Does the first generic exclusivity system provide an economic incentive for early generic entrance under the patent linkage system?

Introduction: A period of exclusivity for the first generics, as part of the patent linkage system, was established in South Korea to provide an economic incentive for early generic entry. This study describes the dynamics of generic penetration and assesses the first mover market share advantages under the patent linkage system. Methods: Pairs of originators and their corresponding generics granted the first generic exclusivity from 2015 to 2020 were identified. We categorized generics into first movers and latecomers, described the penetration curves of generics, and estimated the saturated market share of generics, first movers, and latecomers. Volume-based monthly prescriptions were used to describe the generics' penetration curves. A logistic growth model was adopted to estimate the saturated market shares of generics. Results: We identified 28 pairs of originators and generics, presented penetration curves, and estimated generics market shares. The saturated market share of generics was 30%, and the time to saturation was approximately 33 months. The shapes of penetration varied by nationality, route, and number of generics. The existence of latecomers was associated with the decreased penetration speed over time and decreased market share of generics. However, the first mover market share advantages or latecomers' disadvantages were consistently observed. Conclusion: The generic uptake in South Korea is delayed, limited, and context-dependent. However, first generics' market share advantage suggests that a period of exclusivity, as part of the patent linkage system, could provide an economic incentive for early generic entrance.

Patenting and patent challenges in South Korea after introducing a patent linkage system.

BACKGROUND: South Korea introduced the patent linkage system in 2015 as part of the implementation of free trade agreements with the United States. This study assessed trends in brand-name drug patenting and generic patent challenges in South Korea after the introduction of the system. METHODS: From 2012-19, we constructed a novel dataset that combines information about listed patents with their corresponding brand-name drugs and patent challenges against these brand-name drugs. We analyzed brand-name drug patenting and generic patent challenges and elucidated factors in timely patent challenges using event history analysis. RESULTS: During the study period, 659 brand-name drugs listed their patents in the K-Orange Book and patent challenges against 95 brand-name drugs were initiated. The number of listed patents and their nominal patent term varied by the characteristics of the brand-name drugs. Patent challenges of generic drugs were marginal in South Korea even though the surge of patent challenges of generics were noticed right after the introduction of the patent linkage system. CONCLUSIONS: Patenting and patent challenges are critical factors when introducing generic drugs into the market under the patent linkage system. However, the impact of the patent linkage system on patenting and patent challenges could be varied by the specific form of the patent linkage system and the contexts of pharmaceutical markets.

Who initiates price competition when generic entrants are introduced into the South Korean pharmaceutical market?

Background: Price competition has the potential to reduce health expenditures without hindering pharmaceutical innovation. However, empirical evidence on price competition after generic drugs are introduced is scarce. This study investigates product- and substance-level determinants of price competition following the entry of generics into the South Korean market. Methods: We selected substances that were approved by the Ministry of Food and Drug Safety from 2000 to 2019, linked their corresponding pharmaceutical products, measured the degree of price competition under various scenarios, and utilized multilevel analysis to investigate the determinants of price competition. Results: A total of 986 substances and 12,109 corresponding pharmaceutical products were identified. Only 11% of products were affected by price competition in the 10% scenario. However, the number increased to 43% when we measured price competition at the substance level. Major domestic manufacturers mainly initiated price competition at the product level, while foreign manufacturers were reluctant to initiate price competition. At the substance level, the maximum reimbursement price was a significant determinant of price competition. Conclusion: Price competition at the product level is rare in South Korea. In contrast, the market is quite price competitive at the substance level. Policy options could be introduced to encourage "discounted generic" substitution in an effort to maximize the effects of price competition at the substance level. Major domestic manufacturers are essential in the introduction of discounted generics into the South Korean health system.

Understanding patient and physician responses to various cost-sharing programs for prescription drugs in South Korea: A multilevel analysis.

Introduction: Patient and/or physician responses are a pivotal issue in designing rational cost-sharing programs under health insurance systems. Objectives: This study aims to understand patient and/or physician responses to cost-sharing programs designed for prescription drugs in South Korea. Methods: As a framework, we took advantage of a tiered cost-sharing program, including from copayment to coinsurance (threshold 1) and reduced coinsurance (threshold 2). Given the hierarchical structure of prescriptions nested within patients, we utilized a multilevel analysis to assess effects of various cost-sharing programs on patient and/or physician responses using National Health Insurance claims data from 2018. Results: We found that a tiered cost-sharing program was effective in changing the behaviors of patients and/or physicians. Threshold 1 was found to be more effective than threshold 2 in changing their behaviors. At the prescription level, sensitivity to cost-sharing programs was associated with prescribed days of treatment and locations of prescription. In a similar vein, sensitivity to cost-sharing programs was associated with gender and age group of patients. Conclusion: A simplified cost-sharing program with extended intervals should be considered to rationalize cost-sharing programs. Specifically, a cost-sharing program designed for long-term prescriptions for chronic diseases together with an emphasis on cost transparency is required to better guide price-conscious decisions by patients and/or physicians.

Perceived impact of the patent linkage system on pharmaceutical market from the viewpoint of the domestic manufacturers in South Korea.

BACKGROUND: The United States requires a patent linkage system in other countries as part of free trade agreements. However, introducing a patent linkage system could be a significant barrier to the timely approval of generic drugs. This study aimed to evaluate the perceived impact of the patent linkage system in South Korea held by domestic manufacturers and analyze variations in evaluating the system according to the characteristics of domestic manufacturers. METHODS: In 2020, we conducted a questionnaire survey of 39 domestic manufacturers. The survey consisted of perceptions of the system, factors affecting patent challenges, and the perceived impact of the system. A 5-point Likert scale was used to rate each item. Domestic manufacturers were categorized into three groups based on their experience of listing a patent and acquiring first generic exclusivity. RESULTS: More than half of the manufacturers surveyed had experience of listing a patent. The patent linkage system could protect the involved patents. However, manufacturers perceived that they could successfully challenge the validity of the involved patents and then obtained market approval for generic drugs. Manufacturers responded that market size, expectations for succeeding in litigation, and expectations for manufacturing the drug were the most relevant factors when they initiated patent challenges. Manufacturers reported that the system, in particular the first generic exclusivity, enhanced the research and development capability of generic manufacturers, increased their domestic sales, and improved access to generic drugs. CONCLUSIONS: The perceived impact of the patent linkage system was limited to the domestic market and generic drugs. In narrowing the impact to the effects on the domestic industry, the system had positive impacts of the system on generic manufacturers. The first generic drug exclusivity lies at the center of this positive perception. However, manufacturers perceived that the current system did not provide enough incentives for domestic manufacturers to be granted first generic drug exclusivity through patent challenges.

Importance of a usual source of care in choosing low-priced generic drugs: a cross-sectional study.

BACKGROUND: The potential to lower pharmaceutical spending exists if physicians prescribe low-priced generics. This study aimed to empirically investigate the determinants of choosing low-priced generic drugs in South Korea. METHODS: The 2018 HIRA-NPS dataset was used for this study. Among 1.45 million individuals, we identified the patients who were prescribed atorvastatin 10 mg for more than 60 days in 2018 as the study subjects, separated the subjects into high- and low-priced groups based on their average unit price, and applied a series of logistic regression models to elucidate the factors affecting low-priced drug choice. RESULTS: Out of 60,984 subjects, only 10,228 (17%) were categorized into the low-priced group. The majority of the subjects (31%) were prescribed drugs at the maximum reimbursement price. Age of the subject, the frequency of visits to the institution, the existence of a usual source of care, and the institution type that a subject mainly visited for prescriptions were associated with being prescribed low-priced generics. CONCLUSION: The association of being prescribed low-priced generics with the primary care institution and the usual source of care could be interpreted as evidence for the role of primary care in the continuity of patient-centred care. Creating health systems under which professionals act as perfect agents of a patient and/or an insurer is required.

Generic drugs with a discounted price compared to their corresponding brand-name drugs could be prescribed for patients. Therefore, spending on pharmaceuticals could be saved if physicians prescribed low-priced generics and/or patients switched from high-priced drugs to low-priced drugs. Policymakers have introduced several ways to encourage choosing low-priced generic drugs. This study focussed on the factors associated with choosing low-priced generic drugs in South Korea. Contrary to our expectations, only a few patients (17% of the total patients) choose low-priced generics, indicating potential to save pharmaceutical expenditure. Geriatric patients, patients who mainly visited primary healthcare institutions, and patients who had a usual source of care were more likely to choose low-priced generics. This study also suggested various ways to encourage choosing low-priced generic drugs in health systems.

Understanding long-listed pharmaceutical products without competition in South Korea: policy implications in managing generic entrants and pharmaceutical expenditures.

BACKGROUND: The nature of competition within the pharmaceutical sector has received a great deal of attention from policymakers and researchers. This is the first study to comprehensively analyze long listed single-source products within the South Korean market. METHODS: Long listed single-source products are defined as pharmaceutical drugs that are available in the market for at least 8 years, without competition. We analyzed the determinants that lead to long listed single-source products in the market, and then evaluated their impact on health systems by examining the subsequent price responses of manufacturers. RESULTS: Based on the number of drugs and their market values, pharmaceuticals categorized as long listed single-source products constitute a substantial portion of the market. Characteristics of the market are closely associated with generic entrants. In particular, the market size of a substance is associated with generic entrants, while the price of a brand-name drug is related to being long listed single-source products. CONCLUSIONS: Our analysis supports the creation of a regulatory and/or reimbursement system in order to support robust and effective competition within the marketplace. The first step toward rationalizing the system is to provide widespread information on drugs with limited competition or no competition.

Patent challenges and factors associated with successful patent challengers under the patent linkage system: recent evidence from South Korea after the Korea United States free trade agreement.

OBJECTIVES: The patent linkage system upgraded patent challenges to an important factor in granting timely market approval for generic drugs. We aim to understand patent challenges and identify the factors that are associated with successful patent challengers under the patent linkage system in South Korea. METHODS: We constructed a novel dataset that combined information on manufacturers with detailed data about their patent challenges after introduction of the patent linkage system. Based on the number of successful patent challenges, manufacturers were categorized into non-challengers, passive challengers, and aggressive challengers. Then, two types of logistic models were applied to identify the factors associated with successful and aggressive challengers. FINDINGS: Only 39 active ingredients were challenged by 77 manufacturers from March 2015 to December 2019. Of 171 manufacturers, 94 (55 %) were non-challengers, 58 (34 %) were passive challengers who had succeeded in fewer than 4 patent challenges, and 19 (11 %) were aggressive challengers who had succeeded in 4 or more patent challenges. Higher sales, more employees, and a greater number of reimbursed drugs were associated with being a patent challenger, while a greater number of reimbursed drugs was associated with being an aggressive challenger. CONCLUSION: Some manufacturers utilize patent challenges to strengthen their product portfolios in the market. However, under the patent linkage system, the frequency of patent challenges is limited in South Korea compared to the United States. In particular, patent challenges against drugs in injection form and biologics are very rare.

Market Exclusivity of the Originator Drugs in South Korea: A Retrospective Cohort Study.

Introduction: Generic entry is a well-known driver of competition and cost containment. Objectives: We aim to measure the market exclusivity of originator drugs and to determine what influences the entry of generics in South Korea. Methods: A list of originator drugs approved by the authority from 2000 to 2013 and their corresponding generics were paired. An event history model was applied for a statistical estimation for the duration until generic entry and to identify abbreviating or prolonging factors on the duration. Results: A total of 2,061 pairs of originator and generics were identified. The market exclusivity for the originator drugs, including NDAs and non-NDAs, has not notably changed. However, competition among non-NDAs was less common than we expected. We found delayed time to entry of generics in the long run, particularly for non-NDAs in injection forms and biologics, and this finding is partially associated with market attractiveness. Conclusion: The authority should address the delayed availability of certain types of generic drugs. The government could provide information on off-patent pharmaceuticals with no generic competition, designate their corresponding submissions as prioritized in the review process, and provide additional market exclusivity when entering the market via a long period of exclusivity.

Understanding the trends in international agreements on pricing and reimbursement for newly marketed medicines and their implications for access to medicines: a computational text analysis.

BACKGROUND: Health systems are struggling with unprecedented drug spending and governments have devised various policy options to manage high-priced medicines. Meanwhile, some pricing and reimbursement processes are currently moving under the jurisdiction of international agreements. This study aims to understand trends in international agreements from the perspectives of pricing and reimbursement policies for newly marketed medicines. METHODS: We proposed the framework to interpret the international agreements as code and applied computational text analysis to understand international agreements as data. In particular, we selected the AUSFTA, KORUS, and TPP to assess the progress and evolution in international agreements and investigate the existing relevant content on the pricing and reimbursement of newly marketed medicines. RESULTS: Similar to the provisions for intellectual property, the scope of international agreements regarding pricing and reimbursement decisions are broadened and strengthened. Over time, the domain of transparency, re-naming procedural fairness, has changed significantly more than the remaining domains. Pharmaceutical companies will have more opportunities to advocate for their positions, to protect their interests in decision processes, to investigate the decisions on listings and setting the amounts of reimbursement, and to challenge these decisions. CONCLUSIONS: Recently signed international agreements favor companies over governments with underscoring procedural fairness and timely access. However, access to affordable medicines is the goal towards which international agreements should aim. In a similar vein, substantial fairness and the accountability of companies should be discussed when negotiating agreements or adopting international agreements through domestic legislation.

The Burden of Cervical Cancer in Korea: A Population-Based Study.

This study used the Korean National Health Insurance (NHI) claims database from 2011 to 2017 to estimate the incidence and the incidence-based cost of cervical cancer and carcinoma in situ of cervix uteri (CIS) in Korea. The primary outcome was the direct medical cost per patient not diagnosed with cervical cancer (C53) or CIS (D06) 2 years prior to the index date in the first year after diagnosis. A regression analysis was conducted to adjust for relevant covariates. The incidence of cervical cancer tended to decrease from 2013 to 2016, while that of CIS increased. In particular, the incidence rate of CIS in women in their 20 s and 30 s increased by 56.8% and 28.4%, respectively, from 2013 to 2016. The incidence-based cost of cervical cancer and CIS was USD 13,058 and USD 2695 in 2016, respectively, which increased from 2013. Multivariate regression analysis suggested that age was the most influential variable of the cost in both patient groups, and the cost was highest in those aged over 60, i.e., the medical cost was significantly lower in younger women than their older counterparts. These findings suggest that targeting younger women in cervical cancer prevention is a reasonable option from both economic and public health perspectives.

Is greater generic competition also linked to lower drug prices in South Korea?

BACKGROUND: Although the association between the price of generic drugs and market competitiveness has been explored in various high-income countries, this association has not been empirically evaluated in South Korea. We aim to determine the association between the prices of generic drugs and market competitiveness in South Korea. METHODS: A list of originator drugs approved by the national authority from 2000 to 2019 and their corresponding generic drugs were grouped along with the baseline information. The market was categorized into four groups based on the number of manufacturers: duopoly (2 manufacturers); low- (3-25 manufacturers); medium- (26-75 manufacturers); and high-competition (more than 76 manufacturers) markets. Price variance, calculated as the difference between the maximum price and minimum price divided by the maximum price, was obtained. A multivariate regression model was applied to regress price variance on the characteristics of market competitiveness, controlling for the characteristics of the originator drugs and their price level in the market. RESULTS: A total of 986 originator drugs were identified and then divided into duopoly (31%), low- (56%), medium- (9%), and high-competition (4%) markets; the median of the price variance for these markets was 0.013, 0.077, 0.200, and 0.228, respectively. In a multivariate regression model, price variance was associated with the characteristics of the originator drug, including the Anatomical Therapeutic Chemical classification, the route of administration, and the approval year. Controlling for the characteristics of the originator drugs, market competitiveness was positively associated with price variance. CONCLUSIONS: The positive association between price variance and market competitiveness is still consistent in South Korea, where rare price competition among a large number of generic manufacturers has been reported. However, no significant price variance was observed between medium- and high-competition markets. These findings support policies for managing a large number of generic manufacturers in South Korea.

Incidence, cost and gender differences of oropharyngeal and noncervical anogenital cancers in South Korea.

BACKGROUND: Human papillomavirus (HPV) is associated with a significant public health burden, yet few studies have been conducted in Asia, especially on noncervical cancers. We estimated the incidence and cost of oropharyngeal and noncervical anogenital (anal, vulvar, vaginal, penile) cancer in Korea. METHODS: We conducted a retrospective cohort study using Korea's National Health Insurance (NHI) claim database from 2013 to 2016. The main outcome measures were the number of respective cancer incidences during the study period and the annual costs per patient in the first year after diagnosis, which was adjusted by relevant variables based on the regression analysis. RESULTS: During the study period, 8022 patients with these cancers were identified, and oropharyngeal cancer comprised 46% of them. The crude incidence rate for male oropharyngeal cancer was significantly higher than that of females (3.1 vs. 0.7 per 100,000 as of 2016, respectively). Additionally, the crude incidence of male oropharyngeal cancer increased from 2.7 in 2013 to 3.1 in 2016, whereas that of female and other cancers was stable during the study period. The mean annual incidence-based cost per patient in 2016 was highest for oropharyngeal cancers (21,870 USD), and it was significantly higher in males than in females based on then regression analysis (p < .001). CONCLUSIONS: Oropharyngeal cancer comprises the highest number of HPV-associated noncervical cancer incidences in Korea, and the incidence and cost of oropharyngeal cancer was significantly higher among males than females. More aggressive public health policy toward males may decrease gender gap of oropharyngeal cancer.

Trends in the Utilization of Sodium Hyaluronate Eye Drops, Including Disposable and Multiuse Forms, in South Korea: A 14-Year Longitudinal Retrospective Cohort Study.

INTRODUCTION: Sodium hyaluronate eye drops are frequently prescribed for dry eye disease in South Korea. OBJECTIVES: This study analyzed the trends in the utilization of sodium hyaluronate eye drops and evaluate the impact of the introduction of high-priced disposable forms in the South Korean market. METHODS: The yearly claims data for sodium hyaluronate eye drops from 2002 to 2015 were retrieved from the National Health Insurance Service-National Sample Cohort. Prescriptions of sodium hyaluronate eye drops were sorted by the characteristics of patients and health care institutions. RESULTS: The number of prescriptions has continuously increased and the share of disposable forms in total prescriptions reached 37% in 2015. Particularly, the prevalence of prescriptions (general users) has increased during the study period from 2,562/100,000 persons in 2002 to 14,732/100,000 persons in 2015, while the incidence of prescriptions (new users) has remained steady during the study period, approximately 3,500/100,000 persons. More female patients were noted in terms of general users and new users, and the proportion of male patients was higher in new users than in general users. The average age of general users increased during the study period, while that of new users slightly decreased. Finally, the distribution of prescription category was significantly different between sex and age groups in frequently prescribed users. CONCLUSIONS: Eye drops in disposable forms, which are safe and more convenient to use, have expanded the market in South Korea and caused equity issues in utilization. Thus, the utilization of eye drops should be closely monitored from the perspectives health equity.

Recent trends in tablet subdivision and factors affecting subdivision in South Korea: A cross-sectional study.

Tablet subdivision by physicians or patients frequently occurs in various clinical settings for multiple reasons, including dose adjustment, alleviation of swallowing difficulties, or cost savings. However, not all tablets are suitable for subdivision, and it might cause side effects. It is informative to know which medicines are regularly subdivided, which healthcare institutions prescribe subdivided medicines, and to whom the medicines are prescribed from the perspectives of quality of care and patient safety. In this study, we aimed to examine recent trends in tablet subdivision and to address factors associated with subdivision of tablets both at the patient and healthcare institution levels.The yearly claims data in 2016 retrieved from the National Patients Sample provided by the Health Insurance Review and Assessment (HIRA-NPS). This study used descriptive statistics to examine characteristics of medicines that were frequently prescribed in subdivided forms, and retrieved information regarding the medicines to assess the appropriateness for tablet splitting. Then, we selected five medicines, and performed a multivariate logistic regression analysis to estimate the effect of the variables of interest on tablet subdivision.We presented the top 25 medicines prescribed in subdivided forms in 2016, and confirmed these medicines could be relevantly halved according to their Summary of Product Characteristics. Of the 25 medicines, 14 (56%), 5 (20%), and 3 (12%) medicines belonged to the respiratory system (R), nervous system (N), and systemic hormonal preparations (H), according to the first category of Anatomical Therapeutic Chemical (ATC) classification system, respectively. Being female at the patient level and tertiary healthcare institutions and private owned institutions at the institution level were positively associated with subdivision of medicines.Subdivision of tablets frequently occurred for vulnerable populations with various reasons. Female and geriatric patients are prescribed split medicines for clinical reasons, while low-income patients are prescribed nonsplit medicines for cost savings. It would be better if medicines were not so small, and if they had dividing lines on their surfaces to enable successful splitting of the tablet and to protect the health of vulnerable patients. Furthermore, avoid splitting those pharmacotherapies with a narrow therapeutic range, and provide a pharmacist assistance and a splitting device for unavoidable splitting.

The speed of adoption of new drugs and prescription volume after the amendments in reimbursement coverage: the case of non-vitamin K antagonist oral anticoagulants in South Korea.

BACKGROUND: The speed of adoption of new drugs and frequencies of substitutions leads to changes in health care expenditures as well as patient outcomes. In this study, we aim to understand the speed of adoption of new drugs and their prescription volume in health care institutions and evaluate the impact of policy options to manage pharmaceutical expenditure. METHODS: We conducted a retrospective cohort study of health care institutions prescribing NOACs, including Apixaban, Dabigatran, and Rivaroxaban, to address the speed of adoption and their substitution from October 1, 2010, through December 31, 2015, using the National Health Insurance Service-National Sample Cohort. Two threshold time points, including the extension of reimbursement with the need for the letter of opinion and the withdrawal of the letter of opinion, were noted in this study. Then, we applied a survival analysis to elucidate factors that affected the speed of adoption of NOACs, and interrupted time series analysis to estimate the effect of amendments in reimbursement coverage in prescription volume. RESULTS: Among 934 health care institutions in a study population, 334 institutions (36%) had prescribed NOACs at least one time during the study period, indicating that health care institutions were conservative in adopting new drugs. However, the speed of adoption was related to the characteristics of health care institution. We also found that prescriptions of NOACs before the withdrawal of the need for the letter of opinion were marginal, and the prescription volume of NOACs was significantly increased after the withdrawal of a letter of opinion. CONCLUSIONS: Health care institutions were conservative in adopting new drugs, and the speed of adoption is not closely related to an increased prescription volume in the short run. Thus, policies that are centered on managing pharmaceutical expenditure should be devised with considering the impact of introducing new drugs in the long run. A letter of opinion, which was devised to manage prescriptions of NOACs, was effective in managing pharmaceutical expenditures in health care institutions, particularly for tertiary institutions. Conversely, the withdrawal of the need for the letter of opinion should be implemented with caution.

Marketing and Pricing Strategies of Blockbuster Drugs in the South Korean Market: A 15-Year Retrospective Cohort Study for Choline Alfoscerate.

INTRODUCTION: Understanding marketing strategies and price competition among manufacturers is essential to manage health care expenditures, particularly those related to blockbuster drugs. OBJECTIVES: To assess marketing and pricing strategies of blockbuster drugs in South Korea. METHODS: Baseline information on manufacturers who were granted marketing approval for choline alfoscerate in various forms was retrieved. Accumulation of manufacturers in the market was also identified, and manufacturers were categorized into first movers and latecomers based on their marketing time. Then, an event history analysis and a regression analysis were applied to estimate the duration of marketing and their price competition. RESULTS: Currently, 109, 83, and 26 manufacturers produce choline alfoscerate in capsule, tablet, or syrup form, respectively, indicating that many manufacturers have marketed generics and the majority of the generics are categorized as latecomers. The size of the manufacturer was a significant factor in marketing new medicines, while the variable was not related to the marketing of modified drugs. Furthermore, price competition in the market was rare and only a few major firms initiated price competition. CONCLUSION: The Korean market appears to be an example of perfect competition when we focus on the number of manufacturers. However, the market is near-monopolistic when examining the price of generic drugs. While product competition between different forms of drugs is effective in lowering price, product competition within the same form of a drug does not exist in the market.

Generic atorvastatin and rosuvastatin in the South Korean market: time of introduction in relation to manufacturer characteristics.

Background: The competition for and market dynamics of generic medicines can be understood by analyzing manufacturers' behavior. In this study, we analyzed the various types of generic atorvastatin and rosuvastatin that were introduced onto the South Korean market from 2002 to 2018 and their corresponding manufacturers. Methods: Based on publicly available data, we selected drugs containing atorvastatin and rosuvastatin as active ingredients for the analysis. We calculated the time between the date of marketing approval for the first generic and that of the remaining generics. Then, we categorized manufacturers that marketed generics into first movers and latecomers. Results: We confirmed that many manufacturers have marketed generic drugs in South Korea and that manufacturers can be categorized as first movers and latecomers. Interestingly, latecomers account for a large portion of the manufacturers of generics, and they have entered the market steadily, even after the market matured with a number of manufacturers. Additionally, the characteristics of the manufacturers were closely related to manufacturers' behaviors in the market. Conclusions: The order-of-entry effect, which is commonly observed in other markets, is marginal in the South Korean market, and this phenomenon is mainly explained by the rare price competition among generic manufacturers.

Understanding of for whom, under what conditions and how the compulsory licensing of pharmaceuticals works in Brazil and Thailand: A realist synthesis.

When pharmaceuticals are not fully available mainly due to the high cost of medicines, a government can issue compulsory licensing (CL). It is well documented that Brazil and Thailand have notably attempted CL. A realist review was undertaken to understand the identical social interventions in comparative settings, and to draw practical implications for attempting CL relevant for middle-income countries in the era of high-cost medicines. CL is not only a politically well-devised measure to achieve universal health coverage, but also a tentative commitment, which is determined both at the country level and at the global level. At the country level, political will, with catalytic roles of civil activism, is important in order to guarantee the right to health. Through this will, the governments can achieve universal health coverage. In addition, electoral systems, political leaders, and a constitution are necessary to attempt CL. In addition, CL should operate along with other policy instruments, including a comprehensive essential medicines list, CL-friendly phrasing in patent law, and a competent pharmaceutical industry. At the global level, the balance of power between the WTO regime and the global justice movement is critical. This provides global-level context that can either encourage or prevent CL.

How Much Time Before Attempting Compulsory Licensing of Pharmaceuticals? A Non-parametric Event History Model With P-splines.

Compulsory licensing (CL), provided by the Agreement on Trade-Related Aspects of Intellectual Property Rights, enables countries, including high-income countries, to ensure the protection of public health in the context of stringent intellectual property regimes. This study investigated associations between the time to attempted CL and a series of factors at the drug and country level. We used a dataset of all attempted CL that occurred from 1995 to 2014, calculated the duration as the difference in years between the year of global marketing of a certain drug and the year of attempted CL in a certain country, and applied a nonparametric event history model. We found that the Doha Declaration was quite effective in shortening the time to attempted CL. Additionally, even though global justice movements have encouraged some countries to attempt CL for various medicines since 2012, the time to CL attempts in this period became significantly longer compared to those that occurred immediately after the Doha Declaration. Our findings show that the subject of CL has not successfully expanded to oncology medicines from HIV/AIDS medicines and that recently approved medicines are not yet subjects of CL. Furthermore, our duration model suggests a learning-by-doing effect in attempting CL: previous experience of CL not only triggers CL for the same drugs in other countries but also accelerates CL for other drugs within the country.