[Federal Register Volume 79, Number 91 (Monday, May 12, 2014)]
[Pages 26974-26975]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-10787]

[[Page 26974]]



Food and Drug Administration

[Docket No. FDA-2014-N-0505]

Proteomics in the Clinic; Public Workshop; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop; request for comments.


    The Food and Drug Administration (FDA) is announcing the following 
public workshop entitled ``Proteomics in the Clinic.'' FDA seeks input 
from interested stakeholders on how best to develop a regulatory 
framework targeted toward the complex issues involved in transforming 
research-level assays into validated in vitro diagnostics (IVDs) that 
can be used with patients. The topic to be discussed is the state of 
the art and challenges surrounding validation of proteomic 
methodologies for IVD tests.

Date and Time: The public workshop will be held on June 13, 2014, from 
8:30 a.m. to 5 p.m.
    Location: The public workshop will be held at the FDA White Oak 
Campus, 10903 New Hampshire Ave., Building 31 Conference Center, the 
Great Room (Rm. 1503), Silver Spring, MD 20993-0002. Entrance for the 
public workshop participants (non-FDA employees) is through Building 1 
where routine security check procedures will be performed. For parking 
and security information, please refer to http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    Contact Person: Julia Tait Lathrop, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 5564, Silver Spring, MD 20993-0002, 240-402-5034, 
email: [email protected].
    Registration: Registration is free and available on a first-come, 
first-served basis. Persons interested in attending this public 
workshop must register online by 4 p.m. on June 4, 2014. Early 
registration is recommended because facilities are limited and, 
therefore, FDA may limit the number of participants from each 
organization. If time and space permits, onsite registration on the day 
of the public workshop will be provided beginning at 7:30 a.m.
    If you need special accommodations due to a disability, please 
contact Susan Monahan, Center for Devices for Radiological Health, Food 
and Drug Administration, 10903 New Hampshire Ave. Bldg. 66, Rm. 4321, 
Silver Spring, MD 20993-0002, 301-796-5661, email: 
[email protected] no later than 4 p.m. on May 30, 2014.
    To register for the public workshop, please visit FDA's Medical 
Devices News & Events--Workshops & Conferences calendar at http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm. 
(Select this public workshop from the posted events list.) Please 
provide complete contact information for each attendee, including name, 
title, affiliation, email, and telephone number. Those without Internet 
access should contact Julia Tait Lathrop to register (see Contact 
Person). Registrants will receive confirmation after they have been 
accepted. You will be notified if you are on a waiting list.
    Streaming Webcast of the Public Workshop: This public workshop will 
also be Webcast. Persons interested in viewing the Webcast must 
register online by 4 p.m. on June 4, 2014. Early registration is 
recommended because Webcast connections are limited. Organizations are 
requested to register all participants, but to view using one 
connection per location. Webcast participants will be sent technical 
system requirements after registration and will be sent connection 
access information after June 9, 2014. If you have never attended a 
Connect Pro event before, test your connection at https://collaboration.fda.gov/common/help/en/support/meeting_test.htm. To get 
a quick overview of the Connect Pro program, visit http://www.adobe.com/go/connectpro_overview. (FDA has verified the Web site 
addresses in this document, but FDA is not responsible for any 
subsequent changes to the Web sites after this document publishes in 
the Federal Register.)
    Comments: FDA is holding this public workshop to discuss with 
interested stakeholders the issues surrounding validation of proteomic 
methodologies for IVD tests. In order to permit the widest possible 
opportunity to obtain public comment, FDA is soliciting either 
electronic or written comments on all aspects of the workshop topics. 
The deadline for submitting comments related to this public workshop is 
July 11, 2014.
    Regardless of attendance at the public workshop, interested persons 
may submit either electronic comments regarding this document to http://www.regulations.gov or written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852. It is only necessary to send one set of 
comments. Identify comments with the docket number found in brackets in 
the heading of this document. In addition, when responding to specific 
questions as outlined in section II of this document, please identify 
the question you are addressing. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday, and will be posted to the docket at http://www.regulations.gov.
    Transcripts: Please be advised that as soon as a transcript is 
available, it will be accessible at http://www.regulations.gov. It may 
be viewed at the Division of Dockets Management (see Comments). A 
transcript will also be available in either hardcopy or on CD-ROM, 
after submission of a Freedom of Information request. Written requests 
are to be sent to the Division of Freedom of Information (ELEM-1029), 
Food and Drug Administration, 12420 Parklawn Dr., Element Bldg., 
Rockville, MD 20857. A link to the transcripts will also be available 
approximately 45 days after the public workshop on the Internet at 
http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm. (Select this public workshop from the posted events list).


I. Background

    Basic research in proteomics, the study of all of the proteins and 
their interactions in an individual, has led to new understanding of 
proteins' contributions to health and disease. It has also driven the 
advancement of powerful analytical technologies used to explore these 
contributions. Translating these discoveries and technologies into IVD 
tests presents expanded opportunities to improve patient care; however, 
the complexity of these technologies raises challenging questions on 
how to evaluate the safety and effectiveness of these tests. FDA is 
holding this public workshop to invite discussion with industry, 
academia, government, and the public on how best to adapt current 
regulatory strategies to the challenges presented by proteomic 
approaches to IVDs, while still accelerating and supporting the 
introduction of innovative diagnostic tests into the clinic.
    Over the past 20 years, basic proteomic research has spurred 
intense innovation in biochemical analytic technologies (e.g., mass 
spectrometry, multiplex arrays, bioinformatics). This research has led 
to new insights into how proteins interact to maintain health and to 
cause disease; however, it is only recently that these technologies 

[[Page 26975]]

matured to the point that their introduction into the clinic appears 
practical and useful. Fundamental to using IVDs in the clinic is the 
need to demonstrate that the tests are safe and effective--that the 
results claimed are accurate and precise and that the interpretation of 
the results are supported by science. FDA's regulatory process is 
designed to ensure that intended use claims are supported with 
appropriate data. However, the range of variables that can be included 
in proteomic IVDs such as technological approaches, variety of sample 
types and preparation methods, data capture, and analysis algorithms, 
poses unique regulatory challenges, as more complex the information 
gathered, more challenging is the validation of results. At this point, 
what we need is a regulatory framework, tuned to proteomic 
technologies, which will facilitate the introduction of validated IVDs 
into the clinic.
    The intent of this workshop is not to discuss the limitations and 
strengths of the proteomic discovery process. The theoretical 
analytical performance of proteomic technologies have been well 
demonstrated, and in the past few years a number of initiatives have 
been launched to bring standardization and quality control to the 
discovery and pre-clinical development of proteomic-based assays. 
However, this level of quality control does not ensure that these 
assays have been validated for their intended use as IVDs tests that 
are used for diagnosis of disease and clinical management of patients; 
e.g., assessment of risk, monitoring of disease, prediction of response 
to therapy, and selection of treatment.
    Strategies are needed that will guide the successful transfer of 
research and discovery-level assays into the clinic. This includes 
their use in clinical trials, so that the analytical and clinical 
validity of the test procedure and outcome are assured. As a general 
rule, the requirements for analytical and clinical validation of IVDs 
are much greater than the studies that are commonly performed in a 
research and development setting. To support the least burdensome 
approach to assay development, FDA is willing to discuss unconventional 
approaches to IVD validation driven by, for example, the theoretical 
precision of multiple reaction monitoring assays. However, theoretical 
performance must be balanced by the recognition that there are few, if 
any, recognized reference standards for the analytes or the assays with 
which to assess the performance of proteomic IVDs. The impact of the 
lack of standards may be substantial: Assays that combine the 
measurements of several, if not dozens, of individual analytes into a 
single, actionable ``score'' may require validation of each individual 
analyte separately and in combination. Thus, the objective of this 
public workshop is to obtain feedback from academia, government, 
industry, clinical laboratories, and other stakeholders on the 
development of a regulatory approach that may reduce the burden of 
assay validation while assuring that the assays are safe and effective.

II. Topics for Discussion at the Public Workshop

    We plan to include the following topics at the public workshop.
     State of the art: Current state of proteomic IVD landscape 
and FDA's perspectives;
     Community initiatives: Overview of community (governmental 
and non-governmental) initiatives to help standardize proteomic 
technologies and provide quality control to discovery;
     Success stories: Description of FDA experience in the 
clearance of IVDs that use proteomic technologies, with lessons learned 
and challenges discovered in bringing proteomic-based assays to the 
clinic; and
     Case study open discussion: In an open discussion, FDA 
will present a hypothetical case study that includes assay design and 
validation issues with which FDA has experience. The goal is to 
stimulate discussion with attendees regarding what expectations from 
FDA are reasonable, what validation by manufacturers is possible and 
other challenges inherent in bringing these tests to the clinic and the 
Agency. Possible points of discussion will be solicited from the 
attendees, and may include:
    [cir] How can or should the FDA use community-developed reference 
standards/assays to assess IVD validity?
    [cir] How can manufacturers assess accuracy in a multiplex/
multipeak assay without a reference standard for the analytes?
    [cir] Are there general rules for assay validation that cannot or 
should not be applied to different platforms?
    [cir] How can or should late-stage validation considerations be 
incorporated into early-stage assay development?

    Dated: May 7, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-10787 Filed 5-9-14; 8:45 am]