Yonsei Student Pharmacist
THE
BLUE
VANGUARD 2018
NOVEMBER
Vol. 14
4-5 INTERVIEWS
A look into MSD Korea's ground-breaking digital detailing service, Call ME
14-15 COLUMN
Digital healthcare platforms : the newest trend of medical care 22-23 NATIONAL ISSUES
Online drug sale: promise or peril?
EDITOR’S NOTE
EDITOR'S NOTE
KIM GRACE
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THE BLUE VANGUARD
Technology, Marketing, and Medicine. The erratic confluence of these three is now an overture for an entirely innovative healthcare procedure, paving way for its transformation into “Digital Healthcare”. In consistence with this trend, Yonsei Pharmacy’s The BlueVanguards pinpoints down this issue with a series of intriguing articles-each and every meticulously written. In our 14th story, we address the anew platforms, embark on an interview opportunity with the ICE manager of MSD Korea to herald the renowned “Digital detailing service, CallME”, while augmenting the scope to “Online Drug Sales”. We, as student pharmacists, aim to continually envision the transformative healthcare trends, anticipate and absorb the changes, and thus act with deliberate speed. Sharing our thoughts as such, we endeavor to step back, face the situational-driven healthcare strategies, and ask challenging questions so as to manage our ways through the endless rounds of adventures ahead of us-all of which is the true virtue of The BlueVanguards.
CONTENTS
CONTENTS
4 PHARMACUETICALS
6
Pharmaceutical firms' entry into health functional food market
8
Lorcaserin, the Holy Grail of Anti-Obesity Medications
10 12 14 16
Alnylam Developed New Drug of RNAi
COLUMN Game Addiction: can it be classified as a disorder? Digital healthcare platforms Drug Repositioning in the 21st century
INTERVIEWS A look into MSD Korea’s groundbreaking digital detailing service, CallME
NATIONAL ISSUES
18
Who is responsible for the side effects of drugs purchased at convenience stores?
drug sale: promise or 20 Online peril?
INTERNATIONAL ISSUES
22
A Breath of Relief, NICE publishes new guidelines on an asthma treatment
24 26
Xiidra, a new approach to dry eye disease Are the drugs you take safe? : Varsartan 2018 VOL.14
3
INTERVIEWS
A look into
MSD Korea’s
ground-breaking
digital detailing service,
CALL ME
Grace Eun Yi Kim kimgr2002@gmail.com
T
he renowned ‘MSD Manuals’ has been an initial stop on the road for understanding medicine, but MSD Korea even further touches onto an electronic platform to better enhance the understandings of patient care. Its ground-breaking e-detailing service, CallME, not only delivers needed information to doctors, but also makes
the latest healthcare information easily accessible with high accuracy.
The BlueVanguards of Yonsei Pharmacy was able to kick off a series of Q&A’s with the ICE (Integrated Customer
Engagement) Lead, Seung Ah, Jung. ICE team branches out to CallME and MCM (Multi-Channel Marketing). The following discussion took place in September, 2018.
Q. What are the current goals and/or motto that the company is focused on, and how does this team work to support hitting those goals? A. ‘Patients First’. The very core of our character as a company has always been, and remains, to put patients first. We are all accountable for delivering high quality products and services, and by setting this vision at the very core of our values, we believe that all sorts of economic growth and health improvements will congenitally come. As you said, ‘MSD Manuals’ is indeed the ‘holy bible’ for health practitioners, yet had we not put patients as our primary focus, then such recognition wouldn’t have been possible. That is, all drug-use guidance that we provide merely specifies a wide range of the active ingredient, in which we would never limit the information to our own brand. Doesn’t this ring you a bell? Because we aspire to improve the health and wellness of people just by putting patients first, all our actions must be measured against our responsibilities to those who need or use our information.
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INTERVIEWS
Q. Who of which particular profession will be providing this service? A. Our CallME team is essentially an e-MR (e-Medical Representative) team, where a variety of professions collaborate to provide needed information to doctors; hence, the team does not limit its duty to pharmaceutical sales. That is, aside from merely promoting products, experts of this team have an excellent understanding of pharmacology and the science of medications. This way, the prime focus would be ‘educating’ and ‘providing needed information’. Hence, with frequently updated information, the highly specialized experts would help in having effective treatment outcomes, and we believe that this is what makes MSD’s CallME team more valuable to healthcare providers.
Q. How could MSD Korea integrate and adapt social media with detailing service? A. As explained, the detailing service adapts not only mobile apps but also internet-based phone calls. This puts MSD’s health guide provision only a heartbeat away from doctors, enhancing both accessibility and also reliability.
Q. What is this so-called service, CallME?
Q. Where do you see MSD Korea and its digital detailing service in the next few years?
A. CallME is a digital detailing service for the purpose of formulating a partnership with doctors. As you all know, drug-use and guidance are becoming personalized, and in cases where patients intake several drugs, DDI (Drug-Drug Interaction) and ADR (Adverse Drug Reaction) stand as the utmost concern along with optimal treatment options. For doctors who need fast and easily accessible information, but also ones that are up-to-date, the team would give an exact and an evidence-based consultation of treatment options simply by a phone call. A phone application is also provided, in order to ease their way in treatment selection. In fact, our CallME team extends our scope and touches onto a face-to-face orientation. A growing number of doctors participate in these activities and so our team does our best to fulfill their information needs.
A. Believe it or not, MSD Korea has in fact launched its very first partnered health care platform in 2002. Although it wasn’t as innovative as it is now, a once partnered health care has now hit over ten thousand medical customers and proves that it’s a truly ground-breaking digital marketing. The cornerstone to our success is, I believe, our ever-adamant codes of conduct, where we underlie patients as the very first focus. The only difference from 2002 is that we have paved our way by adapting trending technological usage with health guidance, and I see the same, or even improved outcomes if we put our core values as the main motivator, while having any trending digital platform that could use to ease access for information. Not only do we receive ‘calls’ digitally, but also by opening symposiums; by continually dedicating to this work, without doubt, CallME would be one of the most reliable sources as is for our renowned ‘MSD Manuals’. B
2018 VOL.14
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PHARMACUETICALS
Pharmaceutical Firms’ Entry into Health Functional Food Market
‘P
EunChan Lee
bihs1@naver.com
robiotics’, ‘Vitamins’, ‘Ginseng capsules’. What are they and why do we see them so often in stores? These are ‘health functional foods’ which are different from medicines in that the latter is for health maintenance and improvement by helping human body maintain normal function and activating physiological functions, while the former is for treatment and prevention of diseases. Demands for health functional food have been increasing with the social health-oriented trends like well-being and LOHAS (Lifestyles of Health and Sustainability. Keeping up with the trend, pharmaceutical firms have been fostering house brands for health functional food. To distinguish their product from the already established competitors, pharmaceutical firms have been utilizing relevant technical skills and special marketing strategies.
Yuhan Corporation’s health functional food house brand, ‘New origin’ Yuhan Corp., which has maintained a leading position in domestic pharmaceutical industry, released a premium health functional food brand named ‘New Origin’ this year. It launched several health functional foods including red ginseng, deer antlers, vitamin, lutein, milk thistle and probiotic under the motto of ‘establishing new standards for foods’. Yuhan Corp. differentiated New Origin’s health functional foods from those of other brands by utilizing accumulated know-hows as the industry leader. Its red ginseng product is distinguished from other products by containing not only roots but fruits and leaves in a bottle for the first time in Korea. New origin also applied ‘supercritical extraction’, a technique to extract substances using supercritical fluid in manufacturing lutein for the first time in Korea. By using supercritical extraction of ‘marigold’, its lutein keeps effective substances almost intact and does not leave harmful residues like hexane.
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THE BLUE VANGUARD
New origin’s special marketing strategy Pharmaceutical firms have been trying to differentiate their products from existing health functional foods, by not only using advanced technologies but also developing special marketing strategies. ‘New Origin’s marketing strategies have been successful. It opened its first ‘concept store’ in IFC mall located in Yeouido, attracting nearby office workers and becoming the new attraction for neighboring residents. The concept store consists of a restaurant as well as product sales room. The restaurant provides various salads, sandwiches and teas made of health functional food ingredients. For example, customers can enjoy salads with grinded vitamin C as a dressing. By operating the restaurant, ‘New origin’ demonstrates that its health functional food’s ingredients are originated from nature and can be adapted not only to tablets or capsules for functionality, but also to foods. Furthermore, DNA genetic testing vouchers are offered to customers who purchase health functional food over a specific sum of money. By developing special marketing strategies, over eight million customers have visited the store in the span of 4 months ever since it opened.
PHARMACEUTICALS
Why pharmaceutical firms jump into ‘health functional food’ market? There are some reasons why pharmaceutical firms have been investing in the health functional food market. First, the market is growing fast and expected to grow constantly with the increasing aging population. According to the Ministry of Food and Drug Safety(MFDS), domestic market size of health functional food increased 51% during 4 years from 2013 to 2017, reaching above 2 trillion won in 2017. Second, health functional foods have relatively lower entry barrier than that of medicine. Health functional food requires lower development cost and can come into the market in a much shorter time than the medicine. Third, pharmaceutical firms can utilize their relevant research and development know-hows and the infrastructures already established. Finally, marketing of health functional food is less restricted than that of the medicine. Utilizing these advantages, pharmaceutical firms have been investing into health functional food for short-term profits, securing funds for developing new medicines in the long term.
Proper ways for pharmaceutical firms to proceed with health functional food Although pharmaceutical firms have been settling up in the health functional food market, there are still a lot of things to get through. As a late comer in the market, pharmaceutical firms’ health functional foods have been considered to be less competitive compared to existing products in terms of brand recognition and marketing competitiveness. To distinguish their products from existing ones, they should actively utilize their drug manufacturing know-hows, infrastructures including their own distribution network. More importantly, although business diversification is necessary for securing funds for new medicine development, they should be cautious not to put the cart before the horse. Pharmaceutical firms’ intrinsic roles like development of new drugs should be given top priorities. If these conditions are met properly, pharmaceutical firms’ health functional foods will benefit not only themselves but also customers, contributing to general health promotion. B 2018 VOL.14
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PHARMACEUTICALS
Lorcaserin,
The Holy-Grail Of Anti-Obesity Drugs MEDICATIONS Jieun Ryoo
gina1996@naver.com
Want to lose some weight? Here is the “magic” pill recently confirmed to be safe that might bring great changes to obese patients’ lives world-wide.
T
hese days, the prevalence of overweight and obese people is quite dramatically rising due to a lack of exercise,
unhealthy diet plans and maybe even environmental pollution. Therefore, many anti-obesity medications are becoming popular each day. The current holy-grail among many anti-obesity medications is lorcaserin, commonly
known as Belviq. It was first developed by Arena Pharmaceuticals to be used as anti-obesity medication on June 28, 2012. The pill, costing around 220~290 dollars per month, is about 10 milligrams and is taken orally twice a day.
Then how does lorcaserin work? Lorcaserin is as a 5-HT2C receptor agonist. 5-HT2C receptors are serotonin receptors located in various brain regions including cerebellum, cortex, hippocampus, amygdala, thalamus, and hypothalamus. It decreases one’s appetite by activating 5-HT2C receptors located in hypothalamus, the control site for appetite. The activation of 5-HT2C receptors in the hypothalamus increases proopiomelanocortin (POMC) level and causes one to feel full by decreasing appetite. During translation, cleavage enzyme removes 44 amino acid sequences from 285 amino acid polypeptide precursor called pre-proopiomelanocortin and forms POMC, which is 266 aa sequence long.
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THE BLUE VANGUARD
POMC is then cleaved into multiple peptide hormones, including an appetite-regulating hormone alphaMelanocyte-Stimulating Hormone (α-MSH), which is packaged inside large vesicles and released by exocytosis when needed. Therefore, an increase in POMC level results in suppression of hunger, making one feel a lot fuller. It was also confirmed to be extra effective for middle-aged people since POMC neurons’ functions tend to degrade over age, requiring a lower dose to reach the same effect as in young people.
PHARMACEUTICALS
Why is it such a blockbuster? Although there had been extensive research on diet pills for decades, this drug is the first among many to be approved in over ten years. It is the first slimming pills that does not have damaging impacts on hearts. A recent clinical experiment involving twelve thousand obese people with risks of heart problems confirmed the safety of lorcaserin. The twelve thousand participants were divided into two groups; one received lorcaserin and the other received placebos for about three years. The two separate groups showed relatively same number of cardiovascular problems before the experiment. After three years, the drug helped patients lose about 4.2 kgs per year. On the other hand, patients who took placebos lost only about 1.4 kgs. Moreover, it was proven that the drug tends to show minor improvements in factors associated with cardiovascular diseases including levels of blood glucose, triglycerides and heart rates.
The experiment also showed no apparent side effects like increasing the rate of cardiovascular diseases using this medication, striking a major difference from most other diet pills. The rest of the weight-losing pills have some negative effects on the heart which can possibly give rise to heart attacks, strokes and pulmonary hyperextensions. Moreover, excess weight causes faster heart rates and weakens heart muscles, leading to congestive heart failures. Slimming pills often times include stimulants and those stimulants also fasten heart rates, making one feel very alert and far less interested in eating. Therefore they often cause arrhythmia and irregular heartbeats and were rather soon dumped from markets. Unlike these stimulants, lorcaserin simply activates serotonin receptors and makes patients feel satiated.
Conclusion It is true that the lorcaserin is the first anti-obesity drug that has no negative impacts on cardiovascular problems. However, it is still not the ultimate solution to solving weight issues. In order for weight loss to succeed in the long run, one has to change eating and exercising habits along with taking lorcaserin medications. Hopefully, lorcaserins will not only help obese people but also shed a new light on upcoming research on slimming pills. B
2018 VOL.14
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COLUMN PHARMACEUTICALS
Alnylam Developed New Drug of RNAi
H
ow do our bodies work? Proteins are made from genes in cell’s nucleus, and each of them carries out their own roles to maintain a normal state. However, what if the information in the nucleus was wrong from the beginning? Wrong DNA sequences make wrong proteins, and this makes our bodies unable to perform normal functions. This is the main concept of gene-related diseases. Researchers have studied how to treat the gene itself, the root cause of genetic diseases, for a long time. And they are solving that complicated ‘the balls of string’.
HyeongGu Kwon
rgr4208@naver.com
Discovery of RNAi What if it is too hard and risky to change the genetic information in cells? Then it can also be a good idea to stop the intermediate processes. This is how RNAi tech works. Proteins get their own form through the process of transcription and translation. RNAi interferes with the translation process. Short double-stranded RNAs, called dsRNA or hpRNA, are cut by Dicer, cytoplasm protein, making siRNA(small interfering RNA). siRNA makes a complex of proteins called RISC(RNA-induced silencing complex). When RISC detects target mRNA by binding with the siRNA, it degrades and silences target mRNA. This phenomenon was first discovered by Andrew Fire and Craig Mello, a 2006 Nobel prize laureate, in 1998. They researched ‘Caenorhabditis elegans’ by injecting dsRNA to observe ‘overexpression’ of target genes, and the result was the direct opposite. That was the first check of RNAi. At first, this discovery was a great sensation. RNAi was simple to treat and easy to target overexpressed genes. Many people believed that this technology would lead the pharmaceutical industry by creating a new drug of concept. However, RNAi technology failed to carry on its glory.
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THE BLUE VANGUARD
Limitation of RNAi method Despite all the research and lab performance, RNAi technology was only valid in ‘in vitro’. RNA fragments are no longer effective in ‘in vivo’. They are just nucleic acids in the body, which are too unstable to break down by a nucleic acid degrading enzyme and are filtered out of body. Researchers had to find the way to reach RNA fragments into cells without disintegrating in the body, which means to protect RNA from blood stream and kidney filtration. Investors began to have doubts about RNAi drug delivery. Eventually, big pharmaceutical companies lost interest and began to discontinue their research. Despite such problems, here is one company with overcame that sort of adversities.
PHARMACEUTICALS
About Patisiran Patisiran, the first drug of RNAi technology, developed by Alnylam, got FDA approval. It cures heredity transthyretin amyloidosis, which abnormal proteins accrue in the body and damage the function of the heart and nerves. Alnylam designed this RNAi drug by packaging siRNA in lipid carrier to be delivered well to target site. This technique is called ‘stable nucleic-acid lipid particle (SNALP)’. This way has defects that lipid carriers are accumulate in liver and kidney, but this defect fits on heredity transthyretin amyloidosis(TTR) because transthyretin protein accrues especially in liver. The following data is clinical data at phase 2.
Ref) Suhr, O. B. et al. (2015). Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: A phase II multi-dose study. Orphanet Journal of Rare Diseases, 10 Retrieved
People who are treated with Patisiran got TTR level down with symptom improvement. About 80 days after treatment, the TTR level came back what it was, by continuous translation of amyloids. And there were no severe adverse effects. Alnylam are developing another delivery technology, like modifying siRNA structure, not complacent with lipid carrier method. Their success will be the motivation of developing CRISPR-cas9 new drug or other gene editing therapy. By editing defective genes, people get customized gene medicine and much longer healthy life. B
2018 VOL.14
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COLUMN
Game addiction:
ㅈ
www.bluevan
| Interviewsas | COLUMN | National Issues | Intern B it Pharamceuticals can be classified disorder?
Game addiction:
can it be classified as a disorder? Kyungeun Lee
kyungeun0217@naver.com
T
he 18th Asian Games closed in a great success in Jakarta-Palembang, hosting 12,000 athletes and officials from
45 countries. Among the forty sports that were featured in the two-week tournament, eSports debuted as a demonstration sport in this Asian Games. Representatives from eigtheen countries competed in six video-games
: Arena of Valor, Clash Royale, Hearthstone, League of Legends, Pro Evolution Soccer and StarCraft II. ESports will be introduced as an official medal sport in 2022 Asian Games in Hangzhou, China, and it is seeking for recognition in the Olympics. In fact, International Olympic Committee (IOC) held a forum on inclusion of eSports in July, so it may happen
in the near future. However, Thomas Bach, president of IOC, concerned that the so-called “killer games” would promote
violence or any kind of demonstration. Another sound of concern is that streaming eSports in the largest international multi-sport event will provoke game addiction among the spectators.
World Health Organization (WHO) announced “gaming disorder” as one of mental, behavioral or neurodevelopmental disorders in the latest edition of International Classification of Disease (ICD). It is characterized by the pattern of gaming behavior as described below: 1) impaired control over gaming (e.g., onset, frequency, intensity, duration, termination, context) 2) increasing priority given to gaming to the extent that gaming takes precedence over other life, interests and daily activities 3) continuation or escalation of gaming despite the occurrence of negative consequences When these symptoms severely interrupt with personal, family, social, educational, occupational or other important areas and found either continuously or recurrently for more than 12 months, diagnosis of gaming disorder is assigned. In the past, “addiction” in a medical setting was limited to substances such as alcohol, tobacco and drugs. Throughout the years, the boundary has expanded to intangible factors, such as pathological gambling, so games are starting to be considered as an intoxicant. In fact, a growing number of neurological evidence supports that games activate the brain’s reward system in a similar way as drugs do. When a person expects or undergoes rewarding experiences, dopamine is released and affects neurons in nucleus accumbens and other areas of brain, especially the prefrontal cortex. According to fMRI study by Simone Kuhn of Gehn University in 2011, 14-year-old frequent gamers had more gray areas in the left ventral striatum, which is a condition found in those addicted to gambling, due to increased dopamine release. Moreover, when pleasure system is
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THE BLUE VANGUARD
COLUMN
ngaurd.com
national Issues
Kyungeun Lee
kyungeun0217@naver.com
repeatedly stimulated, excess dopamine alters the dopamine receptors and neural connections. Thus, more rewards or reward-predicting stimuli are required to produce the same level of pleasure, leading to tolerance. Furthermore, excess dopamine changes some areas in the brain, such as amygdala, provoking negative emotions in the absence of addicted substance. Due to withdrawal, addicts express fear, anger and stress and crave for more and more substance. In addition, prolonged exposure to aggressive and brutal games can cause the game addicts to be more tolerant to violence and bullying even in real life. For example, the study of Jae Yop Kim on 1140 Korean teenagers shows that game addicted teenagers committed twice as much sibling abuse as non-addicted teenagers did. This phenomenon is caused not only by withdrawal and emotional explosion, but also by the lack of ability to distinguish escapist fantasy world of games from reality. However, many people are still skeptical about classifying game addiction as a disorder in clinical or scientific sense. Doug Hyun Han, a researcher at Chung-Ang University Hospital, claimed that game addiction is not a cause, but a symptom of other problems. Based on his research, he found out the problematic gamers have similar brain activities with people with ADHD, schizophrenia, autism and poor impulse control. Although the causal relationship between game addiction and disease is not clarified, this evidence suggests that people with behavioral or cognitive problems tend to be more captivated by the world of games. Therefore, game addiction is aroused as a symptom of another disease, or even as self-medication. Others are worried that labeling as game disorder may lead to false epidemics of compulsive behaviors, such as sex and eating. In the 21st century, the internet has changed the way people work, spend their leisure time and communicate with each other. Thus, before over-diagnosing a disorder, the line between hobby in a daily life and pathological addiction should be drawn clearly. Overall, classification of game addiction as a disorder is highly controversial, and many argue that it is taking a regular behavior too seriously. However, as long as there is a professional sound of concern about it, people should open the possibility and scrutinize the issue to further clarify the situation. Even though game addiction is not officially considered as a disease, it is still a worldwide problem, so prevention and treatment should be made. Game can be a beneficial hobby and even stress-relieving. Nevertheless, once it overwhelms one’s life, game is no longer a hobby, but a destructor that ruins life. B
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COLUMN
Digital Healthcare Platfor ms : the Newest Trend of Medical Care Kim Yong Wook
demosca1911@naver.com
H
ave you ever used mobile healthcare applications such as “Samsung Health“? A lot of people are using these app lications for medical purposes, or just for interest. Un
fortunately, most of data from these applications are not
being used by doctors, who really make medical decisions.
Reason for it might be that their reliability of data is not secured, or just there is no system to use their data. Today, many people are developing a system that delivers digital data in daily life to medical field to make ‘digital healthcare’. Digital healthcare refers to making solution to problems of healthcare industry with ICT (Information and Communications Technologies). The digital healthcare sector has a possibility to develop through rich data and the latest IT technology. In addition, the healthcare is a huge market occupying 18% of global GDP. Therefore, a lot of companies are trying to develop the digital healthcare platforms. For example, Samsung is developing the Samsung Digital Health Platform and Simband, and Apple is developing Health Kit. A digital healthcare platform is a system that collects users’ health data from healthcare devices and makes them usable for medical purpose. The main concept of digital health care consists of three steps : measuring data, integrating data, and analyzing data. From this point of view, digital healthcare platforms are trying to be involved in all these steps. For example, Validic, which is one of the major digital healthcare platforms collects data such as sleep time, blood pressure, amount of exercise, consumption of
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THE BLUE VANGUARD
alcohol and caffeine from healthcare devices. Then, the platform integrates and analyzes the daily health data to send them to medical team. As a result, medical institutions can access to people’s daily health data and apply them to medical decisions. This process is how the digital healthcare platforms work. There are other companies that are developing digital healthcare platforms. Apple is one of the most developed
COLUMN
companies. Since 2014, Apple has launched new systems for digital healthcare platform. An interesting character of these systems is the partnership with other various companies. They collaborate with digital health services and wearable device companies. Also they collaborate with ins urance companies, medical institutions,
and EMR companies. Collaboration with the with the former companies shows that digital healthcare need technologies covering various fields that can not be covered by a single company. And the latter shows digital healthcare platforms can be a part of the system. Samsung is also planning to develop digital healthcare platforms. They have made partnerships with various
healthcare companies and announced Simgand to public. However, digital healthcare platforms may not be as successful as we expect. A representative of Noom, a company that provides services for diabetes and health habits, said that people in medical field have negative opinions about analyzing the various health data generated by users and digital healthcare platforms. Google also ran Google Health, a healthcare platform in the past, but eventually stopped offering services in 2009. This is because of the conservative nature of the medical community and the inability to achieve the goal due to numerous medical regulations.
The digital healthcare platform is a very attractive business area and many companies are working together to develop it. This system is very innovative and will generate a great benefit once its introduction is completed. However, the digital healthcare platform may be necessary to only few people. Most healthy people don’t have to monitor their daily life. They might refuse to provide their personal information to be used in this system. Doctors may think this system requires lots of additional work to them. These opinions makes digital healthcare platforms as ‘good but unnecessary thing’. Companies therefore need to find motivation to persuade all stakeholders involved in medical care, such as patients, health care providers, and insurance companies. B
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COLUMN
DRUG REPOSITIONING
In The 21st Century Dayoung Kim
961211dy@gmail.com
A
ccording to Pharmaceutical Research and Manufacturers of America, drug development in the traditional way takes 2.6 billion dollars and at least 10 years on average. In spite of this high cost, only less than 12% of lead compounds are finally approved to be sold in the pharmaceutical market at the end. On the other hand, drug repositioning, DR, takes away such risks. Being one of the most perspective approaches of drug development, DR is a process of discovering new therapeutic effect of drugs or compounds that failed from clinical trials or ones that have already been marketed. There are a couple of ways that can be applied to DR: on-target and off-target effect.
The Benefits of DR compared to conventional ones Conventional drug development processes consist of preclinical research and clinical trial that ranges from phase I to phase IV. However, with DR, several steps can be eliminated, leading to a significant cost and time reduction. Preclinical research conducting an in vivo animal testing is the stage of identifying whether a new drug causes toxicity. Information gathered from this stage is reviewed by researchers for use in the clinical trial, where actual humans are tested. A Clinical trial is composed of four phases: Phase I ~ Phase IV. In Phase I, researchers primarily focus on how a new drug interacts with the human body, monitoring safety of the drug. On top of that, side effects and pharmacokinetic data are also studied. In phase II, the efficacy of the drug is tested by administering the drug to a group consisted of only patients. Side effects after a short-term dose, and pharmacokinetic data are also evaluated. However, the size of the group is not large enough to assure the effect at this stage. Phase III, the last stage before being marketed, provides the most reliable safety data with a larger size of the group and a longer duration of the study. Thus, adverse drug reaction that had not been observed can appear in this stage. Phase IV, namely, ‘post market surveillance’ is conducted for studying unexpected adverse drug reaction and novel indication unobserved under trial condition. On the other hand, drug development with DR can eliminate preclinical research and phase I of clinical trial. This is due to the fact that DR deals with drugs that failed from the late stage of clinical trial, meaning it is a drug that has already identified with its pharmacokinetic effect and safety.
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COLUMN
Strategy 1: On-target Effect
Strategy 2: Off-target Effect
On-target effect in drug repositioning is the discovery of a new efficacy that can cure new disease with the original target and mechanism of existing drugs. One biologically active molecule and reaction pathway have to do with several diseases, not with only one disease. Thus, as new biological phenomena or disease mechanism are revealed, an unanticipated efficacy can be found with the same target. In other words, one biological active molecule is related to several diseases, so the original target can be applied to treatment of other disease that originally unintended. For instance, Raloxifene, a selective estrogen receptor modulator, was originally developed for osteoporosis, and now also has become a drug of invasive breast cancer medication through on-target drug repositioning. In addition, CXCR4, a coreceptor for HIV-1 entry into CD4+ T cell, was developed as a target for HIV treatment and a clinial trial was conducted. However, heavy weight was put on the drug development due to its poor oral bioavailability, cardiac disturbance, teratogenic potential. After all, it was later found our that CXCR4 was associated with SDF-1 receptor which has a vital role in adhesion of hematopoietic stem cell to bone marrow. From this discovery, Mozobil (plerixafor, CXCR4 antagonist) in combination with G-CSF, was found to be a new efficacy as a stimulator of the release of hematopoietic stem cell to peripheral blood which is beneficial in transplanting patients with Non- Hodgkin lymphoma or multiple myeloma.
An off-target effect which is another way of drug repositioning can be applied to drug development by discovering a novel target molecule and the mechanism of a drug. Unlike on-target effect, this method deals with the same disease and studies relationship between the drug and new target. Usually, a drug acts not only on intended target but also on several other target molecules, which can be valuable targets for other diseases as well as causes of adverse drug reactions. Thalidomide is an example of an off-target drug repositioning. The drug once withdrawn from the pharmaceuticals due to its severe adverse reaction, was newly evaluated with its therapeutic effects. Originally, its on-target effect was anti-nausea medication while its off-target effect was inhibition of formation of new blood vessels. By applying this offtarget effect, the drug was found to interfere with tumor growth. As a result, thalidomide was repositioned as a drug of multiple myeloma and leprosy. On top of that, Telmisartan, an anti-hypertensive drug, was originally developed as an inhibitor of angiotensin type 2 receptor. While animal testing, it was discovered that the drug has another function of activating PPAR Îł receptors and improving insulin sensitivity. For this off target effect, telmisartan approved as an anti-hypertensive drug with activity of regulating insulin sensitivity in type 2 diabetics.
Nevertheless drug repositioning is not an up-to-date method for drug development, approaches for DR has been turned into other fashion. In the past, most of drugs that found new therapeutic effect through drug repositioning had occurred just by coincidence. However, today’s DR is conducted systematically in combination with advanced technology. Genome Wide Association study (GWAS) is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. Specifically, relationship between disease-associated single nucleotide polymorphisms (SNPs) and human diseases is focused in DR and this data can be used in identifying novel targets and alternative indication of existing drugs. According to National Institute of Health in 2015, drugs that have been linked to disease traits through genetic studies are reported to be twice as likely to be clinically approved compared to drugs with no such links. For instance, it is revealed that statins, originally developed as an anti-hyperlipidemia drug targeting HMGCR enzyme, also have relations with HMGCR as a gene for LDL cholesterol based on GWAS data. For this study, new therapeutic effect of statin was found as treatment of hypercholesterolemia. In rapidly changing world and improving technologies, the ways drugs are developed also change. Therefore, as a pharmacist, an ability to recognize the change and adapt to new trend is one of the necessary skills in modern days. B
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NATIONAL ISSUES
Who is responsible for the side effects of drugs purchased at convenience stores? Junseo Oh
ojoojo1194@naver.com
The risk of expanding safety household drug
R
ecently, Korean pharmaceutical market has stopped sales and distribution of Valsartan drugs made in China which were the raw materials used as antihypertensive drugs. The problematic Valsartan component was made in China’s pharmaceutical company ‘Zhejiang Huahai’, and the carcinogenic substance NDMA was detected as an impurity. Accordingly, on July 7 of this year, the Ministry of Food and Drug Administration (KFDA) suspended production and imports of 219 finished drugs in Korea. Two days later, on July 9, the KFDA carried out a procedure for collecting 219 items for which the use of the raw material was confirmed. After the outbreak of the Valsartan incident, pharmacists at the frontline started complaining about extreme fatigue. Exhaustion originated not only from continued protests from patients who expected to receive their prescribed antihypertensive medicine, but also from confirmation calls from relevant agencies to check they were properly preparing their medicine once again. As a result, pharmacists in the frontline had to get in touch with patients who had been prescribed the hypertension medication and they have refilled prescriptions one by one. Even drugs that are produced after a complete clinical trial are not completely safe. Furthermore, even if particular
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pharmaceuticals have been used for a long period of time and have proven safe, they have the possibility of showing side effects. One example is Tylenol. The hepatotoxicity of acetaminophen, the main component of Tylenol, is well known. In addition, convenience stores classify Tylenol as a household drug, as well as a drink that gives adverse effect to the liver. First of all, according to the agenda listed in the ‘Sales System of Safety Household Drug out of Pharmacy’, which is one of the Ministry of Health and Welfare’s pharmacy policies, it is recommended to complete the safety household drug seller training of four hours. But such education is not done properly. It has become an issue that a drug with large side effects can be easily purchased without guidance of a pharmacist. Drugs have been given to patients by part-time workers with no proper safety measures, increasing the risk. Furthermore, if the customers have suffered a serious adverse drug reaction due to drug misusage that led to death, then the responsibility for customers’ death becomes unclear. It is unclear whether the convenience store owner will have to take the responsibility or the part-time at the convenience store, or the guest. However, as in the case for the “Valsartan incident”, if the drug is purchased under
NATIONAL ISSUES
the supervision of a pharmacist at the pharmacy, when a problem occurs to customers, it is obvious who is responsible for that problem. As seen in the Tylenol and Valsartan cases mentioned above, all medicines can have
unexpected hazards. Even medicines that have undergone a number of clinical trials can be dangerous. Due to these reasons, drugs should be purchased only in pharmacies.
Accessibility or safety? Since the regional distribution of health care resources is concentrated in large cities, the gap in accessibility between different regions is one of the most important problems in Korea’s health care system. The fact that there are many convenience stores in large cities and the fact that many of patients live in metropolitan areas also means that the policy implications of selling safety household drugs are inevitably low. This can be seen as lessening the accessibility of pharmacists and pharmacy services. If drugs were sold at a convenience store, patients would go to the pharmacy and consult with pharmacists. As can be seen from the above-mentioned outbreak of Valsartan accident and Tylenol dangers, ‘Sales System of OTC drug out of Pharmacy’ is likely to cause problems in reducing safety rather than expanding accessibility. Let us discuss whether accessibility is more important or safety is important in drug sales. First of all, as a result of conducting an online survey on the expansion of safety household items from August 1 to 2 at the Citizens’ Coalition for Economic Justice, most people said that they need a sales system of safety household drug in convenience store. Also, to enforce that system when almost six years have elapsed, the market size of safety household drug has grown out of hands. For these reason, safety cannot be pursued at all. However, the problem of accessibility and safety is not a problem that can be solved just by expanding efficacy group of safety household drugs. We need a new policy about problems of drug sales, namely the “Late-Night
Public Pharmacy”. In a successful case in the European Union, under mid-long term plans are being put in place to ‘building a social safety net for mild illnesses’, the late-night public pharmacy project is being carried out by local governments. In contrast, in Korea, late-night public pharmacy has been operating on a minor level by voluntary dedication of individual pharmacists. Therefore, late-night public pharmacy in Korea must be enforced by refurbishing existing policies and establishing new ones. Until now we investigated present problem of convenience store drugs, we must correct that problem in a calm and orderly way. B
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NATIONAL ISSUES
Online Drug Sale: Promise or Peril ? You Sun Choi
clauchoik@gmail.com
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elling twenty capsules of Reductil 10mg at 110,000 won. Price includes prescription cost of 20,000 won and medicine worth 95,000 won originally. Shipping expenses on the seller. You might think it’s a bit pricey, but keep in mind that cheapest prescriptions still come at 10,000 won minimum. If interested, see contact below.
Posted on online second-hand market sites, messages as the one above induce potential customers to illegally purchase medicines that have been terminally withdrawn from the commercial drug market. When the same drug is searched on an online weight-loss community, forums titled ‘selling’ or ‘buying’ appear to have been posted steadily for several years now. These purchasing agencies thrive on social media as well, where overseas sellers provide procurement services that include delivering drugs only authorized outside Korea, or require a doctor’s prescription. Over the last decade, e-commerce has been on the rise and is now undoubtedly a leading business platform. Just about every aspect of e-commerce has evolved in the past years, transforming even the way we buy our medicine. Innovative B2C pharmaceutical models have been adopted by several countries including the United States, Canada and Japan. Nonetheless Korea, frequently regarded as an IT powerhouse and being at the vanguard of omnichannel commerce is, surprisingly, lagging behind this market trend. This is due to regulations imposed by
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the current Pharmaceutical Law, which prohibits the sale of drugs at places except authorized drugstores and retail shops. As drug usage is directly associated with public health, strict guidelines in manufacture and distribution are required to be followed. Moreover, the Korean Pharmaceutical Association (KPA) stands strongly against online drug sale, claiming that it will create disorder in the distribution channel and failure to control drug misuse or abuse would inevitably lead to deterioration of people’s health. Despite robust legal restraints, however, the number of cases for illegal online drug sale is rising each year. This situation was brought to the surface by the most recent inspection carried out by the Ministry of Food and Drug Safety, which also revealed that abortion pills, of all drugs, is grabbing a larger share of the pie. According to the audit data submitted to the Ministry, the proportion of illegally traded abortion pills rose from a 0.08% in 2016 to 4.6% in 2017, and this already comprises 9.2% of 12,000 illegitimate sale cases cracked down this year so far. Given that abortion is banned by law in Korea, abortion pills imported through
NATIONAL ISSUES
unverified courses is posing a health threat to women. an individual may bring in up to six bottles of medicine Do costs outweigh the benefits of online drug sale? if no prescription is issued, and up to three-months’ The current state of affairs call for a reevaluation of quantity if prescription is attached. Taking advantage buying drugs on the Web. The opinion of KPA is rational, of this loophole in the system, consumers venture into since drugs traded online have unidentified supply chains overseas purchase of drugs that are domestically restricted. and are susceptible to tampering. In fact, the top listing Commercial transaction over the Internet is practically among illegally traded drugs online are ETCs for erectile border-less; online shopping sites equipped with automatic dysfunction, of which a majority is fake. Counterfeit pills translation functions add the icing to the cake, satiating may contain less or a totally different type of the active customers’ desire to seek for convenience and diversity. ingredient, thus increasing the risk of adverse reaction. Namely, nicotine gum is classified as an OTC, but its Patients are to take full responsibility for any damage advertisement and sale pivots around open market giants caused, and there is no way to compensate for smuggled such as G-market, Coupang and Auction. Meanwhile, drugs. Moreover, online drug purchase lacks a proper open markets only act as a broker in the telemarketing medication counseling from a professional, and taking pills business and hold no responsibility on overseas purchase, at one’s discretion intensifies drug abuse. Furthermore, leaving buyers wholly accountable for their actions. there are other problems intrinsic of online C2C trade, Surging safety concerns regarding indiscreet online such as inadvertent disclosure of personal information trade gave rise to congresswoman Kim Sang Hee’s recent and inaccessibility to the Internet by elderly and the poor. proposition to revise the Pharmaceutical Law. This revision Nevertheless, it is beyond the capacity of health consists of altogether prohibiting overseas drug purchase. authorities to put a stop to illegal drug trade altogether. Except for those who are given the right to import drugs by Because the Ministry of law, i.e. pharmaceutical Food and Drug Safety does companies, or special Commercial transaction over the not possess investigation occasions allowed for Internet is practically border-less; power over the Internet, it research purposes alone, no online shopping sites equipped with must request cooperation individual will be allowed from the police. The goautomatic translation functions to have their medicine to method of clamping delivered from outside the add the icing to the cake, satiating down illicit drug trade is country. This amendment customers’ desire to seek for rather complicated. If the would allegedly reduce the convenience and diversity. seller’s IP address is in risk of medication errors and Korea, the police can chase protect people’s health from after personal information to get on to the offender. adverse drug reactions. But if the IP address is located overseas, it is essential The revised law may beat out bogus drugs from the to get assistance from the Korea Communications market but would definitely not be welcomed by the Standards Commission in order to block the website. public. Multilateral measures must be taken beforehand to Given these circumstances, public sentiment supporting exterminate the sale of counterfeit medicine. On the premise online drug sale is on the rise. Those in favor claim that that online pharmacies were allowed, sellers could be pharmaceutical products should keep up with the evolving required to register on the PharmaceuticalAssociation. Those trend of e-commerce to placate consumers’ demands. Along pharmacies that meet the requirements of a predetermined with the aging population, there is an increasing fraction of set of standards will be distinguished from other drug customers who are unable to access local pharmacies as sellers by an official license marked on their website. frequently as they ought to. Online purchase and delivery Consumers, on the other hand, could look up of drugs would undoubtedly make life much easier for the authorization details to make sure they are utilizing a disabled and aged. Furthermore, website-based pharmacies legitimate supplier. People see the Ministry of Food come in handy in comparing prices between different and Drug Safety as highly reliable. Public institutions providers, thus gaining support from price-conscious buyers. may act as educational information for consumers, Strained public opinion aside, some suggest that a such as precautions when purchasing drugs off the lack of consistency between the Pharmaceutical Law and Internet, or the risk of falling for deceptive advertising. the Customs Law is aggravating the situation. While As far as there is demand, consumers will always the Pharmaceutical Law strictly prohibits online trade of find out ways to circumvent the law and make any drug or sale of ETC without prescription issued by a online drug purchase an endless fight. Irrelevant of physician, the Customs Law merely evaluates whether the allowing online drug sale, the pharmaceutical society product is for self-consumption or not as a criterion for tax should always strive for fresher attempts to reconcile imposition or exemption. Thus, under the Customs Law necessities of consumers with nation’s health. 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INTERNATIONAL ISSUES
A breath of relief New guidelines from nice uphold Bronchial Thermoplasty as a safe and readily available option for severe asthma patients Su Min Jenny Yoon jenny.yoon.jy@gmail.com
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n the United Kingdom, around 5.4 million people suffer from asthma, and one out of twenty have severe asthma. Last week, a new asthma procedure called Bronchial Thermoplasty has been announced to be available on the NHS by the end of this year. The National Institute for Health and Care Excellence (NICE) claimed it can be offered on NHS and more frequently than before because recent studies have proven the procedure to be safe and effective. This new asthma procedure, which does not rely on drugs such as steroids, is a novel technique that uses radio frequency to degrade muscle tissue in the lungs.
Asthma treatments in the past Most people are aware that asthma is a long term inflammatory disease of the lung’s airways that is caused by genetic and/or environmental factors such as allergens and medication. Normally, a patient’s symptoms include shortness of breath, coughing, and chest tightness. However, for severe asthma patients, these symptoms are much worse. Severe asthma cripples a patient’s life in ways ranging from not being able to step outdoors during pollen season to the inability to take a few steps to the bathroom. While an efficient treatment is crucial to alleviate these symptoms, most patients have a hard time finding the right combination of medicine. Usually, the prescribed medicine are inhaled corticosteroid (steroid hormones that reduces the inflammation in airways) for long term control medication, and beta agonists which stop asthma attacks for quick-relief. However, because the types, degree, and severity of symptoms can change over time and are unique to each patient, finding the correct combination and dosage of medication can be a very challenging task that take up to several years. Also, there may be few available medication that target a specific subtype of asthma, such as eosinophilic asthma. Oral and intravenous steroids usually last ten days to two weeks, and visiting the ER is common for severe asthma patients. This difficult quest for finding the right combination requires the patients to take very frequent trips to the hospital (every eight weeks), which can be burdensome.
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About Bronchial Thermoplasty However, Bronchial Thermoplasty (BT) may be the light at the end of the tunnel for patients with severe asthma. This procedure involves using a bronchoscope and small wire probe extending into the lungs in three separate procedures: one for each lower lobes of the lung and another for both upper lobes. The probe is maneuvered to touch the airway walls, and then is heated using ten-second bursts of radiowaves that heat the lining of the lungs to around 65 degrees Celsius. This heating destroys parts of the smooth muscle tissues, reducing the ability to constrict during an asthma attack. After the initial treatment, two further sessions of three weeks intervals complete the procedure.
INTERNATIONAL ISSUES
Catheter placed distally in airway, electrode array expanded and controller activated
Electrode array partially collapsed and moved 5mm proximal to previous activation
Electrode array expanded and adjacent but not overlapping activation completed
Why the attention now? Back in 2011, Bronchial Thermoplasty was approved by the US FDA but was not readily offered by doctors due to uncertainties regarding the safety and efficacy of the procedure. Up until recently, NICE guidelines stated that Bronchial Thermoplasty could only be carried out under special arrangements with clinical governance, consent and audit. This meant that informed consent of the risks of harm was required from both the patient and medical staff before the procedure could proceed. However, recently the advisory committee of health professionals at NICE changed the recommendation to standard arrangements after reviewing new data on the safety of the procedure. Under standard arrangements, doctors can now readily provide the treatment as a option for the patients in specialist centers that have on-site access to intensive care. In a clinical study, BT has been found to reduce asthma symptoms by 5 years. Now that the procedure is offered on the NHS, it costs between 7,099 and 7,257 euros per patient. Since the annual-per-person medical cost of asthma is estimated to be 1,600 euros, over 5 years this number adds up to 8000 euros. According to this estimate, patients will be able to save up to 900 euros. Thus, BT will not only bring down the frequency and duration of visits to the hospital, but also reduce the overall medical cost.
Electrode array partially collapsed and moved 5mm proximal to previous activation
Asthma Attack
Post BT Treatment
Constricted airway during an asthma attack Contracted airway smooth muscle
Electrode array expanded and adjacent but not overlapping activation completed
BT reduces asthma attacks by reducing airway smooth muscle muscle
Looking forward UK is not the only country where BT is becoming more accessible. Just recently in February of this year, Apollo Hospitals in Chennai, India, has successfully performed Bronchial Thermoplasty on a patient who has been suffering severe asthma for over 40 years. As successful cases and studies show, BT can significantly reduce money and time that severe asthma patients pour into treatment in the long run. Now that NICE has extended the procedure for wider use, it may just open the door for patients to take relaxing strolls outside, and perhaps even smell a flower during blooming season. B
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INTERNATIONAL ISSUES
Xiidra®, A New Approach To Dry Eye Disease Ye Ji Jeon
yejijeon97@naver.com
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ave you ever felt irritation or itchiness from dry eyes while staring at electronic devices or reading books? Most people would say ‘yes’ to this question. According the surveys done by US census and BOSS (Beaver Dam Offspring Study) tell us that about 30 million American adults are suffering from consistent dry eye disease, and Gallup poll is expecting this number to continuously increase steadily for the next ten years. As known, dry eye disease is a common problem which is difficult to cure completely. Until now, the treatment only alleviated symptoms. However, now we do not have to worry since a new medication for dry eye disease is being developed: Xiidra®. Xiidra® developed by the pharmaceutical company Shira, is the first FDA-approved prescription medication for dry eye disease ever since Restasis was approved thirteen years ago. So, what is Xiidra® and how does it work? To understand Xiidra® better, we should first understand what a dry eye disease is.
Past perspective on dry eye disease — Dry Eye Disease or Dry Eye Syndrome? In the past, the dry condition of our eyes was called ‘Dry Eye Syndrome’. The word ‘Syndrome’, is a term commonly used when the cause or mechanism of the disease is not fully understood yet. Therefore, the medication for dry eye was given without complete understanding of the condition and only complemented insufficient tear generation. This kind of treatment was not enough to fully cure the disease;
it only alleviated the symptoms temporarily and did not prevent recurrence. However, nowadays along with new scientific findings, a new perspective to understand the dry eye finally changed the name of the condition to ‘Dry Eye Disease’, instead of ‘Syndrome’. So, how does the dry eye disease occur based on the new perspective?
A new perspective on dry eye disease — the disease mechanism and how Xiidra® works The new perspective on dry eye disease explains it in terms of inflammatory response mediated by T cells at the surface of the eye. There are two major type of T cells for dry eye disease: TH1 and TH17. First, TH1 and TH17 moves into the eyeball through bloodstream. At the surface of these T cells, there are integrin receptors called LFA-1. Its ligand is called ICAM-1, which is specifically expressed at cornea and conjunctiva under dry conditions. The T-cells moving
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through the bloodstream bind to ICAM-1 by LFA-1. The combination of LFA-1 and ICAM-1 induces TH1 to generate IFN-gamma, which is a inflammatory cytokine that leads to damage of goblet cells and apoptosis of conjunctival epithelial cells. TH17 also produces an inflammatory cytokine called MMP-9, which breaks up the connection between epithelial cells of cornea and damages the cornea. These mechanism ultimately lead to the symptoms of dry eye disease such as irritation and itchiness.
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The interaction between LFA-1 of T cells and ICAM-1 plays significant role in dry eye disease, and Xiidra® focuses on this step. Lifitegrast, a component of Xiidra®, acts as an antagonist of integrin receptor. To be specific, Lifitegrast binds to LFA-1 instead of ICAM-1, thereby inhibiting ICAM-1 from attaching to LFA-1. By blocking the attachment sites of ICAM-1, the drug finally prevents dry eye disease from occuring. Furthermore, we could prevent the damage of cornea as well as occurrence of other symptoms by dry eye disease, and break out of the vicious cycle by completely treating the disease itself.
The significance of Xiidra® — What’s better than the existing medication? Now in Korea there are two major treatments for dry eye disease which are anti-inflammatory drugs: a Cyclosporin eye drop, Restasis®, and a steroid eye drop. However, these medications cannot satisfy all the following conditions: long-term safety and tolerability, rapid onset of action, whether the medication acts at a crucial step of inflammation cycle, and whether the medication improves both symptoms and condition (progress) of the disease. Unlike existing medication, Xiidra® satisfies all of the conditions above. Therefore, it is much more efficient in treating the disease completely, rather than just alleviating the conditions. Additionally, Xiidra®‘s effectiveness compared to Restasis® was also demonstrated by clinical trrial. While Restasis takes about 6 weeks to relieve the symptoms of dry eye disease, Xiidra® only takes about 2 weeks.
The most significant point of development of Xiidra® is in the medical field in that it suggests a novel perspective of dry eye disease based on ocular surface inflammation. It is expected to widen the range of choices for dry eye disease treatment and its mechanism would play a significant role in dealing with similar diseases and symptoms. It would also help our understanding toward anti-inflammatory drugs and its side effects, which would be a key to open a new chapter of medication for various diseases. B
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INTERNATIONAL ISSUES
Are The drugs You Take Safe? -Varsartan
Jeyoung Son
A
wpdud3944@naver.com
nnouncement from ‘Ministry of Food and Drug safety(MFDS)’ in July 7th, European Medicines Agency(EMA) published a notice that they are taking back the hypertension drugs that use ‘valsartan’ of Zhejiang Huahai
Pharmaceutical Co.,Ltd as a raw material. After then, in July 9th, that carcinogenic materials were detected
from ‘varsartan’ was reported in all media platforms and became an international concern.
To be healthier and to cure many diseases, we intake medicines. But ironically, in those that were made for treating illnesses, materials that pose harm was detected. The so-called medicine, ‘varsartan’ is what many patients intake to treat hypertension. EMA said that they detected carcinogen ‘N-nitrosodimethylamine(NMDA)’ in the varsartan of Zhejiang Huahai and they are analyzing the influences between the NMDA and the incidence rate of a cancer in July 9th. N-nitrosodimethylamine(NMDA) is a byproduct of varsartan and causes cancers. It is an industrial chemical which has high hepatotoxicity. If patients take the NMDA for a long time, it leads to liver cancer. International Agency for Research on Cancer(IARC) categorized the NMDA as a 2A group having the potency as a carcinogen.
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Accordingly, MFDS suspended the productions and sales of complete medicines that have already been approved by the MFDS to use varsartan. An a consequence, the raw materials cannot be imported and sold in the market. In Korea, the total productions and importation of varsartan was 484,682kg for the last three years and especially the ones manufactured from Huahai corporation was 2.8% of the total amounts. The ministry also said that the all medicines containing varsartan will not be prescribed, being managed by DUR system. The investigation of the byproduct is now on-going and they will promptly take actions like doing a recall or discarding the products according to the results. However, the manager added that this tentative measure is for the protection of patients as a
INTERNATIONAL ISSUES
prevention because there is no evidence about the relation between the amount of detected NMDA and harmfulness not yet. In August 6th, MFDS and Ministry of Health and Welfare(MOHW) announced a pre-investigation report about valsartan. All investigations of medicines that have been imported and produced in Korea was completed. Any drugs produced by similar method to Huahai corporation did not exceed the temporary standard NMDA level(0.3 ppm). However, some that were not produced by Huaha’s manufacturing process is now on investigation and some of products of ‘Daebong LS, corporation’ exceed the 0.3 ppm level. Hence, the total 59 medicines that use the valsartan of ‘Daebong LS’ are on a stop in its sales and also its production are now prohibited. To reinforce the management of NMDA in valsartan, the level of NMDA of medicines will be under 0.3 ppm. The criterias for these judgements are the guide line of ICH, several studies and consultation of specialists. Also the government’s representative said that EMA applied the same standard and considering the carcinogenic risk of NMDA, the decision is reasonable. Meanwhile EMA reported a study on health risk assessment of NMDA. According to the report, there is a possibility that one person of the five thousand people who takes the 320mg medicine containing NMDA for seven years can have cancer. Finally, all actions for the carcinogenic risk of hypertension medicines was completed in 23rd August. Summarizing the report, 1) The investigations of all medicines that contain valsartan was completed and the ‘Valsanin tablet 80mg’ of Myungmoon pharm, corporation exceeded the standard level and its selling and prescription was stopped. 2)For the tight surveillance of the medicine’s impurities, the self management of impurities will be mandatory. Also the registration of abroad pharmaceutical firms will be implemented and the administration system will be reinforced by legislation. Furthermore, only safe medicines that satisfy the standard NMDA level in valsartan will be distributed in the market. 3) The government is studying about the influence on patients that intake the controversial medicines based on the patients’ information which Health Insurance Review & Assessment Service(HIRA) has for epidemiological survey. 4) The patients who were prescribed the medicines containing NMDA can be re-prescribed with alternative drugs for free, one time only at the hospital or pharmacy that prescribed the drugs before. 5) The patients taking the prohibited medicines must not stop taking the medicines by themselves and consult with doctors. The controversy about the carcinogens in hypertension-treating drugs is decreasing by the final reports of MFDS. However, in 13th October the government said that they will exercise the right to indemnity and proceed damage suit. The representative of Division of Pharmaceutical Benefits said that nobody takes responsibility for the damage and dumped all the loss on National Healthcare Insurance Service. After the end of the year, the outline of the sum for right to indemnity and total scale of suit for each pharmaceuticals will reveal. He explained that until now the re-prescription and exchange of medicines are ongoing so the cancellation of the restriction of the medicines’ selling must be continued. Some of the pharmaceuticals argued that the law suit is unfair and the evidence that the NMDA causes cancer is still disputable. They added that pharmaceuticals didn’t have any intentions to do that and they made the drugs following the MFDS’s guidelines so if the lawsuit is in progress, they have very small social responsibility about this circumstance. A government representative said that the carcinogenesis of NMDA should be studied by MFDS. The MOHW will just clarify who is responsible for the financial loss of national healthcare insurance service. Like this, the finding of carcinogen of hypertension drugs leaves a huge blow for the government, pharmaceuticals and people. This incidence made people doubt the safety of medicines and the whole medical field by extension. Also the pharmaceuticals took damage to the trust of people and the government got a huge loss of the budget. Upon this case, the government and pharmaceuticals should make definite criteria for harmfulness of medicines and prevent the dangerous situation like this. B 2018 VOL.14
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MEMBERS Editor-In-Chief Kim Eun Yi
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Kim Da Young Journalist
Ryoo Ji Eun Journalist
Journalist Lee Eun Chan
Journalist Yoon Su Min
Lee Kyung Eun Journalist
Journalist Oh Jun Seo
Designer Park Yoon Sung
Jeon Ye Ji Journalist
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Address
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