MODULE 1: ADMINISTRATIVE INFORMATION

Module 1 contains all administrative documents (e.g., applications forms, claims of

categorical exclusion and certifications), and labeling.

1.1 FORMS

1.1.2 Signed and Completed Application Form (356h)

It is the application to market a New Drug or Biologic or an Antibiotic drug for Human Use.
The applicant shall submit a completed and signed application form that contains the
following:

1. The name and address of the applicant; the date of the application; the application
number; the name of the drug product, including its established, and chemical names; the
dosage form and strength; the route of administration; and the drug product's proposed
indications for use.
2. Establishment information for drug substance and drug product manufacturer should
include: address, contact person, contact information, U.S. agent identification and
contact information (for foreign applicants only). A statement indicating that the
manufacturer is ready for inspection is also typically included in this section. Any outside
firms, including contract testing laboratories, used should also be listed, as appropriate, in
this section. All Drug Master Files (DMFs) that are referenced in the application must be
listed. This information is often extensive and can, therefore, be provided as an
attachment to Form FDA 356h.
3. For foreign firms, a U.S. agent must be assigned. The U.S. agent is authorized to
submit and receive correspondence on behalf of the foreign firm. If the person signing the
application does not reside or have a place of business within the United States, the
application is required to contain the name and address of, and be countersigned by, an
attorney, agent, or other authorized official who resides or maintains a place of business
within the United States.
4. Note that the form must be dated in two places, top of the first page and bottom of the
second page. A form that is not signed and dated can result in FDA refusal to accept an
application.

1.2 COVER LETTER

Cover letter should be on the letterhead of the Applicant or the Applicant Agent and should
state:

Date
“To” Address
Reference:
RLD information
Drug Product Manufacturer information
Drug Substance manufacturer information including DMF number
 Dissolution Studies information as per the OGD requirement
Expiration dating period and stability information
Labeling similarity statement
Residual Solvents Data Package information
Sterility assurance data statement
BA/BE studies and Site information
Contact person full address and email
Signature of the Responsible person

Form FDA 3674

This is the FDA form of Certification of compliance, under 42 U.S.C. $ 282(j)(5)(B),

with requirements of clinicalTrails.gov Data Bank (42 U.S.C. $ 282(j)).

Form 3674 must accompany with original submissions of ANDA submitted under 505 of the
Federal Food and Cosmetic Act of $ 351 of the Public Health Service Act.

The purpose of this form is to ensure sponsors of trials register those trials with
clinicalTrial.gov, data base established by the NIH and FDA.

The form is placed at immediate of the cover letter.

1.3.3 Debarment Certification-GDEA (Generic Drug Enforcement Act)/Other:

1. Debarment Certification (original signature)

2. List of Convictions statement (original signature)

Debarment: is the suspension or exclusion of a company or person from participation in

applications from the manufacture or distribution of Generic Drugs.

In accordance with the GDFA 1992, ANDA contains debarment certification and list of
conviction statements.

Debarment Certification: It say the applicant did not and will not use in any capacity the
services of any person debarred under section (a) and (b) 3.6 of the GDFA

List of Convictions: Means a list of all relevant convictions of the applicant and affiliated
persons responsible for the development or submission of the application.

Firm with no convictions to list should submit a statement to the effect.

The list must contain all such convictions that occurred within five years before the date of
application.
The best of SPONSOR’S knowledge, no person affiliated with SPONSOR, that was
responsible for the development or submission of thes application has been convicted of an
offense described in subsections (a) or (b) of the GDEA 1992

A signed and dated document that contains the following language is required for the Generic
Drug Enforcement Act:

Example

Generic Drug Enforcement Act – 1992

Certification Made Pursuant to the Generic Drug Enforcement Act of 1992

on behalf of [Generic Company Name's Inc. / Ltd.], the applicant, I hereby certify,
pursuant to Section 2(k) Generic Drug Enforcement Act of 1992, 21 USC 335a (k), that the
applicant has not used, is not using and will not in the future use in any capacity the services
of any person who has been debarred pursuant to Section 2 (a) and or Section 2 (b) Generic
Drug Enforcement Act of 1992, 21 USC 335a (a) and/or (b), in connection with this
application.

Applicant further certifies that there have been no conviction of applicant for any of the types
of crimes set forth in Section 2(a) and Section 2(b) of the Generic Drug Enforcement Act of
1992, 21 USC 335a (a) and/or (b), within the five years prior to the date of this certification,
nor has any person affiliated with the applicant, who is responsible in whole or in part, for
the development or the submission of this application been convicted of any crime of the
type listed in Section 2(a) and Section 2(b) of the Generic Drug Enforcement Act of 1992, 21
USC 335a (a) and/or (b), within the five years prior to the date of this certification.

[Signature of Responsible Person]

-------------------
[Name of Responsible Person] Date
Regulatory Affairs Director
[Applicant Company Name Inc. / Ltd.]
[Signature of Responsible Person]

1.3.4 Financial Certifications

Bioavailability/Bioequivalence Financial Certification (Form FDA 3454)

Disclosure Statement (Form FDA 3455, submit copy to Regulatory Branch Chief)

Bioavailability and bioequivalence studies are commonly referred to as biostudies.

FDA form 3454 is certification of financial interests and arrangements clinical investigators.

It is completed by the applicant only

FDA evaluates clinical studies submitted in marketing applications required by law for new
human drugs.

The applicant is responsible for making the appropriate certification or disclosure statement
where the applicant either contracted with one or more clinical investigators to conduct the
studies or submitted studies conducted by other not under contract to the applicant.

In the United States, the sponsor of clinical trail must certify that they have not entered into
any financial arrangements with the clinical investigators such that the value of compensation
to the investigator could be affected by the out come of the study defined in 21 CFR 54.2.

– FDA form 3454

ANDA submissions as failure to include certification could result in a refusal to file.

The sponsor of clinical trail have entered into any financial arrangements with clinical
investigator provide the disclosure statement.
– FDA form 3455

The sponsor completed form 3454, indicating that they have not entered into any financial
agreements with the clinical investigators where by the out come of the study could be
effected.

Each investigator that has participated in the study must sign and date a Disclosure statement.
Facilities that routinely perform bioequivalence studies are familiar with this requirement and
provide the disclosure statements with the final study report.

In most cases, the investigators have not participated in financial arrangements and do not
hold financial interests that must ve requires, and therefore Form 3455 is not required.
Instead the following language con be included in this section

The sponsor completed form FDA 3454, indicating that they have not entered into any
financial agreements as described in Form 3455.

1.3.5

This section is typically prepared by attorney specializing in patents as related to ANDA.

1.3.5.1 Patent Information

This section contains information for patents and exclusivities of the RLD.

All the patents listed for the RLD in the Electronic Orange Book Approved Drug Products
with Therapeutic Equivalence Evaluations.

1.3.5.2 Patent Certification

Patents claiming drug, drug product or method of use: The sponsor/applicant provides
certification with respect to each patent issued by the US patent and trademark office that, in
the opinion of the applicant and to the best of its knowledge, claims the reference listed drug
or that claims a use of such listed drug for which the applicant is seeking approval under
section 505(j) of the act and for which information is required to be filed under section
505(b) and (c) of the act and 21 CFR 314.53. For each such patent, the applicant shall
provide the paten t number and certify in its opinion and tio the best of its knowledge on of
the following circumstances:

1. That the patent information has not been submitted to FDA. The applicant shall
entitle such a certification “Paragraph I Certification”
2. That the patent has expired. The applicant shall entitle such a certification “Paragraph
II Certification”
3. The date on which the patent will expire. The applicant shall entitle such a
certification “Paragraph III Certification”
4. That the patent is invalid, unenforceable4, or will not be infringed by the
manufacture, use, or sale of the drug product for which the abbreviated application is
submitted. The applicant shall entitle such a certification “Paragraph IV Certification”.
This certification shall be submitted in the following form:

I (name of applicant, certify that patent No.________ (is invalid, unenforceable, or will not
be infringed by the manufacturer, use, or sale of ) (name of proposed drug product) for which
this application is submitted.

The certification shall be accompanied by statement that the applicant will comply with the
requirements under 21 CFR 314.95(a) with respect to providing a notice to each owner of the
patent or their representatives and to the holder of the approved application for the listed
drug, and with the requirements under 21 CFR 314.95(a) with respect to the content of the
notice.

If the ANDA refers to a listed drug that is itself a licensed generic product of a patented drug
first approved under section 505(b) of the act, the appropriate patent certification under
paragraph (a)(12)(i) of 21 CFR 94 with respect to each patent that claims the first approved
patented dug or that claims a use for such drug.

No Relevant patents: If, in the opinion of the applicant and to the best of its knowledge,
there ate no patents described in paragraph (a)(12)(i) of 21 CFR 314.94, a certification in the
following form should be provided:

“In the opinion and to the best knowledge of (name of applicant), there are no patents
that claim the listed drug referred to in this application or that claim a use of the listed
drug”.

Method of Use Patent: (A) If patent information is submitted under section 505(b) and (c)
of the act and 21 CFR 314.53 for a patent claiming a method of using the listed drug, and the
labeling for the drug product for which the applicant is seeking approval does not include any
indications that are covered by the use patent, a statement explaining that the method of use
patent does not claim any of the proposed indications should be included. (B) If the labeling
of the drug product for which the applicant is seeking approval includes an indication that,
according to the patent information submitted under section 505(b) and (c) of the act and 21
CFR 314.53 of in the opinion of the applicant, is claimed by a use patent, an application
certification under paragraph (a)(12)(i)(A)(4) of 21 CFR 314.94 (“Paragraph IV Certification
under paragraph (a)(12)(i) is required..

Method of Manufacturing Patent: An applicant is not required to make a certification with

respect to any patent that claims only a method of manufacturing the listed drug.

Licensing agreements: If the ANDA is for a drug or method of using a drug claimed by a
patent and the applicant has a licensing agreement with the patent owner, a certification
under paragraph (a)(12)(i)(A)(4) of 21 CFR 314.94(“Paragraph IV Certification) as to that
patent and a statement hat it has been granted a patent license should be provided.

Exclusivity Statement: A statement as to whether, according to the information published in

the list, the reference listed drug is entitled to a period of marketing exclusivity under section
505(j)(4)(D) of the act.
.

References

This section contains reference to previously submitted information

Applicants need to provide precise and detailed reference data to the FDA in order to clearly
identify the previously submitted file.

Here the applicant provide DMF numbers and list letter of access (LOA)

LOA letters should be clear copies and display recent dates with correct vendor names and
address.

Types of DMF files

Type I – Manufacturing site, facilities, operating procedures and personal

Type II – Drug substance, Drug substance intermediates
Type III – Packaging materials
Type IV – Excipients or material used in their preparations
Type V – FDA accepted reference information

US agent letter of Authorization

Basis for Submission

NDA# :

Ref Listed Drug:

Firm:
ANDA suitability petition required?
If Yes, then is change subject to PREA (change in dosage form, route or active ingredient)
see section 1.9.1

Comparison between Generic Drug and RLD-505(j)(2)(A)

1. Conditions of use
2. Active ingredients
3. Inactive ingredients
4. Route of administration
5. Dosage Form
6. Strength

Environmental Impact Analysis Statement Request for Waiver

Request for Waiver of In-Vivo BA/BE Study(ies):

Draft Labeling (Mult Copies N/A for E-Submissions)

1.14.1.1

4 copies of draft (each strength and container)

1.14.1.2

1 side by side labeling comparison of containers and carton with all differences annotated
and explained

1.14.1.3
1 package insert (content of labeling) submitted electronically
***Was a proprietary name request submitted?
(If yes, send email to Labeling Reviewer indicating such)

Listed Drug Labeling

1.14.3.1

1 side by side labeling (package and patient insert) comparison with all differences annotated
and explained

1.14.3.3
1 RLD label and 1 RLD container label