Sally Furniss
Well-known member
A review of production technologies for influenza virus vaccines, and their suitability for deployment in developing countries for influenza pandemic preparedness
20 December 2006
http://www.who.int/vaccine_research/diseases/influenza/Flu_vacc_manuf_tech_report.pdf
Contents
1 Acronyms and abbreviations....................................................................................5
2 Preamble......................................................................................................................6
3 Influenza vaccines: background...............................................................................7
3.1 Seasonal influenza vaccine..........................................................................................7
3.1.1 Annual cycle of influenza vaccine production...............................................................7
3.1.2 Inactivated influenza vaccines; composition.................................................................8
3.1.3 Live attenuated influenza vaccines...............................................................................8
3.1.4 Novel influenza vaccines..............................................................................................9
3.2 Pandemic influenza vaccine.........................................................................................9
3.2.1 Vaccine production capacity.........................................................................................9
4 Review of influenza vaccine production technologies.........................................11
4.1 Scale..........................................................................................................................11
4.1.1 Laboratory and pilot-scale manufacture.....................................................................12
4.1.2 Industrial-scale manufacture......................................................................................12
4.2 Assumptions...............................................................................................................12
5 Inactivated influenza vaccines (IIV); egg-based manufacture.............................12
5.1 Introduction.................................................................................................................12
5.2 Laboratory scale.........................................................................................................12
5.2.1 Manufacturing process...............................................................................................12
5.2.2 Resource required......................................................................................................13
5.3 Industrial scale............................................................................................................14
5.3.1 Manufacturing process...............................................................................................14
5.3.2 Resource required......................................................................................................14
5.4 Inactivated influenza vaccine production in eggs: summary......................................15
5.4.1 General considerations...............................................................................................15
5.4.2 Advantages of egg-based IIV production....................................................................15
5.4.3 Disadvantages of egg-based IIV production...............................................................15
5.4.4 Outstanding questions and issues..............................................................................16
6 Inactivated influenza vaccines: cell-culture-based manufacture........................16
6.1 Introduction.................................................................................................................16
6.1.1 Cell lines.....................................................................................................................17
6.2 Laboratory-scale.........................................................................................................17
6.2.1 Manufacturing process...............................................................................................17
6.2.2 Resource required......................................................................................................18
6.3 Industrial scale............................................................................................................18
6.3.1 Manufacturing process...............................................................................................18
6.3.2 Resource required......................................................................................................18
6.4 Inactivated influenza vaccine production in cell culture: summary.............................18
6.4.1 General considerations...............................................................................................18
6.4.2 Advantages of cell-culture-based IIV manufacture.....................................................19
6.4.3 Disadvantages of cell-culture-based IIV manufacture................................................19
6.4.4 Outstanding issues and questions..............................................................................19
7 Live attenuated influenza vaccines; egg-based manufacture.............................20
7.1 Introduction.................................................................................................................20
7.2 Laboratory scale.........................................................................................................20
7.2.1 Manufacturing process...............................................................................................20
7.2.2 Resource required......................................................................................................20
7.3 Industrial scale............................................................................................................20
7.3.1 Manufacturing process...............................................................................................20
7.3.2 Resource required......................................................................................................20
7.4 LAIV production in eggs: summary.............................................................................21
7.4.1 General considerations...............................................................................................21
7.4.2 Advantages................................................................................................................21
7.4.3 Disadvantages............................................................................................................21
7.4.4 Outstanding issues/questions.....................................................................................22 Page 3 of 34
Influenza vaccine production technologies 20 December 2006
8 Live-attenuated influenza vaccines: cell-culture-based manufacture................23
8.1 Introduction.................................................................................................................23
8.2 LAIV production in cell-culture: summary...................................................................23
9 Production of influenza vaccines in chicken-embryo fibroblasts.......................24
9.1 Introduction.................................................................................................................24
9.2 Laboratory scale.........................................................................................................24
9.2.1 Manufacturing process and resource required...........................................................24
9.3 Industrial scale............................................................................................................24
9.3.1 Manufacturing process...............................................................................................24
9.3.2 Resource required......................................................................................................24
9.4 LAIV production in CEFs; summary...........................................................................24
9.4.1 General considerations...............................................................................................24
9.4.2 Advantages................................................................................................................25
9.4.3 Disadvantages............................................................................................................25
9.4.4 Outstanding issues and questions..............................................................................25
10 Conclusions..............................................................................................................25
10.1 Egg-based manufacture of IIV...............................................................................27
10.2 Cell-culture-based manufacture of IIV....................................................................27
10.3 Egg-based manufacture of LAIV............................................................................27
10.4 Action points and next steps..................................................................................28
11 References.................................................................................................................29
20 December 2006
http://www.who.int/vaccine_research/diseases/influenza/Flu_vacc_manuf_tech_report.pdf
Contents
1 Acronyms and abbreviations....................................................................................5
2 Preamble......................................................................................................................6
3 Influenza vaccines: background...............................................................................7
3.1 Seasonal influenza vaccine..........................................................................................7
3.1.1 Annual cycle of influenza vaccine production...............................................................7
3.1.2 Inactivated influenza vaccines; composition.................................................................8
3.1.3 Live attenuated influenza vaccines...............................................................................8
3.1.4 Novel influenza vaccines..............................................................................................9
3.2 Pandemic influenza vaccine.........................................................................................9
3.2.1 Vaccine production capacity.........................................................................................9
4 Review of influenza vaccine production technologies.........................................11
4.1 Scale..........................................................................................................................11
4.1.1 Laboratory and pilot-scale manufacture.....................................................................12
4.1.2 Industrial-scale manufacture......................................................................................12
4.2 Assumptions...............................................................................................................12
5 Inactivated influenza vaccines (IIV); egg-based manufacture.............................12
5.1 Introduction.................................................................................................................12
5.2 Laboratory scale.........................................................................................................12
5.2.1 Manufacturing process...............................................................................................12
5.2.2 Resource required......................................................................................................13
5.3 Industrial scale............................................................................................................14
5.3.1 Manufacturing process...............................................................................................14
5.3.2 Resource required......................................................................................................14
5.4 Inactivated influenza vaccine production in eggs: summary......................................15
5.4.1 General considerations...............................................................................................15
5.4.2 Advantages of egg-based IIV production....................................................................15
5.4.3 Disadvantages of egg-based IIV production...............................................................15
5.4.4 Outstanding questions and issues..............................................................................16
6 Inactivated influenza vaccines: cell-culture-based manufacture........................16
6.1 Introduction.................................................................................................................16
6.1.1 Cell lines.....................................................................................................................17
6.2 Laboratory-scale.........................................................................................................17
6.2.1 Manufacturing process...............................................................................................17
6.2.2 Resource required......................................................................................................18
6.3 Industrial scale............................................................................................................18
6.3.1 Manufacturing process...............................................................................................18
6.3.2 Resource required......................................................................................................18
6.4 Inactivated influenza vaccine production in cell culture: summary.............................18
6.4.1 General considerations...............................................................................................18
6.4.2 Advantages of cell-culture-based IIV manufacture.....................................................19
6.4.3 Disadvantages of cell-culture-based IIV manufacture................................................19
6.4.4 Outstanding issues and questions..............................................................................19
7 Live attenuated influenza vaccines; egg-based manufacture.............................20
7.1 Introduction.................................................................................................................20
7.2 Laboratory scale.........................................................................................................20
7.2.1 Manufacturing process...............................................................................................20
7.2.2 Resource required......................................................................................................20
7.3 Industrial scale............................................................................................................20
7.3.1 Manufacturing process...............................................................................................20
7.3.2 Resource required......................................................................................................20
7.4 LAIV production in eggs: summary.............................................................................21
7.4.1 General considerations...............................................................................................21
7.4.2 Advantages................................................................................................................21
7.4.3 Disadvantages............................................................................................................21
7.4.4 Outstanding issues/questions.....................................................................................22 Page 3 of 34
Influenza vaccine production technologies 20 December 2006
8 Live-attenuated influenza vaccines: cell-culture-based manufacture................23
8.1 Introduction.................................................................................................................23
8.2 LAIV production in cell-culture: summary...................................................................23
9 Production of influenza vaccines in chicken-embryo fibroblasts.......................24
9.1 Introduction.................................................................................................................24
9.2 Laboratory scale.........................................................................................................24
9.2.1 Manufacturing process and resource required...........................................................24
9.3 Industrial scale............................................................................................................24
9.3.1 Manufacturing process...............................................................................................24
9.3.2 Resource required......................................................................................................24
9.4 LAIV production in CEFs; summary...........................................................................24
9.4.1 General considerations...............................................................................................24
9.4.2 Advantages................................................................................................................25
9.4.3 Disadvantages............................................................................................................25
9.4.4 Outstanding issues and questions..............................................................................25
10 Conclusions..............................................................................................................25
10.1 Egg-based manufacture of IIV...............................................................................27
10.2 Cell-culture-based manufacture of IIV....................................................................27
10.3 Egg-based manufacture of LAIV............................................................................27
10.4 Action points and next steps..................................................................................28
11 References.................................................................................................................29