FDA发布生物仿制药声明，糖尿病福音来了！
今日，FDA发布了一则关于提高生物仿制药和可互换胰岛素产品开发效率的声明，据药智新闻记者获悉，此声明是为了帮助更多的糖尿病患者获得更好的治疗方法。声明中还解释了《生物相似或可互换胰岛素产品的临床免疫原性注意事项》指导草案。
声明中提到对于患有糖尿病的患者来说，获得可以负担得起的胰岛素可能是一个生死攸关的问题。如果治疗不当，糖尿病会导致严重的甚至危及生命的并发症，包括心脏病、器官衰竭和失明。而持续、终生获得胰岛素对患者生存和生活质量至关重要。然而，FDA意识到胰岛素的高成本，使很多患者都不能获得很好的治疗，这也是FDA非常重视的一个问题。
针对这个问题，FDA将致力于继续提高胰岛素产品的市场竞争力，这可能会降低患者和付款人的成本，增加准入和产品的选择。这包括促进开发用于治疗Ⅰ型和Ⅱ型糖尿病患者的安全有效的胰岛素产品，包括与已经被批准的胰岛素产品生物相似或可与之互换的产品。
为了通知打算申请FDA批准和已经被批准的胰岛素产品生物相似或可与之互换的胰岛素产品的产品开发人员，FDA今天发布了一份给药企的指南原则的草案——《生物相似或可互换胰岛素产品的临床免疫原性注意事项》。该草案是为了通过阐明可能需要或可能不需要哪些数据和信息来证明如草案要求的胰申请岛素产品的生物相似性或互换性，从而帮助指导有效的产品开发。该草案反映了FDA数十年来在胰岛素产品方面的经验，这些经验以及广泛的临床应用，有助于对这些产品有一个强有力的科学理解。该草案还反映了在FDA 2019年5月的公开听证会上对利益相关者反馈的考虑，在听证会上，利益相关者被邀请就开发生物仿制药和可互换胰岛素产品提供意见。
值得注意的是，FDA在草案中建议，在某些情况下，对某些申请的生物仿制药和可互换胰岛素产品的批准不需要进行比较性临床免疫原性研究。一般来说，免疫原性研究调查对治疗蛋白的免疫反应的存在及其临床影响，从而影响治疗是否有效和安全。在草案所述的情况下，FDA通常预期某些生物仿制药和可互换胰岛素产品的免疫原性对临床影响的风险最小。因此，虽然生物仿制药和可互换胰岛素产品的应用预计将包括免疫原性评估，但该评估可能包括一个科学理由，说明为什么对该特定的胰岛素产品不需要进行评估免疫原性的比较临床研究。草案中所述的建议反映了对科学考虑的广泛的多方面评估，可能会出现更有效的开发计划，最终能够更快地将生物仿制药或可互换胰岛素产品推向市场。
生物仿制药或可互换胰岛素产品的申请需要符合严格的法定标准，申请人需要提交足以证明生物仿制药或可互换性的数据和信息，包括临床药理学研究，化学成分，制造等信息，以及全面和平稳的比较分析评估。对于一些申请的生物相似或可互换的胰岛素产品，可能仍需要进行比较临床免疫原性研究，以解决免疫原性方面的不确定性。例如，如果某些杂质或剂型存在差异，则可能需要进行临床免疫原性比较研究，但这将是个别应用背景下的个案科学测定。
目前FDA正处在2020年3月23日前的一个过渡期，为了建立一个坚实的监管基础，以审查和批准生物类似物和可互换的胰岛素产品。2020年3月23日起，批准的生物制品新药申请（NDAs）将获得法律规定生物制品许可证（BLAs）。在生物产品（如胰岛素产品）的获得BLAs后，申请批准的生物仿制药或可互换产品的申请人可将该产品用作“参考产品”。参考产品是指已经获得FDA批准的生物产品，与生物仿制品或可互换产品进行比较。因此，胰岛素产品从经批准的NDAs转变为获得BLAs将使这些产品面临潜在的生物相似性和可互换性竞争。获得批准的生物仿制药和可互换胰岛素产品有望增加患者获得胰岛素产品的机会，降低胰岛素产品的成本。
该草案的发布目的是提高生物相似性和可互换产品开发和批准过程的效率，并最大限度地为生物相似产品开发提供科学和管理上的指导，也是FDA生物仿制药行动计划中的关键目标。FDA也将继续研究以提高患者获得所需药物的机会。
声明原文
Access to affordable insulin can be a matter of life and death for Americans with diabetes. If not appropriately treated, diabetes can lead to serious and life-threatening complications, including heart disease, organ failure and blindness. And consistent, lifelong access to insulin is imperative to patient survival and quality of life. However, we are aware that the high cost of insulin raises serious concerns about the ability of many patients to access insulin products. This is an issue the FDA takes very seriously; therefore, today we are announcing new draft guidance that is intended to help facilitate the development of, and improve patient access to, life-saving insulin products.
The FDA is committed to continuing our efforts to help increase market competition among insulin products, which may potentially lower costs for patients and payors and increase access and product choice. This includes facilitating the development of safe and effective insulin products for the treatment of patients with Type 1 and Type 2 diabetes, including products that are biosimilar to, or interchangeable with, an approved insulin product.
To inform product developers who intend to seek the FDA’s approval of proposed insulin products that are biosimilar to, or interchangeable with, an approved insulin product, the FDA today issued a draft guidance for industry, “Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products.” This draft guidance is intended to help guide efficient product development by clarifying what data and information may – or may not – be needed to support a demonstration of biosimilarity or interchangeability for a proposed insulin product, as defined in the draft guidance. The draft guidance reflects, among other things, the FDA’s decades of experience with insulin products which, along with wide clinical use, has contributed to a robust scientific understanding of these products. The draft guidance also reflects consideration of stakeholder feedback provided at the FDA’s May 2019 public hearing on this topic at which stakeholders were invited to provide input on developing biosimilar and interchangeable insulin products.
Significantly, the FDA recommends in the draft guidance that, under certain circumstances, a comparative clinical immunogenicity study would not be necessary for approval of certain proposed biosimilar and interchangeable insulin products. In general, immunogenicity studies investigate the presence of an immune response to the therapeutic protein and its clinical impact, which can influence whether the therapy will work well and be safe.
In the circumstances described in the draft guidance, the FDA generally expects the risk of clinical impact from immunogenicity to be minimal for certain proposed biosimilar and interchangeable insulin products. As such, while applications for biosimilar and interchangeable insulin products would be expected to include an immunogenicity assessment, that assessment could include a scientific justification of why a comparative clinical study to assess immunogenicity is not necessary for that particular proposed insulin product.
The recommendations described in the draft guidance, which reflects extensive multidisciplinary evaluation of scientific considerations, may result in a more efficient development program that could ultimately bring biosimilar or interchangeable insulin products to the market more quickly.
Applications for proposed biosimilar or interchangeable insulin products need to meet strict statutory standards, and applicants will need to submit data and information sufficient to demonstrate biosimilarity or interchangeability, including, among other things, a comparative clinical pharmacology study, adequate chemistry, manufacturing and controls information, and a comprehensive and robust comparative analytical assessment. For some proposed biosimilar or interchangeable insulin products, a comparative clinical immunogenicity study may still be needed to address residual uncertainty regarding immunogenicity. For example, a comparative clinical immunogenicity study may be needed if there are differences in certain impurities or novel excipients, but that would be a case-by-case scientific determination in the context of individual applications.
On March 23, 2020, approved New Drug Applications (NDAs) for biological products will be deemed to be licenses for the biological products (i.e., approved Biologics License Applications (BLAs)) under section 351 of the Public Health Service Act. After an approved NDA for a biological product (such as an insulin product) is deemed to be an approved BLA, the product can be used as a “reference product” by an applicant seeking approval of a proposed biosimilar or interchangeable product. A reference product is the biological product, already approved by the FDA, against which a proposed biosimilar or interchangeable product is compared. This will enable, for the first time, submission of applications for products that are proposed as biosimilar to, or interchangeable with, the transition products. As such, the transition of insulin products from approved NDAs to deemed BLAs will open up those products to potential biosimilar and interchangeable competition. The availability of approved biosimilar and interchangeable insulin products is expected to increase access and reduce costs of insulin products, which millions of Americans take each day to maintain stable blood glucose.
The FDA is working now, in advance of the March 23, 2020 transition, to build a solid regulatory foundation for the review and approval of biosimilar and interchangeable insulin products.
The issuance of this draft guidance supports key goals in the FDA’s Biosimilars Action Plan, which aims to improve the efficiency of the biosimilar and interchangeable product development and approval process and to maximize scientific and regulatory clarity for the biosimilar product development community. We’ve accomplished many of the projects outlined in the Biosimilars Action Plan, and we’re continuing our work on others to enhance patient access to needed medicines. The FDA will begin accepting comments from the public on the draft guidance on Nov. 29.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
参考来源
Statement on efforts to help make development of biosimilar and interchangeable insulin products more efficient http://suo.im/4InXHq
Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products http://suo.im/4PUefh