FDA’s Generic Drug Program in 2020 Helped Ensure Availability of High-Quality, Affordable Drugs Amid COVID-19


2021-02-12 06:30:15 FDA


By: Sally Choe, Ph.D., Director, Office of Generic Drugs, Center for Drugs Evaluation and Research  Generic drugs play a vital role in facilitating access to lifesaving medicines for Americans and remain a public health priority for the U.S. Food and Drug Administration. Right now, there are more than 10,000 FDA-approved generic drugs and nine out of 10 prescriptions in the U.S. are filled by generics. Generic drugs have saved the health care system close to $2.2 trillion dollars in the past decade.  That is good news for the health of Americans. Amid the challenges of a worldwide pandemic and rapidly advancing science, the FDA’s generic drug program continued steadfast efforts to help increase the availability of safe, effective, high-quality, more affordable drugs in the U.S. Altogether in 2020, the FDA’s generic drug program moved steadily forward even as the COVID-19 pandemic presented additional complexities, resulting in new realities and unique challenges.  Last year, as the COVID-19 public health emergency unfolded, the agency quickly pivoted to making generic drug submissions involving potential treatments and supportive therapies for patients with COVID-19 the top priority. Generic medicines, such as intravenous drugs for patients placed on ventilators and steroids that helped reduce COVID-19 deaths, were used to help fight the effects of the virus on patients.  The FDA’s Office of Generic Drugs (OGD) identified and  implemented tools and strategies to confront the pandemic, including the creation of a system for identifying generic drugs critical to the treatment of patients with COVID-19, and then subsequently taking regulatory and scientific action to accelerate their assessment. This system for identifying generic drugs to address the COVID-19 public health emergency involved establishing infrastructure and resolving assessment issues to support prompt actions involving critically-needed generic drugs.  The FDA also worked diligently to support manufacturers of already approved generic drug products who needed to make changes to manufacturing processes or facilities to address disruptions caused by the pandemic. The generic drug products they produced included antibiotics, sedatives for ventilated patients, anticoagulants, and pulmonary medications, among others. We developed regulatory and scientific approaches to help efficiently restart generic drug development programs interrupted by the pandemic. For instance, we directly assisted applicants with bioequivalence studies impacted by the global pandemic, including answering their questions about protocol revisions and information collection.  While simultaneously working on the response to COVID-19, the FDA made significant progress last year with daily efforts to improve access and reduce the cost of medicines by helping to support competition. Carrying on our regular, non-COVID related work, we were encouraged to see how our past efforts to improve the generic drug program’s efficiency, quality, and predictability added to our resilience with supporting rapid approval of safe, effective generic medicines for use in fighting the sudden occurrence of the pandemic.  In 2020, we approved or tentatively approved 948 generic drug applications, called Abbreviated New Drug Applications (ANDAs), including 72 first generics. We also approved 30 generics under the Competitive Generic Therapy (CGT) pathway, including a quarterly record of 17 CGT approvals in the first quarter of fiscal year 2020. Generic drug approvals can have a real impact for American patients. For example, for the first time, patients with multiple sclerosis now have a generic of Tecfidera (dimethyl fumarate) capsules, patients with toxoplasmosis now have a generic of Daraprim (pyrimethamine) tablets, and patients experiencing severe hypoglycemia now have a generic of glucagon for injection.  OGD’s proactive and collaborative approaches to supporting generic drug development and assessment can lead to the development and submission of higher quality generic drug applications and therefore more timely access to safe, effective generics. One important tool used to communicate with prospective generic drug applicants is called controlled correspondence. A controlled correspondence inquiry is submitted to the agency by (or on behalf of) a generic drug manufacturer or related industry, requesting information on a specific element of generic drug product development. In 2020, OGD responded to 3,711 controlled correspondence inquiries submitted by industry – a record!  Another tool is the Pre-ANDA Program, which was established under the Generic Drug User Fee Amendments of 2017 (GDUFA II). This program provides product development assistance to generic drug developers through written communications and meetings that help clarify regulatory expectations early in the development process and during application assessment. This program provides a special focus on complex generic drug products, such as some inhaled or injectable products, which can be more challenging for generic drug developers to copy, often leading to a lack of generic competition even after patents and exclusivities no longer block generic drug approval. In 2020, we received 121 product development and pre-submission pre-ANDA meeting requests. Beyond directly approving generic drugs, OGD continued its implementation of the FDA’s Drug Competition Action Plan (DCAP) by taking steps to: improve the efficiency of the generic drug development, assessment, and approval process; maximize scientific and regulatory clarity with respect to complex generic drugs; and close loopholes that allow brand name drug companies to “game” FDA rules in ways that delay the generic competition Congress intended. This included publication of guidances for industry, Manual of Policy and Procedures, and other policy actions.  For example, public dockets were opened and guidances were issued to seek user feedback on how to enhance the Orange Book, which celebrated its 40th anniversary in 2020. We look forward to making this key resource as useful as possible for stakeholders, including any improvements that can be made to advance the agency’s goal of improving access to safe, effective, high-quality, and affordable treatment options for Americans. Our related efforts are listed on the DCAP web page, which is updated regularly. We also continued to leverage OGD science and research through recommendations in general and in product-specific guidances (PSGs). PSGs can help applicants develop generic drugs that can meet our high approval standards. Recommendations in PSGs help make industry’s research and development decisions more efficient and cost-effective by identifying the most appropriate methodology and evidence needed to support a specific generic drug’s comparison with the brand name drug.  In another effort to support the development of complex generics, in August 2020, the FDA announced an award of a five-year grant from the GDUFA Science and Research Program that went to the Universities of Maryland and Michigan to establish the Center for Research on Complex Generics. The $5 million grant aims to enhance research collaborations with the generic drug industry to further OGD’s mission of increasing access to safe, effective, high-quality, and more affordable generic drug products. This goal will be pursued through collaborative research, training, workshops, laboratory projects to meet development needs, a Complex Generics Scholars program, and exchange of resources between the FDA, the generic drug industry, and stakeholders. OGD’s work also extended beyond our borders to ensure Americans continue to have access to lower cost, safe, effective, and high-quality medicines. Last year, we maximized our involvement in the International Pharmaceutical Regulators Programme by sharing information with more than 30 regulatory agencies and through harmonization initiatives to promote scientific and regulatory exchange and identify topics for potential international harmonization efforts for generic drugs. We also continued to leverage and strengthen bilateral partnerships with Health Canada and the European Medicines Agency to advance collaborative efforts intended to address complex scientific and regulatory issues for generic drugs.  The FDA’s 2020 Office of Generic Drugs Annual Report provides a comprehensive look at what was accomplished and illustrates how the agency is well-positioned to continue its critical work in 2021. Because of the commitment of the OGD staff along with everyone in the Center for Drug Evaluation and Research, and across the FDA, the generic drug program is stronger than ever, even during a time of unprecedented global health challenges. We remain steadfast in our dedication to seamlessly taking timely actions to assess and approve generic drugs on behalf of American patients and consumers.
作者:Sally Choe,博士,药品评价与研究中心仿制药办公室主任 仿制药在促进美国人获得救命药品方面发挥着至关重要的作用,并且仍然是美国食品和药物管理局的公共卫生优先事项。目前,FDA批准的仿制药超过1万种,在美国,每10个处方中就有9个是仿制药。仿制药在过去十年中为医疗保健系统节省了近2.2万亿美元。这对美国人的健康是个好消息。 在全球大流行和快速发展的科学的挑战中,FDA的仿制药项目继续坚定地努力帮助增加安全、有效、高质量和更廉价的药物在美国的可获得性。2020年,FDA的仿制药项目稳步向前,尽管COVID-19大流行带来了更多的复杂性,导致了新的现实和独特的挑战。 去年,随着COVID-19突发公共卫生事件的展开,该机构迅速转向将涉及COVID-19患者潜在治疗和支持疗法的仿制药提交作为重中之重。仿制药,如用于呼吸机患者的静脉注射药物和有助于减少COVID-19死亡的类固醇,被用于帮助对抗病毒对患者的影响。 FDA仿制药办公室(OGD)确定并实施了应对这一大流行病的工具和战略,包括创建一个系统,用于识别对治疗COVID-19患者至关重要的仿制药,然后随后采取监管和科学行动,加速对其进行评估。这一针对新冠肺炎突发公共卫生事件的仿制药识别系统包括建立基础设施和解决评估问题,以支持针对急需仿制药的迅速行动。 FDA还努力支持已获批准的仿制药产品的制造商,他们需要改变生产流程或设施,以解决疫情造成的干扰。他们生产的仿制药产品包括抗生素、给通气病人使用的镇静剂、抗凝血剂和肺部药物等。我们制定了监管和科学方法,以帮助有效地重新启动因大流行而中断的仿制药开发项目。例如,我们直接协助申请人进行受全球大流行影响的生物等效性研究,包括回答他们关于方案修订和信息收集的问题。 在开展应对COVID-19工作的同时,FDA去年也取得了重大进展,每天都在努力通过帮助支持竞争来改善药品的获取和降低药品成本。在进行常规的非COVID相关工作时,我们感到鼓舞的是,我们过去为提高仿制药项目的效率、质量和可预测性所做的努力,支持快速批准安全、有效的仿制药,用于抗击疫情的突然发生,从而增强了我们的复原力。 2020年,我们批准或暂定批准了948个仿制药申请,称为缩写新药申请(ANDAs),其中首个仿制药72个。我们还批准了竞争仿制药疗法(CGT)途径下的30种仿制药,包括2020财年第一季度17种CGT批准的季度记录。 仿制药的批准可以对美国患者产生真正的影响。例如,多发性硬化症患者现在第一次有了Techidera(富马酸二甲酯)胶囊的仿制药,弓形虫病患者现在有了Daraprim(乙胺嘧啶)片的仿制药,出现严重低血糖的患者现在有了注射用胰高血糖素的仿制药。 OGD在支持仿制药开发和评估方面采取的积极主动和协作的方法可导致开发和提交更高质量的仿制药申请,从而更及时地获得安全、有效的仿制药。与潜在的仿制药申请者沟通的一个重要工具叫做受控通信。由非专利药品制造商或相关行业(或其代表)向该机构提交受控制的函询,要求提供关于非专利药品产品开发的某一特定要素的信息。2020年,OGD共回复了3711份由工业界提交的受控函询--创纪录! 另一个工具是Pre-ANDA方案,该方案是根据2017年《非专利药品使用费修正案》(GDUFA II)建立的。该计划通过书面沟通和会议为仿制药开发人员提供产品开发援助,帮助澄清在开发过程早期和应用评估期间的监管期望。该方案特别关注复杂的仿制药产品,如一些吸入或注射产品,这些产品对仿制药开发商来说可能更具挑战性,即使在专利和排他性不再阻碍仿制药批准之后,往往导致缺乏仿制药竞争。2020年,我们收到121个产品开发和预提交pre-ANDA会议请求。 除了直接批准仿制药外,OGD还继续执行FDA的药品竞争行动计划(DCAP),采取措施:提高仿制药开发、评估和批准过程的效率;最大限度地澄清复杂的非专利药品的科学和监管问题;并堵住一些漏洞,这些漏洞允许名牌药品公司“游戏”FDA的规则,以拖延国会预期的仿制药竞争。这包括出版工业指南、政策和程序手册以及其他政策行动。 例如,开放了公共日程表,并发布了指南,以征求用户关于如何加强《橙皮书》的反馈意见,该《橙皮书》在2020年庆祝了40周年。我们期待着使这一关键资源对利益攸关方尽可能有用,包括为推进该机构改善美国人获得安全、有效、高质量和负担得起的治疗选择的目标所能做出的任何改进。我们的相关努力列在DCAP网页上,该网页定期更新。 我们还继续利用OGD的科学和研究,通过一般的建议和特定产品的指导(PSG)。PSGs可以帮助申请人开发出能够满足我们高审批标准的仿制药。PSGs中的建议通过确定支持特定仿制药与品牌药进行比较所需的最适当的方法和证据,帮助业界的研究和开发决策更有效率和更具成本效益。 在支持复杂仿制药开发的另一项努力中,2020年8月,FDA宣布授予GDUFA科学和研究计划一项为期五年的赠款,用于马里兰大学和密歇根大学建立复杂仿制药研究中心。这笔500万美元的赠款旨在加强与仿制药行业的研究合作,以进一步推动OGD的使命,即增加获得安全、有效、高质量和更可负担得起的仿制药产品的机会。这一目标将通过合作研究、培训、研讨会、实验室项目来满足开发需求、复杂的仿制药学者计划以及FDA、仿制药行业和利益相关者之间的资源交流来实现。 OGD的工作还延伸到我们的境外,以确保美国人继续获得成本更低、安全、有效和高质量的药品。去年,我们最大限度地参与了国际药品监管机构方案,与30多个监管机构分享信息,并采取协调举措,促进科学和监管交流,确定仿制药国际协调努力的潜在主题。我们还继续利用和加强与加拿大卫生部和欧洲药品管理局的双边伙伴关系,推动旨在解决仿制药的复杂科学和监管问题的合作努力。 FDA的《2020年仿制药办公室年度报告》全面介绍了所取得的成就,并说明了该机构如何在2021年继续开展关键工作。 由于OGD工作人员与药物评估和研究中心以及整个FDA的所有人的承诺,仿制药项目比以往任何时候都更加强大,即使是在全球健康面临前所未有的挑战的时候也是如此。我们仍然坚定不移地致力于无缝地采取及时的行动,代表美国患者和消费者评估和批准仿制药。