On November 21, CCADD invited Glen de Vries, the president and co-founder of Medidata, to speak at the Graduate School of Convergence Science and Technology (GSCST), Seoul National University. Medidata is one of the leading companies that has established a system to trace the drug development chain from the early stage of clinical trials to post-market surveillance. Mr. de Vries talked about his company's vision for “The Next Generation of Clinical Development” using the data science technology. He also shared the firm's novel approaches to streamline clinical trials and drug development. Mr. de Vries said, "Korea is one of the few countries that have successfully built a high-quality health care system and universalized IT services at the same time.” He continued, “Thus, the future of the Korean pharmaceutical industry will be reshaped by the IT's innovative role in clinical research.” 

More than 40 people gathered to hear Mr. de Vries’ lecture, who included not only the graduate students of GSCST, but also the employees of several start-ups in Gyeonggido Business & Science Accelerator (GBSA).The event was reported in a newspaper article.  

Prof. Howard Lee emphasized the importance of the holistic approach to ensure the safe use of biological agents, particularly in the field of rheumatology, at a policy forum sponsored by the Korean College of Rheumatology, held at the Seoul Foreign Correspondents' Club, Press Center, on November 14, 2018. Biological agents, since first introduced in the late 1990s, have changed the way that physicians managed patients with various connective tissue diseases, of which rheumatoid arthritis is a typical example. "Because biological agents are way different from small-molecule drugs in terms of their safety profiles, which most physicians are not familiar with", Prof. Lee said, "they have to be used carefully, preferably only by those who were trained how to correctly prescribe them and those who are experienced in detecting the adverse reactions, which often clinically manifested in atypical forms." "Reactivation of latent tuberculosis and increased occurrence of opportunistic infections are some examples", Prof. Lee added. Registries of patients using biological agents can be a useful tool to track down and detect adverse effects of biological agents, which are not easy to be screened out in clinical trials before marketing approval. In that sense, Prof. Lee requested the rheumatology society to be more proactive by initiating and maintaining a series of safety measures, hopefully under a full collaboration with and support by the regulatory agency. Most of the panelists at the forum agreed with Prof. Lee. 

ACTRiS and P-MATCH are the acronym of the two research projects CCADD has been undertaking, each representing the AI-based Clinical Trial Resource Information System and the the Precision Machine Learning AssisTed Clinical Trial Eligibility Assessment using Hospital Records, respectively. From the very moment of its establishment, CCADD has been quite keen on branding a new concept that it produced by using a professionally-designed and aesthetically-executed logo.

The ACTRiS and P-MATCH logos are easily recognizable through the use of a bold and capitalized sans-serif typeface except for a small 'i' in ACTRiS. The iconic figure left to the text in the logos symbolizes a pill or capsule cut in half. The figure is also cut in two, a triangle (left) and the remaining dome-shape (right), each denoting A and P, which are starting letters in ACTRiS and P-MATCH, respectively. Furthermore, a square dot after PMATCH makes the two logos attain some level of consistency between them. There are three variations in color: green, dark gray and white on black.

Chloe Minkyeong Lee of StudioPEEK created the logos, who also designed the logo of CCADD. The ACTRiS logo will feature at the web-based clinical trial information system CCADD is currently working on.

Prof. Howard Lee demanded that generic approval in Korea be tightened by not allowing the so-called 'joint-bioequivalence' or 'consigned-bioequivalence' route at a Korea National Assembly Forum, co-sponsored by Rep. Yoon Il-Kyu of the ruling Democratic Party and the Korean Doctor's Weekly. The forum was held to go over various regulatory issues associated with the recent recall of valsartan-containing anti-hypertensive agents by the Ministry of Food and Drug Safety in a haphazard way, prompted by a similar regulatory action by the European Medicines Agency, which was caused by a concern that the active ingredient manufactured by a Chinese company contained NMDA, which could be carcinogenic in humans.

According to Prof. Lee, there were at least three regulatory practices that could have prompted the valsartan debacle in Korea: too low bar for generic entry into the market, lack of a consistent quality assurance system to ensure the quality of generics and their sources (active pharmaceutical ingredients), and too generous pricing for generics. "These unique regulatory systems for generics in Korea have favored the incompetent generic maker to enter the market rather unruly", Prof. Lee emphasized. Prof. Lee added, "Many pharmaceutical companies, most which were not unsure of their quality, got generics approved through the join- or consigned-bioequivalence testing, and this system needs to be abolished."

More detailed story about the Forum can be found in the following articles in Korean or English. 

"The recent recall of valsartan API made by Zhejiang Huahai (China) following detection of a potential carcinogen has revealed the weak and scientifically unsound basis of the generic approval system in Korea", Prof. Lee spoke in a telephone interview with KBS. Prof. Lee detailed about this issue in a newspaper column. The number of recalled valsartan generics in Korea was 115, which was way greater than that in the UK (only 8) and Japan (only 1). The reason behind this difference was that Korea has maintained a relatively low bar for the approval of generics. For example, any company can sell generics if they could obtain them from anyone who has a marketing authorization of the generic. In other words, the company is not necessarily responsible for the quality of the generic, nor they have to show that they could make a qualified generic, which meets all of the regulatory requirements including the proof of bioequivalence. 

As a result, there are numerous generics for a single original product. This, in turn, has introduced an exceptionally high competition among the companies, which has implicitly encouraged unethical business practices such as kick-back and unlawful rebates. The issue also has brought some quality issues to manufacturing of generics in Korea. For example, many companies have switched their API source after approval, mostly to a low-quality Chinese company, of which Zhejiang Huahai may be one. 

Therefore, to preempt the recurrence of this quality API source issue for generics in Korea, the approval system has to be heightened, Prof. Lee summarized.    

The best model for humans is human. Drug development has long been suffering from the lack of translatability and predictability of the preclinical animal experiments to humans. Dr. Richard Klausner, former Director of the US National Cancer Institute, commented in 1998, “the history of cancer research has been a history of curing cancer in the mouse. … and it simply didn’t work in humans.” Twenty years fast forward, drug development scientists are still struggling with the same issue.

Microtracing/microdosing is an innovative technology that can revolutionize the current paradigm of clinical drug development. Typically, a very small amount of the drug, i.e., ‘microdose’, which is less than 100 micrograms (or 30 nmoles for proteins), is administered to humans. Since this is much smaller than 1/100 of the pharmacologically active dose, microtracing/microdosing technology can be employed at a very early stage of clinical drug development even when there is limited animal toxicology data. Furthermore, in order to trace minute doses, an accelerator mass spectrometer (AMS) is required and the compound should be labeled, typically with ¹⁴C. The microtracing/microdosing study allows clinical drug development scientists for generating the intravenous pharmacokinetics, mass balance, metabolite profiling, and absolute bioavailability data much easier, faster, and at a lower cost.  

Dr. Howard Lee has spearheaded the employment of microtracing/microdosing technology for drug development in Korea since 2012, supported by three government grants. Dr. Lee has successfully d a new research ecosystem for the microtracing/microdosing study, which helped him perform the first microtracing/microdosing study under a full investigational new drug (IND) application in 2014. The result of this study was published at the most reputable journal in the field. Dr. Lee has conducted two additional microtracing/microdosing studies, and has recently won a two-year grant of $1 mil, in which microtracing/microdosing technology will be applied to a new drug development study with biologics.

Min Ji has graduated from Hankuk Univeristy of Foreign Studies in February 2018 with a bachelor's degree in Bioscience and Biotechnology. She is now working as a researcher at CCADD, and considers applying for a graduate school next half this year.

Prof. Howard Lee has been recently awarded a government grant from the Korea Clinical Trials Global Initiative or KCGI to develop a clinical trial resource integration system, and a grant kick-off meeting was held on March 15, 2018. The total research funding was $560,000, which is equivalent to 500 million Korean Won. The title of Prof. Lee's proposed research plan was the AI-based Clinical Trial Resource Information System or ACTRiS, which is pronounced 'Act Ris'. All of the CCADD members have contributed a lot to planning and completing the research plan for ACTRiS, and they will also actively participate in the grant one way or another. In ACTRiS, Prof. Jang Hee Hong, Choongnam University College of Medicine and Choongnam University Hospital, will be leading a subset project to develop an integrated web-based system for review activities by the Institutional Review Board, particularly for multisite clinical trials. Additionally, Prof. Jin Wook Choi, Seoul National University Hospital, and Prof. Hyun Joong Kong, Choongnam University Hospital, have joined to lead the IT development projects. Furthermore, codings and programming works will be outsourced to Mebixon, a leading life science solution development company in Korea.    

What makes ACTRiS unique is its active employment of state-of-the-art user experience technologies, which will be led by Prof. Joongseek Lee, along with his UX lab at the Graduate School of Convergence Science and Technology, Seoul National University. Not only that, several aspects and system components of ACTRiS will be fortified by applying AI technologies. For example, the accuracy and completeness of the contents in ACTRiS will be automatically checked and corrected by AI. 

"It means a lot to CCADD that we finally secured this start-up grant for the smart clinical trials initiative in Korea, which is expected to officially start next year", Prof. Lee said. "This signifies the vision that CCADD set out was right. Smart clinical trial is the future."