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. Multi-use nozzle jet injectors had circumvented regulatory standards through certain loopholes. Devices developed prior to the Medical Device Amendments Act of 1976 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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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 publishing Dr. Sabin’s comments, the New York Times wrote that he said “jet injector guns that will be widely used in an assembly-line procedure may themselves spread disease” (New York Times, 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.
  • (New York Times, 1976) New York Times. Questions on Vaccine. New York, New York. 27 September 1976; pg. 30.
  • (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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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 1959 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 research 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 demonstrate 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.
  • (Ismach, 1962) Ismach, Aaron. “Multi-dose jet injection device.” United States Patent 3,057,349. 9 October 1962.
  • (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.

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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.

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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.

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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]

 

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CDC Evaluates the Risk of Multi-Use Nozzle Jet Injectors

Following the 1996 CDC/WHO conference, CDC continued to evaluate and engage in discussions on the risks of multi-use nozzle jet injectors (MUNJI). The timeline below shows the reports, conferences, and one collaborative study in which CDC investigated MUNJI devices. The timeline also shows a shift in CDC’s stance on jet injectors, from viewing MUNJI devices being permissible in dire situations to MUNJI’s being inherently unsafe and discouraging their use altogether.

 

1999 CDC Reports MUNJIs Pose Medium Risk in a JAMA article
In a 1999 Journal of the American Medical Association article by Rebecca Voelker is the revelation that the CDC viewed jet injectors with a reusable nozzle that was not swabbed between patients as a medium risk for cross-contamination (Voelker, 1999).
Therefore, even before the publishing of subsequent research on jet injector safety which demonstrated it did not matter if the nozzle was swabbed or unswabbed (i.e., Hoffman et al., 2001; Hoffman et al., unpublished; Sweat et al., 2000), the CDC viewed MUNJIs as a medium risk.

1999 Voelker - Eradication Efforts Need Needle-Free Delivery- CDC Diagram- Reusable nozzle is a medium risk

(Voelker, 1999)

 

2000 Am-O-Jet Fails Safety Test
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 had an identical design to the Ped-O-Jet. This study tested the potential for cross-contamination via the Am-O-Jet amongst calves and pigs. The design of the study replicated previous in vivo jet injector studies (Sweat et al., 2000). Dr. Bruce Weniger of the CDC and coauthor of the study stated, “We have detected contamination well above currently [sic] levels that we would consider indeterminate or uninterpretable” (FDA, 1999). In other words, the researchers found the rates of contamination were significant.

 

2002 (Feb. 8) CDC Report – General Recommendations on Immunization
CDC urged the use of MUNJI devices to be limited only in dire situations and when other, safer methods are not viable. The report stated,

Efforts are under way for the research and development of new high-workload JIs using disposable-cartridge technology that avoids reuse of any unsterilized components having contact with the medication fluid pathway or patient’s blood…the use of existing multiple-use-nozzle JIs should be limited . . . [and] considered when the theoretical risk for bloodborne disease transmission is outweighed by the benefits of rapid vaccination with limited manpower in responding to serious disease threats (e.g., pandemic influenza or bioterrorism event), and by any competing risks of iatrogenic or occupational infections resulting from conventional needles and syringes… (CDC, 2002).

CDC’s shift to dire use only was a minuscule step forward from the agency’s warning eight-years prior, which noted if jet injectors became contaminated there is a risk for disease transmission (CDC, 1994).

 

2002 (Sept 16) CDC & WHO Meeting – Consultation on MUNJI Safety Evaluation
CDC and WHO hosted a meeting at CDC Headquarters in Atlanta to discuss the safety of MUNJI devices. Amongst the invited attendees were WHO, CDC, FDA, USAID, PATH, International Vaccine Institute, and members of academia. During this time, the CDC endorsed the use of MUNJI devices in dire situations until disposable-cartridge jet injectors became standardized (Weniger, 2005).

 

2004 (March 30) WHO & CDC Meeting – Consultation on MUNJI Safety Evaluation
WHO and CDC hosted a subsequent meeting on jet injector safety at WHO Headquarters in Geneva, Switzerland. The goal of this meeting was to establish criteria for a new generation of jet injector devices. The attendees attempted to answer several important questions relating to the matter of cross-contamination. Questions such as: “How infectious is blood? How do we measure it? How do you model the risk? What level of risk acceptable?” (FDA, 2005).

The attendees were in agreement that a fraction of a picoliter can transmit infection. This conclusion was far different from the previous, widely-accepted yet unofficial belief that Hepatitis B is transmissible in 10 picoliters of blood or greater (FDA, 2005).

The attendees deemed it was inappropriate to make health officials decide what was an “acceptable” level of risk from using MUNJIs (Weniger, 2005). The objective of the health industry is not to contemplate risk but to sustain life and improve health.

The attendees questioned the relevance of prior animal models and recommended all future jet injector safety trials use human HBsAg carriers and the most sensitive PCR assays for detecting contamination within ejectates (Weniger, Jones & Chen). The use of Hepatitis B surface antigen (HBsAg) was not purely to assess if Hepatitis B is transmissible via jet injection but to use HBsAg, a highly infectious pathogen, as a threshold in evaluating safety. The idea being if a highly infectious pathogen is transmissible than that model of jet injector is unsafe.

Most importantly, during this meeting the CDC finally decided to abandon its attempt in developing safer MUNJI devices and discouraged the use of all MUNJI devices under any circumstance (Weniger, 2005).

2004 (May 25-26) Seventh Annual Conference on Vaccine Research
Dr. Bruce Weniger, of CDC, summarized the downfall of MUNJI devices within his poster presentation at the Seventh Annual Conference on Vaccine Research. Dr. Weniger wrote, “The U.S. military withdrew them [MUNJIs] in 1997, and WHO and CDC now caution against their use” (Weniger, 2004).

 

2004 (June 8-10) WHO Conference – Fifth Global Vaccine Research Forum
At WHO’s Proceedings of the Fifth Global Vaccine Research Forum, Dr. Weniger again stated the risks and hazards of multi-use nozzle jet injectors. “Subsequent bench studies of it [Med-E-Jet] and the more common Ped-O-Jet indicated that their nozzles could become contaminated with hepatitis B virus and pose a risk for transmission between consecutive vaccines” (WHO, 2005).

 

2005 MUNJIs Are “Inherently Unsafe”
Dr. Bruce Weniger, of the CDC, believed MUNJIs were inherently unsafe.

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).

 

2006 (Dec. 1) CDC Report – General Recommendations on Immunization
CDC reported disposable-cartridge jet injectors overcame the risks of cross-contamination posed by MUNJIs. “In the 1990s, a new generation of JIs was introduced with disposable cartridges serving as dose chambers and nozzle. With the provision of a new sterile cartridge for each patient and correct use, these devices avoid the safety concerns for multiple-use-nozzle devices” (CDC, 2006a).

 

2006 CDC Report – Needle-free Intradermal Influenza Study
CDC stated MUNJIs are “inherently unsafe.”

Safety concerns arose over multi-use-nozzle jet injectors (MUNJIs)…which use the same nozzle to inject consecutive patients without intervening sterilization. A hepatitis B outbreak in the mid 1980s caused by one MUNJI as well as other published and unpublished studies of this and other devices, indicated blood and tissue fluid containing pathogenic agents could be transmitted among patients. This led to discontinuation and recommendations against their use in public health, and market removal in 1997 of the most common device, the Ped-O-Jet®.

Since the 1990s, a new generation of safer disposable-cartridge jet injectors (DCJIs) have appeared. DCJIs avoid the inherently unsafe design of MUNJIs, since the disposable cartridge has its own sterile orifice and nozzle and is discarded between patients (CDC, 2006b).

 

2011 (Jan. 28) CDC Report – General Recommendations on Immunization
CDC reiterates the risks and hazards of jet injectors.

Jet injectors that use the same nozzle for consecutive injections without intervening sterilization were used in mass vaccination campaigns from the 1950s through the 1990s; however, these were found to be unsafe because of the possibility of bloodborne pathogen transmission and should not be used (CDC, 2011).

 

1999 – 2006 CDC’s Needle-Free Injection Technology Webpage
From 1999 to 2006, the CDC had an entire webpage devoted to needle-free injection technology. Although the site, http://www.cdc.gov/nip/dev/jetinject.htm, has since been long taken down. The webpage once provided links to reports from international and government health agencies containing information about the risks and hazards of jet injectors and links to Department of Defense websites that detailed the withdrawal of the devices by one manufacturer and the discontinuation of their use by the military. Fortunately through web.archive.org this webpage along with a substantial number of its reports were archived. CDC’s jet injector webpage can be accessed here.

 

Conclusion
CDC discouraged the use of multi-use nozzle jet injectors only after a protracted investigation and numerous meetings. CDC first investigated the safety of jet injectors in 1977, and actively investigated MUNJI devices from 1993 to 2004. Their ultimate decision, to discourage MUNJI use under any circumstance, was long overdue considering their partners at the WHO discouraged the use of MUNJIs six-years earlier.

It is important to note that although up until 2004 the CDC endorsed the use of MUNJIs in dire emergencies the devices had not actually been used in a mass vaccination campaign within the U.S. since 1997 during a meningitis outbreak at Michigan State University (Paneth et al., 2000) and within the U.S. military since December 9th of 1997 (DoD, 1997). Whereas the WHO was quick to abandon MUNJI technology, the CDC wished to keep the devices as a contingency plan. It is my opinion that the agency’s reluctance to abandon the technology was ill-considered as it delayed the inevitable and prevented any seroepidemiological studies on prior MUNJI use.

Unequivocally, CDC’s jet injector studies demonstrated MUNJIs pose a risk in transferring blood-borne pathogens between patients. Since 2004, CDC has viewed MUNJIs as “inherently unsafe,” and has repeatedly discouraged their use.

Yet to date, CDC Headquarters in Atlanta has never listed multi-use nozzle jet injectors as a risk factor in transmitting blood-borne pathogens, even despite the high prevalence of Hepatitis C amongst those who had the greatest exposure to mass jet injector inoculations—Vietnam era veterans.

 

References:

  • (CDC, 1994) Centers for Disease Control and Prevention. General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morb Mortal Wkly Rep 43:(RR-1):7–8, 1994.
  • (CDC, 2002) Centers for Disease Control and Prevention. General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). Morb Mortal Wkly Rep February 8, 2002;51 (No. RR-2): 1-35.
  • (CDC, 2006a) Center for Disease Control and Prevention. Recommendations of the advisory committee on immunization practices-(ACIP). Morb Mortal Wkly Rep. 55:(RR-15), 2006.
  • (CDC, 2006b) Centers for Disease Control and Prevention. Needle-free Intradermal Influenza Study. CDC-ISO-4785. 5 March 2006.
  • (CDC, 2011) Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices-ACIP. Morb Mort Wkly Rep. Vol. 60. No. 2. 28 Jan. 2011.
  • (DoD, 1997) Memorandum: Jet Hypodermic Injection Units. Philadelphia: Defense Logistics Agency. 9 December 1997.
  • (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 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).
  • (Paneth et al., 2000) Paneth N, Kort EJ, Jurczak D, Havlichek DA Jr, Braunlich K, Moorer G, Vanderjagt D, Sienko D, Leiby P, Gibbons C. Predictors of vaccination rates during a mass meningococcal vaccination program on a college campus. J Am Coll Health. 2000 Jul;49(1):7-11.
  • (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.
  • (Weniger, 2004) Weniger BG. Trends, challenges and opportunities for jet injection technology (presentation). National Foundation for Infectious Diseases. Seventh Annual Conference on Vaccine Research. 25-26 May 2004. Arlington Virginia.
  • (Weniger, 2005) Weniger B. Safety of Multi-use-nozzle Jet Injectors (MUNJIs) for Bloodborne Pathogen Cross-contamination (draft). Conference Notes. 7 August 2005.
  • (Weniger, Jones & Chen) Weniger BC, Jones TS, & Chen RT. The Unintended Consequences of Vaccine Delivery Devices Used to Eradicate Smallpox: Lessons for Evaluating Future Vaccination Methods.
  • (WHO, 2005) WHO. Proceedings of the Fifth Global Vaccine Research Forum. WHO/IVB/05.09. 2005.

 

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WHO Assesses the Safety of Jet Injectors

Following the 1996 CDC/WHO conference, the WHO actively engaged in meetings and conducted further evaluations on the safety of multi-use nozzle jet injectors (MUNJI). During this time, WHO continued to discourage the use of MUNJI’s under any circumstance. The timeline below shows the reports, conferences, and studies in which the WHO investigated MUNJI devices.

 

1986 WHO Report – Selection of Injection Equipment for the Expanded Program on Immunization
In October of 1986, the World Health Organization (WHO) changed its policy on the use of jet injectors. The policy change was the direct result of a hepatitis outbreak due to the use of a MUNJI device. WHO’s highly publicized statement said,

Until further studies clarify the risks of disease transmission associated with jet injectors, general caution in their use is recommended (WHO, 1986).

Their use should be restricted to special circumstances where the use of needles and syringes is not feasible because of the large numbers of persons to be immunized within a short period of time (WHO/UNICEF, 1987).

 

1995 WHO Requests the Help of Dr. Peter Hoffman
In 1995, the World Health Organization requested the help of Dr. Peter Hoffman of United Kingdom’s Public Health Laboratory Service. Dr. Hoffman was brought on to create a model to detect whether low, but infectious, volumes of blood were being transferred via various jet injectors (Fields, 1996). In a personal interview with this author in 2013, Hoffman stated,

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).

This would mark WHO’s first investigation into the safety of multi-use nozzle jet injectors.

 

1995 CDC & WHO Meeting – Review the Safety of Jet Injectors
CDC met with WHO in London in 1995 to rewrite the safety standards for all jet injectors. Also present for the meeting were Dr. Hoffman and a representative from PATH. CDC and WHO both agreed the safety standard for jet injectors should be raised to a “zero tolerance” level (Fields, 1996). This meeting subsequently led to a CDC/WHO conference on jet injector safety in 1996.

 

1996 CDC & WHO Conference – Jet Injectors for Immunization, Current Practice and Safety, Improving Designs for the Future
CDC and WHO invited various health agencies, manufacturers, and consumers to discuss the safety of jet injectors. The goal of this meeting was for all involved parties to discuss ways in achieving a zero-risk jet injector.

During the conference Dr. Hoffman gave a presentation titled, Animal-model Assessment of Jet Injector Safety, in which he described a laboratory investigation for testing cross-contamination from jet injectors (Fields, 1996).

 

1996 WHO Discourages Use of Jet Injectors
WHO unofficially reversed its 1994 policy and advised against the use of jet injectors under any circumstances. The change in policy resulted from fears of spreading blood-borne pathogens, such as Hepatitis B, Hepatitis C, and HIV with Ped-O-Jet injectors during a massive meningitis outbreak in Nigeria in 1996 (Mohammed et al., 2000). However, this policy change was not widely publicized until 1998 (Fields, 1996). Article – Nigeria Forced to Use Ped-O-Jet Injectors in 1996 Despite Fears of Spreading Hepatitis and AIDS

 

1997 Hoffman’s Initial Investigation of Med-E-Jet
Hoffman’s initial laboratory investigation in 1997 tested the volume of contamination after a Med-E-Jet injector administered an injection into calves. Working with Dr. Hoffman and the WHO was Dr. RA Abuknesha from King’s College, London. Dr. Abuknesha developed an enzyme-linked immunosorbent assay (ELISA) to detect Human Serum Albumin, which was used as a marker to detect blood within the ejectates from the jet injectors (FDA, 1999; Friede, 2003). Results from this investigation showed systemic contamination of the ejectate (WHO, 1997). At the time, Hoffman and WHO concluded,

the path of contamination may have been reflux within the jet stream. This could possibly have occurred at the end of the shot when the liquid pressure at the nozzle of the injector dies to a level lower than that of the liquid column within the skin and subcutaneous tissue of the animal…The implication of these results is that, for jet injection to be safe, the entire fluid path must be changed between injections (WHO, 1997).

While it is true that the enzyme-linked immunosorbent assay (ELISA) is used to detect Human Serum Albumin (HSA) and HSA is found within blood, saliva, and skin cells, it is also true that the researchers took extensive precautionary measures to avoid any false positives within the data.

 

1997 WHO & CDC Conference – Steering Group on the Development of Jet Injection For Immunization
Hoffman’s initial findings of the Med-E-Jet were presented at the conference. Members were also informed that contamination was believed to be due from an undesirable phenomenon called retrodgrade flow. The consensus at the conference was other jet injectors, such as the Ped-O-Jet, should be evaluated to see if they succumb to retrograde flow as well. Further laboratory and field trials were planned. Also, members agreed in pursuing development of zero-risk devices, such as disposable-cartridge jet injectors (WHO, 1997).

 

1998 (March 25) WHO Conference – Technet Consultation
At a conference in Copenhagen, WHO presented preliminary findings of it’s laboratory investigation by Hoffman and colleagues. “The results so far obtained with three injector models show that there is an unacceptable level of downstream contamination, irrespective of whether the nozzle is discarded after each injection” (WHO, 1998a). Preliminary analysis of the Ped-O-Jet found 29 percent of the samples (29 out of 100) contained more than 10 picoliters of blood. The Medivax, protector cap needle-free injector, found a 31 percent contamination rate (11 out of 35 samples). The Med-E-Jet found a 72.7 percent contamination rate (16 out of 22 samples). The researchers further speculated contamination was the result of retrograde flow which “probably [occurs] at the end of the injection when the internal pressure of the injector drops” (WHO, 1998a).

Based upon these findings WHO stated,

Multidose, needle-free injectors with a reusable fluid path should only be used for immunization if they pass standard WHO safety tests. On this basis the latest evidence suggests that none of the models that have been tested [i.e., Ped-O-Jet, Med-E-Jet & Medivax] in the laboratory can be used for immunization” (WHO, 1998a).

This is worth repeating. The most widely used jet injector in the world, the Ped-O-Jet, did not pass WHO’s safety test and therefore cannot be used for administering immunizations. This would also mean the Ped-O-Jet should never have been used.

During this conference WHO officially discouraged the use of jet injectors under any circumstance and recommended the use of needles and syringes. “Until safe needle-free injectors are identified through independent safety testing, only needles and syringes should be used for immunization” (WHO, 1998a).

 

1998 (October) WHO Report – Safety of Injections
For the first time, WHO publishes warnings against the use of multi-use nozzle jet injectors. “Needle-free injectors designed for use with multi-dose vials and with a multiple-use fluid path should not be used for immunization. These injectors have an inherent risk of bloodborne disease transmission,” stated the report (emphasis added) (WHO, 1998b).

 

1998 (October) Ped-O-Jet Field Trial in Brazil
In October of 1998, WHO conducted a simulated field trial with Ped-O-Jet injectors to assess the degree of blood transmission via multi-use nozzle jet injectors. The investigation was a collaborative effort between WHO, the Brazilian Ministry of Health and Dr. Hoffman. The field trial administered saline injections to patients infected with Hepatitis B and Hepatitis C in the Brazilian cities of São Paulo and Belém (Hoffman et al., 2000). The researchers replicated de Souza Brito’s 1992 study but used a new ELISA method for detecting the presence of occult blood (Hoffman et al., unpublished).

In the first test, volunteers received a saline injection with a Ped-O-Jet injector, immediately followed by three subsequent shots into three test tubes. Covering the top of each test tube was a plastic film which was “used to replicate the effect of skin as a barrier to contamination transfer.” The ejectates within these three test tubes were assayed. These subsequent shots represented what the following three persons standing in the vaccination line would have received. The researchers were assessing if blood would be cross-contaminated to subsequent vaccinees when the nozzle of the jet injector was not swabbed (Hoffman et al., unpublished; Hoffman et al., 2000).

Positive samples were defined as any ejectate containing 10 picoliters of blood or more. Results for the first test, when the nozzle was not swabbed, found 13 out of 117 (11.1%) of the samples collected after the first inoculation had greater 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; Hoffman et al., 2000).

In the second test, immediately following an injection the nozzle of the Ped-O-Jet was swabbed with a piece of cotton soaked in ethyl alcohol. Three subsequent shots were fired into three test tubes and the ejectates were assayed.

Results of the second test, when the nozzle was swabbed, found 9 out of 117 (7.7%) of the samples collected after the first inoculation had greater than 10 picoliters of blood. Results of the second “shot” found 3 out of 117 (2.7%) of the samples were positive and the third “shot” found no contamination (Hoffman et al., unpublished; Hoffman et al., 2000).

These results signify several findings: 1) Swabbing the nozzle of the Ped-O-Jet did not eliminate but only slightly reduced the degree of contamination. This finding indicates contamination was present inside the injector’s internal fluid pathway, beyond the reach of swabbing the nozzle. This undesirable phenomenon is known as retrograde flow. The researchers stated, “This trial has confirmed previous laboratory modeling carried out by the same investigating team in London, showing that significant blood contamination can be transferred by jet injectors” (Hoffman et al., unpublished).

2) Once the Ped-O-Jet became contaminated it remained contaminated up to the following two subsequent injections.

3) Cross-contamination occurred despite the presence of visible bleeding at the injection site. “Blood contamination did not seem to correlate with the rapidity or profundity of bleeding at the injection site, nor with individual injectors used,” said the researchers.

In 29 samples more than 10 picoliters of blood was cross-contaminated via the Ped-O-Jet. In 14 out of the 29 positive samples, there was no visible bleeding at the injection site. Out of these 14 instances where no visible bleeding was observed, 11 samples were first shots and 3 samples were second shots (Hoffman et al., unpublished). These findings indicate that despite the lack of any visible bleeding at the injection site the Ped-O-Jet became so grossly contaminated that transmission of a relevant volume of blood occurred into the subsequent two injections.

Dr. Martin Friede, from WHO’s Initiative for Vaccine Research, described the significance of Hoffman’s findings at a 2005 FDA panel discussion on jet injector safety. Dr. Friede stated,

The devices that we have seen without a protection cap, we have data from the calves and the data from the Hoffman study in Brazil to show that frequent contamination of the ejected did take place. And that contamination was clearly of a level of blood that we are convinced can carry disease. So the devices which do not have a protection cap which are to be used for giving intramuscular injection we are convinced that these carry a significant risk (emphasis added) (FDA, 2005).

The field trial took cautionary measures to avoid false positives from the use of Human Serum Albumin (HSA) as a marker for detecting blood, since HSA is also found within saliva and skin cells. “Throughout this work, great care was exercised to exclude extraneous contamination with human serum albumin (HSA),” said Hoffman. “Operators wore face masks and gloves whilst handling unsealed specimen vials and during sample collection.” Moreover, measures were in place for assessing any pre- and post-injection HSA contamination which would have altered the data (Hoffman et al., unpublished).

 

2001 Hoffman et al. Publish Findings on Jet Injector Safety
Hoffman and colleagues finally published the results of their laboratory investigation in 2001. Four different types of jet injectors were analyzed: Ped-O-Jet/Am-O-Jet, Medivax, Jet2000, and Med-E-Jet. The Am-O-Jet was an identical design to the Ped-O-Jet device (American Jet Injector; Weniger & Papania, 2008). Two of the jet injectors–Medivax and Jet2000–were prototypes.

“All injectors tested transmitted significant (over 10 pl) volumes of blood; the volumes and frequency of contamination varied with injector” (Hoffman et al., 2001). These findings were astonishing. If 10 picoliters is a sufficient amount of blood for transmitting blood-borne pathogens 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. 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 higher 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).

Hoffman’s laboratory investigations took cautionary measures so as to not let HSA alter the data of the ELISA. “Stringently applied protocols” were utilized which included the need for “an extremely clean environment.” Injection sites of calves were cleansed twice with methanol. Vaccinators rinsed their hands with ethanol before handling a jet injector and bulk reagents (Hoffman et al., 2001).

Another limitation of the ELISA method is the necessity for diluting a sample that has been frozen. Daya Ranamukha-arachchi, a molecular biologist at the Office of Science at the Center for Devices and Radiological Health within the FDA, stated, “Under cold storage conditions serum albumin can bind to collection tubes…so you have to go through a series of dilutions in order to get within the dynamic range of detection” (FDA, 2005). Through this method some of the quantity of contamination can be lost.

Dr. Hoffman estimated a 30 to 50 percent loss of blood within the samples of his study. “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 and colleagues (2001) concluded cross-contamination occurred because the newly deposited jet stream in the skin had developed a pressure greater than the declining pressure in the jet injector causing a backwards flow. This backwards or rather retrograde flow of fluid—and now blood and bodily fluids—shoots back into the internal fluid pathway of the jet injector.

 

2004 (March 30) WHO & CDC Meeting – Consultation on MUNJI Safety Evaluation
WHO and CDC hosted a subsequent meeting on jet injector safety at WHO Headquarters in Geneva, Switzerland. The goal of this meeting was to establish criteria for a new generation of jet injector devices. Attendees of the meeting came to a consensus on several points: 1) A fraction of a picoliter can transmit infection, thus making the 10 picoliter threshold irrelevant (FDA, 2005). 2) No level of risk is acceptable with the use of MUNJIs. Therefore jet injectors need to show they pose zero-risk to vaccinees (Weniger, 2005). 3) Previous animal models are irrelevant in assessing the risk for humans (Weniger, 2005). Future jet injector safety trials should use human HBsAg carriers and use the most sensitive PCR assays for contamination within ejectates (Weniger, Jones & Chen). The PCR assay is a more sensitive assay than the ELISA, a difference of ~3 picoliters and ~13 picoliters, respectively.

 

2005 (Aug 9) FDA Hearing – MUNJI Safety
WHO partook in a panel discussion on jet injectors at the FDA. Dr. Martin Friede, of the WHO, gave an in depth discussion on the risks of jet injectors and stated WHO’s ultimate position on MUNJIs. “The determination of the safety of MUNJIs is the responsibility of national regulatory agencies. WHO will not determine the safety. This is the responsibility of the national regulatory agencies,” said Friede (FDA, 2005).

WHO was willing to investigate and report its findings on MUNJI devices and even openly discourage against their use. However, ultimately the WHO did not want to get involved within any national regulatory determination.

 

Conclusion
The WHO was always quick to restrict and warn against the use of multi-use nozzle jet injectors. The agency was actively involved in investigating MUNJIs for many years before respectfully bowing-out in 2005. It is my belief that a more prominent position by the WHO would have been to conduct epidemiological studies evaluating the risks of MUNJIs used in mass vaccination campaigns.

For an agency, such as the WHO, to publish numerous studies throughout the 1960s and 1970s on how MUNJIs were a better way for administering immunizations and to subsequently investigate the risks of cross-contamination by MUNJIs throughout the 1990s then it would be logical and moral for the WHO to investigate how many people became infected with a blood-borne pathogen after receiving immunizations with MUNJI devices.

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.
  • (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.
  • (Friede, 2003) Friede M. Safety Evaluation of Re-designed Multi-Use-Nozzle Jet Injectors (presentation). Innovative Administration Systems for Vaccines Conference, Rockville, Maryland. 18-19 December 2003.
  • (Hoffman et al., 2000) Hoffman PN, Abuknesha RA, Andrews NJ, Brito de Souza G, Carrasco P, Weckx LY, Moia LJMP, Silva AEB, Lloyd J. Avaliação de segurança em injetores à pressão para vacinação no Brasil. Centro de Vigilância Epidemiológica (CVE) Boletim Informativo. July 2000;15(57):3-5.
  • (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 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).
  • (Mohammed et al., 2000) Mohammed I, Abdussalam N, Alkali AS, Garbati MA, Ajayi-Obe EK, Audu KA, Usman A, Abdullahi S. A Severe Epidemic of Meningococcal Meningitis in Nigeria, 1996. Royal Society of Tropical Medicine and Hygiene, 2000 (94): 265-270.
  • (Weniger, 2005) Weniger B. Safety of Multi-use-nozzle Jet Injectors (MUNJIs) for Bloodborne Pathogen Cross-contamination [draft]. Conference Notes. 7 August 2005.
  • (Weniger, Jones & Chen) Weniger BC, Jones TS, & Chen RT. The Unintended Consequences of Vaccine Delivery Devices Used to Eradicate Smallpox: Lessons for Evaluating Future Vaccination Methods.
  • (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, 1986) WHO/EPI. WHO/UNICEF Joint Guidelines. Selection of Injection Equipment for the Expanded Programme on Immunization. 1986. WHO/UNICEF/EPI.T5/ 86.27597.
  • (WHO/UNICEF, 1987) WHO/UNICEF. Expanded Program on Immunization-Joint WHO/UNICEF Statement on Immunization and AIDS. 1987. pp 18-19.
  • (WHO, 1997) World Health Organization. Steering group on the development of jet injection for immunization. May 14, 1997. [draft]
  • (WHO, 1998a) World Health Organization. Technet Consultation. Expanded Programme on Immunization. Conference 16-20 March 1998. Copenhagen. WHO/EPI/LHIS/98.05.
  • (WHO, 1998b) World Health Organization. Safety of injections in immunization programmes: WHO recommended policy. Geneva: World Health Organization, Global Programme on Vaccines and Immunizations, document WHO/EPI/LHIS/96.05, Rev. 1, Oct 1998;1-11.

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Impact of CDC’s 1993-94 Unpublished Study – Part I

CDC’s third evaluation into multi-use nozzle jet injectors created a cataclysmic change within the agency. No longer were jet injectors viewed as risk-free. The benefits these devices previously provided within mass immunization campaigns were now being thwarted by a growing fear of transmitting infectious viruses.

As a direct result of the investigation by Grabowsky and colleagues, CDC immediately issued a new, heightened warning on the risks of using multi-use nozzle jet injectors. The warning within the MMWR General Recommendations on Immunization, dated the 28th of January 1994 preceded Grabowsky filing his unpublished draft with CDC in April of 1994. The CDC warning stated,

The multiple-use nozzle jet injector most widely used in the United States (Ped- O-Jet) has never been implicated in transmission of bloodborne diseases. However…laboratory studies in which blood contamination of jet injectors has been simulated have caused concern that the use of multiple-use nozzle jet injectors may pose a potential hazard of bloodborne-disease transmission to vaccine recipients. This potential risk for disease transmission would exist if the jet injector nozzle became contaminated with blood during an injection and was not properly cleaned and disinfected before subsequent injections. The potential risk of bloodborne-disease transmission would be greater when vaccinating persons at increased risk for bloodborne diseases such as HBV or human immunodeficiency virus (HIV) infection because of behavioral or other risk factors (emphasis added) (CDC, 1994).

The wordage within this report demonstrates CDC viewed the results of the Med-E-Jet and Ped-O-Jet were significant. For instance, breaking down the above sentence in bold will help clarify. “Laboratory studies [references CDC’s in vitro experiments on the Med-E-Jet and Ped-O-Jet] in which blood contamination of jet injectors [plural, thus referring to more than one brand of device] has been simulated have caused concern that the use of multiple-use nozzle jet injectors may pose a potential hazard of bloodborne-disease transmission.” Herein the CDC acknowledged results from both of these devices “caused concern” over transmission. It is also interesting to note the CDC acknowledged the potential that all “blood-borne” pathogens could be transferred via jet injection. Although Hepatitis C was known of during the time of this report, as Dr. Grabowsky had stated this was before universal precautions were instituted, not much was yet known about Hepatitis C, and CDC was investigating these risks on a disease by disease basis, so Hepatitis C was not intentionally omitted.

While CDC casted warnings concerning the risks of jet injectors, the agency also acknowledged the speed and cost-efficient benefits the devices brought to mass vaccination campaigns. With a reluctance in completely abandoning the technology the report also discussed ways the CDC believed consumers could minimize the risks associated with these devices.

Multiple-use nozzle jet injectors can be used in certain situations in which large numbers of persons must be rapidly vaccinated with the same vaccine, the use of needles and syringes is not practical, and state and/or local health authorities judge that the public health benefit from the use of the jet injector outweighs the small potential risk of bloodborne-disease transmission. This potential risk can be minimized by training health-care workers before the vaccine campaign on the proper use of jet injectors and by changing the injector tip or removing the jet injector from use if there is evidence of contamination with blood or other body fluid. In addition, mathematical and animal models suggest that the potential risk for bloodborne-disease transmission can be substantially reduced by swabbing the stationary injector tip with alcohol or acetone after each injection. It is advisable to consult sources experienced in the use of jet injectors (e.g., state or local health departments) before beginning a vaccination program in which these injectors will be used. Manufacturer’s directions for use and maintenance of the jet injector devices should be followed closely (CDC, 1994).

 

In the following years, CDC researchers spoke-out, warning of the risks posed by multi-use nozzle jet injectors. Dr. Bruce Weniger was the former Lead Researcher on Vaccine Technology within the CDC and one of—if not thee—leading expert on jet injection technology. Weniger compared CDC’s studies of the Med-E-Jet from 1986 and Ped-O-Jet from 1994. To recap, the jet injector nozzle was artificially contaminated and then fired into a vial. The ejectate fluid in the vial represents what would have been injected into the next person in the vaccination line. The data below shows the number of samples which tested positive for Hepatitis B surface antigen.

10- Weniger Slide Comparing CDC's Jet Injector Studies
(Weniger, 2003)

 

Dr. Weniger stated,

Comparing both the Med-E-Jet involved in the outbreak, in red on the right, with a Ped-O-Jet, in green on the left, they [CDC] were able to detect substantial proportions of the next injections from both devices, regardless of whether they followed manufacturer recommendations to swab or wipe the nozzles with acetone or alcohol before the next injection. As you can see, 38% and 6% of next injections with the Ped-O-Jet contained HBV, unswabbed or swabbed, respectively, compared to 80% and 64% of the outbreak-associated Med-E-Jet (emphasis added) (Weniger, 2005).

 

Indeed results of the Ped-O-Jet found rates of contamination lower than the Med-E-Jet, but contamination was exhibited nonetheless. As Dr. Weniger stated, CDC detected substantial proportions of Hepatitis B surface antigen within ejectates from both devices.

Former Deputy Director of CDC’s Hepatitis Laboratories Division Martin Favero, who had previously remained silent, voiced his concerns of jet injectors within a 1998 paper, titled, Potential for Cross-Contamination With Needleless Injector. Favero, along with his coauthor Pugliese, wrote,

Medical devices that are used on patients in fields containing potentially
infectious body fluids can become contaminated and transmit infectious agents to other sites on the patient or to other patients if the devices are not properly cleaned and sterilized or disinfected after each use. One such device is the needleless, or jet, injector, which is used widely in medicine and dentistry to deliver local anesthetic in procedures such as bone marrow aspirations, lumbar punctures, and cutaneous and intraoral injections (Pugliese & Favero, 1998).

Next Article –  Impact of CDC’s 1993-94 Unpublished Study – Part II

 

References:

  • (CDC, 1994) Centers for Disease Control and Prevention. General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morb Mortal Wkly Rep 43:(RR-1):7–8, 1994.
  • (Pugliese & Favero, 1998) Pugliese G., MS Favero. Potential for Cross-Contamination with Needleless Injector. Infection Control and Hospital Epidemiology. Nov. 1998. pg. 850.
  • (Weniger, 2003) Weniger BG. Jet Injection of Vaccines: Overview and challenges for mass vaccination with jet injectors. Innovative Administration Systems for Vaccines (conference). Rockville, Maryland, USA, 18-19 December 2003.
  • (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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Brazilian Government Notes Risk of Ped-O-Jet Injectors: Prompts Investigations by CDC and WHO in the Early 1990s

The Brazilian Ministry of Health implemented safety testing upon Ped-O-Jet injectors in the late 1980s and early 1990s. The investigation was intended to uphold the safety of jet injectors but rather discovered the most widely-used device, the Ped-O-Jet, was a safety risk.

In 1987, a Measles Control Program was initiated within the São Paulo region of Brazil. A total of 8.7 million children aged nine-months to fourteen years were vaccinated with Ped-O-Jet injectors. Despite a hepatitis outbreak at a Los Angeles clinic with a Med-E-Jet injector, the healthcare workers in São Paulo believed the Ped-O-Jet was different and posed no risk (de Souza Brito, 1996).

The Brazilian Ministry of Health conducted a study to assure the safety of the Ped-O-Jet during routine military vaccinations in 1991 (de Souza Brito, 1996). The study aimed to answer three questions:

  1. What is the frequency of visible bleeding at the site of jet injection in the skin?
  2. What is the frequency of occult blood in the next vaccine shot dose?
  3. Is there any correlation between visible bleeding and occult blood of the next dose?

Glacus de Souza Brito and his fellow researchers led the investigation. It was observed amongst three vaccination sites the percent of vaccinees who bled immediately after the Ped-O-Jet was removed ranged from 2.2 to 23.3 percent. The average percent of bleeders was 3.6 percent (104 out of 2885). The researchers found “instantaneous bleeding took place after injection in a significant proportion of cases and that there was therefore a risk of downstream infection of subsequent subjects” (WHO, 1998).

The presence of blood prompted researchers to asses the possibility of cross-contamination. The subsequent shot after administering a vaccination was fired into a vial and analyzed. Amongst the three vaccination sites results detected blood within 0.2 to 6.6 percent of the ejectates, with the average being one percent (28 cases out of 2885 vaccinees).

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). This finding is significant. There was no visible bleeding at the injection site in 27 out of 28 of the ejectates which contained blood, indicating blood transferred within microscopic levels not visible to the human eye.

Dr. Martin Friede of the WHO later noted, the researchers used blood detection stripes which can only detect around 2,000 picoliters of blood and therefore failed to detect blood within levels lower than 2,000 picoliters. The results demonstrated one percent of the ejectates contained 2,000 picoliters of blood (FDA, 2005). Therefore, the results found blood was being cross-contaminated via the Ped-O-Jet within volumes which could contain infectious viruses like Hepatitis B and Hepatitis C.

In 1992 a mass Measles Vaccination Campaign was launched across the entire country of Brazil. The government purchased 10,000 Ped-O-Jet injectors to vaccinate an estimated 50 million children between the ages of nine-months to fourteen years within a month period. During this mass vaccination campaign, a possible hepatitis B outbreak by Ped-O-Jet injectors was investigated but no statistical association was found. However, despite these findings the Brazilian government found the Ped-O-Jets were unsafe and stopped using the devices (Fields, 1996; de souza Brito, 1996).

These investigations by de Souza Brito were significant in raising safety concerns of jet injectors amongst the WHO and CDC. By 1994, Dr. de Souza Brito collaborated with researchers at the CDC to further investigate the inherent risks of Ped-O-Jet injectors. CDC Retests the Safety of Jet Injectors in 1993-94

 

References:

  • (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).
  • (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.
  • (WHO, 1998) World Health Organization. Technet Consultation. Expanded Programme on Immunization. Conference 16-20 March 1998. Copenhagen. WHO/EPI/LHIS/98.05.

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