Regulatory
Global marketing and sale of biomedical technology requires regulatory approval by various national regulatory bodies. In the US, medical devices, pharmaceuticals, biotechnology and combination products are regulated by the Food and Drug Administration (FDA). It is important for developers of medical technology to understand regulatory requirements, as each type of biomedical technology has its own regulatory pathway, associated timeline and costs required to obtain approval to market the product.
Medical Devices
Medical devices are divided into three classes, each with different regulatory requirements based on risk stratification as outlined below.
| Class | Risk | Regulatory Requirements |
|---|---|---|
| Class I | Present minimal potential harm to the user |
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| Class II | More complex, higher risk that are not life-sustaining |
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| Class III | Support or sustain human life |
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The process of regulatory approval within the United States for a medical device can take one of two general paths based on the intended use of a medical device and also on indications for use.
510(k) Pre-market Notification
The 510(k) review process allows the manufacturer to notify the FDA that a Class II device is “substantially equivalent” to an existing approved (predicate) device, thereby minimizing the need for clinical trials to substantiate safety and effectiveness. Approximately 44% of medical devices fall into this category and up to 15% of these will require clinical data to demonstrate substantial equivalence. Obtaining 510(k) clearance to market a medical device typically takes three to five months after submission to the FDA.
Pre-Market Approval (PMA)
A Pre-Market Approval (PMA) review process is required for Class III devices, which are determined to be new and/or life supporting or otherwise critical. 
Approximately 1% to 2% of medical devices fall into this category. The PMA process requires documentation of the device's safety and effectiveness through pre-clinical testing (bench testing, biocompatibility, animal studies, etc.) and clinical testing (through an Investigation Device Exemption), a process that may take up to 6 years. The PMA undergoes scientific review by appropriate FDA personnel and advisory committees, and typically takes 12 to 24 months upon submission to the FDA to receive approval.
Pharmaceuticals
The regulatory pathway for pharmaceuticals is a much longer process than for medical devices. To be marketed in the United States most all pharmaceuticals are subject to the New Drug Approval (NDA) process.. Preclinical testing data (safety, toxicity, pharmacokinetics, dosage recommendations, chemical composition, formulation and manufacturing), which may take up to five years or more to complete, is submitted to the FDA to obtain permission to begin clinical testing as an Investigational New Drug (IND).
Pharmaceutical clinical testing consists of several phases, with increasing numbers of human subjects tested during each phase. Phase I clinical studies involve testing the drug on a small number of healthy volunteers (typically fewer than 100 people) to verify the safety and tolerability of the drug in humans. Phase I studies usually take from six months to one year to complete.
Phase II clinical studies take longer, approximately one to three years to complete, and are usually randomized, double-blinded studies. During Phase II studies, the drug is tested on a few hundred patients who are afflicted with the disease the drug is targeted to treat. The purpose of this phase of testing is to establish that the drug is safe and effective in treating the disease. Minimum and maximum effective dose are also determined during this phase of testing.
Phase III clinical studies are usually multicenter, randomized, double-blinded trials, and involve use of the drug in several hundred to thousands of patients with the target disease. This phase of clinical testing may last from one to four years and provides additional safety and effectiveness testing of the investigational drug.
Once a drug has successfully completed preclinical and clinical testing as outlined above, a New Drug Application (NDA) is submitted to the FDA. Regulatory review may take as long as two years or more after submission, and approval is based on substantial evidence of safety and efficacy of the drug to treat the target patient population.
Biotechnology
The regulatory pathway for biotechnology products such as biopharmaceuticals differs from that for drugs and medical devices. Following successful preclinical testing demonstrating its safety, a biological product can be tested clinically in humans under an investigational drug application (IND). A Biologics License Application (BLA) is required by the FDA to market a biotechnology product. Obtaining a biologics license is similar to the New Drug Application (NDA) process for regular pharmaceuticals.
Combination products
Combination products are those containing a combination of drugs, devices and/or biologics that are physically, chemically or otherwise combined such as drug-eluting stents, prefilled syringes or photosensitizing drug with an activating light/laser source. Clinical trials for combination products are more comprehensive, costly, and complicated than those required for individual drugs, devices, or biologics as the individual properties of each component must be investigated, as well as the properties of the components when used in combination. The FDA's Office of Combination Products assigns an FDA center (Center for Drug Evaluation and Research, Center for Devices and Radiological Health, or Center for Biologics Evaluation and Research) to have primary jurisdiction over the review of combination products, and also coordinates reviews involving more than one agency center.