We at Skin Cancer and Reconstructive Surgery Center wanted to upgrade our Photodynamic Therapy (PDT) treatment of AK’s and superficial BCC by switching from the Blu-U light to a red light source. Red light spectrum has been shown to be a deeper penetrating light for photodynamic therapy and, thus, has gained greater worldwide acceptance – except in the United States. In the US, a red light marketed under the name Aktilite CL 128 made a brief appearance with Metvixia (methyl aminolevulinate) photosensitizer. The company (Gladerma) pulled the products from US market for business reasons at end of 2012.
Aktilite lamp itself was small and had a limited surface for one-directional illumination. We wanted to implement a better light source and found a plethora of devices manufactured in China on Alibaba.com – the super website for manufacturers and distributors. These devices were superior to Aktilite in many ways – circumferential light source for greater area coverage and more even treatment. The lamps offer red, blue, and yellow light in one machine. The light density has a much greater range. The distributor cost is under $1500 with shipping. Our excitement to acquire this technology was tempered by a small government agency – the Food and Drug Administration.
FDA regulates radiation emitting electronic products. Manufacturers and distributors of these products are subject to the Federal Food Drug & Cosmetic (FD&C) Act. While the FDA approves and regulates the production, sale, and clinical research of medical devices, it does not directly regulate the practice of medicine. So, it can be argued that we buy the machine and start delivering superior care to our patients that few in the US currently do.
The problem arises in liability. Medical malpractice carriers may have a problem with use of a non-FDA approved device. Case law has shown that violating the FDCA may be evidence of a breach of the standard of care and consequently result in a determination that malpractice has occurred. Of course, this would only happen if a patient is injured. Although PDT is safe with temporary side effects, a scenario can arise where a skin cancer within the field of treatment causes significant injury and the PDT treatment is blamed. Whether true or not, the use of non-FDA approved device would have a negative impact on the case.
Given our pursuit of new and innovative therapies for skin cancer, we retained a consultant to help us get FDA approval for a red light PDT machine – Emergo Group. Here is what we learned about the FDA approval process.
FDA classifies devices as Class I, II, and III.
Class I devices are defined as non-life sustaining. These products are the least complicated and their failure poses little risk. FDA requires registration of this device if sale, distribution, and marketing is intended. These devices may fall under GMP requirements (Good Manufacturing Practices).
Class II devices are more complicated and present more risk than Class I, though are also non-life sustaining. They are also subject to GMP requirements and may be subject to 510K approval process. Many of these devices are exempt from 510K requirements (basic facial implants, dressings, sutures, low power lasers, and scopes).
Class III devices sustain or support life, so that their failure is life threatening. Therapeutic light device is a radiation emitting electronic product defined as Class III. Full approval is required.
There two primary routes for obtaining approval for medical device marketing – 510K premarket clearance and PMA (Premarket Approval).
510K clearance is a simpler process that takes up to 1.5 years to complete. The cost of the process may be $50,000 – $100,000. The approval of a new red light PDT system could fall under this process because substantially equivalent products are already on the market – Blu-U and Aktilite.
The PMA process is the real thing. It takes 3.5 – 5 years to complete and costs over $300,000. Outside consultants do not accept these projects due to the length and complexity, and as such are done in-house. The PMA process involves about five 510K submissions.
In either of the above routes, FDA may request an IRB (Institutional Review Board) clinical trial. In PMA process, this is the norm. Once approval for clinical trial is granted, the device can be used on patients in a clinical trial setting as data is collected under the supervision of the IRB process. This is called granting of IDE (Investigational Device Exemption). At this point the device can be marketed while FDA awaits final post-marketing data submission. The cost to get to this point can be as little as $50,000.
FDA also requires the manufacturers to follow GMP requirements (Good Manufacturing Practices) set under the QSR (Quality System Regulation). It requires that domestic or foreign manufacturers have a quality system for the design, manufacture, packaging, labeling, storage, installation, and servicing of finished medical devices intended for commercial distribution in the United States. To facilitate this function, FDA inspects manufacturer’s facilities and has offices in China where much of medical device manufacturing occurs.
With this background, it is easy to understand why the makers of Levulon or Metvixia have not committed resources to get FDA approval for use in basal cell carcinoma treatment in the US. In Canada and Europe, these drugs have the approval for BCC by their FDA equivalents. Spending extra $500,000 for FDA approval does not bring the equivalent ROI (return on investment).
For us at SCARS Center, the integration of Red Light PDT will require at least $50,000 in legal and submission costs and 1.5 years. Interesting issues arise once FDA grants approval for a manufacturer’s device for marketing under Brand A. The manufacturer can sell the device to other distributors who can relabel and repackage the device as Brand B and sell it with a simple FDA registration. This is more prevalent in more robust markets as aesthetic lasers, where multiple relabelers and repackagers are in the market. So, the coattail benefits of approval of a device are long and usable by other distributors.
Our options for adding red light to PDT are limited to IPL (intense pulse light) devices or KTP or pulse dye lasers that already have FDA approval.