[Federal Register Volume 85, Number 72 (Tuesday, April 14, 2020)]
[Notices]
[Pages 20696-20698]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-07816]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-3380]


Developing and Labeling In Vitro Companion Diagnostic Devices for 
a Specific Group of Oncology Therapeutic Products; Guidance for 
Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled ``Developing 
and Labeling In vitro Companion Diagnostic Devices for a Specific Group 
of Oncology Therapeutic Products'' and encourages the submission of 
premarket approval application (PMA) supplements containing the needed 
information to modify the intended use of specific companion 
diagnostics as described in this notice (i.e., companion diagnostics 
that identify patients with nonsmall cell lung cancer (NSCLC) whose 
tumors have epidermal growth factor receptor (EGFR) exon 19 deletions 
or exon 21 (L858R) substitution mutations and are suitable for 
treatment with a tyrosine kinase inhibitor approved by FDA for that 
indication). This guidance describes considerations for the development 
and labeling of in vitro companion diagnostic devices (referred to as 
companion diagnostics in this document) to support the indicated uses 
of multiple drug or biologic oncology products (referred to as 
therapeutic products or oncology therapeutic products in this 
document), when appropriate. The guidance includes factors for 
considering when broader labeling (i.e., labeling that is expanded) of 
a companion diagnostic would be appropriate. Oncology companion 
diagnostics with broader indications will optimally facilitate clinical 
use. The guidance announced in this notice finalizes the draft guidance 
entitled ``Developing and Labeling In Vitro Companion Diagnostic 
Devices for a Specific Group or Class of Oncology Therapeutic 
Products'' dated December 2018.

DATES: The announcement of the guidance is published in the Federal 
Register on April 14, 2020.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''

[[Page 20697]]

    Instructions: All submissions received must include the Docket No. 
FDA-2018-D-3380 for ``Developing and Labeling In vitro Companion 
Diagnostic Devices for a Specific Group of Oncology Therapeutic 
Products.'' Received comments will be placed in the docket and, except 
for those submitted as ``Confidential Submissions,'' publicly viewable 
at https://www.regulations.gov or at the Dockets Management Staff 
between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this guidance to the 
Office Policy, Guidance and Policy Development, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 5431, Silver Spring, MD 20993-0002; the Division of 
Drug Information, Center for Drug Evaluation and Research, Food and 
Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th 
Floor, Silver Spring, MD 20993-0002; or the Office of Communication, 
Outreach and Development, Center for Biologics Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 
3128, Silver Spring, MD 20993-0002. Send one self-addressed adhesive 
label to assist that office in processing your requests. See the 
SUPPLEMENTARY INFORMATION section for electronic access to the guidance 
document.
    Submit PMA supplements to the Center for Devices and Radiological 
Health Document Control Center, 10903 New Hampshire Ave., Bldg. 66, Rm. 
G609, Silver Spring, MD 20993-0002.

FOR FURTHER INFORMATION CONTACT: Reena Philip, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3316, Silver Spring, MD 20993-0002, 301-796-6179; 
Julie Schneider, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2208, Silver 
Spring, MD 20993-0002, 240-402-4658; or Stephen Ripley, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a final guidance for industry 
entitled ``Developing and Labeling In vitro Companion Diagnostic 
Devices for a Specific Group of Oncology Therapeutic Products.'' This 
guidance describes considerations for the development and labeling of 
companion diagnostics to support the indicated uses of multiple 
therapeutic oncology products, when appropriate. This guidance builds 
upon existing policy regarding labeling of companion diagnostics. In a 
prior guidance entitled ``In Vitro Companion Diagnostic Devices'' 
(August 2014), the Agency stated that if evidence is sufficient to 
conclude that the companion diagnostic is appropriate for use with a 
specific group of therapeutic products (as discussed in the guidance), 
the companion diagnostic's intended use/indications for use should name 
the specific group, rather than specific products. This guidance 
expands on the policy statement in the 2014 guidance by recommending 
that companion diagnostic developers consider a number of factors, 
including but not limited to those discussed in this guidance, when 
determining whether their test could be developed, or the labeling for 
approved companion diagnostics could be revised through a supplement, 
to support a broader labeling claim such as use with a specific group 
of oncology therapeutic products (rather than listing an individual 
therapeutic product(s)). To describe FDA's thinking on the topic, the 
guidance discusses a specific example of companion diagnostics for a 
specific biomarker, disease, and specimen type (specific epidermal 
growth factor receptor mutations in tumors of patients with nonsmall 
cell lung cancer in tissue specimens).
    Trials designed to support approval of a specific therapeutic 
product and a specific companion diagnostic have led to companion 
diagnostic labels that reference only a specific therapeutic 
product(s). Such specificity in labeling can limit a potentially 
broader use of a companion diagnostic that may be scientifically 
appropriate. In clinical practice, an oncologist generally considers 
the mutation profile of the tumor along with other factors when 
determining the treatment for a patient, such as the toxicity profile 
of the therapeutic product, the patient's preference, and formulary 
options. When a companion diagnostic is labeled for use with a specific 
therapeutic product, the clinician may need to order a different 
companion diagnostic (i.e., one that includes other therapeutic 
products in the labeling), obtain an additional biopsy(ies) from a 
patient, or both, to have additional therapy treatment options.
    The guidance describes considerations for when broader labeling may 
be scientifically appropriate and when it may not. FDA recommends 
developers of therapeutic oncology products and associated companion 
diagnostics collaboratively consider development programs that may 
result in broader labeling of companion diagnostics that are most 
clinically useful. Developers are encouraged to discuss development 
programs that could result in broader labeling with the Center for 
Biologics Evaluation and Research (CBER), Center for Devices and 
Radiological Health (CDRH), or Center for Drug Evaluation and Research, 
in coordination with the Oncology Center of Excellence, as appropriate, 
early to determine if the approach described in this guidance is 
appropriate for consideration.

[[Page 20698]]

Developers whose approved companion diagnostics may be appropriate for 
broader labeling are encouraged to contact CDRH or CBER, as appropriate 
to discuss. Developers of the companion diagnostics discussed in the 
guidance as an example should see the ``Other Issues for 
Consideration'' section of this notice for information regarding 
broader labeling for those companion diagnostics.
    This guidance finalizes the draft guidance entitled ``Developing 
and Labeling In Vitro Companion Diagnostic Devices for a Specific Group 
or Class of Oncology Therapeutic Products'' dated December 2018 (83 FR 
63166). Comments received on the draft guidance were taken into 
consideration when finalizing the guidance. Based on the comments 
received, clarifications were made and information regarding the 
content of broader labeling was added.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Developing and Labeling In Vitro Companion 
Diagnostic Devices for a Specific Group of Oncology Therapeutic 
Products.'' It does not establish any rights for any person and is not 
binding on FDA or the public. You can use an alternative approach if it 
satisfies the requirements of the applicable statutes and regulations.

II. Other Issues for Consideration

    Based on publicly available information, which includes valid 
scientific evidence (i.e., clinical and scientific experience) with 
specific companion diagnostics and the associated therapeutic products, 
FDA has concluded that certain statements set forth in the FDA-approved 
labels of these companion diagnostics, related to intended use with 
therapeutic products, can be modified. The specific companion 
diagnostics are those discussed as an example in the guidance announced 
in this notice (i.e., companion diagnostics that identify patients with 
NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) 
substitution mutations and are suitable for treatment with a tyrosine 
kinase inhibitor approved by FDA for that indication). FDA believes it 
is appropriate for sponsors to consider modifying the intended use of 
these companion diagnostics to describe the specific group of oncology 
therapeutic products, rather than listing individual therapeutic 
product(s). The guidance states that, rather than listing individual 
therapeutic product(s), the intended use for the indication for the 
specific companion diagnostics would be, ``identifying patients with 
NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) 
substitution mutations and are suitable for treatment with a tyrosine 
kinase inhibitor approved by FDA for that indication.'' It is possible 
for the companion diagnostics to also have other indications, not 
captured by the broader indication. FDA encourages the submission of 
PMA supplements, identifying the change and referring to this notice as 
the reason for the change, to request modification of the intended use 
of these companion diagnostics. This broader labeling may enable 
greater flexibility for clinicians in choosing the most appropriate 
therapeutic product based on a patient's biomarker status.
    In the Federal Register document that announced the availability of 
the draft guidance, FDA requested feedback on specific issues, 
including challenges with developing the evidence needed to support 
broader companion diagnostic labeling, challenges with submitting a PMA 
supplement to broaden the labeling of an approved companion diagnostic 
and actions FDA can take to facilitate or encourage broader companion 
diagnostic labeling in oncology. Comments that stakeholders submitted 
to the docket for the draft guidance are generally supportive of the 
concept of broader labeling for companion diagnostics in oncology to 
facilitate the treatment of patients with cancer. To encourage 
implementation of broader labeling of companion diagnostics in 
oncology, FDA is finalizing the guidance and encouraging submission of 
PMA supplements containing the needed information for FDA review of the 
modified labeling of the companion diagnostics discussed in the 
guidance as an example.

III. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information found in FDA regulations and guidance. These collections of 
information are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3521). The collections of information in 21 CFR parts 801 and 809 have 
been approved under OMB control number 0910-0485; the collections of 
information in 21 CFR part 807, subpart E, have been approved under OMB 
control number 0910-0120; the collections of information in 21 CFR part 
814, subparts A through E, have been approved under OMB control number 
0910-0231; the collections of information in 21 CFR part 814, subpart H 
have been approved under OMB control number 0910-0332; the collections 
of information in the guidance document ``Requests for Feedback and 
Meetings for Medical Device Submissions: The Q-Submission Program'' 
have been approved under OMB control number 0910-0756; and the 
collections of information in the guidance ``De Novo Classification 
Process (Evaluation of Automatic Class III Designation)'' have been 
approved under OMB control number 0910-0844.

IV. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics, 
or https://www.regulations.gov.

    Dated: April 8, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-07816 Filed 4-13-20; 8:45 am]
 BILLING CODE 4164-01-P