0167 ss 12-2020 final

Orphan Products Development; Food and Drug Administration Orphan Drug
Designation
OMB No. 0910-0167
SUPPORTING STATEMENT
A. Justification
1. Circumstances Making the Collection of Information Necessary
This is a request for OMB approval of the information collection requirements in the
Orphan Drug Regulations, 21 CFR Part 316. These provisions implement sections
525 through 528 of the Orphan Drug Act Amendments to the Food, Drug, and
Cosmetic Act. These regulations specify the procedures for sponsors of orphan drugs
to use in obtaining the incentives provided for in the Act and set forth the procedures
that FDA will use in administering the Act.
Section 525 of the Act (21 USC 360aa) requires the Agency to provide written
recommendations on studies required for approval of a marketing application for a
drug for a rare disease or condition. Section 526 of the Act (21 USC 360bb) provides
for designation of drugs as orphan drugs when certain conditions are met. Section 527
of the Act (21 USC 360cc) provides conditions under which a sponsor of an approved
orphan drug enjoys exclusive FDA marketing approval for that drug for the orphan
indication for a period of seven years.
Section 528 of the Act (21 USC 360dd) is to encourage sponsors to make
investigational orphan drugs available for treatment of persons in need on an open
protocol basis before the drug has been approved for general marketing. Open
protocols may permit patients who are not part of the formal clinical investigation to
obtain treatment where adequate supplies exist and no alternative effective therapy is
available.
These regulations describe the information to be submitted by sponsors to request
eligibility for the incentives by implementing a program as outlined in the Orphan
Drug Act. The following provisions identify the information collections contained in
the regulation.
We are consolidating into this request for approval 0910-0787, “Guidance for
Industry, Researchers, Patient Groups, and Food and Drug Administration Staff on
Meetings With the Office of Orphan Products Development”. The guidance describes
three collections of information: (1) The submission of a meeting request (for
informal and formal meeting), (2) the submission of a meeting package (for formal
meetings), and (3) the submission of draft meeting minutes (for formal and certain
informal meetings).
The collection of information described in this guidance is intended to provide
background information in support of consistent procedures to promote well-managed
meetings between OOPD and stakeholders. In some cases, these meetings may
represent a critical point in the orphan product development process and may even
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have an impact on the eventual availability of products for patients with rare diseases
and conditions. It is therefore important that these meetings be scheduled within a
reasonable time, conducted effectively, and documented where appropriate.
2. Purpose and Use of the Information Collection
Orphan-drug designation provides financial incentives for the development of a drug
for the diagnosis, prevention, or treatment of a rare disease or condition.
FDA uses the requested information to make the determination that the drug is for a
legitimately rare disease or condition and issues an orphan-drug designation.
Secondly, the information describes the sponsor’s plan for clinical and preclinical
studies.
The guidance regarding meetings provides recommendations to industry, researchers,
patient groups, and other stakeholders (collectively referred to as “stakeholders”)
interested in requesting a meeting with FDA’s Office of Orphan Products
Development (OOPD) on issues related to orphan drug designation requests,
humanitarian use device (HUD) designation requests, rare pediatric disease
designation requests, funding opportunities through the Orphan Products Grants
Program and the Pediatric Device Consortia Grants Program, and orphan product
patient-related topics of concern. This guidance document is intended to assist these
groups with requesting, preparing, scheduling, conducting, and documenting meetings
with OOPD and will provide for more productive meetings with stakeholders.
3. Use of Improved Information Technology and Burden Reduction
Improved technology for submission of orphan drug designation and meeting requests
is currently being developed by the Office of Orphan Products Development in FDA.
Changes made in such technologies will be adopted when appropriate within the
procedures of FDA orphan products development programs.
4. Efforts to Identify Duplication and Use of Similar Information
Since the collection of data is specifically for application for incentives under the
Orphan Drug Act, there is little possibility that other agencies are collecting similar
information.
5. Impact on Small Businesses or Other Small Entities
The provisions of the Orphan Drug Act and the provisions contained in the
regulations are favorable to small business interests. The orphan-drug designation
provision entitles the sponsor to Federal income tax credits for clinical studies, and
eligibility for grants to fund studies of orphan products. The Orphan Drug
Exclusivity Provision provides protection from competition by other companies that
is administered by FDA. The FDA must by law insure that a competitive product
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does not enter the market by withholding approval of a subsequent new drug
application or biological license.
6. Consequences of Collecting the Information Less Frequently
The frequency of the collection of the data is entirely controlled by the sponsor
requesting eligibility for one of the incentives of the Orphan Drug Act. There are no
legal obstacles to reduce the burden.
7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
The method of collection is consistent with the guidelines of 5 CFR 1320.6. There
are no special circumstances for this collection of information.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside
the Agency
In accordance with 5 CFR 1320.8(d), FDA published a 60-day notice for public
comment on the information collection provisions was published in the Federal
Register of October 2, 2020 (85 FR 62306) to which no comments were received.
9. Explanation of Any Payment or Gift to Respondents
There are no payments or gifts provided to respondents.
10. Assurance of Confidentiality Provided to Respondents
In preparing this Supporting Statement, we consulted our Privacy Office to ensure
appropriate identification and handling of information collected.
This ICR collects personally identifiable information (PII) or other data of a personal
nature. PII is collected in the context of the subject individuals’ professional capacity
and the FDA-related work they perform for their employer (e.g., point of contact at a
regulated entity). The PII submitted via Form FDA 4035(The Food and Drug
Administration Orphan Drug Designation Request Form) and Form FDA 3671 (The
Common European Medicines Agency (EMA)/Food and Drug Administration (FDA)
Application Form for Orphan Medicinal Product Designation) is name, business email
address, business telephone number, and business fax telephone number.
Sponsors seeking orphan designation of the same drug for the same disease or
condition from both FDA and EMA may use this common application form for
regulatory filing purposes. The Food and Drug Administration Orphan Drug
Designation Request Form 4035 is intended to benefit sponsors who desire to seek
orphan designation of drugs intended for rare diseases or conditions from only FDA.
Both forms are intended to complement, not supersede, the relevant regulatory
frameworks currently in effect. When using the common application form, the sponsor
must comply with all applicable regulatory requirements in each jurisdiction in which
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designation is sought.
Under the Freedom of Information Act (FOIA) (5 U.S.C. 552), the public has broad
access to government documents. However, FOIA provides certain exemptions from
mandatory public disclosure of government records (5 U.S.C. 552(b)(1-9)). FDA will
make the fullest possible disclosure of records to the public, consistent with the rights
of individuals to privacy, the property rights of persons in trade and confidential
commercial or financial information.
The Orphan Drug Act provides that the designation of a drug as an orphan drug
should be a public event. Accordingly, 21 CFR 316.28 provides that public notice be
made of all drugs designated as orphan-drugs and will include the name and address
of the sponsor, the name of the drug, the rare disease or condition for which the drug
was designated, and the proposed indication for use. Similarly, public notice is made
identifying sponsors’ drugs and indications for use that have obtained Orphan Drug
Exclusivity. 21 CFR 316.32 provides that FDA will neither publicly disclose the
existence of a request for nor the substance of the request until final action is taken.
Further, FDA will not publicly disclose the existence of a pending marketing
application for a designated orphan drug unless the existence of the request has been
previously disclosed or acknowledged.
Determinations of public availability of data and information contained in pending
and approved marketing applications will continue to be in accordance with existing
provisions of 21 CFR Parts 20 and 314.430.
11. Justification for Sensitive Questions
No questions of a sensitive nature are contained in the proposal.

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12. Estimates of Annualized Burden Hours and Costs
12 a. Annualized Hour Burden and Cost
21 CFR Section;
Activity

Content and format of a
request for designation;
request for verification
of status; amendment to
designation
§§ 316.20, 316.21,
316.26 (Form FDA
4035)
§ 316.22; Notifications
of changes in agents
§ 316.24(a); Deficiency
letters and granting
orphan-drug
designation
§ 316.27; Submissions
to change ownership of
orphan-drug
designation
§ 316.30; Annual
reports
§ 316.36; Assurance of
the availability of
sufficient quantities of
the orphan drug;
holder's consent for the
approval of other
marketing applications
for the same drug
Guidance
Recommendations:
Meeting requests to
OOPD and related
submission packages
Total
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No. of
Respondents

No. of
Responses
per
Respondent
534
1.25

Total
Annual
Responses

Average
Burden
per
Response
668
135

Total
Hours

90,180

534

1.25

668

32

21,376

132

1

132

2

264

20

1

20

2

40

104

1

104

5

520

744

1

744

3

2,232

1

3

3

15

45

2,508

1

2,508

3.595

9,016

123,673

There are no capital costs or operating and maintenance costs associated with this collection of information

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 four years, that 534 persons or
organizations per year will request orphan drug designation and it is anticipated
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there will be no requests for a formal recommendation on design or preclinical or
clinical studies.
FDA estimates that the effort required for consideration in both sections 525 and 526
(21 CFR Parts 316.10 & 316.20, respectively) is an average of 110 hours of
professional time and 25 hours of support staff time per application (110 + 25 = 135
hours). Estimates of annual activity and burden for foreign sponsor nominations of a
resident agent, change in ownership of designations, and inadequate supplies of a
drug in exclusivity, are based on total experience by FDA with such requests since
1983.
For 316.10, 316.12, and 316.14, no requests for recommendations are anticipated.
12b. Annualized Cost Burden Estimate
Activity
Request for Orphan
Designation

Form FDA 4035
Change in
Ownership
Foreign Sponsor
Nominate
Annual Report
Inadequate Supplies
Deficiency Letters
Meetings

No. of Hours
73,480
16,700

Cost per Hour
Professional $85
Support Staff

18,036
3,340
132
132
208
312
744
1,488
30
15
40

Total Cost
$6,245,800
417,500

Professional $85
Support Staff 25
Professional $85
Support Staff 25
Professional $85
Support Staff 25
Professional $85
Support Staff 25
Professional $85
Support Staff 25
Professional $85
Support Staff 25

7,508
1,508

1,533,060
83,500
11,220
3,300
17,680
4,725
63,240
37,200
2,250
375
3,400
638,180
37,700
$9,099,130

For purposes of calculating costs to respondents, we utilized an estimated average for
professional response time at $85.00 per hour and $25.00 per hour for support hour.
The hourly input per requirement utilizes the information in the preceding table. The
two totals in the “No. of Hours” column is separated based on professional and
support staff costs and when added together represents the total burden hours for that
activity. For instance, for “Requests for Orphan Designation,” 73,480 + 16,700 =
90,180 as seen in item 12a of this document, first line of the table. Those separated
totals are multiplied by either the professional or support staff cost. For instance,
“Requests for Orphan Designation,” 73,480 x $85 = $6,245,800; 16,700 multiplied
by $25 = 417,500.
13. Estimates of Other Total Annual Costs to Respondents and/or Record
Keepers/Capital Costs
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There are no capital, start-up, or operating or maintenance costs associated with
this information collection.
14. Annualized Cost to the Federal Government
FDA estimates that the equivalent of eleven full time positions ranging from GS-9
clerical personnel to GS-15 medical officers ($2,750,000 for personnel costs and
benefits) will be required to implement the collection of information, response to
applicants, guidance and recommendation to sponsors required by the applicable law
and regulations. The estimates are based on knowledge of resources used by the FDA
Office of Orphan Products Development in implementing the Orphan Drug Act over
the last 30 years. Since the number of applicants is expected to continue to increase,
past FDA experience will be a good predictor of future resources.
15. Explanation for Program Changes or Adjustments
The total number of requests for orphan designation have increased as a result of
increased interest by the public and pharmaceutical industry in developing products
for people with rare diseases and conditions. The burden was adjusted to reflect this
increase. Since there is an increase of applications, sponsors who request a
designation from only the FDA have the option of submitting the FDA Orphan Drug
Designation Request Form (FDA Form 4035). The estimated annual hourly burden,
formerly estimated as 106,407 hours, has increased by 8,250 hours to a total
estimated annual hourly burden of 114,657 hours.
We are consolidating into this request for approval 0910-0787, “Guidance for
Industry, Researchers, Patient Groups, and Food and Drug Administration Staff on
Meetings With the Office of Orphan Products Development” which represents an
additional increase in total burden hours of 9,016 hours.
Therefore, the increase in total burden hours is 17,266.
For the purpose of ease of entry in ROCIS the previously entered eight ICs was
reduced to one IC.
16. Plans for Tabulation and Publication and Project Time Schedule
The objectives of the collection are not for publication of statistical material and do
not employ statistical methods.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
FDA is not seeking approval to exempt display of the expiration date for OMB
approval.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
Not applicable.
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