Faulty Design Created Inherent Risk – Part 3

Jet Injectors = Jet Infectors

January 17, 2016

Retrograde Flow
P.N. Hoffman, a scientist at the Laboratory of Hospital Infection in London, studied the risks and hazards of jet injectors at the request of the World Health Organization. In a personal interview, Hoffman recalled his study by saying:

I was part of a team studying a small range of jet injectors, trying to establish general truths rather than study specific injectors. I was observing whether there were any problems of blood transmission between sequential recipients of injections rather than trying to fix any specific problem (Hoffman, 2013).

     Hoffman assessed the potential of cross-contamination via jet injectors amidst low volumes of blood detection. Hoffman’s calf study assessed four different types of jet injectors. He promised manufacturers he would not disclose the brand names of the devices tested but would only identify them by their unique characteristics (Hoffman et al., 2001). I,however, have deciphered which injectors were used: Ped-O-Jet/Am-O-Jet, Medivax, Jet2000, and Med-E-Jet. The Am-O-Jet is an identical design to the Ped-O-Jet device (American Jet Injector; Weniger & Papania, 2008). Two of the jet injectors (i.e., Medivax and Jet2000) were prototypes.

 
Hoffman found, “All injectors tested transmitted significant (over 10 pl) volumes of blood; the volumes and frequency of contamination varied with injector” (Hoffman et al., 2001). 10 picoliters (pl) of blood, which is not visible to the human eye, is an accepted threshold for transmitting the Hepatitis B virus, and has been used as the unofficial threshold for an impermissible amount of contamination.

In my interview, I asked Dr. Hoffman how much blood would be required to transmit the hepatitis C virus? Hoffman responded,

There is a greater knowledge base on hepatitis B than hepatitis C in this area. It is generally assumed that hepatitis C is about 10-times less infectious than hepatitis B. This means hepatitis C having a transmission volume starting at around 100 picolitres, but it is probable that a greater volume would usually be required (Hoffman, 2013).

     Interesting, yet remember these values are still microscopic. Since my interview with Dr. Hoffman the transmissibility rates of viral hepatitis are still unknown and are left to professional opinion.

 
The National Institute of Health has helped me comprehend these figures. In response to my inquiry on the topic the NIH stated,

a picoliter is 10-12 or one trillionth the size of a liter…to put this in perspective, if a drop of blood were a microliter in volume, it would look no bigger than a period on this page. A picoliter would be a million times smaller (NIH, 2013).

     The thought of infectious blood being so small makes me cautious of shaking someone’s hand or touching foreign objects.
Hoffman’s findings were astonishing. If 10 picoliters is a sufficient amount of blood for transmitting Hepatitis B then this value (i.e., 10 pl) can be used as a threshold level in determining a contamination rate amongst the sampling of jet injectors. Results found the Ped-O-Jet had a 34.2 percent contamination rate. The Med-E-Jet had a 97.4 percent contamination rate. The two prototype injectors were also found to transmit relevant amounts of blood. The Medivax had a 95.8 percent contamination rate. The Jet2000, which had a single-use plastic protector cap that protected the reusable nozzle, had a 42.0 percent contamination rate.

 

In an extended sampling, the Med-E-Jet nozzle was wiped with alcohol between subsequent injections. Results found a lower contamination rate than in the initial series where the nozzle head was not wiped (Hoffman et al., 2001). In other words, there was still contamination even after the nozzle was swabbed. These results demonstrate when the nozzle is swabbed only superficial contamination is removed and sterilization of the internal fluid pathways is neglected.
The results also found a significant number of samplings consisted of greater than 50 picoliters of blood. The Ped-O-Jet had a 16.6 percent contamination rate at this lower threshold. The Med-E-Jet had a 85 percent contamination rate. The Medivax had a 85.4 percent contamination rate. The Jet2000 had a 20.1 percent contamination rate (Hoffman et al., 2001).

 

A limitation of the ELISA method is the necessity for diluting a sample that has been frozen. Through this method some of the quantity of contamination can be lost. Dr. Hoffman stated, “Freezing solutions with low concentrations of proteins causes loss of detectable protein, probably due to the absorption of surfaces. We estimate…losses of analyte of around 30 – 50 %, and so our results are underestimates of blood contamination” (Hoffman et al., 2001).
Hoffman remarked on the results in a journal article as “disappointing.” In studying the contamination of the jet injector, he identified a phenomenon which he termed “ballistic contamination.” This occurred because the newly deposited jet stream in the skin had developed a pressure greater than the pressure in the jet injector causing a backwards flow. This backwards or rather retrograde flow of fluid and now blood and bodily fluids shoots out of the skin and onto the jet injector nozzle and into the internal fluid pathway (Voelker, 1999).
So the question would arise, are these isolated incidents or natural phenomenon of the jet injection process?

 

Hoffman and colleagues found the retrograde flow was a natural phenomenon in the injection process. For all the naysayers let me use the Fair Use Law to the limits and quote Hoffman himself,

some of the liquid injected form[ed] a pocket below the injection site. This will be under maximum pressure towards the end of the injection process, before sufficient dispersion into surrounding tissues has occurred to release pressure. This will coincide with a lessening of pressure from the injector. When the pressure from the injector is exceeded by the back-pressure from the tissue pocket, backflow through the pathway in the skin created by the injector could occur. This liquid will contain blood from the destruction of small blood vessels during the injection process and can have different pathways after it has emerged from the skin according to the type of injector. Injectors that have direct skin contact will form a continuous fluid pathway between the skin and injector. As the outward pressure from the injector dies away at the end of an injection, back-pressure from the fluid in the tissue pocket will cause blackflow out of the skin to inside the injector’s fluid pathway (Hoffman et al., 2001).

     Kale and Momin (2014) stated that during Phase 2 of the three-stage injection process there would be a backwards flow, where the jet spray would shoot back-out of the hole towards the jet injector. This would be an expected phenomena in every injection due to the continuous depletion of pressure where the volumetric rate of hole formation would eventually be less than the volumetric rate of the jet impinging the skin. This continuous decrease in pressure would create a retrograde, or rather backwards flow, whereupon the jet injector’s nozzle, internal fluid pathway and drug reservoir would become contaminated.

 
In remarking on Hoffman’s study, the World Health Organization stated, “The implication of these results is that, for jet injection to be safe, the entire fluid path must be changed between injections” (WHO, 1997).

 
The magnitude of Hoffman’s study called for further investigations. Hoffman’s findings were later replicated in published and unpublished studies by (1) the World Health Organization, (2) the São Paulo State Ministry of Health in Brazil, and (3) the University of Florida (Weniger, 2002).

 
(1) A 1997 report by the World Health Organization cited an unpublished in vitro study conducted by the Program for Appropriate Technology in Health (PATH), which assessed gross contamination upon the jet injector nozzle. The tests sought to detect contamination in three areas: 1) On the surface of the skin that was injected, 2) in down-stream inoculations between patients, and 3) upon the surfaces of the jet injector that had contact with skin. Contaminants were tested to a sensitivity level of one picoliter, or rather 10-6 milliliter. “Although these tests were not as sensitive as the PHLS tests [by Hoffman], they showed systematic contamination of both the ejectate and the internal fluid pathway.” That is to say there was enough blood to contain a blood-borne pathogen in both the ejectate (i.e., the dose the next vaccinee would receive) and within the jet injector (WHO, 1997).

 
(2) An unpublished Brazilian study, referred to above, tested older model multi-use jet injectors. In this study, a saline solution was injected into human subjects and then sequentially injected three times into three test tubes. The ejectates were tested to detect any blood contamination up to 10 picoliters. Dr. Martin Friede of the World Health Organization stated, “whether it was wiping with the nozzle or wiping without the nozzle, we had between 7 and 11 percent of the ejectates contaminated with blood” (FDA, 2005).

 
(3) Sweat and colleagues (2000) replicated and extended Hoffman’s study by testing the potential of cross-contamination of the Ped-O-Jet amongst calves and pigs. This study modeled all of the previous in vivo studies in that it injected a saline solution into a vaccinee (i.e., either a calve or pig) and then subsequently fired the ejectate into a vial. The subsequent injection represents what the next person or animal in line would receive.

 
“We have detected contamination well above current levels that we would consider indeterminate or uninterpretable,” said Dr. Bruce Weniger, a coauthor of this study (FDA, 1999). In other words, researchers found rates of contamination were significant.

Faulty Design Created Inherent Risk – Part 4

Acknowledgements
I greatly thank Dr. Peter Hoffman for taking the time in answering my questions. I am also thankful for the Health Protection Agency of the United Kingdom for providing me with a paid copy of Hoffman’s study.

References:

  • (American Jet Injector) American Jet Injector, Lansdale, PA; 19446-4520, USA; amojet@aol.com (the Am-O-Jet™ is an exact design of the out-of-patent Ped-O-Jet® device).
  • (FDA, 1999) Food and Drug Administration. General Hospital & Personal Use Devices panel: open session. Department of Health and Human Services Meeting. Rockville, MD. 2 August 1999.
  • (FDA, 2005) FDA. General Hospital and Personal Use Devices Panel of the Medical Devices Advisory Committee. August 9, 2005. 35th Conference. Washington, D.C.
  • (Hoffman et al., 2001) Hoffman PN, Abuknesha RA, Andrews NJ, Samuel D, Lloyd JS. A model to assess the infection potential of jet injectors used in mass immunization. Vaccine 19 (2001): 4020-4027.
  • (Hoffman, 2013) Hoffman, PN. Personal communication. February 28, 2013.
  • (Kale & Momin, 2014) Kale TR, Momin M. Needle free injection technology – An overview. Innovations in Pharmacy. 2014, Vol. 5, No. 1, Article 148. pp. 1-8. Available at: http://z.umn.edu/INNOVATIONS.
  • (NIH, 2013) National Institute of Health. Personal Communication. September 4, 2013.
  • (Sweat et al., 2000) Sweat JM, Abdy M, Weniger BG, Harrington R, Coyle B, Abuknesha RA, Gibbs EP. Safety testing of needle free, jet injection devices to detect contamination with blood and other tissue fluids. Ann NY Acad Sci 2000;916(31):681-682.
  • (Voelker, 1999) Voelker R. Eradication Efforts Need Needle-Free Delivery. JAMA. 1999. Available at: https://web.archive.org/web/20010524044635/http://jama.ama-assn.org/issues/v281n20/ffull/jmn0526-2.html.
  • (Weniger, 2002) Weniger BG. Bifurcated needles vs. jet injectors for smallpox vaccination. ACIP. 2002-Jan-09: pp 1-8. [Draft].
  • (Weniger & Papania, 2008) Weniger BG, Papania MJ. Alternative Vaccine Delivery Methods [Chapter 61]. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines, 5th ed. Philadelphia, PA: Saunders (Elsevier); 2008;1357-1392.
  • (WHO, 1997) World Health Organization. Steering group on the development of jet injection for immunization. May 14, 1997. [draft]

 

 

© Shaun Brown and Jet Infectors, 2016 – 2017
Fair Use Notice (17 U.S.C. § 107)


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