title: Rheological and molecular weight comparisons of approved hyaluronic acid products - preliminary standards for establishing class III medical device equivalence.
abstract: Hyaluronic acid of various molecular weights has been in use for the treatment of osteoarthritis knee pain for decades. Worldwide, these products are regulated as either as drugs or devices and in some countries as both. In the US, this class of products is regulated as Class III medical devices, which places specific regulatory requirements on developers of these materials under a Pre-Market Approval process, typically requiring data from prospective randomized controlled clinical studies. In 1984 pharmaceutical manufacturers became able to file an Abbreviated New Drug Application for approval of a generic drug, thus establishing standards for demonstrating equivalence to an existing chemical entity. Recently, the first biosimilar, or 'generic biologic', was approved. Biosimilars are biological products that are approved by the FDA because they are 'highly similar' to a reference product, and have been shown to have no clinically meaningful differences from the reference product. For devices, Class II medical devices have a pathway for declaring equivalence to an existing product by filing a 510 k application for FDA clearance. However, until recently no equivalent regulatory pathway was available to Class III devices. In this paper, we consider the critical mechanical performance parameters for intra-articular hyaluronic products to demonstrate indistinguishable characteristics. Analogous to the aforementioned pathways that allow for a demonstration of equivalence, we examine these parameters for an existing, marketed device and compare molecular weight and rheological properties of multiple batches of a similar product. We propose that this establishes a scientific rationale for establishing Class III medical device equivalence.
authors.affiliation: a Cambridge Polymer Group , Boston , MA , USA.
authors.forename: Gavin J C
authors.initials: GJ
authors.lastname: Braithwaite
authors.affiliation: b OrthogenRx, Inc. PA Biotechnology Center of Bucks County , Doylestown , PA , USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Daley
authors.affiliation: b OrthogenRx, Inc. PA Biotechnology Center of Bucks County , Doylestown , PA , USA.
authors.forename: David
authors.initials: D
authors.lastname: Toledo-Velasquez
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000737:chemistry* / Q000592:standards* / Q000627:therapeutic use; D002850:Chromatography, Gel; D004864:Equipment and Supplies / Q000592:standards*; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000592:standards* / Q000627:therapeutic use; D007834:Lasers; D062307:Medical Device Legislation; D008970:Molecular Weight; D012212:Rheology; D012542:Scattering, Radiation; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D059451:Biosimilar Pharmaceuticals; D006820:Hyaluronic Acid
keywords: Hyaluronic acid; biosimilar; generic; medical device equivalence; molecular weight; rheology