[Federal Register Volume 83, Number 114 (Wednesday, June 13, 2018)]
[Notices]
[Pages 27605-27609]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-12632]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-1307]


Drug and Device Manufacturer Communications With Payors, 
Formulary Committees, and Similar Entities--Questions and Answers; 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a guidance for industry entitled ``Drug and Device 
Manufacturer Communications With Payors, Formulary Committees, and 
Similar Entities--Questions and Answers.'' This guidance provides 
answers to common questions regarding the communication of health care 
economic information (d) about approved prescription drugs and approved 
or cleared medical devices by medical product manufacturers, packers, 
distributers, and their representatives (firms) to payors, formulary 
committees, or other similar entities with knowledge and expertise in 
the area of health care economic analysis (collectively referred to as 
payors). This guidance also provides answers to common questions about 
both firms' dissemination of information to payors about medical 
products that are not yet approved or cleared for any use and firms' 
dissemination of information to payors about unapproved uses of 
approved or cleared medical products. The Agency is issuing this 
guidance to explain FDA's current thinking on frequently asked 
questions regarding these topics in order to provide clarity for firms 
and payors. FDA is also announcing that a proposed collection of 
information has been submitted to the Office of Management and Budget 
(OMB) for review and clearance under the Paperwork Reduction Act of 
1995.

DATES: The announcement of the guidance is published in the Federal 
Register on June 13, 2018. Submit written comments on the collection of 
information by July 13, 2018.

ADDRESSES: To ensure comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
Fax: 202-395-7285, or emailed to [email protected]. All 
comments should be identified with the OMB control number 0910-New and 
title ``Recommendations for Drug and Device Manufacturer Communications 
With Payors, Formulary Committees, and Similar Entities.'' Also include 
the FDA docket number found in brackets in the heading of this 
document.
    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

[[Page 27606]]

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.''
    Instructions: All submissions received must include the Docket No. 
FDA-2016-D-1307 for ``Drug and Device Manufacturer Communications With 
Payors, Formulary Committees, and Similar Entities--Questions and 
Answers; Guidance for Industry; Availability.'' 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 
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; 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; or to 
the Office of Communication, Education and Radiation Programs, Division 
of Small Manufacturers, International and Consumer Assistance, Center 
for Devices and Radiological Health, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 66, Rm. 4613, 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.

FOR FURTHER INFORMATION CONTACT: 
    Regarding the guidance: Kristin Davis, Office of Policy, Office of 
the Commissioner, 10903 New Hampshire Ave., Bldg. 32, Rm. 4252, Silver 
Spring, MD 20993-0002, 301-796-0418; Sheila Ryan, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 3320, Silver Spring, MD 20993-0002, 301-
796-1200; 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; or Ana Loloei Marsal, 
Center for Devices and Radiological Health, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5452, Silver 
Spring, MD 20993-0002, 301-796-8774.
    Regarding the information collection: Domini Bean, Office of 
Operations, Food and Drug Administration, Three White Flint North, 
11601 Landsdown St., 10A-12M, North Bethesda, MD 20852, 301-796-5733, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry and 
review staff entitled ``Drug and Device Manufacturer Communications 
With Payors, Formulary Committees, and Similar Entities--Questions and 
Answers.'' This guidance provides answers to common questions regarding 
firms' communications of HCEI about their approved prescription drugs 
to payors. The guidance also provides answers to common questions 
regarding firms' communications of HCEI about their approved or cleared 
medical devices to payors. In addition, the guidance addresses common 
questions relating to firms' dissemination to payors of information 
about medical products \1\ that are not yet approved or cleared for any 
use and about unapproved uses of approved/cleared medical products. For 
purposes of this guidance, the term ``payors'' collectively refers to 
payors, formulary committees, or other similar entities with knowledge 
and expertise in the area of health care economic analysis that are 
responsible for making product selection or acquisition, formulary 
management, and/or coverage and reimbursement decisions on a population 
basis regarding drugs and/or devices on behalf of health care 
organizations, which may include entities such as integrated health 
care delivery networks, hospitals, and hospital systems.
---------------------------------------------------------------------------

    \1\ The term ``medical product'' refers to both drugs and 
devices.
---------------------------------------------------------------------------

    FDA is aware that payors seek a range of information on 
effectiveness, safety, and cost-effectiveness of approved/cleared 
medical products, including information from firms, to help support 
their medical product selection, formulary management, and/or coverage 
and reimbursement decisions on a

[[Page 27607]]

population basis. This information may differ from and may be in 
addition to the information FDA reviews in order to make drug and 
device approval or clearance decisions. Because coverage and 
reimbursement decisions by payors impact many patients, FDA believes it 
is critical that HCEI provided by firms to payors about their approved 
drugs and approved/cleared devices be truthful and non-misleading.
    With respect to HCEI regarding approved drugs, section 502(a) of 
the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 352(a)), 
as amended by section 114 of the Food and Drug Administration 
Modernization Act of 1997 (Pub. L. 105-115) and section 3037 of the 
21st Century Cures Act (Pub. L. 114-255), includes a provision 
regarding communication of HCEI about such drugs to payors. Section 
502(a) of the FD&C Act indicates that HCEI provided to payors carrying 
out their responsibilities for the selection of drugs for coverage or 
reimbursement shall not be considered to be false or misleading if the 
HCEI relates to an FDA-approved indication for the drug, is based on 
competent and reliable scientific evidence, and includes, where 
applicable, a conspicuous and prominent statement describing any 
material differences between the health care economic information and 
the FDA-approved labeling for the drug. Section III.A of this guidance 
provides FDA's current thinking on key concepts in section 502(a) of 
the FD&C Act and recommendations for how firms can communicate HCEI 
about approved drugs to payors in accordance with this section to help 
ensure that payors have information needed to make informed drug 
selection, formulary management, and/or coverage and reimbursement 
decisions and to help ensure that the information is not false or 
misleading. Section III.A also discusses how FDA's requirements for 
submission of promotional materials apply to HCEI about approved drugs 
disseminated by firms to payors. If a firm disseminates HCEI about an 
approved drug in accordance with this guidance, FDA does not intend to 
consider such information false or misleading. In addition, FDA does 
not intend to use HCEI about approved drugs disseminated consistent 
with this guidance as evidence of a new intended use.
    When FDA published a notice announcing the availability of the 
draft guidance document in the Federal Register of January 19, 2017 (82 
FR 6568), the Agency specifically requested comments from interested 
parties on the extent to which the principles provided in section III.A 
of the draft guidance could be applicable to communications of HCEI 
about approved/cleared devices (82 FR 6568 at 6571). We also stated 
that, to the extent that interested parties believe that different 
considerations should apply to medical devices or that guidance is 
needed on additional issues with respect to medical device firms' 
communications of HCEI about approved/cleared medical devices to 
payors, FDA is interested in input on those topics as well (Id.). FDA 
received 23 comments on the draft guidance; 3 comments expressed 
support for applying the recommendations in section III.A of the 
guidance to medical devices and no comments opposed applying these 
recommendations to medical devices. In response to this feedback, 
section III.B of the guidance provides FDA's recommendations for how 
firms can communicate HCEI about approved or cleared devices to payors 
to help ensure that device firms' communication of HCEI to payors is 
not false or misleading. These recommendations generally follow the 
recommendations in section III.A of the guidance. If a device firm 
disseminates HCEI about an approved or cleared device in accordance 
with this guidance, FDA does not intend to consider such information 
false or misleading. In addition, FDA does not intend to use HCEI about 
approved or cleared devices disseminated consistent with this guidance 
as evidence of a new intended use.
    FDA also recognizes that due in part to their need, in some 
situations, to plan for and make coverage and reimbursement decisions 
far in advance of the effective date of such decisions, payors are also 
interested in receiving information from drug and device firms about 
medical products that are not yet approved or cleared by FDA for any 
use, and about unapproved uses of approved/cleared medical products. 
Section III.C of the guidance discusses FDA's thinking with respect to 
communication by firms to payors of information about unapproved 
products \2\ and about unapproved uses of approved/cleared medical 
products. The draft guidance provided similar recommendations, but the 
relevant section only addressed communications related to unapproved 
products. As noted above, FDA received 23 comments on the draft 
guidance; 17 of these comments requested that the Agency also provide 
recommendations for firms' communications to payors of information 
about unapproved uses of approved/cleared medical products. No comments 
opposed providing recommendations on this topic. In response to these 
comments, section III.C of this guidance provides FDA's recommendations 
on firms' dissemination to payors of information about both unapproved 
products and about unapproved uses of approved/cleared medical 
products. As with firms' communications to payors of HCEI about 
approved prescription drugs and approved or cleared devices, it is 
essential that information provided by firms about their unapproved 
products and about unapproved uses of their approved/cleared medical 
products be truthful and non-misleading. Therefore, section III.C also 
lays out a series of recommendations to help achieve these goals.
---------------------------------------------------------------------------

    \2\ As used in this guidance, the term ``unapproved products'' 
refers to drugs and devices that are not yet approved/cleared by FDA 
for any use (but which must be approved/cleared to be legally 
marketed), including products for which firms have submitted or plan 
to submit a new drug application, a biologics license application 
(including an application submitted under the 351(k) pathway), an 
abbreviated new drug application, a premarket approval application, 
a 510(k) submission, a De Novo submission under section 513(f)(2) of 
the FD&C Act (21 U.S.C. 360c(f)(2)), or a Humanitarian Device 
Exemption application.
---------------------------------------------------------------------------

    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 drug and device manufacturer communications 
with payors, formulary committees, and similar entities. 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. This guidance 
is not subject to Executive Order 12866.

II. Paperwork Reduction Act of 1995

    In compliance with 44 U.S.C. 3507, FDA has submitted the following 
proposed collection for OMB review and clearance:
    Title: Recommendations for Drug and Device Manufacturer 
Communications With Payors, Formulary Committees, and Similar Entities; 
OMB Control No. 0910--NEW.
    The information collection supports Agency guidance and includes 
Third-Party Disclosure recommendations regarding information that firms 
should include in HCEI for prescription drugs if they choose to 
disseminate such materials (``HCEI materials'') to payors, in 
accordance with section 502(a) of the FD&C Act. Specifically, FDA 
recommends that various aspects of study design and methodology of an 
economic analysis (i.e., type of analysis, modeling technique, patient 
population, perspective/viewpoint, treatment

[[Page 27608]]

comparator, time horizon, outcome measures, cost estimates, and 
assumptions); factors that limit generalizability of an economic 
analysis; limitations to an economic analysis; and sensitivity 
analyses, if applicable, be included in HCEI materials disseminated to 
payors to allow for informed decision-making.
    Furthermore, FDA recommends that firms include other information 
when disseminating HCEI materials, as applicable, to provide a balanced 
and complete presentation. Such information includes a statement of the 
FDA-approved indication of the drug and a copy of the most current FDA-
approved labeling. Under section 502(a) of the FD&C Act, firms must 
also include a conspicuous and prominent statement to describe any 
material differences between the HCEI and the FDA-approved labeling. 
HCEI materials should also disclose whether certain studies or data 
sources were omitted from an economic analysis and how the omission of 
those studies or data sources may alter the conclusions presented in 
the analysis. Moreover, FDA recommends that HCEI materials disclose 
important risk information associated with the approved use of the 
drug, and pursuant to section 502(a) of the FD&C Act, must disclose any 
additional risk information related to assumptions that vary from the 
approved labeling. Finally, HCEI materials should disclose potential 
financial or affiliation biases to the extent reasonably known by firms 
at the time of dissemination.
    The guidance provides similar recommendations for HCEI materials 
disseminated to payors about approved or cleared devices.
    If firms choose to make communications to payors about unapproved 
products or unapproved uses of approved/cleared products, FDA 
recommends that firms include a clear statement with their 
communications that the product or use is not approved/cleared and that 
the safety or effectiveness of the product or use has not been 
established. In addition, FDA recommends providing information related 
to the stage of product development (e.g., the status of any study(ies) 
in which a product/new use is being investigated and how it relates to 
the overall product development plan; whether a marketing application 
for the product or new use has been submitted to FDA or when such a 
submission is planned). FDA also recommends that communications that 
include factual presentations of results from studies also describe 
material aspects of study design and methodology and disclose material 
limitations related to the study design, methodology, and results. 
Moreover, FDA recommends that firms provide followup information to 
payors if previously communicated information becomes materially 
outdated as a result of significant changes or as a result of new 
information regarding the product or its review status.
    Description of Respondents: For information that should be included 
when HCEI about approved prescription drugs is disseminated to payors, 
respondents to this collection of information are firms that 
manufacture prescription human drugs products, including biological 
products; for information that should be included when HCEI about 
approved or cleared medical devices is disseminated to payors, 
respondents to this collection of information are firms that 
manufacture medical devices; for information that should be included in 
communications with payors about unapproved products and about 
unapproved uses of approved/cleared products, respondents to this 
collection of information are firms that manufacture prescription human 
drug products, including biological products, and medical devices.
    As noted, in the Federal Register of January 19, 2017, we published 
a notice announcing the availability of the draft guidance document and 
included an analysis under the PRA of the information collection burden 
associated with recommendations found in the draft guidance. Although 
no comments were received in response to the four information 
collection topics solicited in the notice, we revised the guidance as 
discussed above. These revisions resulted in a significant increase to 
the number of respondents to the information collection and also 
recommended new data elements. However, because our estimate reflects 
the average burden of the information collection distributed among all 
respondents, we believe any increase resulting from revisions to the 
guidance would be nominal.
    Based on the post-marketing submissions of promotional materials 
using Form FDA 2253 received in calendar year 2016 for approved human 
prescription drugs, including prescription biological products, FDA 
estimates that approximately 440 manufacturers will disseminate 4,400 
distinct HCEI materials for approved human prescription drugs annually. 
FDA estimates that approximately 236 manufacturers will disseminate 
2,360 distinct HCEI materials for approved/cleared devices annually. 
FDA estimates it will take firms approximately 20 hours to compile and 
draft the information that this final guidance recommends should be 
included when disseminating HCEI materials for approved human 
prescription drugs and approved/cleared devices. Based on the number of 
human prescription drugs and devices approved/cleared and the number of 
efficacy supplements approved/cleared (i.e., approving/clearing a new 
use for an approved/cleared product) in a calendar year, FDA estimates 
that approximately 717 manufacturers will prepare 1,434 distinct 
communications of information to payors about their unapproved products 
or unapproved uses of approved/cleared products annually. FDA estimates 
it will take firms approximately 0.5 hour to compile and draft the 
information that this final guidance recommends should be provided with 
communications to payors about unapproved products or unapproved uses 
of approved/cleared products. Additionally, FDA estimates that 50 
percent of the firms will spend approximately 2 hours to compile and 
provide 718 distinct communications of followup information regarding 
previously communicated information to payors about their unapproved 
products or unapproved uses of approved/cleared products annually. We 
therefore estimate the burden of the information collection as follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                 Number of                      Average  burden
     Type of information         Number of     responses per   Total annual      per  response      Total hours
                                respondents     respondent       responses          (hours)
----------------------------------------------------------------------------------------------------------------
Recommended information to               440              10           4,400  20................          88,000
 be included when firms
 choose to disseminate HCEI
 materials to payors about
 approved prescription drugs.

[[Page 27609]]

 
Recommended information to               236              10           2,360  20................          47,200
 be included when firms
 choose to disseminate HCEI
 materials to payors about
 approved or cleared medical
 devices.
Recommended information to               717               2           1,434  .5 (30 minutes)...             717
 be included when firms
 choose to disseminate
 information about
 unapproved products or
 unapproved uses of approved
 or cleared products.
Followup information to                  359               2             718  2.................           1,436
 payors regarding previously
 communicated about
 unapproved products or
 unapproved uses of approved
 or cleared products.
                             -----------------------------------------------------------------------------------
    Total...................  ..............  ..............  ..............  ..................         137,353
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    This guidance also refers to previously approved collections of 
information found in FDA regulations. The collections of information in 
21 CFR 314.81(b)(3)(i) (Form FDA 2253) have been approved under OMB 
control number 0910-0001.
    FDA is issuing this final guidance subject to OMB approval of the 
collections of information. Before implementing the information 
collection provisions of the guidance, FDA will publish a notice in the 
Federal Register announcing OMB's decision to approve, modify, or 
disapprove the collections of information, including OMB control 
number(s) for newly approved collections.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm, or https://www.regulations.gov.

    Dated: June 7, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-12632 Filed 6-12-18; 8:45 am]
 BILLING CODE 4164-01-P