To develop new therapies for musculoskeletal diseases and injuries, academic and industrial investigators must work together as they navigate the maze of federal requirements, legal hurdles, and manufacturing processes.
At the Orthopaedic Research Society (ORS) symposium “From your lab to the market: Understanding the industrial product development pathway,” four panelists provided practical information and insights regarding the pathways and processes required to bring inventions to the commercial market.
The product development process
Scott P. Bruder, MD, PhD, vice president, Johnson & Johnson Regenerative Medicine, opened the program by reviewing the “5 Rs” in the evolution of orthopaedic device development: remove, repair, replace, regenerate, and reproduce. Dr. Bruder also examined the timelines and expenses involved in product development.
A product that qualifies under the U.S. Food and Drug Administration’s (FDA) 510(k)—meaning that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device—may take three years to bring to market, at a cost of $5 million to $20 million. A Class III, life-supporting or life-sustaining, device may take six years and cost $20 million to $200 million to develop. Biologics may take up to eight years to develop, at a cost of $50 million to $300 million.
The product development process includes several steps, including preclinical research, intellectual property, business development (including reimbursement issues), regulatory affairs and quality, clinical research, and process development. “You can enter the pathway at any point,” said Dr. Bruder, “but you must traverse the entire pathway.”
Achieving appropriate reimbursement is important to both industry and surgeons. “Simply because you build it does not mean they will come,” said Dr. Bruder. The success of any new product depends on the acceptance and appreciation of the surgical community.
Addressing the issues of patents and intellectual property, David S. Smith, JD, of the Pittsburgh office of Pepper Hamilton LLP, began by dispelling the notion that a patent is a license to make a product. “In reality,” he said, “a patent gives you the ability to prevent others from making your product.”
In answer to the question, “What can be patented?” Mr. Smith pointed to a 1980 U.S. Supreme Court Ruling (Diamond v. Chakrabarty), which found that patentable subject matter included “anything under the sun that is made by man.” The requirement for human intervention is crucial, he said, noting that new patent applications are being received by the federal government at a rate of 1,000 a day.
Most orthopaedic patents would be classified as utility patents, which must meet three basic requirements: useful, novel, and not obvious. Mr. Smith proceeded to review the elements of a patent application, drilling down through the key points of the disclosure section, the parts of a written description and the hierarchy of claims statements—“the essence of the patent.”
The challenge faced by clinician scientists involved in emerging biotechnology is that “it’s hard to describe what has been invented,” said Mr. Smith, who went on to provide several strategies that could be used, including fingerprinting the physical and chemical details and describing the function of the product (saying what it does, rather than what it is).
In all cases, time is important, said Mr. Smith, because an inventor only has 20 years from the date of the first patent filing until its expiration. Parallel timelines, such as the FDA-approval process, may leave a manufacturer with little time to market a product before the patent expires. He also noted that now patent applications become public just 18 months after the first filing.
Additionally, Mr. Smith noted, different agencies can have totally opposite viewpoints regarding new devices. Laws governing the Patent Office, he pointed out, read that it “shall issue” new patents to devices that meet the specified requirements, while FDA regulations require that the agency “shall deny” approval to applications unless they meet the requirements.
In closing, Mr. Smith advised attendees that “Charges of patent infringement are legal, not scientific. If you have concerns, talk to an attorney, not to your colleagues.”
“I’m from the government and I’m here to help you,” said Aric D. Kaiser, MS, of the FDA’s Center for Devices and Radiological Health, Office of Device Evaluation. He reviewed the agency’s charges and mission, outlined its organizational structure, particularly with regard to orthopaedic devices, and listed the four major product areas: drugs, biologics, devices, and combination products.
The newest area is combination products, which do not fall into a specific category, but may comprise a drug and a biologic or a device and a drug. The new Office of Combination Products reviews all requests for designation, which determines how a product will be regulated, based on its primary mode of action.
Mr. Kaiser also reviewed the types of submissions and the data required when an application is filed. “You have to give us pretty much everything,” he admitted, including descriptions of the product/component and the manufacturing process, laboratory and animal study reports, any clinical experience, laboratory practices, tissue practices, trial design, investigator selection, institutional review board applications, informed consent forms, adverse event reports, and other data.
“Regulatory compliance is mandatory. It’s not something you choose to do—it’s what you must do. It’s in your best interest to contact us early, and whenever you have a question,” he concluded.
The final speaker, F. Jerry Volenec, PhD, discussed the process development pathway. He recommended the formation of high performance project teams to manage the development of new products and walked the audience through a “stage gate” process.
“From the moment that a project moves from research into process development—the ‘Go’ stage—until it reaches commercial viability,” he explained, “a company needs to describe the work, identify the output, and conduct regular reviews.” Milestone events are used to determine the progress of a product in development, and the project team must have a wide range of skill sets, ranging from project management to biochemistry, pharmacology, and engineering. “As we develop experience with the project on a small scale,” noted Dr. Volenec, “we identify what we can do commercially.”