Difference between revisions of "Team:CSMU Taiwan/Safety"
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</a> | </a> | ||
<div style="border: solid 1px;padding: 0 5px;"> | <div style="border: solid 1px;padding: 0 5px;"> | ||
| − | <p>Phase1: Ensure the safety<br>→Check the safe dosage<br>→Find a few patients and give them the medicine to see how effective it is<br>→Continue to adjust the dosage amount and other medicine related parameters | + | <p>Phase1: Ensure the safety<br>→Check the safe dosage<br>→Find a few patients and give them the medicine to see how effective it is<br>→Continue to adjust the dosage amount and other medicine related parameters</p> |
| + | </div> | ||
<div style="border: solid 1px;padding: 0 5px;"> | <div style="border: solid 1px;padding: 0 5px;"> | ||
<p>Phase 2: Drug Test<br>→Find a large amount of patients , see if the medicine achieve the safety and effectivity we expected<br>→the Ministry of Health and Welfare approves the result</p> | <p>Phase 2: Drug Test<br>→Find a large amount of patients , see if the medicine achieve the safety and effectivity we expected<br>→the Ministry of Health and Welfare approves the result</p> | ||
| + | </div> | ||
<div style="border: solid 1px;padding: 0 5px;"> | <div style="border: solid 1px;padding: 0 5px;"> | ||
<p>Phase 3<br>→Apply for marketing authorization of the government: Taiwan Food and Drug Administration, TFDA<br>→Get the Medicament license, then we can produce our products</p> | <p>Phase 3<br>→Apply for marketing authorization of the government: Taiwan Food and Drug Administration, TFDA<br>→Get the Medicament license, then we can produce our products</p> | ||
| + | </div> | ||
<div style="border: solid 1px;padding: 0 5px;"> | <div style="border: solid 1px;padding: 0 5px;"> | ||
<p>Phase 4: Marketing<br>→Sell the products to the market<br>→Requires a long-term follow-up because most adverse drug reaction are unpredictable<br><br></p> | <p>Phase 4: Marketing<br>→Sell the products to the market<br>→Requires a long-term follow-up because most adverse drug reaction are unpredictable<br><br></p> | ||
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<h4>Patent Application</h4> | <h4>Patent Application</h4> | ||
<div style="border: solid 1px;padding: 0 5px;"> | <div style="border: solid 1px;padding: 0 5px;"> | ||
| − | <p>Experiment Stage: | + | <p>Experiment Stage:</p> |
<ul> | <ul> | ||
| − | <li>Note if any protocol/design have the potential to apply for patent.</li> | + | <li><p>Note if any protocol/design have the potential to apply for patent.</p></li> |
| − | <li>Keep every record of the experiments.</li> | + | <li><p>Keep every record of the experiments.</p></li> |
</ul> | </ul> | ||
| + | </div> | ||
<div style="border: solid 1px;padding: 0 5px;"> | <div style="border: solid 1px;padding: 0 5px;"> | ||
<p>Commercialize Stage:</p> | <p>Commercialize Stage:</p> | ||
| − | <ul | + | <ul> |
| − | <li>Note if any of the process infringes other people’s patents, they could sue you</li> | + | <li><p>Note if any of the process infringes other people’s patents, they could sue you</p></li> |
| − | <li>Do a search to check if any patent already exists.<br>(Consult the Incubation Center of our Academy ) </li> | + | <li><p>Do a search to check if any patent already exists.<br>(Consult the Incubation Center of our Academy ) </p></li> |
</ul> | </ul> | ||
</div> | </div> | ||
Revision as of 08:28, 20 October 2019
Introduction
The ultimate aim of technology is to create a better world for human beings. However, risks arise during the development of these techniques, varying from physical harm to privacy invasion. The advantages of technology can never be fully demonstrated if these potential hazards presents, therefore, safety should be of the top priority no matter for researchers or users.
Our team aims to develop a more essential influenza rapid test tool. Meanwhile, creation of a new diagnostic tool takes more than research and development. Implementation of such a device means it will be brought into direct contact with society. To ensure that our work is safe for the end user and to prevent miscommunication about the purpose of the technology, it is also essential to consider the social aspects that our tool will bring.
To sum up, in the safety section, we are going to explore four different aspects of our project, respectively Biosafety, Lab Safety, Regulations, and Ethics.
Biosafety
Labsafety
Regulations
Ethics
Biosafety
Our team complies with the third edition of Laboratory Biosafety Manual released by World Health Organization.
Moreover, according to Taiwan Centers for Disease Control(Taiwan CDC), some of the current status for Biosafety are stated as bellow:
1. Legislative and Regulatory Changes
In 2018, Taiwan CDC completed editing, revision, and announcement of the “Guideline for Governing Management of Select Agents and Toxins”, “Guidance on the Inventory of Select Agents and Toxins”, “Security Guidance for Select Agent or Toxin Facilities”, “Guidance for Suitability Assessments”, “Drills and Exercise Guidance”, and “Select Agents or Toxins Biosafety/ Biocontainment Plan Guidance”. We also accomplished the amendment of the “Regulations Governing Management of Infectious Biological Materials” on January 31, 2019, categorizing select agents and toxins as a special section.
What our team did to comply with it
Although no select agents or toxins on the list are involved in our experiment, we still looked through the guidance carefully.
Nucleoprotein and hemagglutinin of Influenza A and Influenza B virus are our target protein for SELEX, meanwhile whole influenza viruses are used to test the inhibition ability of our selected aptamers. In addition, in the Charactization and Improvement section, we improved the water solubility of HA1(Hemagglutinin for H1N1). The subtypes we chose are classified as seasonal influenza, which are surprisingly potential select agents too.
Apart from complying to the Biosafety manual for Level 2 labs, we also took some effort looking through Dual Use Research of Concern, DURC. After discussing with our instructor, we drafted a Risk mitigation plan.
2. Biosafety Mechanism Registration
By December 2018, 502 entities reported biosafety management units to Taiwan CDC, of which 496 entities established biosafety committees and 6 entities designated a biosafety specialist staff. These included 20 government agencies, 153 medical institutions, 54 academic research institutions and 275 other groups.
What our team did to comply with it
We are proud to announce that our institution, Chung-Shan Medical University, is one of the registered entity! We have applied for agreement to use virus in our experiment at the safety committee of CSMU, and the safety committee checked our facility, gave us a quiz regarding associated operations before permitting us. In addition, CDC tracks our usage regarding all contagious agents including influenza virus.
3. Biosafety Inspections of High-Containment Laboratories
Since 2006, Taiwan CDC has routinely inspected BSL-3 and above laboratories to monitor operations and ensure safety. In 2009, TB-containment laboratories, which process culture manipulation for identification and drug-susceptibility tests, were added to inspections. In 2019, Taiwan CDC completed the annual routine laboratory biosafety and biosecurity inspecting of 22 high-containment laboratories (refers to Level 3 and Level 4 biosafety and animal biosafety laboratories.) and RG3 pathogens storage facilities.
In addition, Taiwan CDC supervised the local government health bureaus to complete the laboratory inspecting of 75 BSL-2 microbiology laboratories of biotechnology industries. In order to strengthen biosafety and biosecurity of the entities that possess or use select agents and toxins, Taiwan CDC has counselled and visited the facilities of 7 entities in 2018.
What our team did to comply with it
All of our experiments regarding virus were conducted in the Biosafety Level-2 laboratories. Under the supervision of CDC, our instructor manages the lab strictly and obeys to all guidance written in the manual. For example, we were never allowed to enter the lab before putting on gloves, masks and lab coats. The wastes were always carefully collected and dispensed. Most importantly, our instructor seldom leaves us alone when performing experiments that could infect disease accidentally.
4. Laboratory Biosafety Education and Training
In 2018, 4 e-learning courses on laboratory biosafety were recorded. Taiwan CDC also organized 3 biorisk management and 3 select agents and toxins training course sessions, with a total attendance of 429 laboratory workers. Taiwan CDC developed “Laboratory biosafety management information system” (ver. 2.0) which helps to conduct and oversee the condition of management of storage and transformation of infectious biological material. We held 10 operation training and 2 systematic data maintenance symposiums to help all entities getting familiar with the system, and 508 laboratory workers attended.
What our team did to comply with it
We have organized to watch these videos when facing the same situations the videos focused on.
5. Laboratory Biorisk Management
In 2018, the bio-risk management system using CWA 15793 standard was introduced to 17 biotechnology-relatived microbiology laboratories. By focusing on continuous improvement and the Plan-Do-Check-Act (PDCA) cycle, this system will identify and monitor all aspects of laboratory biosafety and biosecurity.
6. Future Prospects
Taiwan CDC has participated in the Global Health Security Agenda (GHSA) for several years and realized the international concern of Biological Select Agents and Toxins (BSAT). In 2016, we applied JEE Tool (Joint External Evaluation Tool) published by WHO to assess the epidemic prevention system of our nation which includes reviewing the level of BSAT management. For the JEE Tool, the highest score for each indicator is score 5-sustaninable. Taiwan was scored 3-developed capacity in BSAT management. As a result, by 2018, Taiwan CDC has improved the insufficiency of BSAT management and has made a great progress on it. We believe by the time of 2020, we will reach a higher score on BSAT management on JEE tool, to prove the nation’s ability of managing BSAT can be as well as other advanced countries.
What our team did to comply with it
Not only did our team complied with the rules, we aimed to contribute to elevate the biosafety of lab and public health. In the section of design, we developed an AI system that is able to predict the spread of influenza.
To sum up, since our experiment involves in virus experiments, we paid special attention towards this issue to secure the safety for both the researchers and public.
Lab safety
Experiments regarding proteins of our iGEM project were conducted in the Biosafety Level-1 laboratories, whereas experiments associated with virus were conducted in the Biosafety Level-2 Laboratories. Both labs are under the regulation of Environmental Safety and Health Center of Chung Shan Medical University. The emergency exits and basic risk assessment are the first things to check every day prior to experiments.
Training
All members of the laboratory were well-trained by the mentors and had ability to conduct experiments in a safe environment. People who entered the laboratory should follow the established laboratory safety principles of our school. Master’s degree students of the lab and our instructor helped us to complete the safety training.
Special courses
Conference for Lab Safety, Microscope and Common Equipment Usage held by Department of Biomedical Sciences.
By attending the conference, we learned several important issues regarding lab safety as listed below:
1. Safety precautions and operating notice of commonly used instruments:
Freeze Dryer:
The order to start the machine is of great importance. First, we should turn on the machine in the middle to warm it up for about 30-60 minutes. Then we turn the pump open. Note that if any water drop slides into the liquid, the pump will rise. Therefore, remember to drop the water droplets slowly from below.
Low Temperature High Speed Centrifuge:
Balance is very important! Balance the weight before putting the samples into the machine. Do not mess with the tools provided by a different company from the machine manufacturer. For example, if we want to centrifuge with 15 cc centrifuge tube, we use the centrifugal sleeve provided by the manufacturer instead of plugging the tube into any other centrifugal sleeve. Under high speed centrifugation, unbalance could cause great damage to the middle shaft of the machine (which is the heart of it), and would be very dangerous to operators since the samples could burst out from the machine in a very high speed. Don’t put any thing on the machine when it is operating as well.
Laminar Flow (Hood):
The flow should be turned on for at least 20 mins before usage. The hood must be pulled down when the UV lights are on.
Autoclave:
Don’t put any PC materials into the machine or it could melt. Always remember to check if both the drainage knob and exhaust knob has been tightly closed before powering up the machine. Ensure that the door is fully sealed, however, don’t over-tighten the bolt as it may result in damage to the gasket. Before taking out the materials, turn the exhaust knobs loose. Gloves are necessary.
Ultrasonic washer:
The volume of water column needs to be adjusted according to the black indicator line. The water will drain out if it exceeds the line .
Micro scales:
Items must be placed in the middle of the scale. Always check the gradienter to see if the scale is standing at a horizontal platform .
2. School institutions that we can consult with when facing questions with the safety of experiments
˙ Always feel free to ask for help at the Environmental Safety and Health Center! If there is any problem regarding the instruments, please call the department for help, and the department will contact the company to handle it.
3. Other suggestions for improving the safety of laboratory operations:
If you’re uncertain about any step during the experiment, STOP! Never feel embarrassed to ask for help !!
MSDS
Material Safety Data Sheet, MSDS. Every chemical, reagents in the lab are printed and collected in this data folder. The folder is placed in a significant place near the door, which is easy to find and read in case of emergency.
Biohazard waste Management
All kinds of waste produced in the working area of the laboratory are considered biohazard waste, including every experiment and consumptive material. Those biohazard wastes would be collected into a specially labelled red plastic bag, and be sent to the Environmental Safety and Health Center of Chung Shan Medical University for further disposure process.
Regulations
All of our experiments are performed under laws and guidance as mentioned in the lab safetyand biosafetysection
Diagnostic tools have direct contact with the society. Numerous regulations and verification have to be approved before the product launch. Although our product is still in the research and development stage, during the process of consulting with government officials, biomedical companies and professors, we collected laws and regulations teams could face during the product legalization and marketing stage.
1. Animal Health Research Institute Council of Agriculture, Executive Yuan
We learned regulations associated with influenza epidemic prevention. Since our product aims to extend the usage of our rapid test to avian flu, the researcher and the director of Epidemiology Division “Fan Lee” gave us lots of information regarding avian flu control in Taiwan. It is sad to know that although laws are established, the government actually faces challenges when carrying it out. It dawned on to us that our AI system would be of great help when facing this situation. (see Design)
2. Adimmune Corporation’s Biotechnological Company(iHP)
We learned regulations regarding using virus in experiments and vaccine development including human clinical tests.
3. Doctor of the Laws Huei-Chih Niu, specializes in Health Care Law and Bioethics and Legal Policy for Gene Technology.(iHP)
We learned the laws associated with Experiments &Product design(00:00), Commercialization and Market Launch(01:48), and public promotion(08:10) including the attribution of responsibility if any unexpected situation arises.
Experiment stage(00:00):
→Submit Application
→Review Board determine from the feasibility of science and the safety of ethics in the projects(including visiting our lab to see if we meet the requirements of basic operation)
→reject/rewrite/adjust
→everything complies with the regulation
→move on to clinical trial
Clinical Trial and Market Launch
Phase 0
→Pass the examination of Institutional Review Board, IRB
(complies to Declaration of Helsinki)
Declaration of Helsinki
Phase1: Ensure the safety
→Check the safe dosage
→Find a few patients and give them the medicine to see how effective it is
→Continue to adjust the dosage amount and other medicine related parameters
Phase 2: Drug Test
→Find a large amount of patients , see if the medicine achieve the safety and effectivity we expected
→the Ministry of Health and Welfare approves the result
Phase 3
→Apply for marketing authorization of the government: Taiwan Food and Drug Administration, TFDA
→Get the Medicament license, then we can produce our products
Phase 4: Marketing
→Sell the products to the market
→Requires a long-term follow-up because most adverse drug reaction are unpredictable
Patent Application
Experiment Stage:
Note if any protocol/design have the potential to apply for patent.
Keep every record of the experiments.
Commercialize Stage:
Note if any of the process infringes other people’s patents, they could sue you
Do a search to check if any patent already exists.
(Consult the Incubation Center of our Academy )
See ethics for more about Associated Responsibilities
4.The incubation center of Chung-Shan Medical University
We discussed the legal issues related to our product, what we should notice before conducting technology transfer, and the kind of patent right recommended for us to apply.
Ethics
Ethics plays a crucial role in scientific research. All products our team developed and designed aims to give human beings a better and healthier life, hence the physically and mentally health, and the privacy of users should be of prior.
The diagnostic tool (rapid test paper), therapeutic vaccine, air purifier, and AI system involves different aspects of ethical issues, and we discussed these problems with Doctor of the Laws Huei-Chih Niu, specializes in Health Care Law and Bioethics and Legal Policy for Gene Technology.
Responsibilities
As mentioned in the Regulation section, even after the product is successfully launched, long-term follow-up is still required because most adverse drug reaction are unpredictable, so some questions came to our mind:
- Since our products composes of gene, and the affection of gene is unpredictable maybe it’ll take three to five years to see its side effect.
When this happens, is it the manufacturer, the product designer, or the government who should be responsible for the problem?
In other words, after all, the government had made an endorsement of the product, and the manufacturer sells it to the market with the endorsement. If a sudden problem occurs in the future, who should be responsible for it?
: There are two different logics here
- Consumer Protection Law and Products Liability
If the products has met the technology and standards of the time when launched to the market, and the government also approved the launch according to that standard. But then a problem which was unpredictable at that time arises after several years, we could not be blame the manufacturer. - Opposite view of the logic above
Since the consumers trusted the government, the product itself, and the company. But when accident happens, it is unreasonable to say that no one should be responsible for it. Therefore either the government or manufacturer should be responsible for it.
- Public Promotion
How do people feel commonly towards GMP products? How can we promote our product?
:This is a complicated question. The main problem is how consumers feel For example, if an epidemic becomes very serious one day, nothing else except the vaccine cures disease, people will use it no matter what risk it composes. : But if we have other choices, as long as any other competing company deliberately sets a rumor, the vaccine will not be accepted by the public.
The feelings towards this kind of technology products of Taiwanese people are bipolar,
- sometimes they are superstitious. As long as it‘s high-tech, everyone rushes to buy it.
- sometimes they are very sensitive, considering high-tech as high-risk and not even willing to try
Hence, it depends on public education and commercial means.
I think that because the sensitivity of this issue (DNA)is a bit higher than food, it is harder to predict how consumers will feel.
The main concern for consumers should be safety, whether the aptamer(DNA) will cause mutation or not.
- As long as it isn’t injected into germ cells, rarely will it cause any harm.
: Therefore you will have to explain it to the public.
To sum up, the feeling of consumers should also be taken into consideration, which is also a part of ethical issues that most people forget!