Once a device, but not always a device

BioFabUSA helps members stay up-to-date on regulatory decisions which may affect medical product availability and regulation. In 2018, the FDA indicated their intent to reclassify hyaluronic acid (HA) intra-articular products indicated for use in patients with osteoarthritis (OA) of the knee from a device to a drug.

BioFabUSA helps members stay up-to-date on regulatory decisions which may affect medical product availability and regulation. In 2018, the FDA indicated their intent to reclassify hyaluronic acid (HA) intra-articular products indicated for use in patients with osteoarthritis (OA) of the knee from a device to a drug.

Osteoarthritis of the knee is a common disorder that is often initiated by a predisposing condition, such as an injury, which changes the chemical composition of the articular cartilaginous surface. This results in progressive cartilage loss and exposure of bone over time, leading to bone degeneration, pain, and inflammation. One of the more common treatments for pain in knee OA patients is HA intra-articular injections. Although analyses of HA studies have concluded that that the overall effect of HA did not provide clinically-significant improvement to patients, HA injections can provide temporary pain relief when other therapeutic options have failed.

HA is naturally present in the cavities of synovial joints, where it functions as a structural element, promotes viscoelastic properties of synovial fluid, and assists in joint lubrication. Medically, HA injections act in the same way. In fact, it is due to these shock-absorbing qualities that the FDA initially designated HA intra-articular products as Class III devices in 1995. At that time, it was thought that the primary action of injected HA was mechanical. However, this mechanical mechanism of action is limited due to HA’s short half-life; other accompanying mechanisms, such as anti-inflammatory, analgesic, and chondroprotective effects might be responsible for any longer-term clinical activity.

It has been scientifically proven that these accompanying mechanisms occur due to chemical interactions between cellular components and HA. HA binds to specific receptors in the joint affected by OA. HA-bound receptors trigger various intracellular signaling events, such as cytokine release and stimulation of cell cycle proteins, which promote anti-inflammatory effects and stimulate cell activity and proliferation. Evidence of these molecular interactions producing the intended therapeutic effects have been described in scientific literature, and act as the basis for injected HA’s designation as a drug in regulatory agencies abroad. The FDA’s intent to reclassify HA intra-articular products as drugs signals their desire to align the US with the rest of the world.

The reclassification of HA from device to drug should lead tissue-engineered medical product (TEMP) developers planning to use HA to seek early guidance from the Office of Combination Products (OCP) on product jurisdiction. An informal ot formal Request for Designation (RFD) may be submitted to OCP to obtain a determination of the regulatory classification of a product. The FDA guidance documents, How to Prepare a Pre-Request for Designation (Pre-RFD) and How to Write a Request for Designation (RFD), identify the information FDA needs from a sponsor to determine the regulatory classification of a product as a drug, device, biologic, or combination product, and to assign the product to the appropriate Center for review and regulation. Refer to the ARMI|BioFabUSA blog post PMOA Points the Way! for more information on product jurisdiction.

Clarification on drug and device jurisdiction can be found in the FDA guidance document, Classification of Products as Drugs and Devices & Additional Product Classification Issues. For questions on how the FDA regulations might affect your company’s medical product premarket or postmarket stance, request a BioFabConsulting meeting with Drs. Richard McFarland and Becky Robinson-Zeigler at BioFabConsulting@www.armiusa.org.

More News

BioFabUSA, a program of ARMI, is a public-private partnership with more than 170 members, including companies, academic institutions and not-for profit organizations.

Technology

ARMI

The Advanced Regenerative Manufacturing Institute (ARMI) is a member-based, nonprofit organization whose mission is to advance the bioeconomy of the United States. The institute’s work will positively impact not only manufacturing but also healthcare and education and workforce development in the country.

Commercialization

The Advanced Regenerative Manufacturing Institute (ARMI) is a member-based, nonprofit organization whose mission is to advance the bioeconomy of the United States. The institute’s work will positively impact not only manufacturing but also healthcare and education and workforce development in the country.