As described in this and the previous sections, pre-clinical studies have shown that Arthrosamid®/”Hydrogel” is biocompatible, non-absorbable, non-biodegradable and non-migratory (Bello et al., 2007; Charles River, 2011; Zarini et al., 2004). Long-term clinical data has confirmed this (Mouritsen et al., 2014; Negredo et al., 2015). It is therefore reasonable to conclude that Arthrosamid® is stable and safe for the lifetime of the device.

The intended purpose of Arthrosamid® is summarised below:

Intended purpose of Arthrosamid®
Indication	Arthrosamid® is intended to be used for symptomatic treatment of knee osteoarthritis in adults.
Disease to be treated	Knee osteoarthritis.
Patient population	Adult patients diagnosed with osteoarthritis.
Intended application	Arthrosamid® is intended to be injected intra-articularly in the knee joint.
Intended user	Arthrosamid® is intended to be used by a qualified physician familiar with intra-articular injection procedures, such as orthopaedic surgeons or rheumatologists.
Effect on the human body	Arthrosamid® diminishes pain and improves function of the knee affected by osteoarthritis.
Tissues in contact with the device	Knee joint.
Duration of use	Long-term (>30 days)*.
Contact with mucosal membranes	Arthrosamid® is in contact with the synovial membrane of the knee joint.
Invasive / non-invasive	Invasive.
Implantable / non-implantable	Implantable.
Single use / reusable	Single use.
Recommended dose	6 ml**.
Contraindications	Arthrosamid® should not be injected: If an active skin disease or infection is present at or near the injection site If the joint is infected or severely inflamed If a degradable intra-articular injectable such as hyaluronic acid is present, it must be expected to be absorbed according to the manufacturer’s information for the specific product, before injection with Arthrosamid® If the patient has previously received treatment with a different non-absorbable injectable/implant If the patient has received a knee arthroplasty or has any foreign material in the knee If the patient has undergone knee arthroscopy within the last 6 months In hemophilia patients or in patients in uncontrolled anticoagulant treatment
Warnings	Arthrosamid® must not be injected intra-vascularly, extra-articularly or in the synovial tissue or capsule Do not inject corticosteroids along with Arthrosamid®
Precautions required by the manufacturer	Arthrosamid® should be used with caution in patients with e.g. autoimmune disorders and uncontrolled diabetes as well as in patients undergoing major dental work or surgery Prophylactic antibiotic treatment must be administered prior to injection Usual precautions associated with invasive joint procedures should be followed Pharmaceuticals or biological substances should not be injected into the hydrogel Safety and effectiveness have not been established in patients under 18 years, in pregnant or lactating women, or in patients having foreign material implanted in the knee Only use Arthrosamid® if the packaging and products are intact and undamaged. Do not re-sterilize Arthrosamid®.

Table 6. Intended purpose of Arthrosamid®. *Twelve months clinical follow-up data is presented for Arthrosamid® (see 5.4.1 and 5.4.4), whereas long-term clinical data is available for Contura’s hydrogels for other indications for up to 8 or 10 years (3.1.2.10), and it is therefore reasonable to believe that this permanent implant/hydrogel is stable and safe for the lifetime of the device (3.1.2.10).**The recommended dosage of 6 ml is based on the total volume of gel injected in the “proof-of-concept” study (2 x 3 ml for the majority (96%) of the patients) and on data from the CON-OA study (5.4.4). One injection of 6 ml compared to 2 x 3 ml reduces the risk of infection, and prophylactic antibiotics are only given once.

The Science of Arthrosamid® (2.5 iPAAG)