 | | | A key component of the commercialization process is the regulatory path for a particular product, which can vary widely for each product category. Drugs can take 10 years to get to market from the lab, but devices can make it within a couple of years. Diagnostics may face even less of a regulatory hurdle. Obviously, the longer a product remains in clinical trails and the larger those trials are, the more expensive development will be and the longer companies will have to wait for a return on their investment. Good news for NUCATS investigators! You can find learn more about the regulatory process and obtain regulatory assistance through NUCATS. Below are some high level descriptions of the regulatory process in the United States. | |
Therapeutics generally fall into two categories that follow a similar regulatory path at the Food and Drug Administration (FDA): - small molecule drugs - regulated by the Center for Drug Evaluation and Research (CDER)
- biologics, like antibodies or proteins - regulated by the Center for Biologics Evaluation and Research (CBER)
In either case, investigators must go through a number of steps before starting clinical trials, including: - toxicology, pharmacokinetic and pharmacodynamic data in preclinical models
- prove the ability to manufacture the therapeutic in stringent current Good Manufacturing Practice (cGMP) conditions, or contract with someone else's cGMP facility to do so. NU does not currently have a cGMP scale up facility for clinical trials.
Once all the data are acquired, investigators or companies can file an Investigational New Drug Application (IND). IND approval launches a three phase clinical development process. - Phase I - small and short trials, generally focused on determining safety and drug characteristics like absorption, distribution, metabolism, and excretion (ADME) in humans; usually healthy volunteers
- Phase II - much larger trials in the target population, with a focus on determining efficacy and optimal dosing
- Phase III - the largest, costliest and most time consuming trials; dedicated to evaluating the drug in populations the way it would be used after FDA approval.
Successful completion of the three phases can cost well upwards of $100 million and take up to a decade. The process culminates in a New Drug Application (NDA) for chemical entities or a Biologic License Application (BLA) for biologics. Sometimes approval is contingent on completion of Phase IV trials. | |
Medical devices are regulated by the Center for Devices and Radiological Health (CDRH) within the FDA. CDRH follows a classification system for medical devices: - Class I - things you would normally think of as fairly benign objects, like tongue depressors and bandages; though not subject to extensive tests, even these devices are subject to some regulation.
- Class II - generally things like powered wheelchairs and infusion pumps, which would not normally carry risk of serious injury without some sort of catastrophic failure and for which special controls exist
- Class III - high risk items like implantable devices
If the device is novel and/or seeking approval for a new indication, it will likely require Pre-market Approval (PMA), a time consuming and costly process. - All Class III devices, whether novel or not, require PMA, as do some Class II devices.
- PMA applications require detailed and stringent testing of all materials, rigorous quality systems and convincing clinical data.
A Class II device that can claim substantial equivalence to other devices on the market may be eligible for a shorter, cheaper path to market called a Pre-Market Notification, or more commonly known as a 510(k) application. - A 510(k) may not even require the collection of any new clinical data, whereas all PMAs will require clinical studies.
Clinical studies in support of PMA or 510(k) applications must first go through the Investigational Device Exemption (IDE) process at CDRH. | |
In vitro diagnostic kits are regulated as medical devices and subject to the same stipulations above. Completely new products that are not substantially equivalent to existing diagnostics are automatically classified as Class III devices and subject to the PMA process.
Some companies have developed a service model for diagnostics, using their own proprietary screening, mostly those that do genetic analysis of tumors or genetic profiling of individuals. These "home brew" outfits have traditionally been subject to less regulation under the Clinical Laboratory Improvement Amendments (CLIA), though there is debate over how to properly regulate these companies in the future. | |
In response to the rise of combination products like drug-eluting stents, the FDA has established an Office of Combination Products (OCP). The OCP: - assigns primary regulatory responsibility to one of the three product centers at FDA mentioned in the above sections (CDER, CBER, or CDRH) and
- coordinates oversight of the combination device by the relevant product centers
The primary center is chosen based on the primary mode of action for the product. For instance, a drug-eluting stent acts primarily as a stent (a medical device). The drug is used to augment safety and effectiveness. In this case, regulation falls primarily under CDRH. However, because the stent elutes a drug, CDER is also involved in regulatory oversight to ensure that the drug is being manufactured under cGMP conditions and meets other necessary requirements. Full guidance and more information about combination products can be found on the OCP web site. | | | |
| |
