Determination of Similarity Margin in Comparative Clinical Studies to Support the Development of Biosimilar Products of Neupogen® (Filgrastim, Granulocyte Colony-Stimulating Factor [G-CSF]). 2018

Lei Nie, and Donna Przepiorka, and Albert Deisseroth, and Rajeshwari Sridhara, and Thomas E Gwise
Division of Biometrics IV, OB/OTS/CDER/FDA, Silver Spring, MD, 20993-0002, USA. lei.nie@fda.hhs.gov.

To demonstrate a biological product is biosimilar to a reference product, the applicant needs to show that the product is highly similar and has no clinically meaningful differences. Comparative clinical studies are often conducted to support the conclusion of no clinically meaningful differences, as a part of totality of evidence. The FDA has published several guidance documents to facilitate the development of biosimilar products. While the guidance documents define the role and objective of comparative clinical studies, they do not provide details about the determination of the similarity margin. In this paper, we illustrate a similarity margin derivation for a surrogate endpoint in comparative clinical studies conducted to assess whether clinically meaningful differences exist between Neupogen® (Filgrastim, granulocyte colony-stimulating factor) and products proposed to be biosimilar to Neupogen®.

UI MeSH Term Description Entries
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D004335 Drug and Narcotic Control Control of drug and narcotic use by international agreement, or by institutional systems for handling prescribed drugs. This includes regulations concerned with the manufacturing, dispensing, approval (DRUG APPROVAL), and marketing of drugs. Drug Regulations,Narcotic Control,Pharmaceutical Policy,Drug Control,Narcotic and Drug Control,Pharmaceutic Policy,Control, Drug,Control, Narcotic,Controls, Drug,Controls, Narcotic,Drug Controls,Drug Regulation,Narcotic Controls,Pharmaceutical Policies,Policies, Pharmaceutical,Policy, Pharmaceutical,Regulation, Drug,Regulations, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069585 Filgrastim A recombinant granulocyte colony-stimulating factor (G-CSF) that is used in the treatment and prevention of NEUTROPENIA, preparation and collection of blood progenitor cells, and for use in PERIPHERAL BLOOD STEM CELL TRANSPLANTATION. Filgrastim-sndz,G-CSF Recombinant, Human Methionyl,Granix,Neupogen,R-metHuG-CSF,Recombinant-Methionyl Human Granulocyte Colony-Stimulating Factor,Tbo-Filgrastim,Topneuter,Zarxio,G CSF Recombinant, Human Methionyl,R metHuG CSF,Recombinant Methionyl Human Granulocyte Colony Stimulating Factor,Tbo Filgrastim
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D059451 Biosimilar Pharmaceuticals Biological products that are imitations but not exact replicas of innovator biological products. Biosimilar,Biosimilars,Follow-on Biologics,Subsequent Entry Biologics,Biologics, Follow-on,Biologics, Subsequent Entry,Follow on Biologics,Pharmaceuticals, Biosimilar

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