OMB INFORMATION COLLECTION

Docket No. 02n-0417

Supporting Statement

Applications for FDA Approval to Market a New Drug: Patent Listing
Requirements and Application of 30-month Stays on Approval of
Abbreviated New Drug Applications Certifying That a Patent Claiming a
Drug Is Invalid or Will Not Be Infringed

(0910-0513)

A. Justification

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

> The Food and Drug Administration (FDA) is proposing to amend its
> regulations regarding the content and format of new drug applications
> (NDAs), 505(b)(2) applications (the Federal Food, Drug and Cosmetic
> Act (21 U.S.C. 355)) (Tab A), and abbreviated new drug applications
> (ANDAs). The final rule (Tab B) would clarify the types of patents
> that NDA applicants must submit to FDA and revise the patent
> declaration statement (forms FDA 3542 and 3542a) (Tab C) submitted by
> NDA applicants. The proposal would also revise the regulations
> regarding the effective date of approval for certain ANDAs and
> 505(b)(2) applications. Under federal law, if an ANDA or 505(b)(2)
> application contains a certification stating that the patent covering
> the reference listed drug is invalid or will not be infringed, the
> applicant must provide a notice of certification of invalidity or
> noninfringement to the NDA holder and to the patent owner. If a
> lawsuit for patent infringement is brought within 45 days of the
> notice, federal law prevents FDA from making the approval of an ANDA
> or 505(b)(2) application effective for 30 months (although this period
> may be shortened or lengthened by court decision or court order). The
> proposal would state that the 30-month stay in the effective date of
> an ANDA or 505(b)(2) application operates only once, and this would
> have the effect of reducing the number of notices that ANDA and
> 505(b)(2) application applicants must provide to NDA applicants and to
> patent owners.
>
> FDA requests Office of Management and Budget (OMB) approval of the
> information collection requirement in \"Applications for FDA Approval
> to Market a New Drug: Patent Listing Requirements and Application of
> 30-month Stays on Approval of Abbreviated New Drug Applications
> Certifying That a Patent Claiming a Drug Is Invalid or Will Not Be
> Infringed,\" 21 CFR 314.50, 314.52, 314.53, 314.94 and 314.95 (Tab D).
> The agency estimates that the proposed rule\'s total information
> collection is 499,805 hours. This information is needed to ensure
> compliance with the statutory and regulatory requirements that
> information concerning patents that claim a drug, or a method of using
> a drug, that is the subject of a pending or approved NDA be submitted
> to us if they could reasonably form the basis of a patent infringement
> lawsuit. The form is designed to ensure that all such patents are
> submitted, and that only information concerning patents that satisfy
> the statutory and regulatory requirements is submitted.
>
> Section 505(b)(1) requires NDA applicants to file with the application
> the patent number and the expiration date of any patent which claims
> the drug for which the applicant submitted the application and with
> respect to which a claim of patent infringement could reasonably be
> asserted if a person not licensed by the owner engaged in the
> manufacture, use, or sale of the drug. If a patent which claims such
> drug is issued after the filing date but before approval of the
> application, the NDA applicant must file this same information with
> respect to the new patent. Under Section 505(c)(2), if a patent is
> issued after approval of the NDA, the holder must file this same
> information within 30 days after the date that the patent involved is
> issued.

21 CFR 314.50(h) and 314.53(b) and (c) - Reporting

> This provision would be affected by the changes described in proposed
> §§ 314.53(b) and (c). In brief, § 314.50(h) instructs NDA applicants
> to submit the patent information described in § 314.53. Proposed §
> 314.53(b) would clarify the types of patents that NDA applicants must
> submit, while proposed § 314.53(c) would revise the two patent
> declarations that NDA applicants must submit. The revised patent
> declarations would require NDA applicants to provide greater detail
> regarding the claims that cover the drug product that is the subject
> of an NDA, amendment to an NDA, or an NDA supplement.

21 CFR 314.52(a)(3), 314.94(a)(12) and 314.95(a)(3) - Reporting

> These provisions would pertain to 505(b)(2) application applicants and
> to ANDA applicants respectively. In brief, the proposal would have the
> effect of requiring these applicants to send only one notice of
> invalidity of noninfringement of patent to NDA holders and to patent
> owners if the applicant certifies that the patent is invalid or will
> not be infringed.

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

> We will collect this information as part of the NDA or, in the case of
> later-obtained patents, as amendments to the NDA. When the NDA is
> approved, we will collect this information in a separate submission
> that reflects the patents that cover the drug as we have approved it,
> including the specific methods of use of the drug for which we granted
> approval.
>
> We use the patent information in the reports to list patents in our
> approved drug products list titled, \"Approved Drug Products With
> Therapeutic Equivalence Evaluations.\" Federal law specifically
> requires us to publish such patent information. ANDA and 505(b)(2)
> application applicants can then consult the listed patent information
> to prepare their patent certification statements or to identify
> patents that claim a specific drug substance, drug product, or method
> of use for that product.

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

> The rule would not specifically prescribe the use of automated,
> electronic, mechanical, or other technological collection techniques
> or other forms of information technology. Respondents are free to use
> whatever forms of information technology that may best assist them in
> complying with the rule.

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

> The information that is collected is not already available to FDA.
> Such information is available only from NDA applicants and NDA
> holders, and will vary for each drug. Because our patent listing
> function is ministerial, only the NDA applicant or NDA holder has the
> ability to identify the patents for which relevant information is to
> be submitted.
>
> FDA is the only agency that reviews and approves NDAs, 505(b)(2)
> applications, and ANDAs. We thus have not undertaken literature
> searches or contacted staff of other organizations with respect to
> this information collection. Section 505(b)(1) of the act requires NDA
> applicants to provide patent information as part of the NDA. Sections
> 505(b) and 505(j) of the act require certain 505(b)(2) application
> applicants and ANDA applicants to provide a notice of certification of
> invalidity or noninfringement of patent to patent owners and NDA
> holders in certain situations; this notification is part of the
> application process. Therefore, no duplication of data exists.
>
> The importance of obtaining such data relates to adherence to the law
> and regulatory requirements for patent submissions, and ensuring that
> ANDA and 505(b)(2) applicants adhere to the appropriate legal and
> regulatory requirements for certifying to those patents. Adherence to
> those requirements, in turn, governs whether and when we can approve
> such ANDA and 505(b)(2) applications.

5\. [Small Business]{.underline}

This information collection would not have a significant impact on small
businesses.

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

> Failure to collect the information could result in incomplete,
> erroneous, or misleading patent information being listed by FDA and
> prompt 505(b)(2) application applicants and ANDA applicants to make
> incorrect patent certifications, thereby exposing those applicants to
> potential litigation for patent infringement. Ultimately, the failure
> to collect the information could have an adverse effect on the
> protection of patented drug products and on the availability of
> generic drug products.

7\. [Consistency with the Guidelines in 5 CFR 1320.5(d)(2)]{.underline}

> The final rule\'s reporting requirements are consistent with the
> guidelines in 5 CFR 1320.5(d)(2). The final rule would not require
> reporting to occur more frequently than the quarterly basis described
> in §320.5(d)(2)(i), nor would it require multiple copies of the
> reports.
>
> We will not require respondents to keep records more than 3 years. No
> statistical data is used. The collection does not include a pledge of
> confidentiality. Respondents are not required to submit trade secrets,
> proprietary, or other confidential information.

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

> The agency relied on its expertise with these applications to estimate
> the amount of time and cost needed to prepare the reports described in
> the rule. As required by section 3506(c)(2)(B) of the Paperwork
> Reduction Act of 1995 (PRA), FDA provided opportunity for public
> comment on the information collection requirements of the proposed
> rule that published in the Federal Register on October 24, 2002 (Vol.
> 67, No. 206, p. 65448) (Tab E). The proposed rule received over 35
> comments to which FDA responded in the preamble of the final rule.

9\. [Payment or Gift to Respondents]{.underline}

> FDA did not provide any payment or gifts to respondents.

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

> Assurances of confidentiality (beyond those already existing in
> federal law and FDA regulations) are unnecessary.

11\. [Sensitive Questions]{.underline}

> No questions of a sensitive nature are asked.

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

> In 1998-2002, the annual number of original applications we have
> received containing a certification of invalidity or noninfringement
> of patent (paragraph IV certification) has been 61, 58, 79, 90, and
> 82, respectively. The annual average is 74 ((61 certifications +58
> certifications +79 certifications + 90 certifications + 82
> certifications) / 5 years = 74 certifications/year). Because the final
> rule requires notice of a paragraph IV certification filed in the
> original ANDA or 505(b)(2) application or when the application is
> amended to include a paragraph IV certification or when such notice
> did not provide a full opportunity for a 30-month stay, this would
> mean that these applicants would usually provide only one notice to
> NDA holders and patent owners, and would provide a second notice only
> in the rare instance when the ANDA or 505(b)(2) applicant on its own
> initiative cut short the 45 day period following notice. We increase
> the frequency of response to account for these rare second notices.
> There may still be multiple certifications made by ANDA or 505(b)(2)
> applicants which will not require notice. In previous estimates, we
> have combined the information collection burden for both the notice
> and the certification. For purposes of the final rule, we assume that
> the certification information collection burden is 4 hours and the
> information collection burden for the notice is 12 hours. We also
> account for the multiple number of certifications that may have to be
> provided by an ANDA or 505(b)(2) applicant. Under pre-existing
> regulations, we have had NDA holders submit two or more patents for a
> single NDA. While this may continue to occur, we believe that the
> final rule may reduce the number of patents submitted for listing
> because we have clarified the type of patents that must be submitted.
> The number of patents submitted could increase because we allow
> polymorph patents to be submitted or it could decrease if no test data
> exist to demonstrate that a drug product containing the polymorph will
> perform the same as the drug product contained in the NDA. We, thus,
> estimate the number of annual certifications at 1.5 x 74 (the number
> of original certifications). Thus, the information collection burden
> for §§ 314.50(i)(1)(i) and 341.94(a)(12) (certifications) would be 444
> hours (74 respondents x 1.5 response per respondent x 4 hours per
> response = 444 hours. The information collection burden for §§
> 314.52(a)(3) and 314.95(a)(3) (notices) would be 897 hours (74
> respondents x 1.01 response per respondent x 12 hours per respondent.
>
> To estimate the number of enhanced patent declarations that will be
> submitted annually, we referred to historical data on patent
> submissions. For the years 1998-2002, the numbers of patents submitted
> to us were 159, 205, 321, 280, and 268 respectively, for an annual
> average of 246.6 ((159 patents + 205 patents + 321 patents + 280
> patents + 268 patents) /5 years = 247 patents per year). Because many
> of these individual patents are included in multiple NDA submissions,
> there could be multiple declarations for a single patent. From our
> review of submissions, we believe the duplicate patent listings to be
> 20 percent of the number of unique patents. Therefore, we estimate
> 49.2 (246.6 patents x 20 percent) patent declarations will be multiple
> listings, and there will be 296 (247 declarations + 49 declarations =
> 296 declarations) total annual patent declarations. As we received 115
> and 99 NDAs in 2000 and 2001, respectively, we assume there will be
> 107 ((115 applications + 99 applications) / 2 years = 107
> applications/year) instances where an NDA holder would be affected by
> the patent declaration requirements and that each of these holders
> would, on average, submit 2.8 (296 declarations / 107 instances = 2.8)
> declarations per instance.
>
> However, § 314.53(b) and (c) have different impacts on the hours per
> response. On the one hand, § 314.53(b) might decrease the reporting
> burden because it would specify certain patents that must not be
> submitted, and thus discourage NDA applicants and holders and patent
> owners from submitting information on those patents. On the other
> hand, § 314.53(b) will require NDA applicants and holders or patent
> owners to submit patent information on different forms of the active
> ingredient described in the NDA, and this could result in more patent
> information being submitted or less patent information if test data do
> not exist to demonstrate that a drug product containing the polymorph
> will perform the same as the drug product described in the NDA. We
> cannot determine whether the potential net effect will increase,
> decrease, or not change the overall burden associated with submitting
> patent information, so we have not assigned any change in the total
> reporting burden for the change in patent information alone.
>
> In contrast, 314.53(c) makes the patent declaration more detailed. The
> change in the declaration will increase the burden hours per response
> under § 314.50(h) (the provision under which we covered patent
> declarations described in § 314.53(c)) because respondents will be
> required to be more precise in their declarations. Based on other
> rules that require respondents to compile and submit information in
> their possession, we estimate that the two new patent declaration will
> result in an additional information collection burden of 18 hours.
> However, the previous burden hour estimate of 1,666 hours for § 314.50
> covered paragraphs (a) through (f), in addition to paragraphs (h) and
> (k). We are unable to determine how many of the 1,666 hours were
> devoted to patent declarations, so we simply add 18 hours to the 1,666
> hour estimate for § 314.50(a) through (f), (h), and (k), resulting in
> a burden hour estimate of 1,684 hours (1,666 hours + 18 hours) to
> account for a respondent\'s need for more time to make and verify the
> patent declaration. Thus, the information collection burden for §
> 314.50(a) through (f), (h), and (k) will increase to 498,464 hours
> (296 annual responses x 1,684 hours per response = 498,464 hours).
>
> The overall reporting burden is as follows:

Table 1.-Estimated Annual Reporting Burden

  ------------------- ------------- ----------- ----------- ---------- ----------
  21 CFR Section      No. of        Frequency   Total       Hours per  Total
                      Respondents   of          Annual      Response   Hours
                                    Responses   Responses              

  314.50(a) - (f),    107           2.8         296         1,684      498,464
  (h), (k) (citing 21                                                  
  CFR 314.53) Forms                                                    
  FDA 3542 and                                                         
  4542(a)                                                              

  314.50(i)(1)(i) and 74            1.5         111         4          444
  314.94(a)(12)                                                        

  314.52(a)(3) and    74            1.01        74          12         897
  314.95(a)(3)                                                         

  Total                                                                499,805
  ------------------- ------------- ----------- ----------- ---------- ----------

> [\
> Burden Costs]{.underline}
>
> We estimate the annual reporting cost associated with this rule to be
> \$293,999 (not including previous cost estimates for § 314.50(a)
> through (f) and (k), which the final rule does not amend). Based on
> the total average hourly compensation of \$55.14, the cost would be
> \$992 (\$55.14 per hour x 18 hours per declaration) per event.[^1] The
> burden on individual firms would depend on the number of declarations
> they submit, but the estimated annual burden to all declarants would
> be \$293,000 (\$992 per declaration x 295.8 events).

13\. [Annual Cost to Respondents]{.underline}

> There are no total capital or start-up costs or service costs
> projected for this rule due to the minimal nature of the recordkeeping
> and reporting requirements.

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

> We estimate the annualized cost to the federal government to be
> negligible. While we cannot predict whether the final rule would
> result in an increase, decrease, or no change in the volume of patent
> information submitted to FDA, our patent duties are solely ministerial
> and consist largely of listing patent information in \"Approved Drug
> Products With Therapeutic Equivalence Evaluations.\"
>
> The proposed change regarding the 30-month stay and its potential to
> reduce the number of notices going from ANDA and 505(b)(2) applicants
> to NDA holders and patent owners would have little or no direct impact
> on the federal government because we do not receive copies of these
> notices. We do receive documentation to show that the NDA holder and
> patent holder received notice from the ANDA or 505(b)(2) applicant,
> but this is a ministerial action and, other than filing the
> documentation as part of the ANDA or 505(b)(2) application, we take no
> action regarding such documentation. Furthermore, because we estimate
> that the number of notices would decrease by 37 (from 37 respondents
> filing two notices per year to 37 respondents filing only one notice
> per year), we believe the government\'s cost savings associated with
> 37 pieces of documentation are also negligible.

15\. [Changes from Previous Approval]{.underline}

> The rule would represent a slight increase over the previous
> information collection burden.

16\. [Statistical Reporting]{.underline}

Information collected under this requirement will not be published.

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

We do not seek an exemption from displaying the expiration date.

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

> We are not requesting any exemption from the certification statement
> identified in Item 19 of form OMB Form 83-1.

[^1]: Hourly rate for \"lawyer\" from 2000 National Compensation Survey
    ([http://www.bls.gov/ncs/ocs/sp/ncbl0402.pdf)]{.underline} is
    \$38.70, adjusting for inflation at 2.85% (unadjusted CPI-U) and 40%
    benefits.