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`Applications Covered by Section
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`505(b)(2)
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`DRAFT GUIDANCE
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`This guidance document is being distributedfor comment purposes only.
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`Comments and suggestions regarding this draft document should be submitted within 60 days of
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`publication of the Federal Register notice announcing the availability of the draft guidance. Submit
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`comments to Dockets Management Branch (HFA-3 05), Food and Drug Administration, 5630 Fishers
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`Lane, rm. 1061, Rockville, MD 20857. All comments should be identified with the docket number
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`listed in the notice of availability that publishes in the Federal Register.
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`For questions on the content of the draft document contact Virginia Beakes, (301) 594-2041.
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`U. S. Department of Health and Human Services
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`Food and Drug Administration
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`Center for Drug Evaluation and Research (CDER)
`October 1999
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`AstraZeneca Exhibit 2172 p. l
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`
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`Guidance for Industry
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`Applications Covered by Section
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`505(b)(2)
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`DRAFT GUIDANCE
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`For additional copies, contact:
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`Drug Information Branch
`Division ofCommunications Management, HFD-2I 0
`Centerfor Drug Evaluation andResearch (CDER)
`5600 Fishers Lane
`
`Rockville, MD 20857
`(Tel) 301-827-45 73
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`http://wwwfda. gov/cder/guidance/index. htm.
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`US. Department of Health and Human Services
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`Food and Drug Administration
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`Center for Drug Evaluation and Research (CDER)
`October 1999
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`
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`Table of Contents
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`I.
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`WHAT IS THE PURPOSE OF THIS GUIDANCE? ......................................................................................................... .. 1
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`II. WHAT IS A 505(B)(2) APPLICATION? .......................................................................................................................... .. 2
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`A. WHAT TYPE OF INFORMATION CAN AN APPLICANT RELY ON? ........................................................................... .. 2
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`B.
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`WHAT KIND OF APPLICATION CAN BE SUBMITTED AS A 505(B)(2) APPLICATION? ...................................................... .. 3
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`III. WHAT ARE SOME EXAMPLES OF 505(B)(2) APPLICATIONS? ............................................................................. .. 4
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`IV. WHAT CAN‘T BE SUBMITTED AS 505(B)(2) APPLICATIONS? .............................................................................. .. 6
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`V. WHY DOES IT MATTER IF AN NDA IS A 505(B)(2) APPLICATION? .................................................................... .. 6
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`VI.
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`PATENT AND EXCLU SIVITY PROTECTIONS THAT COULD AFFECT A 505(B)(2) APPLICATION............... .. 7
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`A. WHAT TYPE OF PATENT AND/OR EXCLUSIVITY PROTECTION IS A 505(B)(2) APPLICATION ELIGIBLE FOR? .............. .. 7
`B.
`WHAT COULD DELAY THE APPROVAL OR FILING OF A 505(B)(2) APPLICATION? ......................................................... .. 7
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`VII.
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`WHAT SHOULD BE INCLUDED IN 505(B)(2) APPLICATIONS? ......................................................................... .. 7
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`REFERENCES ................................................................................................................................................................................ .. 10
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`GLOSSARY ................................................................................................................................................................................... .. 11
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`GUIDANCE FOR INDUSTRYI
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`Applications Covered by Section 505(b)(2)
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`I.
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`WHAT IS THE PURPOSE OF THIS GUIDANCE?
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`This guidance identifies the types of applications that are covered by section 505(b)(2) of the Federal
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`Food, Drug, and Cosmetic Act (the Act). A 505(b)(2) application is a new drug application (NDA)
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`described in section 505(b)(2) of the Act. It is submitted under section 505(b)(1) of the Act and
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`approved under section 505(c) of the Act. This guidance also provides filrther information and
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`amplification regarding FDA's regulations at 21 CFR 314.54.
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`Section 505 of the Act describes three types of new drug applications:
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`(1) an application that contains
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`full reports of investigations of safety and effectiveness (section 505(b)(1)); (2) an application that
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`contains filll reports of investigations of safety and effectiveness but where at least some of the
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`information required for approval comes from studies not conducted by or for the applicant and for
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`which the applicant has not obtained a right of reference (section 505(b)(2)); and (3) an application that
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`contains information to show that the proposed product is identical in active ingredient, dosage form,
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`strength, route of administration, labeling, quality, performance characteristics, and intended use, among
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`other things, to a previously approved product (section 505(j)). Note that a supplement to an
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`application is a new drug application.
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`Section 505(b)(2) was added to the Act by the Drug Price Competition and Patent Term Restoration
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`Act of 1984 (Hatch-Waxman Amendments). This provision expressly permits FDA to rely, for
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`approval of an NDA, on data not developed by the applicant. Sections 505(b)(2) and (j) together
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`replaced FDA's paper NDA policy, which had permitted an applicant to rely on studies published in the
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`scientific literature to demonstrate the safety and effectiveness of duplicates of certain post-1962
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`pioneer drug products (see 46 FR 273 96, May 19, 1981). Enactment of the generic drug approval
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`provision of the Hatch-Waxman Amendments ended the need for approvals of duplicate drugs through
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`the paper NDA process by permitting approval under 505(j) of duplicates of approved drugs (listed
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`1This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) at the Food and
`Drug Administration. This guidance document represents the Agency's current thinking on the types of applications
`that may be submitted pursuant to section 505(b)(2) of the Act. It does not create or confer any rights for or on any
`person and does not operate to bind FDA or the public. An alternative approach may be used if such approach
`satisfies the requirements of the applicable statute, regulations, or both.
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`drugs) on the basis of chemistry and bioequivalence data, without the need for evidence from literature
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`of effectiveness and safety. Section 505(b)(2) permits approval of applications other than those for
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`duplicate products and permits reliance for such approvals on literature or on an Agency finding of
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`safety and/or effectiveness for an approved drug product.
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`Definitions for specific terms used throughout this guidance are given in the Glossary.
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`11.
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`WHAT IS A 505(B)(2) APPLICATION?
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`A 505(b)(2) application is one for which one or more of the investigations relied upon by the applicant
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`for approval "were not conducted by or for the applicant and for which the applicant has not obtained a
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`right of reference or use from the person by or for whom the investigations were conducted" (21 U.S.C.
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`3 5 5 (b)(2)).
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`A.
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`What type of information can an applicant rely on?
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`What type of information can an applicant rely on in an application that is based upon studies
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`“not conducted by or for the applicant and for which the applicant has not obtained a right of
`reference?”
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`1.
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`Published literature
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`An applicant should submit a 505(b)(2) application if approval of an application will rely
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`to any extent on published literature (a literature-based 505(b)(2)). Ifthe applicant
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`has not obtained a right of reference to the raw data underlying the published study or
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`studies, the application is a 505(b)(2) application; if the applicant obtains a right of
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`reference to the raw data, the application may be a filll NDA (i.e., one submitted under
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`section 505(b)(l)). An NDA will be a 505(b)(2) application if any of the specific
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`information necessary for approval is obtained from literature or from another source to
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`which the applicant does not have a right of reference, even if the applicant also
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`conducted clinical studies to support approval. Note, however, that this does not mean
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`any reference to published general information (e.g., about disease etiology, support for
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`particular endpoints, methods of analysis) or to general knowledge causes the
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`application to be a 505(b)(2) application. Rather, reference should be to specific
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`information (clinical trials, animal studies) necessary to the approval of the application.
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`2.
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`The Agency ’5finding ofsafety and eflecttvenessfor an approved drug
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`An applicant should submit a 505(b)(2) application for a change in a drug when
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`approval of the application relies on the Agency's previous finding of safety and/or
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`effectiveness for a drug. This mechanism, which is embodied in a regulation at 21 CFR
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`314.54, essentially makes the Agency's conclusions that would support the approval of
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`a 505(j) application available to an applicant who develops a modification of a drug.
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`Section 314.54 permits a 505(b)(2) applicant to rely on the Agency's finding of safety
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`and effectiveness for an approved drug to the extent such reliance would be permitted
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`under the generic drug approval provisions at section 505(j). This approach is intended
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`to encourage innovation in drug development without requiring duplicative studies to
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`demonstrate what is already known about a drug while protecting the patent and
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`exclusivity rights for the approved drug.
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`It is possible that an applicant could submit a 505(b)(2) application that relies both on literature
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`and upon the Agency’s finding of safety and effectiveness for a previously approved drug
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`product (e.g., to support a new claim).
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`B.
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`What kind of application can be submitted as a 505(b)(2) application?
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`I.
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`New chemical entity (NCE)/new molecular entity (NA/IE)
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`A 505(b)(2) application may be submitted for an NCE when some part of the data
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`necessary for approval is derived from studies not conducted by or for the applicant
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`and to which the applicant has not obtained a right of reference. For an NCE, this data
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`is likely to be derived from published studies, rather than FDA's previous finding of
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`safety and effectiveness of a drug. Ifthe applicant had a right of reference to all of the
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`information necessary for approval, even if the applicant had not conducted the studies,
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`the application would be a considered a 505(b)(1) application.
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`2.
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`Changes to previously approved drugs
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`For changes to a previously approved drug product, an application may rely on the
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`Agency's finding of safety and effectiveness of the previously approved product,
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`coupled with the information needed to support the change from the approved product.
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`The additional information could be new studies conducted by the applicant or
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`published data. This use of section 505(b)(2), described in the regulations at 21 CFR
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`314.54, was intended to encourage innovation without creating duplicate work and
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`reflects the same principle as the 505(j) application:
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`it is wastefiil and unnecessary to
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`carry out studies to demonstrate what is already known about a drug. The approach
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`was described in a letter to industry dated April 10, 1987, from Dr. Paul D. Parkman,
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`then Acting Director of the Center for Drugs and Biologics. This guidance helps to
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`clarify and amplify the approaches stated in the April 10, 1987, letter and in the
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`regulations.
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`An applicant should file a 505(b)(2) application if it is seeking approval of a change to
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`an approved drug that would not be permitted under section 505(j), because approval
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`will require the review of clinical data. However, section 505(b)(2) applications should
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`not be submitted for duplicates of approved products that are eligible for approval
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`under 5050) (see 21 CFR 314.101(d)(9)).
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`In addition, an applicant may submit a 505(b)(2) application for a change in a drug
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`product that is eligible for consideration pursuant to a suitability petition under Section
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`505(j)(2)(C) of the Act. In the preamble to the implementing regulations for the Hatch-
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`Waxman amendments to the Act, the Agency noted that an application submitted
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`pursuant to section 505(b)(2) of the Act is appropriate even when it could also be
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`submitted in accordance with a suitability petition as defined at section 505(j)(2)(C) of
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`the Act (see 57 FR 17950; April 28, 1992).
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`III. WHAT ARE SONIE EXANIPLES OF 505(B)(2) APPLICATIONS?
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`Following are examples of changes to approved drugs for which 505(b)(2) applications should be
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`submitted. Please note that in particular cases, changes of the type described immediately below may
`not require review of information other than BA or BE studies or data from limited confirmatory testing.2
`In those particular cases, approval of the drug may also be sought in a 505(j) application based on an
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`approved suitability petition as described in section 505(j)(2)(C) of the Act. The descriptions below
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`address the situation in which the application should be filed as a 505(b)(2) application because
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`approval of the application will require review of studies beyond those that can be considered under
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`section 505(j). Some or all of the additional information could be provided by literature or reference to
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`past FDA findings of safety and effectiveness for approved drugs, or it could be based upon studies
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`conducted by or for the applicant or to which it has obtained a right of reference.
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`0 Dosage form. An application for a change of dosage form, such as a change from a solid oral
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`dosage form to a transdermal patch, that relies to some extent upon the Agency's finding of
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`safety and/or effectiveness for an approved drug.
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`0 Strength. An application for a change to a lower or higher strength.
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`0 Route ofadministration. An application for a change in the route of administration, such as a
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`change from an intravenous to intrathecal route.
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`0
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`Substitution ofan active ingredient in a combination product. An application for a change
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`in one of the active ingredients of an approved combination product for another active ingredient
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`that has or has not been previously approved.
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`Following are additional examples of applications that may be accepted pursuant to section 505(b)(2)
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`of the Act. Some or all of the additional information could be provided by the literature or reference to
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`2 Limited confirmatory testing is explained in further detail in 54 FR 288872, 28880 (July 10, 1989) and 57 FR 17950,
`17957-58 (April 28, 1992).
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`past FDA findings of safety and effectiveness for approved drugs, or it could be based on studies
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`conducted by or for the applicant or to which it has obtained a right of reference.
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`0 Formulation. An application for a proposed drug product that contains a different quality or
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`quantity of an excipient(s) than the listed drug where the studies required for approval are
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`beyond those considered limited confirmatory studies appropriate to a 505(j) application.
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`0 Dosing regimen. An application for a new dosing regimen, such as a change from twice daily
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`to once daily.
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`0 Active ingredient. An application for a change in an active ingredient such as a different salt,
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`ester, complex, chelate, clathrate, racemate, or enantiomer of an active ingredient in a listed
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`drug containing the same active moiety.
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`0 New molecular entity. In some cases a new molecular entity may have been studied by parties
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`other than the applicant and published information may be pertinent to the new application. This
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`is particularly likely if the NME is the prodrug of an approved drug or the active metabolite of
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`an approved drug. In some cases, data on a drug with similar pharmacologic effects could be
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`considered critical to approval.
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`0 Combination product. An application for a new combination product in which the active
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`ingredients have been previously approved individually.
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`o
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`Indication. An application for a not previously approved indication for a listed drug.
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`0 Rx/OTC switch. An application to change a prescription (Rx) indication to an over-the-counter
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`(OTC) indication.
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`o OTC monograph. An application for a drug product that differs from a product described in
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`an OTC monograph (21 CFR 330.11), such as a nonmonograph indication or a new dosage
`form.
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`0 Naturally derived or recombinant active ingredient. An application for a drug product
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`containing an active ingredient(s) derived from animal or botanical sources or recombinant
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`technology where clinical investigations are necessary to show that the active ingredient is the
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`same as an active ingredient in a listed drug.
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`0 Bioinequivalence. Generally, an application for a pharmaceutically equivalent drug product
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`must be submitted under section 5050) of the Act and the proposed product must be shown to
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`be bioequivalent to the reference listed drug (21 CFR 314.101(d)(9)). Applications for
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`proposed drug products where the rate (21 CFR 3 l4.54(b)(2)) and/or extent (21 CFR
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`3 l4.54(b)(l)) of absorption exceed, or are otherwise different from, the 5050) standards for
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`bioequivalence compared to a listed drug may be submitted pursuant to section 505(b)(2) of the
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`Act. Such a proposed product may require additional clinical studies to document safety and
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`efficacy at the different rate and extent of delivery. Generally, the differences in rate and extent
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`of absorption should be reflected in the labeling of the 505(b)(2) product. The proposed
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`product does not need to be shown to be clinically better than the previously approved
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`product; however, a 505(b)(2) application should not be used as a route of approval for poorly
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`bioavailable generic drug products unable to meet the 505(j) standards for bioequivalence. If
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`the proposed product is a duplicate of an already approved product, it should not be submitted
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`as a 505(b)(2) application (21 CFR 314.101(d)(9)).
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`For example, a 505(b)(2) application would be appropriate for a controlled release product
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`that is bioinequivalent to a reference listed drug where:
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`1.
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`The proposed product is at least as bioavailable as the approved
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`pharmaceutically equivalent product (unless it has some other advantage, such
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`as smaller peak/trough ratio); or
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`2.
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`The pattern of release of the proposed product, although different, is at least as
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`favorable as the approved pharmaceutically equivalent product.
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`IV. WHAT CAN'T BE SUBMITTED AS 505(B)(2) APPLICATIONS?
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`0 An application that is a duplicate of a listed drug and eligible for approval under section 505(j)
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`(see 21 CFR 314.101(d)(9)); or,
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`0 An application in which the only difference from the reference listed drug is that the extent to
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`which the active ingredient(s) is absorbed or otherwise made available to the site of action is
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`less than the listed drug (21 CFR 314.54(b)(1)); or,
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`0 An application in which the only difference from the reference listed drug is that the rate at
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`which its active ingredient(s) is absorbed or otherwise made available to the site of action is
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`unintentionally less than that of the listed drug (21 CFR 314.54(b)(2)).
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`V.
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`WHY DOES IT MATTER IF AN NDA IS A 505(B)(2) APPLICATION?
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`Unlike a filll NDA for which the sponsor has conducted or obtained a right of reference to all the data
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`essential to approval, the filing or approval of a 505(b)(2) application may be delayed due to patent or
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`exclusivity protections covering an approved product. Section 505(b)(2) applications must include
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`patent certifications described at 21 CFR 314.50(i) and must provide notice of certain patent
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`certifications to the NDA holder and patent owner under 21 CFR 314.52.
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`v1.
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`PATENT AND EXCLUSIVITY PROTECTIONS THAT COULD AFFECT A
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`505(B)(2) APPLICATION
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`A.
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`What type of patent and/or exclusivity protection is a 505(b)(2) application
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`eligible for?
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`A 505(b)(2) application may itself be granted 3 years of Waxman-Hatch exclusivity if one or
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`more of the clinical investigations, other than BA/BE studies, was essential to approval of the
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`application and was conducted or sponsored by the applicant (21 CFR 314.50(j);
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`314.108(b)(4) and (5)). A 505(b)(2) application may also be granted 5 years of exclusivity if it
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`is for a new chemical entity (21 CFR 314.50(j); 314.108(b)(2)). A 505(b)(2) application may
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`also be eligible for orphan drug exclusivity (21 CFR 31420-31636) or pediatric exclusivity
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`(section 505A of the Act).
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`A 505(b)(2) application must contain information on patents claiming the drug or its method of
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`use (21 CFR 314.54(a)(1)(V)).
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`B.
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`What could delay the approval or filing of a 505(b)(2) application?
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`Approval or filing of a 505(b)(2) application, like a 505(j) application, may be delayed because
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`of patent and exclusivity rights that apply to the listed drug (21 CFR 314.50(i), 314.107, and
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`314.108 and section 505A of the Act). This is the case even if the application also includes
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`clinical investigations supporting approval of the application.
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`VII. WHAT SHOULD BE INCLUDED IN 505(B)(2) APPLICATIONS?
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`The Act (sections 505(b)(1) and (b)(2)) and FDA regulations (21 CFR 314.54) distinguish between
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`505(b)(1) and (b)(2) applications. Although the two types of applications must meet the same
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`standards for approval (see section 505(b) and (c) of the Act), they differ in source of information to
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`support safety and effectiveness, the patent certification requirements, BA/BE evidence, exclusivity bars,
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`and processing within the FDA. The requirements for 505(b)(1) and 505(b)(2) applications are
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`described at 21 CFR 314.50. Additional requirements for certain 505(b)(2) applications are described
`at 21 CFR 314.54.
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`A 505(b)(2) application should include the following:
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`0
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`Identification of those portions of the application that rely on information the applicant does not
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`own or to which the applicant does not have a right of reference (for example, for reproductive
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`toxicity studies).
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`0
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`Ifthe 505(b)(2) seeks to rely on the Agency's previous finding of safety or efficacy for a listed
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`drug or drugs, identification of any and all listed drugs by established name, proprietary name (if
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`any), dosage form, strength, route of administration, name of the listed drug's sponsor, and the
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`application number (21 CFR 3 14.54(a)(1)(iii)). Even if the 505(b)(2) application is based
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`solely upon literature and does not rely expressly on an Agency finding of safety and
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`effectiveness for a listed drug, the applicant must identify the listed drug(s) on which the studies
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`were conducted, if there are any.
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`If the 505(b)(2) application is for an NCE and the 505(b)(2)
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`applicant is not relying on literature derived from studies of an approved drug, there may not be
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`a listed drug.
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`Ifthere is a listed drug that is the pharmaceutical equivalent to the drug proposed
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`in the 505(b)(2) application, that drug should be identified as the listed drug.
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`0
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`Information with respect to any patents that claim the drug or the use of the drug for which
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`approval is sought (21 CFR 3 l4.50(h)). This patent information will be published in the Orange
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`Book when the application is approved.
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`0
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`Information required under 314.500) if the applicant believes it is entitled to marketing
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`exclusivity (21 CFR 314.54(a)(l)(vii)).
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`o A patent certification or statement as required under section 505(b)(2) of the Act with respect
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`to any relevant patents that claim the listed drug and that claim any other drugs on which the
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`investigations relied on by the applicant for approval of the application were conducted, or that
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`claim a use for the listed or other drug (21 CFR 314.54(a)(l)(vi)).
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`Ifthere is a listed drug that is the pharmaceutical equivalent of the drug proposed in the
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`505(b)(2) application, the 505(b)(2) applicant should provide patent certifications for the
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`patents listed for the pharmaceutically equivalent drug. Patent certifications should specify the
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`exact patent number(s), and the exact name of the listed drug or other drug even if all relevant
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`patents have expired.
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`0
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`If an application is for approval of a new indication, and not for the indications approved for the
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`listed drug, a certification so stating (21 CFR 314.54(a)(l)(iv).
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`o A statement as to whether the listed drug(s) identified above have received a period of
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`marketing exclusivity (21 CFR 314.108(b)). If a listed drug is protected by exclusivity, filing or
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`approval of the 505(b)(2) application may be delayed.
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`o A Bioavailability/Bioequivalence (BA/BE) study comparing the proposed product to the listed
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`drug (if any).
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`0
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`Studies necessary to support the change or modification from the listed drug or drugs (if any).
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`Complete studies of safety and effectiveness may not be necessary if appropriate bridging
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`studies are found to provide an adequate basis for reliance upon FDA’s finding of safety and
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`effectiveness of the listed drug(s).
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`Before submitting the application, the applicant should submit a plan to the appropriate new
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`drug evaluation division identifying the types of bridging studies that should be conducted. The
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`applicant should also identify those components of its application for which it expects to rely on
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`FDA’s finding of safety and effectiveness of a previously approved drug product. The division
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`will critique the plan and provide guidance.
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`REFERENCES
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`April 10, 1987, letter from then Acting Director of the Center for Drugs and Biologics to all NDA and
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`ANDA holders and applicants.
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`"Abbreviated New Drug Application Regulations; Proposed Rule," Federal Register. Vol. 54, No.
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`130, Monday, July 10, 1989, page 28872.
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`"Abbreviated New Drug Regulations; Final Rule," Federal Register. Vol. 57, No. 82, Tuesday, April
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`28, 1992, page 17950.
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`"Abbreviated New Drug Application Regulations; Patent and ExclusiVity Provisions; Final Rule,"
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`Federal Register. Vol. 59, No. 190, Monday, October 3, 1994, page 50338.
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`AstraZeneca Exhibit 2172 p. 13
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`GLOSSARY
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`505(b)(2) application: an application submitted under section 505(b)(1) of the Act for a drug for
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`which one or more of the investigations relied on by the applicant for approval of the "application were
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`not conducted by or for the applicant and for which the applicant has not obtained a right of reference
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`or use from the person by or for whom the investigations were conducted" (21 U. S.C. 355(b)(2)).
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`Active ingredient: "any component that is intended to filI‘nlSh pharmacological activity or other direct
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`effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or
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`any function of the body of man or of animals. The term includes those components that may undergo
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`chemical change in the manufacture of the drug product and be present in the drug product in a modified
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`form intended to filI‘nlSh the specified activity or effect" (21 CFR 60.3(b)(2)).
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`Active moiety: "the molecule or ion, excluding those appended portions of the molecule that cause the
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`drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent
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`derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or
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`pharmacological action of the drug substance" (21 CFR 314.108(a)).
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`Investigations relied on for approval:
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`those without which the application cannot be approved (i.e.,
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`animal and human safety tests as well as clinical investigations of effectiveness).
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`Listed drug: "a new drug product that has an effective approval under section 505(c) of the act for
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`safety and effectiveness or under section 505(j) of the act, which has not been withdrawn or suspended
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`under section 505(e)(1) through (e)(5) or (j)(5) of the act, and which has not been withdrawn from sale
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`for what FDA has determined are reasons of safety or effectiveness. Listed drug status is evidenced by
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`the drug product's identification as a drug with an effective approval in the current edition of FDA's
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`“Approved Drug Products with Therapeutic Equivalence Evaluations” (the list) or any current
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`supplement thereto, as a drug with an effective approval. A drug product is deemed to be a listed drug
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`on the date of effective approval of the application or abbreviated application for that drug product" (21
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`CFR 314.3(b)).
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`Literature: published reports of well-controlled studies that support safety or effectiveness; proposed
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`and final monographs published in the Federal Register; the data supporting a Federal Register notice
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`announcing a product’s safety and/or effectiveness.
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`Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations and any
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`current supplement to the publication.
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`Pharmaceutical equivalent or duplicate: "drug products that contain identical amounts of the
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`identical active drug ingredient, i.e., the same salt or ester of the same therapeutic moiety, in identical
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`dosage forms, but not necessarily containing the same inactive ingredients, and that meet the identical
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`compendial or other applicable standard of identity, strength, quality, and purity, including potency and,
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`AstraZeneca Exhibit 2172 p. 14
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`where applicable, content uniformity disintegration times and/or dissolution rates" (21 CFR 320.1(c)).
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`Products with different mechanisms of release can be considered to be pharmaceutical equivalents or
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`duplicates.
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`Referenced listed drug: "the listed drug identified by FDA as the drug product upon which an
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`applicant relies in seeking approval of its abbreviated application" (21 CFR 314.3(b)).
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`Right of reference or use: "the authority to rely upon, and otherwise use, an investigation for the
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`purpose of obtaining approval of an application, including the ability to make available the underlying
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`raw data from the investigation for FDA audit, if necessary" (21 CFR 314.3(b)).
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`Sponsors have the right of reference to any studies: (1) they conduct, (2) that are conducted for them,
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`or (3) for which they formally obtain a documented right ofreference.
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`An applicant is not considered to have a right ofreference to published studies, because the applicant
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`does not have access to the raw data. However, if the raw data are in the public domain, a right of
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`reference is unnecessary.
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`Suitability petition: A citizen petition submitted to the Agency seeking permission to file an
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`abbreviated new drug application for a change from a listed drug in dosage form, strength, route of
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`administration, or active ingredient in a combination product. (See section 505(j)(2)(C) of the Act)
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`AstraZeneca Exhibit 2172 p. 15
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