[Federal Register Volume 70, Number 58 (Monday, March 28, 2005)]
[Notices]
[Pages 15633-15635]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-5978]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005N-0098]


Food and Drug Administration/Drug Information Association Cross 
Labeling; Public Meeting; Combination Products and Mutually Conforming 
Labeling

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public meeting; request for comments.

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SUMMARY: The Food and Drug Administration (FDA), in cooperation with 
the Drug Information Association (DIA), is announcing a public meeting 
to solicit views and provide an interactive forum for discussion of 
stakeholders' perspectives about, and experiences with, the legal and 
public health issues that arise when sponsors seek to develop or market 
a product of one type (device, drug, or biological product) that would 
be labeled for use with an already approved product of a different 
type, and the approved product's labeling would not be changed. The 
input received at the meeting and comments made to the docket after the 
meeting will be considered in developing draft guidance on this topic.

DATES: The public meeting will be held on May 10, 2005, from 8:30 a.m. 
to 5 p.m. Attendees must register to attend. Submit written or 
electronic requests to speak at the public meeting by April 26, 2005. 
Submit written or electronic comments by July 8, 2005.

ADDRESSES: The public meeting will be held at the Bethesda North 
Marriott Hotel & Conference Center, 5701 Marinelli Rd., North Bethesda, 
MD. A copy of the meeting's program and registration information is 
available on the Internet athttp://www.diahome.org/Content/Events/05028.pdf, by contacting the Drug Information Association, P.O. Box 
827192, Philadelphia, PA 19182-7192, or 215-442-6100.
    Submit written comments to the Division of Dockets Management (HFA-
305, Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT:
    For information about the public meeting contact: Suzanne O'Shea, 
Office of Combination Products, Food and Drug Administration (HFG-3), 
suite 200, 15800 Crabbs Branch Way, Rockville, MD 20855, 301-427-1934, 
FAX: 301-427-1935, e-mail: [email protected].
    To register to speak at the public meeting contact: Amanda Carmody, 
Drug Information Association, P.O. Box 827192, Philadelphia, PA 19182-
7192, e-mail: [email protected], or 215-442-6176.

SUPPLEMENTARY INFORMATION:

I. Background

    An increasing number of combined uses for drugs and devices, drugs 
and biological products, or devices and biological products are being 
developed where the two products are independently approved, 
manufactured, and distributed. In some cases, when one product is 
already approved for a particular indication, route of administration 
or dose, another sponsor may develop a separate product to be used with 
the approved product for an indication, route of administration or dose 
different from the one specified in the current labeling of the 
approved product. Frequently, the sponsors of the two products work 
together to develop safety and effectiveness data and to bring the two 
products to market with mutually conforming labeling, i.e., labeling 
for each product that provides directions for using that product with 
the other sponsor's product. In such cases, the two products are 
considered a combination product under Sec.  3.2(e)(3) (21 CFR 
3.2(e)(3)), which states that a combination product includes:
    A drug, device, or biological product packaged separately that 
according to its investigational plan or proposed labeling is 
intended for use only with an approved individually specified drug, 
device, or biological product where both are required to achieve the 
intended use, indication, or effect and where upon approval of the 
proposed product the labeling of the approved product would need to 
be changed, e.g., to reflect a change in intended use, dosage form, 
strength, route of administration, or significant changed in dose* * 
*.
    In order for the two products to have mutually conforming labeling 
of the type contemplated by Sec.  3.2(e)(3), the sponsor of the 
approved product ordinarily must submit a supplement to its marketing 
application\1\ to amend the currently approved labeling to include 
directions for using the two products together. When sponsors work 
together to develop mutually conforming labeling, they usually have an 
ongoing relationship that enables them to resolve scientific or legal 
issues that may arise as a result of the two products being the 
responsibility of two independent sponsors. For this reason, FDA 
encourages sponsors to work together as much as possible when bringing 
to market independently developed, manufactured, and distributed 
products that are intended to be used together.
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    \1\ In some cases, a new 510(k) might be required.
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    On occasion, however, the two sponsors do not work together, and 
the sponsor of a new product unilaterally develops a product intended 
to be used with an already approved or cleared product. The sponsor of 
the new product is frequently willing to develop data demonstrating the 
safe and effective use of both products used together. When the new 
product is intended to be used with the approved product in a way that 
is significantly different from ways described in the current labeling 
of the approved product (e.g., for a different indication, route of 
administration or dose), refusal by the sponsor of the approved product 
to submit a supplement\2\ may preclude mutually conforming labeling. In 
some cases, when the two sponsors do not work together, requiring that 
the two products have mutually conforming labeling could prevent the 
development of new products. FDA is concerned that valuable products 
may not be developed, manufactured, or distributed because of sponsor 
concerns about mutually conforming labeling.
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    \2\ Or in some cases, a new 510(k).
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    Therefore, FDA is considering whether the agency should review and 
approve or clear drug-device, biologic-device, or drug-biologic 
products, where:
     One sponsor's new product is intended for use with another 
sponsor's approved or cleared product;
     The approved or cleared product would be used in a way 
that is significantly different from the use described in its current 
labeling, e.g., a different indication, route of administration, or 
dose;
     Data are available to demonstrate the safe and effective 
use of the two products together;
     There is no cooperation, ongoing relationship, or right of 
reference between the sponsors of the two products; and
     The sponsor of the new product asks FDA to review the new 
product for use with the approved product under

[[Page 15634]]

one drug, device, or biological product marketing application, 
depending on the regulatory identity of the new product.
    In this situation, the sponsor of the approved product would not 
submit a supplement to its marketing application, or in some cases a 
new 510(k), to permit the inclusion of directions for using the 
approved product together with the new product. If the new product were 
to be approved or cleared, the labeling of the new product would 
provide directions for using the two products together, but the 
labeling of the approved product would not mention the new product or 
the use of the two products together. In other words, the two products 
would not be cross labeled and would not have mutually conforming 
labeling.

II. Hypothetical Situation

    The following hypothetical is a concrete example of the type of 
situation that may be of most interest at the public meeting:
    Company A\3\ is currently marketing an approved drug product for 
intramuscular injection. Company B develops a device to deliver Company 
A's approved drug product for a different indication, to be delivered 
by a different method. No change in formulation to the drug product is 
needed.
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    \3\ Companies A and B could be drug, device, or biological 
product companies. The two products that will be used together could 
be a drug and a device, a drug and a biological product, or a 
biological product and a device. For the sake of convenience only, 
this hypothetical refers to Company A as the manufacturer of an 
already approved drug, and Company B as the sponsor of a device to 
be used with drug product A.
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    Company B approached Company A to see if Company A would submit a 
supplemental new drug application to include the new indication and 
route of administration in the drug product labeling, but Company A 
refused. Company A also refused to provide a right of reference to data 
in its application.
    Because Company B has been unable to obtain the cooperation of 
Company A, Company B approaches FDA and asks whether FDA would consider 
approving a device application stating that the device is intended to 
be used with drug product A delivered by the new route of 
administration for the new indication. Company B is willing to conduct 
all necessary studies to demonstrate that drug product A is safe and 
effective when delivered by the new route of administration by device B 
for the new indication.
    The end user would obtain the device from Company B and the drug 
product from Company A. The drug product labeling would make no mention 
of device B, the new indication, or that the drug product can be 
delivered by the new route of administration.

III. Proposed Issues

    The core issue is whether FDA should consider reviewing and 
possibly approving or clearing a new product (such as product B in the 
hypothetical) labeled for use in conjunction with an approved product 
(such as product A in the hypothetical) when there is no supplement for 
the combined use to the marketing application for the approved 
product,\4\ and the labeling of the approved product would not mention 
the new product, or the use of the two products together. FDA has 
identified the following issues as being relevant to the core issue. 
Persons wishing to speak at the public meeting may address the 
following issues or other relevant issues.
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    \4\ Or in some cases, a new 510(k).
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A. Public Health Issues

    1. What are the product development implications of mutually 
conforming labeling? Are products not developed because of a perception 
that mutually conforming labeling will be, or might be, required?
    2. How important is it that drug and device labeling be consistent 
with respect to intended use, dose, dosage form, strength and route of 
administration for the safe and effective use of the drug and device 
together?
    3. Should the decision whether mutually conforming labeling is 
needed for the safe and effective use of the products together be made 
on a case by case basis? If so, what factors should FDA consider in 
determining whether mutually conforming labeling is necessary?
    4. To what degree should labeling conform? Does the labeling of the 
two products need to be identical? Consistent? Not contradictory? Is 
conformity more important for some parts of the labeling than others?
    5. Under what circumstances can adequate instructions for use be 
conveyed in one product's label? For example, should FDA policy take 
into account the possibility that the labeling for a re-usable device 
might be lost over time?
    6. How should FDA policy take into account the possibility that the 
product for which no supplemental marketing application was submitted 
(i.e., the approved product) might be reformulated or redesigned? Is it 
possible for Company B to sufficiently monitor product A to ensure that 
Company B is aware of formulation changes? Is it possible to identify 
in advance the characteristics of product A that should be monitored?
    7. If mutually conforming labeling is not always required, what 
process should FDA follow in order to determine when it is required and 
when it is not required? When is the best time in the review process to 
make this determination?
    8. Other public health issues; how can they be resolved?

B. Legal Issues

    1. Why do manufacturers of the two products sometimes not cooperate 
in bringing the new product to market? Are there any steps FDA can take 
to increase the likelihood of cooperation between the two 
manufacturers?
    2. How can FDA ensure that its approval of Company B's product does 
not improperly rely upon Company A's proprietary information?
    3. How might approval of Company B's product affect the legal 
adequacy of the labeling for Company A's product?
    4. What effect, if any, should the exclusivity of Company A's 
product have on whether FDA approves Company B's product without 
mutually conforming labeling? Should the existence of generic versions 
of Company A's product affect whether FDA approves Company B's product?
    5. Would any other regulatory tools, such as conditions of approval 
on Product B, be useful in ensuring the appropriate degree of FDA 
oversight of the products used together?
    6. Do the legal issues that arise in the absence of mutually 
conforming labeling exist independently of Sec.  3.2(e)(3), or can some 
of these issues be addressed by revisions or clarifications to this 
part of the definition of a combination product?
    7. Other legal issues; how can they be resolved?

IV. Goals of the Public Meeting

    The purpose of this public meeting is to provide an interactive 
forum for discussion of FDA and industry perspectives about, and 
experiences with, the legal and public health issues that arise when 
sponsors seek to develop or market a product of one type (device, drug, 
or biological product) that would be labeled for use with an approved 
product of a different type and the approved product's labeling would 
not be changed.
    The public meeting will be divided into two sections. Public health 
issues will be discussed in one session; legal issues will be discussed 
in the other session. Each session will begin with

[[Page 15635]]

formal presentations from members of industry and FDA. Following the 
formal presentations, time will be allotted to hear from members of the 
public who have pre-registered as speakers. After the pre-registered 
speakers, there will be a moderated discussion open to all members of 
the audience.
    FDA is considering issuing draft guidance on this issue and 
believes it is important to receive input from all interested parties 
through a public meeting.

V. Speakers

    Members of the public who would like to make a short statement 
(approximately 5 minutes) should register with DIA (see ADDRESSES) by 
April 26, 2005. Requests to speak should include the speaker's name and 
affiliation, and should identify the appropriate panel (public health 
or legal issues). DIA will notify persons who register by April 26, 
2005, of the approximate time of their turn to speak. Speakers will be 
scheduled in the order DIA receives the requests.
    If you need special accommodations due to a disability, please 
contact, at least 7 days in advance: Amanda Carmody, Drug Information 
Association, at [email protected] or 215-442-6176.

VI. Request for Comments and Transcripts

    Regardless of attendance at the meeting, interested persons may 
submit to the Division of Dockets Management (see ADDRESSES) written or 
electronic comments on the topics presented in this document. The 
agency welcomes comments before and after the meeting. Two paper copies 
of mailed comments are to be submitted, except that individuals may 
submit one paper copy. Comments are to be identified with the docket 
number found in brackets in the heading of this document. Received 
comments are available for public examination in the Division of 
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday. 
Comments and a transcript of the public meeting will be made available 
on the Office of Combination Products Web site at www.fda.gov/oc/combination.

    Dated: March 21, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-5978 Filed 3-25-05; 8:45 am]
BILLING CODE 4160-01-S