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A review of production technologies for influenza virus vaccines, and their suitability for deployment in developing countries for influenza pandemic preparedness
20 December 2006
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
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