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.

Comparative Studies of Hyaluronic Acid Concentration in Normal and Osteoarthritic Equine Joints

“…Finally, Figure 1C shows the viscosity and the shear stress of the material as the shear rate increases. A Newtonian plateau is observed at low and medium shear rates along with a shear thinning behavior at higher shear rates in good agreement with previous studies [32][33][34][35][36][37][38].…”

Triborheological Study under Physiological Conditions of PVA Hydrogel/HA Lubricant as Synthetic System for Soft Tissue Replacement

“…The evaluation of complex viscosity (η*), elastic (G′), and viscous (G″) modulus (Figure 5c) showed that at low frequencies, the sample exhibited an elastic behavior (G′ > G″), while at high frequencies, it presented a viscous behavior (G″ > G′). This behavior is typical of substances in solution, known as "weak gels", and is contrary to the results of pure HA, which initially behaves viscously (G″ > G′) [54,63,64,65]. Additionally, the number of FT cycles should increase the elastic modulus, which is related to the gel strength and porosity, because the cycles stimulate the formation of crystalline junction zones among…”

An Effective Translation: The Development of Hyaluronan-Based Medical Products From the Physicochemical, and Preclinical Aspects

“…For all the above-mentioned reasons, it is important to identify the Mw of the polysaccharide (Braithwaite et al, 2016 ). A good method for the determination of the average molecular weight of native and modified HA is size exclusion chromatography combined with multiangle light scattering (SEC-MALLS) (Cožíková et al, 2017 ).…”