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4
Vaccine Demand and Supply
The state of vaccine demand, supply, and innovation on the global level is quite different from that in the United States. Consequently, this chapter examines these trends on a global basis and then explores the domestic conditions of vaccine supply and demand.
GLOBAL DEMAND AND SUPPLY
Demand
The potential size of the worldwide pediatric vaccine market is determined by two factors: the annual worldwide birth cohort (approximately 143 million live births per year) (World Bank, 1993) and the number of vaccines a child receives through adolescence. Eight of the vaccines recommended by the World Health Organization's (WHO's) Expanded Program on Immunization (EPI) should be administered during or shortly after the first year of life (see Appendix G for immunization schedule). According to one estimate, almost 1.5 billion doses of vaccine were used around the world in 1990 (Baudrihaye, 1992) (Table 4-1). Of this amount, North America, Europe, and Japan used just 14 percent of the total, while purchases by the United Nations Children's Fund (UNICEF), the Pan American Health Organization (PAHO), and WHO accounted for approximately 63 percent of the total vaccine used (Baudrihaye, 1992).
Although the number of potential vaccinees in developing countries is
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TABLE 4-1 Estimated Worldwide Usage of Vaccines, 1990 (in millions of doses)
Vaccine
North America Europe, and Japan
UNICEF PAHO, and WHO
Other
Total
BCG
5
160
20
185
DTP
40
219
50
260
Hepatitis B
15
35
50
Influenza
75
10
85
Measles and combined
15
131
30
165
Meningococcal
10
20
30
60
Polio (OPV, IPV)
60
450
190
700
Rabies
1
3
4
8
Total
211
983
358
1,552
Percentage of total
14
63
23
100
SOURCE: Adapted from N. Baudrihaye, European Federation of Pharmaceutical Industries Association, Brussels, 1992; with additional information provided by Akira Homma, PAHO, 1993; John Gilmartin, UNICEF, 1993; Terrel Hill, UNICEF, 1993.
much larger than that in the industrialized world (almost 80 percent of the 143 million live births occur in the developing world), the amount spent on vaccines in the industrialized world greatly exceeds that spent by UNICEF, PAHO, and WHO. The total worldwide value of human vaccines sold in 1992 has been estimated to be as high as $3 billion (Technology Management Group, 1993), of which only $65 million represented UNICEF purchases (John Gilmartin, UNICEF, personal communication, 1993).
Regional Demand
Assessments of country-level demand for vaccines must take into account the size of the target population, estimated extent of immunization coverage, anticipated vaccine wastage, number of scheduled doses, and any special immunization campaigns or strategies that would lead to a surge in demand. Determination of demand for vaccines is more problematic when special, intensive immunization strategies are considered (World Health Organization/Children's Vaccine Initiative, 1992c). For example, the ongoing global campaign to eradicate polio in the Americas has led to increased demand for and, at brief intervals, temporary shortages of polio vaccine (Pan American Health Organization, 1992). In 1992, UNICEF
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purchased 351 million doses of oral polio vaccine (OPV), which cost $25.6 million including air freight delivery (John Gilmartin, UNICEF, personal communication, 1993; World Health Organization/Children's Vaccine Initiative, 1992b). It is estimated that to duplicate polio eradication efforts elsewhere in the world, the annual purchase of OPV must increase to $87 million (Agency for Cooperation in International Health, 1992).
Vaccine wastage has been identified as another major problem, not only in terms of cost but also in terms of forecasting the demand for vaccine (World Health Organization/Children's Vaccine Initiative, 1992c). Between 1982 and 1992 the demand for EPI vaccines rose 10-fold (Agency for Cooperation in International Health, 1992; UNICEF, 1991b). This kind of growth in demand has forced UNICEF to try to predict the number of doses needed, so that manufacturers will have enough time to increase their production. This has not been an easy task, primarily because the month-to-month variation in demand for a vaccine can vary as much as sevenfold (World Health Organization/Children's Vaccine Initiative, 1992c). Up until 1990, UNICEF's annual forecast of worldwide vaccine demand was fairly accurate. However, in both 1991 and 1992, countries requested substantially less vaccine from UNICEF than estimated (Terrel Hill, UNICEF, personal communication, 1993). The precise reasons for the decreased country demand for UNICEF-supplied vaccine are not fully understood at this time. It is likely, however, that increased local production of vaccines in some countries has led to decreased country-level demand. In addition, improved national census data in many countries may have resulted in a more realistic assessment of vaccine need. Of great concern, however, is that the decreased demand for vaccine may be a result of a slippage in immunization coverage in many countries (Terrel Hill, UNICEF, personal communication, 1993).
Supply
Vaccines are manufactured by both industrialized and developing countries around the world. It is estimated that almost 60 percent of the diphtheria and tetanus toxoids and pertussis vaccine (DTP) currently being used in the world is actually produced in the country that uses it (World Health Organization/Children's Vaccine Initiative, 1992a). The annual production of 500 million doses of EPI vaccines by the People's Republic of China is equivalent to roughly half of all vaccines purchased by UNICEF each year (Agency for Cooperation in International Health, 1992). Currently, OPV is produced or bulk finished in over 25 nations (of which half are considered to be developing countries). (The quality control requirements for the production of OPV differ from those for the finishing
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of OPV bulk vaccine. For countries to mount full production of OPV, they must maintain expensive monkey colonies, which are needed for neurovirulence testing and must have considerable staff expertise and training. In contrast, finishing a vaccine that has already been fully tested may reduce the need for such large investments in quality control.) Tetanus toxoid is made in almost 40 countries, DTP is manufactured in approximately 30 countries, and measles and BCG (bacillus Calmette-Guérin) vaccines are produced in approximately 20 countries (Agency for Cooperation in International Health, 1992).
The vaccine supply grid developed by Amie Batson and Peter Evans of the World Health Organization (Figure 4-1) depicts the 130 countries that currently produce vaccines according to per capita gross national product and population size. A number of donor agencies are using the grid to evaluate strategies for helping countries buy vaccines, share vaccine production capabilities, or establish production facilities.
Population expansion, more comprehensive immunization, and greatly increased demands for polio vaccine because of global eradication goals have raised questions about the stability of the global vaccine supply (World Health Organization/Children's Vaccine Initiative, 1992a). According to UNICEF, the demand for OPV peaked in 1990 and declined slightly in 1991 and 1992 (Terrel Hill, UNICEF, personal communication, 1993). The largest single user country, India, is expected to become self-sufficient in OPV production in 1993, thereby reducing demand from UNICEF by at least 50 million doses per year (John Gilmartin, UNICEF, personal communication, 1993). UNICEF's ability to procure adequate levels of vaccine into the future is a concern, given rising vaccine prices and competing priorities for increasingly limited resources (UNICEF, 1991a, 1992a); in addition, some donors, such as the Rotary Foundation, have decreased the amount included in their pledges. Preliminary projections of vaccine requirements through 1995 suggest that there may be significant shortfalls in vaccine supply if UNICEF is unable to secure the procurement of EPI vaccines at very low prices into the future. There is also concern that there are now insufficient funds to buy additional EPI vaccines required for such activities as measles control and neonatal tetanus eradication (Agency for Cooperation in International Health, 1991).
At the 1991 International Meeting on Global Vaccine Supply in Kumamoto, Japan, several issues that may affect the future viability of EPI were discussed. Among them were the need to strengthen monetary, logistical, and supply mechanisms for integrating new vaccines into EPI and the need to improve substandard manufacturing capabilities in some countries (Agency for Cooperation in International Health, 1991).
There is mounting concern about the quality of many of the locally produced vaccines used in EPI programs (Hlady et al., 1992; World Health
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FIGURE 4-1
Vaccine supply grid of countries that produce vaccines according to per capita gross national product (GNP) and population size. SOURCE: Amie Batson and Peter Evans, World Health Organization, 1993.
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Organization, 1992). It has been estimated that more than half of the vaccines produced around the world do not meet accepted WHO standards of quality (Lancet, 1992). Many countries lack functioning national control authorities, and as a result, quality control of locally produced vaccines is emerging as a top-priority concern of EPI and the Children's Vaccine Initiative (CVI).
Procurement
UNICEF is the largest single purchaser of vaccine (in doses) for the developing world. The number of doses of EPI vaccines supplied by UNICEF more than doubled in 5 years (Table 4-2). In 1985, UNICEF bought roughly 366 million doses at a cost of approximately $18 million; by 1992, this had increased to 850 million doses at a total cost of some $65 million, including air freight delivery (UNICEF, 1991a, 1992a,b). Polio vaccine and DTP account for the largest number of doses in the UNICEF procurement; this is followed by tetanus toxoid (TT), and BCG and measles vaccine (Table 4-2).
Every 2 years, UNICEF issues a tender for the purchase of vaccines. UNICEF purchases EPI vaccines from all companies that are prequalified to supply vaccine and that submit bids. Companies whose bids are higher than the winning bid are often asked to resubmit an offer. In theory, the lowest bidder receives two-thirds of the UNICEF market, with each successively higher bidder receiving one-third of the remaining market (Peter Evans, Expanded Program on Immunization, World Health Organization, personal communication, 1993). In general, the lowest bidder is unable to
TABLE 4–2 Vaccines Procured by UNICEF, 1985 and 1990
Vaccine
No. of Doses in 1985 (in thousands)
Percent of Total
No. of Doses in 1990 (in thousands)
Percent
BCG
66,296 (4)a
18.11
132,004 (5)
13.65
DTP
89,485 (4)
24.45
183,881 (4)
19.01
DT
20,153 (5)
5.51
13,144 (5)
1.36
Measles
36,215 (5)
9.90
86,313 (7)
8.92
OPV
116,772 (5)
1.90
388,510 (6)
40.17
TT
37,049 (4)
10.12
163,400 (6)
16.89
Totals
365,970 (9)
967,254 (11)
a Values in parentheses are number of suppliers.
SOURCE: Data supplied by UNICEF, 1993.
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provide UNICEF with two-thirds of the total doses required for any vaccine; therefore, several suppliers provide each vaccine, with preference given to the lowest bidders.
UNICEF has used competitive vaccine bids for many years. From 1985 through 1990, the number of suppliers grew from 9 to 11 (Table 4-2). European vaccine manufacturers supply 90 percent of the vaccines used by UNICEF (this includes Connaught Laboratories, Ltd., [Canada], a subsidiary of Pasteur-Mérieux Sérums et Vaccins) (John Gilmartin, UNICEF, personal communication, 1993). Currently, U.S. vaccine manufacturers are invited to participate in the bidding, but have not made offers since at least 1982. That year, a U.S. vaccine manufacturer was criticized in congressional hearings for selling vaccine to PAHO at prices substantially below those quoted to the U.S. government (U.S. Congress, Senate, 1982). This continues to be a sensitive issue in the United States.
To supply vaccine to UNICEF, a company must request and pay for a WHO-organized evaluation of its manufacturing facilities and the country's national biologics control authority. Several lots of the company's vaccine are then tested at one or more of the WHO's collaborating centers, a process also paid for by the company. Only when the vaccine is determined to meet WHO standards, when the facility is approved, and when the national control authority is determined to be reliable is the company licensed to supply UNICEF with vaccines. UNICEF and WHO do not have the capability to monitor the consistency of vaccine lots produced by manufacturers as is currently done in the United States by the U.S. Food and Drug Administration (see Appendix C).
No manufacturers based in developing countries supplied UNICEF with vaccines in 1990 (Table 4-3). Compared with their international competitors, most vaccine manufacturers in developing countries have several disadvantages. They must frequently import raw materials, often paying substantial import duties on these materials. And because vaccine manufacturing is more capital intensive than labor intensive, the low-cost labor pool in developing countries does not offer any advantages. In fact, some have charged that locally produced vaccines are often more expensive than those procured through UNICEF and PAHO (Baudrihaye, 1992; Vandersmissen, 1992).
Through its procurement system, UNICEF has actively sought to expand the base of suppliers both to ensure a stable vaccine supply and to keep the prices charged for EPI vaccines comparatively low (U.S. Congress, Senate, 1982). (In this regard, UNICEF might be reluctant to purchase a ''super" vaccine, such as might result from the CVI, from a single supplier.) UNICEF vaccine prices are a fraction of those commanded elsewhere in the world, including the United States (Table 4-4). Until quite recently, yearly EPI vaccine price increases have barely exceeded inflation. However, in
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TABLE 4–3 Companies That Supplied EPI Vaccines to UNICEF, 1990
Company
BCG
DTP
TT
Measles
Polio
Connaught Laboratories, Ltd. (Canada)
X
X
X
X
X
Con Pharma (Canada)
X
X
Eisai (Japan)
X
Evans-Medical, Ltd. (United Kingdom)
X
X
Behringwerke (Hoechst) (Germany)
X
X
X
Pasteur Mérieux Sérums et Vaccins (France)
X
X
X
X
X
Inter-Export (Yugoslavia)
X
X
Japan BCG (Japan)
X
Sclavo (Italy)
X
X
SmithKline Beecham (United Kingdom)
X
X
Swiss Serum Vaccine Institute (Switzerland)
X
X
SOURCE: Data supplied by UNICEF, January 1993.
TABLE 4–4 UNICEF prices for EPI Vaccine, 1992
Vaccine
No. of Doses
Cost($)/Dose
Cost($)/Series
BCG
1
0.065
0.065
DTP
3
0.0575–0.075
0.173–0.225
Measles
1
0.16
0.16
TT
3–5
0.0325–0.05
0.0975–0.25
OPV
3
0.07–0.085
0.210–0.255
Total
11–13
0.705–0.955
SOURCE: UNICEF Price List, 1992.
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1992, vaccine prices increased 23 percent above the 1990 tender price (Steele, 1992). Vaccine manufacturers have indicated that the low prices quoted to UNICEF for EPI vaccines cannot continue indefinitely because the costs of manufacturing vaccines, research and development, and capital investments are all increasing (Meérieux, 1992; Vandersmissen, 1992).
Although some 90 percent of the vaccine purchased by UNICEF and PAHO are made by several of the largest manufacturers, these purchases amount to less than 10 percent of these company's vaccine revenues (Agency for Cooperation in International Health). Indeed, some companies that supply vaccines to UNICEF do so to utilize their excess capacity, and the prices that they charge generally cover the marginal cost of production (Dupuy and Freidel, 1990; Robbins and Freeman, 1988). Because these vaccine purchases have a minimal impact on the total vaccine revenues of those companies that sell vaccine to UNICEF and PAHO, some have suggested that dependence on these international vaccine suppliers puts the global vaccine supply in a precarious position (Agency for Cooperation in International Health, 1992; Institute of Medicine, 1986). Even though a major UNICEF supplier's exit from the vaccine business might have a minor impact on the firm's bottom line, there is concern that it might have a significant negative impact on the supply of high-quality vaccines to the developing world.
Innovation
There are a number of childhood diseases, including malaria and acute respiratory infections, that claim millions of lives annually and for which effective vaccines are not yet available. Unfortunately, the research and development of new and improved vaccines for exclusively developing-country markets by commercial manufacturers is limited. Most public-sector vaccine institutes in Europe do not have the resources or the mandates required to conduct new vaccine development for developing-country markets. The low prices quoted to UNICEF/PAHO cover the marginal costs of production, but they do not appear to provide sufficient market incentives for international vaccine companies to invest in vaccine research and development.
Furthermore, despite a number of successful programs such as the WHO/UNDP Program for Vaccine Development and the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases, there is no significant international or multinational fund dedicated to the early stages of vaccine development and testing of vaccine for use in the developing world.
New and improved vaccines that are developed and manufactured for
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industrialized-country markets do "trickle down" eventually (sometimes after many years) to some developing countries. In some cases, vaccines developed by and for the DOD have been introduced into some developing countries on an ad hoc basis by commercial manufacturers. However, the target groups for these vaccines tend to be adults, not infants and children. This is because the DOD's primary responsibility is to protect young-adult soldiers—not infants and children. Commercial manufacturers have been reluctant to invest in the costly clinical trials required to demonstrate further vaccine efficacy in infants and young children probably because the returns are likely to be small compared with those from other investment opportunities. The prices of new vaccines have been beyond the means of most developing countries and such international buyers as UNICEF and PAHO. As a consequence, no new vaccines have been added to the UNICEF procurement scheme since its inception, despite recommendations that hepatitis B vaccine be included in national immunization programs.
DEMAND AND SUPPLY IN THE UNITED STATES
Demand
The pediatric vaccine market in the United States is predictable, limited, and stable. The size of the market is constrained by two factors: the annual birth cohort—approximately 4 million live births per year (World Almanac and Book of Facts, 1992) and the number of vaccines a child receives through adolescence. Thirteen of the eighteen separate vaccinations recommended by the Advisory Committee on Immunization Practices should be administered during or shortly after the first year of life (see Appendix G for immunization schedule). Three of the remaining four vaccines should be given before age 6 years.
Currently, about 20 million doses of DTP and OPV are distributed each year in the United States (National Vaccine Injury Compensation Trust Fund, 1992). Prior to the measles epidemic of 1989–1991 and the requirement for a second dose of measles vaccine, approximately 10 million doses of measles-mumps-rubella vaccine (MMR) were distributed each year. In 1990, 19 million doses of MMR were distributed; in 1991, this figure dropped to 16 million (National Vaccine Injury Compensation Trust Fund, 1992).
Over the last decade, the public sector has purchased an increasing share of the vaccines sold in the United States (Table 4-5). Currently, almost half of all vaccines purchased in this country are procured with federal or state funds at contract prices. The current trend toward public-sector
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TABLE 4–5 Publicly Purchased Doses as a Percentage of Net Doses Distributed in the United States, 1985–1991
Year
DTP
MMR
OPV
1985
15
38
32
1986
29
44
39
1987
45
51
46
1988
33
47
44
1989
35
50
44
1990
40
45
48
1991
43
51
52
1992
54
45
NOTE: Data for 1992 DTP sales to the public are not yet available
SOURCE: Division of Immunization. Centers for Disease Control and Prevention, 1993.
procurement of vaccines is of considerable concern to the large commercial manufacturers (Douglas, 1992, 1993; Saldarini, 1992, 1993; Williams, 1993). They argue that sales to the public sector offset those to the private sector, and increasing public sector procurement will lead to further increases in the prices charged to private-sector clients (Garnier, 1993). Those involved in vaccine manufacturing also contend that if the U.S. government emerges as the sole purchaser of vaccines, company investments in vaccine-related research and development would likely decline (Douglas, 1992; Katz, 1993; Saldarini, 1992; Six, 1992). Others (Edelman, 1993; Shalala, 1993) however, suggest that the effects of any large-scale federal procurement policy on the U.S. vaccine industry are uncertain—policies on pricing, funding for product development, and competitive production of vaccines could entice additional manufacturers to enter this industry (Institute of Medicine, 1986; Shalala, 1993).
Supply
Forty vaccines and toxoids and an additional 10 immune globulins and antitoxins are licensed and available for use in the United States (see the box "Vaccines, Toxoids, Immune Globulins, and Antitoxins Available in the United States, 1993). The current supply of most childhood vaccines is plentiful in the United States. This is not to say, however, that all children who should be immunized are or that potential shortages cannot occur. Nevertheless, the problem of less-than-optimal vaccine coverage in the United States is due more to problems of access and to the failure of the
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FIGURE 4-2
CBER biotech INDs received, compared to total. SOURCE: Application Review and Policy, Therapeutics Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration.
FIGURE 4-3
CBER INDs received, by category. SOURCE: Application Review and Policy, Therapeutics Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration.
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biotechnology companies worldwide (most of them in the United States) conducting vaccine-related R&D (Oryx Press, 1992).
There is also considerable international activity in the area of vaccine innovation. A number of U.S. companies are entering into cross-licensing arrangements with European and Japanese partners, and European companies are acquiring firms that have access to the U.S. market. In 1989, Institut Mérieux acquired Connaught Laboratories, Inc., and Merck and Company entered into a product development and licensing agreement with Pasteur Mérieux Sérums et Vaccins in 1993. Chiron, a U.S. biotechnology firm, joined with Ciba-Geigy, an established Swiss-based pharmaceutical firm, to purchase the financially troubled Sclavo, an Italian manufacturer of vaccines in 1990 (Chiron Corporation, 1991). A number of biotechnology companies involved in vaccine-related R&D have entered into strategic alliances with Japanese companies (National Research Council, 1992).
A review of the vaccines licensed for use in the United States since 1986 shows that approximately half are new (Table 4-11). This is markedly different from the situation just 10 years ago. A majority of the vaccines licensed in the 1970s were improvements of old vaccines (Institute of Medicine, 1985). A recently licensed vaccine against typhoid resembles a product, in some respects, that might be used in the CVI, but it was developed in part by and for the DOD.
The current vaccine development process in the United States, from basic research through to the production, distribution, and marketing of vaccine products, although poorly integrated, does lead to the development and production of new vaccines for the domestic market, primarily because vaccine manufacturers perceive there to be adequate returns on their investment. An indication of the level of vaccine innovation is the sheer number of vaccines in various stages of development in the United States (Table 4-12). As can be seen, however, few of the vaccines currently being developed by established vaccine manufacturers are for exclusive use in the developing world, simply because such vaccines are perceived to be without sufficient returns on investment. As noted earlier, some vaccines developed by or for the DOD have been introduced into some developing countries on an ad hoc basis by commercial manufacturers. A few small biotechnology firms are working on vaccines of potential benefit to the developing world. As discussed in Chapter 3 and later in this report, few of these companies have the capacity to take a vaccine through to licensure and full-scale manufacture. Most of the development-stage companies working on vaccines of relevance to the developing world do so as part of cooperative research and development agreements (CRADAs) with the U.S. Department of Defense, and to a lesser extent, with the National Institute of Allergy and Infectious Diseases. At this time, the Walter Reed Army Institute of Research has almost 40 CRADAs with private-sector firms, the vast majority
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of which are development-stage biotechnology companies based in the United States (LTC Willis. A. Reid, Chief, Office of Research and Technology Applications, Walter Reed Army Institute of Research, personal communication, 1993).
By all accounts, the worldwide vaccine industry appears to be entering a new era of activity and innovation. In the United States, commercial vaccine manufacturers and biotechnology firms are pursuing the development of innovative vaccine products targeted to the industrialized-world market. The development and manufacture of vaccines for exclusively developing-world markets are not attractive investments for either commercial vaccine manufacturers or biotechnology firms because they are unlikely to offer adequate returns on investments under current market arrangements.
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TABLE 4-11 Vaccines Licensed for Use in the United States Since 1986
Vaccine and Company
Review Time (months)
FDA Approval
Characteristics
BCG live
18.1
05/1990
New approval of an old vaccine for limited indication (treatment of carcinoma-in-situ of the urinary bladder
Connaught Laboratories, Inc.
BCG vaccine
29.5
08/1990
New approval of old vaccine (also indicated for the treatment of carcinoma-in-situ of the urinary bladder
Organon Teknika Corporation
Diphtheria and tetanus toxoids and acellular pertussis vaccine, adsorbed (DTaP)
51.5
12/1991
New acellular pertussis component; shared manufacture with Takeda Chemical Industries, Ltd.
Lederle-Praxis Biologicals
Diphtheria and tetanus toxoids and acellular pertussis vaccine, adsorbed (DTaP)
27.1
08/1992
New acellular component; shared manufacture with Biken (Research Foundation of Osaka University)
Connaught Laboratories, Inc.
Diphtheria and tetanus toxoids and pertussis vaccine, adsorbed and Haemophilus influenzae type b conjugate
14.9
03/1993
New vaccine
Lederle-Praxis Biologicals
Haemophilus influenzae type b meningococcal outer membrane conjugate vaccine
24.9
12/1989
New vaccine (18–60 months)
Merck & Co., Inc.
Haemophilus influenzae type b meningococcal outer membrane conjugate vaccine
4.1
12/1990
Infant indication
Merck & Co., Inc.
Haemophilus influenzae type b conjugate vaccine (tetanus toxoid conjugate)
27.8
03/1993
New vaccine
Pasteur Mérieux Sérums et Vaccins
Haemophilus influenzae type b and diphtheria CRM 197 protein conjugate vaccine
22.5
12/1988
New vaccine (18–60 months)
Praxis Biologics, Inc.
Haemophilus influenzae type b conjugate vaccine
6.9
10/1990
Infant indication
Praxis Biologics, Inc.
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Vaccine and Company
Review Time (months)
FDA Approval
Characteristics
Haemophilus influenzae type b conjugate (diphtheria toxoid conjugate)
55.4
12/1987
New vaccine (18–60 months)
Connaught Laboratories, Inc.
Hepatitis B vaccine, recombinant
18.0
07/1986
New vaccine
Merck & Co., Inc.
Hepatitis B vaccine, recombinant
20.8
08/1989
Independent introduction
SmithKline Beecham
Influenza virus vaccine
17.3
08/1988
New introduction of old vaccine
Evans Medical, Ltd.
Japanese encephalitis virus, inactivated
30.8
12/1992
New vaccine
Research Foundation of Osaka University
Connaught Laboratories, Inc.
Poliovirus vaccine, inactivated
16.1
11/1987
Enhanced poliovirus vaccine
Connaught Laboratories, Inc.
Poliovirus vaccine, inactivated
93.3
12/1990
Independent introduction
Pasteur Mérieux Sérums et Vaccins
Rabies vaccine, adsorbed
93.3
03/1988
Independent introduction
Michigan Department of Public Health
Rabies vaccine
42.4
12/1991
Independent introduction
Connaught Laboratories, Inc.
Typhoid vaccine, live oral (Ty21a)
92.5
12/1989
New vaccine
Swiss Serum & Vaccine Institute, Berne
SOURCES: New Drug Approvals in 1991, Pharmaceutical Manufacturers Association, January 1992; New Drug Approvals in 1990, Pharmaceutical Manufacturers Association, January 1991; New Drug Approvals in 1989, Pharmaceutical Manufacturers Association, January 1990; Biotechnology Medicines, Pharmaceutical Manufacturers Association, 1990, Douglas Reynolds, Connaught Laboratories. Swiftwater, Pennsylvania, October 1992; Carolyn Hardegree, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration.
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TABLE 4.12 Selected Vaccines in Development
Product and Company U.S.
Development Status
Adenohepatitis B virus vaccine
Phase I
Wyeth-Ayerst
Acellular pertussis vaccine
Phase I/II
Massachusetts Department of Public Health
Acellular pertussis component
Phase I
Michigan Department of Public Health
Diphtheria and tetanus toxoids and acellular pertussis vaccine, adsorbed
Phase III (infant efficacy study)
Lederle-Praxis Biologicals
Diphtheria and tetanus toxoids and acellular pertussis vaccine, adsorbed
Phase III
North American Vaccine
Diphtheria and tetanus toxoids and accellular pertussis vaccine, adsorbed and inactivated polio vaccine
Phase III
North American Vaccine
TetrammuneTM Diphtheria and tetanus toxoids and pertussis vaccine, adsorbed, and Haemophilus influenzae type b vaccine
PLA submitted (recommended for approval by FDA advisory committee, ages 2 months up to 7th birthday)
Lederle-Praxis Biologicals
Diptheria and tetanus toxoids and acellular pertussis vaccine, adsorbed, and Haemophilus influenzae type b conjugate vaccine
Phase II (for booster dose at 15–18 months of age or when both vaccines recommended to be given simultaneously)
Lederle-Praxis Biologicals
PropediaTM Diphtheria and tetanus toxoids and pertussis vaccine, adsorbed and Haemophilus influenzae type b vaccine (diphtheria toxoid conjugate)
PLA submitted (for 15–60 months of age as final booster dose in Hib series or as n single dose primary immunization at 15–60 months of age)
Connaught Laboratories, Inc.
Act HIBTM + DTP; Diptheria and tetanus toxoids Act HIB and pertussis vaccine, adsorbed, reconstituting Haemophilus influenzae type b conjugate vaccine (tetanus protein conjugate)
Submitted as part of PLA for alone (for 2–60 months of age)
Connaught Laboratories, Inc./Pasteur Mérieux Sérums et Vaccins
Act HIBTM + DTaP; Diptheria and tetanus toxoids and acellular pertussis vaccine, adsorbed, reconstituting Haemophilus influenzae type b conjugate vaccine (tetanus protein conjugate)
Phase II for 15–60 months of age
Connaught Laboratories, Inc./Pasteur Mérieux Sérums et Vaccins
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Product and Company
Development Status
Diphtheria and tetanus toxoids and pertussis vaccine, Haemophilus influenzae type b, hepatitis B vaccine
Phase I (by summer of 1993)
Merck & Co., Inc./Connaught Laboratories, Inc.
Diphtheria and tetanus toxoids and pertussis vaccine, Haemophilus influenzae type b, hepatitis B vaccine and inactivated polio vaccine
Phase I (by summer of 1993)
Merck & Co., Inc./Connaught Laboratories, Inc.
Diphtheria and tetanus toxoids and pertussis vaccine, hepatitis B and Haemophilus influenzae type b conjugate vaccine
Pre-clinical studies completed; preparing IND submissions
Michigan Department of Public Health/ SmithKline Beecham
Diphtheria and tetanus toxoids and acellular pertussis vaccine and hepatitis B vaccine and Haemophilus influenzae type b conjugate vaccine
Pre-clinical studies completed; preparing IND submissions
Michigan Department of Public Health/ SmithKline Beecham
Diptheria and tetanus toxoids and pertussis vaccine, adsorbed, and poliovirus vaccine, inactivated
PLA submitted
Connaught Laboratory, Inc./Pasteur Mérieux Sérums et Vaccins
Act HIBTM Haemophilus influenzae type b conjugate vaccine (tetanus protein conjugate)
PLA submitted
Connaught Laboratories, Inc./Pasteur Mérieus Sérums et Vaccins
Haemophilus influenzae type b conjugate vaccine
Phase III
Massachusetts Department of Public Health
Haemophilus influenzae type b conjugate vaccine, hepatitis B vaccine
Phase Ill
Merck & Co., Inc.
VAQTATM hepatitis A vaccine
Phase III
Merck & Co., Inc.
Hepatitis B vaccine
Phase II
Connaught Laboratories. Inc.
Hepatitis B vaccine
Phase III
Amgen/Johnson & Johnson
Herpes vaccine
Phase I (adults)
Lederle-Praxis Biologicals
PrymeTM lyme disease vaccine (recombinant OspA lipoprotein for Lyme borreliosis)
Phase I
Connaught Laboratories, Inc.
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Product and Company
Development Status
Lyme disease vaccine (recombinant OspA lipoprotein for Lyme borreliosis)
Phase I (by summer of 1993)
SmithKline Beecham
M-M-R®II measles, mumps, rubella, and varicella
Phase III
Merck & Co., Inc.
Measles, mumps, rubella virus vaccine, live
Project currently inactive
Connaught Laboratories, Inc./Pasteur Mérieux Sérums et Vaccins
Meningococcal group B vaccine (outer membrane protein)
Phase III for 2 years of age and older
Connaught Laboratories, Inc.
Pneumococcal conjugate vaccine (streptococcal conjugate vaccine, diphtheria toxoid and tetanus protein conjugates for otitis media and pneumonia)
Phase I
Connaught Laboratories, Inc./Pasteur Mérieux Sérums el Vaccins
Pneumococcal conjugate vaccine, streptococcal pneumonia vaccine, enhanced
Phase I/II
Lederle-Praxis Biologicals
Pneumococcal conjugate vaccine
Phase II
Merck & Co., Inc.
Respiratory syncytial virus vaccine
Phase I/II
Lederle-Praxis Biologicals
Rhesus rotavirus vaccine
Phase III
Wyeth-Ayerst
Rhesus rotavirus vaccine
Phase II
Merck & Co., Inc.
Sabin IPV inactivated Sabin polio vaccine
Phase III (age 2 months and up)
Lederle-Praxis Biologicals
Salmonella, live attenuated
Phase I
Lederle-Praxis Biologicals
Streptococcal group B vaccine
Phase I
North American Vaccine
Varivax® varicella vaccine
PLA submitted
Merck & Co., Inc.
SOURCES: Pharmaceutical Manufacturers Association. 1990. New Medicines in Development for Children. Washington, D.C.; Pharmaceutical Manufacturers Association. 1990. Biotechnology Medicines. Washington, D.C.; Douglas Reynolds, Connaught Laboratories, Inc., October 1992; Glenna Crooks and Ronald B. Ellis, Merck & Co., Inc., May 1993; Jane Scott, Lederle-Praxis Biologicals, February 1993; George Siber, Massachusetts Biologic Laboratories, June 1993; Robert Meyers, Michigan Department of Public Health, May 1993; Dan Soland, SmithKline Beecham, June 1993.
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NOTE
1.
When the Division of Biologics (DBS) became a part of the Food and Drug Administration in 1972, the Commissioner of Food and Drugs appointed vaccine advisory panels to evaluate the safety and effectiveness of biological products licensed prior to 1972 (USC § 601.22, 21 CFR Ch.l). Several vaccines were found not to be safe and/or effective or in many other cases the manufacturers did not submit the required information for evaluation of their vaccines, but requested the FDA to revoke the licenses without prejudice.
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Representative terms from entire chapter:
influenzae type