[Federal Register Volume 73, Number 10 (Tuesday, January 15, 2008)]
[Notices]
[Pages 2504-2507]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-571]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2008N-0007]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Orphan Drugs; Common European Medicines Agency/Food 
and Drug Administration Application Form for Orphan Medicinal Product 
Designation (Form FDA 3671)

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the agency. Under the Paperwork Reduction Act of 1995 
(the PRA), Federal agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on the procedures by which 
sponsors of orphan drugs may request eligibility for the incentives by 
implementing a program as outlined in the Orphan Drug Act and the joint 
adoption by FDA and the European Medicines Agency (EMEA) of the Common 
EMEA/FDA Application Form for Orphan Medicinal Product Designation 
(form FDA 3671).

DATES:  Submit written or electronic comments on the collection of 
information by March 17, 2008.

ADDRESSES:  Submit electronic comments on the collection of information 
to: http://www.fda.gov/dockets/ecomments or http://www.regulations.gov. 
Submit written comments on the collection of information to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should 
be identified with the docket number found in brackets in the heading 
of this document.

FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of the Chief 
Information Officer (HFA-250), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal 
agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined

[[Page 2505]]

in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests 
or requirements that members of the public submit reports, keep 
records, or provide information to a third party. Section 3506(c)(2)(A) 
of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to 
provide a 60-day notice in the Federal Register concerning each 
proposed collection of information, including each proposed extension 
of an existing collection of information, before submitting the 
collection to OMB for approval. To comply with this requirement, FDA is 
publishing notice of the proposed collection of information set forth 
in this document.
    With respect to the collection of information, FDA invites comments 
on these topics: (1) the clarity and ease of use of this proposed 
common application form; (2) whether the proposed collection of 
information is necessary for the proper performance of FDA's functions, 
including whether the information will have practical utility; (3) the 
accuracy of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (4) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (5) ways to minimize the burden of the 
collection of information on respondents, including the use of 
automated collection techniques, when appropriate, and other forms of 
information technology.

Orphan Drugs; Common EMEA/FDA Application Form for Orphan Medicinal 
Product Designation (Form FDA 3671) (OMB Control Number 0910-0167)--
Extension

    Sections 525 and 526 of the Federal Food, Drug, and Cosmetic Act 
(the act) (21 U.S.C. 360aa and 360dd) give FDA statutory authority to 
do the following: (1) Provide recommendations on investigations 
required for approval of marketing applications for orphan drugs, (2) 
designate eligible drugs as orphan drugs, (3) set forth conditions 
under which a sponsor of an approved orphan drug obtains exclusive 
approval, and (4) encourage sponsors to make orphan drugs available for 
treatment on an ``open protocol'' basis before the drug has been 
approved for general marketing. The implementing regulations for these 
statutory requirements have been codified under part 316 (21 CFR part 
316) and specify procedures that sponsors of orphan drugs use in 
availing themselves of the incentives provided for orphan drugs in the 
act and sets forth procedures FDA will use in administering the act 
with regard to orphan drugs. Section 316.10 specifies the content and 
format of a request for written recommendations concerning the non-
clinical laboratory studies and clinical investigations necessary for 
approval of marketing applications. Section 316.12 provides that, 
before providing such recommendations, FDA may require results of 
studies to be submitted for review. Section 316.14 contains provisions 
permitting FDA to refuse to provide written recommendations under 
certain circumstances. Within 90 days of any refusal, a sponsor may 
submit additional information specified by FDA. Section 316.20 
specifies the content and format of an orphan drug application which 
includes requirements that an applicant document that the disease is 
rare (affects fewer than 200,000 persons in the United States annually) 
or that the sponsor of the drug has no reasonable expectation of 
recovering costs of research and development of the drug. Section 
316.26 allows an applicant to amend the applications under certain 
circumstances. Section 316.30 requires submission of annual reports, 
including progress reports on studies, a description of the 
investigational plan, and a discussion of changes that may affect 
orphan status. The information requested will provide the basis for an 
FDA determination that the drug is for a rare disease or condition and 
satisfies the requirements for obtaining orphan drug status. Secondly, 
the information will describe the medical and regulatory history of the 
drug. The respondents to this collection of information are 
biotechnology firms, drug companies, and academic clinical researchers.
    The information requested from respondents represents, for the most 
part, an accounting of information already in the possession of the 
applicant. It is estimated, based on frequency of requests over the 
past 5 years, that 171 persons or organizations per year will request 
orphan-drug designation and none will request formal recommendations on 
design of preclinical or clinical studies.
    The Common EMEA/FDA Application Form for Orphan Medicinal Product 
Designation (form FDA 3671) is intended to benefit sponsors who desire 
to seek orphan designation of drugs intended for rare diseases or 
conditions from both the European Commission and FDA by reducing the 
burden of preparing separate applications to meet the regulatory 
requirements in each jurisdiction. It highlights the regulatory 
cooperation between the United States (US) and the European Union (EU) 
mandated by the Transatlantic Economic Council (TEC). The TEC mandate 
involves the following: (1) Removal of barriers to transatlantic 
commerce; (2) rationalizing, reforming, and, where appropriate, 
reducing regulations to empower the private sector; (3) achieving more 
effective, systematic, and transparent regulatory cooperation to reduce 
costs associated with regulation to consumers and producers; (4) 
removing unnecessary differences between jurisdictional regulations to 
foster economic integration; and (5) reinforcing the existing 
transatlantic dialogue structures in regulatory cooperation, both by 
intensifying our sector-by-sector US-EU regulatory cooperation and our 
dialogue between OMB and the European Commission services on 
methodological issues.
    At present, when seeking orphan designation of the same drug for 
the diagnosis, treatment, or prevention of the same rare disease or 
condition in the US and in the European Community, a sponsor must 
submit a designation request to FDA (in accordance with section 526 of 
the act) and a separate designation application to EMEA (in accordance 
with Regulation (EC) No. 141/2000 of December 16, 1999, and Commission 
Regulation (EC) No. 847/2000). In most cases, the two documents are 
formatted differently to meet regulatory demands, but the required core 
information elements are similar, with the exception of some unique 
regulatory requirements exclusive to each jurisdiction. Therefore, FDA 
and EMEA believe that a common application form will help reduce the 
sponsor's regulatory burden and costs to produce and submit 
differently-formatted request/application. In addition, a common 
application form may also streamline the administrative and substantive 
regulatory review processes, and aid in information exchange between 
the agencies. In accordance with the Confidentiality Arrangements 
concluded on September 12, 2003, between the European Commission, EMEA, 
and FDA/Department of Health and Human Services (DHHS),\1\ FDA and EMEA 
have agreed in principle to adopt a template for the common application 
form as proposed in form FDA 3671.
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    \1\ See ``Confidentiality Arrangements Concluded Between the EU 
(EC and EMEA) and the US FDA/DHHS Implementation Plan for Medicinal 
Products for Human Use'' at http://www.fda.gov/oia/arrangements0904.html.
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    Any sponsor seeking orphan designation of the same drug for the 
same disease or condition from both FDA and EMEA may use this common 
application form for regulatory filing purposes. A sponsor may also use 
this

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common application form when seeking designation only from FDA. This 
common application form is intended to complement, not to supersede, 
the relevant regulatory frameworks currently in effect. The sponsor 
must comply with all applicable regulatory requirements in each 
jurisdiction in which it seeks designation when using this common 
application form.
    To use the common application form, the sponsor must provide the 
required information in each applicable section as instructed in the 
explanatory notes. Certain information elements are identified in the 
form as required exclusively by either FDA or EMEA regulations, and as 
such they must be included only in the application to that 
jurisdiction. Where additional explanations and/or supportive documents 
are necessary, the sponsor should sequentially append them at the end 
of the common application form in the order they appear in the form. 
The sponsor must also complete the declaration and signature page. For 
FDA, the completed common application form and required appended 
documents must be submitted to the Office of Orphan Products 
Development (HF-35), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857. For EMEA, the completed documents must be 
submitted to European Medicines Agency, 7 Westferry Circus, Canary 
Wharf, London E14 4HB, United Kingdom.
    FDA estimates the reporting burden of this common application form 
as follows. Between January 2000 and May 2006, FDA and EMEA received 
226 comparable orphan designation requests/applications of the same 
drugs for the same diseases or conditions, or an average of 35 per 
year. With the ease of a common application form, FDA anticipates the 
number of such requests/applications may increase over time. Therefore, 
generally there is one request/application per respondent and, at the 
extreme, all respondent are US-based, FDA believes up to 40 such 
respondents may use the common application form each year. The 
respondents will be primarily pharmaceutical companies or other for-
profit organizations. For applications submitted exclusively to FDA, we 
do not believe the new form will result in any increased burden on the 
respondents and therefore we estimate no additional burden for those 
respondents. FDA believes the information required for the EMEA 
submission, for the most part, is very similar to that in the FDA 
submission, which is already in the respondents' possession. The 
respondents, however, may have to search existing data sources or 
gather additional needed data, such as on the prevalence or the 
availability of alternative methods of diagnosis, prevention, and 
treatment of the rare disease or condition of interest in the European 
Community, to complete the EMEA submission. FDA estimates that it will 
take an additional 32 hours--16 hours of professional time and 16 hours 
of support time--to compile information required for the EMEA 
submission. Hence, the estimated total annual human resource hours, at 
most, would be 1,280 hours for the EMEA submission.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1.--Estimated Annual Reporting Burden\1\
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                                                          Annual No. of    Annual Frequency per     Total Annual        Hours per
              21 CFR Section and FDA Form                  Respondents            Response           Responses           Response         Total Hours
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316.10,                                                                 5                     1                  5                130                650
316.12,
316.14
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316.20,                                                               171                   2.0                342                130             44,460
316.21,
316.26
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316.20,                                                                40                     1                 40                 32              1,280
316.21,
316.26
                                                        .................  ....................  .................  .................  .................
Form FDA 3671
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316.22                                                                 30                     1                 30                  2                 60
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316.30                                                                500                     1                500                  2              1,000
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316.36                                                                 .2                     3                 .6                 15                  9
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Total                                                                                                                                             47,559
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.


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    Please note that in January 2008, the FDA Web site is expected to 
transition to the Federal Dockets Management System (FDMS). FDMS is a 
Government-wide, electronic docket management system. After the 
transition date, electronic submissions will be accepted by FDA through 
the FDMS only. When the exact date of the transition to FDMS is known, 
FDA will publish a Federal Register notice announcing that date.

    Dated: January 7, 2008.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E8-571 Filed 1-14-08; 8:45 am]
BILLING CODE 4160-01-S