The Program for Appropriate Technology in Health (PATH), funded by the Bill and Melinda Gates Foundation, has been a major contributor in the development of safer jet injection technology. Although during the development of safer, next generation jet injectors, PATH needed to assess how bad were the Ped-O-Jet injectors.
Around 2003-2004 PATH conducted a “simple” test to assess the safety of the HSI-500, a prototype jet injector manufactured by Felton International, Inc. The “simple” test was an in vitro fluorescein contamination test, which made any contamination visible due to the use of a fluorescein dye. The highly concentrated fluorescein dye was used as a surrogate for high titer Hepatitis B infection (FDA, 2005).
“The fluorescein assay really exceeds the PCR [polymerase chain reaction] methods in terms of a detection limit,” explains Darin Zehrung, the Associate Technical Officer at PATH. “So it’s very sensitive, it’s very specific in terms of an assay. And we believe a good surrogate aside from human testing to demonstrate cross-contamination safety” (FDA, 2005).
For this experiment PATH used the Ped-O-Jet injector as a comparative model. The HSI-500 and the Ped-O-Jet injector were both sterilized and administered an injection into a test fixture containing a fluorescein dye. Each of the jet injectors then fired the subsequent shot into vials and the ejectates were evaluated. The threshold for contamination was defined as detection of more than 10 picoliters within the 0.5 cc sample. Results for the Ped-O-Jet found 75 out of 100 (75%) samples contained more than 10 picoliters of fluorescein. Results for the HSI-500 found no contamination (Zehrung, 2004). These results indicated the Ped-O-Jet cross-contaminated a sufficient volume of fluorescein from the infected host to the next dose.
PATH had conducted performance and safety evaluations on the Ped-O-Jet, as noted within these pictures. Note in the photograph on the right, a drop of fluid remains on the nozzle tip post-injection.
In March of 2004, PATH attended a CDC/WHO conference on jet injector safety which focused on establishing safety requirements for disposable-cartridge jet injectors. The meeting delved into evaluating several unknown factors. “The questions are how infectious is blood? How do we measure it? How do you model the risk? What level of risk is acceptable?” (FDA, 2005). Members of the conference were in agreement that quantities smaller than 10 picoliters could be infectious.
Based upon this conclusion, PATH altered the threshold of contamination from 10 picoliters to 0.04 picoliters. PATH conducted their fluorescein test a second time using the new 0.04 picoliter threshold level. Results demonstrated cross-contamination with the Ped-O-Jet but no cross-contamination with the HSI-500 jet injector.
Mr. Zehrung explained the results of the experiment in detail at a 2005 FDA conference on jet injector safety. For reasons unknown Mr. Zehrung refers to the Ped-O-Jet as a “first generation MUNJI device.” Although in other sources, he disclosed this was in fact the Ped-O-Jet injector (Zehrung, 2003; Zehrung, 2004).
Mr. Zehrung: So you may not be able to see these pictures. This is a first generation MUNJI device. I think that those are familiar with these technologies know what that device would be called. And you can see after injection into the test fixture, there is contamination at the injection site. There’s a combination of splash back as well as contact contamination during the injection process. You see that it’s contaminated with the fluorescein dye.
The same is true for the protector cap injector. This is the protector cap on the nozzle face itself. It’s hard to see in this photo, but this protector cap post injection into the test fixture is also contaminated. But the down stream sample collected after injection into the text fixture is demonstrated to be free of cross- contamination.
So this is a slide showing the comparison of first generation MUNJI testing with this method versus a protector cap injector. These are the number of samples. So for a 100 samples with the first generation MUNJI device, all were contaminated, a 100 percent with an average contamination rate of 268 picoliters. In comparison with the protector cap injector for 300 samples, all samples were free of cross-contamination (FDA, 2005).
This is worth repeating. Mr. Zehrung presented images from the test which demonstrated the Ped-O-Jet as well as the injection site were both contaminated with fluorescein dye. This type of contamination is known as splash-back. The protector cap for the PCNFI was also contaminated with fluorescein. These results demonstrate that no matter the model or generation of jet injector gross-contamination upon the injection site and the nozzle are natural phenomenon of jet injection.
Results of the Ped-O-Jet found contamination in 100 out of 100 (100%) of the samples. The average volume of fluorescein contamination within the ejectates was 268 picoliters. This shows gross cross-contamination by the Ped-O-Jet. Mr. Zehrung stated of these results, “we believe that this [i.e., the fluorescein testing] is a very useful and powerful method to demonstrate contamination risk with the earlier devices” (FDA, 2005).
PATH’s fluorescein testing of the Ped-O-Jet further illuminates the degree of contamination these devices posed.
- (FDA, 2005) FDA. General Hospital and Personal Use Devices Panel of the Medical Devices Advisory Committee. August 9, 2005. 35th Conference. Washington, D.C.
- (Zehrung, 2003) Zehrung D. PATH’s Experience from Jet Injector R&D and Field Assessment in Developing Countries. Presentation for Innovative Administration Systems for Vaccines. Rockville, Maryland. 18 December 2003.
- (Zehrung, 2004) Zehrung D. Jet Inject for Mass Immunization: Design Update and Safety Testing Strategy. Presentation for Global Vaccine Research Forum. 10 June 2004.