SUPPORTING STATEMENT FOR

**MEDICAL DEVICES; HUMANITARIAN USE DEVICES**

**21 CFR Part 814 -- Subpart H**

###### OMB Number 0910-0332

**A. Justification**

1.  **[Circumstances Necessitating Information Collection]{.underline}**

> The Food and Drug Administration (FDA) is requesting Office of
> Management and Budget (OMB) approval of the requirements set forth in
> this information collection. This collection enforces the requirements
> of 21 CFR Part 814, Subpart H (Attachment A) and the Final Rule
> published in the November 3, 1998 Federal Register.

The purpose of the regulation is to implement the humanitarian use
device (HUD) provision of the Safe Medical Devices Act of 1990 (the
SMDA) (Pub. L. 101-629) and its amended rule (21 CFR 814 Subpart H). The
HUD provision has been incorporated into section 520(m) (21 U.S.C.
360j(m)) of the Federal Food, Drug, and Cosmetic Act (the act), as
amended by the Food and Drug Administration Modernization Act of 1997
(FDAMA). Under section 520(m) of the act, FDA is authorized to exempt a
HUD from the effectiveness requirements in sections 514 and 515 of the
act (21 U.S.C. 360d and 360e) provided that the device (1) is used to
treat or diagnose a disease or condition that affects fewer than 4,000
individuals in the United States; (2) would not be available to a person
with such a disease or condition unless the exemption is granted, and
there is no comparable device, other than another HUD approved under
this exemption, available to treat or diagnose the disease or condition;
and (3) the device will not expose patients to an unreasonable or
significant risk of illness or injury, and the probable benefit to
health from using the device outweighs the risk of injury or illness
from its use, taking into account the probable risks and benefits of
currently available devices or alternative forms of treatment. Section
203 of FDAMA made several changes to section 520(m) of the act, and
implements the amendments to the HUD provision mandated by FDAMA.

FDA is requesting Office of Management and Budget (OMB) approval for the
collection of information required by the amendments to 21 CFR 814
promulgated under the statutory mandate of section 520(m) of the act, as
amended by FDAMA.

**Section 814.102 -- Reporting**

Prior to submitting an HDE application, the applicant shall submit a
request for HUD designation to FDA\'s Office of Orphan Products
Development.

**Section 814.104 -- Reporting**

After receiving a HUD designation, the applicant shall submit an HDE
application to FDA. Included in the application, as required by Section
814.104(b)(5), is a report prepared by a Certified Public Accountant or
an attestation by a responsible person of the organization verifying
that the amount charged does not exceed the cost of the device\'s
research, development, fabrication, and distribution. The requirement
for an attestation or a report is waived if the amount charged is
\$250.00 or less.

As required by Section 814.110(a), an applicant seeking a new indication
for use of a HUD approved under this subpart H shall obtain a new
designation of HUD status in accordance with the procedures under
§814.102 and shall submit an original HDE in accordance with the
requirements under §814.104.

**Section 814.106 -- Reporting**

An HDE applicant may amend a pending HDE or HDE supplement to revise
existing information or provide additional information.

FDA may request the HDE applicant to amend an HDE or HDE supplement with
any information regarding the device that is necessary for FDA to
complete review of the HDE or HDE supplement. A copy of final printed
labeling submitted to FDA following approval of an HDE application but
before marketing, as provided for in Section 814.116(b), will be
processed as an amendment to the HDE.

An HDE applicant may resubmit an HDE or HDE supplement after withdrawing
it or after it is considered withdrawn or after FDA has refused to
accept it for filing or has denied approval of the HDE or HDE
supplement.

If FDA refuses to file the HDE, the applicant may submit an amendment to
request in writing, in accordance with Section 814.112(b), an informal
conference with the Director of the Office of Device Evaluation to
review FDA's decision not to file the HDE.

If FDA is proposing to withdraw approval of an HDE, the holder of the
approved application may submit an amendment to request in writing, in
accordance with Section 814.118(d), an opportunity for an informal
hearing.

**Section 814.108 -- Reporting**

After FDA approval of an original HDE, the holder shall submit
supplements for review and approval by FDA before making a change
affecting the safety or effectiveness of the device for which the holder
has an approved HDE, unless the change is of a type for which FDA has
advised that an alternate submission is permitted.

**Section 814.116(e)(3)** - FDA believes that it will receive
approximately 1 request to withdraw an HDE application per year, based
on withdrawals submitted in FY 2000-2004. FDA estimates it will take no
longer than 1 staff hour to complete each written withdrawal notice.

### 

### Section 814.124(a) - Reporting

This section allows physicians in an emergency situation to administer a
HUD prior to obtaining Institutional Review Board (IRB) approval. In
such a situation, the physician is required to provide written
notification to the IRB within 5 days after emergency use.

**Section 814.124(b) -- Reporting**

A holder of an approved HDE shall notify FDA of any withdrawal of
approval for the use of a HUD by a reviewing IRB within 5 working days
after receipt of the withdrawal of approval.

**Section 814.126(b)(1) -- Reporting**

The holder of an approved HDE shall submit a periodic report. The report
is required to demonstrate continued compliance with the humanitarian
device exemption (HDE) requirements.

### Section 814.126(b)(2) - Recordkeeping

> An HDE holder shall maintain records of the names and addresses of the
> facilities to which the HUD has been shipped, correspondence with
> reviewing IRBs as well as any other information requested by a
> reviewing IRB or FDA. Such records shall be maintained in accordance
> with the HDE approval order.

**2. [How, by Whom, and for What Purpose Information Used]{.underline}**

> The information gathered by this collection enables FDA to determine
> whether an HDE holder is in compliance with the HDE requirements. It
> will also allow FDA to determine whether to: (1) grant HUD designation
> of a medical device; (2) exempt a HUD from the effectiveness
> requirements in sections 514 and 515 of the act (21 U.S.C. 360d and
> 360e) provided that the device meets requirements set forth in section
> 520(m) of the act; and (3) grant marketing approval(s) for the HUD.
> Failure to collect this information would prevent FDA from making that
> determination.

**3. [Consideration of Information Technology]{.underline}**

> There are no technical or legal obstacles to the collection of this
> information. The principal data to be submitted will be submitting a
> request for HUD designation under 21 CFR 814.102 and the HDE
> application under 21 CFR 814.104. The use of computer technology and
> automation has the potential to reduce the time needed to compile
> records.
>
> In the **Federal Register** of March 20, 1997 (62 FR 13430), FDA
> published a final rule establishing procedures for electronic records,
> electronic signatures, and electronic submissions. Under certain
> circumstances, this will permit the agency to accept electronic
> records, electronic signatures, and handwritten signatures executed to
> electronic records as generally equivalent to paper records and
> handwritten signatures executed on paper. Organizations may use
> appropriate technology in accordance with this rule to comply with HDE
> requirements.
>
> The intended effect of this rule is to permit use of electronic
> technologies in a manner that is consistent with FDA\'s overall
> mission and that preserves the integrity of the agency\'s enforcement
> activities. These regulations apply to records submitted in electronic
> form that are called for in Title 21 of the Code of Federal
> Regulations (CFR).
>
> Regarding Electronic Submissions: CDRH is advising the public about
> electronic submissions both on the FDA Webpage (at
> http://www.fda.gov/oc/electronicsubmissions/interfaq.htm), and through
> the CDRH website at (http://www.fda.gov/cdrh/elecsub.html). Basically,
> CDRH is advising the public that CDRH will accept electronic
> submissions with previous approval in PDF format.
>
> The site states: "The Center for Devices and Radiological Health
> (CDRH) is accepting medical device applications in electronic form.
> The Office of Device Evaluation (ODE) is currently developing formal
> guidelines regarding electronic submissions. Until they are finalized,
> CDRH is requesting industry to give prior notification of their desire
> to submit an application in electronic form. This lead time is needed
> to discuss any special considerations with the submitter prior to
> development of the documents.
>
> The application should be submitted in a PDF format since the ODE
> staff will use Acrobat Exchange to review the submission. This will
> assure that what a reviewer sees on the screen is the same as what
> would have been seen on paper. PDF stands for Portable Document
> Format. Applications may be submitted on floppy diskettes or CD-ROM.
>
> Industry should also contact the Director of the ODE Division to which
> its device pertains.
>
> It should be understood that an electronic application does not change
> the order in which submissions are reviewed. No preferential treatment
> will be given to manufacturers who submit an electronic application.
> In addition at least one paper copy of the submission is also
> required. Additional copies of some reports may be requested in order
> to help facilitate the review."
>
> To date, the use of electronic forms of recordkeeping and submissions
> to FDA remains voluntary.

**4. [Efforts to Identify Duplication and Similar Information Already
Available]{.underline}**

FDA believes that the information being collected will not duplicate
information already available. A HUD sponsor will be provided with the
opportunity to obtain marketing clearance through the HDE application
procedures instead of through either the premarket notification
procedures or the premarket approval application procedures.

**5. [Small Business]{.underline}**

> This information collection will not have a significant economic
> impact on a substantial number of small entities. While the number of
> HDE applications FDA will approve is unknown, FDA believes that it
> will approve approximately 8 HDE applications per year. Moreover,
> submission of HDE applications is entirely voluntary. Respondents who
> believe that it will not be in their business's interest to submit an
> HDE application will be unlikely to do so. Moreover, the HDE
> regulation helps small businesses by exempting them from the
> requirement for full PMAs. Furthermore, section 814.104(b)(5)
> minimizes the burden on all entities by allowing a responsible
> individual of the HDE holder\'s organization to submit an attestation
> regarding the charges, in lieu of a CPA for which the organization
> would be compelled to pay.

**6. [Consequences of Less Frequent Information Collection and Technical
or Legal Obstacles]{.underline}**

> This information is necessary to FDA to determine whether a device is
> eligible for HUD designation and thus exempted from the effectiveness
> requirements of Sections 514 and 515 of the act (21 U.S.C. 360d and
> 360e). (Attachments B and C). It is also necessary to determine
> whether an HDE holder is in compliance with the HDE requirements
> (sections 510(m)(3) and (5)) of the act.
>
> If FDA did not receive information from potential HUD applicants, FDA
> would have no basis for granting HUD exemptions. The frequency of
> FDA\'s receipt of HDE applications will be determined by the frequency
> with which applicants submit HDE applications. This frequency cannot
> be reduced without unnecessarily delaying marketing clearance
> decisions under section 520(m) of the act.

7.  **[Consistency With the Guidelines in 5 CFR 1320.6]{.underline}**

> This collection of information is consistent with the guidelines
> prescribed in 5 CFR 1320.6.

8.  **[Consultation Outside the Agency]{.underline}**

> Notice has been published in the Federal Register on (June 16, 2005)
> (70 FR 35098) soliciting comments on this information collection prior
> to its submission to the Office of Management and Budget (OMB) as
> required by 5 CFR 1320.8(d). No comments were received. (Attachment
> D).
>
> The Food and Drug Administration (FDA) also sought comment from
> interested parties, including consumers, researchers, healthcare
> practitioners, the device industry, and professional and trade
> associations on a new statute enacted on April 1, 2004 requiring HHS
> to report to Congress on barriers to the availability of medical
> devices for pediatric uses. This was done through participation in a
> stakeholder meeting, holding a series of meetings in 2004 with the
> American Academy of Pediatrics, and publishing a notice in the
> *Federal Register* requesting comment. FDA received 25 comments in
> response to the notice. These comments are available under Public
> Docket No. 2004N-0254 and at
> [www.fda.gov/cdrh/pediatricdevices/comments.pdf](http://www.fda.gov/cdrh/pediatricdevices/comments.pdf).

9.  **[Payment or Gifts to Respondents]{.underline}**

FDA will not provide payment or gifts to sponsors under the HUD
provisions.

10. **[Confidentiality of Information]{.underline}**

Section 814.122(a) states that any record in the HDE file, including all
data and information submitted with or incorporated by reference into
the HDE, any HDE supplement, any report under §814.126, any master file,
or any other related submission, will be available for public disclosure
in accordance with the restrictions and conditions available to PMA
files under §814.9(b) through (h), the public information regulations at
21 CFR part 20, and any other applicable regulation governing
confidentiality of information or public disclosure of information. The
confidentiality of information is not affected by the amendments.

11. **[Sensitive Questions]{.underline}**

> The information collected does not include questions pertaining to
> sexual behavior, attitude, religious beliefs, or any other matters
> that are commonly considered private or sensitive in nature.

**12. [Estimates of Burden Hours and Explanation]{.underline}**

# Table 1 provides a summary of the estimated annual reporting burden for sponsors that elect to submit an HDE application. Table 2 provides a summary of the estimated annual recordkeeping burden for sponsors. An explanation of the hour burden estimates and annualized hour burden cost follows the tables.

# TABLE 1 -- Estimated Annual Reporting Burden^1^

+-----------+-----------+-----------+-----------+-----------+-----------+
| CFR       | Number    | Annual    | Total     | Hours     | Total     |
| Section   |           |           |           |           |           |
|           | Of        | Frequency | Annual    | Per       | Hours     |
|           |           |           |           |           |           |
|           | Re        | Per       | Responses | Response  |           |
|           | spondents |           |           |           |           |
|           |           | R         |           |           |           |
|           |           | espondent |           |           |           |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 814.102   | 20        | 1         | 20        | 40        | 800       |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 814.104   | 8         | 1         | 8         | 320       | 2560      |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 814.106   | 8         | 2         | 16        | 50        | 800       |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 814.108   | 20        | 1         | 20        | 80        | 1600      |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 814.      | 1         | 1         | 1         | 1         | 1         |
| 116(e)(3) |           |           |           |           |           |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 8         | 5         | 1         | 5         | 1         | 5         |
| 14.124(a) |           |           |           |           |           |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 8         | 1         | 1         | 1         | 2         | 2         |
| 14.124(b) |           |           |           |           |           |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 814.      | 35        | 1         | 35        | 120       | 4200      |
| 126(b)(1) |           |           |           |           |           |
+-----------+-----------+-----------+-----------+-----------+-----------+
| TOTAL     |           |           |           |           | 9968      |
+-----------+-----------+-----------+-----------+-----------+-----------+

> ^1^There are no capital costs and operating or maintenance costs
> associated

##### TABLE 2 Estimated Annual Recordkeeping Burden for HDE Holders

+-----------+-----------+-----------+-----------+-----------+-----------+
| CFR       | Number of | Annual    | Total     | Hours per | Total     |
|           |           |           |           |           |           |
| Section   | Record    | Frequency | Annual    | Record    | Hours     |
|           |           |           |           |           |           |
|           | Keepers   | Of Record | Records   | Keeper    |           |
|           |           |           |           |           |           |
|           |           | Keeping   |           |           |           |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 814.126   | 35        | 1         | 35        | 2         | 70        |
|           |           |           |           |           |           |
| \(b\) (2) |           |           |           |           |           |
+-----------+-----------+-----------+-----------+-----------+-----------+
| Total     | ......    | ......    | ......    | ......    | 70        |
+-----------+-----------+-----------+-----------+-----------+-----------+

**[Explanation of Report Burden Estimate:]{.underline}**

> Overall, the information requested from respondents represents, for
> the most part, an accounting of information already in the possession
> of the applicant.
>
> **§814.102** -- It is estimated that 20 applicants per year will
> submit a request for HUD designation. It is estimated to require 40
> staff hours to complete each HUD designation request.
>
> **§814.104** -- FDA estimates that 8 applicants per year will submit
> an HDE application after receiving HUD designation. FDA estimates that
> it will require an average of 320 staff hours to complete each HDE
> application. **§814.104(b)(5)** is information required to be
> submitted as part of an HDE application. **§814.110 (a)** requires
> that a new indication for use of a HUD approved under this part be
> submitted as a new HDE application complying with **§814.104**;
> however, information may be included by reference from the previous
> HDE application.
>
> **§814.106** -- It is estimated that 2 times per year FDA will request
> or the applicant or holder will submit additional information or
> resubmit an HDE or HDE supplement for approximately 8 of the submitted
> HDE applications. FDA estimates that it will require an average of 50
> staff hours to complete each amendment or resubmitted application.
> Requests for an informal conference, under **§814.112(b)**, if FDA
> refuses to file the HDE application, will be processed as an HDE
> amendment. Responses to approvable letters, **§814.116(b)**, will be
> processed as HDE amendments. A request for an opportunity for an
> informal hearing, under prior to FDA issuing an order withdrawing
> approval, under **§814.118(d)**, will be processed as an HDE
> amendment.
>
> **§814.108** -- FDA anticipates that it will receive approximately 20
> supplements for the submitted HDE applications. It is estimated that
> it will take approximately 80 staff hours to complete each
> supplemental application.
>
> **§814.116(e)(3)** - FDA believes that it will receive approximately 1
> request to withdraw an HDE application per year, based on withdrawals
> submitted in FY 2000-2004. FDA estimates it will take no longer than 1
> staff hour to complete each written withdrawal notice.
>
> **§814.124(a)** - FDA anticipates that 5 physicians will use HUDs in
> emergency situations before obtaining IRB approval. FDA estimates that
> notification under this section will take an average of one hour per
> response.
>
> **§814.124(b) --** FDA anticipates that 1 holder of an approved HDE
> will notify FDA of IRB withdrawal of approval. FDA estimates that it
> will take an average of one staff hour to notify FDA of IRB
> withdrawal.
>
> **§814.126(b)(1)** - FDA anticipates that because of this amendment,
> the 35 HDE holders will remain active and therefore, estimates that 35
> periodic reports will be received. FDA also estimates that it will
> take an average 120 of staff hours to complete a periodic report as a
> result of this amendment.
>
> **[Explanation of Recordkeeping Burden Estimate:]{.underline}**
>
> **§814.126(b)(2)** - FDA anticipates that 35 HDE holders per year will
> maintain records of certain information. It is estimated that it will
> take an average of 2 staff hours to maintain this information.

b.  **[Estimated Annualized Cost for the Burden Hours]{.underline}**

Multiplying the total reporting and recordkeeping hours (10,038) by an
average rate of \$50 per hour, yields an estimate annual cost to
respondents of \$501,900.

**13. [Annualized Cost to Respondents]{.underline}**

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

**14. [Annual Cost to the Government]{.underline}**

FDA estimates that 22.5 full time equivalent (FTE) positions will be
required to fully implement the collection of information and response
to applicants and holders required as a result of the requirements of
section 520(m) of the act and the implementing regulation. These
positions are expected to cost the government about \$2,704,080 on
average, based on the mix of staff expertise required to implement the
HUD. The positions range from GS-5 clerical personnel to GS-15 medical
officers; and the average cost for each position is \$118,600 (\$113,600
for personnel costs and benefits and \$5,000 of operating funds per year
at a total cost of \$118,600 for each full time position).

**15. [Changes in Burden]{.underline}**

The burden represented by this collection has decreased by 1,360 hours
(11,368 -- 10,038) since the last time OMB approved this information
collection. This decrease in burden can be attributed to an alteration
of the number of anticipated responses to CFR §§ 814.104, 814.106,
814.108, 814.126(b)(1). Additionally, recordkeeping has increased due to
a boost in the number of anticipated HDE holders that need maintain
certain information under §814.126(b)(2).

**16. [Statistical Reporting]{.underline}**

FDA does not intend to publish the results of this information
collection.

**17. [Exemption for Display of Expiration Date]{.underline}**

No exemption approval is requested.

**18. [Exemption to Certification Statement]{.underline}**

There are no exemptions to the certification statement identified in
Item 19 of OMB Form 83-I.

# **[Collection Of Information Employing Statistical Methods]{.underline}**

The use of statistical methods is not applicable.

[List of Attachments:]{.underline}

Attachment A - U.S. Code of Federal Regulations, 21 CFR Part 814 Subpart
H.

Attachment B - Federal Food, Drug, and Cosmetic Act, Sections 514 (21
U.S.C. 360d).

Attachment C - Federal Food, Drug, and Cosmetic Act, Sections 515 (21
U.S.C. 360e).

Attachment D - U.S. Code of Federal Regulations, 5 CFR 1320.8(d).