生物仿制药研发趋势及FDA生物仿制药指导原则草案解析

1st Interchangeable Product
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The 1st biological product to be licensed as interchangeable is granted a period of exclusivity. During the exclusivity period, a subsequent biological product relying on the same reference product cannot be licensed as interchangeable. Exclusivity calculus is based on date of approval, date of first commercial marketing, and patent litigation milestones.
Rachel E. Sherman, Biosimilar Guidance Webinar February 15, 2012
Wel J. “Least squares fitting of an elephant.” Chemtech Feb. 128-129 (1975).
生物仿制药生产过程
美国生物仿制药法规适用范围
“Biological Product” in the Public Health Service Act (PHS Act) now includes “protein”: . . . a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product …applicable to the prevention, treatment, or cure of a disease or condition of human beings… Historically, some proteins have been approved as drugs under section 505 of the FD&C Act and other proteins have been licensed as biologics under section 351 of the PHS Act. Under the BPCI Act, a protein, except any chemically synthesized polypeptide, will be regulated as a biological product.
生物仿制药研发趋势及 FDA生物仿制药 指导原则草案解析
龚兆龙博士
CEO 北京莱博药业
2012年10月
Biosimilar 与生物仿制药
Google Biosimilar 2011: 2,350,000 results 2012: 311,000个 2012找到相关结果约:1,190,000个
Section 7002(b)(2) of the Affordable Care Act, amending section 351(i) of thePHS Act.
美国生物仿制药定义
BPCI：A 351(k) application must include information demonstrating that the biological product: • Is biosimilar to a reference product; • Utilizes the same mechanism(s) of action for the proposed condition(s) of use -- only to the extent known for the reference product; • Condition(s) of use proposed in labeling have been previously approved for the reference product; and • Has the same route of administration, dosage form, and strength as the reference product.
美国生物仿制药法规适用范围
Protein： Any alpha amino polymer with a specific defined sequence that is greater than 40 amino acids in size. Chemically synthesized polypeptide: Any alpha amino acid polymer that (1) is made entirely by chemical synthesis; and (2) is less than 100 amino acids in size
美国生物仿制药定义
Biosimilar or biosimilarity is defined in Section 351 of the PHS Act to mean that “the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components,” and that “there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product”.
美国FDA生物仿制药指导原则
美国FDA批准的生物制品
美国FDA批准的生物仿制药
来源中投证券 添加日期：2011-09-22
生物仿制药：标准
Biosimilarity? How close do the proposed biosimilar products (figures B-E) compare to the reference product (figure A)?
欧盟生物仿制药管理规范
欧盟已批准的生物仿制药
来源：中投证券 添加日期：2011-09-22
美国生物仿制药法规
Generic:
Federal Food Drug and Cosmetic Act (FFDCA)The Abbreviated New Drug Application process in section 505(j) was established through the 1984 Hatch-Waxman Amendments to the FFDCA thus creating the generic drug program for “small molecule” drugs
生物制剂不同于化学药物：不能准确复制
传统药物：容易精确复制
美国生物仿制药立法目的
Biologics Price Competition and Innovation (BPCI) authorizes the FDA to oversee an “abbreviated pathway” for approval of biologics that are “biosimilar” to already approved products. Utilizing knowledge from the reference products, the abbreviated pathway will eliminate unnecessary (and therefore unethical) testing of biosimilars in animals and humans.
美国生物仿制药申报材料
A 351(k) application must include information demonstrating biosimilarity based on data derived from:
FDA may determine, in its discretion, that an element described above is unnecessary in a 351(k) application.
BPCI Act Exclusivity
Reference Product
• • A 351(k) application may not be submitted until 4 years after the date of first licensure of the reference product. A 351(k) application may not be approved until 12 years after the date of first licensure of reference product.
国内生物仿制药发展趋势
高起点：经验、资金、人才
大品种：瞄准国际重磅炸弹药 政府支持力度大
市场潜力大：人口结构、医保、经济发 展
竞争激烈：国内外竞争，需下调预期利 润
国内生物仿制药发展趋势
国内已上市的国产单抗及FC融合蛋白药物共8个，进口品种10个；国产在研提交生 产申请的6个、提交临床申请（包含已批准）的27个，进口提交临床申请的22个。
Advances in current state- of-the art analytical methods enhance the likelihood that a product will be highly similar to another product by better targeting the original product's physicochemical and functional properties.