Clinical Safety of ArthramidVet® 2.5% iPAAG Hydrogel

Both in vitro and in vivo studies have taken place, designed to generate data on the safety of ArthramidVet® and to support regulatory submissions for market authorisation. Most current OA treatments are focused on reducing symptoms, and there are few effective treatments that address the underlying cause of the disease. Besides, some treatments are associated with significant toxicities and contra-indications, and their use is restricted because of competition and welfare concerns. Multiple studies have now shown that 2.5% iPAAG is safe for use in animals and humans.

A neurotoxic mode of action would require the presence of acrylamide monomer in the joint. No sources of acrylamide are present due to extensive washing and autoclaving through the manufacturing process and is validated at lot release testing of each batch. Any potential cytotoxic effects of ArthramidVet® have also been independently tested using cell growth analysis via BCA-Staining. This method represents one of the easiest methods to determine any possible detrimental effects of substances, and cell culture techniques also allow a rapid yet sensitive diagnosis of the biological reactivity of materials. The BCA-Staining test predicts cytotoxic or necrotic effects of medical devices or materials with good correlation to animal experiments and high sensitivity. Under this testing model it has been shown that no cytotoxic or banned substances are released from 2.5% iPAAG.

The active substance used to manufacture 2.5% iPAAG is the same as the finished product, i.e. cross-linked polyacrylamide hydrogel (CAS No. 9003-05-8). The product is known to be exceptionally stable, and extensive washing occurs during the manufacturing process to remove any potential contaminants. In contrast, monomers of acrylamides are known to be neurotoxic to animals and humans, whereas polyacrylamides are non-toxic. More than 500,000 humans have been treated with Contura 2.5% iPAAG medical devices worldwide, with no evidence of neurotoxicity.

Furthermore, any possible toxic effects of residual monomers from manufacturing have been calculated using recommendations from the United States Environmental Protection Agency (2007). Levels did not raise biological safety concerns, either in data-derived or worst-case scenarios. The European Medical Agency (EMA) likewise recently ruled that 2.5% iPAAG as not falling within the scope of regulation concerning residues for veterinary medicinal products.

In vivo, studies investigating the safety of ArthramidVet® at 1x, 2x, and 5x the standard recommended dose have been performed for regulatory purposes with follow up examinations done at Days 1, 3, 7, and 14 after treatment. The safety of the product was evaluated using physical examination, (including joint health and mobility), and evaluation of complete blood haematology, serum biochemistry and acute phase proteins (SAA). While results showed mild variations between individuals and groups, they were unrelated to the treatment and consistent with normal variations due to breed, exercise, diet, climate, and history.  This finding aligns with numerous other published clinical studies where no adverse reactions have been recorded with ArthramidVet®.

Tnibar (2017) also investigated any potential neurotoxic effects by studying the nerve endings in the synovial membrane of 2.5% iPAAG treated goats. The nerve endings were seen intact with normal morphology and in normal numbers, regardless of the clinical result and the same as saline treated controls.

In conclusion, 2.5% iPAAG has had widespread use in human medicine for many years and together these studies are consistent in their findings that it is safe, non-pyrogenic and neuro-innocuous.

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