Interim Report

Access to Orphan Drugs in South Korea : Blind Spot of the Korean Health System

UAEM Korea

- 1 -

Table of Contents

Introduction

I. Background A. Epidemiology of rare diseases in Korea B. Characteristics of Orphan Drug Industry in Korea C. Characteristics of Orphan Drug Supply in Korea D. Cases of Supply Failure by Multinational Pharmaceutical Companies E. Case Study: Gleevec F. Case Study: Lipiodol

II. Stimulating the production of domestic pharmaceutical companies A. Current Policies that Support the Development of Orphan Drugs in Korea B. Policies that Support the Development of Orphan Drugs in Other Countries C. SWOT Analysis on Domestic Orphan Drug Industry D. Policy Suggestions

III. Establishing State-Owned Pharmaceutical Companies A. Rationale B. Public Pharmacy in Foreign Countries C. Discussion on Public Pharmacy in Korea D. Blueprints on Public Pharmacy E. Alternatives

Conclusion

Appendix I. List of designated rare diseases in Korea II. List of designated orphan drugs in Korea

- 2 -

Introduction

The South Korean government introduced social health insurance in 1977, achieving Universal Health Coverage in 1989. (Kwon, Lee, & Kim, 2015) With 97% of the population under the coverage of national health insurance, the Korean health system meets the health need of the majority of the population. (IQVIA, 2018) Yet, the Korean health system shows weakness in delivering healthcare for minority groups including rare disease patients. Rare disease patients in South Korea have difficulty in accessing orphan drugs - treatments for rare diseases - primarily due to the unstable supply. As pharmaceutical prices in Korea are used as reference prices in other countries, including China, if transnational pharmaceutical companies receive prices lower than what they demand, they often decide not to launch drugs or withdraw from supplying drugs in Korea. (Choi, 2018) This tendency of transnational pharmaceutical companies, so-called ‘Korea passing’, led to several cases of orphan drug supply failure in Korea. (Park, 2018) Not only that, even when drugs are available in Korea, many times patients cannot afford orphan drugs. Unreliable supply systems and high drug prices hinder the access to orphan drugs in Korea. Sustainable Development Goal 3 states that we should "ensure healthy lives and promote well- being to all at all ages" and one of the essentials targets for achieving Goal 3 is Target 3.B that emphasizes the need to "provide access to affordable essential medicines and vaccines". As part of such initiative, rare disease patients should be guaranteed the access to affordable orphan drugs (UN, n.d.). To improve the access to orphan drugs, Korea should increase the domestic production of orphan drugs and implement policies that relieve the economic burden on patients. This paper consists of three sections, respectively focusing on establishing a sustainable supply system of orphan drugs, ensuring affordable prices of orphan drugs, and suggesting the roles of universities in this issue. Under Section A, ‘Supply’, there are three parts: Part I. Background, Part II. Domestic Private Production, and Part III. State-owned Pharmaceutical Company. Part I will provide the Korean context of rare diseases and orphan drugs. It will explore the cases of supply failure in the past and characterize global and domestic orphan drug industries. Part I will serve as a guide to those who have no prior knowledge in this issue. Part II will concentrate on stimulating the domestic production of orphan drugs. Based on the characteristics of domestic orphan drug industry, Part II will suggest policies to stimulate the growth of the industry, however, with utmost

- 3 - consideration to patients’ accessibility. Yet, entirely relying on a private sector for maintaining sustainable supply has its own risks. Public investment may not be fully translated into public return. The access to orphan drugs cannot be risked as they treat diseases that would otherwise have catastrophic health consequence. Accordingly, governments should take greater part in ensuring the access to orphan drugs. Part III will discuss the possibility of state-owned pharmaceutical companies. Although the current President Moon failed to meet the promise to establish a public pharmaceutical company, public provision of orphan drugs is still an attractive option. Referring to successful experience in other countries, this paper will suggest recommendations to lay the foundation for public pharmaceutical companies in the future. The contents of Section B, ‘Affordability’, are to be specified. Some contents will include establishing a national fund for orphan drugs and expanding the role of the Korea Orphan and Essential Drug Center (KOEDC) as well as improving the current financial support to raise the patients’ access to orphan drugs. Section C, ‘Universities’, will cast light onto possible roles that can be played by universities in innovating the access to orphan drugs in Korea. Moreover, universities consist of not only professors, researchers, or administrators but also active student bodies. The section will discuss how university students can contribute to improve the access to essential medicines in general.

- 4 -

Figure 1 Access to Orphan Drugs in Korea

Figure 1 illustrates the overall structure of the paper. Problems pointed out in Section A, ‘Supply’, apply to the cases in which orphan drugs are not available through national health insurance. Affordability, the main theme of Section B, is yet another huddle for accessing orphan drugs. This is the case when orphan drugs are physically available, however expensive to the extent that access is deteriorated. Access to orphan drugs should be a pivotal goal for the government. Everyone has “the right to health, the right to essential medicines”, and thus the right to orphan drugs. Orphan drugs particularly require governmental intervention as they are mostly costly without alternatives while rare diseases, if untreated, lead to catastrophic health outcomes. Also, orphan drug industry is economically promising. The global orphan drug market is expected to increase at a 12% compound annual growth rate (CAGR), reaching 224-billion USD by 2024. (IQVIA, 2018) This is considerable given that the prescription drug sales are expected to increase at the rate of 6.9%

- 5 -

(CAGR) from 2019 to 2024. (IQVIA, 2018) This global rise in demand for orphan drugs provides an opportunity for domestic pharmaceutical companies to enter the growing market. On top of that, orphan drug designation allows for numerous benefits such as market exclusivity, tax exemption, and fast track for approval. Orphan drugs can be “Niche Busters”, drugs of which global sales are between 100-million and 500- million KRW and the number of patients is between ten thousand and one million. The market for developing blockbusters is already oversaturated. It is strategic for domestic pharmaceutical companies to focus on developing potential niche busters. The concepts of state-owned pharmaceutical companies and national fund for orphan drugs are not new and so is the emphasis on domestic drug development. Yet, with the new socialist initiatives in public health like Mooncare, the pharmaceutical industry and policies on orphan drugs have changed. Based on up-to-date information, this paper will make amendments to previously discussed ideas and suggest innovative solutions, especially with a keen eye on the role of academic institutions. This research aims to shift the focus of the Korean pharmaceutical industry from making profits to meeting the health needs of the population.

Work Cited Choi, E. (2018). China referencing Korea’s pharmaceutical prices as apprehended... Transnational Pharmaceutical Companies Getting

Cold Feet (“우려했던 중국의 한국약가 참조”..다국적사 초긴장). HIT News. Retrieved from http://www.hitnews.co.kr/news/articleView.html?idxno=2830 IQVIA. (2018). IQVIA Market Prognosis 2018-2022: Asia / Australia - South Korea. London. Kwon, S., Lee, T., & Kim, C. (2015). Republic of Korea Health Systems Review. Park, S. (2018). Access to Medicines and Price Transparency: Beyond

the Trade-off (의약품 접근성과 약가 투명성 : 트레이드오프인가 ?). Health and Welfare Policy Forum (보건복지포럼), (November), 63–78. United Nations. (n.d.). Sustainable Development Goal 3. Retrieved from https://sustainabledevelopment.un.org/sdg3

- 6 -

I. Background

A. Epidemiology of rare diseases in Korea

1. Definition of rare disease and orphan drugs

Rare diseases refer to diseases that affect only a small percentage of the population; orphan drugs, medicines to treat those diseases. Yet, specific definition of rare diseases and orphan drugs differs across countries. In Korea, rare diseases refer to diseases with 20,000 patients or fewer. (Ministry of Health and Welfare, 2015) Currently, 1,017 diseases are designated as rare diseases. (Kim, 2019) The complete list is available in Appendix I. By the Rare Disease Management Act, the Ministry of Health and Welfare compiles requests for rare disease designation and annually updates the list. (Ministry of Health and Welfare) Orphan drugs are defined as drugs for treating rare diseases or diseases without available treatment. (Korean Food and Drug Administration, 1998) To meet the legal definition of orphan drugs, for domestically produced drugs, the annual total production cost should be five-billion KRW or lower; for imported drugs, the annual total sales should be five-million USD or lower. (Korean Food and Drug Administration) There are 256 orphan drugs designated in Korea, as shown in Appendix II.

2. Demographics of rare disease patients

In December 2016, the number of rare disease patients was estimated to be about 4.7 million. (Ko, 2019) Among all rare disease patients, 47.1% of them resided in the Seoul Metropolitan Area. (Ko) Other demographic factors - sex, age, and National Health Insurance tier - of rare disease patients are described in Table 1.

- 7 -

Table 1 Demographics of Rare Disease Patients in Korea

Data source: Analyzing the status of rare diseases and ways to improve support for rare diseases patients in Korea

- 8 -

3. Rare disease profile

Table 2 Examples of prevalent rare diseases and the number of patients

Data source: Analyzing the status of rare diseases and ways to improve support for rare diseases patients in Korea

Among the five most prevalent rare diseases, the top two were diseases of the musculoskeletal system and connective tissue. Yet, the most economically burdensome diseases with highest copayment did not turn out to be the most prevalent diseases. Diseases with highest annual copayment were as follows.

- 9 -

Table 3 Examples of rare diseases with high annual copayment

Data source: Analyzing the status of rare diseases and ways to improve support for rare diseases patients in Korea

B. Characteristics of Orphan Drug Supply in Korea

1. Characteristics of Global Orphan Drug Industry

- 10 -

The global orphan drug industry was worth 154-trillion KRW in 2018, and it is anticipated to be 292-trillion KRW in 2024. (Evaluate Pharma, 2019) This expected growth is ascribed to two factors: technological development and legislative support for favorable business environment. Technology to diagnose rare diseases has advanced enough that the rate of rare disease diagnosis is faster than that of population growth of rare disease. Also, governments are actively supporting the development of orphan drugs. The U.S. federal government supports orphan drug R&D; Europe enacted a law for orphan drug in 2002 to encourage the development of orphan drugs; while the Japanese government implemented the ‘Japanese Medicines Act’ to facilitate the regulatory approval of orphan drugs. (Korea-China Science & Technology Cooperation Center, n.d.) As a result, the number of applications for orphan drug designation is increasing while the number of designations is decreasing which means that more and more pharmaceutical companies seem to be interested in orphan drugs industry. Between 2000 and 2011, Food and Drug Administration (FDA) designated 1,251 orphan drugs and approved 116 of them. In this period, orphan drug designation in the USA increased continuously. (Korea Health Industry Development Institute, 2019) Using these benefits, orphan drug developers made a huge profit. Total revenue of top 50 orphan drugs that multinational pharmaceutical companies is about 9-billion USD in 2010. Yet, between 2011 and 2016, the growth rate of total revenue was only 1.1%. This is because many orphan drugs’ patents expired. The most profitable orphan drug was Remicade from Johnson & Johnson. The multinational company first launched Remicade to treat Crohn’s disease; however, it expanded the indication of the medicine afterwards. With the patent of Remicade expired, now several generics for Remicade are available in the market. The second most profitable orphan drug was Enbrel from Pfizer, a cure for rheumatoid arthritis. There are several orphan drugs that are anticipated to be profitable. The most prominent one is Humira from Abbvie and the second one is Avastin from Roche. The expected value of each drug is 8.7-billion and 8-billion USD. On the other hand, chemotherapy is the field that is expected to yield most profit. 566 medicines were chemotherapy medicines that Food and Drug Administration (FDA) evaluated in 2016.

- 11 -

2. Characteristics of Orphan Drug Industry in Korea

The number of patients with rare diseases in Korea is about 500 thousand. The number of rare diseases is about 7,000, but only 950 diseases are supported by Ministry of Health and Welfare (MOHW). Globally the whole medicine industry stagnated but orphan drug industry is growing continuously. South Korea is of no exception. Orphan drug industry in Korea grows 13.75% annually, and orphan biomedicine industry grows 26.5% annually.

Table 4 Orphan drug industry in Korea (products and price in KRW)

Whole products (million KRW) Production

Whole orphan drugs 252 (98,986) 20 (3,846)

Biologics 47 (62,795) 6 (2,880)

Medicine 205 (36,499) 14 (1,275)

Data source: (MFDS, 2019)

The number of orphan drug designation by Ministry of Food and Drug Safety (MFDS) is increasing annually, and the rate of increase is about 1%. Recently, several Korean pharmaceutical companies are trying to develop orphan drugs to be designated by FDA every year. Since 2015, the number of orphan drugs that is developed by Korean pharmaceutical companies and designated by FDA increased every year. There were 16 orphan drugs of this case in 2018.

- 12 -

∙ Figure 2 The number of orphan drugs exported

The size of orphan drug industry in Korea is also growing. The sales of orphan drug in Korea increased from 21.6 billion KRW (2013) to 595 billion KRW (2017). This cannot be a positive sign because the number of imported medicines also increased from 144 billion KRW (2013) to 225 billion KRW (2017). This shows that Korea is dependent on import. In other words, Korea orphan drug industry is being controlled by few multinational pharmaceutical companies.

Table 5 Production of orphan drugs by Korean

2013 2014 2015 2016 2017

(million KRW) 21,689 31,383 49,088 47,594 59,592

Increase rate (%) 44.7 56.4 -3.0 25.2

Data Source : (KHIDI, 2019)

Table 6 Importation of orphan drugs

2013 2014 2015 2016 2017

(billion KRW) 144 153 177 217 225

- 13 -

Increase rate (%) 5.7 15.6 22.2 3.8

Data Source : (KHIDI, 2019)

C. Characteristics of Orphan Drug Supply in Korea

1. The number of approved medicines and ingredients in Korea

The number of approved orphan drugs is decreasing between 2014 and 2018. (Table 7) Nonetheless, the number of domestically developed orphan drugs was much lesser than that of imported orphan drugs.

Table 7 Approved orphan drugs (2014-2018)

2014 2015 2016 2017 2018

Total 20 49 14 18 17

Domestic 0 2 0 0 6

Imported 20 47 14 18 11

% Imported 100% 95.9% 100% 100% 64.7%

Data source: (MFDS, Drug Approval Report 2014-2018)

The total number of approved ingredients is decreasing but the percentage of imported orphan drug ingredients is 100% in 2014, 2017 and 2018.

Table 8 Approved ingredients

2014 2015 2016 2017 2018

- 14 -

Total 12 35 NA 18 9

Domestic 0 2 NA 0 0

Imported 12 33 NA 18 9

% Imported 100% 94.3% NA 100% 100%

Data source: (MFDS, Drug Approval Report 2014-2018) NA = data not available

2. Supply problems of orphan drugs in Korea

As Korea heavily relies on imports from multinational pharmaceutical companies, the supply of orphan drugs is unstable. Only 67.9% of imported orphan drugs were available at the market. (Park, 2015) Multinational pharmaceutical companies refused to supply their products due to the low price suggested by the National Health Insurance Service (NHIS). Since Korea is listed as a reference country for determining drug prices in other countries, such as China, Japan, and countries in the Middle East, multinational pharmaceutical companies decide not to supply drugs at prices lower than they demanded. So-called ‘Korea passing’ results in two phenomena. First, even when drugs are designated as orphan drugs, drugs are not available at the market. This case includes 33.5% of orphan drugs and 37.6% of orphan drug ingredients. Secondly, even when orphan drugs are under the coverage of National Health Insurance (NHI), drugs are not supplied at the market. 55.1% of orphan drugs were listed for reimbursement by NHI but not available at the market. This gets worse because only 6.4% of approved orphan drugs were produced domestically. (Kim, 2011) 93.2% of approved orphan drugs were imported. There are several reasons why pharmaceutical companies do not supply the medicines. First, some medicines could not be supplied due to technical problems or other problems. Amsidyl for acute myeloid leukemia and Incodin for inflammation are examples of this case. Nonetheless, Gleevec, Fuzeon, and Sprycel were not supplied since pharmaceutical companies decided not to, for their profits. Furthermore, compulsory licensing for Gleevec and Fuzeon failed because of the

- 15 - refusal of pharmaceutical companies. There were 253 products of essential medicines that were discontinued to supply for last 3 years. Korea needs to encourage domestic production of orphan drugs not to be controlled by multinational pharmaceutical companies. If Korea companies produce orphan drugs, the supply of orphan drug will be stable. Now, Korea Orphan & Essential Drug Center (KOEDC) is supplying some medicines for desperate patients.(Kim & Gwak, 2006) Patients can apply for orphan drugs they were prescribed to KOEDC. Then KOEDC find those medicines and deliver to patients without their own profits. Patients can visit KOEDC in Seoul, fax documents or use smart app of KOEDC. KOEDC reviews those applied documents including prescription and decides whether to supply or not. If medicine is in stock, KOEDC deliver this medicine immediately at the first cost. However, if medicine is not in stock, KOEDC imports this medicine and delivers. The price of medicine can be different by reimbursement. More specifically, patients can only pay copayment for reimbursement medicine but in the case of non-reimbursement, patients need to pay medicine’s first cost and pharmacy cost. Although KOEDC’s office is located in Seoul, patients in other provinces can access to orphan drugs through local pharmacies.

∙ Figure 3 Application of medicine through KOEDC

- 16 -

D. Cases of Supply Failure by Multinational Pharmaceutical Companies

Table 9 The list of orphan drugs that failed to be supplied

Year Producer Disease Current status

2001 gleevec Chronic myeloid leukemia Price renegotiated

2004 Fuzeon HIV/AIDS Free supply through KOEDC

2007 Sprycel Chronic myeloid leukemia Supply without refund

2008 Prezista HIV/AIDS Free supply through KOEDC

2009 Elaprase Hunter syndrome Resupply after tariff exemption (Mucopolysaccharidoses Ⅱ)

2009 Naglazyme Mucopolysaccharidoses Ⅳ Supply with refund

2009 Myozyme Pompe disease Supply with refund

2009 NovoSeven hemophilia Price renegotiated

2018 Syprine Wilson disease Generic supplied

2018 Lipiodol transarterial chemoembolization Price renegotiated

2018 Xolair Allergic asthma Price negotiation failed

2019 Radicut Lou Gehrig’s disease (ALS) Supply refused

E. Case Study: Gleevec

Gleevec, so-called ‘miracle cancer drug’, is a treatment for chronic myeloid leukemia. It was developed by Novartis, a multinational pharmaceutical company. In 2001, Novartis decided

- 17 - not to supply Gleevec as the price negotiation with Korea Ministry of Health and Welfare (MOHW) was not successful. At the first price negotiation, Novartis requested 25,000 KRW per tablet, while MOHW suggested 17,862 KRW per tablet. Novartis wanted a similar price in Korea since other countries including Japan, Germany and USA accepted high price of Gleevec. Desperate patients demanded compulsory licensing of Gleevec, but the Korean government did not take such responsibility. Novartis decided to supply Gleevec to 230 patients for free just for two months. In 2003, the government and Novartis preceded the second price negotiation for Gleevec and settled on 23,045 KRW which was 83% of the world’s average Gleevec price. After the second negotiation, patient copayment of Gleevec was 497,770 KRW per month. In 2014, the price of Gleevec decreased and Gleevec was supplied at 11,077 KRW per tablet. Since 2013, generics of Gleevec, such as Supect, have been developed in Korea. (Jung, 2017)

F. Case Study: Lipiodol

Lipiodol is a contrast agent that is usually used for transarterial chemoembolization (TACE) to cure liver cancer. It was developed by Guerbet, a French multinational pharmaceutical company. In 2018, Guerbet demanded Health Insurance Review & Assessment Service (HIRA) to increase the price of Lipiodol. At first, lipiodol was set as 52,560 KRW per ampule in 1999; however, now Guerbet is demanding for five times of its first price. Otherwise, Guerbet said it won’t supply lipiodol in Korea in 2018 which might cause an emergent situation in major hospitals. Then government had a negotiation to set the price of Lipiodol at a reasonable level and finally the price was set as 3.6 times of is first price. In 2012, Lipiodol was under shortage prevention program but access to lipiodol was not improved. Still Guerbet insisted Lipiodol’s price for 260,000 KRW. As experience, the price of medicine goes lower gradually after the end of its patent but the price of lipiodol is continuously increasing. Furthermore, Lipiodol is an ‘Old truck’ which means that has only an approval in France in 1965 not in Korea. This was possible because Guerbet is a well-known company for its contrast agent. The usage of lipiodol enlarged 7 times than its first usage for last 50 years. Korean government considered to produce Lipiodol domestically but concluded that producing it is impossible. The reason for this is that materials of Lipiodol are so rare. In this

- 18 - situation, congress and experts had a conversation to set up control tower of essential medicines but they did not conclude anything.

- 19 -

Work Cited

Jung, C. R., Lee, J. W., & Ko, K. (2017). A Critical Study of the Arguments for and against a Moratorium on Glivec (글리벡 급여정지를 둘러싼 찬반논쟁에 대한 비판적 고찰). Korean J Med Ethics (한국의료윤리학회지), 20(3), 257-275. Kim, H. E., & Gwak, H. S. (2006). Current Status and Expectations of Orphan Drugs in Korea – In point of supplying medicines for the rare diseases (국내 희귀의약품의 현황 및

과제 – 희귀질환에 대한 의약품 공급을 중심으로). Kor. J. Clin. Pharm. (한국임상약학회지), 16(2), 107- 112 Kim, J. (2019). Adding 91 More Diseases to the National List of Rare Diseases

with Designation 국가관리대상 희귀질환 91 개 추가 지정. Ministry of Health and Welfare Press. Retrieved from http://www.mohw.go.kr/react/al/sal0301vw.jsp?PAR_MENU_ID=04&MENU_ID=0403&page=1& CONT_SEQ=351196 Kim, T. W. (2011). Analysis of Distribution and Supply System of Orphan Drugs

(희귀의약품 유통현황 분석 및 공급방안 고찰). 숙명여자대학교 임상약학대학원. Ko, K. (2019). Analyzing the status of rare diseases and ways to improve support for rare diseases patients in Korea. Korea-China Science & Technology Center (한중과학기술협력센터). Current status of orphan drug in major asia countries (희귀의약품에 대한 아시아 주요국가의 현황). Korean Food and Drug Administration. Regulation on Orphan Drug Designation. , (1998).Ministry of Health and Welfare. Rare Disease Management Act. , (2015). Korea Health Industry Development Institute (한국보건산업진흥원). (2019).

Analysis of domestic and foreign Orphan drug industry and development status(국내외 희귀의약품

시장 및 연구개발 현황 분석). 한국보건산업진흥원 보건산업브리프, 283.

- 20 -

Park, S. (2015). Discontinued Orphan Drugs in Korea: Policy Suggestions.

(희귀의약품의 공급 중단 실태와 정책과제). 보건복지포럼.

II. Stimulating the production of domestic pharmaceutical companies

A. Current Policies that Support the Development of Orphan Drugs

Drug Preclinical Clinical Regulatory Other Discovery Approval (After I II III IV approval)

R&D funding

Expedited approval

Reduction in user fee

Exemption of review fees for item approval

Exemption of data

- 21 -

Assignment of project managers

Reduced requirement for GMP assessment

Preliminary regulatory review

Accelerated safety evaluation

Extension of re- examination

Market exclusivity

Tax deduction

Exemption of data for re- examination

Green = economic incentives - 22 -

Blue = regulatory incentives

R&D funding: The Ministry of Health and Welfare provides the R&D grant for pre-clinical and clinical I and II studies to selected companies, universities or other research institutes. The duration of R&D grant is either two or three years. Exemption of data required for approval: Before sales or import, pharmaceutical companies should submit data from clinical trials. In the case of Orphan drug, companies do not have to submit those data. Additionally, Orphan drug also gets exemption in submitting data used to clarify its safety: results of clinical study can be utilized to show its pharmacological action. In particular, if orphan drug is necessary in urgent situation, results of Phase 2 clinical trial can substitute results from Phase 3. Accelerated safety evaluation: Orphan drug is the subject of accelerated evaluation, and the data necessary for drug approval can be submitted after the drug has been marketized. Extension of re-examination period: Although market exclusivity is not separately granted, re- examination period - a period in which the safety of drug is re-evaluated - is nearly synonymous with market exclusivity, since generics of orphan drugs are banned during a re-examination period. The re-examination period of orphan drugs is 10 years, which is longer than that of non-orphan drugs, 4~6 years. Exemption of data for re-examination: After launching a drug on the market, a pharmaceutical company should submit the data on the safety of the drug. In the case of orphan drugs, such data can be omitted. Tax Deduction: 20% of income tax or corporate tax is deduced by the Ministry of Health and Welfare. In the case of Small and Medium-sized enterprises, 30% of income tax or corporate tax is deducted. This does not specifically target orphan drugs but also to medicines that are included in newly growing industry such as gene medicine, antibody drug conjugate, cell therapy products using stem cell, and biosimilar and in the category of original technology. In other words, there is no financial aid only for Orphan drug. Support for clinical trials: When pharmaceutical companies can be supported for clinical trials such as writing down the plan of clinical trial, collecting subjects necessary for clinical trials and enforcement of joint clinical trial globally

- 23 -

Preliminary regulatory review: The approval of orphan drug sales and import can be prioritized over those of other drugs. Reduction in fees: Fees, which are required to submit an application for approval, get pre-review and approval, are reduced.

B. Policies that Support the Development of Orphan Drugs in Other Countries

1. Orphan Drug Act in U.S. (1983)

There are many causes that pharmaceutical company should consider before developing orphan drugs. Given the size of orhan drug in past, it was an uneasy job to be engaged in orphan drugs, leading few companies to monopolize the market of orphan drugs. For relieving the hardness of developing orphan drugs, U.S. government established Orphan Drug Act (ODA) in 1983 to boost R&D of Orphan drugs in pharmaceutical companies. ODA can be categorized in two: (1) financial support (2) institutional support. Financial support usually occurs in the form of exemption in costs such as getting exemption of application for marketing. All orphan drugs are exempted from the cost of applying for marketing. When it comes to tax, company can charge to deduct 50% of federal income tax. This is carried for 20 years or until profit is generated. User fees for NDA (Non-Disclosure Agreement) or BLA are also waived that are necessary in application, approval which is approximately $2,000,000. Funds needed in R&D is also supported in various ways. Costs which are indirectly or directly needed for clinical trials, are supported up to $14,000,000 annually. Company can get financial support with this OPGP. In 1st clinical study, 0.2 million dollars per year is supported for three years and 0.4 million dollars per year are supported for 2nd and 3rd clinical study up to 4 years. This program also includes financial aid for office. Even with the financial support, due to risks in being assigned as orphan drug, R&D of orphan drug was not activated to sufficient extent. To shorten time necessary in R&D, FDA

- 24 - implemented policies such as: Fast-track (being started from 1988), Accelerated approval (1992), Priority review (1992), Breakthrough therapy (2012). In addition, FDA assigns 10~15 companies that can get support from FDA in every year. Institutional support usually occurs in the form of shortening periods necessary for being allowed. Orphan drugs are the target of Fast-track review and applicants can also request for Fast- track review. Also, for orphan drugs, period required for approval process is shortened. Maximum day necessary for approval is 60 days which is directly related to fast-track. Although there is no precise statement that those policies can be applied to “orphan drug”, U.S. applied supports in procedure also to orphan drug, considering the fact that orphan drugs are suitable to conditions that is needed before applying that policies. In addition, laws that can protect benefits of pharmaceutical companies are legislated such as market Exclusivity, which bans permission of same or similar medication that can be used to same diseases for seven years from the day when medicines get market authorization. There is a law that can accelerated marketing procedures. Since 2007, drug developer can use application procedure not only for FDA but also for EMEA (European Medicines Agency) to get marketing approval. If the drug is designated as orphan drug both in U.S and EU, a single annual report can be submitted instead of submitting reports individually. To orphan drugs, government recognizes the necessity of using them before getting marketing approval. Therefore, patients can use orphan drugs before marketing approval which are also suitable to following conditions: ⑴ medicine that are for fatal disease, ⑵ If there is no substitute, ⑶ If drugs are on clinical study or on active phase (Right before marketing approval)

2. EU

There is an “emergency licensing system” which allows medicine to be used with limit, even if there is not enough data on efficiency in terms of safety. Similar to ODA in U.S., financial support and institutional support also exist in EU. In the case of financial support and institutional support for development, Orphan drug can get financial support from EMEA in terms of application for approval and post-approval activities.

- 25 -

Fee for plan of clinical trial and follow-up investigation are supported: in the case of SMEs, 100% of cost is deducted and 75% is deducted to non-SMEs. Entire cost necessary for approval is exempted. Particularly to SMEs, whole cost used in post-activities is supported for an year of marketing approval. Companies are supported 100% when they got review after submitting application for getting marketing authorization. Different from other medications, patients can use orphan drugs without approval even in 3rd phase of clinical study or in the middle of approval. However, the speed of access is various depending on the market size of each country in EU. 50% fee is exempted for application before getting authorization in terms of marketing. Samely, 50% exempted fees are applied to annual post-authorization activities. In addition, fee will be reduced for review fee and preauthorization inspection fee. Market exclusivity that protects pharmaceutical companies for getting enough benefits also exist in EU. Permission of same or similar medication that can be used for same diseases are not allowed for 10 years from the day when medicines get permission of marketing. However, if the drug is not suitable to the criteria which designated drugs as orphan drugs initially or if unreasonable profits are generated, then market exclusivity can be withdrawn.

3. Japan

In Japan, there are financial support in the form of deduction, tax exemption. Orphan drugs can get not only 10% deduction of corporate tax but also additional 6% of tax reduction in research and R&D cost. 50% of expenses for conducting clinical trials is also supported. There is a financial support in the marketing stage such as exemption of tax in terms of MAA (Marketing Authorization Application). At the stage of marketing, there is market exclusivity in Japan, however, it is different from the notion in USA or in EU. After permission of medicine, same medicine which are used to treat same disease are not allowed. 10 years are guaranteed as market exclusivity period. Re- examination period, which takes a similar role to market exclusivity, is lengthened from six years to ten years. - 26 -

Support that are provided during research includes free consultation which companies can get in any stage of research and development. Also, it takes 12 months to be authorized for general pharmaceutical firms, but in case of Orphan drug, it takes ten months to get authorization. Generally, 12 months are necessary for reviewing but only to orphan drug, review period is ten months.

C. SWOT Analysis on the Domestic Orphan Drug Industry

Strength Opportunity - “Rights-attached health-committed - Increasing size of global orphan drug president” market (Open Society Foundations, 2019) - Possibility to seek for M&A with - Increasing financial or administrative overseas pharmas support for orphan drug development - Potential to cooperate with other - Orphan drugs industry considered as governments due to overlapping alternatives of blockbuster model interests - Growing awareness of domestic - Korea watched by international pharmaceutical companies to develop society, expected to act as a ‘bridge’ orphan drugs between developing/developed - Shifting focus to open innovation to countries strengthen internal capacities - Advanced GMP facilities

Weakness Threat - Relatively small pool of patients to - More comprehensive provision of carry out clinical trials exclusive benefits to orphan drug - Tendency to aim for FDA approval industry in other countries, such as from developmental stage(Domestic the U.S.

- 27 -

market not big enough) - More competitiveness of - Cultural factors that draw back transnational pharma industries facilitation of M&A with external - Varying degree of registration entities standards that inhibit overseas market - Scattered academic centers and entrance limited capacity to carry out big-scale projects

- 28 -

D. Policy Suggestions

1. Pool patients for clinical trials

One of the major obstacles in orphan drug R&D is the difficulty in recruiting enough patients for clinical trials. The orphan drug R&D in Korea usually stops at the first phase of clinical trials and stops at the second phase of clinical trials in the US. This is mostly because, by definition, patients of rare diseases are low in number. In this sense, clinical trial is the greatest bottleneck for orphan drug development. A possible solution is to form a network of countries that could share rare disease patients for clinical trials. Since the bottleneck issue is not confined to Korea, the other countries would be interested in forming a network as well. In the network, patients from different countries could be recruited for the same clinical trial. A similar effort for collaborative international clinical trials exists in Europe. The European Society for Paediatric Oncology proposed an international clinical trial model where hospitals in different countries in Europe could run the same clinical trials for childhood cancer. For childhood cancer, there were small groups of patients as well and this problem would be resolved with the collaborative clinical trial platform amongst the EU countries (Kearns, n.d.). This was facilitated within the EU system where they can have a standardized regulation for clinical trials (European Society for Paediatric Oncology, n.d.). In the case of Korea, such a network could be formed under the Korea National Enterprise for Clinical Trials (KoNECT), which already has experience of forming networks with other countries (Korea National Enterprise for Clinical Trials, n.d.). The network would consist of countries that has similar national health system as Korea such as the National Health Insurance. Therefore, similar government agencies from the member of countries could be in charge of the network to allow easier cooperation. Countries such as Thailand, Taiwan, Japan, and the Philippines could be examples of member countries for this network. The international clinical trials would be organized at the international coordination center to set up the conditions and guidelines for the clinical trial to be carried out. The information on the clinical trials would be sent to the national coordination center at each participating member. The national coordination center would organize

- 29 - clinical trials at different hospitals in the country. Then, the data from the clinical trials would be collected and stored at the international coordination center for the member countries to access when needed. The possible limitation of this network would be the differing clinical trials regulation amongst the member countries. Also, there will be difficulties in forming a joint regulation and agreement amongst the member countries on how international clinical trials will be run.

2. Impose rules to secure domestic supply during re-examination period for reliable supply

Currently, re-examination period is ten years for orphan drugs without alternatives and four or six years for orphan drugs with alternatives. (Ministry of Food Drug and Safety, 2017) During the re-examination period, generics cannot be made which practically gives those drugs market exclusivity. However, it can be problematic if this hinders adept supply in response to demands, for example when the pharmaceutical industries decide upon a higher price which becomes an obstacle to access to treatment. On top of that, imported products account for the majority of domestic orphan drugs which renders drug importers most beneficiaries of market monopoly. Therefore, appropriate policy measures should be taken to secure the supply of orphan drugs during the re-examination period. In order to secure supply stability, countries that grant market exclusivity on orphan drugs such as the US, EU, and Taiwan are depriving pharmaceutical companies of market exclusivity when their drugs are not sufficiently supplied to meet demand quota. (Lee, 2019) Thus, it is implying the stability of supply as part of the market exclusivity system of orphan drugs. To be more specific, Taiwan allows for exemption during market exclusivity period when the supply does not meet demand, or when the central government decides that the price is set too high. Korean re-examination policy should also consider imposing these measures to secure domestic supply of orphan drugs.

3. Divert from closed model of R&D to open innovation system through active M&A

- 30 -

Considering the global trend, M&A is an essential factor to increase competitiveness and secure mid-to-long-term development capacity. As of 2018, the number of bio/pharma industry M&A deals have reached 1,438 which is the highest in 10 years. Big pharmas are continuing to invest in 1 bioventures and seeking Open-innovation by M&A. When looking at the outbound0F figure, Korean outbound has reached $18 million which is relatively small compared to other countries’ figures. The number of cases account for only 7% of the total deals, whereas Hongkong reached 52% and Japan reached 39%. In 2018, there were 38 domestic M&A out of 41 total established M&A. (Lim, Chang, & Eom, 2014) Closed-R&D model with limited self-capacity is being shifted to open-innovation system in which revolutionary ideas and new technologies are shared within similar sectors. Pharma industry is trans-boundary in nature, since countries’ borders are meaningless when it comes to taking actions for treating disease. No pharmaceutical industries limit their supply market to their own countries. Therefore, Korean pharmaceutical industry should actively take part in cross-border M&A to set ground for a long-term growth.

3. Focus more on development of biopharmaceuticals, which are high value-added products

The global pharmaceutical market is expected to grow by an annual average of 5.9% from 2016 to 2021, to $1.46 trillion by 2021. (Evaluate Pharma, 2019) With the development of biotechnology, the emergence of innovative biopharmaceuticals such as stem cell therapies and gene therapies has shifted the focus of global new drug development from synthetic drugs to biopharmaceuticals. Biopharmaceuticals generally have better efficacy and fewer side effects than synthetic drugs, resulting in high success rates in the overall process. Also, the conversion rate of biopharmaceuticals by clinical stage is also higher than that of synthetic drugs. The probability of transition from phase 2 to phase 3, is 34.4% for biopharmaceuticals, 32.9% for vaccines and 26.5% for synthetic drugs from 2006 to 2015. Thus, it can be encouraged to focus on development of biopharmaceuticals.

1 Outbound refers to M&A case in which domestic entity takes over overseas entity. (Lim et al., 2014) - 31 -

In Korea, biopharmaceutical exports have soared from 2015, reducing the trade deficit of the entire pharmaceutical industry. A number of pharmaceutical companies, including Bukwang Pharm, Reyon Pharm, and Handok Pharm, are investing in bio-venture companies that are developing new drugs and are striving for an open innovation strategy. Of these, Bukwang Pharm invested KRW 3.9 billion 10 years ago in Anthrogen, a stem cell drug development company, bringing financial benefits of KRW 883 billion. This case can be benchmarked by other bioventures or pharma industry for the purpose of smoother orphan drug development and inducing higher benefit.

- 32 -

Work Cited Anthony K et al., (2014), The current status of orphan drug development in Europe and the US, Intractable & Rare Diseases Research, (January), 2-6 Enrique Seoane-Vazquez et al., (2008), Incentives for orphan drug research and development in the United States, Orphanet Journal of Rare Diseases, 5-6. European Society for Paediatric Oncology. (n.d.). Clinical Trials in Paediatric Oncology. Retrieved from siope.eu/european-research-and-standards/clinical-trials-in-paediatric- oncology/%0A Evaluate Pharma. (2019). Orphan Drug Report 2019. Lee, S. & Lee, J (2013), Rare Disease Research and Orphan Drug Development, For.J.Clin. Pharm, Vol 23, No.1, 4-8. Lee, Y. (2019). Domestic and Overseas Orphan Drug Industry and Analysis of Current R&D Status. In KHIDI Brief (Vol. 283). Lim, D., Chang, J., & Eom, Y. (2014). Samjong INSIGHT (Vol. 65). Ministry of Food Drug and Safety. (2017). Guide to Drug Approval System in Korea. Open Society Foundations. (2019). Access to Medicines and Innovation in South Korea. (January), 1–23. Park, S (2015), Discounted Orphan Drugs in Korea: Policy Suggestion, Health and Welfare Policy Forum (보건복지포럼 ), (February), 67. Kearns, Pamela. (n.d.). Clinical Trials in Europe: The Framework and Perspective [PDF Document]. Retrieved from https://pdfs.semanticscholar.org/7224/0e90898c31de5357480a7af1fc03ec2368c6.pdf Kearns, Pamela. (n.d.). Towards more and better cure - the critical role of collaborative clinical trial platforms [PDF document]. Retrieved from https://www.siope.eu/wp- content/uploads/2017/11/Kearns_ICCD_2018.pdf Korea National Enterprise for Clinical Trials. (n.d.). Establishment of North East Asia Network (동북아 네트워크 구축). Retrieved from https://www.konect.or.kr/kr/contents/business_new_6/view.do Kwak, S. & Jeong, S (2019), Analysis of Orphan Drug market and R&D status in Korea, KHIDI Brief, Vol 283, 4-5.

- 33 -

III. Establishing State-Owned Pharmaceutical Companies

A. Rationale

'Public pharmacy' is a pharmaceutical company established and operated by the government to efficiently and systematically conduct the production, distribution, and management of national essential drugs and orphan drugs. The importance of stable medicine supply has emerged with the advent of public health risks such as swine flu, Severe Acute Respiratory Syndrome (SARS), and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) as well as the risk of new infectious diseases and bioterrorism. Besides, the need for government's active intervention has been pointed out through the experience of private pharmaceutical companies rejecting the supply of orphan drugs and the unstable supply of shortage prevention drugs. In this regard, the discussion over public pharmacy has emerged as a solution that can ensure the sustainable production and supply of essential and orphan drugs.

B. Public Pharmacy in Foreign Countries

1. Status quo

Table 10 Publicity of the Global Pharmaceutical Production and Supply System

Data source : (Kim, Kim, & Lee, 2015)

- 34 -

* s: The public ownership of the means of pharmaceutical production * p: The public funding of pharmaceutical expenditures * i: The control of prices and intellectual property rights of pharmaceuticals

2. Case Comparison (Kim et al., 2015)

2.1. The U.S.

Both the U.S. and Korea completely depend on the market for the production of medicines due to the absence of public pharmacies. However, unlike the U.S., the Korean pharmaceutical industry is not as developed as that of the U.S., which leads Korea to rely on imports. The size of the pharmaceutical market in Korea was 16.3 billion USD while the size of the pharmaceutical market in the U.S. was 373.3 billion USD, which means the size of Korea’s pharmaceutical market is only 4.4% of the U.S. (KHIDI (한국보건산업진흥원), 2019)

2.2 Thailand, Indonesia

Korea, Thailand, and Indonesia share similarities in that the history of the national social security system and the pharmaceutical industry is not long. Also, all three countries have high control over price and intellectual property rights. Moreover, the need for compulsory licensing has emerged in three countries. Thailand conducted compulsory licensing on seven medicines from 2006 to 2007 because price negotiations on HIV/AIDS treatments with pharmaceutical companies broke down while the burden of government on healthcare expenditure was growing. Indonesia conducted compulsory licensing in 2004, 2007, and 2012 for a total of nine items (including HIV/AIDS and hepatitis B treatments). In 2012, the Decree of the President of the Republic of Indonesia proposed the urgent need to control HIV/AIDS and hepatitis B and to expand accessibility on Antiretroviral (ARV). Considering that the free access system on ARV was first

- 35 - implemented in 2004, the implementation of compulsory licensing in Indonesia would have been inevitable for the feasibility and sustainability of the system under limited financial resources. Unlike Thailand and Indonesia, compulsory licensing was rejected by the government in Korea. In Korea, the need for compulsory licensing on Gleevec (treatment for leukemia) in 2002-2003 and Fuzeon (treatment for HIV/AIDS) in 2008-2009 has been drawn by civil and patient organizations but rejected by KIPO (Korean Intellectual Property Office). KIPO said that both cases are not particularly necessary for the public good. This is due to the political and economic contexts that require Korea to meet stricter legal and institutional requirements as a high-income country joining OECD. Also, Thailand and Indonesia own public pharmaceutical companies while Korea does not. Thailand established a public pharmacy in 1966 named Government Pharmaceutical Organization (GPO) where most medicines for national major diseases are produced. Thailand saved 3.1 billion baht (about 100 billion KRW in 2016) of its drug budget due to GPO. Indonesia has four public pharmaceutical companies and three of them focus on the production of generics.

2.3 Poland

Both Korea and Poland are high-income countries that joined OECD relatively recently. Due to this political context, there is pressure from the international community to meet the legal requirements of high-income countries even though the history of the capitalist system is short, and the level of pharmaceutical development is not high. However, while the publicness remains in Poland as a historical legacy of the socialist system, the production of healthcare services and pharmaceuticals in Korea heavily relies on the market.

C. Discussion on Public Pharmacy in Korea

1. History

- 36 -

In Korea, discussion over the establishment of public pharmacy came up to the surface, but it soon faded away. In June 2017, the passing of the National Essential Drug Supply and Management Act triggered the controversy. Three months later, legislation on the establishment of a public pharmaceutical company was proposed to the National Assembly but it was rejected due to its cost-effectiveness. While Korean Medical Association (KMA), Korea Alliance of Patients Organization, and Korean Federation Medical Activist Groups for Health Rights (KFHR) supported the establishment of public pharmacy, Korea Institute for Health and Social Affairs (KIHASA) and the Ministry of Health and Welfare (MOHW) expressed skepticism. The discussion concluded with an alternative idea: a control tower that can organically connect existing production facilities and provide a timely supply of essential medicines.

2. Evaluation

The biggest reason for bill rejection is mostly related to the cost-effectiveness of public pharmacy. There is a widespread concern that public pharmacy can break the market order by providing medicines at a low price, which can be regarded as an excessive market intervention by the government. Also, some raise concerns that the stable supply of medicines for public health emergencies can still be achieved by private pharmaceutical companies. Since there are about 200 private pharmaceutical companies in Korea and the utilization rate of manufacturing facilities is only 70% (Jin, Lee, & Yu, 2017), it is more cost-effective to conduct private consignment production by using the idle production facilities of private companies, rather than establishing the public pharmacy. Regarding a request for consignment production of orphan drugs from government organizations, 68% of the respondents (26 private pharmaceutical companies) showed a positive attitude. (Jin et al., 2017) Moreover, some points out that it is rather more urgent to expand the R&D investment for private pharmaceutical companies considering the low domestic vaccine self-sufficiency rate (50% in 2017, 14 out of 28 items) and at the same time strengthen the role of existing organizations such as Korea Orphan & Essential Drug Center (KOEDC). However, public pharmacy is still an attractive option in that it can improve the publicity of essential and orphan drugs’ accessibility to a meaningful extent. The public pharmacy can

- 37 - contribute to improving drug accessibility by producing low-profit drugs that private pharmaceutical companies are reluctant to produce. Also, independent R&Ds with utilitarian value can be conducted. Last but not least, the public pharmacy can prevent supply withdrawal of essential drugs, thus enabling the stable supply of national essential medicines for emergencies.

D. Blueprints on public pharmacy

1. Operating Plan

If a public pharmaceutical company was founded in Korea, it would be established and operated under the Ministry of Health and Welfare. It would include labs, farms, distribution centers as affiliated facilities. The function of the public pharmacy would include the production and import of public pharmaceuticals (including Vaccines, Shortage prevention drugs, orphan drugs, essential medicines, Foreign aid medicines, Medicines for public health emergency), the production of compulsory licensing drugs, the import of parallel import drugs, the investigation/promotion of the demand and management of public pharmaceuticals, and the domestic/international cooperation related to public pharmaceuticals. Public pharmacy would be mostly financed by National Health Promotion Fund. Also, revenue from the public pharmacy’s business and donations would assist the operation of public pharmacy. (Kwon, 2017) Several regulations would be made to maximize the publicness of pharmaceuticals: a provision that profit should not exceed a certain percentage of production cost.

2. Different Types of Establishment

- 38 -

Table 11 Types of Public Pharmacy

3. Concerns

The biggest concern on public pharmacy is its cost-effectiveness and sustainability. Those who oppose the public pharmacy points out that the continuous operation cannot be guaranteed since it cannot generate a minimum profit for operation. The primary reason for its low cost-effectiveness derives from the types of drugs that public pharmacy produces. Public pharmacy would mainly deal with four types of medicines: low-priced rare drugs, high-priced rare drugs, generics, and vaccines. First, low-priced rare drugs are unlikely

- 39 - to generate profits from exports due to low price-competitiveness compared to that of China. Also, in case of high-priced rare drugs, it is uncertain whether the production will be possible since compulsory licensing, a precondition for producing high-priced rare drugs, is rarely executed due to the concerns about trade conflicts and international pressures. (Although high-priced drugs do not necessarily mean that they are patented, they tend to be priced higher.) Moreover, there is a criticism that the production of generics in public pharmacies can destroy the market order of the Korean pharmaceutical industry. Because the main source of income for Korean private pharmaceutical companies is generics, the public pharmacy can shake the private sector to its core if they provide them at a relatively low price. Whether public pharmacy should produce generics or not is a huge dilemma in that generics can improve the sustainability of public pharmacies but at the same time, destroy the market order of the private sector. Finally, in the case of vaccines, some point out that there will be no meaningful improvement in its development, production, and supply even if a public pharmacy is established. It’s because the government has already provided enormous support on vaccines to the private sector, and government organizations such as the Ministry of Food, Drug, and Safety (MFDS) and Centers for Disease Control and Prevention Korea (KCDC) are already involved in consignment production, supply management, and R&D.

E. Alternatives

1. Non-profit Social Enterprise

A non-profit organization (NPO) named “One World Health”, an organization exempt from federal income tax under section 501(c)(3) of Title 26 of the United States, fills the gaps left by governmental, temporary, and narrowly focused healthcare efforts. (OneWorld Health, 2020) One World Health, funded by Bill & Melinda Gates Foundation and the UK government, is providing treatment for neglected diseases in developing countries. The mission of this organization is to conduct R&D and medicine dissemination on neglected diseases. To achieve this goal, One World Health established a cooperative system with companies,

- 40 - non-profit hospitals and the governments of developing countries. Through this cooperation, the company gets financial support for R&D and participants for clinical trials, while the governments secure the supply of treatments for neglected diseases, thus creating a win-win relationship. Likewise, the establishment of a domestic non-profit social enterprise can be considered.

2. Establishment of Multinational Public Pharmacy

Consistent investment in R&D and construction of production facilities are prerequisites of the sustainable medicine supply. However, in a single country that lacks a sufficient number of patients and finances, it is such a difficult task to achieve these goals alone, which suggests the need for cooperation with other countries. The low efficiency of operation, which is considered to be the biggest drawback, can be overcome through the cooperation between other countries: the establishment of multinational public pharmacy through funding from each country. Considering that most rare diseases are congenital or genetic, it is desirable to form a network between neighboring countries that share similar race and regional tendencies. For example, while cystic fibrosis is a rare disease that is prevalent among Caucasians, it is not among Asians. Still, there are concerns regarding multinational public pharmacies: how to assess each country’s contributions, how to transfer a clinical trial patient from one country to another, and what if public pharmacies are being used politically.

3. Strengthening Related Laws

The current role of KOEDC is limited to the procurement of medicines even though KOEDC is the only organization dealing with the issues of orphan drugs in Korea. Therefore, it is required that KOEDC play a more active role and expand its authority (e.g. Securing inventory of rare drugs in advance). Besides, private pharmaceutical companies should be restricted to reject a request for consignment production from government organizations until the publicness of pharmaceuticals

- 41 - is guaranteed to a meaningful extent. Given that private pharmaceutical companies are one of the biggest opponents of establishing public pharmacy, it is their responsibility to ensure drug accessibility to some extent.

- 42 -

Work Cited Jin, B., Lee, J., & Yu, H. (2017). A Study on the Trends of Domestic Pharmaceutical Industry and the Current Status of Production Facilities (국내 제약산업의 동향 및 생산시설 현황 분석). KPBMA Brief

(한국제약바이오협회정책보고서), 13(KPBMA (한국제약바이오협회)), 38–39. Kim, S., Kim, C., & Lee, T. (2015). Pharmaceutical Production and Supply Regimes: A typology based on ‘Publicness’ (공공성 개념에 기초한 의약품 생산

공급 체제의 유형화). Journal of Critical Social Welfare (비판사회정책), 48, 91– 145. Retrieved from http://www.dbpia.co.kr.oca.korea.ac.kr/journal/articleDetail?nodeId=NODE06507253&language=k o_KR Korea Health Industry Development Institute (한국보건산업진흥원). (2019). Market Size of the Pharmaceuticals by Country (국가별 의약품 시장규모). Retrieved August 18, 2020, from KHISS (보건산업정보통계센터) website: http://210.179.230.152:8083/statHtml/statHtml.do?orgId=358&tblId=DT_153

58N_AJA&conn_path=I2# Kwon, M. A Proposal for the Supply and Management of National Essential Drugs (국가필수의약품의 공급 및 관리에 관한 법률안). , (2017). OneWorld Health. (2020). Our Approach. Retrieved August 18, 2020, from OneWorldHealth.com website: https://www.oneworldhealth.com/

- 43 -

Appendix

Ⅰ. List of Designated Rare Diseases

Korean Number Rare Disease ICD 1 A31.9 Atypical mycobacteriosis, familial, x-linked 2 A81.0 Creutzfeldt-Jakob disease 3 A81.0 Subacute spongiform encephalopathy

4 D55.0 Anaemia due to glucose-6- phosphate dehydrogenase [G6PD] deficiency

5 D55.0 Favism 6 D55.0 G6PD deficiency anaemia 7 D55.2 Anaemia due to disorders of glycolytic enzymes 8 D55.2 Haemolytic nonspherocytic (hereditary), type Ⅱ anaemia 9 D55.2 Hexokinase deficiency anaemia 10 D55.2 Pyruvate kinase[PK] deficiency anaemia 11 D55.2 Triose-phosphate isomerase deficiency anaemia 12 D56.0 Alpha thalassaemia 13 D56.1 Beta thalassaemia 14 D56.1 Cooley’s anaemia 15 D56.1 Severe beta thalassaemia 16 D56.1 Intermedia thalassaemia 17 D56.1 Major thalassaemia 18 D56.2 Delta-beta thalassaemia 19 D56.3 Thalassaemia trait 20 D56.4 Hereditary persistence of fetal haemoglobin [HPFH] 21 D59.3 Atypical haemolytic-uraemic syndrome

22 D59.5 Paroxysmal nocturnal haemoglobinuria [Marchiafava-Micheli]

23 D60.0 Chronic acquired pure red cell aplasia 24 D61.0 Constitutional aplastic anaemia 25 D61.0 Aplasia, (pure) red cell (of) congenital 26 D61.0 Aplasia, (pure) red cell (of) infants 27 D61.0 Aplasia, (pure) red cell (of) primary 28 D61.0 Blackfan-Diamond syndrome 29 D61.0 Familial hypoplastic anaemia 30 D61.0 Fanconi’s anaemia 31 D61.0 Pancytopenia with malformations 32 D61.3 Idiopathic aplastic anaemia

- 44 -

33 D61.9 Hypoplastic anaemia NOS 34 D61.9 Medullary hypoplasia 35 D61.9 Panmyelophthisis 36 D64.4 Congenital dyserythropoietic anaemia 37 D64.4 Dyshaematopoietic anaemia(congenital) 38 D66 Hereditary factor Ⅷ deficiency 39 D66 Deficiency factor Ⅷ (with functional defect) 40 D66 Haemophilia NOS 41 D66 Haemophilia A 42 D66 Classical haemophilia 43 D67 Hereditary factor Ⅸ deficiency 44 D67 Christmas disease 45 D67 Factor Ⅸ deficiency (with functional defect) 46 D67 Plasma thromboplastin component[PTC] deficiency 47 D67 Haemophilia B 48 D68.0 Von Willebrand’s disease 49 D68.0 Angiohaemophilia 50 D68.0 Factor Ⅷ deficiency with vascular defect 51 D68.0 Vascular haemophilia 52 D68.1 Hereditary factor Ⅺ deficiency 53 D68.1 Haemophilia C 54 D68.1 Plasma thromboplastin antecedent [PTA] deficiency 55 D68.2 Hereditary deficiency of other clotting factors 56 D68.2 Congenital afibrinogenaemia 57 D68.2 AC globulin deficiency 58 D68.2 Proaccelerin deficiency 59 D68.2 Ⅰ[Fibronogen] deficiency of factor 60 D68.2 Ⅱ[Prothrombin] deficiency of factor 61 D68.2 Ⅴ[Labile] deficiency of factor 62 D68.2 Ⅶ[Stable] deficiency of factor 63 D68.2 Ⅹ[Stuart-Prower] deficiency of factor 64 D68.2 ⅩⅡ[Hageman] deficiency of factor 65 D68.2 ⅩⅢ[Fibrin-stabilizing] deficiency of factor 66 D68.2 Dysfibrinogenaemia (congenital) 67 D68.2 Hypoproconvertinaemia 68 D68.2 Owren’s disease 69 D68.5 Antithrombin deficiency 70 D68.5 Protein C deficiency 71 D68.5 Protein S deficiency 72 D68.6 Antiphospholipid syndrome

- 45 -

73 D69.1 Qualitative platelet defects 74 D69.1 Bernard-Soulier[giant platelet] syndrome 75 D69.1 Glanzmann’s disease 76 D69.1 Grey platelet syndrome 77 D69.1 Thromboasthenia (haemorrhagic)(hereditary) 78 D69.1 Thrombocytopathy 79 D69.30 Evans’ syndrome 80 D70 Agranulocytosis 81 D70 Agranulocytic angina 82 D70 Congenital agranulocytosis 83 D70 Infantile genetic agranulocytosis 84 D70 Kostmann’s disease 85 D70 Neutropenia NOS 86 D70 Congenital neutropenia 87 D70 Cyclic neutropenia 88 D70 Periodic neutropenia 89 D70 Neutropenic splenomegaly 90 D70 Werner-Schultz disease 91 D71 Functional disorders of polymorphonuclear neutrophils 92 D71 Cell membrane receptor complex [CR3] defect 93 D71 Chronic (childhood) granulomatous disease 94 D71 Congenital dysphagocytosis 95 D71 Progressive septic granulomatosis 96 D76.1 Haemophagocytic lymphohistiocytosis 97 D76.1 Familial haemophagocytic reticulosis 98 D76.1 Histiocytoses of mononuclear phagocytes 99 D76.3 Reticulohistiocytoma(giant-cell) 100 D76.3 Sinus histiocytosis with massive lymph- adenopathy 101 D80.0 Hereditary hypogammaglobulinaemia 102 D80.0 Autosomal recessive agammaglobulinaemia (Swiss type)

103 D80.0 X-linked agammaglobulinaemia [Bruton] (with growth hormone deficiency)

104 D80.0 Agammaglobulinemia, primary 105 D80.1 Nonfamilial hypogammaglobulinaemia

106 D80.1 Agammaglobulinaemia with immunoglobulin-bearing B-lymphocytes

107 D80.1 Common variable agammaglobulinaemia [CVAgamma] 108 D80.1 Hypogammaglobulinaemia NOS 109 D80.2 Selective deficiency of immunoglobulin A[IgA]

110 D80.3 Selective deficiency of immunoglobulin G [IgG] subclasses

- 46 -

111 D80.4 Selective deficiency of immunoglobulin M[IgM] 112 D80.5 Immunodeficiency with increased immunoglobulin M[IgM] Antibody deficiency with near-normal immunoglobulins or with 113 D80.6 hyperimmunoglobulinaemia

114 D80.8 Other immunodeficiencies with predominantly antibody defects

115 D80.8 Kappa light chain deficiency

116 D81.0 Severe combined immunodeficiency [SCID] with reticular dysgenesis

117 D81.1 Severe combined immunodeficiency [SCID] with low T-and B-cell numbers

118 D81.2 Severe combined immunodeficiency [SCID] with low or normal B-cell numbers

119 D81.3 Adenosine deaminase[ADA] deficiency 120 D81.4 Nezelof’s syndrome 121 D81.5 Purine nucleoside phosphorylase[PNP] deficiency 122 D81.6 Major histocompatibility complex class I deficiency 123 D81.6 Bare lymphocyte syndrome 124 D81.7 Major histocompatibility complex class Ⅱ deficiency 125 D81.8 Biotin-dependent carboxylase deficiency 126 D81.8 Omenn syndrome 127 D81.9 Severe combined immunodeficiency disorder [SCID]) NOS 128 D82.0 Wiskott-Aldrich syndrome 129 D82.0 Immunodeficiency with thrombocy- topenia and eczema 130 D82.1 Di George’s syndrome 131 D82.1 Pharyngeal pouch syndrome 132 D82.1 Thymic alymphoplasia 133 D82.1 Thymic aplasia or hypoplasia with immunodeficiency 134 D82.2 Immunodeficiency with short-limbed stature

135 D82.3 Immunodeficiency following hereditary defective response to Epstein-Barr virus

136 D82.3 X-linked lymphoproliferative disease 137 D82.4 Hyperimmunoglobulin E [IgE] syndrome Common variable immunodeficiency with predominant abnormalities of B-cell 138 D83.0 numbers and function Common variable immunodeficiency with predominant immunoregulatory T-cell 139 D83.1 disorders 140 D83.2 Common variable immunodeficiency with autoantibodies to B-or T-cells 141 D84.0 Lymphocyte function antigen-1[LFA-1] defect 142 D84.1 Defects in the complement system 143 D84.1 C1 esterase inhibitor[C1-INH] deficiency 144 D86.0 Sarcoidosis of lung

- 47 -

145 D86.1 Sarcoidosis of lymph nodes 146 D86.2 Sarcoidosis of lung with sarcoidosis of lymph nodes 147 D86.3 Sarcoidosis of skin 148 D86.8 Sarcoidosis of other and combined sites 149 D86.8 Iridocyclitis in sarcoidosis(H22.1*) 150 D86.8 Multiple cranial nerve palsies in sarcoidosis(G53.2*) 151 D86.8 Sarcoid arthropathy(M14.8*) 152 D86.8 Sarcoid myocarditis(I41.8*) 153 D86.8 Sarcoid myositis(M63.3*) 154 D86.8 Uveoparotid fever[Heerfordt] 155 E16.10 Congenital hyperinsulinaemia 156 E20.1 Pseudohypoparathyroidism 157 E22.0 Acromegaly and pituitary gigantism 158 E22.0 Arthropathy associated with acromegaly(M14.5*) 159 E22.0 Overproduction of growth hormone 160 E23.0 Kallmann’s syndrome 161 E23.0 Sheehan’s syndrome 162 E24.0 Pituitary-dependent Cushing’s disease 163 E24.0 Overproduction of pituitary ACTH 164 E24.0 Pituitary-dependent hyperadrenocorticism 165 E24.1 Nelson’s syndrome 166 E24.3 Ectopic ACTH syndrome

167 E25.0 Congenital adrenogenital disorders associated with enzyme deficiency

168 E25.0 Congenital adrenal hyperplasia 169 E25.0 21-Hydroxylase deficiency 170 E25.0 Salt-losing congenital adrenal hyperplasia 171 E25.9 Adrenogenital syndrome NOS 172 E26.8 Bartter’s syndrome 173 E27.1 Primary adrenocortical insufficiency 174 E27.1 Familial glucocorticoid deficiency 175 E27.1 Addison’s disease 176 E27.1 Autoimmune adrenalitis 177 E27.2 Addisonian crisis 178 E27.2 Adrenal crisis 179 E27.2 Adrenocortical crisis 180 E27.4 Adrenal haemorrhage 181 E27.4 Adrenal infarction 182 E27.4 Adrenocortical insufficiency NOS 183 E27.4 Hypoaldosteronism

- 48 -

184 E34.8 Pineal gland dysfunction 185 E34.8 Progeria 186 E55.0 Rickets, active 187 E55.0 Infantile osteomalacia 188 E55.0 Juvenile osteomalacia 189 E70.0 Classical phenylketonuria 190 E70.1 Other hyperphenylalaninaemias 191 E70.2 Disorders of tyrosine metabolism 192 E70.2 Alkaptonuria 193 E70.2 Ochronosis 194 E70.2 Tyrosinaemia 195 E70.2 Tyrosinosis 196 E70.3 Oculocutaneous albinism 197 E70.3 Ocular albinism 198 E70.3 Chediack(-Steinbrinck)-Higashi syndrome 199 E70.3 Cross syndrome 200 E70.3 Hermansky-Pudlak syndrome 201 E70.3 Waardenburg´s syndrome 202 E70.8 Disorder of histidine metabolism 203 E70.8 Disorder of tryptophan metabolism 204 E71.0 Maple-syrup-urine disease 205 E71.1 Hyperleucine-isoleucinaemia 206 E71.1 Hypervalinaemia 207 E71.1 Methylmalonic acidaemia 208 E71.1 Isovaleric acidaemia 209 E71.1 Propionic acidaemia 210 E71.3 Disorders of fatty-acid metabolism 211 E71.3 Adrenoleukodystrophy[Addison-Schilder] 212 E71.3 Muscle carnitine palmityltransferase deficiency 213 E71.3 Very long chain acyl-CoA dehydrogenase(VLCAD) deficiency(VLCAD) 214 E72.0 Disorders of amino-acid transport 215 E72.0 Cystine storage disease(N29.8*) 216 E72.0 Cystinosis 217 E72.0 Cystinuria 218 E72.0 Fanconi(-de Toni)(-Debré)syndrome 219 E72.0 Hartnup’s disease 220 E72.0 Lowe’s syndrome 221 E72.1 Disorders of sulfur-bearing amino-acid metabolism 222 E72.1 Cystathioninuria 223 E72.1 Homocystinuria

- 49 -

224 E72.1 Methioninaemia 225 E72.1 Sulfite oxidase deficiency 226 E72.1 Hyperhomocysteinemia 227 E72.2 Disorders of urea cycle metabolism 228 E72.2 Argininaemia 229 E72.2 Argininosuccinic aciduria 230 E72.2 Citrullinaemia 231 E72.2 Hyperammonaemia 232 E72.3 Disorders of lysine and hydroxylysine metabolism 233 E72.3 Glutaric aciduria 234 E72.3 Hydroxylysinaemia 235 E72.3 Hyperlysinaemia 236 E72.4 Disorders of ornithine metabolism 237 E72.4 Ornithinaemia (typesⅠ, Ⅱ) 238 E72.4 Ornithine transcarbamylase deficiency 239 E72.5 Disorders of glycine metabolism 240 E72.5 Hyperhydroxyprolinaemia 241 E72.5 Hyperprolinaemia (typesⅠ, Ⅱ) 242 E72.5 Non-ketotic hyperglycinaemia 243 E72.5 Sarcosinaemia 244 E72.8 Disorders of β-amino-acid metabolism 245 E72.8 Disorders of γ-glutamyl cycle 246 E73.0 Congenital lactase deficiency 247 E74.0 Glycogen storage disease 248 E74.0 Glycogen storage disease 1b type A 249 E74.0 Glycogen synthase deficiency 250 E74.0 Cardiac glycogenosis 251 E74.0 Andersen’s disease 252 E74.0 Cori’s disease 253 E74.0 Forbes’ disease 254 E74.0 Hers’ disease 255 E74.0 McArdle’s disease 256 E74.0 Pompe’s disease 257 E74.0 Tarui’s disease 258 E74.0 von Gierke’s disease 259 E74.0 Liver phosphorylase deficiency 260 E74.2 Disorders of galactose metabolism 261 E74.2 Galactokinase deficiency 262 E74.2 Galactosaemia 263 E74.4 Disorders of pyruvate metabolism and gluco-neogenesis

- 50 -

264 E74.4 Deficiency of phosphoenol-pyruvate carboxykinase 265 E74.4 Deficiency of carboxylase pyruvate 266 E74.4 Deficiency of dehydrogenase pyruvate 267 E74.8 Oxaluria 268 E75.0 GM₂-gangliosidosis 269 E75.0 Sandhoff’s disease 270 E75.0 Tay-Sachs’ disease 271 E75.0 GM₂gangliosidosis NOS 272 E75.0 Adult GM₂gangliosidosis 273 E75.0 Juvenile GM₂gangliosidosis 274 E75.1 Gangliosidosis NOS 275 E75.1 GM₁-gangliosidosis 276 E75.1 GM₃-gangliosidosis 277 E75.1 Mucolipidosis Ⅳ 278 E75.2 Fabry’s(-Anderson) disease 279 E75.2 Gaucher’s disease 280 E75.2 Krabbe’s disease 281 E75.2 Niemann-Pick’s disease 282 E75.2 Farber’s syndrome 283 E75.2 Metachromatic leukodystrophy 284 E75.2 Sulfatase deficiency 285 E75.4 Neuronal ceroid lipofuscinosis 286 E75.4 Batten’s disease 287 E75.4 Jansky-Bielschowsky’s disease 288 E75.4 Kufs’ disease 289 E75.4 Spielmeyer-Vogt’s disease

290 E75.5 Cerebrotendinous cholesterosis [van Bogaert-Scherer-Epstein]

291 E75.5 Wolman’s disease 292 E76.0 Mucopolysaccharidosis, type Ⅰ 293 E76.0 Hurler syndrome 294 E76.0 Hurler-Scheie syndrome 295 E76.0 Scheie syndrome 296 E76.1 Mucopolysaccharidosis, type Ⅱ 297 E76.1 Hunter’s syndrome 298 E76.2 β-Glucuronidase deficiency 299 E76.2 Mucopolysaccharidosis, types Ⅲ, Ⅳ, Ⅵ, Ⅶ 300 E76.2 Maroteaux-Lamy (mild)(severe) syndrome 301 E76.2 Morquio(-like)(classic) syndrome 302 E76.2 Sanfilippo (types B)(type C)(type D) syndrome

- 51 -

303 E77.0 Defects in post-translational modification of lysosomal enzymes 304 E77.0 Mucolipidosis Ⅱ[Ⅰ-cell disease] 305 E77.0 Mucolipidosis Ⅲ [Pseudo-Hurler polydystrophy] 306 E77.1 Defects in glycoprotein degradation 307 E77.1 Aspartylglucosaminuria 308 E77.1 Fucosidosis 309 E77.1 Mannosidosis 310 E77.1 Sialidosis[mucolipidosisⅠ] 311 E79.1 Lesch-Nyhan syndrome 312 E80.2 Hereditary coproporphyria 313 E80.2 Porphyria NOS 314 E80.2 Acute intermittent(hepatic) porphyria 315 E83.0 Disorders of copper metabolism 316 E83.0 Menkes (kinky hair)(steely hair) disease 317 E83.0 Wilson’s disease 318 E83.1 Haemochromatosis 319 E83.2 Acrodermatitis enteropathica 320 E83.3 Disorders of phosphorus metabolism and phosphatases 321 E83.3 Acid phosphatase deficiency 322 E83.3 Familial hypophosphataemia 323 E83.3 Hypophosphatasia 324 E83.3 Vitamin-D-resistant osteomalacia 325 E83.3 Vitamin-D-resistant rickets 326 E84.0 Cystic fibrosis with pulmonary manifestations 327 E84.1 Cystic fibrosis with intestinal manifestations 328 E84.1 Distal intestinal obstruction syndrome 329 E84.1 Meconium ileus in cystic fibrosis(P75*) 330 E85.0 Non-neuropathic heredofamilial amyloidosis 331 E85.0 Familial Mediterranean fever 332 E85.0 Hereditary amyloid nephropathy 333 E85.1 Neuropathic heredofamilial amyloidosis 334 E85.1 Amyloid polyneuropathy(Portuguese) 335 E85.2 Heredofamilial amyloidosis, unspecified 336 E85.4 Organ-limited amyloidosis 337 E85.4 Localized amyloidosis 338 E88.0 α-1-Antitrypsin deficiency 339 E88.1 Congenital systemic lipodystrophy 340 F80.3 Acquired aphasia with epilepsy [Landau-Kleffner] 341 F84.2 Rett’s syndrome 342 G10 Huntington’s disease

- 52 -

343 G10 Huntington’s chorea 344 G11.0 Congenital nonprogressive ataxia

345 G11.1 Early-onset cerebellar ataxia(onset usually before the age of 20)

346 G11.1 Early-onset cerebellar ataxia with essential tremor

347 G11.1 Early-onset cerebellar ataxia with myoclonus[Hunt’s ataxia]

348 G11.1 Early-onset cerebellar ataxia with retained tendon reflexes

349 G11.1 Friedreich’s ataxia(autosomal recessive) 350 G11.1 X-linked recessive spinocerebellar ataxia

351 G11.2 Late-onset cerebellar ataxia(Onset usually after the age of 20)

352 G11.3 Cerebellar ataxia with defective DNA repair 353 G11.3 Ataxia telangiectasia[Louis-bar] 354 G11.4 Hereditary spastic paraplegia 355 G11.8 Other hereditary ataxias 356 G11.9 Hereditary ataxia, unspecified 357 G11.9 Hereditary cerebellar ataxia NOS 358 G11.9 Hereditary cerebellar degeneration 359 G11.9 Hereditary cerebellar disease 360 G11.9 Hereditary cerebellar syndrome

361 G12.0 Infantile spinal muscular atrophy, type Ⅰ[Werdnig-Hoffman]

362 G12.1 Other inherited spinal muscular atrophy 363 G12.1 Progressive bulbar palsy of childhood [Fazio-Londe] 364 G12.1 Adult form spinal muscular atrophy 365 G12.1 Childhood form, type Ⅱ spinal muscular atrophy 366 G12.1 Distal spinal muscular atrophy

367 G12.1 Juvenile form, typeⅢ [Kugelberg-Welander] spinal muscular atrophy

368 G12.1 Scapuloperoneal form spinal muscular atrophy

369 G12.2 Motor neuron disease

370 G12.8 Other spinal muscular atrophies and related syndromes 371 G12.9 Spinal muscular atrophy, unspecified 372 G23.0 Hallervorden-Spatz disease 373 G23.0 Pigmentary pallidal degeneration

374 G23.1 Progressive supranuclear ophthalmoplegia [Steele-Richardson-Olszewski]

375 G25.8 Stiff-man syndrome

- 53 -

376 G31.81 Subacute necrotizing encephalopathy[Leigh] 377 G35 Multiple sclerosis 378 G35 Multiple sclerosis (of) NOS 379 G35 Multiple sclerosis (of) brain stem 380 G35 Multiple sclerosis (of) cord 381 G35 Multiple sclerosis (of) disseminated 382 G35 Multiple sclerosis (of) generalized 383 G36.0 Neuromyelitis optica[Devic] 384 G40.4 Lennox-Gastaut syndrome 385 G40.4 West’s syndrome 386 G41.0 Grand mal status epilepticus 387 G41.0 Tonic-clonic status epilepticus 388 G41.1 Petit mal status epilepticus 389 G41.1 Epileptic absence statu 390 G41.2 Complex partial status epilepticus 391 G41.8 Other status epilepticus 392 G41.9 Status epilepticus, unspecified 393 G47.4 Narcolepsy and cataplexy 394 G51.2 Melkersson’s syndrome 395 G51.2 Melkersson-Rosenthal syndrome 396 G56.4 Complex regional pain syndrome typeⅡ 397 G57.80 Complex regional pain syndrome type II of lower limb 398 G60.0 Hereditary motor and sensory neuropathy 399 G60.0 Charcot-Marie-Tooth disease 400 G60.0 Déjerine-Sottas disease 401 G60.0 Hereditary motor and sensory neuropathy, types I-IV 402 G60.0 Hypertrophic neuropathy of infancy

403 G60.0 Peroneal muscular atrophy(axonal type, hypertrophic type)

404 G60.0 Roussy-Lévy syndrome 405 G61.0 Guillain-Barré syndrome 406 G61.0 Miller Fisher Syndrome 407 G61.8 Multifocal Motor Neuropathy 408 G61.8 Chronic inflammatory demyelinating polyneuropathy 409 G70.0 Myasthenia gravis 410 G70.2 Congenital and developmental myasthenia 411 G71.0 Muscular dystrophy Autosomal recessive, childhood type, resembling Duchenne or Becker muscular 412 G71.0 dystrophy 413 G71.0 Benign [Becker] muscular dystrophy

414 G71.0 Benign scapuloperoneal with early contractures [Emery-Dreifuss] muscular dystrophy

- 54 -

415 G71.0 Distal muscular dystrophy 416 G71.0 Facioscapulohumeral muscular dystrophy 417 G71.0 Limb-girdle muscular dystrophy 418 G71.0 Ocular muscular dystrophy 419 G71.0 Oculopharyngeal muscular dystrophy 420 G71.0 Scapuloperoneal muscular dystrophy 421 G71.0 Severe[Duchenne] muscular dystrophy 422 G71.1 Myotonic disorders 423 G71.1 Dystrophia myotonica[Steinert] 424 G71.1 Chondrodystrophic myotonia 425 G71.1 Symptomatic myotonia 426 G71.1 Myotonia congenita NOS 427 G71.1 Dominant[Thomsen] myotonia congenita 428 G71.1 Recessive[Becker] myotonia congenita 429 G71.1 Neuromyotonia[Isaacs] 430 G71.1 Paramyotonia congenita 431 G71.1 Pseudomyotonia 432 G71.2 Congenital myopathies 433 G71.2 Congenital muscular dystrophy NOS Congenital muscular dystrophy with specific morphological abnormalities of the 434 G71.2 muscle fibre(G71.2) 435 G71.2 Central core disease 436 G71.2 Minicore disease 437 G71.2 Multicore disease 438 G71.2 Fibre-type disproportion 439 G71.2 Myotubular (centronuclear) myopathy 440 G71.2 Nemaline myopathy 441 G71.3 Mitochondrial myopathy, NEC 442 G71.3 Mitochodrial myophathy, encephalopathy, lactic acsidosis, and stroke-like episodes 443 G71.9 Hereditary myopathy NOS 444 G72.3 Hypokalaemic periodic paralysis (familial) 445 G73.1 Lambert-Eaton syndrome(C00-D48†) 446 G95.0 Syringomyelia and syringobulbia 447 H35.01 Coats 448 H35.05 Eales´ disease 449 H35.51 Retinitis pigmentosa 450 H35.58 Stargardt’s disease 451 H35.59 Leber Congenital Amaurosis 452 H35.59 Unspecified hereditary retinal dystrophy 453 H49.8 Kearns-Sayre syndrome

- 55 -

454 H51.8 Ocular motor apraxia, Cogan type 455 I27.0 Primary pulmonary hypertension 456 I27.8 Eisenmenger's complex 457 I27.8 Eisenmenger's syndrome 458 I42.0 Irreversible dilated cardiomyopathy 459 I42.1 Obstructive hypertrophic cardiomyopathy 460 I42.1 Hypertrophic subaortic stenosis 461 I42.2 Nonobstructive hypertrophic cardiomyopathy 462 I42.3 Endomyocardial(eosinophilic) disease 463 I42.3 Endomyocardial(tropical) fibrosis 464 I42.3 Loffler’s endocarditis 465 I42.4 Endocardial fibroelastosis 466 I42.4 Congenital cardiomyopathy 467 I47.2 Catecholaminergic polymorphic ventricular tachycardia 468 I67.5 Moyamoya disease 469 I73.1 Thromboangiitis obliterans[Buerger] 470 I78.0 Rendu-Osler-Weber disease 471 I82.0 Budd-Chiari syndrome 472 J84.0 Alveolar proteinosis 473 J84.18 Idiopathic pulmonary fibrosis 474 K00.51 Dentinogenesis imperfecta 475 K50.0 Crohn’s disease of small intestine 476 K50.1 Crohn’s disease of large intestine 477 K50.8 Crohn’s disease of both small and large intestine 478 K74.3 Primary biliary cirrhosis 479 K75.4 Autoimmune hepatitis 480 K83.0 Primary cholangitis/Sclerosing cholangitis 481 L10.0 Pemphigus vulgaris 482 L10.2 Pemphigus foliaceus 483 L12.0 Bullous pemphigoid 484 L12.1 Cicatricial pemphigoid 485 L12.1 Benign mucous membrane pemphigoid 486 L12.3 Acquired epidermolysis bullosa 487 M08.0 Juvenile rheumatoid arthritis

488 M08.0 Juvenile rheumatoid arthritis with or without rheumatoid factor

489 M08.1 Juvenile ankylosing spondylitis 490 M08.2 Juvenile arthritis with systemic onset 491 M08.3 Juvenile polyarthritis (seronegative) 492 M08.3 Chronic juvenile polyarthritis

- 56 -

493 M30.0 Polyarteritis nodosa 494 M30.1 Polyarteritis with lung involvement [Churg- Strauss] 495 M30.2 Juvenile polyarteritis 496 M31.0 Goodpasture’s syndrome 497 M31.1 Thrombotic microangiopathy 498 M31.1 Thrombotic thrombocytopenic purpura 499 M31.2 Lethal midline granuloma 500 M31.3 Wegener’s granulomatosis 501 M31.3 Necrotizing respiratory granulomatosis 502 M31.4 Aortic arch syndrome [Takayasu] 503 M31.7 Microscopic polyarteritis

504 M32.1 Systemic lupus erythematosus with organ or system involvement

505 M33.0 Juvenile dermatomyositis 506 M33.1 Other dermatomyositis 507 M33.2 Polymyositis 508 M34.0 Progressive systemic sclerosis 509 M34.1 CR(E)ST syndrome Combination of calcinosis, Raynaud’s phenomenon, (o)esophageal dysfunction, 510 M34.1 sclerodactyly, telangiectasia 511 M34.8 Systemic sclerosis with lung involvement(J99.1*) 512 M34.8 Systemic sclerosis with myopathy(G73.7*) 513 M35.0 Sicca syndrome[Sjögren] 514 M35.0 Sjogren’s syndrome with keratoconjunctivitiis(H19.3*) 515 M35.0 Sjogren’s syndrome with lung involvement(J99.1*) 516 M35.0 Sjogren’s syndrome with myopathy(G73.7*)

517 M35.0 Sjogren’s syndrome with renal tubulo-interstitial disorder(N16.4*)

518 M35.1 Mixed connective tissue disease 519 M35.2 Behçet’s disease 520 M35.3 Polymyalgia rheumatica 521 M35.4 Diffuse(eosinophilic) fasciitis 522 M35.5 Multifocal fibrosclerosis 523 M35.6 Relapsing panniculitis[Weber-Christian] 524 M61.1 Fibrodysplasia ossificans progressiva M8220/0, 525 Familial adenomatous polyposis (D12.6) 526 M88.0 Paget’s disease of skull 527 M88.8 Paget’s disease of other bones 528 M88.9 Paget’s disease of bone, unspecified 529 M89.0 Complex regional pain syndrome type I

- 57 -

530 M94.1 Relapsing polychondritis 531 N04.0 Nephrotic syndrome with minor glomerular abnormality 532 N04.0 Nephrotic syndrome with minimal change lesion

533 N04.1 Nephrotic syndrome with focal and segmental glomerular lesions

534 N04.1 Nephrotic syndrome with focal and segmental hyalinosis 535 N04.1 Nephrotic syndrome with focal and segmental sclerosis 536 N04.1 Nephrotic syndrome with focal glomerulonephritis

537 N04.2 Nephrotic syndrome with diffuse membranous glomerulonephritis

538 N04.3 Nephrotic syndrome with diffuse mesangial proliferative glomerulonephritis

539 N04.4 Nephrotic syndrome with diffuse endocapillary proliferative glomerulonephritis

540 N04.5 Nephrotic syndrome with diffuse mesangiocapillary glomerulonephritis

Nephrotic syndrome with membranoproliferative glomerulonephritis, types 1 and 3, or 541 N04.5 NOS 542 N04.6 Nephrotic syndrome with dense deposit disease

543 N04.6 Nephrotic syndrome with membranoproliferative glomerulonephritis, type 2

544 N04.7 Nephrotic syndrome with diffuse crescentic glomerulonephritis

545 N04.7 Nephrotic syndrome with extracapillary glomerulonephritis

546 N25.1 Nephrogenic diabetes insipidus 547 P35.0 Congenital rubella syndrome 548 Q03.1 Dandy-Walker syndrome 549 Q04.3 Agyria of brain 550 Q04.3 Lissencephaly 551 Q04.3 Pachygyria 552 Q04.3 Cerebellar agenesis 553 Q04.6 Schizencephaly 554 Q05.0 Cervical spina bifida with hydrocephalus 555 Q05.1 Thoracic spina bifida with hydrocephalus 556 Q05.1 Dorsal spina bifida with hydrocephalus 557 Q05.1 Thoracolumbar spina bifida with hydrocephalus 558 Q05.2 Lumbar spina bifida with hydrocephalus 559 Q05.2 Lumbosacral spina bifida with hydrocephalus 560 Q05.3 Sacral spina bifida with hydrocephalus 561 Q05.4 Unspecified spina bifida with hydrocephalus 562 Q05.5 Cervical spina bifida without hydrocephalus

- 58 -

563 Q05.6 Thoracic spina bifida without hydrocephalus 564 Q05.6 Dorsal spina bifida NOS 565 Q05.6 Thoracolumbar spina bifida NOS 566 Q05.7 Lumbar spina bifida without hydrocephalus 567 Q05.7 Lumbosacral spina bifida NOS 568 Q05.8 Sacral spina bifida without hydrocephalus 569 Q05.9 Spina bifida, unspecified 570 Q06.2 Diastematomyelia 571 Q07.0 Arnold-Chiari syndrome 572 Q11.2 Lenz microphthalmia syndrome 573 Q14.1 X-linked juvenile retinoschisis 574 Q17.2 Microtia 575 Q20.0 Common arterial trunk 576 Q20.0 Persistent truncus arteriosus 577 Q20.1 Double outlet right ventricle 578 Q20.1 Taussig-Bing syndrome 579 Q20.2 Double outlet left ventricle 580 Q20.3 Discordant ventriculoarterial connection 581 Q20.3 Dextrotransposition of aorta 582 Q20.3 Transposition of great vessels (complete) 583 Q20.4 Single ventricle 584 Q20.5 Discordant atrioventricular connection 585 Q20.5 Corrected transposition 586 Q20.5 Laevotransposition 587 Q20.5 Ventricular inversion 588 Q21.2 Atrioventricular septal defect 589 Q21.2 Common atrioventricular canal 590 Q21.2 Endocardial cushion defect 591 Q21.2 Ostium primum atrial septal defect (typeⅠ) 592 Q21.3 Tetralogy of Fallot

Ventricular septal defect with pulmonary stenosis or atresia, dextroposition of aorta 593 Q21.3 and hypertrophy of right ventricle

594 Q21.4 Aortopulmonary septal defect 595 Q21.4 Aortic septal defect 596 Q21.4 Aortopulmonary window 597 Q21.8 Eisenmenger’s defect 598 Q22.0 Pulmonary valve atresia 599 Q22.4 Tricuspid atresia 600 Q22.5 Ebstein’s anomaly

- 59 -

601 Q22.6 Hypoplastic right heart syndrome 602 Q23.0 Congenital stenosis of aortic valve 603 Q23.0 Congenital aortic atresia 604 Q23.0 Congenital aortic stenosis 605 Q23.1 Congenital insufficiency of aortic valve 606 Q23.1 Bicuspid aortic valve 607 Q23.1 Congenital aortic insufficiency 608 Q23.1 Congenital aortic regurgitation 609 Q23.2 Congenital mitral stenosis 610 Q23.2 Congenital mitral atresia 611 Q23.3 Congenital mitral insufficiency 612 Q23.4 Hypoplastic left heart syndrome

Atresia, or marked hypoplasia of aortic orifice or valve, with hypoplasia of ascending 613 Q23.4 aorta and defective development of left ventricle (with mitral valve stenosis or atresia)

614 Q23.8 Other congenital malformations of aortic and mitral valves

615 Q23.9 Congenital malformation of aortic and mitral valves, unspecified

616 Q24.4 Congenital subaortic stenosis 617 Q24.5 Malformation of coronary vessels 618 Q24.5 Congenital coronary(artery) aneurysm 619 Q24.6 Congenital heart block 620 Q25.1 Coarctation of aorta 621 Q25.1 Coarctation of aorta (preductal, postductal) 622 Q25.2 Atresia of aorta 623 Q25.3 Stenosis of aorta 624 Q25.3 Supravalvular aortic stenosis 625 Q25.5 Atresia of pulmonary artery 626 Q26.0 Congenital stenosis of vena cava 627 Q26.0 Congenital stenosis of vena cava (inferior)(superior) 628 Q26.1 Persistent left superior vena cava 629 Q26.2 Total anomalous pulmonary venous connection 630 Q26.3 Partial anomalous pulmonary venous connection 631 Q26.4 Anomalous pulmonary venous connection, unspecified 632 Q26.5 Anomalous portal venous connection 633 Q26.6 Portal vein-hepatic artery fistula 634 Q28.2 Wyburn Mason syndrome 635 Q38.3 Aglossia 636 Q44.2 Atresia of bile ducts

- 60 -

637 Q44.7 Alagille’s syndrome 638 Q61.1 Polycystic kidney, autosomal recessive 639 Q61.1 Polycystic kidney, infantile type 640 Q61.9 Meckel syndrome 641 Q64.1 Exstrophy of urinary bladder 642 Q64.1 Ectopia vesicae 643 Q64.1 Extroversion of bladder 644 Q74.0 Cleidocranial dysostosis 645 Q74.3 Arthrogryposis multiplex congenita 646 Q75.0 Craniosynostosis 647 Q75.0 Acrocephaly 648 Q75.0 Imperfect fusion of skull 649 Q75.0 Oxycephaly 650 Q75.0 Trigonocephaly 651 Q75.1 Craniofacial dysostosis 652 Q75.1 Crouzon’s disease 653 Q75.4 Mandibulofacial dysostosis 654 Q75.4 Franceschetti syndrome 655 Q75.4 Treacher Collins syndrome 656 Q77.0 Achondrogenesis 657 Q77.0 Hypochondrogenesis 658 Q77.1 Thanatophoric short stature 659 Q77.2 Short rib syndrome 660 Q77.2 Asphyxiating thoracic dysplasia[Jeune] 661 Q77.3 Chondrodysplasia punctata 662 Q77.3 Rhizomelic chondrodysplasia punctata(type 1-3) 663 Q77.3 X-linked dominant chondrodysplasia 664 Q77.4 Achondroplasia 665 Q77.4 Hypochondroplasia 666 Q77.4 Osteosclerosis congenita 667 Q77.5 Dystrophic dysplasia 668 Q77.6 Chondroectodermal dyplasia 669 Q77.6 Ellis-van Creveld syndrome 670 Q77.7 Spondyloepiphyseal dysplasia 671 Q77.7 Spondyloepiphyseal dysplasia tarda

672 Q77.8 Other osteochondrodysplasia with defects of growth of tubular bones and spine

673 Q77.8 Acromicric dysplasia

674 Q77.9 Osteochondrodysplasia with defects of growth of tubular bones and spine, unspecified

- 61 -

675 Q78.0 Osteogenesis imperfecta 676 Q78.0 Fragilitas ossium 677 Q78.0 Osteopsathyrosis 678 Q78.1 Polyostotic fibrous dysplasia 679 Q78.1 Albright(-McCune)(-Sternberg) syndrome 680 Q78.2 Osteopetrosis 681 Q78.2 Albers-Schönberg syndrome 682 Q78.3 Camurati-Engelmann syndrome 683 Q78.4 Enchondromatosis 684 Q78.4 Maffucci’s syndrome 685 Q78.4 Ollier’s disease 686 Q78.5 Metaphyseal chondrodysplasia, Schmid type 687 Q78.5 Pyle’s syndrome 688 Q78.6 Multiple congenital exostoses 689 Q78.6 Hereditary multiple exostoses 690 Q78.6 Diaphyseal aclasis 691 Q78.9 Pseudoachondroplastic dysplasia 692 Q79.0 Congenital diaphragmatic hernia 693 Q79.1 Other congenital malformations of diaphragm 694 Q79.1 Absence of diaphragm 695 Q79.1 Congenital malformation of diaphragm NOS 696 Q79.1 Eventration of diaphragm 697 Q79.2 Exomphalos 698 Q79.2 Omphalocele 699 Q79.3 Gastroschisis 700 Q79.4 Prune belly syndrome 701 Q79.5 Other congenital malformations of abdominal wall 702 Q79.6 Ehlers-Danlos syndrome 703 Q79.8 Other congenital malformations of musculoskeletal system 704 Q79.8 Absence of muscle 705 Q79.8 Absence of tendon 706 Q79.8 Accessory muscle 707 Q79.8 Amyotrophia congenita 708 Q79.8 Congenital constricting bands 709 Q79.8 Congenital shortening of tendon 710 Q79.8 Poland’s syndrome

711 Q79.9 Congenital malformation of musculoskeletal system, unspecified

712 Q79.9 Congenital anomaly of musculoskeletal system NOS 713 Q79.9 Congenital deformity of musculoskeletal system NOS 714 Q80.2 Lamellar ichthyosis

- 62 -

715 Q80.3 Congenital bullous ichthyosiform erythroderma 716 Q81.0 Epidermolysis bullosa simplex 717 Q81.1 Epidermolysis bullosa letalis 718 Q81.1 Herlitz’ syndrome 719 Q81.2 Epidermolysis bullosa dystrophica 720 Q82.3 Incontinentia Pigmenti 721 Q82.4 Ectodermal dysplasia (anhidrotic) 722 Q85.0 Neurofibromatosis (nonmalignant) 723 Q85.0 Neurofibromatosis(nonmalignant) type 1, type 2 724 Q85.0 Von Recklinghausen’s disease 725 Q85.1 Tuberous sclerosis 726 Q85.1 Bourneville’s disease 727 Q85.1 Epiloia 728 Q85.8 Peutz-Jeghers syndrome 729 Q85.8 Sturge-Weber(-Dimitri) syndrome 730 Q85.8 Von Hippel-Lindau syndrome 731 Q86.0 Fetal alcohol syndrome (dysmorphic)

732 Q87.0 Congenital malformation syndromes predominantly affecting facial appearance

733 Q87.0 Acrocephalopolysyndactyly 734 Q87.0 Acrocephalosyndactyly(Apert) 735 Q87.0 Cryptophthalmos syndrome 736 Q87.0 Cyclopia 737 Q87.0 Goldenhar syndrome 738 Q87.0 Gorlin-Chaudhry-Moss syndrome 739 Q87.0 Moebius syndrome 740 Q87.0 Oro-facial-digital syndrome 741 Q87.0 Robin syndrome 742 Q87.0 Whistling face 743 Q87.0 Carpenter´s syndrome

744 Q87.1 Congenital malformation syndromes predominantly associated with short stature

745 Q87.1 Aarskog syndrome 746 Q87.1 Cockayne syndrome 747 Q87.1 De Lange syndrome 748 Q87.1 Dubowitz syndrome 749 Q87.1 Noonan syndrome 750 Q87.1 Prader-Willi syndrome 751 Q87.1 Robinow-Silverman-Smith syndrome 752 Q87.1 Russel-Silver syndrome 753 Q87.1 Seckel syndrome 754 Q87.1 Smith-Lemli-Opitz syndrome

- 63 -

755 Q87.1 Sjogren-Larsson syndrome 756 Q87.2 Holt-Oram syndrome 757 Q87.2 Klippel-Trénaunay-Weber syndrome 758 Q87.2 Nail patella syndrome 759 Q87.2 Rubinstein-Taybi syndrome 760 Q87.2 VATER syndrome 761 Q87.3 Beckwith-Wiedemann syndrome 762 Q87.3 Sotos syndrome 763 Q87.3 Weaver syndrome 764 Q87.4 Marfan’s syndrome 765 Q87.8 Alport syndrome 766 Q87.8 Laurence-Moon(-Bardet)-Biedl syndrome 767 Q87.8 Zellweger syndrome 768 Q87.8 CHARGE syndrome 769 Q90.0 Trisomy 21, meiotic nondisjunction 770 Q90.1 Trisomy 21, mosaicism (mitotic nondisjunction) 771 Q90.2 Trisomy 21, translocation 772 Q90.9 Trisomy 21 NOS 773 Q91.0 Trisomy 18, meiotic nondisjunction 774 Q91.1 Trisomy 18, mosaicism (mitotic nondisjunction) 775 Q91.2 Trisomy 18, translocation 776 Q91.4 Trisomy 13, meiotic nondisjunction 777 Q91.5 Trisomy 13, mosaicism (mitotic nondisjunction) 778 Q91.6 Trisomy 13, translocation 779 Q91.7 Trisomy 13 Syndrome 780 Q92.2 Trisomy 10p 781 Q93.3 Wolff-Hirschhorn syndrome 782 Q93.4 Deletion of short arm of chromosome 5 783 Q93.4 Cri-du-chat syndrome 784 Q93.5 Angelman syndrome 785 Q93.5 CATCH22 syndrome 786 Q93.5 18q monosomy 787 Q93.5 Smith-Magenis syndrome 788 Q93.5 Williams syndrome 789 Q96.0 Karyotype 45, X 790 Q96.1 Karyotype 46, X iso(Xq) 791 Q96.2 Karyotype 46, X with abnormal sex chromosome, except iso(Xq) 792 Q96.3 Mosaicism, 45, X/46, XX or XY 793 Q96.4 Mosaicism, 45, X/other cell line(s) with abnormal sex chromosome 794 Q98.0 Klinefelter’s syndrome karyotype 47, XXY

- 64 -

795 Q98.1 Klinefelter’s syndrome, male with more than two X chromosomes 796 Q98.2 Klinefelter’s syndrome, male with 46,XX karyotype 797 Q99.2 Fragile X syndrome 798 NA Alstrom syndrome

799 NA Arthrogryposis, renal tubular dysfunction, and cholestasis (ARC syndrome)

800 NA Cowden syndrome 801 NA Dent disease 802 NA Glucose transporter type1 (GLUT1) deficiency 803 NA KID syndrome (Keratitis-ichthyosis-deafness) 804 NA Kabuki syndrome 805 NA Gorham-Stout disease (GSD) 806 NA Campomelic dysplasia 807 NA Multiple epiphyseal dysplasia (MED) 808 NA Denys-Drash syndrome 809 NA Craniometaphyseal dysplasia 810 NA Rasmussen's encephalitis 811 NA Langer-Giedion syndrome 812 NA Miller-Dieker syndrome 813 NA Congenital amegakaryocytic thrombocytopenia 814 NA Alexander disease 815 NA Antley-Bixler syndrome 816 NA Congenital Ichthyosis 817 NA Erdheim-Chester disease 818 NA Intestinal lymphangiectasia 819 NA Joubert syndrome 820 NA Gitelman syndrome 821 NA Canavan disease 822 NA Cadasil 823 NA Currarino syndrome 824 NA Cronkhite-Canada syndrome 825 NA Tufting enteropathy (Intestinal epithelial dyspalsia)

826 NA Parry-Romberg syndrome (Progressive hemifacial atrophy)

827 NA Fraser syndrome 828 NA Hay-Wells syndrome 829 NA Allan-Herndon-Dudley syndrome 830 NA Pallister-Killian syndrome 831 NA Cohen syndrome 832 NA Progressive familial intrahepatic cholestasis 833 NA Schwachman-Diamond syndrome

- 65 -

834 NA Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)

835 NA Familial hypercholesterolemia homozygote 836 NA Iron-refractory iron deficiency anemia 837 NA Haddad syndrome 838 NA Pearson syndrome 839 NA 3MC syndrome (Malpuech-Michels-Mingarelli-Carnevale) 840 NA Walker-Warburg syndrome 841 NA Coffin Siris syndrome 842 NA Alternating hemiplegia of childhood 843 NA Schinzel Giedion syndrome 844 NA Mowat-Wilson syndrome 845 NA Congenital central hypoventilation syndrome 846 NA 1p36 microdeletion syndrome

847 NA Childhood ataxia with central nervous system hypomyelination

848 NA Hypermanganesemia with dystonia 849 NA 2q11 microduplication syndrome 850 NA Distal 10q trisomy syndrome 851 NA 15q11.2 microdeletion syndrome 852 NA Goldberg Shprintzen syndrome 853 NA Aicardi-Goutieres syndrome

CARASIL syndrome (Cerebral autosomal recessive arteriopathy with subcortical 854 NA infarcts and leukoencephalopathy)

855 NA Congenital short bowel syndrome 856 NA COL4A1-related disorder

857 NA DYRK1A syndrome or DYRK1A-related intellectual disability syndrome

858 NA KBG syndrome 859 NA Kleefstra syndrome 860 NA Pelizaeus Merzbacher disease

861 NA Short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome

862 NA Candidiasis, familial, 2, autosomal recessive (CANDF2) 863 NA Gorlin syndrome 864 NA Goltzs syndrome 865 NA Rabson-Mendellhal syndrome, leprechaunism 866 NA Leber`s hereditary optic neuropathy 867 NA Loeys-Dietz syndrome 868 NA ROHHAD syndrorme 869 NA Meier-Gorlin syndrome

- 66 -

870 NA Aniridia cerebellar ataxia mental deficiency 871 NA Birt-Hogg-Dubé syndrome 872 NA Wolfram syndrome 873 NA Inclusion body myositis 874 NA IPEx syndrome 875 NA Geleophysic dysplasia 876 NA Coffin-Lowry syndrome 877 NA Cryopyrin associated periodic fever syndrome (CAPS) 878 NA Idiopathic pulmonary hemosiderosis 879 NA Diffuse pulmonary lymphangiomatosis 880 NA Potocki-Lupski syndrome 881 NA Floating-Harbor syndrome 882 NA Pitt-Hopkins syndrome 883 NA Hadju-Cheney syndrome 884 NA Vici syndrome 885 NA Hereditary pancreatitis 886 NA congenital hepatic fibrosis 887 NA Congenital chloride diarrhea (Chronic chloride diarrhea) 888 NA Congenital Zika syndrome 889 NA Paroxysmal Kinesigenic Dyskinesia (PKD) 890 NA Episodic ataxia type 2 891 NA Orbital lymphangioma 892 NA Chronic progressive external ophthalmoplegia 893 NA 11p13 deletion (WAGR syndrome) 894 NA 11q deletion syndrome (Jacobsen syndrome)

895 NA 8q13 microdeletion syndrome (Mesomelia-synostoses syndrome)

Deletion 8q24.1 Langer–Giedion syndrome (LGS); Trichorhinophalangeal syndrome 896 NA type II (TRPS2) 897 NA Emanuel syndrome 898 NA 1q21.1 microdeletion syndrome 899 NA 2q24 microdeletion syndrome 900 NA 2q32q33 microdeletion syndrome 901 NA 2q33.1 microdeletion syndrome 902 NA 3p deletion 903 NA 3q deletion 904 NA 3q29 microdeletion syndrome 905 NA Partial deletion of the short arm of chromosome 4 906 NA 4q21 microdeletion 907 NA 4q34 microdeletion 908 NA 7q11.23 microduplication syndrome 909 NA Recombinant 8 syndrome

- 67 -

910 NA monosomy 8p 911 NA 8p11.2 deletion syndrome 912 NA 8q21.11 microdeletion syndrome 913 NA 8q22.1 microdeletion syndrome 914 NA 9p deletion 915 NA tetrasomy 9p 916 NA Distal monosomy 10q 917 NA 10q22.3q23 microdeletion syndrome 918 NA Distal trisomy 11q 919 NA Distal monosomy 14q 920 NA 15q tetrasomy (isodicentric 15 chromosome syndrome) 921 NA 16p deletion (ATR-16 syndrome) 922 NA 16p11.2p12.2 microdeletion syndrome 923 NA Ring chromosome 18 924 NA 18p deletion 925 NA Distal trisomy 20q 926 NA Trisomy 20p; 20p duplication 927 NA Chromosome Xq28 duplication syndrome

- 68 -

Ⅱ. List of Orphan Drugs

Orphan Drug Manufacturer

1 가싸이바주 Roche Diagnostics GmbH, Sandhoferstrasse 116, D-68305 Mannheim, Germany 2 세레델가캡슐(엘리글루스타트) Genzyme Ireland, Ltd. 3 동종 배아줄기세포유래 망막색소상피세포 (주)차바이오앤디오스텍 4 AVI-CO-004 정 (주)에빅스젠 5 레볼레이드정 Glaxo Operation UK Limited, UK 6 옵디보 점적정맥주사 20 밀리그램, 100 밀리그램 오노약품공업주식회사, 오사카부 오사카시 주오구 큐타로마치 1-8-2 7 HL2351 주 ㈜한독 8 타핀라캡슐 Glaxo Operations UK Ltd, UK (bulk 제조)

Glaxo Wellcome, S.A., Spain (포장) 9 미정 Pharmaceutics International Incorporated (Pii)

10819 Gilroy Road

Hunt Valley, MD 21031

미국

10 테라심주(니모투주맙, 50mg/10mL/1vial, 정맥주사) CIMAB S.A., Cuba(수탁제조원: The center of Molecular Immunology, Havana, Cuba) 11 욘델리스 주사 Baxter Oncology GmbH 12 토리셀주 Pierre Fabre Medicament Production 13 알라센스 산(ALASENS powder) Research-and-Development Institute of Organic Intermediates and Dyes 14 미정 Toko Pharmaceutical Industries Co., Ltd (동광약품공업주식회사) 15 포토디타진 주 Veta-Grand, 123557 Moscow, M. Gruzinskaya st., 38 Bld.1

16 디기팹(DigiFab) Protherics PLC UK

- 69 -

17 글리올란 m e d a c Gesellschaft fur klinische Spezialpraparate mbH, Hamburg Germany 18 페데아 주(Pedea inj.) Orphan Europe SARL, Immeuble "Le Wilson" - 70, avenue du General de Gaulle, F-92800 Puteaux, France 19 길레니아캡슐 0.5 밀리그램(핀골리모드) Novartis Pharma Stein AG 20 제브타나주 (카바지탁셀) Aventis Pharma, Dagenham (주소: Rainham Road South DAGENHAM Essex RM10 7XS, UNITED KINGDOM) 21 모조빌주(Mozobil Inj.) Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142, 미국 22 트루바다정 Gilead Science 23 엔플레이트주(바이알) Amgen Inc. 24 오르파딘 캡슐 제조의뢰자 Swedish Orphan Biovitrum International AB(Sweden) 25 미팩트(MEPACT) Takeda Ireland Ltd. Takeda Italia Farmaceutici S.p.A.

26 이스토닥스 (로미뎁신) Celgene Corporation 27 자이티가정 250 밀리그램 Patheon, Inc. 28 팜피라서방정(팜프리딘) Biogen Idec 29 렘트라다주 Genzyme Corporation 30 듀오도파 겔 Fresenius Kabi Norge AS, Svinesundveien 80, 1753 Halden, Norway 31 텍피데라캡슐 바이오젠아이덱 32 아르제라주(오파투무맙) Glaxo Operations UK Limited, UK 33 동종 제대혈유래 중간엽줄기세포 메디포스트(주) 34 Entyvio® Takeda Pharma A/S

35 린파자캡슐 50 밀리그램(올라파립) Patheon Pharmaceuticals Inc., 2110 East Galbraith Road Cincinnati OH 45237-1625 USA 36 콜밤캡슐 별첨 37 유스솔루션 미정 38 레블리미드 Celgene Europe Limited 39 수크레이드 QOL Medical, LLC (위탁제조원: Primapharm, Inc)

- 70 -

40 자카비정 5mg, 15mg, 20mg (룩소리티닙 인산염) Novartis Pharma Stein AG, Schaffauserstrasse , CH-4332 Stein, Switzerland 41 애드세트리스 Takeda Global Research and Development Centre(Europe) Ltd.

42 쿼드(QUAD)정 Gilead Sciences, Inc. Foster City, CA94404 43 엑스탄디캡슐 40 밀리그램(가칭) Catalent Pharma Solutions, LLC. (St. Petersburg, FL 33716, USA)

44 레볼레이드정 25 밀리그램(엘트롬보팍올라민) Glaxo Operation UK Limited, UK

레볼레이드정 50 밀리그램(엘트롬보팍올라민)

레볼레이드정 75 밀리그램(엘트롬보팍올라민)

레볼레이드정 100 밀리그램(엘트롬보팍올라민)

45 오바지오정(테리플루노마이드) Genzyme Corporation 46 포말리스트 Celgene Internationl Sarl 47 HYNR-CS 주(상품명: 뉴로나타-알) 코아스템(주) 48 아뎀파스정(리오시구앗) Bayer Pharma AG 49 임브루비카 140 밀리그램(이브루티닙) Catalent CTS Inc, 10245 Hickman Mills Dr. KansasCity, MO 64137 USA 50 Sterile Talc Powder, SCREROSOL Intrapleural Aerosol Bryan Corporation

51 임브루비카캡슐 140 밀리그램(이브루티닙) Catalent CTS Inc 및 Anderson Brecon Inc. 52 실반트주 Cilag AG, 스위스 53 아디포플러스 (주) 안트로젠 54 자베스카캡슐 100 밀리그람 Actelion Pharmaceuticals Deutchland GmbH 55 클로라주 (Clolar inj.) Genzyme Europe BV, Gooimeer 10, 1411DD Naarden, 네덜란드 56 볼리브리스 5mg 정 Glaxo Group Limited, UK 볼리브리스 10mg 정

57 제바린키트주사 제조자 : Baxter Pharmaceutical Solutions LLC, 미국(제조의뢰자 : Bayer Schering Pharma AG, 독일) 58 레볼레이드정 25 밀리그람 Glaxo Operations UK Limited, 레볼레이드정 50 밀리그람 UK

- 71 -

59 라다클로린 주사 35mg(Radachlorin Inj. 35mg) Rada-Pharma Co., Ltd. Bldg.35, Perovskiyproezd Moscow, 111024 RUSSIA 60 셀센트리정(Celsentri tablets) 화이자, 독일 61 레티서트 Bausch & Lomb, Inc (Industrial Estate, Cork Road, Waterford, Ireland 아일랜드) 62 파미온 탈리도마이드 캡슐 50MG 계약제조원: 파미온 수탁제조원 Penn

63 자베스카캡슐 100 밀리그람 Actelion Pharmaceuticals Deutschland GmbH 64 사빈주 Topo Target A/S, Symbion Science Park, Fruebjergvej 3, DK- 2100, Copenhagen, Denmark 65 우바덱스 멸균액 10ml Ben Venue Laboratories Inc. 300 Nothfield Road, PO Box 46568, Ben ford, Ohio 44146

66 이노베론정 Eisai Company Limited, Misato Plant, 950 Hiroki, Misato-Machi, Kodama-Gun, Saitama-Ken, Japan 67 솔리리스(Soliris) Ben Venue Laboratories Inc., Bedford, OH 44146-0568 68 졸레어주사(오말리주맙) 최종공정 : Novartis Pharma Stein AG, 스위스 (자세한 사항은 첨부된 “대상질환 및 제조원” 파일 참조 69 트리세녹스 Nippon Shinyaku Co., Ltd. (14, Nishinosho-Monguchi-cho, Kisshoin, Minami-ku, Kyoto, Japan)

70 비리어드정 Gilead Science 71 아제라주 Glaxo Operations UK Ltd., Harmire Road, Barnard Castle, Durham, DL12 8DT, UK 72 카프시트주/카프시트액 한국팜비오(위탁제조원 : (주) 휴온스) 73 베리너트주 CSL Behring GmbH, 독일 74 Thissen Laboratories SA: Rue de la Papyree 2-6, B-1420 Braine- L'Alleud, Belgium 75 시스타단 산(Cystadane powder) Orphan Europe SARL, Immeuble "Le Wilson" - 70, avenue du General de Gaulle, F-92800 Puteaux, France 76 케피반스 (Kepivance) Amgen Manufacturing, Limited(Manufacturing) Swedish Orphan Biovitrum AB(License) - 72 -

77 토리셀 Pierre Fabre Medicament Production, 프랑스 78 데피텔리오(Defitelio) Gentium S.p.A (Italy) 79 티사브리주 300 밀리그램(나탈리주맙) Biogen Idec 80 서튜러정 100mg (베다퀼린) Kemwell Pvt. Ltd., Bangalore, India 81 포텔리지오주 20 밀리그램 Otsu Pharmaceutical Plant, Toyobo Co., Ltd. (일본) 82 웰진 제노비타 바이오테크널러지,대만 83 Orphan Europe SARL, Immeuble "Le Wilson" - 70, avenue du General de Gaulle, F-92800 Puteaux, France 84 헌터라제 (주)녹십자 85 잘코리캡슐 200mg, 250mg Pfizer Manufacturing Deutschland GmbH, Freiburg, Germany

86 젤보라프 Roche S,p,A., Via Morelli 2 20090 Segrate (Milano), Italy

87 루코네스트(Ruconest) Pharming Group N.V. (The Netherlands) 88 카프렐사정 IPR Pharmaceuticals Inc., San Isidro Industrial Park. Canovanas 00729. Puerto Rico 89 시그니포주(파시레오타이드 0.3mg, 0.6mg, 0.9mg/mL) Novartis Pharma GmbH 90 라다클로린 주사 35mg(Radachlorin Inj. 35mg) Rada-Pharma Co., Ltd. Bldg.35, Perovskiyproezd Moscow, 111024 RUSSIA 91 니펜트주사 10mg 호스피라사,미국 (제조소: 파크데일사, 미국) 92 레밋치연질캡슐 2.5 마이크로그램(날푸라핀염산염) Toray Industries, Inc. 93 조피고주(라듐-223 염화물) Institute for Energy Technology(IFE) 94 포스카비르(Foscavir) Clinigen 95 타핀라캡슐 50 밀리그램, 타핀라캡슐 75 밀리그램 Glaxo Operations UK Limited, UK 96 압노바비스쿰에프 20mg 주사액(에프- ABNOBA GmbH 2)[비스쿰알붐(숙주목:프락시니)20mg 에서추출한 15mg 압축액 ] 97 비미짐 별첨 98 다잘렉스주(다라투무맙) 1. Biogen Inc. 미국 2. Janssen Sciences Ireland UC, 아일랜드 3. Vetter Pharma Fertigung GmbH & Co. KG, 독일 4. Cilag A.G, 스위스 99 HM43239 한미약품(주)

- 73 -

100 미정 미정 101 Catalent Pharma Solutions USA 102 앰겔러티 100 밀리그램/밀리리터 프리필드시린지주 Eli Lilly and Company, (갈카네주맙, 유전자재조합) 미국, Indianapolis, Indiana(IN) 46285 103 SCM-CGH 에스씨엠생명과학주식회사 104 메이젠트필름코팅정(시포니모드) Novartis Pharma Stein AG(스위스) 105 애드세트리스주 Pierre Fabre Medicament Production 등 106 엔트렉티닙캡슐 100 밀리그램, 엔트렉티닙캡슐 200 밀리그램 Mayne Pharma Inc., 1240 Sugg Parkway, Greenville, NC 27834, USA 107 Brineura BioMarin Pharmaceutical Inc. 108 노보세븐알티주(활성형 엡타코그알파, 유전자 재조합 Hagedornsvej 1, DK-2820, 혈액응고인자 VIIa) Gentofte, 덴마크

109 발베사정(얼다피티닙) 3mg, 4mg, 5mg Janssen-Cilag SpA, 이탈리아 110 엔트렉티닙캡슐 100 밀리그램, 엔트렉티닙캡슐 200 밀리그램 Mayne Pharma Inc., 1240 Sugg Parkway, Greenville, NC 27834, USA 111 비트락비캡슐 25 mg, 비트락비캡슐 100 mg, 비트락비액 20 PCI (Penn mg/ml Pharmaceutical Services Ltd.) Tredegar (미국) 및 Orion corporation, Orion Pharma, Salo (핀란드) 112 스트렌식주 40mg/mL, 스트렌식주 100mg/mL Alexion Europe SAS 113 듀테트라베나진(Deutetrabenazine) Norwich Pharmaceuticals, Inc. 114 파미온 탈리도마이드 캡슐 50mg 계약제조원: Pharmion Corpoartion, 미국 수탁제조원: Penn Pharmaceutical, 영국 115 리모듈린주 1mg/mL(트레프로스티닐 소디움) Baxter Pharmaceutical Solution 리모듈린주 2.5mg/mL(트레프로스티닐 소디움) LLC/927 Curry Park, 리모듈린주 5mg/mL(트레프로스티닐 소디움) Bloomington, IN 47402-3068, USA 리모듈린주 10mg/mL(트레프로스티닐 소디움)

116 레블리미드 Celgene International Sarl 117 졸린자 캡슐 Patheon, Inc. 118 폴로틴 주사 20mg/ml Baxter Oncology GmbH, Germany 119 피레스파정 200 밀리그램(피르페니돈) 시오노기제약주식회사, Settsu Plant 5-1, Mishima 2-chome, Settsu, Osaka 566-0022, Japan

- 74 -

120 에리벳지캡슐 150mg Patheon Inc. Toronto Region Operations, 2100 Syntex Court, Mississauga, Ontario L5N 7K9, Canada 121 카이남로주 200 밀리그램(미포멀슨나트륨) Genzyme Corporation 122 피라질주 30 밀리그램(이카티반트) Shire Human Genetic Therapies AB 123 레프라갈주(아갈시다제 알파) Shire Human Genetic Therapies AB 124 비프리브주 (400 유니트) Shire Human Genetic Therapies AB 125 델티바정 50 밀리그램 오츠카제약(주), 일본 126 여보이주 5mg/mL(이필리무맙) Baxter Pharmaceutical Solutions, LLC, 927 South Curry Pike, Bloomington, Indiana 47403 127 메키니스트정 Glaxo Operations UK Limited, UK 128 세리티닙캡슐 150 밀리그램 Novartis Pharma Stein AG, Schaffhauserstrasse CH-4332 Stein, Switzerland 129 미정 Merck Sharp & Dohme, Carlow 130 포토론 주사 벨메드프레파라티, 벨라루스 공화국 131 라이프리버 (LifeLiver) 라이프리버(주) 132 CG200745 전공정위탁제조(제조의뢰자), 보령제약 133 자이델릭 정 100 mg, 150 mg PATHEON INC.

(TORONTO REGION OPERATIONS, Mississauga, Canada)

134 미정 화이자, 미국 135 에다라본 Mitsubishi Tanabe Pharma Corporation 136 이노투주맙 오조가마이신 Wyeth

401 N. Middletown Road, Pearl River, NY 10965

미국

137 카나키누맙 Novartis Pharma Stein AG, Schaffhauserstrasse 4332, Stein, Switzerland (완제의약품) 138 크리조티닙 Pfizer Manufacturing Deutschland GmbH., 독일 139 나노리포좀 이리노테칸 Ajinomoto Althea, Inc, 11040 Roselle Street, San Diego, CA 92121, USA

- 75 -

140 브렌툭시맙 베도틴 Y 141 아파티닙메실레이트 부광약품(주) 142 동종지방유래 중간엽 줄기세포 (주)안트로젠 143 로미타피드메신살염 Aegerion Pharmaceuticals Inc. 144 다루나비르/코비시스타트 Janssen Ortho, 미국 145 엘로투주맙 Bristol-Myers Squibb Holdings Pharma, Ltd., Road 686, KM 2.3 Manati PR00674, Puerto Rico, USA 146 레슬리주맙 Baxter Pharmaceutical Solution LLC 147 메폴리주맙 GlaxoSmithKline Manufacturing S.P.A, Parma, Italy 148 세벨리파제 알파 Synageva BioPharma Corp. 149 아타자나비어/코비시스타트 Patheon Inc. 111 Consumers Drive, Whitby, Ontario, Canada, L1N 5Z5 150 인체흉선세포로 면역시킨 말의 항흉선면역글로부린 Pharmacia & Upjohn Company

(주소 : 7000 Portage Road, Kalamazoo, Michigan 49001, USA) 151 카르필조밉 Patheon Manufacturing Services, LLC.Patheon Manufacturing Services, LLC. 152 아스포타제알파 제조의뢰자: Alexion Pharmaceuticals Inc. 153 에쿨리주맙 Y 154 코비메티닙 F.Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland 155 리포좀시타라빈 Pacira Pharmaceuticals, Inc. 156 자가혈액유래 수지상세포 JW 크레아젠 157 미정 AstraZeneca AB(SE-151 85 Sodertalje Sweden) 158 닌테다닙 Boehringer Ingelheim Pharma GmbH & Co.KG

Binger Strasse 173 D-55216 Ingelheim / Rhein, Germany

159 ALN-TTR02 Alynam Pharmaceuticals Inc.

160 리오시구앗 Bayer Pharma AG 161 젠자임세레자임주 400U Genzyme Corporation 162 알글루코시다제알파 Genzyme Cooporation 163 넥소브리드 (NexoBrid) MediWound

- 76 -

164 알렉티닙 Excella GmbH, Nurnberger Strasse 12, 90537 Feucht, Germany 165 블리나투모맙 Amgen Inc. 166 이델라리시브 PATHEON INC.

(TORONTO REGION OPERATIONS, Mississauga, Canada)

167 셀렉시팍 Excella GmbH 168 아탈루렌 PTC Therapeutics, Inc. 169 프로프라놀롤염산염 Y 170 이다루시주맙 Boehringer Ingelheim Pharma GmbH & Co.KG

Binger Strasse 173 D-55216 Ingelheim / Rhein, Germany

171 페그인터페론베타-1a (주사제) Biogen 172 소마툴린오토젤 60/90/120 밀리그램주사 Y 173 유데나필(경구제) Y 174 콜밤캡슐 50 밀리그램, 250 밀리그램 New Zealand Pharmaceuticals Ltd. 175 임브루비카캡슐 140 밀리그램(이브루티닙) 첨부 지정신청서 참고 176 ASLAN001 ASLAN Pharmaceuticals Pte. Ltd. 177 멕키니스트정 0.5 밀리그램 및 2 밀리그램 GlaxoSmithKline (트라메티닙디메틸설폭시드) Manufacturing S.p.A (이탈리아) Glaxo Wellcome, S.A (스페인) 178 임브루비카캡슐 140 밀리그램(이브루티닙) 첨부 지정신청서 참고 179 블린사이토주 35 마이크로그램 기허가와 동일 180 라이답 연질캡슐 25 밀리그램 Catalent (Gammelsbacher Str. 2 D-69412 Eberbach/Baden, Germany) 181 여보이주 50 밀리그랢/10 밀리리터(이필리무맙,유전자재조합) Baxter Pharmaceutical Solutions, 외1건 LLC, USA

182 헴리브라피하주사 쥬가이제약주식회사(일본) 183 애드세트리스주 Pierre Fabre Medicament Production 등 184 라핀나캡슐 50 밀리그램 및 75 밀리그램 (다브라페닙메실산염) Glaxo Operations UK Ltd (trading as Glaxo Wellcome Operations) (영국) Glaxo Wellcome, S.A (스페인) 185 와킥스 Patheon (France), Rottendorf pharma (France) - 77 -

186 탁자이로주 Cook Pharmica LLC 187 사프롭테린 Y 188 아이클루시그정 Pateon Inc., 캐나다 189 미정 원료및완제 : Dr.Reddy's Laboratories Limited, 포장: Fisher Clinical Service 190 카보메틱스 Patheon Inc. 191 미정 (주)안트로젠 192 인크렐렉스 Hospira 193 로미플레이트주 250 마이크로그램(로미플로스팀) Kyowa Hakko Kirin Co., Ltd., Takasaki Plant 194 오파콜캡슐 Y 195 LCB01-0371 ㈜레고켐제약 196 온카스파주 Sigma-Tau Pharmaceuticals, Inc., Indianapolis, IN 46268, 미국 197 자이카디아캡슐 150 밀리그램(세리티닙) Novartis Pharma Stein AG, Schaffhauserstrasse CH-4332 Stein, Switzerland 198 락손(Raxone)정 첨부문서[서식 1]참고 199 브라가티닙 (brigatinib) Penn Pharmaceutical Services Ltd. (영국) 200 LCI699(미정) Novartis Pharma Stein AG, Lek Pharmaceuticals d.d. (포장) 201 SMT-NK 주 (주)에스엠티바이오 202 소마버트 Pfizer Manufacturing Belgium NV, Belgium 203 HM15136 한미약품(주) 204 올랄라투맙 10mg/mL Y 205 갈라폴드캡슐(미갈라스타트염산염) Almac Pharma Services Limited 206 ASP0113 Astellas Pharma Global Development, Inc. 207 미정 (주)안트로젠 208 타리무스점안액 0.1% Senju Pharmaceutical Co., Ltd., Japan 209 타핀라캡슐 50 밀리그램 및 75 밀리그램 (다브라페닙메실산염) Glaxo Operations UK Ltd (trading as Glaxo Wellcome Operations) (영국) Glaxo Wellcome, S.A (스페인) 210 애드세트리스주 Pierre Fabre Medicament Production

- 78 -

211 니라파립 (niraparib), 100mg, 캡슐 Charles River Laboratories Contract Manufacturing PA, LLC, 미국 212 나트파라주 Vetter Pharma-Fertigung GmbH & Co. KG, Schutzenstrasse 87, 99-101, 88212 Ravensburg, Germany

213 CG200745 크리스탈지노믹스(주) 214 솔리리스주 Alexion Pharmaceuticals, Inc. 215 매큐셀정 0.5 밀리그램 및 2 밀리그램 GlaxoSmithKline (트라메티닙디메틸설폭시드) Manufacturing S.p.A (이탈리아) Glaxo Wellcome, S.A (스페인) 216 TTAC-0001 (주)파멥신 217 AVXS-101(미정) AveXis, Inc (Libertyville, IL, United States) 218 길테리티닙(Gilteritinib)(경구제) 아스텔라스제약(주) 219 가텍스주 Hospira, Inc. (Hospira), Patheon Italia S.p.A. (Patheon) 220 JM-010 GLATT GmbH Pharmaceutical Services, Germany 221 MSD Ireland(Carlow) 등 222 Mavenclad NerPharMa S.R.L.(이탈리아)

223 다잘렉스주(다라투무맙) 1. Biogen Inc. 미국 2. Janssen Sciences Ireland UC, 아일랜드 3. Vetter Pharma Fertigung GmbH & Co. KG, 독일 4. Cilag A.G, 스위스 224 벤클렉스타정 AbbVie Ireland NL B.V., Manorhamilton Road, Sligo, Ireland 225 포트라자주 800 밀리그램(네시투무맙, 유전자재조합) Eli Lilly and Company, 미국, Indianapolis, Indiana 46285(제조 및 1 차포장) 226 레파타(Repatha) Amgen Inc. 227 Ninlaro® Y

228 다잘렉스주 1. Cilag A.G, 스위스 2. Vetter Pharma Fertigung GmbH & Co, KG, 독일 229 신리보주(오마세탁신 메페석시네이트) Y 230 바스코스템(Vascostem) (주)알바이오 231 스핀라자(SPINRAZA)주 Biogen Inc. 232 알레센자캡슐 150 밀리그램(알렉티닙염산염) Excella GmbH&Co.KG, Nurnberger Strasse 12, 90537 Feucht, Germany

- 79 -

233 피라지르프리필드시린지(이카티반트아세테이트) Rentschler Biotechnologie GmbH, Erwin-Rentschler-Strasse 21, D- 88471, Laupheim, Germany 234 미정 Kyowa Hakko Kirin Co.,Ltd 235 Alexion Pharmaceuticals, Inc.

236 BLS-M22 (주)바이넥스 237 벤플리타(Vanflyta) Daiichi Sankyo Europe GmbH 238 바벤시오주 MERCK SERONO SA, Succursale d’Aubonne, Zone Industrielle de l’Ouriettaz 1170 Aubonne, Switzerland 239 임브루비카캡슐 140mg(이브루티닙) Catalent CTS LLC 외 240 다잘렉스주(다라투무맙) 1. Biogen Inc. 미국 2. Janssen Sciences Ireland UC, 아일랜드 3. Vetter Pharma Fertigung GmbH & Co. KG, 독일 4. Cilag A.G, 스위스 241 노보세븐알티주(활성형 엡타코그알파, 유전자 재조합 Hagedornsvej 1, DK-2820, 혈액응고인자 VIIa) Gentofte, 덴마크

242 제줄라캡슐 100 밀리그램 Quotient-Science- Philadelphia, LLC, 미국 243 엠플리시티주 300 밀리그램(엘로투주맙, 유전자재조합) / Bristol-Myers Squibb 엠플리시티주 400 밀리그램(엘로투주맙, 유전자재조합) Holdings Pharma Ltd. Liability company, 푸에르토리코 244 살클리사 또는 살클리자 (가칭) Sanofi Chimie (원료), Sanofi-Aventis Deutschland GmbH (완제), Genzyme corporation (라벨 & 포장) 245 제줄라캡슐 100 밀리그램 Quotient-Science- Philadelphia, LLC, 미국 246 루목시티(Lumoxiti) BSP Pharmaceuticals S.p.A. (Italy) 247 레볼레이드정 Glaxo Operations UK Limited (포장외전공정), Glaxo Wellcome S.A (포장공정) 248 오페브연질캡슐 100 밀리그램(닌테다닙에실산염), 오페브연질캡슐 150 밀리그램(닌테다닙에실산염)

249 이노베론필름코팅정 100mg, 200mg, 400mg (주)한독 250 VT-EBV-N 251 Calquence capsule 100mg AstraZeneca AB, SE-151 85 Sodertalje, Sweden 252 루타테라주 Zaragoza(Spain), Ivrea(Italy) 253 HM15912 한미약품(주)

- 80 -

254 트레콘디 Baxter Oncology GmbH 255 폴리비 BSP Pharmaceuticals S.p.A, Italy 256 서튜러정 100 밀리그램(베다퀼린푸마르산염)

- 81 -