LABELLING

CONSIDERATION IN
ANDA
Pundalik Pai
Labelling components
Direct In-Direct

1. Label as actual on 1. Magzine ads

container 2. TV commercials
2. Package Insert 3. Sales materials-Given
3. The carton-In which by MR’s to doctors
drug is dispensed 4. Any other promotional
4. Blister packaging items
5. Anything else
dispensed to patient
with drug product
Labelling Considerations in ANDA
1. ANDA submission in eCTD format
2. 05 Modules in eCTD
3. Labelling component can be found in Module 01,
section 1.14.1 and 1.14.3.
4. Proposed labelling for generic product is called “Draft
Labelling”.
5. A generic product label should be same (exact copy) as
that of its reference product (RLD).
6. From where to get a recent RLD label??
7. Drugs@FDA and Dailymed.
8. Which should be referred to file an ANDA?
Labelling Considerations in ANDA
• Drugs@FDA
• This site has most recently approved version of the package
insert in PDF format.
• DailyMed
• This site has the most updated package insert in SPL format
used by RLD manufacturer.
• The changes are latest and may be pending for approval via
RLD’s annual reports or supplements.
• Which site should we refer???
• Safer side- most recently approved version of the Label that is
FDA approved.
• Good IDEA- Compare both, note the differences from
DailyMed. Why?
What Label is submitted in ANDA?
• ANDA labelling is submitted as in eCTD/ as a separate
CD (Traditional format)
• What does a Labelling submission include??
1. The RLD’s labelling (all components)
2. The Proposed labelling (draft label of generic product)
3. Labelling history document.
4. Side by side comparison of the approved (RLD) label
versus proposed label.
5. A statement that the proposed labelling is same as
RLD’s labelling [except for some allowed differences
described in 21CFR 314.94 (8)(iv)].
What differences are allowed in proposed label??
1. Expiration date
2. Formulation
3. Pharmacokinetics
4. Omission of any indication
5. Labelling revisions as per current FDA labelling
guidelines.
“Carve outs”
6. Also called as section viii submission.
7. Section viii??-
8. It’s a Statement given in Food Drug and Cosmetic Act
section 505(j)(2)(A)(viii)
 “Carve outs”

• Section viii states that;

• An ANDA applicant seeking to omit an approved method
of use covered by a listed patent may submit a section viii
statement acknowledging a given method of use for which
patent has been listed, but does not claim a use for which
the applicant seeks approval.
• Applicable for products where the RLD holds more than
one FDA approved indication.
• The ANDA applicant needs to carve out the
patent/exclusivity protected indication from RLD labelling,
also any data related to that indication e.g clinical trials for
said indication.
 SPL-Structured Product Labelling
• Package insert is submitted in SPL format.
• FDA implemented SPL format requirements on 31st Oct 2005.
• Aim-to support health information management technologies
such as electronic prescribing, the electronic health record
which provides health care providers and patients to access
patient information in electronic format on a national scale.
• Package insert in SPL format is published in DailyMed.
• SPL is specific business application of XML.
 Converted SPL using
Word or PDF Converted

XML FDA
document
stylesheet

What is a FDA stylesheet??

It is a file that supplies instruction for how to format an XML document. Here format is
decided by FDA. As per its requirements.
SPL-Benefit

Through the use of SPL, labeling content will flow directly from the
manufacturers to end consumers in a timely manner, providing accurate and
consistent product information that is accessible to health care professionals,
the general public and computer systems.
 Submission to FDA
Direct upload in eCTD
• In module 1
Draft Labeling (Multi Copies N/A for E-Submissions)
• 1.14.1.1 4 copies of draft for paper submission only (each strength and
container)
• 1.14.1.2 1 side by side labeling comparison of containers and carton with all
differences visually highlighted and annotated
• 1.14.1.3 1 package insert (content of labeling) and SPL submitted Electronically
• 1.14.3 Listed drug labelling
• 1.14.3.1 1 side by side labeling (package and patient insert) comparison with all
differences visually highlighted and annotated
• 1.14.3.3 RLD package insert, 1 RLD label and 1 RLD container label

Via CD- Traditional format

• Labeling pieces organized in Six folders
1.Comparision.pdf, 2. Proposed.pdf, 3. Proposed word doc, 4. Listed.pdf
5. SPL (package insert), 6. History