FDA Device Regulation: 510(k), PMA

In the U.S., medical devices are classified into one of three groups based on potential risk to patients and this plays an important role in determining the appropriate FDA regulatory pathway. The three most common regulatory pathways through which the FDA clears or approves devices are: 1) exemption status, 2) 510(k), and 3) premarket approval (PMA). Early understanding of likely pathways is essential for planning device design and research strategy. All devices with more than a low or non-significant risk potential must be granted clearance, approval, or an Investigational Device Exemption (IDE) from the FDA prior to use in human subjects. Pre-submission, or Q-sub meetings, allow innovators and device companies to meet with the FDA for free and obtain feedback on the potential pathway and research protocols in an effort to have higher success with a future formal application. Early involvement of a regulatory expert or consultant can lead to a reduction in time to market and important cost savings

Strategic Planning and Costs of FDA Regulation

The regulatory burden for medical device innovation varies based on the specific Food and Drug Administration (FDA) pathway required, and early strategic planning for this regu­latory burden is critical. The regulatory strategy and milestones must be integrated with other key components of the innovation process and informed by an understanding of and/or direct communication with all the stakeholders involved, including the customer, engineering/manufacturing team, research and development team, safety/regulatory bodies, the potential payers, and investors. While it is almost never too early to initiate contact with the FDA, inquiries through 513(g) petitions or pre-submission meetings should be focused on specific questions and goals to make the most of these engagements. Regulatory assessments and consultation with experts require upfront costs, but saving time and money in the long term by designing an efficient regulatory strategy can be the difference between success and failure for the academic entrepreneur. Fundraising (private and public) must be considered in the regulatory strategy, as approx­imately 90% of fundraising is based on claims tied to regulatory milestones

An ortholog of the Ro autoantigen functions in 23S rRNA maturation in D. radiodurans

In both animal cells and the eubacterium Deinococcus radiodurans, the Ro autoantigen, a ring-shaped RNA-binding protein, associates with small RNAs called Y RNAs. In vertebrates, Ro also binds the 3′ ends of misfolded RNAs and is proposed to function in quality control. However, little is known about the function of Ro and the Y RNAs in vivo. Here, we report that the D. radiodurans ortholog Rsr (Ro sixty related) functions with exoribonucleases in 23S rRNA maturation. During normal growth, 23S rRNA maturation is inefficient, resulting in accumulation of precursors containing 5′ and 3′ extensions. During growth at elevated temperature, maturation is efficient and requires Rsr and the exoribonucleases RNase PH and RNase II. Consistent with the hypothesis that Y RNAs inhibit Ro activity, maturation is efficient at all temperatures in cells lacking the Y RNA. In the absence of Rsr, 23S rRNA maturation halts at positions of potential secondary structure. As Rsr exhibits genetic and biochemical interactions with the exoribonuclease polynucleotide phosphorylase, Rsr likely functions in an additional process with this nuclease. We propose that Rsr functions as a processivity factor to assist RNA maturation by exoribonucleases. This is the first demonstration of a role for Ro and a Y RNA in vivo