for expectations of participants and developers, provide project staff with regular feedback on course activities, establish participant understanding and conceptual development, and describe how course activities inform overall project operation. Four questions guided the internal
Table 2 Evaluation questions and associated methods. Evaluation questions
Evaluation methods
How do training objectives influence participant knowledge and skills regarding vaccine manufacturing? What knowledge and skills do participants bring to the training?
Pre-training self-assessment of expertise and experience. Observations and interviews with participants and instructors. Daily observations and interviews with project personnel, observation of post-training debriefing sessions. Weekly group responses and surveys, and daily informal interviews during training. Trend analysis of weekly self-assessments and group responses on understanding. Laboratory observation checklist.
How do participants view objectives of the vaccine manufacturing training course? How is communication implemented within the project team and instructors regarding course improvement?
1648
E.B. Tarbet et al. / Vaccine 31 (2013) 1646–1649
Table 3 Results of training course pre-survey. Training course objectives
Knowledge (1 = novice, 5 = expert)
Experience (1 = little, 5 = extensive)
Principles and techniques used in egg-based vaccine production. Principles and techniques used in culturing animal cells for virus propagation. Cell line characterization and quality assurance in a cell culture laboratory. Principles and techniques used for scaling up animal cells in bioreactors for vaccine production. Basics of recombinant vaccine production utilizing large scale fermentation vessels. Steps involved in separation and purification of viral vaccines. Regulatory aspects of viral vaccine production in a cGMP environment.
Avg. = 2.1 Avg. = 1.9 Avg. = 1.5 Avg. = 1.4 Avg. = 1.4 Avg. = 1.6 Avg. = 2.3
Avg. = 1.5 Avg. = 1.4 Avg. = 1.4 Avg. = 1.2 Avg. = 1.2 Avg. = 1.2 Avg. = 2.0
evaluation and multiple methods were used to derive answers to those questions (Table 2). The internal evaluators sought limited information from other instructors, project staff, or BARDA team members. Data collection was derived from multiple sources, including: the pre-training survey; three end-of-week content and understanding surveys; multiple observations of lecture and laboratory activities; a set of three formal group interviews; and periodic informal interviews with participants and instructors. Results of the Pre-Survey indicate that participants lacked expertise in cell culture and influenza virus vaccine production (Table 3). Initial findings from the external evaluation suggest that the training course increased the capacity of all home institutions by deepening and expanding the participants’ knowledge base about the techniques and technologies related to egg- and cell-based vaccine production. In addition, informal sharing or formal training of colleagues by the participants has increased the knowledge and understanding of other people at the home institutions. All participants expressed an interest in additional training. 5. Analysis and limitations For the purposes of this report, analysis was limited to descriptive statistics of quantitatively oriented data, and thematic interpretation of qualitative information. Given the limited number of participants from any given demographic group or location, cross-tabulations of quantitative results by sub-categories (gender, ethnicity, country of origin) is not warranted. In order to maintain a reasonable level of interpretation, analyses were limited to initial descriptive analysis of quantitative data, identification of potential themes, and subsequent interpretation of qualitative information based on those themes. 6. Outcome and lessons learned The overall goal to increase influenza virus vaccine production in developing countries was fully supported and endorsed by the leadership team. Initial findings include: 1. The training course curriculum was implemented with very few changes and met expectations of course participants. 2. Participants brought limited expertise and experience with influenza virus vaccine production to the training course. However, sufficient emphasis on fundamental concepts and skills, and coordinated lecture topics with same-day laboratory activities enabled participant understanding. 3. Participant selection in several countries was based, to some degree, on English language proficiency. This suggests that consideration should be given to sending experts to regional training workshops in member countries as an option to bringing participants to the United States. 4. All participants acknowledged the utility of the training course. Many participants expressed an interest in extending the course beyond three weeks, or having additional program support as
they extend efforts to implement new knowledge, skills, and technologies at their home institutions. 7. Conclusions and summary On the basis of internal and external evaluation of the vaccine manufacturing training course at USU, the following conclusions can be made: 1. The training course increased the participants’ knowledge base about the techniques and technologies related to egg- and cell-based vaccine production and is expected to increase the capacity of all their home institutions. 2. The greatest benefit from this training in the future will come from continuing and on-going partnerships with a few institutions. 3. Developing a detailed understanding of the priorities and needs of each participating institution before the training course begins would allow customized training. 4. Efforts should be made to enroll participants with strong English skills, who have the support of their home institutions to implement what they learn, and who have the ability to train others. The immediate impact of the course is evident from the positive responses and the desire for additional training by all participants. However, the long term impact is more difficult to evaluate, especially after only one year. Impact evaluations, such as individual job performance and organizational performance can be completed, but a number of factors and partners outside the training component must also be considered. Vaccine manufacturing facilities in the U.S. and Western Europe are for the most part privately owned commercial enterprises. However, vaccine manufacturers in developing countries are either government owned, or receive major government support. Therefore, government policies and available funding can directly impact the direction and outcome of local vaccine manufacturers. In addition, training in vaccine production at an international level could not be completed without a host of collaborations. Therefore, the credit for an increase in global influenza vaccine production must be shared by the partners which have provided the necessary assistance, including: leadership provided by the WHO and the U.S. Department of Health and Human Services, funding for training provided by BARDA, vision provided by the Developing Countries Vaccine Manufacturers’ (DCVM) Network [8,9], support from the governments of countries in which the vaccine manufacturers operate, and the facilitation from management of the respective vaccine manufacturers. With that said, we can describe one instance in which vaccine production training had a direct impact on future vaccine manufacturing capacity. In December 2011, South Africa and the Republic of Kazakhstan were added to the group of nations supported by the BARDA and WHO training programs. Three employees from the Research Institute for Biological Safety Problems in Kazakhstan participated in our training course. After attending training at USU, the participants negotiated with the leadership of their Institute to alter the
E.B. Tarbet et al. / Vaccine 31 (2013) 1646–1649
building plans for the manufacturing facilities for influenza vaccines in Kazakhstan. Prior to training, they had planned to build a facility that would focus on egg-based influenza vaccine production. After attending our training course, they changed their plans to include two production lines; one devoted to egg-based vaccines and another to include cell-based technologies. Establishing a cell-based manufacturing process in Kazakhstan will provide the platform to develop additional vaccines, or biologics, and ensure the sustainability of the vaccine manufacturing process in that region. We are currently developing a short workshop that can be completed on-site at the various DCVMs. This will allow us to adapt the training to the needs of the various organizations and hopefully see an immediate impact on more personnel, and subsequent influenza vaccine production. Acknowledgements This training course was supported by grant 1IDSEP10000601-00 from the HHS/ASPR/BARDA. Conflict of interest: The authors declare no conflicts of interest.
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