Notice: Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Orphan Drugs; Common 
European Medicines Agency/Food and Drug Administration Application Form 
for Orphan Medicinal Product Designation (Form FDA 3671)

Federal Register: April 30, 2008 (Volume 73, Number 84)          
                  Page 23468-23470

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

SUMMARY: The Food and Drug Administration (FDA) is 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:  Fax written comments on the collection of information by May 
30, 2008.

ADDRESSES:  To ensure that 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: 202-395-6974, or e-mailed to baguilar@omb.eop.gov. All comments 
should be identified with the OMB control number 0910-0167. Also 
include the FDA 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: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Orphan Drugs; Common European Medicines Agency/Food and Drug 
Administration 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

[[Page 23469]]

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.
---------------------------------------------------------------------------

    \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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/oia/arrangements0904.html. 
---------------------------------------------------------------------------

    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 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.
    In the Federal Register of January 15, 2008 (73 FR 2504), FDA 
published a 60-

[[Page 23470]]

day notice requesting public comment on the information collection 
provisions. No comments were received.

                                                     Table 1.--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                          Annual No. of    Annual Frequency per     Total Annual        Hours per
              21 CFR Section and FDA Form                  Respondents            Response           Responses           Response         Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
316.10, 316.12, and 316.14                                              5                     1                  5                130                650
--------------------------------------------------------------------------------------------------------------------------------------------------------
316.20, 316.21, and 316.26                                            171                   2.0                342                130             44,460
--------------------------------------------------------------------------------------------------------------------------------------------------------
316.20, 316.21, and 316.26                                             40                     1                 40                 32              1,280
Form FDA 3671
--------------------------------------------------------------------------------------------------------------------------------------------------------
316.22                                                                 30                     1                 30                  2                 60
--------------------------------------------------------------------------------------------------------------------------------------------------------
316.27                                                                 25                     1                 25                  4                100
--------------------------------------------------------------------------------------------------------------------------------------------------------
316.30                                                                500                     1                500                  2              1,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
316.36                                                                  1                     1                  1                 15                 15
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total                                                                                                                                             47,565
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: April 23, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-9467 Filed 4-29-08; 8:45 am]

BILLING CODE 4160-01-S