PATH’s Fluorescein Testing on Ped-O-Jet Injectors

The Program for Appropriate Technology in Health (PATH), funded by the Bill and Melinda Gates Foundation, has been a major contributor in the development of safer jet injection technology. Although during the development of safer, next generation jet injectors, PATH needed to assess how bad were the Ped-O-Jet injectors.

Around 2003-2004 PATH conducted a “simple” test to assess the safety of the HSI-500, a prototype jet injector manufactured by Felton International, Inc. The “simple” test was an in vitro fluorescein contamination test, which made any contamination visible due to the use of a fluorescein dye. The highly concentrated fluorescein dye was used as a surrogate for high titer Hepatitis B infection (FDA, 2005).

PATH - Example of a Positive Fluorescein Sample

(Zehrung, 2003)

“The fluorescein assay really exceeds the PCR [polymerase chain reaction] methods in terms of a detection limit,” explains Darin Zehrung, the Associate Technical Officer at PATH. “So it’s very sensitive, it’s very specific in terms of an assay. And we believe a good surrogate aside from human testing to demonstrate cross-contamination safety” (FDA, 2005).

For this experiment PATH used the Ped-O-Jet injector as a comparative model. The HSI-500 and the Ped-O-Jet injector were both sterilized and administered an injection into a test fixture containing a fluorescein dye. Each of the jet injectors then fired the subsequent shot into vials and the ejectates were evaluated. The threshold for contamination was defined as detection of more than 10 picoliters within the 0.5 cc sample. Results for the Ped-O-Jet found 75 out of 100 (75%) samples contained more than 10 picoliters of fluorescein. Results for the HSI-500 found no contamination (Zehrung, 2004). These results indicated the Ped-O-Jet cross-contaminated a sufficient volume of fluorescein from the infected host to the next dose.

PATH had conducted performance and safety evaluations on the Ped-O-Jet, as noted within these pictures. Note in the photograph on the right, a drop of fluid remains on the nozzle tip post-injection.

PATH's Performance Testing of Ped-O-Jet

(Zehrung, 2003)

 

In March of 2004, PATH attended a CDC/WHO conference on jet injector safety which focused on establishing safety requirements for disposable-cartridge jet injectors. The meeting delved into evaluating several unknown factors. “The questions are how infectious is blood? How do we measure it? How do you model the risk? What level of risk is acceptable?” (FDA, 2005). Members of the conference were in agreement that quantities smaller than 10 picoliters could be infectious.

Based upon this conclusion, PATH altered the threshold of contamination from 10 picoliters to 0.04 picoliters. PATH conducted their fluorescein test a second time using the new 0.04 picoliter threshold level. Results demonstrated cross-contamination with the Ped-O-Jet but no cross-contamination with the HSI-500 jet injector.

Mr. Zehrung explained the results of the experiment in detail at a 2005 FDA conference on jet injector safety. For reasons unknown Mr. Zehrung refers to the Ped-O-Jet as a “first generation MUNJI device.” Although in other sources, he disclosed this was in fact the Ped-O-Jet injector (Zehrung, 2003; Zehrung, 2004).

Mr. Zehrung: So you may not be able to see these pictures. This is a first generation MUNJI device. I think that those are familiar with these technologies know what that device would be called. And you can see after injection into the test fixture, there is contamination at the injection site. There’s a combination of splash back as well as contact contamination during the injection process. You see that it’s contaminated with the fluorescein dye.
The same is true for the protector cap injector. This is the protector cap on the nozzle face itself.  It’s hard to see in this photo, but this protector cap post injection into the test fixture is also contaminated. But the down stream sample collected after injection into the text fixture is demonstrated to be free of cross- contamination.
Next slide.
So this is a slide showing the comparison of first generation MUNJI testing with this method versus a protector cap injector. These are the number of samples. So for a 100 samples with the first generation MUNJI device, all were contaminated, a 100 percent with an average contamination rate of 268 picoliters. In comparison with the protector cap injector for 300 samples, all samples were free of cross-contamination (FDA, 2005).

This is worth repeating. Mr. Zehrung presented images from the test which demonstrated the Ped-O-Jet as well as the injection site were both contaminated with fluorescein dye. This type of contamination is known as splash-back. The protector cap for the PCNFI was also contaminated with fluorescein. These results demonstrate that no matter the model or generation of jet injector gross-contamination upon the injection site and the nozzle are natural phenomenon of jet injection.

Results of the Ped-O-Jet found contamination in 100 out of 100 (100%) of the samples. The average volume of fluorescein contamination within the ejectates was 268 picoliters. This shows gross cross-contamination by the Ped-O-Jet. Mr. Zehrung stated of these results, “we believe that this [i.e., the fluorescein testing] is a very useful and powerful method to demonstrate contamination risk with the earlier devices” (FDA, 2005).

PATH’s fluorescein testing of the Ped-O-Jet further illuminates the degree of contamination these devices posed.

References:

  • (FDA, 2005) FDA. General Hospital and Personal Use Devices Panel of the Medical Devices Advisory Committee. August 9, 2005. 35th Conference. Washington, D.C.
  • (Zehrung, 2003) Zehrung D. PATH’s Experience from Jet Injector R&D and Field Assessment in Developing Countries. Presentation for Innovative Administration Systems for Vaccines. Rockville, Maryland. 18 December 2003.
  • (Zehrung, 2004) Zehrung D. Jet Inject for Mass Immunization: Design Update and Safety Testing Strategy. Presentation for Global Vaccine Research Forum. 10 June 2004.

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Experts Claim Cases of Jet Injector Transmission Would Not be Documented

Numerous professionals have stated it would be difficult to impossible to document transmission via jet injectors. Hepatitis C most often progresses asymptomatically and would not be detectable without ongoing active surveillance. However, Hepatitis C was not identified until 1989 and a test to identify the virus was not created until 1992, therefore it would have been impossible to document any incidents of transmission before 1992.

  • Dr. Bruce Weniger, formerly the Lead Researcher on Vaccine Technology within the CDC and known as Mr. Jet Injection, is one of, if not the, leading expert on jet injectors. In Dr. Weniger’s professional opinion, he states,

MUNJIs are inherently unsafe. Their re-use without intervening sterilization of fluid pathways which may be exposed to patient blood or tissue fluid violates established principles that apply to other critical medical devices. One cannot rely of the absence of documented cases of disease transmission beyond the California outbreak. It is unlikely that routine post-marketing surveillance would link sporadic cases to prior MUNJI use (Weniger, 2005).

  • In 1977 the Hepatitis Laboratories Division of the Center for Disease Control secretly conducted safety testing upon the Ped-O-Jet injector. The researchers called for “specifically designed prospective seroepidemiologic studies” to assess the risk of hepatitis transmission via jet injectors (CDC, 1977). Yet no one heeded the call.
  • In 1994 researchers within the CDC retested the safety of the Ped-O-Jet Injector. They noted, “The detection of rare, silent transmission would have been difficult, however, and likely to have been missed without active surveillance” (Grabowsky et al., 1994). Therefore, just because there were no documented cases does not mean transmission of blood-borne pathogens did not occur.
  • In 1996 the CDC and WHO held a conference on jet injector safety, in which participants had noted, “For an asymptomatic infection like hepatitis B, serosurveys would be required to detect transmission of the virus; in the absence of such data, it is impossible to state with any assurance that transmission has not occurred” (Fields, 1996). Hepatitis C most often progresses asymptomatically as well and therefore would not be detectable without ongoing active surveillance.
  • The Armed Forces Epidemiological Board, which is an expert advisory board of civilian physicians and scientists that assists the Department of Defense with medically related issues, stated within a January 9th of 1998 memorandum that no active prospective surveillance studies have been performed to uphold the safety record of jet injectors (AFEB, 1998).

References:

  • (AFEB, 1998) Armed Forces Epidemiological Board. Recommendation on Jet Injectors. AFEB (15-1a) 98-6. January 9, 1998.
  • (CDC, 1977) CDC. DHEW Memorandum: Informal Quarterly Report of October-December 1977. From: Special Investigations Section (Petersen NJ, Bond WW, Carson LA) to: Deputy Director (Favero MS), Hepatitis Laboratories Division, Phoenix, AZ (unpublished).
  • (Fields, 1996) Fields R. Participation in Meeting: Jet injectors for immunization; current practice and safety; improving designs for the future. WHO/CDC Meeting. Atlanta, GA. 2-3 October, 1996. Available at: http://pdf.usaid.gov/pdf_docs/PNABZ997.pdf.
  • (Grabowsky et al., 1994) Grabowsky M, Hadler SC, Chen RT, Bond WW, de Souza Brito G. Risk of transmission of hepatitis B virus or human immunodeficiency virus from jet injectors and from needles and syringes. Unpublished manuscript draft, dated January 3, 1994.
  • (Weniger, 2005) Weniger B. Safety of Multi-use-nozzle Jet Injectors (MUNJIs) for Bloodborne Pathogen Cross-contamination [draft]. Conference Notes. 7 August 2005.

 

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Dr. Sabin Warned of Hepatitis Risk From Jet Injectors in 1976

Dr. Albert Sabin, the creator of the oral polio vaccine, warned jet injectors could spread hepatitis in 1976. Several newspapers had reported upon Dr. Sabin’s comments.

During a meeting amongst health professionals planning a mass vaccination campaign for swine flu, Dr. Sabin interrupted a speaker to voice his concerns.

The York Daily Record reported in 1976, “Sabin…stood up during a speech by state epidemiologist Dr. Richard Parker to challenge the state and national strategy against swine flu.”

The article further stated, “Sabin also warned jet-injector guns could possibly spread disease during a mass immunization campaign” (York Daily Record, 1976).

In response to Dr. Sabin’s comments, the CDC purported that jet injectors are safe to use. The Salt Lake Tribune printed the following:

Defends Jet Gun Safety
Jet injector guns, which can inoculate up to 800 persons an hour, were being used in the immunization clinics. The CDC said that contrary to a charge by Dr. Albert Sabin, the discoverer of oral polio vaccine, the jet guns are safe to use and do not transmit any disease such as hepatitis (Salt Lake Tribune, 1976).

Yet the CDC did not conduct any safety testing upon the jet injector until 1977, in which the Hepatitis Laboratories Division did find the transmission of hepatitis via jet injectors was possible. See article – CDC’s Unpublished Jet Injector Studies – Part I

Dr. Sabin, like several others during his time, was correct to question the safety of jet injectors.

  • In 1962, the Eli Lilly Company warned, “If the nozzle becomes contaminated with blood or serum, it should be replaced or resterilized before further use to prevent the transmission of serum hepatitis virus or other infectious agents from one person to another.” See article – 1962 – Eli Lilly Warns of Hepatitis Transmission Via Jet Injection
  • In 1967, Dr. Sol Rosenthal studied the transference of blood between consecutive vaccinees when using a jet injector. Dr. Rosenthal stated, “It was reasoned that if the detection of the transference of erythrocytes (hemoglobin) or serum could be assayed, one might infer that the parenteral hepatitis agent would likewise be transferred” (Rosenthal, 1967).
  • In 1970, M.G. Kremer raised concern over the cross-contamination of serum hepatitis from jet injectors in the British Medical Journal. Kremer wrote, “The injector is not sterilized between injections, and in many cases it produces a small amount of bleeding at the injection site. The injector could thus become contaminated with blood, thus transmitting, for instance, hepatitis virus to subsequent patients” (Kremer, 1970).
  • During a 1971 National Institute of Health conference on tuberculosis vaccinations, the consensus from members was jet injectors do produce blood during the administering of vaccination and the possibility of transferring hepatitis cannot be excluded (DHEW, 1972). See article – 1971 NIH Conference Recognizes Bloody Jet Injectors Pose Risk For Hepatitis

 

References:

  • (DHEW, 1972) Department of Health, Education and Welfare, Public Health Service, National Institutes of Health. Status of Immunization in Tuberculosis in 1971; DHEW Publication No. (NIH) 72-68, pp. 185-187. Washington, D.C., 1972.
  • (Kremer, 1970) Kremer MG. Jet vaccination [letter]. Brit Med J 1970; 4:303.
  • (Rosenthal, 1967) Rosenthal SR. Transference of blood by various inoculation devices. Am Rev Respir Dis. October 1967; 96(4):815-819.
  • (Salt Lake Tribune, 1976) Salt Lake Tribune. Swine Flu Drive Moves With Few Side Effects. Salt Lake City, Utah. 3 October 1976. pg. 2.
  • (York Daily Record, 1976) York Daily Record. Dr. Sabin Opposes Mass Swine Flu Shots. York, Pennsylvania. 23 September 1976. pg. 2.

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FDA Reviews Jet Injector Safety

Following the 1996 CDC/WHO conference, the FDA initiated a hearing to review the safety of multi-use nozzle jet injectors (MUNJIs). The timeline below shows FDA’s two hearings on jet injector safety, which eventually led to the development of a guidance document.

 

1999 FDA Hearing – Guidance Development For Jet Injectors
In August of 1999, the FDA held its first ever hearing on jet injector safety. The purpose of the panel discussion was to develop a guidance document and identify regulatory standards to help improve the jet injection industry. Amongst the attendees were members of the FDA, Dr. Bruce Weniger of the CDC, PATH, and several jet injector manufacturers.

Dr. Charles Edmiston, associate professor of surgery at Medical College of Wisconsin, served as Chairman of the panel discussion. Dr. Edmiston stated, “we need to keep abreast of how this technology may actually be responsible for transmitting infections in the future, like hepatitis C.” (FDA, 1999).

The panel heard presentations on jet injector use over the last fifty-years, and forty-years of research demonstrating the risk of transmitting infectious pathogens.

Only one attendee upheld the safety of MUNJIs. Robert Harrington, former CEO and President over the Ped-O-Jet, shouted from the audience, “It was used by the Army for 35 years and it [the jet injector nozzle] was always wiped. Never had an issue. Good tracking system. And there’s nothing recorded in the world that says that it wasn’t wiped.” Jet Infectors has since presented evidence demonstrating Mr. Harrington’s comments were outright lies. (See article – Improper Military Jet Injector Vaccinations)

At the conclusion of the conference, the panel gave two recommendations: 1) To continue post market surveillance on the use of MUNJI devices. Post market surveillance monitors the safety of a device, such as a jet injector, after it has been released for public use. 2) To explore creating a standardized method for testing the safety of jet injectors (FDA, 2005a).

Despite the in depth discussions no regulatory changes or guidance document resulted from this conference.

 

2005 (Aug 9) FDA Hearing – MUNJI Safety
The FDA held a second hearing on the safety of MUNJI devices. The meeting was a long overdue extension of the first conference.

Present were members of various departments within the FDA, also Dr. Martin Friede from the WHO, representatives from PATH and other industry consultants and organizations. [Dr. Weniger of the CDC was scheduled to attend but had to cancel.]

The primary focus of the meeting was to “discuss and make recommendations on methods to assess the potential of disease transmission by multiple-use nozzle jet injectors” (Federal Register, 2005), which was one of the recommendations given at the 1999 hearing.

The hearing had been the most comprehensive discussion yet on the risks of MUNJI devices. Dr. Friede of the WHO gave an explicit presentation on the inherent design faults of MUNJIs, presented numerous studies that evaluated cross-contamination and addressed how those studies upheld to later advances in science (FDA, 2005a).

The panelists also addressed pertinent questions such as the adequate volume of blood for transmitting viruses and whether an acceptable level of risk exists when using MUNJIs (FDA, 2005b). Many of the questions had already been discussed within a WHO/CDC meeting held in 2004 but were reiterated for the FDA panel members.

No conclusions were reached by the end of the hearing. The FDA advisory committee did not release a draft guidance on jet injectors until 2009.

 

2009 FDA Draft Report – Draft Guidance for Industry and FDA Staff: Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products
In 2009, the FDA published a draft guidance on needle-free devices for public review and comment. The publication was the first ever guidance document for needle-free devices. Previously multi-use nozzle jet injectors circumvented regulatory standards. Devices developed prior to the 1976 regulation of medical devices were “grandfathered” onto the market. Jet injectors developed after the enactment of the 1976 law cleared regulation on the basis that they were substantially equivalent to multi-use nozzle jet injectors already on the market (Weniger & Papania, 2013). These loopholes allowed MUNJIs to bypass safety testing in the past.

FDA’s draft document served as an instruction manual for those submitting a pre-market application for needle-free devices. The document discussed design features, construction materials, performance testing, sterility issues and product labeling. Applicants finally knew what information the FDA wanted in order to be granted pre-market approval of a prototype.

The draft document acknowledged the risk of cross-contamination with jet injectors and advised against development of such reusable devices. The FDA stated,

Disease transmission may result from cross-contamination in reusable needle-free injectors, e.g., Multi-Use-Nozzle Jet Injectors (MUNJIs). There is a potential for disease transmission when blood contamination of the fluid path or injectable product occurs during a previous injection. Contamination can occur on the skin-contacting surface of the injector or inside the injector from splash-back. It is also possible that the replaceable cap may become contaminated…FDA generally recommends against developing injectors that require between-use cleaning of any component in or around the fluid path (FDA, 2009).

 

2013 FDA Report – Guidance for Industry and FDA Staff: Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products
In June of 2013 the FDA published its final version of the guidance document for needle-free devices. FDA received several comments on the 2009 draft guidance, which led to several changes.

One such change was the heightened language in the section cautioning against the use of multi-use nozzle jet injectors due to the risk of cross-contamination. The final version stated,

The vast majority of injectors are approved or cleared for single patient use. In general, multi-patient use injectors (e.g., reusable needle-free Multi-Use-Nozzle Jet Injectors) raise significant concerns for the risk of blood born pathogen and skin contaminant transmission from patient to patient. For example, there is a potential for disease transmission when blood contamination of the fluid path or the injectable product occurs during a previous injection. Contamination can occur on the skin-contacting surface of the injector or inside the injector from splash-back. It is also possible that the replaceable cap may become contaminated. In addition, in-between use cleaning of any component in or around the fluid path may result in contamination (emphasis added) (FDA, 2013).

Here the FDA clearly advises against the use of multi-use nozzle jet injectors due to significant concerns of cross-contamination of blood-borne pathogens between patients.

 

Conclusion
FDA’s 1999 and 2005 hearings eventually led to the development of a guidance document for premarket submissions of needle-free devices. Ultimately the FDA discouraged the use of MUNJIs due to “significant concerns” of blood-borne disease transmission. By 2013 disposable-cartridge jet injectors were standardized for administering immunizations.

Following the 1999 hearing, the FDA was to continue post market surveillance of MUNJIs devices. Personally, I question how involved was this post-market surveillance. It is my presumption that the FDA only assessed complaints filed under their reporting system known as MedWatch. The FDA should have been in communication with the Department of Defense and Department of Veterans Affairs to inquire if soldiers and veterans, who were the largest population subjected to jet injectors, had experienced any adverse effects or if any large outbreaks, such as Hepatitis C, had emerged.

Lastly and most interestingly, despite the vast amount of information presented on the inherent risks of MUNJIs within these two hearings, the FDA never sought a ban on MUNJI devices. In 2013, I sought clarification on this issue. The FDA stated,

According to FDA’s updated communication on the use of jet injectors to deliver vaccines, data to support their safety and effectiveness have not been submitted to the FDA for evaluation. However, the FDA has not “banned” them. [Full copy of letter here.]

One would wonder, if a medical device has been discouraged due to significant concerns why not impose a ban?

 

References:

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1992 Navy Report Documenting Ped-O-Jet Injections Caused Soldiers to Bleed Vanishes

“There are no records responsive to your request,” states a Freedom of Information Act denial letter from the Department of the Navy.

Yet the report surely had existed at one time. The document was referenced by a source associated with the CDC in 1996.

It remains unclear if the report has been lost amidst boxes of paperwork never catalogued or digitized or if it was outright destroyed pursuant to federal law.

Despite the report simply vanishing, a small fragment of its contents has survived through the source that cited it (Fields, 1996).

The 1992 Navy report by C. McCann, titled, Observations of US Navy Influenza Campaign with Ped-O-Jet Injectors, from Bremerton Naval Base documented the mass inoculations of military personnel with Ped-O-Jet injectors and also recommended one known specification for industry standards.

The Navy’s recommendation requested that the percent of bleeders following Ped-O-Jet injections be “5% or less within 2 seconds” of an injection. This specification is known as the bleeding rate and was once used an evaluation marker to deem what was an acceptable amount of bleeders following jet injection.

Juxtaposing the Navy’s recommendation to the World Health Organization who gave a recommendation that 5% or less bleed within 30 seconds, signifies the Navy would like the threshold to be low and that it be permissible if a lot of soldier’s bled during jet injections.

For the Navy to request that it be acceptable for bleeding to occur after two seconds, demonstrates they must be under the impression that after two seconds the jet injector nozzle would have been removed from the patient’s skin and thus no longer pose a threat in transferring blood and infectious viruses. If this was their line-of-thought, it would show two errors: First, the Navy was not abiding by the manufacturers instructions to hold the jet injector upon the patient’s skin for three seconds following the injection. Otherwise, if the Navy did hold the jet injector in place for a full three seconds and they also reported bleeding at the injection site after two seconds, would grossly implicate that the jet injector was contaminated with blood.

Second, the Navy was only deeming the presence of visible blood as a threat. They were ignorant to the inherent design faults that these jet injectors posed, whereby splash-back contaminated the jet injector nozzle, fluid suck-back (caused by the device being pressurized) literally sucked fluid and blood upon the nozzle orifice back into the internal fluid pathway and drug reservoir, and retrograde flow, whereupon the pressure within the newly constructed hole at the injection site created a reverse flow and fluid, commingled with blood and tissue fluid, exited the injection site and traversed against the jet stream and back into the nozzle orifice.

The Navy’s recommendation for the bleeding rate proves less than 5% of soldiers bled within two seconds. It can also be inferred that more than 5% of soldiers bled after two seconds based upon the fact that the Navy did not make it their recommendation.

Regardless of how soon after an injection a vaccinee bled is a moot point. Subsequent research on jet injection has also shown the occurrence of pathogen transfer without any visible bleeding at the injection site (Brink et al, 1985; de Souza Brito, 1996; Kelly et al., 2008). Even when the Ped-O-Jet was used correctly, and incorrectly, in an unpublished Brazilian study, the device transferred enough blood to contain blood-borne pathogens despite delayed bleeding or the absence of visible bleeding at the injection site (Hoffman et al., unpublished).

 

References:

  • (Brink et al., 1985) Brink PRG, van Loon AM, Trommelen JCM, Gribnau FWJ, Smale-Novakova IRO. Virus transmission by subcutaneous jet injection. J Med Microbiol. December 1985; 20(3): 393-397.
  • (de Souza Brito, 1996) de Souza Brito G. Multi dose jet injectors and safety aspects in Brazil. CDC & WHO Meeting on Jet Injectors. Atlanta, October 2-3, 1996. (communication paper).
  • (Fields, 1996) Fields R. Participation in Meeting: Jet injectors for immunization; current practice and safety; improving designs for the future. WHO/CDC Meeting. Atlanta, GA. 2-3 October, 1996. Available at: http://pdf.usaid.gov/pdf_docs/PNABZ997.pdf.
  • (Hoffman et al., unpublished) Hoffman PN, Abuknesha RA, Andrews NJ, Brito GS, Carrasco P, Weckx LY, Moia LJMP, Silva AEB, Lloyd J. A field trial of jet injector safety in Brazil. (unpublished).
  • (Kelly et al., 2008) Kelly K, Loskutov A, Zehrung D, Puaa K, LaBarre P, Muller N, Guiqiang W, Ding H, Hu D, Blackwelder WC. Preventing contamination between injections with multi-use nozzle needle-free injectors: a safety trial. Vaccine (2008) 26, 1344-1352.

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Inherent Faults of the Ped-O-Jet

In reviewing research on the safety-testing of the Ped-O-Jet, the faults of this widely-used device have emerged. These are issues extending beyond the complaints of the Ped-O-Jet being too heavy for delivering hundreds to thousands of inoculations, issues with the nozzle orifice clogging too easily and the gun’s necessary need for routine maintenance. Without question such performance issues would affect the safety of the device. However, we are focusing on the inherent faults that prevent the Ped-O-Jet from ever being called safe.

Jet Infectors - Ped-O-Jet Diagram

(Ismach, 1978)

 

I. Wiping the external surface of the Ped-O-Jet’s nozzle did not prevent cross-contamination. Whether the nozzle was wiped or not wiped transmission of relevant volumes of blood capable of transmitting blood-borne pathogens were observed (Grabowsky et al., 1994; Hoffman et al., unpublished). This was due to a phenomenon called retrograde flow.

 

II. Retrograde Flow. During the end of jet injection process, the pressure of the jet stream impinging the skin would be less than the pressure of the fluid deposited within the newly constructed hole in the vaccinee’s arm. Since the jet stream was too weak to further deepen the hole, the deposited fluid moved backwards and flowed out of the hole and back into the jet injector. This would be an undesirable, yet expected phenomenon in almost every jet injection due to the continuous depletion of pressure.

  • Joy Baxter and Samir Mitragotri both described the mechanical workings of jet injection in their 2006 paper. Baxter, a researcher for Unilever Research and Development, and Mitragotri, a chemical engineer at Harvard University, wrote, “Backflow of the jet is observed during hole formation if the volumetric rate of hole formation in the skin is smaller than the volumetric flow rate of the jet liquid into the skin” (Baxter & Mitragotri, 2006).
  • In 1997 the World Health Organization (WHO) hypothesized of retrograde flow as preliminary data from safety tests were reported. The WHO stated,

contamination of the fluid path occurs along the jet-stream at the end of the shot when pressures in the liquid column at the site of the injection begin to exceed the pressures at the injector head…Similar conclusions can be reached from the results of parallel tests in-vitro on the PED-O-JET (now AM-O-JET) at the Programme for Appropriate Technology in Health (PATH – USA). These tests confirmed a correlation between the extent of contamination and the level of back-pressure in simulated skin models (WHO, 1997).

  • Peter Hoffman studied cross-contamination via jet injectors at the request of the WHO and found retrograde flow within his laboratory investigations of the Ped-O-Jet. Hoffman stated,

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).

  • In quoting Rebecca Voelker who paraphrased it so simply, “Hoffman said jet injection builds pressure in the skin that is greater than the pressure in the injector, causing a small backflow of blood onto the device” (Voelker, 1999).
  • In 1977, researchers Philip Neufeld and Leon Katz from the Bureau of Medical Devices at Canada’s Department of National Health and Welfare studied the Ped-O-Jet. The researchers noted “a low-pressure ‘tail’ at the end of the injection” (Neufeld & Katz, 1977). Here is evidence that low-pressure at the end of the injection existed in the Ped-O-Jet in the 1970s during the height of this device. The low-pressure at the end of the injection indicates the likelihood of retrograde flow, in which the vaccine, commingled with blood, went back into the Ped-O-Jet.

 

 

III. The Ped-O-Jet’s check-valve did not prevent fluid and blood on the nozzle tip from being sucked back into the internal fluid pathway and drug reservoir.

Close-up of the Ped-O-Jet Nozzle

 

Ped-O-Jet Ball Check Outlet Valve #44(Ismach, 1962)

  • Inventor of the Ped-O-Jet, Aaron Ismach, stated within his 1962 patent that his invention is “free from danger of sucking fluid back from a patient either during or after the firing cycle is completed so that the danger of cross-infection is almost completely avoided” (Ismach, 1962). His assertion reveals MUNJIs faced issues with check-valves. Subsequent researcher has revealed the Ped-O-Jet was no exception to this inherent design fault.
  • In 1977, CDC’s Hepatitis Laboratories Division conducted safety testing on the Ped-O-Jet. The researchers observed a drop of fluid remained on the injector nozzle after firing and would disappear back into the nozzle orifice within 3 to 5 seconds. The researchers concluded, “These manipulations causing disappearance of the fluid drop are common during clinical use of the jet injector” (CDC, 1977).
  • In 1994, the CDC retested the safety of the Ped-O-Jet. After artificially contaminating the underbelly of a shaved rabbit with Hepatitis B surface antigen (HBsAg), a sterile Ped-O-Jet was placed upon the site and administered an injection. The subsequent injection was fired into a vial and tested for HBsAg. The results found the ejected fluid of the next shot fired was positive for HBsAg in 19 out of 50 (38%) of the samples (Grabowsky et al., 1994). Cross-contamination of HBsAg from the skin surface to the ejectate of the subsequent shot was due to either fluid suck-back or retrograde flow.
  • The CDC collaborated with American Jet Injector Corporation and the University of Florida to test the safety of the Am-O-Jet, a MUNJI device. The Am-O-Jet was an identical design of the Ped-O-Jet. Within this study the researchers admit the check-valve had been redesigned; thus further implicating the inherent design faults of previous Ped-O-Jet models. It is noteworthy to add, the researchers found rates of contamination were significant with the Am-O-Jet (Sweat et al., 2000).

 

IV. Every time the Ped-O-Jet became contaminated it remained contaminated for the following two consecutive shots. This means once the Ped-O-Jet became contaminated with blood, the next two people in line would be exposed to that blood. Once the Ped-O-Jet became contaminated with a blood-borne pathogen, the next two people in line would be exposed to that blood-borne pathogen.

Transmission

  • CDC’s 1977 investigation of the Ped-O-Jet found, after the nozzle was contaminated, the ejected fluid of the next shot fired was positive for HBsAg in 4 out of 5 (80%) of the samples. The second shot fired after the nozzle was contaminated was positive in 3 out of 5 (60%) of the samples. The third, fourth and fifth shots fired were all negative. These results indicated that once the Ped-O-Jet became contaminated it remained contaminated for the next two consecutive shots (CDC, 1977).
  • CDC’s 1994 investigation of the Ped-O-Jet administered a sterile injection to the underbelly of a HBsAg-contaminated rabbit and then administered a subsequent shot into five vials. The test was repeated 10 times. So each test consisted of five samples and ten tests were conducted creating a total of 50 samples. The researchers only reported that 19 of the 50 samples were HBsAg-positive indicating that more than just the first shots were contaminated. We can presume that all ten of the first shots were positive and therefore nine of the seconds shots tested were positive (Grabowsky et al., 1994).
  • In WHO’s 1998 field trial in Brazil, researchers administered a Ped-O-Jet injection to patients infected with Hepatitis B and Hepatitis C. After administering an injection, the subsequent three injections were fired into three separate vials. Results found that 13 out of 117 (11.1%) of the subsequent first shots contained more than 10 picoliters of blood. Results of the second “shot” found 4 out of 117 (3.4%) of the samples were positive and the third “shot” found no contamination (Hoffman et al., unpublished).

 

V. In studies upon humans, cross-contamination of blood occurred via the Ped-O-Jet despite the lack of visible bleeding at the injection site or any visible blood contamination upon the Ped-O-Jet’s nozzle.

  • The Brazilian Ministry of Health conducted a study to assure the safety of the Ped-O-Jet during routine military vaccinations in 1991. The researchers found, “there was little to no correlation between visible bleeding and detection of occult blood in the successive vaccine doses. Only one person had both” (de Souza Brito et al., 1994; de Souza Brito, 1996). There was no visible bleeding at the injection site in 27 out of 28 (96.4%) of the ejectates which contained blood, indicating blood transferred within microscopic levels not visible to the human eye.
  • In 1998 the WHO chose to replicate the Brazilian study. In this field trial, human volunteers infected with Hepatitis B and Hepatitis C received an injection with a Ped-O-Jet injector. There was no visible bleeding at the injection site in 14 of the 29 (48.2%) of the ejectates which contained blood. Of which 11 samples of no visible bleeding were the first shot after becoming contaminated and 3 samples were the second shot after becoming contaminated (Hoffman et al., unpublished).

This same phenomenon has been observed within other jet injector models. Even though these other studies did not use the Ped-O-Jet, they establish the occurrence of cross-contamination despite the lack of visible bleeding is an established and systemic phenomenon associated with jet injection.

  • In a Dutch study, researchers assessed the degree of cross-contamination after using a Med-E-Jet injector on mice chronically infected with lactic dehydrogenase (LDH) virus (a highly infectious pathogen). Results found 16 out of 49 (33%) mice became infected with the LDH virus after receiving injections from a Med-E-Jet injector. Most shockingly, researchers observed “post-injection bleeding was relatively uncommon,” occurring in only two out of 49 (4%) of the mice. Assuming the two bleeders were amongst the mice who became infected with LDH, indicates at least 14 out of 16 (88%) of the mice became infected despite the lack of visible bleeding (Brink et al., 1985).
  • A field trial for a protector cap needle-free injector, known as the HSI-500 and as the JIMI, upon humans infected with Hepatitis B found the Hepatitis B virus was cross-contaminated regardless of the single-use protector cap being placed over the nozzle. The study also found, there was no visible bleeding at the injection site in 7 out of the 17 (41.1%) injections that tested positive for Hepatitis B. This indicates that cross-contamination of Hepatitis B virus successfully occurred within microscopic levels of blood not visible to the human eye. This study also demonstrated that Hepatitis B was able to permeate the single-use protector cap and enter the jet injectors internal fluid pathway (Kelly et al., 2008).

 

These inherent faults, as described above, are evidence the Ped-O-Jet allowed cross-contamination of blood and blood-borne pathogens between subsequent vaccinees. The Ped-O-Jet was not superior to any revival device but suffered the same undesirable effects that impacted all jet injectors.

 

References:

  • (Baxter & Mitragotri, 2006) Baxter J, Mitragotri S. Needle-free liquid jet injections: mechanisms and applications. Expert Rev Med Devices Sep 2006;3(5):565-74.
  • (Brink et al., 1985) Brink PRG, van Loon AM, Trommelen JCM, Gribnau FWJ, Smale-Novakova IRO. Virus transmission by subcutaneous jet injection. J Med Microbiol. December 1985; 20(3): 393-397.
  • (CDC, 1977) CDC. DHEW Memorandum: Informal Quarterly Report of October-December 1977. From: Special Investigations Section (Petersen NJ, Bond WW, Carson LA) to: Deputy Director (Favero MS), Hepatitis Laboratories Division, Phoenix, AZ (unpublished).
  • (de Souza Brito, 1996) de Souza Brito G. Multi dose jet injectors and safety aspects in Brazil. CDC & WHO Meeting on Jet Injectors. Atlanta, October 2-3, 1996. (communication paper).
  • (de Souza Brito et al., 1994) de Souza Brito G, Chen RT, Stefano IC, Campos AM, Oselka G. The risk of transmission of HIV and other blood-born diseases via jet injectors during immunization mass campaigns in Brazil. 10th International Conference on AIDS, Yokohama, 7-12 August 1994;10(1):301 (abstract no. PC0132, http://www.aegis.com/conferences/10wac/pc0132.html).
  • (Grabowsky et al., 1994) Grabowsky M, Hadler SC, Chen RT, Bond WW, de Souza Brito G. Risk of transmission of hepatitis B virus or human immunodeficiency virus from jet injectors and from needles and syringes. Unpublished manuscript draft, dated January 3, 1994.
  • (Hoffman et al., unpublished) Hoffman PN, Abuknesha RA, Andrews NJ, Brito GS, Carrasco P, Weckx LY, Moia LJMP, Silva AEB, Lloyd J. A field trial of jet injector safety in Brazil. (unpublished).
  • (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 immunisation. Vaccine. 16 July 2001;19(28-29):4020-4027.
  • (Kelly et al., 2008) Kelly K, Loskutov A, Zehrung D, Puaa K, LaBarre P, Muller N, Guiqiang W, Ding H, Hu D, Blackwelder WC. Preventing contamination between injections with multi-use nozzle needle-free injectors: a safety trial. Vaccine (2008) 26, 1344-1352.
  • (Neufeld & Katz, 1977) Neufeld PD & Katz L. Comparative evaluation of three jet injectors for mass immunization. Canadian journal of public health, 1977, 68: 513-516.
  • (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 May 26, 1999;281(20):1879-1881.
  • (WHO, 1997) World Health Organization. Steering group on the development of jet injection, Geneva, 18-19 March 1997. Geneva: World Health Organization, Global Programme on Vaccines and Immunizations, document, 1997;1-37.

 

© Shaun Brown and Jet Infectors, 2016 – 2017
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1966 CDC Oblivious to Risk of Bleeding During Smallpox & Measles Ped-O-Jet Vaccinations

In 1966 the Center for Communicable Diseases planned a mass smallpox and measles vaccination campaign in Western and Central Africa. The 259-page “Manual of Operations” thoroughly planned and strategized for a mass vaccination in a foreign land, chartering unknown territory. The manual reveals what CDC knew and thought about jet injectors during the 1960s.

Documented within the pages are several references to bleeding following jet injections:

  • pg. 31 “An individual will be required who can wipe off excess smallpox vaccine from the vaccination site, who might also dispense cotton when local bleeding occurs.”
  • pg. 36 “There might also be a further gap of 15-20 yards between the injection area and the area where cotton, vaccination certificates, etc. are dispersed.” The mention of cotton is indicative of bleeding following the jet injection.

However, the most incriminating portion of the manual, on page 38, shows CDC was oblivious to the risk of bleeding during the mass vaccination campaigns.

Post-vaccination Swabbing
Following intradermal injection there is frequently a residue of vaccine remaining on the skin surface which may run down the arm and after intradermal and particularly subcutaneous injection, there may be some temporary bleeding at the site of inoculation. Bleeding is of little consequence except that it is occasionally alarming to the vaccinee, but a residua of smallpox vaccine on the skin surface is undesirable because of the possibility of autoinoculation or spread of virus to others and to the environment in general.

For these reasons, cotton or other absorbent material should be part of the routine supplies of an operating field team. A local volunteer can be assigned the task of swabbing the vaccination sites and dispensing cotton to vaccinees as indicated (emphasis added).

1966 CDC - Weset and Central African Smallpox Eradication:Measles Control Program - Manual of Operations pg. 38

“Bleeding is of little consequence,” stated the CDC. Clearly, the administration was ignorant to the risk of transmitting blood-borne viruses. The CDC’s disregard for bleeding during jet injections would also indicate the presence of blood was either underreported or not reported within their studies on jet injection in the 1960s.

In preparation for mass vaccination campaigns in distant and remote areas, the manual described how to cold sterilize jet injectors. On pages 257 to 258, the vaccinator is instructed to “scrub disassembled parts with a scrub brush in a pan of soapy (bar soap) water.” Then after rinsing in clean water to reassemble the jet injector and “fill chamber with tincture of iodine solution (gun in cocked position) and leave for 5 minutes.” Followed by flushing the gun with 10 shots of sterile water.

CDC stated this sterilization method has been proven effective.

This process for sterilization was tested by contaminating four injectors with dirt containing 20,000 aerobic and anaerobic organisms per gram (dirt treated so that spores were present). With this degree of contamination, no growth was obtained from any of the guns.

Yet testing for organisms is not the same as testing for viruses. This manual gave no consideration to sterilizing against infectious viruses.

Seven months after the manual’s publication, a memorandum was issued stating the number of times for flushing the iodine solution was insufficient. Residual traces of iodine were found within the injector and were affecting the potency of the measles vaccine, as noted on page 259. This calls into question the CDC’s method for cold sterilization of jet injectors.

In 1977 the CDC finally investigated if serum hepatitis could be transmitted via jet injectors. Article – CDC’s Unpublished Jet Injector Studies – Part 1

 

A full copy of CDC’s 1966 manual, West and Central African Smallpox Eradication/Measles Control Program – Manual of Operations, is accessible here.

© Shaun Brown and Jet Infectors, 2016 – 2017
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VA’s Double Standard: VA Recognizes Non-military Exposures as Risk Factors Despite the Lack of Scientific Proof

VA Media Relations officer Ndidi Mojay stated in a 2016 news article, “We would consider changing the way we process HCV air gun claims if available science indicated that there was some likelihood that contaminated air guns actually transmitted HCV.”

Currently VA acknowledges the nexus between Hepatitis C and jet injectors as “biologically plausible,” but refuses to comment any further on the issue. VA’s current stance on jet injectors does not preclude a veteran from obtaining service-connection but it does not guarantee it either. Decisions within the Veterans Benefits Administration have been inconsistent on jet injectors. Inconsistent Renderings in VA: Comparing Granted vs. Denied Jet Injector Claims

Yet the VA has recognized non-military exposures, such as intranasal cocaine use, tattooing and body piercing as risk factors for Hepatitis C despite the lack of scientific proof. From 2005 to the present, VA has even acknowledged the lack of scientific data for these exposures upon their website  (https://www.hepatitis.va.gov/provider/reviews/transmission.asp).

Jet Infectors - VA Hepatitis C Virus Transmission

“There are no conclusive data to show that persons with a history of exposures such as intranasal cocaine use, tattooing or body piercing are at an increased risk for HCV infection based on these exposures solely. It is believed, however, that these are potential modes of HCV acquisition in the absence of adequate sterilization techniques.”

Despite the lack of “conclusive data,” these exposures are listed as recognized risk factors upon VA’s website (https://www.hepatitis.va.gov/provider/reviews/screening.asp).

Jet Infectors - VA Hepatitis C Screening

VA has long held a double standard by recognizing non-military exposures as risk factors for Hepatitis C despite the lack of scientific proof. Yet jet injectors, which were widely used within the military, will not be recognized officially as a risk factor until scientific evidence emerges.

This is a double standard that benefits the Department of Veterans Affairs and not the people it was created to serve—veterans.

However, despite VA’s enigmatic stance, several things remain certain:

  • VA has unofficially acknowledged the nexus within its memorandum and by the mere granting of service-connection in a substantial number of cases.  Military Jet Gun Injections Transmitted Hepatitis: an assessment of VA claims
  • The evidence citing an association between Hepatitis C and jet injectors has emerged, it is now a question of whether or not the VA will acknowledge the evidence.

Footnote:
The above VA links have been archived and can be accessed here:

https://web.archive.org/web/20171015144741/https://www.hepatitis.va.gov/provider/reviews/transmission.asp
https://web.archive.org/web/20171015145220/https://www.hepatitis.va.gov/provider/reviews/screening.asp

© Shaun Brown and Jet Infectors, 2016 – 2017
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PCNFIs Fail to Prevent Contamination

Protector cap needle free injectors (PCNFI) were intended to be the safer mode of jet injection. The idea of placing a protective barrier between the patient’s skin and reusable nozzle allowed for the safety regulators sought and the expediency consumers wanted. As the timeline will show the concept of PCNFIs, although innovative, failed safety-testing and was abandoned as a means of administering immunizations.

Currently, several PCNFI devices are used as medical instruments. These devices are being used consecutively upon a single patient to administer anesthesia and medicine. As long as these devices are adequately sterilized through autoclaving before being used on a subsequent patient they pose no threat in the transmission of pathogens.

Am-O-Jet______________________________________________________________________________
1995
Robert Harrington, the former President and CEO of Vernitron Medical Products which previously owned Ped-O-Jet, creates the American Jet Injector company. He uses an identical design of the Ped-O-Jet to create the Am-O-Jet injector (FDA, 1999), which came in an electric model and a non-electric foot-pedal model.

1996 July
Am-O-Jet receives FDA 510(k) premarket approval on July 26th of 1996 (FDA, 1996).

1996 October
Harrington attends the CDC/WHO conference on jet injector safety and introduces his Am-O-Jet injector as a viable option for mass jet injection (Fields, 1996).

1997 May
Harrington attends the WHO/CDC conference on jet injector safety and announces plans to conduct safety-trials utilizing his Am-O-Jet injector. In the plan for one such trial, the Am-O-Jet would be used upon 1,000 Brazilian military recruits. After each injection the ejectate of the subsequent “shot” would be sent to United Kingdom’s Public Health Laboratory Service for testing (WHO, 1997). However, this field trial never used the Am-O-Jet or a protector cap. The study used Ped-O-Jet injectors owned by Brazil’s Ministry of Health. Moreover, the study used civilian volunteers infected with Hepatitis B and Hepatitis C and not military recruits.

1997 November
Keystone Industries conducts a product recall on the Ped-O-Jet over liability concerns that the device could transmit blood-borne pathogens. Article – Ped-O-Jet Withdrawal Letter to DoD Over Risk of Disease Transmission

1999
Harrington speaks at a FDA panel discussion on jet injector safety. “What is the future of Am-O-Jet’s high workload injectors? We believe in a traditional reusable nozzle, reusable work path. We’re continuing the production of that model,” said Harrington, who refuses to believe any safety risk exists with Ped-O-Jet / Am-O-Jet injectors (FDA, 1999). Moreover, Harrington outright lies, stating the device was used correctly within the U.S. military for 35-years and no evidence exists to the contrary. Article – Improper Military Jet Injections

2000
Am-O-Jet undergoes a Small Business Innovative Research Phase I project in conjunction with Dr. Bruce Weniger of the CDC, and Dr. James Sweat from the University of Florida. This safety-test replicated and expanded upon a previous safety study on jet injectors. Five different experiments were conducted in this series, including use of a plastic disposable nozzle. Within this study a saline solution was injected into a pig with the Am-O-Jet. The subsequent “shot” was fired into a vial and the ejectate was assessed for contamination using an ELISA (i.e., a highly sensitive test to detect albumin). Results of the study were not adequately reported although backsplash and contamination were observed (Sweat et al., 2000).

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

The results of Sweat and colleagues study were not fully published. Presumably Mr. Harrington did not wish to reveal results which would implicate his jet injector. Following this study, development of the Am-O-Jet was abandoned.

 

FELTON INTERNATIONAL___________________________________________________________
1998
Felton International, a jet injector developer and manufacturer, bought the rights to 17 Russian jet injectors from the Chemical Automatics Design Bureau of Voroenzh, Russia and MedEquipment. The BI-100 jet injectors utilize a protector cap between patients (Leon & Loskutov, 2005; Weniger, 2013).

2002 September
Felton Int. conducts three field evaluations for a prototype protector cap needle-free injector in Senegal. The device, which was shaped like a gun, was found to be bulky and hard to handle. In conjunction with PATH, the device’s grip was redeveloped into a “torch” grip design (Zehrung, 2003).

2003
Felton Int. receives an award from the U.S. Army for $119,570.00 to conduct a Phase I study on the development of a needle-free jet injection system. “The Phase I effort comprises detailed pharmacokinetic studies and preliminary and detailed device design. The fabrication of a size appropriate injector for test rodents will also be undertaken in Phase I.” (SBIR, 2003a).

Felton Int. receives a second award from the U.S. Army for $688,615.00 to conduct a Phase II study of their prototype jet injector.

The second phase of this project will consist of the following three tasks: 1) Develop and quantify a prototype needle-free injector. This task includes product, environmental and human safety testing. A protector cap will be used to prevent pathogen transfer between patients; 2) Conduct trials on non-human primates to determine the percent of enzyme delivered, the peak level of enzyme activity and the duration of the enzyme at that level; 3) Determine the efficacy of this enzyme as a bioscavenger by exposing injected rodents to OP or pesticides; and 4) Deliver a prototype injector to the Army for chemical warfare studies (SBIR, 2003b).

Felton goes on to state their overall goal:

The overall goal of this project is to provide the Army with a system to allow rapid injection of the enzyme into soldiers in the event of a chemical attack on the battlefield. In order to achieve this goal, the usability, safety and efficacy of the device will be proven. For the military, this device would allow rapid injection of troops prior to a potential chemical exposure. In this situation, troops should be injected 12 hours prior to possible exposure and re-injected weekly as long as the threat continues(SBIR, 2003b).

2003 November
Felton Int. presented a prototype protector-cap needle-free injector at the Joint Service Scientific Conference on Chemical & Biological Defense Research.

2004
PATH conducts an in vitro fluorescein test upon the HSI-500. Use of fluorescein dye made any contamination visible. Results of this test showed contamination upon the protector-cap but no contamination within the ejectate (FDA, 2005).

2004 August – October
Felton Int., in conjunction with PATH, conducted a pilot study at Huntington Medical Research Institute Liver Center in Los Angeles, California. The study assessed the safety of the prototype HSI-500, a protector-cap needle-free injector, upon 5-15 civilian volunteers who had a high titer of Hepatitis B. The aim of the study was to detect HBV within the ejectate following an injection into a HBV-carrier and to assess injection site bleeding (Zehrung, 2004). Results of the pilot study found no contamination, and led to the approval and development of a larger scale study in 2006 (Kelly et al., 2008).

2005 October
Felton Int. presented a prototype protector-cap needle-free injector to the Department of Defense Research. The presentation, titled Reintroducing High Workload Needle Free Jet Injectors to the US Military Medical Community, displayed the HSI-500 PCNFI device (Leon & Loskutov, 2005). The device was also known as the JIMI which was an acronym meaning Jet Injector for Mass Immunization.

2006 July – October
Felton Int. and PATH conducted a large-scale study upon the safety of the HSI-500. The study was conducted in Beijing, China among HBV-positive adults. Despite the cap’s design to prevent cross-contamination, “the study ended early because the PCNFI failed to prevent contamination in the first batch tested (8.2% failure rate). The injections were very well tolerated, with most followed by no bleeding (81.2%) or mild bleeding (7.8%).” Data collected also found moderate bleeding (0.5%).

Most shockingly, the published data demonstrates but the researchers failed to discuss, that cross-contamination of HBV occurred without any visible bleeding at the injection site. In 7 out of the 17 injections that tested positive for cross-contamination researchers observed no visible bleeding at the injection site (see Table 1 within the study). This indicates that cross-contamination of blood-borne viruses successfully occurred within microscopic levels of blood not visible to the human eye (Kelly et al., 2008).

Following this study any development and testing upon the HSI-500 (JIMI) was abandoned. PCNFIs were deemed unsafe for administering immunizations upon consecutive patients.

Since Felton International (now Pulse Needle-Free Systems) received funding from the U.S. Army, I reached out to the company to further clarify if at anytime was the HSI-500 or any other of their devices utilized upon any military personnel. Ed Stevens, the company’s President stated, “No, that study never involved military personnel.  (It was not a human study.) Felton/Pulse devices were never used on U.S. military personnel, and now our products are only used on animals.”

 

Conclusion____________________________________________________________________________
Two publicized PCNFIs both failed to prevent contamination. The Am-O-Jet, a Ped-O-Jet that allowed a protector cap to cover the nozzle, failed to prevent cross-contamination in a laboratory trial on pigs (Sweat et al., 2000). Another PCNFI, the JIMI injector also known as the HSI-500, showed promising results in a pilot study at Huntington Medical Center, although later failed to prevent cross-contamination of hepatitis B in a field trial in China (Kelly et al., 2008). Further development of PCNFI devices for administering immunizations were abandoned and the industry focused on development of disposable-cartridge jet injectors for administering immunizations.

 

References:

  • (FDA, 1996) Food & Drug Administration. 510(k) Premarket Notification: American Jet Injector Corp. – K962017. Accessible at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K926017.
  • (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.
  • (Fields, 1996) Fields R. Participation in Meeting: Jet injectors for immunization; current practice and safety; improving designs for the future. WHO/CDC Meeting. Atlanta, GA. 2-3 October, 1996. Available at: http://pdf.usaid.gov/pdf_docs/PNABZ997.pdf.
  • (Kelly et al., 2008) Kelly K, Loskutov A, Zehrung D, Puaa K, LaBarre P, Muller N, Guiqiang W, Ding H, Hu D, Blackwelder WC. Preventing contamination between injections with multi-use nozzle needle-free injectors: a safety trial. Vaccine (2008) 26, 1344-1352.
  • (Leon & Loskutov, 2005) Leon NJ & Loskutov AY. Reintroducing High Workload Needle Free Jet Injectors to the U.S. Military Medical Community. Presentation to Department of Defense Research. 1 October 2005.
  • (SBIR, 2003a) Small Business Innovation Research. Felton International: Developing Human-Compatible Needleless Delivery Systems for Administering Bioscavengers – Phase I. 2003. Accessible at: https://www.sbir.gov/sbirsearch/detail/165599.
  • (SBIR, 2003b) Small Business Innovation Research. Felton International: Developing Human-Compatible Needleless Delivery Systems for Administering Bioscavengers – Phase II. 2003. Accessible at: https://www.sbir.gov/sbirsearch/detail/165601.
  • (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.
  • (Weniger, 2013) Weniger BG. Jet Injection Bibliography. 11 July 2013.
  • (WHO, 1997) World Health Organization. Steering group on the development of jet injection for immunization. May 14, 1997. [draft]
  • (Zehrung, 2003) Zehrung D. PATH’s Experience from Jet Injector R&D and Field Assessment in Developing Countries. Presentation for Innovative Administration Systems for Vaccines. Rockville, Maryland. 18 December 2003.
  • (Zehrung, 2004) Zehrung D. Jet Inject for Mass Immunization: Design Update and Safety Testing Strategy. Presentation for Global Vaccine Research Forum. 10 June 2004.

© Shaun Brown and Jet Infectors, 2016 – 2017
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Impact of CDC’s 1993-94 Unpublished Study – Part II

Following Grabowsky and colleagues evaluation of the Ped-O-Jet, officials within the CDC initiated meetings to discuss the risks of multi-use nozzle jet injectors (MUNJI).

1995 CDC / WHO Meeting – Review the Safety of Jet Injectors
In November of 1995, the CDC and World Health Organization (WHO) gathered for a meeting in London titled, Review the Safety of Jet Injectors. Those present were CDC and WHO experts on device safety, vaccine safety, and laboratory testing. Amongst the attendees were Dr. Robert Chen of the CDC, John Lloyd of the WHO, Dr. Peter Hoffman from the United Kingdom’s Public Health Laboratory Service, and a representative from PATH (Fields, 1996). Dr. Chen had previously been involved in CDC’s safety testing of the Med-E-Jet and Ped-O-Jet (Chen).

The goal of this meeting was to rewrite the safety standards for all jet injector devices. CDC and WHO both agreed, the “risk of cross infection must be zero” (PATH, 1996). The CDC explained this “zero tolerance” level means “no contamination should be detectable on any reusable surface of the deice that comes into direct or indirect contact with the patient’s skin” (Fields, 1996). Both agencies agreed for these devices to be attractive to consumers, they should remain “competitive with [the] current price of autodestruct syringes.” Moreover, both agencies recommended that jet injectors should be regulated and undergo testing to ensure safety performance (PATH, 1996).

WHO announced that Dr. Peter Hoffman of the UK’s Public Health Laboratory Service would be overseeing “the design and implementation of a new laboratory safety test to evaluate all injectors against this new standard” of zero tolerance (Fields, 1996).

 

1996 CDC & WHO Conference – Jet Injectors for Immunization, Current Practice and Safety, Improving Designs for the Future
In October of 1996, members of CDC’s National Immunization Program along with the WHO extended the discussion on jet injectors to include various health agencies, manufacturers, and consumers. The goal of this meeting was for all involved parties to discuss the safety of existing jet injectors and to develop more stringent specifications for the development of a new generation of jet injectors. Amongst the attendees of the meeting were CDC researchers Dr. Robert Chen and Walter Bond, as well as Dr. Glaucus de Souza Brito from the Brazilian Ministry of Health, former Ped-O-Jet CEO Robert Harrington and the current owners of Ped-O-Jet, Keystone Industries.

Walter Bond, who was a part of all three of CDC’s jet injector studies, served as an expert panelist on jet injector safety. “Existing jet injectors, such as Ped-O-Jet,” stated Bond, “are not particularly easy to contaminate, but once they are contaminated, they can indeed transmit disease” (Fields, 1996).

Also during the meeting, the committee identified the need for additional safety testing. “Examining ejectates from Ped-O-Jet vaccinations given to new military recruits in the U.S.…would represent best-use circumstances for the jet injector,” concluded the committee (Fields, 1996). However, in the following year Keystone Industries informed the Department of Defense (DoD) of its intent to withdraw and stop manufacturing the Ped-O-Jet over risk of cross-contamination. Consequently, in December of 1997 DoD stopped using all MUNJI devices, including the Ped-O-Jet. The study, which intended to examine the ejectates of Ped-O-Jet vaccinations from military recruits, was never conducted.

The 1996 joint CDC/WHO meeting also identified several countries had allowed jet injector devices to be grandfathered-in and thus bypass safety regulations.

During the Atlanta meeting in October 1996 it became clear that jet injectors in the United States, U.K., France and Italy had been ‘grandfathered in’ without national regulatory controls. The reason for this appeared to be the long history of use of jet injectors without recorded mishap.

The Food and Drug Administration of the United States informed the Atlanta meeting that they intend to review the status of jet injection devices with a view to develop such regulation in the near future (WHO, 1997).

 

The CDC/WHO conference led to further discussions about jet injector safety within CDC and WHO, initiated discussions within the FDA, and would later prompt the manufacturer of Ped-O-Jet to withdraw it’s product from the Department of Defense.

These subsequent discussions have been outlined within the following articles:

 

References:

  • (Chen) Chen, Robert. Curriculum Vitae. Accessed January of 2015.
  • (Fields, 1996) Fields R. Participation in Meeting: Jet injectors for immunization; current practice and safety; improving designs for the future. WHO/CDC Meeting. Atlanta, GA. 2-3 October, 1996. Available at: http://pdf.usaid.gov/pdf_docs/PNABZ997.pdf.
  • (PATH, 1996) PATH. Low-workload Jet Injectors For Vaccine Delivery: 1987-1996. Program for Appropriate Technology in Health. 18 September 1996. pp. 1-5.
  • (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
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