JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
JET INJECTION FOR VACCINATION: HISTORICAL AND CLINICAL OVERVIEW –FOCUS ON INFLUENZA
Food and Drug Administration Silver Spring, Maryland, 9 January 2011
Bruce G. Weniger, MD, MPH CAPT, USPHS (ret.) International Professor, Research Institute for Health Sciences, Chiang Mai University Associate Editor, (Elsevier) 1
JET INJECTION FOR VACCINATION
DISCLOSURE/DISCLAIMER: Member, Scientific Advisory Group, PATH’s Disposable-syringe Jet Injector Initiative, 2008-present No financial interest or economic relationship with jet injection industry Views presented herein are my own, not necessarily shared by the jet injector industry or PATH
Bruce G. Weniger, MD, MPH CAPT, USPHS (ret.) International Professor, Research Institute for Health Sciences, Chiang Mai University Associate Editor, (Elsevier) 2
Page 1 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
JET INJECTION FOR VACCINATION
What is Jet Injection? MUNJIs vs. DSJIs Clinical Aspects for Efficacy and Safety Polio Eradication and Global Health Standard of Care in Vaccine Delivery
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What is Jet Injection? Aquapuncture device Squirts pressurized liquid Galante et Cie. à Through orifice (~0.15 mm Ø) à Like child’s water pistol 1860s: Invented in France
1940s: Single-user devices à Insulin and other drugs Hypospray®, R.P. Scherer Corp.
1950s: Adapted by U.S. Army for high-speed vaccination sessions à “Multi-use-nozzle jet injectors” à 600-1000 injections per operator per hour Ped-O-Jet® MUNJI 4
Page 2 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
JET INJECTION FOR VACCINATION
✓What is Jet Injection? MUNJIs vs. DSJIs Clinical Aspects for Efficacy and Safety Polio Eradication and Global Health Standard of Care in Vaccine Delivery
5
MUNJIs vs. DSJIs Multi-use-Nozzle Jet Injectors (MUNJIs) Nozzles reused without intervening sterilization Unsafe: cross-contamination of blood-borne pathogens à Withdrawn from public-health use by 1990s
Hypospray®
Ped-O-Jet® Med-E-Jet® Imo-Jet®
Some types still used in dentistry and podiatry ! 6
Page 3 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
MUNJIs vs. DSJIs Disposable-syringe Jet Injectors (DSJIs) Introduced in 1990s / 2000s to avoid cross-contamination risk of MUNJIs Each patient gets sterile, single-use dose-chamber and nozzle à Some syringes auto-disabling to prevent refilling and reuse in developing world
Biojector® 2000 jet stream
LectraJet® HS (investigational) M3 ® PharmaJet® (Among others
not shown) LectraJet
Bioject® ZetaJet™
Medi-Jector VISION™ Injex®
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JET INJECTION FOR VACCINATION
✓What is Jet Injection? ✓MUNJIs vs. DSJIs Clinical Aspects for Efficacy and Safety Polio Eradication and Global Health Standard of Care for Vaccine Delivery
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Page 4 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Clinical Aspects for Efficacy and Safety Bibliography on Jet Injection
Maintained since 1990s: Paper reprints = 6 feet of shelf space Many now in .pdf electronic files 9
Clinical Aspects for Efficacy and Safety 60-year Evidence Base in Literature JI immune response = or occasionally > needle-syringe Live vaccines Inactivated vaccines à Bacille Calmette-Guérin à Botulism à Measles à Cholera à Mumps à Diphtheria-Tetanus-Pertussis à Measles-Mumps-Rubella à Hepatitis A à Measles-Smallpox (vaccinia) à Hepatitis B à Rubella à Influenza à à Smallpox (vaccinia) Japanese encephalitis à Meningococcus A, C à Yellow fever à Plague à Polio (IPV) Routes à Tetanus, Tetanus-Diphtheria à IM, ID (MUNJIs, one DCJI) à Tularemia-Typhoid à SC (DCJIs, investigationals) à Typhoid, Typhoid-Paratyphoid à Investigationals: HIV, DNA, cancer, etc. Jet injection local reactions usually > needle-syringe Mostly reported as “tolerable” 10
Page 5 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Clinical Aspects for Efficacy and Safety Continuous DoD Use Since 1960s U.S. Department of Defense à 1960s to 1997 by all services Until withdrawal of Ped-O-Jet® MUNJI in 1997 for cross- contamination risk à Since 1997 by Navy and Coast Guard Using safe Biojector® 2000 DSJI For recruited sailors and dependent spouses and children Most all vaccines FY2004: ~0.5 million doses by DSJI (source: Bioject, Inc.) Supportive unpublished clinical data since 1950s from military medical research à Recent analyses of current influenza products in use
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Use of Biojector® 2000 in U.S. Military
Biojector® 2000 Location Applications No. Injections Customer Oct. 2003 - Oct. 2004 Naval Hospital Great Great Lakes, IL Mass immunization, Healthcare operations Lakes, USS Red Rover for military recruits Over 350,000
US Coast Guard Cape May, NJ Mass immunization, Healthcare operations Training Center for military recruits 35,000
Naval Hospital and Pensacola, FL Immunization for adult and pediatric associated outpatient patients 50,000 medical clinics Naval Ambulatory Care Port Immunization for adult patients, Clinic Hueneme, CA Mass immunization for service members 20,000
Naval Hospital Bremerton, Immunization for adult and pediatric 20,000 Bremerton WA patients Naval Hospital Guam, Pacific Immunization for adult and pediatric Islands, USA patients, 20,000 Mass immunization for service members Courtesy: Bioject Medical Technologies
Page 6 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Product users, cont. Military installations utilizing the product for immunization of troops
Courtesy: Bioject Medical Technologies
Product users, cont. Military installations utilizing the product for immunization of troops
Courtesy: Bioject Medical Technologies
Page 7 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Clinical Aspects for Efficacy and Safety Public Health and Medical Usage U.S. CDC, state, local health agencies à Mass campaigns for polio (1950s), influenza (1976 “swine flu”) à Mass campaigns for meningitis outbreaks, other diseases World Health Organization and developing countries à Smallpox eradication in South America, Africa, parts of Asia à Yellow fever, measles, and other targeted diseases Safe usage of new-generation DSJIs since 1990s à Small number of state/local public health and private providers à 2009 uptake of DSJIs for H1N1 and seasonal influenza Increasing grocery/pharmacy chain purchases for on-site “flu shots” No empirical experience/observation of failed efficacy
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Clinical Aspects for Efficacy and Safety Published Literature on JIs for Influenza 1. Anderson et al. JAMA 1958 2. Benenson AS. Proc Intl Symp Immunology, 1959 3. Benenson AS, et al. Fed Proc, 1959 4. Kirschenheuter F. Zentralbl Arbeitsmed, 1965 5. Clark ML et al. J Lab Clin Med, 1965 6. Kirschenheuter F. Zentralblatt Arbeitsmedizin, 1965 7. Wright M. Occupational Health, 1968 8. Davies JW et al. Canadian J Public Health, 1969 9. Vibes J. Médecine et Maladies Infectieuses, 1971 10. Roberts TE. British Medical Journal, 1973 11. Payler DK et al. Br Med J, 1974 12. Noble GR, et al. Am J Epid, 1975 13. Ehrengut W et al. Dev Biol Stand, 1977 14. McIntosh K et al. J Infect Dis, 1977 15. Ivannikov IuG et al. Zh Mikrobiol Epidemiol Immunobiol, 1980 16. Rudenko LG, et al. Zhurnal mikrobiol, epidemiol, i immunobiol, 1984 17. Vasil'eva et al. Zh Mikrobiol Epidemiol Immunobiol, 1988 18. Spiegel A, et al. Sém. Intl sur les Vaccinations en Afrique, 1994 19. Parent du Châtelet I, et al. Vaccine, 1997 20. Jackson LA et al. Vaccine, 2001 21. Simon JK et al. Vaccine, 2011 16
Page 8 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Clinical Aspects for Efficacy and Safety Earlier label indications for jet injection Removed when “MUNJIs” and their 50-dose vials abandoned by DoD Menomune® meningococcal vaccine, Connaught Laboratories, Swiftwater, PA, July 1990
YF-VAX® yellow fever vaccine, Pasteur Mérieux Connaught, Swiftwater, PA, May 1996
M-M-R® II measles, mumps, rubella combination vaccine, Merck & Co., 1980s through present (2012)
Eli Lilly and Co., Indianapolis, IN, influenza vaccine, 1962 17
Clinical Aspects for Efficacy and Safety Influenza labels for 1976-77 “Swine flu”
Large multi-dose vials for jet injectors
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Page 9 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Clinical Aspects for Efficacy and Safety Clinical Influenza Vaccine Trial by 2 DSJIs: DSJI vs. N-S - IM vs. SC - Dose-ranging
Adult college students (mean age=27y, CI95%: 25-28y) (n=304)
N&S IM (n=99) Vitajet® JI SC (n=96) Biojector® JI IM (n=99)
0.5 mL 0.3 mL 0.2 mL 0.5 mL 0.3 mL 0.2 mL 0.5 mL 0.3 mL 0.2 mL n=33 n=33 n=33 n=31 n=32 n=33 n=33 n=34 n=32
Vaccine: 1998 trivalent inactivated influenza Fluzone®, Pasteur Mérieux Connaught A/Beijing/95 (H1N1) A/Sydney/97 (H3N2) B/Beijing/93 Administered: 22 Sep – 22 Oct 1998
Jackson, et al. Vaccine 2001;19:4703-4709 19
Percent subjects with ≥4-fold rise in HAI titer by day 28 100 90 80 70 60
% 50 40 30 20 10 0 H1N1 H3N2 B Vitajet SC 0.2 mL Vitajet SC 0.3 mL Vitajet SC 0.5 mL Biojector IM 0.2 Biojector IM 0.3 Biojector IM 0.5 Needle&Syringe 0.2 Needle&Syringe 0.3 Needle&Syringe 0.5
Jackson, et al. Vaccine 2001;19:4703-4709
Page 10 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Percent subjects with serum 100 HAI titer >=64 on day 28 90 80 70 60
% 50 40 30 20 10 0 H1N1 H3N2 B Vitajet SC 0.2 mL Vitajet SC 0.3 mL Vitajet SC 0.5 mL Biojector IM 0.2 Biojector IM 0.3 Biojector IM 0.5 Needle&Syringe 0.2 Needle&Syringe 0.3 Needle&Syringe 0.5 Jackson, et al. Vaccine 2001;19:4703-4709
GMTs (95% CIs) to influenza A/H1N1/Beijing/95 by study group, day 28 0.3 mL . 0.5 mL . 400 0.2 mL . 350 300 250 200
GMT 150 100 50 0
C M S C M S C M S S & S & S & t r I t r I t r I o o o je t N je t N je t N a c a c a c it je it je it je V io V io V io B B B Jackson, et al. Vaccine 2001;19:4703-4709
Page 11 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
JET INJECTION FOR VACCINATION
✓What is Jet Injection? ✓MUNJIs vs. DSJIs ✓Clinical Aspects for Efficacy and Safety Polio Eradication and Global Health Standard of Care in Vaccine Delivery
23
Polio Eradication and Global Health IPV Polio Vaccination by DSJI Polio eradication must switch from cheap OPV to expensive IPV (20x cost) à Pre-eradication: overcome decreased immune responses to OPV in remaining hot zones à Post-eradication: avoid reversion to virulence from live virus in OPV WHO Research Agenda: Deliver ID by dose- sparing, needle-free jet injectors? à Avoid difficult Mantoux method for ID route à Avoid dangers and drawbacks of needle-syringes WHO trials of IPV by dose-sparing DSJIs using ID route - 80% dose reduction: 0.5 mL to 0.1 mL Mohammed AJ, et al, NEJM 2010;362:2351-2359 Resik S, et al, J Inf Dis, 2010;201:1344-1352 Other global applications: rabies, BCG,
routine-immunization antigens 24
Page 12 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
JET INJECTION FOR VACCINATION
✓What is Jet Injection? ✓MUNJIs vs. DSJIs ✓Clinical Aspects for Efficacy and Safety ✓Polio Eradication and Global Health Standard of Care in Vaccine Delivery
25
Standard of Care for Vaccine Delivery FDA Policy on “Off-Label” use
*FDA Drug Bulletin, April 1982. Available: www.circare.org/fda/fdadrugbulletin_041982.pdf
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Page 13 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Standard of Care for Vaccine Delivery CDC/ACIP General Rec’s. on Immunization 2011 www.cdc.gov/mmwr/pdf/rr/rr6002.pdf
2006 www.cdc.gov/mmwr/pdf/rr/rr5515.pdf
2002 www.cdc.gov/mmwr/pdf/rr/rr5102.pdf
1994 www.cdc.gov/mmwr/pdf/rr/rr4301.pdf 27
Standard of Care for Vaccine Delivery Other CDC rec’s. for “unlabeled” indications
Use of many routine childhood vaccines à MEN, DTaP, Tdap, HIB-containing products, MMR, VAR, Zoster, DTaP-HBV-IPV, ROT, HPV http://emergency.cdc.gov/coca/ppt/7_27_10_Immunize_FIN2.pdf (slide nos. 4,18,24,25,26) http://www.cdc.gov/mmwr/PDF/rr/rr4805.pdf Japanese encephalitis vaccine for children at travel risk http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6020a6.htm http://www.cdc.gov/ncidod/dvbid/jencephalitis/children.htm Treatment of smallpox vaccine ocular complications http://emergency.cdc.gov/agent/smallpox/training/webcast/04feb2003/files/ae-management.pdf Primaquine for prophylaxis of Plasmodium vivax http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to- travel/malaria.htm
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Page 14 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
Standard of Care for Vaccine Delivery CDC disclaimer for “unlabeled” indications
http://emergency.cdc.gov/coca/ppt/7_27_10_Immunize_FIN2.pdf 29
Standard of Care for Vaccine Delivery Conclusions
A “Standard of Care” has been established for DSJIs as accepted medical /public health practice for delivery of influenza and a number of other vaccines à Large, consistent evidence base for efficacy (safety for DSJIs) à DoD medical practice and internal data, 1960s to present à Long history of usage/promotion by CDC and both global and local U.S. health agencies à Current and past CDC/ACIP General Recommendations on Immunization
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Page 15 JET INJECTION FOR VACCINATION: Historical and Clinical Overview - Focus on Influenza Bruce G. Weniger, MD, MPH Food and Drug Administration, Silver Spring, MD, 9 January 2012
JET INJECTION FOR VACCINATION
✓What is Jet Injection? ✓MUNJIs vs. DSJIs ✓Clinical Aspects for Efficacy and Safety ✓Polio Eradication and Global Health ✓Standard of Care in Vaccine Delivery
Thank You 31
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