Food and drug administration Thinking about New Regulatory Methods for NGS – Part I

Food and drug administration Thinking about New Regulatory Methods for NGS – Part I

Food and drug administration Thinking about New Regulatory Methods for NGS – Part I

The Fda (“FDA”) announced a workshop to become held Feb 20th, 2015, titled “Optimizing FDA’s Regulatory Oversight of Next-gen Sequencing Diagnostic Tests” to acquire public input regarding its regulating next-gen sequencing (“NGS”). Particularly, the company seeks public comment and feedback around the issues and questions elevated in the discussion paper “Optimizing FDA’s Regulatory Oversight of Next-gen Sequencing Tests – Preliminary Discussion Paper” (“FDA Discussion Paper”) (copy here). This publish will reveal FDA’s issues and concerns concerning the analytical performance of NGS. Part II will address the agency’s issues and concerns because they have to do with the clinical performance of NGS.

The Commitment of NGS in Personalized Medicine

Personalized medicine depends on accurate and reliable testing of clinically relevant information. Just about all current Food and drug administration-approved in vitro tests (“IVDs”) measure merely a single or perhaps a small group of drugs (for instance, DNA or proteins). Thus, several patient samples and many tests might be needed to judge a patient’s clinical status or to decide on the best therapy for that patient. In comparison, NGS can identify over 3 billion bases within the human genome and could identify almost 3 million genetic variants in one test. Thus, NGS can identify numerous illnesses or conditions in a single test.

The Difficulties of Controlling NGS

In the past for traditional IVDs, Food and drug administration examines the exam for precision and reliability (analytic performance) and when the outcomes in the test properly identifies the appropriate disease or condition (clinical or diagnostic performance). The exam qualifies when Food and drug administration determines that the IVD has acceptable analytical and clinical performance. For traditional IVDs, the sponsor seeking Food and drug administration-approval offers the data and/or information demonstrating analytical and clinical performance from the test. NGS, in comparison, could possibly evaluate over 3 billion base pairs and for that reason evaluating the analytical performance of every data point would take years. Additionally,“[b]ecause you’ll be able to sequence the entire genome, there is no need to be aware what variant one desires to identify just before running and effectively interpreting an NGS test – an idea that is quite different from how traditional IVDs are utilized.Inches See page 2 of Food and drug administration Discussion Paper. NGS may identify rare variants that it might be impractical for test developers to supply conclusive evidence supporting clinical significance. Furthermore, how you can communicate the value of some genetic variants to physicians and consumers presents challenges towards the agency. See page 2 of Food and drug administration Discussion Paper.

Exploring New Regulatory Methods for NGS

Analytical Performance

Food and drug administration acknowledged that any new method of controlling NGS tests must ensure that the general public has timely use of tests which have sufficient analytical and clinical performance. See page 3 of Food and drug administration Discussion Paper. Just one NGS instrument (Illumina MiSeqDx?) and it is universal sequencing reagents and 2 associated assays for detecting cystic fibrosis (Illumina MiSeqDx? Cystic Fibrosis 139 Variant and Clinical Sequencing Assays) happen to be Food and drug administration- approved. Since it was impractical to identify every possible variant that may appear in a genomic sequence, analytical test performance for that MiSeqDx? system was shown for any representative quantity of subsets of sorts of variants in a variety of sequencing contexts. See page 4 of Food and drug administration Discussion Paper. The company announced that it’s thinking about extending this subset-based method for other NGS sequencing platforms, but additionally invites recommendations for other approaches. One particular approach that Food and drug administration seeks public comment is the introduction of methodologic quality-based standards that laboratories could meet to determine analytical performance produced by the lab. Food and drug administration particularly demands public feedback regarding: (1) worth of a standards-based method of regulatory overview of NGS tests (2) content of standards to become developed which will ensure that conformity towards the standard will ensure test precision and reliability, (3) who should develop such standards, and (4) appropriate mechanisms to make sure compliance. See page 5 of Food and drug administration Discussion Paper. On-page 5 from the Food and drug administration Discussion Paper, the company asks the general public ten specific questions associated with analytical performance:

How are labs presently developing NGS tests and assessing their analytical performance?

Do you know the benefits and risks to public health of getting Food and drug administration individually assess the analytical performance of NGS tests and/or platforms using data posted through the developer with an decided subset of information points for that test?

Do you know the benefits and risks to public health of the standards-based method of controlling NGS analytical performance?

Would a standards-based approach restricted to NGS tests which use Food and drug administration removed or approved components encourage ongoing development and consumer use of NGS tests with appropriate analytically performance?

How much could computational approaches be employed to assess analytical performance? If at all possible, who should develop such approaches, how could Food and drug administration facilitate their development, and just how is it validated?

Would be the concepts for standards outlined above sufficient to make sure that NGS tests have appropriate analytical performance? Otherwise, what else ought to be incorporated? Alternatively, are the concepts for standards in the above list unnecessary, therefore, which of them and why?

How should changes or advances in technology be managed employing a standards-based approach? What kinds of alterations in technology pose probably the most concern and do you know the best standards to deal with individuals concerns?

Who should get the standards: Food and drug administration, an advertisement hoc committee of experts, a Standards Development Organization, others, or a mix of these approaches?

What measures ought to be set up to watch progress and impact, both good and bad, if your standards-based approach were adopted?

How should conformity with standards be assessed?

Attending the general public Workshop

The Workshop is going to be held from 8:30 am to five pm in the Natcher Center in the National Institutes of Health Campus, 9000 Rockville Pike, Bldg. 45 Auditorium, Bethesda, MD 20814. Registration is free of charge and on an initial-come, first-offered basis. Persons thinking about attending must register online by 4 pm, Feb twelfth, 2015. Registration is thru FDA’s Medical Devices News & Occasions-Workshops & Conferences at http://world wide web.food and drug administration.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm. The Workshop is going to be webcast and people attending on-line must register by Feb twelfth, 2015.

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