Submitted by : Amit Sangwan
Submitted to : Mr. Himanshu
Ranbaxy Laboratories Limited
Registration procedure for OTC drugs
a) OTC monograph
b) OTC NDA
Labeling guidelines for OTC drugs
a) content of labeling
b) format of labeling
Over the counter drugs are medicines that
may be sold directly to a consumer without a
prescription from health care
professional, compared to prescription
drugs, which may be sold to consumers
possessing a valid prescription.
They are also called Non-prescription drugs.
Some typical characteristics of OTC
The product can be safely used without a
prescription based on a long history of use.
Consumers can appropriately self-select (or
de-select) the product based on the OTC
label, supported by label user testing.
Potential for misuse or abuse of the product
The benefits of using the product as OTC
clearly outweigh the risks.
Two regulatory pathways for OTC drugs
registration in USA.
OTC Drug Monograph
OTC New Drug Application (NDA)
Office of the Non-prescription Products (ONP)
Office of the New Drugs (OND)
These are the sub offices of the Centre for
Drug Evaluation and Research of US FDA.
These are responsible for review of OTC NDA
and regulations concerning OTC drug
Office of the Non-prescription Products
In 1972: FDA established OTC drug review
procedures for designed of OTC monographs
(regulatory standards) for registration or
marketing of OTC products not covered by
Final monographs are published in Code of
Federal Regulations: 21 CFR parts 331-338.
A Recipe book for marketing an OTC drug.
A list and explanation of GRASE conditions
GRASE = Generally Recognized As Safe and
1) GRASE active ingredients
2) Labeling requirements
warning & directions for use
3) Final formulation testing
Drugs marketed in accordance with a final
monograph can go directly to market and do
not require FDA approval of a marketing
The OTC monograph system is commercially
advantageous as it enables rapid entry of
conforming products to the marketplace.
Through the NDA Drug sponsors proposed
FDA for market approval of :
a) New drugs direct to OTC
b) Already marketed drugs as an OTC drugs.
Drug sponsors submits data in an NDA
demonstrating a drug product is safe and
effective for use by consumers without the
assistance of a healthcare professional. FDA
must review the data within an established
timeframe, and the data submitted in an
NDA remains confidential.
In January 1997 Manual for policies and
procedure (MAPP) 6020.5R Good Review Practice:
establishes a procedure for the review of NDAs
for OTC Products.
Specific Subject Matter Review Division (SSMRD)
of ONP review clinical trials.
Division of Non-prescription Clinical
Evaluation (DNCE) of ONP reviews consumer
behaviour studies and post marketing safety
Prescription to OTC switch
a) full switch (NDA supplement)
b) partial switch (new NDA)
Direct to OTC
Occurs when NDA holder of approved
prescription drug files NDA or supplement for
approval of OTC product.
The NDA holder may gain 3 years of
exclusivity for OTC “conditions of use” if
switch is based on:
New clinical investigation(s).
Conducted or sponsored by the
Essential to approval.
Pre market approval
Drug product specific
May require a user fee
Potential for marketing
Mandated FDA review
May require clinical
a) label comprehension
b) Actual use
No pre market approval
No user fee
No market exclusivity
No mandated timelines
May require clinical
actual use studies not
In the Federal Register of March 17,1999,FDA
published a 21 CFR 201.66, establishing
standardized content and format for labelling
of OTC products.
This labeling regulation cover all OTC drug
and drug-cosmetics products, whether
marketed under NDA, aNDA, or an OTC drug
(1) Title (Drug Facts)
(2) Active ingredient(s)
(7) Other information
(8) Inactive ingredients
(9) Contact information
1) Title: If the Drug Facts labeling appears on more
than one panel or side of the labeling, the title
Drug Facts (continued) must appear at the top of
each subsequent panel containing such
2) Active ingredient: followed by the established
name of each active ingredient and the quantity
of each active ingredient per dosage unit.
[for oral dosage forms] use the dosage unit
stated in the directions for use (e.g., tablet, 5 mL
[for topical dosage forms marketed with discrete
dosage units] use gram, as stated .
Drug products marketed without discrete
dosage units (e.g., topicals) must state the
proportion (rather than the quantity) of each
active ingredient (e.g. 1%).
Its general pharmacological categories
The principal intended action of the drug
If two active ingredients in a drug product have
the same purpose (e.g., two sunscreen or skin
protectant ingredients are present in the drug
product), then the purpose can be stated only
once as long as the purpose is clearly
associated with both active ingredients.
The statement of identity that appears in an
applicable OTC drug monograph shall be stated
as the purpose of the active ingredient.
4) Use: are the specific indications or approved
uses for the drug product.
5) Warning: When applicable, the following
information must appear under the respective
subheadings in the Warnings section.
-“for external use only” for topical drug
-For “rectal” or “vaginal” use only.
-Allergic reaction warnings.-“Allergy alert”.
Do not use :
on irritated skin
• on any area that is infected or reddened
• if you are a diabetic
• if you have poor blood circulation
“Ask a doctor before use if you
have”:Information under this subheading
includes all warnings for persons with certain
pre existing conditions (excluding pregnancy)
and all warnings for persons experiencing
• cough that occurs with too much phlegm
• chronic cough that lasts as occurs with
smoking, asthma, chronic bronchitis, or
“Stop use and ask a doctor if”
this subheading followed by any signs of
toxicity that would necessitate immediately
discontinuing use of the product.
The labeling for all OTC drug products shall
contain a warning as follows : “If pregnant or
breast-feeding, ask a health professional
Keep out of reach of children
6) Directions: followed by the direction for use
described in an applicable OTC drug monograph.
For example :
• do not use more than directed
7) Other information: followed by additional
information that is required by OTC drug
8) Inactive ingredients: : the established names of
inactive ingredients must be listed in alphabetical
order as :
colloidal silicon dioxide, hydroxy propyl
methylcellulose, lactose, magnesium
stearate, polyethylene glycol, povidone, propylene
glycol, titanium dioxide.
Use of bold type
The use of bullets- solid square or circle, 5 point.
Graphic images and
Procedures for handling multiple panels
The FDA mandates that a minimum type size of 6.7
point is required to ensure that people over the age
of 60 can read the label. And do not reduce the type
size below 6.0 point.
Minimum type size:
a) Headings- at least 8 point or 2 point larger
b) Text and subheading- at least 6 point.
A clear, easy-to-read type style, such as
universe, with no more than 39 characters per
Leading- at least 0.5 point(minimum space
Kerning- letters cannot touch.
Principal display panel
The declaration shall appear in conspicuous
and easily legible boldface print or type in
distinct contrast (by
typography, layout, color) to other
Height: width shall not be greater than 3:1.
Letter and numerals on PDP shall be uniform
for all package of substantially the same size
by complying with the following type
-Not less than 1/16th inch in height (area of 5
square inches or less).
-Not less than 1/8th inch in height (area of
more than 5 but not more than 25 square
-Not less than 3/16th inch in height (area of
more than 25 but not more than 100 square
-Not less than 1/4th inch in height (area of
more than 100 square inches).
Except -Not less than 1/2th inch in height (area
of more than 400 square inches).
1) OTCs deliver tremendous value to individual
consumers and the US healthcare system as a
whole. The general sales status of OTCs in
the US marketplace provides the American
consumer with convenient access to
important self-care options.
2) The OTC monograph process has the
advantage of speed to market for qualifying
products, since FDA pre-approval is not
required. The NDA route is more time-
Developed and Approved/ucm317137.htm
6) http://www.fda.gov/downloads/Drugs/GuidanceCompliance Regulatory