FDA Issues Draft Guidance To Streamline Regulatory Oversight Of NGS-Based Tests For Diagnosing Germline Diseases

Personalized or Precision Medicine needs reliable and accurate diagnostic tests to guide clinical intervention and treatment decisions. Traditional testing of germline variants is site-specific and therefore only provides information on one or at most, several variants at a time. Advances in DNA sequencing technology, notably Next Generation Sequencing (NGS), permit the analysis of millions of variants at a time. As a result, one test will provide clinically relevant and actionable data on a multitude of conditions, some of which are unknown until the test has been completed.

The FDA, in partnership with President Obama’s Precision Medicine Initiative (PMI), is working to take advantage of NGS for the development of new personalized therapies while maintaining quality and safety. FDA issued two draft guidances designed to streamline regulatory oversight for NGS tests. This post will review the first draft guidance, “Use of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases” (Guidance).

The Guidance provides FDA’s proposed approach on the content and possible use of standards in providing oversight for whole exome human DNA sequencing (WES) or targeted human DNA sequencing NGS-based tests intended to aid in the diagnosis of individuals with suspected germline diseases or other conditions. Guidance at page 1. FDA notes that for the purpose of the Guidance, the term” germline diseases or other conditions” encompasses those genetic conditions arising from inherited or de novo germline variants.

Recommendations for Design, Development, and Validation of NGS-based Tests for Germline Diseases

The Guidance provides recommendations regarding how a NGS-based test should be designed, developed, and validated. As a general principle, test developers should first define the indications for use statement of their test, and this statement will then determine how the test should perform. Guidance at page 7. Test developers are encouraged to prospectively determine the types of studies that should be conducted as well as the thresholds that should be met for a minimum and target value of performance. Subsequent validation studies should indicate if the predefined performance values have been met. If the test does not meet any one of the predefined performance specifications, the test should be modified and revalidated. Id. The cycle of design, development and validation should be repeated until the test meets the predefined performance specifications.

Comments, Suggestions and Questions

Comments and suggestions regarding the draft Guidance may be submitted within 90 days from the July 8, 2016 publication date of the Guidance in the Federal Register. Comments may be submitted electronically to http://www.regulations.gov or in writing to the Division of Docket Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville Maryland 20852. All comments must be identified with the docket number listed in the Federal Regiser notice.

The public can submit questions about this Guidance concerning devices regulated by CDRH by contacting the Personalized Medicine Staff at 301-796-6206 or at [email protected]. For questions regarding the Guidance as applied to devices regulated by CBER, the public is invited to contact the Office of Communication, Outreach and Development in CBER at 1-800-835-4709 or by email at [email protected]. gov.

Disclaimer

This blog is made available by Foley & Lardner LLP (“Foley” or “the Firm”) for informational purposes only. It is not meant to convey the Firm’s legal position on behalf of any client, nor is it intended to convey specific legal advice. Any opinions expressed in this article do not necessarily reflect the views of Foley & Lardner LLP, its partners, or its clients. Accordingly, do not act upon this information without seeking counsel from a licensed attorney. This blog is not intended to create, and receipt of it does not constitute, an attorney-client relationship. Communicating with Foley through this website by email, blog post, or otherwise, does not create an attorney-client relationship for any legal matter. Therefore, any communication or material you transmit to Foley through this blog, whether by email, blog post or any other manner, will not be treated as confidential or proprietary. The information on this blog is published “AS IS” and is not guaranteed to be complete, accurate, and or up-to-date. Foley makes no representations or warranties of any kind, express or implied, as to the operation or content of the site. Foley expressly disclaims all other guarantees, warranties, conditions and representations of any kind, either express or implied, whether arising under any statute, law, commercial use or otherwise, including implied warranties of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Foley or any of its partners, officers, employees, agents or affiliates be liable, directly or indirectly, under any theory of law (contract, tort, negligence or otherwise), to you or anyone else, for any claims, losses or damages, direct, indirect special, incidental, punitive or consequential, resulting from or occasioned by the creation, use of or reliance on this site (including information and other content) or any third party websites or the information, resources or material accessed through any such websites. In some jurisdictions, the contents of this blog may be considered Attorney Advertising. If applicable, please note that prior results do not guarantee a similar outcome. Photographs are for dramatization purposes only and may include models. Likenesses do not necessarily imply current client, partnership or employee status.