ABBREVIATED NEW DRUG APPLICATION REGULATIONS;

PATENT AND EXCLUSIVITY PROVISIONS - 0910-0305

Docket No. 00N-1666

A. [Justification]{.underline}

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

Section 505 of the Federal Food, Drug, and Cosmetic Act (the act)(21
U.S.C. 355) requires patent owners to submit to FDA information about
patents that cover approved drugs. Generic copies of these drugs may be
approved when the patents expire or if a generic company certifies that
the patent is invalid or will not be infringed. In such cases, the
generic company must notify the patent owner about the certification,
and approval of the drug may not be made effective until after the court
decides the patent infringement suit or a period of 36 months, whichever
occurs first. In addition, section 505 of the act provides several
periods of marketing exclusivity ranging from 3 to 10 years (depending
primarily on the nature of the innovation). If a drug product receives
marketing exclusivity, FDA will not approve (or, in limited cases not
receive) an abbreviated new drug application (ANDA) for the drug
product.

Under the authority found in sections 505 and 701 of the act (21 U.S.C.
371), FDA issued regulations governing patent and exclusivity provisions
in 21 CFR part 314. The regulations provide instructions for new drug
application (NDA) applicants (including section 505(b)(2) of the act
applicants) and ANDA applicants on how to file patent information and
request marketing exclusivity; require patent certification information
for section 505(b)(2) applications and ANDAs; require information for
requests for marketing exclusivity for NDAs (including section 505(b)(2)
applications and certain NDA supplements); and require patent
information for NDAs.

The specific reporting requirements that are the subject of this
information collection are as follows:

21 CFR 314.50(i) Requires the submission of patent certification
information.

21 CFR 314.50(j) Requires the submission of marketing exclusivity
information.

21 CFR 314.52 Requires notice of certification of invalidity or
noninfringement of a patent.

21 CFR 314.53 Requires the submission of patent information.

21 CFR 314.54(a)(1)(vii) Requires the submission of marketing
exclusivity information.

21 CFR 314.70(e) Requires the submission of patent information.

21 CFR 314.70(f) Requires the submission of marketing exclusivity
information.

21 CFR 314.94(a)(12) Requires the submission of patent certification
information.

21 CFR 314.95 Requires notice of certification of invalidity or
noninfringement of a patent.

21 CFR 314.107(c)(4);

(e)(2)(iv); (f) Requires notice of the date of commercial marketing; a
copy of the entry of the order or judgement; notice of the filing of
legal action after notice of certification.

Applicants must provide information on patents to FDA to enable the
agency to determine whether a product is covered by a patent or whether
approval of a proposed drug product would result in patent infringement.
The agency lists the patent information as a reference of potential
applicants. If an applicant believes a patent is invalid or would not be
infringed, Federal law also requires it to notify the patent holder. FDA
approval, in such cases, is affected should there be any patent
litigation. Failure to provide this information would result in an
incomplete application and constitute grounds for refusing to approve
the application.

Applicants submitting NDAs are required under the act to provide
information on certain patents that cover their drug products. The
agency lists this patent information in its publication entitled *List
of Approved Drug Products With Therapeutic Equivalence Evaluations.*

To promote product innovation, the act also gives NDA applicants several
periods of "market exclusivity" ranging from 3 to 10 years (depending
primarily on the nature of the innovation). If a drug product receives
marketing exclusivity, FDA will not approve (or, in limited cases, even
receive) an ANDA for the drug product during that time period.

2\. [Purpose and Use of Information]{.underline}

Federal law requires applicants to provide information on patents to FDA
to enable the agency to determine whether a product is covered by a
patent or whether approval of a proposed drug product would result in
patent infringement. The agency lists the patent information as a
reference for potential applicants. If an applicant believes a patent is
invalid or would not be infringed, federal law also requires it to
notify the patent holder. FDA approval, in such cases, is affected
should there be any patent litigation. Failure to provide this
information would result in an incomplete application and constitute
grounds for refusing to approve the application.

3\. [Use of Improved Information Technology]{.underline}

[Electronic Regulatory Submissions for Archive]{.underline}. The Food
and Drug Administration Modernization Act of 1997 (FDAMA) and the
Prescription Drug User Fee Act (PDUFA) II reauthorization mandate that
the agency develop and update its information management infrastructure
to allow, by fiscal year 2002, the paperless receipt and processing of
investigational new drug applications and new drug applications, as
defined in PDUFA, and related submissions. Moving an
information-intensive activity, such as drug regulatory review, from a
paper-based to an electronic environment will provide a number of
benefits. This is true simply from the perspective of generating,
handling, and storing the huge volumes of paper commonly associated with
applications. In general, these paper applications (often containing
hundreds of volumes) are submitted with several copies, a process that
can take several days longer than preparation of a corresponding
electronic submission, which the agency can easily reproduce.
Preparation of applications in electronic format results in direct cost
savings related to materials, supplies, and paper handling logistics
(i.e., labor, facilities). However, this is expected to be only a small
portion of the potential savings. The most substantial burden reduction
may not be in information recording, reporting, and record-keeping, but
in the flexibility, efficiency, speed, and ease of filing required
information that will result in cost savings to regulated industry, as
well as FDA.

In September 1997, FDA published the Guidance for Industry on "Archiving
Submissions in Electronic Format --- NDAs". This guidance provided for
the receipt and archive of electronic Case Report Forms (CRF) and Case
Report Tabulations (CRT) without an accompanying paper copy. In FY 1998,
FDA established an Electronic Document Room (EDR) to manage the receipt
and handling of all electronic submissions. In January 1999, FDA
published the Guidance for Industry on "Providing Regulatory Submissions
in Electronic Format --- NDAs". This guidance document covers the full
NDA and is not limited to CRTs and CRFs.

FDA has received 264 NDAs with electronic components since January 1999.
Of these 89 were new submissions. In the same period the agency has also
received 273 supplements with electronic components of which 170 were
new supplements. As of the end of August 2000, the agency\'s EDR was
comprised of three groups of NDAs: those that consisted of items 11
and/or 12 only (109 or 42.4%); those that consisted of various items
with or without items 11 and 12 (105 or 40.9%); and those consisting of
nearly all 19 possible NDA data items (43 or 16.7%). A total of 197
(76.7%) of NDAs with electronic components had items 11 and/or 12
submitted in an electronic format.

[Secure E-Mail]{.underline}. During a drug's development cycle,
communications between agency review divisions and the company
developing the drug is sensitive and proprietary. Prior to using secure
E-mail, agency methods of "secure" communication included U.S. mail,
courier, telephone, and facsimile. These methods, some of which are not
entirely secure, can be inefficient or time consuming, and can
significantly contribute to the overall length of time involved in the
drug review process. The widespread use of E-mail across the Internet
offers a more efficient and scaleable means of information exchange.
However, security risks of communicating over the Internet are well
known. The information technology industry is answering security
concerns by developing new standards of cryptographic techniques, E-mail
formats, authentication algorithms, and other related aspects of secure
communications. In 1998, the agency conducted a formal requirements
study for secure E-mail which led to the selection of Worldtalk
Corporation's WorldSecure Server as the base pilot platform. The agency
completed a pilot, the final system design and implemented the
production system in October 1999. The system is used across the Center
for Drug Evaluation and Research to communicate with over 15 companies
and more than 150 individuals in those companies. The system also
provides virus scanning and extensive E-mail filtering capabilities.

[ICH M2]{.underline}. The International Conference on Harmonisation
(ICH) of Technical Requirements for the Registration of Pharmaceuticals
for Human Use was formed to minimize waste in the discovery,
development, regulation, manufacture, marketing, and use of human
therapeutic products worldwide. The regulatory authorities of Europe,
Japan, and the United States joined with their respective pharmaceutical
trade associations in an agreement to take action on harmonization by
participating in the ICH.

The ICH Multi-disciplinary Group 2 (M2) Expert Working Group (EWG) was
established to determine electronic standards and provide solutions to
facilitate international electronic communication in the three ICR
regions. The first effort of the M2 EWG was to establish a series of
recommendations that would form the basis for standardized electronic
communication in each of the three regions. These recommendations
included physical media formats, secure communications, and structured
data formats. Building on these standards, the EWG completed a detailed
specification for the secure, electronic transmission of individual case
safety reports (adverse event reports). The specification is being used
to format and transmit electronic adverse event reports directly from a
company's database to the FDA Adverse Event Reporting System (AERS).

The production of a specification for an electronic common technical
document (CTD) was the next major effort assigned to the M2 EWG. The ICH
Steering committee agreed in March 1999 that this effort should be
undertaken by the M2 EWG in cooperation with the subject matter expert
working groups for each section of the CTD. The CTD working groups are
charged with harmonizing the format and content of the application
documents for new product applications. The resulting ICH guidances,
when implemented, will change the content and format of NDA submissions
to the FDA. The M2 EWG is working with the CTD Step 2 documents to
define the functionality to be included in the electronic submission for
CTD submissions.

4\. [Efforts to Identify Duplication]{.underline}

Because of the unique nature of the information to be collected (an
assessment by the applicant of the relationship between its drug product
and a patented product), duplication of information is unlikely.

5\. [Involvement of Small Entities]{.underline}

Small businesses and individuals may seek marketing approval of a drug
product. The information reported under this rule, however, should
already be in the applicant's possession (if the applicant is the patent
holder or licensee) or can be easily obtained by a small business or
individual through publicly available materials. Therefore, the rule
makes no special provisions for small businesses.

6\. [Consequences if Information Collected Less Frequently]{.underline}

Section 505 of the act requires applicants to provide patent
certification information. Failure to do so would result in an
incomplete application that would not be accepted by the agency. Thus,
without the reporting requirements, applicants would not be in
compliance with the act.

7\. [Consistency with Guidelines in 5 CFR 1320.6]{.underline}

The collection methods are consistent with the guidelines of 5 CFR
1320.6.

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

In the FEDERAL REGISTER of January 3, 2001, the agency requested
comments on the proposed collections of information. No comments were
received.

Consultation with non-agency personnel has been continuous and the
agency has been receiving applications containing patent and exclusivity
information since September 1984. Over 100 comments were received and
addressed in the final rule for this rulemaking in 1994. The patent and
exclusivity issues have been the topics of many conferences and
workshops sponsored, for example, by the Food and Drug Law Institute and
attended by industry representatives.

9\. [Remuneration of Respondents]{.underline}

FDA has not provided and has no intention to provide any payment or gift
to respondents under this provision.

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

Trade secret information collected under section 505 of the act is
protected by law (see 21 U.S.C. 331(j)). Additionally, FDA regulations
state that the agency will not disclose the existence of an application
before the agency sends an approvable letter to the applicant (21 CFR
314.430).

11\. [Questions of a Sensitive Nature]{.underline}

This collection does not contain questions pertaining to sex, behavior,
attitude, religious beliefs, or any other matters that are commonly
considered private or sensitive in nature.

12\. [Estimates of Annualized Hour Burden]{.underline}

Agency staff familiar with these submissions estimate the industry
burden hours to range from 1 to 16 hours for each type of response. FDA
has been receiving and approving NDAs and ANDAs containing patent and
exclusivity information since September 1984; therefore, the figures for
the respondents are an actual count. Data collected for the past few
years was used to make these estimates.

+--------------------+---------+----------+---------+--------+-------+
| Estimated Annual   |         |          |         |        |       |
| Reporting Burden   |         |          |         |        |       |
+====================+=========+==========+=========+========+=======+
| 21 CFR Section     | Number  | Number   | Total   | Hours  | Total |
|                    | of      | of       | Annual  | Per    | Hours |
|                    | Respon- | R        | Re      | Re     |       |
|                    |         | esponses | sponses | sponse |       |
|                    | dents   |          |         |        |       |
|                    |         | Per      |         |        |       |
|                    |         | Re       |         |        |       |
|                    |         | spondent |         |        |       |
+--------------------+---------+----------+---------+--------+-------+

+--------------------+---------+----------+---------+--------+-------+
| [Patent            | 85      | 3.8      | 325     | 2      | 650   |
| Inform             |         |          |         |        |       |
| ation]{.underline} | 97      | 3.4      | 331     | 2      | 662   |
|                    |         |          |         |        |       |
| 314.50(h)          | 37      | 2        | 75      | 16     | 1200  |
|                    |         |          |         |        |       |
| 314.53             | 92      | 2.7      | 250     | 2      | 500   |
|                    |         |          |         |        |       |
| 314.70(e)          | 34      | 2        | 71      | 1      | 71    |
|                    |         |          |         |        |       |
| [Patent            |         |          |         |        | 3,083 |
| Certification      |         |          |         |        |       |
| Inform             |         |          |         |        |       |
| ation]{.underline} |         |          |         |        |       |
|                    |         |          |         |        |       |
| 314.50(i)          |         |          |         |        |       |
|                    |         |          |         |        |       |
| 314.94(a)(12)      |         |          |         |        |       |
|                    |         |          |         |        |       |
| [Notice of         |         |          |         |        |       |
| Certification of   |         |          |         |        |       |
| Invalidity or      |         |          |         |        |       |
| Noninfringement of |         |          |         |        |       |
| a                  |         |          |         |        |       |
| P                  |         |          |         |        |       |
| atent]{.underline} |         |          |         |        |       |
|                    |         |          |         |        |       |
| 314.52             |         |          |         |        |       |
|                    |         |          |         |        |       |
| 314.95             |         |          |         |        |       |
|                    |         |          |         |        |       |
| [Marketing         |         |          |         |        |       |
| Exclusivity        |         |          |         |        |       |
| Inform             |         |          |         |        |       |
| ation]{.underline} |         |          |         |        |       |
|                    |         |          |         |        |       |
| 314.50(j)          |         |          |         |        |       |
|                    |         |          |         |        |       |
| 314.54(a)(1)(vii)  |         |          |         |        |       |
|                    |         |          |         |        |       |
| 314.70(f)          |         |          |         |        |       |
|                    |         |          |         |        |       |
| [Notification of   |         |          |         |        |       |
| Date of Commercial |         |          |         |        |       |
| Marketing; Entry   |         |          |         |        |       |
| of the Order or    |         |          |         |        |       |
| Judgement; Filing  |         |          |         |        |       |
| of Legal           |         |          |         |        |       |
| A                  |         |          |         |        |       |
| ction]{.underline} |         |          |         |        |       |
|                    |         |          |         |        |       |
| 314.107(c)(4),     |         |          |         |        |       |
| (e)(2)(iv),        |         |          |         |        |       |
| (f)(2), (f)(3)     |         |          |         |        |       |
|                    |         |          |         |        |       |
| [                  |         |          |         |        |       |
| TOTAL]{.underline} |         |          |         |        |       |
+--------------------+---------+----------+---------+--------+-------+

13\. [Estimates of Annualized Cost Burden to Respondents]{.underline}

The cost for preparing and submitting the required patent and
exclusivity reports is based on the following wage rates: Upper
management at \$70.00 per hour; middle management at \$35.00 per hour;
and clerical assistance at \$23.00 per hour. Using an averaged wage rate
of \$50 per hour (based on the percentage of time required for each type
of employee), the total cost burden to respondents would be \$
154,150.00.

14\. [Estimates of Annualized Cost Burden to the Government]{.underline}

The estimated annual cost to the Federal government of reviewing patent
and exclusivity information is \$15,000.00. The agency estimates that an
FDA reviewer examining an NDA devotes 5 hours per month, or 60 hours per
year, to reviewing patent and exclusivity information. This results in
0.02 full-time equivalents (FTEs) per NDA, and, based on a cost of
\$100,000 per FTE, a cost of \$2,000 for NDAs (0.02 x \$100,000). For
ANDA's, the agency estimates that reviewers spend 24 hours per month, or
288 hours per year, on patent and exclusivity issues. This results in
0.13 FTEs and a cost of \$13,000 for ANDA's.

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

There is an increase of 1,352 burden hours in this supporting statement
because the agency has received an increase in patent information
submissions, and because some of the data has been recalculated.

16\. [Time Schedule, Publication, and Analysis Plans]{.underline}

Statistical reports were not part of this submission.

17\. [Displaying of OMB Expiration Date]{.underline}

Approval for not displaying expiration date is not needed for this
submission.

18\. [Exception to Certification Statement - Item 19]{.underline}

No exceptions for this Certification Statement submission.

pra0305s.301 3/13/01