Low-cost Generics Research Articles

Which factor reduces pharmaceutical expenditure, number of entrants or price variance? Updated generic drug markets in South Korea

BackgroundIntroducing more generics has been a successful strategy for lowering pharmaceutical prices and expenditure. However, the effect of the strategy depends on the pricing schemes for generics. We aimed to update the South Korean generic markets in terms of effective competition, and to examine the effects of number of manufacturers and price variance on pharmaceutical expenditure.MethodsWe constructed balanced panel data provided by the Health Insurance Review and Assessment Service covering 726 reimbursed substances from 2019 to 2023. We developed original indicators to analyze the generic markets: the maximum-minimum price variance (MMPV) and the maximum-weighted price variance (MWPV). Panel regression with fixed and time-fixed effects was used.ResultsOver the study period, the number of manufacturers increased from 17.81 in 2019 to 20.98 in 2020 and then decreased to 18.70 in 2023. The MMPV increased from 204.70 in 2019 to 230.07 in 2022 and then decreased slightly to 225.34 in 2023. The MWPV increased from 59.70 in 2019 to 72.58 in 2023. Two types of segmented markets were noteworthy: low use of low-cost generics with sufficient manufacturers and high use of low-cost generics with insufficient manufacturers. In the fixed and time-fixed effects panel analyses, the MWPV presented a negative association with the number of manufacturers and a positive association with the MMPV.ConclusionsA newly introduced tiered pricing scheme, designed to differentiate generic prices, was associated with a decrease in the number of manufacturers and an increase in price dispersion. The pricing schemes for generics should be designed with price variance in mind and limit the number of too many generics in South Korea.

Quantifying Challenges to Development of Generics and Biosimilars in Non-Hodgkin's Lymphoma Therapeutics: The Future of Low-Cost Alternatives from Monoclonal Antibodies to CAR-T

Background: There are numerous monotherapies and combination therapies available to treat Non-Hodgkin lymphoma's (NHL), however relatively few of these varied antineoplastics agents have commercially available, lower-cost generic forms in the United States. High cancer drug prices, in particular for socioeconomically vulnerable and underinsured patients, pose challenges to affordable cancer treatment in the United States. In 2017, FDA initiated the Drug Competition Action Plan (DCAP) that aimed to ensure timely market competition by enabling generic drug development, review, and approval, and streamlining regulatory complexities. This regulatory program was designed to limit so-called “gaming” recognized as a cause of delay to generic drug approvals, a phenomenon that has the further deleterious effect of extending brand monopolies beyond what Congress intended with Hatch-Waxman Amendments (1984) establishing modern generic drug regulatory processes. In 2018, FDA announced analogous Biosimilars Action Plan (BAP). However, to date the efficacy of these measures has not been comprehensively assessed in the NHL development landscape. Methods: A model was created by surveying the FDA Orange Book (drug approval database) and Purple Book (biologic product approval database) for initial approval of drugs/biologics with their initial generic/biosimilar approval. Approvals were classified by drug class and availability of generic/biosimilar for the innovator product with approval from 2002 to 2023 (Fig. 1) and t-test were used to determine significance. Results: Of small molecule drug NHL therapeutics approved in the last two decades, only 37% (19/52; Fig. 2) have available, lower-cost generics, with use in more than one indication and time on market both positively and significantly corresponding with availability of generics for the original innovator drug (P < 0.05). Notably, while generic drug approvals dropped during the 2020-2021 period (possibly due to impact of the COVID-19 pandemic), after 2017 implementation of DCAP more generics for common NHL antineoplastics were approved. Conversely, there are relatively few biologic drugs (total of 41 approvals; Fig. 2) with biosimilars, in part due to retained patents and exclusivity, and perhaps indicating a lack of efficacy in BAP among NHL antineoplastics therapies. For off-patent innovator monoclonal antibodies (mAbs), which make up the majority of these therapies, development of biosimilars is effectively blocked by secondary or “process-related” patents which effectively extend the period of non-competition for complex biologic therapies. It is expected that novel bispecific antibody (biAb) therapeutics and novel therapies, such as CD19 CAR-T will also have a delayed time to low-cost biosimilar availability following a similar trend. Conclusions: With drug price and ever-rising insurance and patient payments a critical area of public health, in particular in the United States, availability of lower cost generics and biosimilars is a critical issue for NHL patients. As we move into the maturation of gene therapies and CAR-T therapeutics, it merits consideration of that additional regulatory programs may be needed to incentivize the development of efficacious and lower cost biosimilars. However, it is critical that controlling competition be carefully balanced with investment in both biologic drug entity and process-related innovations among these relatively complex therapeutic entities.

Why higher copayments for opioids did not reduce use among Medicare beneficiaries.

To examine whether higher cost-sharing deterred prescription opioid use. Medicare Part D claims from 2007 to 2016 for a 20% random sample of Medicare enrollees. We obtain estimates of the effect of cost-sharing on prescription opioid use using ordinary least squares and instrumental variables methods. In both, we exploit the variation (change) in cost-sharing within plans over time for a sample of beneficiaries who remain in the same plan. Focusing on changes in cost-sharing within a plan for a constant sample of beneficiaries mitigates potential bias from plan selection and using a constant set of weights derived from use in year (t) eliminates changes in the cost-sharing indexes due to (endogenous) consumer choice in year (t+1). Part D plans adopted benefit changes designed to reduce opioid use, including moving opioids to higher cost-sharing tiers. Increasing plan copayments for hydrocodone or oxycodone was associated with reductions in plan-paid claims and offsetting increases in cash claims. Widespread availability of low-cost generics combined with the anti-clawback provision in Part D mediated the effect of higher cost sharing to curb opioid use. As plans moved generic opioids to higher cost-sharing tiers, beneficiaries simply paid cash prices and aggregate use remained largely unchanged. The anti-clawback provision in Part D, intended to protect beneficiaries from price gouging, limited plans' ability to constrain opioid use through typical demand-side measures such as increased cost-sharing.

과도한 의약품 시장독점 방지를 위한 연장된 특허권 존속기간의 비교

The extended patent term or exclusivity period from pharmaceuticals’ approval date is limited to 14 years in the US or 15 years in the EU. However there are no such restrictions in Korea, so the market exclusivity can be excessively extended. Therefore, the status of extension of patent term in Korea was analyzed and the patent term from the product’s approval date in Korea, the US, Japan, the UK, France, and Germany were compared. For that, the following information from NEDRUG or KIPRIS were collected and analyzed: the filing date of the patent, whether the patent term has been extended, the expiration date of the patent term, approval date, the products’ name, and representative claims. Alecensa, Xalkori, Biktarvy, and Champix were selected for the comparison. Among 597 patents in Korea, 90.1% (538) were extended and 17.1% (102) of patents exceeded 14 years from the approval date. There were 81 and 60 products that have patents whose term exceeds 14 and 15 years from the approval date, respectively. In the comparative cases of 4 products, the patent term from products’ approval date in Korea is longer than 14 or 15 years, whereas the US, the UK, France, and Germany comply with the regulated limitation. The excessive patent protection delays the market entry of lower-cost generics and leads to an increase in financial burden on healthcare cost. To address such problems, a proper limitation on the extension of the patent term from the product’s approval date needs to be established.

Financial impact of generic therapeutic interchange of abiraterone in the oncology care model for the U.S. Oncology Network.

e17019 Background: Therapeutic interchange (TIC) to lower-cost generic products offers significant cost savings to payers and patients while maintaining equivalent quality of care. The Oncology Care Model (OCM) is a value-based care program from Medicare that rewards practices for decreasing the total cost of care (TCOC) compared to historical baseline prices that are adjusted by a trend factor to account for rising cost trends in oncology. One strategy for bending the cost curve is to utilize lower cost medications. A generic version of abiraterone acetate (FDA approved for treatment of Prostate Cancer) was first introduced into the market in late 2018. This led to a concerted approach to interchange the brand product with the generic equivalent in The US Oncology Network (The Network) as an opportunity to reduce TCOC. Here we describe utilization and the financial impact of abiraterone TIC in The Network during OCM performance period 8 (PP8) which enrolled patients from 1/2/2020 to 7/1/2020. Methods: Prescription drugs dispense data for the 14 US Oncology Network practices participating in the OCM were used to determine brand and generic abiraterone utilization. The impact of TIC on TCOC was measured by comparing the cost of the generic product vs. the estimated cost of the brand agents. Results: TIC resulted in an increase in generic abiraterone use from prior performance periods. Generic abiraterone increased from 0% in PP4 to 24% in PP5, 55% in PP6, 67% in PP7 and 80% in PP8 within the Network. We compared the actual cost of all abiraterone dispenses in PP8 vs. the calculated cost (based on Average Wholesale Price less 17.5%) of the brand product if the more expensive brand drugs were used instead. The difference in the actual cost vs estimated cost led to a savings of $4.37 million in PP6, $6.34 million in PP7 and $9.37 million in PP8 (about 1% of TCOC) by using generic versus brand abiraterone alone. Conclusions: TIC from brand to generic abiraterone in The Network generated significant savings for OCM. Continued shift towards lower cost generics will increase savings to CMS in the Oncology Care Model. We estimate that 100% Network adoption of the generic abiraterone could save nearly 1.25% of the TCOC compared to continued use of brand product.

도약인가 정체인가?

This study evaluated the growth of the Chinese pharmaceutical industry in terms of GVC using OECD-TiVA (2021). China's global value-added production and export share, its participation in front-to-back GVCs, and the share of domestic value-added included in intermediate goods exports have all increased rapidly. On the other hand, the Chinese pharmaceutical industry still relies on huge internal and external demand for low-cost generics, and R&D innovation is also not showing clear results in terms of added value at the GVC level. In other words, quantitative growth through increased production is remarkable, but qualitative development through technological innovation is stagnant. If global pharmaceutical companies' IPR checks and the US technology pressure continue, the Chinese pharmaceutical industry will continue to experience difficulties in transitioning to high-value-added industries, and the low-value-added GVC participation structure may become more entrenched. The Chinese government and companies are making efforts to achieve qualitative development by investing intensively in the biopharmaceutical industry, but it is still uncertain whether such an attempt will be successful due to the nature of the industry where the R&D technology cycle is long and the existing global companies are competitive.

Manufacturing and Regulatory Barriers to Generic Drug Competition: A Structural Model Approach

Understanding the drivers of market concentration in the generic pharmaceutical industry is essential to guaranteeing the availability of low-cost generics. In this paper, we develop a structural model to capture the multiple determinants governing manufacturers’ entry decisions; in particular, we focus on how manufacturing complexity and the regulatory environment for generics approval affect concentration in drug markets. We estimate the model using data collated from six disparate sources. We find that manufacturing complexity, as reflected in the number of active ingredients, for example, significantly reduces the likelihood of generics entry. Moreover, the delay in the review process for the generics applications significantly affects the number of firms entering a market. Our policy simulations suggest that a shortened drug approval review time significantly increases the average number of entrants per market and reduces the fraction of markets with no generics entry; however, a notable portion of markets would still lack any generic competition. This paper was accepted by Jayashankar Swaminathan, operations management. Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.4423 .

Generics and Biosimilars: Barriers and Opportunities

Generics and Biosimilars: Barriers and Opportunities

Factors Associated With Generic Drug Uptake in the United States, 2012 to 2017

ObjectivesIn the United States, brand-name prescription drugs remain expensive until market exclusivity ends and lower-cost generics become available. Delayed generic drug uptake may increase spending and worsen medication adherence and patient outcomes. We assessed recent trends and factors associated with generic uptake. MethodsAmong 227 drugs facing new generic competition from 2012 to 2017, we used a national claims database to measure generic uptake in the first and second year after generic entry, defined as the proportion of claims for a generic version of the drug. Using linear regression, we evaluated associations between generic uptake and key drug characteristics. ResultsMean generic uptake was 66.1% (standard deviation 22.1%) in the first year and 82.7% (standard deviation 21.6%) in the second year after generic entry. From 2012 to 2017 generic uptake decreased 4.3% per year in the first year (95% confidence interval, 2.8%-5.8%, P < .001) and 3.2%/year in the second year (95% confidence interval, 1.2%-5.1%). Generic uptake was lower for injected than oral drugs in the first year (38.5% vs 70.0%, P < .001) and second year (50.3% vs 86.9%, P < .001). In the second year, generic uptake was higher among drugs with an authorized generic (86.1 vs 80.1%, P = .045) and those with ≥3 generic competitors (87.7% vs 78.6%, P = .055). ConclusionEarly generic uptake decreased over the past several years. This trend may adversely affect patients and increase prescription drug spending. Policies are needed to encourage generic competition, particularly among injected drugs administered in a hospital or clinic setting.

The Affordability of Guideline-Directed Medical Therapy: Cost Sharing is a Critical Barrier to Therapy Adoption.

The Affordability of Guideline-Directed Medical Therapy: Cost Sharing is a Critical Barrier to Therapy Adoption.

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018

ObjectiveBuprenorphine is an essential medication for the treatment of opioid use disorder (OUD), but studies show it has been underused over the last 2 decades. We sought to evaluate utilization of and spending on buprenorphine formulations in Medicaid and to evaluate the impact of key market and regulatory factors affecting availability of different formulations and generic versions. MethodsWe first identified all buprenorphine formulations approved by the Food and Drug Administration for OUD using Drugs@FDA. We then used National Drug Codes to identify each drug in the Medicaid State Drug Utilization Data and extracted annual utilization rates and spending between 2002 and 2018 by drug and according to whether a brand-name or generic version was dispensed. We compared these trends to market and regulatory factors that affected competition, which we identified through searching the Federal Register, Westlaw, PubMed, and Google News. ResultsBrand-name buprenorphine-naloxone sublingual tablet and film formulations (Suboxone) were dispensed 2.7 times more (n = 634 213 140) and reimbursed 4.4 times more (n = $4 440 556 473) than all other formulations combined (n = 237 769 689; $1 018 988 133). We identified numerous market and regulatory factors that contributed to an estimated 9-year delay in generic versions of the tablet formulation and 6-year delay for generic versions of the film formulation. ConclusionsBrand-name buprenorphine formulations have been widely used in Medicaid, leading to substantial costs, in part because generic versions were delayed by multiple years owing to market and regulatory factors. Timely availability of low-cost generics could have helped encourage OUD treatment with buprenorphine during the height of the opioid crisis.

Societal Cost of Improper Citizen Petitions

The misuse of the Food & Drug Administration’s citizen petition process is one tactic in a large repertoire of legal maneuvering used by pharmaceutical companies to protect their brand-name drug revenue streams from the introduction of low-cost generics. To date, the financial cost to society of these delays has not been calculated in the literature, which likely hinders the push for policy solutions. Drawing from a previously published data set on 249 citizen petitions, this article identifies four petitions that were highly likely to have been the final obstacle to a generic drug entering the market and for which sufficient volume and usage data were available. Using these four dubious citizen petitions, the total financial cost to society of citizen petition delays was $1.9 billion or $3.6 million per day. The total financial cost to government-provided insurance programs in the same period was roughly $782 million. Due to the conservative methodology employed (choosing only four petitions that met the criteria of “but for” this citizen petition the generic would have gone to market), the estimates are likely low. Citizen petitions that contributed to a generic delay as one of many tactics or for which there was not sufficient volume and usage information were eliminated from consideration in this estimate.

Pricing of oral generic cancer medicines in 25 European countries; findings and implications

Introduction: There are appreciable concerns among European health authorities with growing expenditure on cancer medicines and issues of sustainability. The enhanced use of low cost generics could help. Aims: Consequently, there is a need to comprehensively document current and future arrangements regarding the pricing of generic cancer medicines across Europe, and whether these are indication specific, as well as how this translates into actual prices to provide future direction. Methodology: Mixed method approach with qualitative research among senior health authority personnel and their advisers. Quantitative research via health authority databases to ascertain current prices for oral cancer medicines that had lost their patent and the influence of population size and economics on prices. Results: 25 European countries participated. Currently we see (a) variable approaches to the pricing of generic cancer medicines, which will continue; (b) no concerns with substitution for oral generic cancer medicines; (c) substantial price reductions versus originators for generic capecitabine (up to -93.1%), generic imatinib (up to -97.8%) and generic temozolomide (up to -80.7%). Prices for oncology medicines are not indication specific, and are not affected by population size although influenced by pricing approaches. There have also been price increases for some non-patented cancer medicines following manufacturer changes although now stabilising. Conclusion: The considerable price reductions seen for some generics means health authorities should further encourage the use of generic oncology medicines when they become available to fund increased volumes and new valued cancer medicines. Countries are also starting to address price increases for generics following changes in the manufacturer

Prescribing trends of inhaler treatments for asthma and chronic obstructive pulmonary disease within a resource-constrained environment in the Scottish national health service: findings and implications

ABSTRACTBackground: There is an increasing prevalence of asthma and chronic obstructive pulmonary disease (COPD) worldwide, leading to increased inhaler use. However, there are concerns with inhaler compliance resulting in different patented inhalers and longer-acting formulations. As a result, inhalers are now among the highest expenditure items in ambulatory care in Scotland leading to multiple initiatives to keep within budget without compromising care.Method: This study assesses inhaler utilization and expenditure between 2001 and 2017 alongside health authority initiatives.Results: There was an increase by 137% in inhaler utilization between 2001 and 2017, and a two-fold increase in expenditure, driven by the increasing use of patented combination inhalers to address concerns. This is very different to the oral markets where expenditure on proton pump inhibitors, statins, and antihypertensives have fallen considerably recently despite increased volumes due to the increasing use of low-cost generics. However, inhaler expenditure has started to fall with an increasing use of lower cost combinations and initiatives to reduce the steroid burden alongside monitoring patient care.Conclusion: Challenges with using and changing inhalers has meant this market has not followed other high-volume drug classes following patent loss. This is starting to change, with the situation monitored to enhance efficient prescribing alongside continued good quality care.

India to Power the More Widespread use of Biosimilars

All of us have been kept alive by various drugs that we have taken over the years. Most, if not all, of these were generic drugs, i.e. they were in every way identical copies of the original molecule. The patent on the original drug may have expired, enabling other manufacturers to make these copies at low cost. Alternatively, some countries, including India, did not recognize product patents; and therefore, low-cost generics could be made by other manufacturers legally, even when the product was covered by a valid patent in other countries.

THE PATENTED DRUGS UTILIZATION: A STUDY AT NGUYEN DINH CHIEU HOSPITAL IN BEN TRE PROVINCE FROM 2011 TO 2017

Objective: With their new and efficacious active ingredients, patented drugs have important roles in offering high-quality healthcare. However, huge cost-related barriers in accessing patented drugs along with the availability of low-cost bioequivalent generics have great impact on drugs policy in Vietnam. To understand situation of patented drugs utilization at hospitals for a certain period, this pilot study was conducted at Nguyen-Dinh-Chieu Hospital in Ben-Tre Province.&#x0D; Methods: The cross-sectional descriptive study was conducted on the retrospective data of all patented drugs used at Nguyen-Dinh-Chieu Hospital in Ben-Tre Province from 2011-2017. Characteristics of drugs utilization were described by frequency and percentage of drugs quantities and costs. Criteria for the description were as follows: active ingredient, route of administration, therapeutic class and manufacturing country. Data were extracted from the hospital information system and were processed by R software.&#x0D; Results: From 2011 to 2017, there were 212 patented drugs used which related to 145 active ingredients and 20 therapeutic classes. 88% were single active ingredient drugs and 49% were oral drugs. Antimicrobial and cardiovascular drugs represented the largest number of drugs and the highest cost. 79% of patented drugs were manufactured by companies in Europe and the majority came from France and Germany.&#x0D; Conclusion: This study provided initial information about the utilization of patented drugs during a long period of time at a Vietnamese hospital. The understanding gained will aid medical managers in assessment and adjustment of the drugs list, thus, optimizing the hospital budget and the equity in access to drugs within communities.

Indian health diplomacy in East Africa: Exploring the potential in pharmaceutical manufacturing

ABSTRACTIndian engagement in East Africa’s health sector is multifaceted, comprehensive and involves national and subnational actors. It includes exports of low cost generics, building health infrastructure, aid, technical assistance and hosting medical tourists among others. This paper, based on extensive fieldwork conducted with multiple stakeholders in Kenya and Ethiopia, provides an overview of the various components of India’s co-operation in the East African health sector and identifies pharmaceutical manufacturing as a space for Indian actors to leverage their strengths. It focuses on two case studies of manufacturers: a third-generation company in Kenya owned by members of the Indian diaspora, and a newly formed subsidiary of an Indian corporation in Ethiopia. These case studies inform the larger debate on India’s health diplomacy on the continent and the myriad ways in which the Indian state as well as corporates can enhance existing co-operation.

Manufacturing and Regulatory Barriers to Generic Drug Competition: A Structural Model Approach

Understanding the drivers of market concentration in the generic pharmaceutical industry is essential to guaranteeing the availability of low-cost generics. In this paper, we develop a structural model to capture the multiple determinants governing manufacturers' entry decisions; in particular, we focus on how manufacturing complexity and the regulatory environment for generics approval affect concentration in drug markets. We estimate the model using data collated from six disparate sources. We find that manufacturing complexity, as reflected in the number of active ingredients, for example, significantly reduces the likelihood of generics entry. Moreover, the delay in the review process for the generics applications significantly affects the number of firms entering a market. Our policy simulations suggest that a shortened drug approval review time significantly increases the average number of entrants per market and reduces the fraction of markets with no generics entry; however, a notable portion of markets would still lack any generic competition.

Making HPV vaccination available to girls everywhere.

Cervical cancer is currently the fourth leading cause of cancer death among women worldwide, with most cases occurring in low- and middle-income countries. Safe, highly effective vaccines against HPV have been on the market since 2006, yet only 6% of girls worldwide have received this life-saving cancer prevention intervention. International organizations, including PATH, Gavi, and the pharmaceutical companies Merck and GlaxoSmithKline, have provided support to eligible low- and middle-income countries to implement national HPV vaccination programs. Still, glaring disparities in the availability of national HPV vaccination programs and the coverage of the primary target population between the global north and south persist. We illustrate worldwide HPV vaccine implementation and coverage using an online data visualization, which is publicly available and can be used to gain unique insights. We also present three emerging solutions to transform future HPV vaccine delivery in low- and middle-income countries: low-cost generics, single-dose vaccination, and co-administration with other adolescent vaccines. By rapidly expanding access to HPV vaccination to girls everywhere, vaccine-type HPV infections can be virtually eliminated. At high vaccination-coverage levels, more than 80%-or approximately 230000-of the cervical cancer deaths that occur each year can be averted.

Cost-effectiveness analysis of treatment timing considering the future entry of lower-cost generics for hepatitis C.

BackgroundCost-benefit analyses are crucial to inform treatment policies, particularly when the cost of patented drugs is very high. The cost of patented drugs is the limiting factor in hepatitis C treatment. However, hepatitis C drug costs are expected to fall following patent expiration, due to generic drug introduction.MethodsAn existing mathematical model by Shih et al was extended to consider lower-cost future generics in health economic models of hepatitis C. The model compared the cost-effectiveness of treating patients now with patented drugs vs postponing treatment until after patent expiration.ResultsFor ledipasvir-sofosbuvir, this study finds that it is almost always more cost effective to treat hepatitis C with high-cost patented drugs immediately rather than waiting for patent expiry. For ledipasvir-sofosbuvir, a generic would need to enter the market at <16.40% of the patented price for delayed treatment to be cost effective. The further that patent expiry is in the future, the more cost effective delayed treatment becomes; however, uncertainty about generic pricing and market entry times are also higher if patent expiry is in the distant future.ConclusionIt is more cost effective to treat hepatitis C sooner rather than later, regardless of the stage of the disease, and despite the high cost of patented drugs. However, patented drugs are being produced globally for prices much lower than those seen in the UK. Therefore, negotiation of patented drug prices with pharmaceutical companies may be a crucial step in cost effective treatment of hepatitis C.