This year, iGEM NCKU Tainan is focusing on therapeutics. Our Oh My Gut project aims to tackle a problem which is still unknown to many people. We are using synthetic biology to create a comprehensive solution to solve the problem of p-Cresol accumulation in CKD patients, to reduce the risks of getting cardiovascular diseases or other serious complications and help them achieve a better quality of life. We wanted to realize our project from the laboratory and apply it in the real market. Oh My Gut provides solutions to improve the quality of lives of people by setting up an affordable healthcare platform to increase the accessibility to anyone who requires medical advice, attention and products.
To bring our vision and mission into reality, engaging with our customers and stakeholders is crucial. We started with mapping out our target users, which are CKD patients and stakeholders. At first, we proposed that our engineered E. coli Nissle 1917 that possesses the ability to reduce p-Cresol accumulation can be marketed as a probiotic. However, after discussing with Taiwan Food and Drug Administration, we realized that because our product contains pharmacological effects, we need to market it as a drug. Therefore, we decided on marketing our product as a living therapeutic drug called CreSolve. Aside from a living therapeutic drug, we also designed CreSense, a medical device to help measure blood p-Cresol level using our engineered p-Cresol sensing bacteria.
We are very proud that our Oh My Gut project is able to evolve into CreSolve and CreSense which despite being two different products with different business models, all fall under one same goal. CreSolve living therapeutic drug will be directly sold to our distributors, while CreSense will be leased out to healthcare platforms and apply a recurring revenue business model to the suppliance of bacteria refills and microfluidic disc.
In order to understand how therapeutic drugs and medical devices can enter the real market, we started at the bottom, discussing the value proposition of the products and understanding customer’s needs. We subsequently conducted market and competitor research, thoughtfully devise our business model, and wrote our business plan. We aim to interpret the value of our products into a commercial business.
WHAT WE HAVE?
We started by considering what value we want to have in our products and came up with values that we always embedded in mind and to be our value in making the products.
After our discussion with Mr Chen-Ching Chen, head of Tainan Intellectual Property Office, Ministry of Economics to apply Intellectual property for our products, it has two options which are invention patent or utility model patent. For medical device, he suggested us to apply utility model patent regulations as it is a novel add-on device in medical device world, while for the drug, registering it to invention regulation might be a better option.
Method To Deliver
To decide what kind of method to deliver CreSolve, we conducted a survey with the public in NCKU Hospital, discussed with experts and will do a clinical trial in the future to determine what form the drug should be in.
➜ Public Opinion Survey
We asked what form of drug would they think would be easier to consumed. We gave them four options which are capsule, powder, jelly and injection. From the 44 people that we interviewed, it can be concluded that:
- From the results, 68% of people chose capsule because it is more convenient
- Some said they have not tried jelly form of drug
- Injection from public views are more related to serious cases and older people don’t choose injection because they are afraid
- Only 7% of interviewees chose powder since powder usually make them feel like choking and could not bear with the bitter taste of it
➜ Expert's opinion
♦ Li-Hui Huang, Nurse of dialysis center in Chia Yi Chang Gung Memorial Hospital.
She said CKD patients she took care of usually are older people and they normally avoid injection and better choose to consume drugs either it is a powder or capsule hence they enjoy to consume jelly form more rather than the solid form.
♦ I-Ju Chang, Marketing Manager of Synbiotech
The forms of the drug are usually made in powder, liquid or tablet but to determine what form of the drug should we use, we need to do a survey for prices and forms first.
From the suggestion of Synbio Tech, we started to contact pharmaceutical manufacturing companies to learn about drug forms and possible partnership in the future.
♦ Yi-Ching Chen, Marketing Director of Winston Medical Supply Co.
The forms of the drugs are usually customized by the company and to determine what type of form suitable is from the API (Active Pharmaceutical Ingredients) of the drug itself, then determine what form will be suitable to be fermented and processed with our ingredients.
Partnering in manufacture is also one of the possibilities between CreSolution Biotechnology and Winston Medical Supply Co. as long as we have the permission for government and research data with the prototype of the drug.
➜ Product Competitor
CreSolve Living Therapeutic have several products competitors which are Kremezin, a drug focused on absorbing uremic toxins in CKD patients, produced by KUREHA Corporation in Japan and Ketosteril, an amino acid capsule for low protein diet CKD patients, owned by Fresenius Kabi in Germany and available in multiple markets of different countries with efficient manufacturers.
|Name||Year Founded||Project Description||Areas served||Product Price||Strength||Weakness|
|Kremezin||1991||Absorb uremic toxins and their precursors within the gastrointestinal tract, allowing them to be excreted in the feces.||Japan, Korea, Taiwan and Philippines||$7.2 / 2 gram sachet of powder||Its effectiveness has been proven through several clinical trials.||Expensive and is not included in the coverage of the National Health Insurance.|
|Ketosteril||2009||Prevention and treatment of damages due to faulty or deficient protein metabolism in chronic kidney disease||Europe Asia, USA ,Australia||$1.05/ tablet||Proven to give nutritional effects for CKD Patients (doing low protein-diet ) and is cost-effective.||Only for low-protein diet CKD patients.|
➜ A comparison between the products can be seen in our Business Plan
|Component||Quantity||Cost per unit||Cost|
|Electric speed controller||1||$17.96||$17.96|
|Light sensor (tsl-235R)||1||$4.41||$4.41|
Attending Physician, Shun-Chieh Hsu and Dean of Internal Medicine, Kuan-Wen Chen
Our potential customers for the p-Cresol bio-sensing device will be healthcare providers (i.e. hospitals, diagnosis centers, clinics, etc.). During our visit to the Feng Dian United Dialysis Center, we pitched our device that we were designing to Dr. Hsu, the doctor there. The feedback he gave was that our device has to be precise and consistently accurate. Moreover, for a clinic of their size, he pointed out that they usually do not use a centrifuge machine because it is inefficient and uneconomical due to the patient traffic, therefore for the device to be applicable even in a small clinic, it needs to be portable and have no complicated procedures to adhere to before using the device. Besides, the cost of the device is also a major concern for him since most dialysis centers cannot afford the expensive price tag of the devices that are on the market currently. Apart from the quality, practicality and cost-friendly would be one of the considerations for the many small- to medium-sized healthcare providers to adopt our device into their daily operations and services.
Attending Physician, Te-Hui Kuo
While in the process of figuring out our business plan, we have identified physicians to be one of the key mediators to promote CreSolve and CreSense. Therefore, during our visit with Dr.Kuo, we proposed our idea of using a living therapeutic solution to reduce p-Cresol accumulation in CKD patients. As expected from Dr. Kuo’s expertise and experience, the feedback he gave us was that probiotics would typically be considered as a health supplementary product but not a drug which contains a strain of bacteria within it. Apart from the price of the probiotic or drug, he also noted that physicians will consider the exit pathway of the medication as well as the effectiveness of the product. Besides that, he pointed out that CreSense will not be available in the clinic if they are not covered by the National Health Insurance of Taiwan. In addition, he reasoned that often, diagnosis services are not available or provided in clinics are mainly due to it being expensive and are unaffordable for the masses, which in turn become uneconomical for clinics to buy and operate such expensive equipment.
Based on what we found from customer interviews and considerations through a mediator that connects us with customer’s needs, here is our final design of CreSense and CreSolve. After improvements and finalization of the products:
- Oh My Gut team intended to get coverage from major healthcare insurance providers, albeit it national or private, around the world for the consumption of CreSolve and the use of our CreSense to promote the use of both of the products. We aim to improve and enhance the patient’s life by setting up an affordable healthcare platform to increase the accessibility to anyone who requires medical advice, attention and products.
- Taking into consideration the survey thst we have done, CreSolve will be in a capsule form, with freeze-dried bacteria and have a safety reassurance which is our kill switch. As CreSolve is a living therapeutic drug (which is a GMO), building consumer trust is crucial which is why education about the safety of consuming GMO products is important.
- CreSense bio-sensing device needed to be practical and portable in order to be available in healthcare providers especially small clinics. Moreover, the effectiveness of device needs to be optimized, and affordable. Therefore, we designed CreSense bio-sensing device to have a minimum screening price of about $1.6.
- Tsai, Ming-Hsien, et al, “Incidence, Prevalence, and Duration of Chronic Kidney Disease in Taiwan: Results from a Community-Based Screening Program of 106,094 Individuals.” Nephron, vol. 140, no. 3, 2018, pp. 175–184, www.ncbi.nlm.nih.gov/pubmed/30138926, 10.1159/000491708.
- Michishita, Ryoma, et al. “The Association between Changes in Lifestyle Behaviors and the Incidence of Chronic Kidney Disease (CKD) in Middle-Aged and Older Men.” Journal of Epidemiology, vol. 27, no. 8, Aug. 2017, pp. 389–397, 10.1016/j.je.2016.08.013.
- Jha, V, and G Garcia-Garcia. “Chronic Kidney Disease in Disadvantaged Populations.” Indian Journal of Nephrology, vol. 25, no. 2, 2015, p. 65, www.ncbi.nlm.nih.gov/pmc/articles/PMC4379627/, 10.4103/0971-4065.150078
- “1 in 10 People Worldwide Have CKD, but Many Governments Don’t Make Kidney Disease a Priority.” Healio.Com, 2018, www.healio.com/nephrology/chronic-kidney-disease/news/online/%7B7e9674fe-121f-4ec3-a62a-089b73108ffe%7D/1-in-10-people-worldwide-have-ckd-but-many-governments-dont-make-kidney-disease-a-priority.
- THE HIDDEN EPIDEMIC: WORLDWIDE, OVER 850 MILLION PEOPLE SUFFER FROM KIDNEY DISEASES. 2018.
- “KREMEZIN / COVALZIN | KUREHA CORPORATION.” Kureha.Co.Jp, 2014,