# BME100 f2017:Group5 W0800 L2

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# OUR TEAM

 Name: Anna Hoge Name: Joey Gurule Name: Savina Plougmann Name: Anu Pal Name: Curran McGraw

# LAB 2 WRITE-UP

## Device Image and Description

The inhaler that we designed is 2 chambers. The center chamber will hold the medication within it, and the outer contains vegetable glycerin. Also, refrigeration units are scarce in China, so we designed a mini fridge that will contain the inhaler cartridge. Once the cartridge has been the unit for some time, it will stay cool due to the properties of the vegetable glycerin.

## Technical and Clinical Feasibility

Technical Feasibility

What are the technologies needed?

This design requires a bio preservation chamber to keep the organisms cooler. The cooling device will have to be electrically powered, with a battery to prolong its preservation. The chamber which contains the microorganisms need to contain an agar solution of nutrients to sustain the organisms. The aerosolized spray will contain eucalyptus oil and menthol in separate chambers. Each compartment will have to dispense a set amount of its contents into the the mixture for inhalation. The mixture will need to be aerosolized into a mist that can be inhaled. Inhalers can currently release medication in two different ways: though aerosolized spray, or through dry powder spray. “Metered dose inhalers” spray aerosolized medication with manual activation, and “breath activated inhalers” do the same automatically upon inhalation. “Dry powdered inhalers” spray out, as the name implies, a dry powder medicine [1]. We are currently planning on a metered dose inhaler.

What are the challenges?

We will have to set a realistic yet feasible expiration date; one that will allow the product to undergo transportation and reasonable time before use, but can be reasonably attained with our design. To ensure the optimal time of preservation, we will have to balance the amount of nutrients in the agar solution for the organisms. We will have to determine dosage and ensure that the amount of each substance in each dose is consistent and in the proper amount. There will have to be instructions for use and care of the inhaler given to the patient.

What could go wrong?

The microorganisms could become infectious, they could die before the planned expiration date, and the eucalyptus and menthol could harm the microorganism. If the cooling mechanism fails, the organisms will expire before the expiration date. If the dosage is not consistent it can affect the recovery of the patient and potentially harm their health.

Clinical Feasibility

Given the technical feasibility it work in the clinic?

Our inhaler is designed to be patient-friendly and easy-to-use. Studies have shown that proper inhaler technique is correlated with receiving medical professional instruction on proper usage [2]. Demonstrating proper inhaler technique is brief and straightforward, and afterwards, the patient is able to administer his or her own inhaler, placing minimal strain on healthcare professional resources. Since our inhaler dispenses coal-degrading microorganisms, it will likely require a prescription to acquire.

What are the clinical risks?

The clinical risks associated with corticosteroid inhalers include increased risk of pneumonia, gastrointestinal bleeding, hyperglycemia, and hypertension [3, 4], and beta-agonist inhalers can lead to a higher risk of myocardial infarction [3, 4, 5]. Since our inhaler introduces a new kind of therapy, free of synthetic drugs, we are interested in developing our technology to avoid these clinical risks already associated with inhalers.

Since we are introducing microorganisms into the lungs, we risk generating an adverse immune response. It may be essential for us to genetically engineering our microorganisms to evade detection by the host immune system, such as by altering the outer membrane components of our bacteria (to minimize recognition of LPS, if we use gram-negative bacteria, for example). Alternatively, we could disguise our organisms in microns-wide glycerin packages to minimize the time between detection by the host immune response and the initiation of coal breakdown. We may need to resort to isolating the coal-degrading compounds from our microorganisms, and having those be the sole active ingredients in our inhaler, sans microbes.

If we are able to use microorganisms in our inhaler, we would likely want the organisms to die off in the lungs relatively quickly after inoculation, to avoid unwanted evolution in the lungs. Modeling off of how pathogenic bacteria in higher-BLS level labs are modified to lack an essential nutrient-synthesizing gene, and thus cannot survive in a medium without that nutrient, we could remove a similar gene if we use bacteria, or perform a similarly-goaled modification if we use fungi.

Have similar products been in a clinical trial? How long was the trial?

There are an abundance of clinical trials that have studied the efficacy and side-effects of inhalers. One 3 year study found that poor asthma control was associated with poor compliance, which encouraged us to pursue designs that encourage patients to use their inhaler, such as an inhaler that inflates overnight, or a refrigerator unit that glows red if it hasn’t been opened up in 24 hours [6]. Other clinical trials have looked at the success of inhaler use in respiratory distress syndrome in infants. These trials tended to range in length from a few days to a few weeks [7]. A recent 5-day clinical trial tested the combination of corticosteroid and beta-agonist medication inhalers for acute respiratory distress syndrome [8].

To investigate the effect on the type and length of our needed clinical trials from using live organisms in our inhaler, we researched clinical trial guidelines for probiotic development. The FDA essentially announced in 2010 that probiotics intended for a health improvement goal need to be classified as an “investigational new drug” (IND), and thus the FDA must be notified 30 days before clinical trials will commence, and the FDA, although not capable of “approving” an IND, oversees the process of developing the IND before clinical trials, and can halt clinical trials at any time. An overview of clinical studies of probiotics published in Gut Microbes states “It is common for this phased regulatory scheme for the collection of data to take a number of years before completion and before an agency approval of the desired drug for a given indication is achieved (if ever)” [9].

## Market Analysis

Value Creation

Our take on the modern inhaler was inspired by the horrible air quality in many Asian countries due to the massive amounts of coal used to supply energy. Most inhalers today are just anti-inflammatory aids that help open up the airways allowing the easy passage of oxygen to the lungs, and while useful, this doesn’t really solve the problem. Our device would take microorganisms that have been aerosolized and put into a capsule. Once inhaled, these organisms would go to work at breaking down the coal buildup in the lungs, allowing the macrophages of the body clean up the rest naturally.

Manufacturing Cost

Your average albuterol inhaler usually costs about 5-50 dollars with insurance depending on the brand and can range from 30-60 dollars without insurance. As our inhaler is a bit more complex but is supposed to be a daily treatment until all the medicine has been ingested. The price would only be slightly elevated due to the materials being used in the actual can being harder to find and reproduce. The price would range anywhere from 75-100 dollars [10, 11]

Sales Price

The average sales price would range anywhere from 75-100 dollars. This is because the same basic materials are being used to construct the actual inhaler and can. The medicine on the other hand would be made of completely different substances that are much harder to get to reproduce [10].

Market Size

An earlier Global Burden of Disease study that examined health figures for 2010 found that outdoor air pollution contributed to 1.2 million premature deaths, nearly 40 percent of the global total [9]. . (75$-100$ * .05 * 1.2million) = 4.5million-6million

## Fundability Discussion

Although our fundability worksheet shows that our prototype should not be funded, we believe that with more clinical data we can improve our customer validation, clinical feasibility, and regulatory pathway, thus giving our prototype a more fundable score. We expect customer validation in particular to be much higher than the default score of 1 we were required to give. It was also difficult to find data on how many coal workers there were in China, or how many people worldwide are affected by coal pollution, so our market size is a very conservative estimate, and likely is, in actuality, much larger. And with clean, renewable energy a couple decades away, our market size will also be on the rise.

## Works Cited

1. Asthma UK. (n.d.). Preventer inhalers. Retrieved September 13, 2017, from https://www.asthma.org.uk/advice/inhalers-medicines-treatments/inhalers-and-spacers/preventer/

2. Elsevier. (2011, March 02). Inhaler mishandling remains common in real life and is associated with reduced disease control. Retrieved September 13, 2017, from http://www.sciencedirect.com/science/article/pii/S0954611111000096

3. Research gate. (n.d.). Clinical Trials of Postnatal Corticosteroids: Inhaled and ... Retrieved September 13, 2017, from https://www.bing.com/cr?IG=6838420C8BF64EF1BB675906106CA6C6&CID=19E5D0F918316E610EAEDA0519376F2E&rd=1&h=D34bYtOLAIZTPJOLPUpPKTQu0vGA0yJYFmZ9qHpaS1s&v=1&r=https%3a%2f%2fwww.researchgate.net%2fprofile%2fHenry_Halliday%2fpublication%2f12906620_Clinical_Trials_of_Postnatal_Corticosteroids_Inhaled_and_Systemic%2flinks%2f56544f1308ae4988a7b01b3d.pdf%3forigin%3dpublication_detail&p=DevEx,5062.1

4. Au, D. H., Curtis, J. R., Every, N. R., McDonell, M. B., & Fihn, S. D. (2002, March). Association between inhaled beta-agonists and the risk of unstable angina and myocardial infarction. Retrieved September 13, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/11888971

5. Lehanneur, Mathieu. (July 2009). Science-inspired design [Video file]. Retrieved from https://www.ted.com/talks/mathieu_lehanneur_demos_science_inspired_design

6. Donohue, J. F., & Ohar, J. A. (2004, February 17). Effects of Corticosteroids on Lung Function in Asthma and Chronic Obstructive Pulmonary Disease. Retrieved September 13, 2017, from http://www.atsjournals.org/doi/full/10.1513/pats.200402-003MS

7. Festic, E., Carr, G. E., Cartin-Ceba, R., Hinds, R. F., Banner-Goodspeed, V., Bansal, V., . . . Levitt, J. E. (2017, May). Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome. Retrieved September 13, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/28240689

8. Degnan, F. H. (2012, November 01). Clinical studies involving probiotics: When FDA’s investigational new drug rubric applies—and when it may not. Retrieved September 13, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495785/

9. Wong, E. (2013, April 01). Air Pollution Linked to 1.2 Million Premature Deaths in China. Retrieved September 13, 2017, from http://www.nytimes.com/2013/04/02/world/asia/air-pollution-linked-to-1-2-million-deaths-in-china.html?_r=0

10. How Much Does an Albuterol Inhaler Cost? - CostHelper.com. (n.d.). Retrieved September 13, 2017, from http://health.costhelper.com/albuterol-inhaler.html

11. Drum, K. (2017, June 24). Here's why your asthma inhaler costs so damn much. Retrieved September 13, 2017, from http://www.motherjones.com/kevin-drum/2013/10/heres-why-your-asthma-inhaler-costs-so-damn-much/