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- 2026-04-17 19:19:01
- Company
- Champix, conclusion of patent disputes imminent
- by Kim, Jin-Gu Dec 17, 2019 06:34am
- A patent dispute over the Champix(Vareniclin) marks the end. The Patent Court has announced that it will issue a judgment on a patent dispute related to the Champix on the 20th , 4 days later. The result of the Champix patent dispute attracted interest in that it could see the future of domestic salt-modifying drugs after the so-called ‘Solifenacin decision’ earlier this year The legal disputes between the two sides were so intense that the court would postpone the sentence four times. The ruling, originally scheduled for February, was postponed for four months, from May to August to October to December. The jurisdiction of the judiciary is also a matter of how deep. The ruling of the patent court is expected to be applied as a definitive ruling. This is because the Supreme Court's appeal is unlikely, as the expiration date of the material patent is almost imminent. ◆Patent Judge sided with generic company, Pfizer appeals In September 2016, more than 20 domestic companies, including Hanmi Pharmaceuticals, filed a patent dispute with Pfizer. Domestic companies tried to speed up the launch of generics with the strategy of “avoiding patents with salt changes.” It is a strategy that avoids the extended duration of material patents by developing salt-changing generics and raising passive judgments on the scope of rights. The Patent Judge, the first case of a patent dispute, raised the hands of domestic companies. Based on this, domestic companies have launched salt-modifying drugs since last November. Pfizer dissatisfied with the decision of the Judge. The company filed a lawsuit with the Patent Court asking to cancel the decision. The ruling on the lawsuit is sentenced on the 20th. ◆Interpretation over Supreme Court's decision to Solifenacin. During the second trial over Champix, a ruling was imposed elsewhere that would have a modest impact on the case. It was a Solifenacin decision issued by the Supreme Court in January this year. The Supreme Court sided with the original company, Astellas, in a salt-altering patent dispute between the original company and the generic company over Solifenacin, an overactive bladder treatment. The key point of the ruling was that ‘the salt-modified product and the original product had substantially the same active ingredients, therapeutic effects, and uses, and those skilled in the art could easily change the salt’. Interpretations were mixed with this ruling. Pfizer and other originals interpreted the Supreme Court as setting a case for the salt change, which has been the main patent evasion strategy of domestic companies. Of course, the case is expected to affect the results of the Champions suit. On the other hand, some domestic companies draw a line that the case of Solifenacin salt-modifying drug and the Champix salt-modifying drug, which were previously lost, is quite different. They explain that the 'substantial identity' that has been crucial in the Solifenacin decision is a separate part of the decision. They also argues that there is a difference in the ease of realization of technology by trade technicians. ◆If a domestic company loses, 'Change salt patent avoidance' strategy useless The patent court's decision will act as a measure of whether to avoid the patent of salt-modified products in the future. If the patent court raises Pfizer's hand in accordance with the Supreme Court case, domestic companies will not be able to use the patent evasion strategy by changing the salt. On the other hand, if the patent court raises the hands of domestic companies separately from the Soliphenacin case, the avoidance of salt-changing patents by domestic companies is likely to continue strategic vitality. A legal personnel said, “At present, the patent court is expected to apply Solvenasin's judgment as a precedent and side with Pfizer, however, as domestic companies insist, there is some possibility of judging the Solifenacin case and the Champix case separately. Either way, it will have a big impact on our strategy for avoiding salt modifications in the future”. ◆Material patent expires after 7 months, Less possibility of 3 trial appeals On the other hand, even if the patent court raises Pfizer's hand, there is a possibility that domestic companies are unlikely to lead the case to the Supreme Court. This is because the champix material patent expiration is shortly until July 19 next year. Given the time it takes to appeal after the Supreme Court appeals, it is likely that the avoidance of the extended patent duration, which was the original purpose of the patent dispute, has already been achieved. In addition, as domestic sales of Champix have been plunging recently, domestic companies' economic incentives have weakened significantly. According to drug research firm IQVIA, Champix's 3Q revenue was ₩5.7 billion, down 46% from ₩10.6 billion a year earlier. It is a quarter compared to the peak season, ₩21.4 billion in the first quarter 2017. An official in the pharmaceutical industry said, "With a huge drop in sales of successful successes, we know that many pharmaceutical companies have decided to stop the release of Champix salt-modifying drugs regardless of the Soliphenacin case." Champix
- Opinion
- [Column] Self-injectable drug abuse, is SPD the answer?
- by Kim, Jung-Ju Dec 17, 2019 01:40am
- Self-injectable obesity treatment Saxenda has been under fire constantly, because the obesity treatment has been abused as a weight management injection generating not only safety concerns but also questionable profit for the interest group. Apparently, the government said it would provide answer to it in November. Some likely suggestions are individual unit packaging and separation of prescription and dispensing (SPD) system. Undue profit generated from abusing Saxenda? Demands for Saxenda has soared when the words got out that the injection is great option for controlling obesity. Accordingly, frequency of prescription and administration showed steep growth since then. However, it is questionable if the users in need of Saxenda are taking appropriate procedure to acquire the treatment at a moderate price. Before a medical profession makes a decision on the necessity of Saxenda administration and dose, user’s demand can make decisions first. As a result, inappropriate prescription of the injection raises concern of adverse reaction and safety. Other than the user’s demand, it also has been meddled with prescriber’s interest in profit. Abnormal amount of financial profit has been generated when prescribing and dispensing the injection, and such push in profitability has been pointed out as a reason for the abuse. Also it is problematic that some of the healthcare institutes and drug distributors are illegally supplying the treatment for the sake of financial gain. Besides making illegal profit, illegal supply of drug could bring serious safety issues. Is Saxenda abuse preventable? Plenty of reasons can be suggested for the abuse. But the user’s perception is the biggest reason. Drug users seeing Saxenda as a weight loss tool for esthetic purpose, rather than a health condition treatment, is one of the main reasons. And doctor’s perception is as problematic. The doctors are the ones to judge the necessity of the treatment use, and a drug prescription and frequency are decided by them as well. The doctor could be prescribing the treatment to the users to increase patient visit frequencies and profit. The user’s abuse can be shifted or prevented by educating and raising awareness of the risk. But doctors need more than a mere training and public service announcement; they need proper regulatory management. The health regulator could intervene doctors with insurance-covered medical service fee review, and pharmacist with the SPD system. Illegal drug supply can worsen the situation and its severity level. Countermeasure on illegal distribution is necessary not only to prevent drug abuse, but also to secure the order in distribution process and to stabilize medical expenditure in the National Health Insurance. Is SPD the answer to prevent self-injectable drug abuse? There are a number of suggestions to prevent drug abuse. Preventing and managing drug abusing by changing the perceptions of user and prescriber has limitations. This is why the regulatory management is needed. Besides the review procedure of insurance-covered medical service fee, the regulator could take account of SPD system as one of options for the regulatory management. The purpose of SPD system is to appropriately integrate economic feasibility and safety of drug use. Moderate use of drug consists of economic feasibility, safety and convenience. And it is the reason the injection was exempted from the SPD system. If an injection were to be dispensed at a pharmacy, the user would have to take it to a healthcare institute to get a shot. But self-injection is an exception and it can be shot either by a medical profession or the user themselves. However, the dual option of administration has become a loophole and it has created a side effect of drug abuse. Therefore, the regulator should positively consider applying SPD system on self-injectable items as well. The treatment was labeled ‘self-injectable’ for the sake of convenience, given the safety is guaranteed. To keep safety and economic feasibility from drug abuse, a handful of drug users should deal with inconvenience of administering the injection at a healthcare institute. The SPD system is not the only measure to prevent and manage self-injectable drug abuse. The government and insurer should endeavor to educate users and prescribers to change their drug use behaviors, while regulatory amendments on review and evaluation, and illegal distribution management are made, simultaneously. The interest group may additionally demand for increased dispensing fee and other means of compensation for SPD. But we should count on the interest groups to logically and reasonably handle the situation.
- Company
- Venture capital investment on bio sector breaks record again
- by Kim, Jin-Gu Dec 16, 2019 10:55pm
- The new investment volume in pharmaceutical and bio industry is expected to mark the highest figure in the history, despite multiple risks occurred in the year. Following last year’s record-breaking volume, this year’s investment volume is to break the last year’s record. Korean Venture Capital Association (KVCA) recently published a Venture Capital Market Brief, as of October 2019. The report found the accumulated new investment volume all across industries reached 3.52 trillion won until the October. Apparently, pharmaceutical, bio and medical sector marked the highest ratio of the entire volume. The sector received investment of 984.1 billion won as of October, taking up about 27.9 percent of the total accumulated investment volume. Last year alone, the sector’s investment volume surpassed 841.7 billion won. Following after the top invested sector, the ICT service sector was invested with 782.5 billion won (22.2 percent) showing a gap of 200 billion won with the top sector. Based on the trend, the pharmaceutical, bio and medical sector’s new investment volume in the year is expected to exceed one trillion won for the first time in the history. After placing itself on the top spot last year, the pharmaceutical, bio and medical sector’s new investment volume has been widening the gap between the second place. The sector actually outperformed itself despite a series of fallouts in the year, like revoked approval on Kolon Life Science’ Invossa-K, and failed Phase 3 trials by SillaJen, Helixmith and HLB. KVCA reported 17 out of 21 special technology listing cases were from the pharmaceutical, bio and medical sector. 11 companies from the sector either have already been listed or are to be listed until the end of the year. The association official explained the background of skewed new investment volume and said “Ever since the special technology listing system was implemented from 2005, the pharmaceutical, bio and medical industry’s share of the overall special technology listing has been the biggest at 78.6 percent”.
- Company
- Huons, challenges localization of Hyaluronidase
- by Lee, Seok-Jun Dec 16, 2019 10:55pm
- Huons Group will challenge the global hyaluronidase market worth ₩3 trillion. HuonsLab, a bio research and development company specializing in Huons Group, announced on 16th that it has signed a commissioned research agreement contract with Panzen, a cell line development company, to develop ‘human gene recombinant hyaluronidase’ cell line development and production process development. Panzen, founded in 1999 is engaged in research and development of biopharmaceutical products at home and abroad, including recombinant cell lines and process development. This year, Korea's own biosimilar anemia treatment (EPO) 'Panpotin' was approved in Korea. Hyaluronidase is a recombinant enzyme protein that breaks down hyaluronic acid and is used as a drug diffusion agent. Hyaluronidase has been recently developed to increase the use of Hyaluronic acid fillers for cosmetic purposes, and to increase drug delivery ability in accordance with the trend of developing antibody treatment or protein drugs subcutaneously rather than intravenously. According to GosReports, the global market for hyaluronidase is estimated to be ₩2.70 trillion by 2020. Huon's Lab challenges the localization of human genetic recombinant hyaluronidase. Huon’s Lab plans to establish a development system from the development of human gene recombinant hyaluronidase cell line with Panzen, which has the know-how and technology for the development of recombinant protein-producing cell line and process development. “We are expanding our bio business at the group level to lead the global healthcare market” said Wan-seop Kim, Huon's CEO. "Recombinant human hyaluronidase is an important technology that can be used in various therapeutics. If successful, it can be competitive in the global biologics technology market.".
- Company
- Collapse of Cialis, 6th place in 4 years
- by An, Kyung-Jin Dec 16, 2019 06:21am
- (Clockwise from top left) Photographs of Cendom, Viagra, Palpal, Cialis The market position of Cialis, which squeezed the market for erectile dysfunction with Viagra, was greatly reduced. In the aftermath of the generic drug market by domestic pharmaceutical companies, sales shrank to one-third of patent expiration. The share rank has changed from 1st to 6th place four years ago. Generic products such as 'Palpal' and 'Cendom' continued to strengthen in the entire erectile dysfunction treatment market. According to IQVIA data on the 11th, the market for erectile dysfunction drugs in the third quarter was ￦28.3 billion, an increase of 8.3% compared to the previous year. This is an increase of 13.8% from ￦25.3 billion in the third quarter 2015. Quarterly market size is steadily rising as generic products launched by domestic pharmaceutical companies are growing. Quarterly Sales of Major Erectile Dysfunction Therapeutics (Unit: KRW million, Source: IQVIA) In terms of sales of erectile dysfunction treatment, Hanmi Pharmaceutical's 'Palpal' has firmly maintained its leading position for four years since 2016. Palpal is a generic product of Viagra (Sildenafil) released in 2012. Palpal sold ￦5.7 billion in the third quarter, accounting for 20.1% of the market for erectile dysfunction. The company's sales grew 10.6% YoY to ￦5.2 billion, maintaining a more than double gap with its second-place Cendom. Palpal, which made an entry mark in the erectile dysfunction treatment market immediately after its patent expiration, exceeded sales of Viagra, the same ingredient as its original product, within a year after its release. In the fourth quarter of 2015, even the original Cialis, which was Tadalafil-based, beat the original erectile dysfunction treatment throne. Since then, it has not missed a market leader. Strong accent for generics were even more pronounced in the Tadalafil market. Chong Kun Dang's 'Cendom' remained second in sales, selling ￦2.5 billion in the third quarter. The company's market share increased to 8.8%, recording a 6.3% year-on-year growth. Cendom is a generic product that was released after the Cialis (Tadalafil) patent expired in September 2015. Since its launch, its market share has gradually increased, surpassing the original Cialis in the fourth quarter of 2017. In the fourth quarter of last year, the company is chasing Palpal by exceeding Viagra sales. Gugu by Hanmi, Another generic product of Tadalafil, ranked fourth overall in the third quarter, selling ￦1.8 billion, a 6.3% increase from the previous year. Original pharmaceuticals from multinational pharmaceuticals showed a sharp decline. Cialis sales in Lilly Korea fell 13.6% YoY to ￦1.5 billion. Compared to ￦5.1 billion in the third quarter of 2015, two-thirds of sales evaporated. At the same time as Cialis expired, it gave Palpal by Hanmi Pharmaceuticals a leading position in sales of erectile dysfunction drugs in Korea. Since then, The sales have been sequentially overtaken by Pfizer Viagra and Chong Kun Dang Cendom. Lilly signed a contract with Handok, a former sales partner, last year Lilly took complete charge of Cialis' domestic distribution, marketing and sales activities. However, there was no sales rebound effect. Cialis was pushed down to the same ingredient generic product, Gugu, in the second quarter of this year, and was lower than SK Chemical's 'MvixS' (Mirodenafil). After four years of patent expiry, the sales ranking has fallen by five steps. The gap with Dong-A 'Zydena (Udenafil), which ranked seventh in the third quarters, is only ￦10 million. Pfizer's Viagra sales are unlikely to recover. Viagra's third quarter sales came in at ￦2.4 billion, similar to the same period last year. The domestic market for erectile dysfunction drugs is estimated at 8.4%. It was once called the pronoun for erectile dysfunction, but its current sales are less than half of its Palpal. Comparison of 2018-2019 3Q revenue of major erectile dysfunction treatments (Unit:￦1million, %, Source: IQVIA)
- Company
- Industry feels growing pressure on metformin risk
- by Chon, Seung-Hyun Dec 16, 2019 06:21am
- Ministry of Food and Drug Safety (MFDS) The pharmaceutical industry’s concern over metformin impurity contamination is growing. The industry’s eyes are focused on the government’s action following its ongoing metformin usage status review. Some of pharmaceutical companies are promptly equipping themselves with impurity analyzer a self-testing. ◆MFDS initiates metformin usage status review, the industry fears of follow-up action An industry source reported on Dec. 15 that Korea’s Ministry of Food and Drug Safety (MFDS) has ordered pharmaceutical companies to assess manufacturing record of pharmaceutical product containing ‘metformin hydrochloride’ and investigate used active pharmaceutical ingredient. MFDS asked companies to report total number of drug items consisting of metformin substance, names and number of manufactured items, and names and number of non-manufactured items until Dec. 17. Molecular structure of metformin Pharmaceutical companies have to provide all information of items even covering ones in distribution at the moment, considering use-by date of complete products. For example, when an items’ use-by date is three years, then the item’s entire manufacturing record after December 2016 should be looked into. The ministry is also calling for a full report on active ingredients used in the metformin products. It means the ministry means to collect detailed information on DMF registration number and manufacturing plant of a complete product containing the ingredient under each serial number. The procedure resembles the ranitidine and nizatidine cases. When they find an issue in specific active ingredient and complete drug, the ministry can take a fast and accurate action based on the information submitted by companies. The pharmaceutical industry predicts the government direction is a part of the ministry’s preparation process, in case impurity is discovered in metformin medicine. Before the government body took an action on ranitidine and nizatidine cases, the ministry had reviewed detailed information on complete product and the active ingredients. MFDS had immediately ordered a sales ban on drugs with valsartan when Europe decided to recall the products, but it held back on the action for ranitidine and nizatidine until the thorough review on complete products and the ingredients was completed. The risk of metformin impurity broke out from Singapore. On Dec. 4, Singapore’s Health Sciences Authority (HSA) recalled three items out of 46 metformin containing drugs they investigated. The result confirmed contamination of N-Nitrosodimethylamine (NDMA) has surpassed daily acceptable level. Since then, the U.S., Europe and Japan initiated impurity testing on metformin drugs. All three regions are recommending companies to conduct self-testing on NDMA levels in their metformin drugs. ◆Companies initiating impurity self-tests and purchasing analyzer Companies in Korea are also encouraged to run self-tests on their metformin-containing items. So far the ministry has not officially instructed companies to test impurity in metformin ingredients. In fact, the ministry has not even ordered them to test NDMA level in complete product or announced a plan to collect all items for further investigation. MFDS’ lack of instruction could be because of the U.S. and Europe have not ordered for a recall on products with alarming impurity level, and also because the problematic metformin ingredient and complete product with the ingredient have not even been imported to Korea. Moreover, there has not been an official procedure of NDMA testing presented by the ministry. The complete products with contaminated metformin recalled in Singapore have not been imported to Korea, yet. However, it has not been confirmed yet if the active ingredient used in the recalled product has been used in Korea. Apparently, the Singaporean regulator has decided to recall the products after testing complete products, not the active ingredient. The pharmaceutical companies in Korea have no other choice, but to test their metformin products according to the active pharmaceutical ingredient impurity risk management measure the ministry has unveiled recently. While announcing the investigation result of nizatidine contamination last month, MFDS ordered companies to conduct a self-test on all of their synthetic active ingredients for impurity like NDMA. Accordingly, synthetic ingredient manufacturer and importer, as well as complete product companies, have to evaluate contamination risk in drugs either during manufacturing or storing processes. Pharmaceutical impurity risk management initiative unveiled by MFDS last month Moreover, pharmaceutical companies have to immediately report any discovery of impurity to MFDS after conducting self-evaluation on suspected items with risk of NDMA-like impurity contamination. Basically, metformin became the first substance to be ‘suspected for contamination risk’ since the ministry’s impurity risk management initiative. The industry seems to be in process of attempting self-analyze NDMA level in metformin medicine. However, the testing process has not been so simple without an official testing procedure and lack of laboratories with proper analysis equipment. Currently, only nizatidine-containing products verified with approved level of NDMA can be distributed, but the testing laboratories are unable deliver testing results in requested time as they are backed-up with all companies with nizatidine products. MFDS has ordered pharmaceutical companies to supply nizatidine-containing item with passing level of cancer-causing NDMA contamination (less than 0.32ppm), verified by testing done for each item serial number. The test can be done by Korean Good Manufacturing Practice (GMP) certified manufacturer, MFDS designated quality test institute, city and provincial-managed environment research lab and Korean Pharmaceutical Traders Association. MFDS ordered pharmaceutical companies to test NDMA level in nizatidine medicine before supplying Some of pharmaceutical companies are even considering on purchasing testing equipment to run it by themselves. But an analyzer costing up to 300 million to 500 million won, beside the six-figure annual maintenance, cost is definitely putting a strain on the company. A pharmaceutical company insider commented, “The company is taking account of equipping impurity risk examination system as its own quality management program. We are also discussing possibility of sharing an ownership and purchase cost of the analyzer”.
- Policy
- Exclusivity for Galvus’ generics applied Aug 2021
- by Lee, Tak-Sun Dec 13, 2019 11:00pm
- Galvus by NovartisAs expected, Ahn-Gook Pharmaceutical obtained the approval for exclusivity for generic product as Galvus (Vildagliptin), a diabetes treatment of DPP-4. The MFDS designated the priority sale items for Ahn-Gook Vildagliptin Tablet 50mg of Ahn-Gook Pharmaceutical and Ahn-Gook Newpharrm Vilagliptin Tablet 50mg of its subsidiary Ahn-Gook Newpharm. As a result, it is not possible to sell any of the late-release drugs, except for Ahn-gook Pharm., From August 30 2021 to May 29 2022. Ahn-Gook Pharmaceuticals first filed a trial for extended period of invalidity on Galvus' patent for the first time as a domestic company on July 14 2017. This succeeded in invalidating the extended duration 187 of the material patent. The company received the affirmed decision. It is the first generic item to submit a permit application in last March. The company obtained a product license last month. Three conditions required for the right of exclusivity for generic product : the first patent challenge, the successful patent challenge, and the first application for permission and The company achieved all 3 conditions perfectly. The ban on late drug sales from August 30 2021. This is because Ahn-Gook advanced 187 during Galvus' patent expiration date, which is expected to expire on March 4, 2022 On the other hand, late-runners outside of Ahn-Gook are trying to circumvent the sale ban by Ahn-Gook’s right of exclusivity for generic product. Hanmi pharmaceticals has a strong chance of obtaining a separate right to sell salt-modified drugs and is currently applying for a permit. Korea United Pharm Inc , Kolmar Korea, and Alvogen Korea have also begun developing late-on drugs.
- Company
- Bayer Korea appoints Freda Lin as a new President
- by Eo, Yun-Ho Dec 13, 2019 10:59pm
- 프레다 린 대표 Bayer Korea has announced an appointment of Freda Ta-Ling Lin as a new President , starting from Jan. 1, 2020. The Korean branch’s top executive position has been vacant since the former President Ingrid Drechsel transferred to Bayer’s Turkish branch. From October, Bayer Korea’s Pharmaceuticals division has been managed by Lee Jina, a head of Cardiovascular Therapeutics Area. New President Freda Lin is a seasoned global leader in sales and marketing with 25 years of vast experience in the pharmaceutical industry. From 2013 to recent, Lin has been leading Bayer Taiwan as a head of Pharmaceuticals division and a President of the region. Previously, Lin has been building her career in the pharmaceutical industry as sales, market and strategic planning executive at GlaxoSmithKline’s Taiwan, China, Asia Pacific, and the U.K. branches. Moreover, Freda Lin is also to simultaneously serve as a head of Pharmaceuticals Division at Bayer Korea. New President Freda Lin said, “I am pleased to serve the role of President and to lead Bayer Korea in a country considered as one of the most innovative countries in the world”.
- Company
- Boryung Holdings appoints Kim Jung Gyun as New CEO
- by Eo, Yun-Ho Dec 13, 2019 10:59pm
- CEO Kim Jung Gyun Boryung Holdings recently convened a board meeting and appointed Chief Operating Officer Kim Jung Gyun as the new Chief Executive Officer. Joined Boryung Pharmaceutical in 2014 as a director, the new CEO Kim Jung Gyun served in Strategic Planning team, Production Management team, Human Resources team and was appointed as an executive director and COO at Boryung Holdings in January 2017. CEO Kim has contributed in increasing sales and improving profitability at Boryung Pharmaceutical by endeavoring on initiatives like ‘internal operational management system,’ ‘investment reprioritization,’ ‘generating open innovation-based new business like Vigen Cell’, and ‘building transparent and horizontal organizational culture’. As the COO of Boryung Holdings, Kim started establishing a holding company and subsidiary ‘Boryung Consumer’ since 2017, and shifted each business division to center board members for set a faster and transparent decision making process. Moreover, Kim reinforced collaboration system between board member executives to expand corporate value. Undergoing a series of changes, Boryung Pharmaceutical’s compound annual growth rate marked 7.1 percent in last three years, and its profitability has been significantly improved. The company is expected to make a record-high sales and operating profit this year. Besides, a vaccine manufacturer and biopharmaceutical R&D affiliate ‘Boryung Biopharma’ has also shown a steep growth and is expected to generate 100 billion won in 2019. CEO Kim stated, “As Korea is a part of top global markets, we should be the fastest to adapt to changes happening outside, constantly seek for opportunity in the global market, and invest on opportunity in future digital healthcare industry consisting of pharmaceutical industry, IT technology and healthcare”. Meanwhile, the current CEO of Boryung Pharmaceutical Ahn Jae-hyun resigned from his other position as a CEO of Boryung Holdings.
- Company
- MFDS to wait and see self-test results on metformin
- by Chon, Seung-Hyun Dec 13, 2019 06:34am
- Ministry of Food and Drug Safety (MFDS) The government seems to have decided to encourage pharmaceutical companies to run their own impurity contamination test on metformin drugs. Unlike the ranitidine and nizatidine incidents, the government means to wait and see the companies’ self-investigation results, rather than to take an action by itself. Basically, metformin would be the first substance to be applied with the recently unveiled impurity risk management initiative. However, the possibility still exists for the government to immediately call for sales ban and other follw-up measures, when a exceeding level of impurity is found in a product, either in Korea or overseas. According to the industry source on Dec. 12, Korea’s Ministry of Food and Drug Safety (MFDS) has not made any official order to pharmaceutical companies regarding findings of cancer-causing impurity in metformin. On Dec. 4, Singapore’s Health Science Authority (HSA) has decided to recall three out of 46 metformin products tested. Apparently, the regulator found N-nitrosodimenthylamin (NDMA) exceeding an acceptable level of daily consumption in metformin products. Since then, the U.S. and European health regulators have also started probing on contaminated metformin products. The U.S. Food and Drug Administration (FDA) is reportedly investigating NDMA discovered in metformin products available in the U.S. It also stated it would recommend recalling products with exceeding levels of NDMA contamination. The European Medicines Agency (EMA) has ordered companies to conduct NDMA contamination testing. Japan’s Ministry of Health, Labor and Welfare recently ordered metformin containing product manufacturers and importers in Japan to analyze and report risk of NDMA contamination in the substance and complete products. So far, MFDS has only stated it would “review investigation results”, and no other specific orders have not been given to the companies. The ministry has not yet ordered the companies to investigate NDMA in metformin active agent or complete product, nor has it stated the ministry would directly collect and investigate the substance. The ministry’s reaction is contrasting from the follow-up measures it had with other pharmaceutical impurity risk incidents. When the European regulator announced it would recall all valsartan products, the Korean ministry immediately banned sales of products with the same active ingredient. And after the sales ban was ordered in the U.S., the ministry once said “nothing to worry about”, but soon after it ordered an all-product ban. Actions on nizatidine followed the ranitidine sales ban. After collecting and testing active ingredient and complete product with similar chemical structure as ranitidine, MFDS banned sales on 13 items with unacceptable level of NDMA. It could be interpreted that the authority is trying to encourage companies to voluntarily test their metformin products. Neither of the U.S. or Europe has called for a recall due to exceeding level of the contamination. And the complete products reported with the impurity to date are not available in Korea, yet. MFDS official explained, “We have already asked companies to test the impurity in all products themselves”. It also means the recently introduced active ingredient impurity risk management initiative would be applied on metformin. In fact, MFDS has already asked pharmaceutical companies to run NDMA-like impurity test on all synthetic active agents, when announcing the investigation result of nizatidine medicine. Accordingly, synthetic ingredient manufacturer and importers, as well as complete product companies, have to evaluate risk of impurity contaminated during the process of manufacturing or storing. Pharmaceutical companies suspecting a risk of discovering NDMA and other harmful impurity in their product should immediately conduct a voluntary test and has to report MFDS as soon as possible when it is actually found. The impurity risk evaluation and testing should be conducted voluntarily, and the result of risk evaluation should reported by May 2020, and the result of test by May 2021. Pharmaceutical impurity risk management initiative presented by MFDS last month Since MFDS has introduced the impurity management initiative, metformin basically became the first case of ‘medicine with high risk’. In other words, MFDS is unlikely to test metformin itself, as of now. Moreover, metformin being a commonly used agent seems to make MFDS hesitant about testing the products proactively. Metformin is the most commonly prescribed first-line treatment for patients with Type 2 diabetes to control glucose level. In Korea alone, 642 of approved complete products contain metformin. Practically, all pharmaceutical companies have at least one metformin medicine. Compared to valsartan and ranitidine market, metformin has a far larger market volume. Pharmaceutical industry research firm UBIST reported outpatient prescription market volume of metformin product reached 420 billion won last year. It soared 63.4 percent in four years from 257.1 billion won in 2014. Currently banned ranitidine products generated about 200 billion won as outpatient prescription, but metformin market easily doubles the ranitidine market. A single dose of metformin is priced at less than a hundred one with reimbursement. Considering the pricing, metformin’s usage volume is overwhelmingly bigger than ranitidine. Yearly trend of outpatient prescription volume of metformin product (unit: KRW 100 million) Source: UBIST If the testing confirms metformin is contaminated with NDMA during the process of storing, active agent and complete product should be reviewed by each serial number. In such case, millions of serialized products would have to be investigated. It is physically impossible for MFDS to directly investigate them all. However, the ministry may initiate a full investigation, depending on the updates from home and abroad. The ministry’s hands-on investigation would be inevitable when active ingredient or complete product in Korea is found with exceeding level of impurity is reported from overseas. And even when a Korean company reports any case of NDMA contamination exceeding an acceptable level, full investigation is likely follow.
