Implementation

In an attempt to approach the Policies and Practices component of the competition in a different manner, our team sought to determine exactly what sort of documentation must be in place before a device such as ours could reach the market.

Target Product Profile

Our collaborators at the Foundation for Innovative New Diagnostics (FIND) advised us on the necessary considerations that would be required from a device such as ours to see it actually go to market. The first step is to develop a Target Product Profile (TPP) detailing the intended use, an explanation of function and procedure, how results are interpreted as well as performance characteristics. Our TPP is detailed below:

Intended Use Statement

This product is a multiplexed point-of-care diagnostic device used for simultaneous diagnosis of several febrile illnesses. It is a qualitative assay that provides colorimetric results for positive diagnosis. This products intended use is a ‘reflex test’ as an alternative for physicians when presented with a negative malarial diagnosis. It can also function as a standalone febrile illness diagnostic tool. Research shows that a test of this sort does not seem to be commercially available.

Summary and Explanation of the Test

This device utilizes an engineered strain of Bacillus subtilis to generate a chromophoric reporter protein in response to pathogenic genetic markers indicative of these diseases. A small blood sample is obtained from the patient and input into the device. It then undergoes isothermal PCR, amplifying DNA present in the sample. Once the allotted time has passed, the sample is forced through several channels each containing a different strain of B. subtilis. After another waiting period, each chamber can be viewed from above to determine if each targeted pathogen is present in the original sample. These synthetic organisms will lie dormant as robust bacterial spores in a microfluidic device, enabling users to input blood samples and differentiate diseases based on colour of the output reporter proteins.

Summary of the Test Procedure

The test begins with rehydration. First, a syringe of sterile water is injected into the top of the device, activating the reagents inside. A blood sample is then taken from the patient and placed upon the input channel. This channels the sample into a chamber containing the necessary reagents for isothermal PCR. This process takes two hours and functions most efficiently at a constant temperature. Once the time period has elapsed, the plunger on the top of the device is depressed. This forces the sample into separate chambers containing engineered bacteria. Once the sample enters the chambers, it is left to process overnight. In the morning, any chambers that positively identified a pathogen will be blue, and all others will remain clear.

Interpretation of Results

The results of this test are easy to interpret. Each chamber is uniquely marked with the name of the pathogen it is testing for. After overnight processing, a technician can simply inspect the chambers to see in which locations a colour change has occurred. A blue color denotes a positive diagnosis, and no color indicates the pathogen was not present. This method is unique in the sense that it can diagnose co-infection.

Performance Characteristics

In order for our device to be practical, we determined that it must have the following characteristics:

Adaptable

Our device must be easily tailored to diagnose diseases endemic to a particular area. By simply changing the target sequence within our B. subtilis strain we are able to target different pathogens that might plague different geographical regions. This device could easily have different versions for different areas.

Affordable

It is of utmost importance that our system be attainable by our end user. Although no current multiplexed standard exists, we have used the pricing suggested by the WHO for an HIV assay, which has a final device cost of no more than $10USD. Our consultation with the Foundation for Innovative New Diagnostics (FIND) helped us realize the number of taxes that will be applied to our device, essentially doubling its original cost. For this reason we seek a final device price of no more than $5 per device.

Robust

Our final device must be able to withstand transport as well as harsh environmental conditions. To make our device as robust as possible, we have used B. subtilis spores. These spores can withstand extreme heat and cold before their rehydration, and provide us with the necessary shelf life required by the World Health Organization (2 years).

Easy to Use

Not all rural clinics have trained technicians. For this reason our device must be simple, requiring very little expertise. In addition, our device overcomes language barriers by displaying only colorimetric results. These results are clear and defined, leaving little room for misinterpretation.

Implementation Considerations

Although our research was mainly concentrated on Tanzania and Ethiopia, our device can be implemented in many other developing countries. Depending on what disease is most common in the region, our system can easily be adapted to identify different target diseases. Because our system is robust, affordable, and adaptable it can benefit many different regions all over the world.

Implementation Procedures

Our team contacted several agencies to learn more about what steps would need to be taken to implement the device in developing countries. In order to implement in Ethiopia, for example, the first step is get registered with Food, Medicine, Health Services Administration and Control Authority (FMHSACA) by submitting an application with required technical documentation and specifications details of the product. If the product is already registered with the World Health Organization (WHO) then FMHSACA usually registers the device provided all of the required documentation is submitted. Otherwise, FMHSACA might choose to run its own safety and quality control tests with the help from Ethiopian Public Health Institute. It is also recommended that the device has a Certificate of Good Manufacturing Practice to ensure successful implementation. Upon completion of the registration process, the device might be included in health care workers’ trainings. The device would also have to be listed in National Guidelines in order for health care professionals to use the product.

Implementation process can vary from country to country. However, in general, if the device meets the standards set by WHO then it would also satisfy the country’s requirements.

Policies Associated with Synthetic Biology and Genetically Modified Organisms

GM organisms and synthetic biology related issues are getting more attention from the policy-makers. Many countries have related laws and regulations in place. In order to implement the device, it is also important to make sure that it follows GMO laws and regulations in the region. Ethiopia, for example, has a Biosafety law in place. The Biosafety Law requires an application to be submitted to Ethiopian Environmental Protection Authority (EEPA). EEPA must confirm that the device satisfies Biosafety laws and an Advance Informed Agreement must be obtained before GM organism/device using GM organisms is brought into the country. Some required information that might be requested in this process include product information, environmental and human health risk assessments, social and economic impact assessment and risk management plans.