Generic Drug Regulation in the US Under the Hatch-Waxman Act

Generic drugs are bioequivalent copies of original drugs patented by brand-name companies. The regulation of generic drugs in the US has paralleled that of brand-name drugs. They were first allowed under US regulations in 1938 upon the initiation of the ‘modern era’ of drug regulation with the enactment of the Federal Food, Drug and Cosmetic Act (FDCA). As with brand-name drugs, regulation of generics underwent significant change in the wake of the 1962 amendments to the FDCA, particularly with the passage of the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Act. This act required the US FDA to establish an abbreviated new drug approval procedure for generic drugs, including a means of evaluating the bioequivalence of generic drugs to that of pioneer drugs, as well as a mechanism for identifying approved pioneer drugs and challenging their patents. The administrative tool developed to assist this process was a listing of approved drugs, patents, and equivalence ratings, commonly called the ‘Orange Book.’ In the aftermath of the Hatch-Waxman Act, the generic drug industry experienced considerable ‘growing pains’: a bribery scandal, disenfranchisement by FDA regulatory reform, persistence of barriers to generic entry, continuing problems with establishing equivalence to pioneer drugs, and lack of congressional support. Recently, as a result of increasing public pressure to address the rising costs of healthcare, the problems of generic drug makers, such as patent listing abuses and the lack of a regulatory review process for biogenerics, have received attention from both the legislative and executive branches of the US government. The FDA issued a proposed rule to close some of the loopholes in the Hatch-Waxman Act in late 2002, while the congressional tussle over various legislative proposals to promote generics has begun anew with the initiation of the 108th Congress. While these activities will determine some near-term outcomes for the generic drug industry, the industries’ long-term prospects will depend on whether it continues to benefit the healthcare system by providing low-cost competition to brand-name products without decimating the brand-name industry’s economic incentive to provide innovative new medicines.     

Fda's Role in the Facilitation of Development of Medical Foods for Rare Conditions: Interactions with Industry

Abstract

In 1984 the Drug Price Competition and Patent Term Restoration Act changed the regulatory climate for generic drugs. This law allowed for the approval of generic «me-too’ copies of many approved drug after the patent had expired. Although the road has not been smooth, the generic drug approval process has had a significant impact on the availability of generic versions of approved drug. This article discusses the evolution and changes that have occurred in generic drug approvals since the 1984 Act.     

Repercussions of the Drug Price Competition and Patent Term Restoration Act of 1984

Recently enacted legislation involving patent terms and the approval of new generic equivalent drug products is described, and the law's potential repercussions are discussed. The Drug Price Competition and Patent Term Restoration Act of 1984 (PL 98-417) consists of two titles that affect introduction procedures and patent requirements for certain types of generic new drug products. Title I allows drug manufacturers to use an abbreviated new drug application when seeking approval to make generic copies of drug products that were approved by the FDA after 1962. Title II encourages drug manufacturers to assume the increased costs of research and development of certain products that were subject to premarketing clearance by restoring some of the time lost on patent life while the product was awaiting FDA approval. Legislative analysts continue to question whether the short-term gains of eased market access to the generic manufacturers will be outweighed by the long-term benefits of patent extensions to the pioneer drug companies. The potential difficulties in the implementation of the Act and unresolved questions of law surrounding the new law are discussed. The possible effects of the new law on the drug manufacturing industry and market composition are described. Since PL 98-417 was implemented in September 1984, little has been settled in the way of implementing its provisions or accurately measuring its nonregulatory impact. It seems certain that the bill will be difficult to regulate and that litigation will proliferate. Furthermore, the impact of the statute on the composition of the drug industry will undoubtedly be substantial.     

专利到期对药品价格和市场份额的影响分析

目的:系统评估国内外药品专利到期后价格及市场份额的变化,为促进我国创新药与仿制药的平衡发展提供循证参考.方法:计算机检索PubMed,Scopus,The Cochrane Library,CNKI,WanFang Data和VIP数据库,搜索与专利到期或专利过期对原研药或仿制药价格及市场份额影响有关的研究,检索时限为...     

Economics and structure of the generic pharmaceutical industry

OBJECTIVE: To review key economic trends of the generic medication market and analyze the changing structure of the generic medication industry. DATA SOURCES: Articles were indexed initially using terms such as generic medications, generic drugs, multisource medications, and multisource drugs. These terms were used to search indexing services such as MEDLINE, International Pharmaceutical Abstracts, CINAHL (a database of nursing and allied health literature), Science Citation Index, Psychological Abstracts, and Wilson Indexes to Journal Articles. STUDY SELECTION: Performed by the authors. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: The generic pharmaceutical market has the potential to play an important role in containing drug costs, although the amount that could be saved through the use of generic medications is not easy to measure. If estimates for the future growth in the use of generic products prove correct, the proportion of pharmaceutical sales attributable to generic products will remain in the 9% to 10% range through the first decade of the 21st century. The generic pharmaceutical industry includes several categories of companies based on business strategies. Further consolidation is expected as more resources are needed to address patent challenges stimulated by the Drug Price Competition and Patent Restoration Act. Companies are also entering into partnerships with research manufacturers to share profits from proprietary products. Future growth of the generic market will require more than increased use of generic products. Therapeutic interchange, involving switching from single-source, patent-protected products to products within the therapeutic class for which there are generic equivalents, represents a major growth opportunity for generic drug manufacturers because the savings potential is more significant than that for straightforward substitution of generic for brandname products. CONCLUSION: As it responds to challenges and opportunities, the generic pharmaceutical industry will continue to be a major force shaping the economics of medication use.     

注射剂原研药与仿制药的政府定价比较

目的:为完善药品政府定价,特别是对于原研药的定价提供参考。方法:通过统计国家发改委药品定价目录中的价格数据,计算注射剂中原研药与仿制药价格的差价率。结果:满足《药品政府定价办法》中对于差价率规定(注射剂差价率35%)的药品仅占总数的26%,且最高的一个差价率超过500%。结论:建议政府采用逐步降价等较温和方法,控制给予原研药的价格优惠程度,并建立动态的价格调控机制,使原研药生产企业与仿制药生产企业利益趋于平衡。     

An Introduction and Then Some: Presentation

Abstract

This paper, entitled “An Introduction and Then Some” was presented at the RAPS sponsored workshop conducted in Morristown, New Jersey on August 7 and 8, 1 985. The purpose of the workshop was to update RAPS members’ knowledge of the work of the FDA’s Division of Generic Drugs, including the implementation of Title I, Abbreviated New Drug Applications, the Drug Price Competition and Patent Term Restoration Act of 1984. The author discusses the major provisions of the Title I of this complex law, and reports on the problems encountered and progress made to date in its implementation.

If our Constitution did not dictate the separation of State and Church, I would be inclined to open this meeting thusly:     

Meta-analysis for bioequivalence review

The problem of drug interchangeability among a brand-name drug and its generic copies is considered. Under current Food and Drug Administration (FDA) regulation, a patient may switch from the brand-name drug to a generic drug if the generic drug is shown to be bioequivalent to the brand-name drug based on bioequivalence testing. After the patent of a brand-name drug is expired, usually there will be a number of generic copies available on the market. The FDA does not indicate that a patient may switch from a generic to another even though both of the generic drugs are bioequivalent to the brand-name drug. As a result, drug interchangeability among the brand-name and its generic copies is a safety concern. In this paper, we propose to perform a meta-analysis for an overview of bioequivalence. The proposed meta-analysis provides an assessment of bioequivalence among generic copies of a brand-name that can be used as a tool to monitor the performance of the approved generic copies of the brand-name drug. In addition, it provides more accurate estimates of inter- and intrasubject variabilities of the drug product.     

仿制药替代潜在最大费用节省研究

目的在仿制药替代背景下,比较原研药和仿制药的价格和采购量,测算仿制药替代的潜在最大费用节省,推动仿制药供应与使用。方法基于陕西省药品招标采购数据,选取2017年12月第一批通过仿制药质量和疗效一致性评价的17个品种(16个品规)药品,对其2017年至2018年的价格、采购量进行分析;采用成本分析法、推测预算法,对采购平台上该通用名、剂型的药品替换为通过仿制药质量和疗效一致性评价单价最低的仿制药,测算年均仿制药替代的潜在最大费用节省。结果价格由高到低依次为原研药、未通过一致性评价的仿制药、通过一致性评价的仿制药;采购量方面,5个品规药品的原研药采购量占比较高,11个品规药品的仿制药采购量占比较高,1个品规药品未发生仿制药替代;对16个品规药品进行仿制药替代后,测算出潜在最大费用节省为3243.63万元。结论仿制药替代可显著节省药品费用,我国的仿制药市场提升空间较大,后续应加快推进仿制药一致性评价和临床使用。     

Longer patents for increased generic competition in the US. The Waxman-Hatch Act after one decade

The 1984 Waxman-Hatch Act had two main objectives. Title I was designed to promote price competition by establishing an abbreviated new drug application (ANDA) process for generic market entry. Title II was designed to encourage drug innovation by restoring some of the patent life lost during the lengthy FDA regulatory process. In this paper, we consider whether these twin objectives have been realised during the first decade of the Act's existence. First, we investigate the pattern of generic and brand name prices and market shares for the major products whose patents expired between 1984 and 1993. A regression model indicates that generic competition has been intensifying significantly in recent periods. Major brand name products now typically lose more than half their market share within the first year after patent expiration. In addition, we examine changes in patent protection for new chemical entities introduced over the period 1984 to 1993. For 1991 to 1993 new drug introductions, the average effective patent life was 11.8 years with 2.3 years resulting from Waxman-Hatch extensions. In the final section of the paper, we consider how the US law compares with that in Europe and discuss possible legislative improvements in the 1984 Act.     

美国2010年最热销的200种药物的排名综观美国医改政策的动向

近年来,美国处方药市场中一个显著的新动向,即价格相对低廉的仿制药品的使用品种不断增加,患者用在药品上费用的支出不断减少。与此相反,使用价格昂贵的创新药物和新药的患者的数量大大减少（特别是治疗慢性病的药品）。这种趋势,即使用创新药物转向使用仿制药物十分强劲。由此看出,美国医改政策的一个侧面。     

江苏省某胸部专科医院肺癌治疗的原研药与仿制药利用分析

目的：在加速仿制药替代的背景下,提出促进仿制药使用的政策建议。方法：选取江苏省某胸部专科医院治疗肺癌的8种既有原研药也有仿制药的品种,按季度分析2018年1月至2020年6月原研药和仿制药使用量占比、使用金额占比、价格比,以及2019年6月至2020年6月执行集中采购前后仿制药替代潜在的费用节省率。结果：2018年第1季度至2020年第2季度,原研药、仿制药使用数量占比分别由22.38%下降至14.26%、77.62%上升至85.87%,使用金额占比分别由39.43％下降至21.56％、60.57％上升至78.44％,仿制药与原研药价格比从2.08上升至2.75。在执行集中采购后,仿制药替代原研药潜在可节约费用1 061 254.51元,费用节省率为55.93％。结论：随着仿制药相关政策的推进,仿制药使用数量和金额占比都在上升,仿制药替代确有降低药品费用支出的作用。因此,加快仿制药一致性评价,同时配合仿制药政策的宣传,着力提高医患对仿制药的认同,再通过集中采购政策,可以促进仿制药利用以节约医疗资源。     

Pharmaceutical policy regarding generic drugs in Belgium

Pressure to control pharmaceutical expenditure and price competition among pharmaceutical companies are fuelling the development of generic drug markets in EU countries. However, in Belgium, the market for generic drugs is underdeveloped compared with other countries. To promote the use of generic drugs, the government introduced a reference pricing (RP) scheme in 2001. The aim of this paper is to discuss Belgian pharmaceutical policy regarding generic drugs and to analyse how the Belgian drug market has evolved following initiation of the RP scheme.The market share held by generic drugs increased following implementation of the RP scheme. Focusing on volume, average market share (by semester) for generic drugs amounted to 2.05% of the total pharmaceutical market from January 1998 to June 2001, compared with 6.11% from July 2001 to December 2003. As new generic drugs are introduced, their market share tends to increase in the first couple of months, after which it levels off. Faced with increasing generic competition, some manufacturers have launched new variants of their original drug, thereby effectively extending the period of patent protection. Strategies consisting of price reductions in return for the abolition of prescribing conditions and the launch of new dosages or formulations appear to have been successful in maintaining the market share of original drugs. Nevertheless, the introduction of the RP scheme was associated with savings amounting to 1.8% of pharmaceutical expenditure by the third-party payer in 2001 and 2.1% in 2002.The findings of this paper indicate that the RP scheme has stimulated the Belgian generic drug market. However, existing policy has largely failed to take into account the role that physicians and pharmacists can play in stimulating generic drug use. Therefore, further development of the Belgian generic drug market seems to hinge on the creation of appropriate incentives for physicians to prescribe, and for pharmacists to dispense, generic drugs. With respect to incentives to advance generic drug use, EU countries have experimented with various forms of budget constraints for physicians, generic substitution by pharmacists and RP schemes, although more evidence is needed of their impact on consumption and prices of generic drugs, pharmaceutical expenditure and health outcomes.     

我国与其它发达国家或地区部分药品零售价比较研究

目的:了解我国药品价格水平,为价格主管部门的政策制定提供参考。方法:采集发达国家或地区部分品牌药和相应普药产品的零售价,分别按汇率和购买力平价转换,研究比较其价格水平。结果与结论:按汇率换算,我国品牌药和普药的价格均处于较低水平;按购买力平价换算,我国药品价格相对于国民购买力与发达国家或地区情况相比处于较高水平;我国品牌药与普药的价格差距较大。建议适当加大政府采购,扩大医疗保险支付的范围和比例,切实保障我国民众在药品方面的需求。