Naresh... anda ppt
Published on: Mar 3, 2016
Transcripts - Naresh... anda ppt
Definition of a Generic Drug
“A drug product that is comparable to a
brand/reference listed drug product in dosage
form, strength, route of administration, quality
and performance characteristics, and intended
Basic Generic Drug Requirements
Same active ingredient(s)
Same route of administration
Same dosage form
Same conditions of use
Inactive ingredients already approved in a similar
Definition of a ANDA
An “Abbreviated New Drug Application”
(ANDA) is an application for a U.S. generic drug
approval for an existing licensed medication or
Advent of Generic drug competition:
Generic drugs always been available in US market.
DESI: Drug Efficacy Study Implementation.
When the DESI program was in progress, the agency
estimated that there were between 5-13 products without
NDA’s that were identical and similar to each of the 13,000
products that held NDA’s under the 1938 Act.
Advent of Generic drug competition:
These products contain same active ingredients in the
same amount and dosage form, often though they claim
some unique characteristics i.e., a different salt or ester,
a different amount, a different dosage form or an extra
As part of the DESI project the FDA thought to introduce
uniformity and control over these products.
First, the agency said that a copy had to be identical,
unless the proponent got FDA permission to vary from
Advent of Generic drug competition:
Second, the manufacturer had to obtain an ANDA
showing that the product was identical.
In essence, it was an application that contain all the
CMC of a full NDA, but omitted any preclinical or clinical
A number of generic firms opposed even these
requirements and significant litigation followed.
Evolution of ANDA:
Physicians were reporting that CHF patients who had
been treated carefully with a specific dose of Digoxin,
went out of control upon getting prescriptions refilled.
Investigations revealed that Digoxin, a pre 1938 drug
that never subject to an NDA, varied from manufacturer
to manufacturer not in quantity of actual drug per tablet,
but in the amount of drug released from the tablet into
The consequences could be life threatening.
The agency responded with an order that each
manufacturer submit an ANDA that included
bioavailability studies showing the rate and extent of
absorption into the body.
Thus, was born an idea of bioequivalence: that
competing products not only be pharmaceutically
identical but also show no significant difference in the
rate and extent of absorption in controlled bioavailability
The ANDA process and bioequivalence permitted the
agency for the first time to declare individual generic
products to be therapeutically equivalent to approved
The FDA began making such declarations in 1975, 1976
and 1979, the agency began to publish them in orange
The generics doesn’t have a great competitive threat
because state pharmacy laws did not permit the
substitution of a generic drug for the innovator drug.
In 1979 the federal trade commission revealed a model
state drug product selection law, which guided state
legislatures how to amend pharmacy laws to permit
druggists to substitute equivalent generics for innovators
without the permission of the prescribing physicians.
Abbreviated New Drug Application
An ANDA contains data which when submitted to
FDA's Center for Drug Evaluation and Research, Office
of Generic Drugs, provides for the review and ultimate
approval of a generic drug product.
Once approved, an applicant may manufacture and
market the generic drug product to provide a safe,
effective, low cost alternative to the American public.
(ANDA): Generics - contd
A generic drug product is one that is
comparable to an innovator drug product in
dosage form, strength, route of
administration, quality, performance
(ANDA): Generics - contd
Generic applicants must scientifically demonstrate that
their product is bioequivalent.
One way to demonstrate bioequivalence is to measure
the time it takes the generic drug to reach the
bloodstream in 24 to 36hrs healthy, volunteers.
This gives the rate of absorption, or bioavailability, of the
generic drug, which they can then compare to that of the
Why is it called “ABBREVIATED”?
The term abbreviated is used in generic drug
applications because, these applications does not
require including preclinical and clinical data to establish
safety and efficacy.
Scientific demonstration of the bioequivalence is
important and must.
Necessary items for ANDA:
i. The composition of drug, stating the name and amount
of each ingredient, whether active or not, contained in
a stated quantity of the drug in the form in which it is to
ii. Identify the place where the drug will be manufactured,
processed, packaged, and labeled and the name of the
supplier of the active ingredient.
iii. Identify any person other than the applicant who
performs a part of those operations.
iv. Include certifications from the applicant and the
methods used in process, and the facilities and
controls used for, the manufacture, processing,
packing, and holding of the drug are in conformity with
current good manufacturing practice.
v. Assure that the drug dosage form and components will
comply with the specifications and tests described in
an official compendium.
vi. If the drug differ from the compendium drug, that the
specifications and tests applied to the drug and its
components are adequate to assure their identity,
strength, quality and purity.
vii. Outline the methods used in, and the facilities, and
controls used for, the manufacture, processing, and
packaging of the drug.
vii. If the drug requires only an ANDA also specifies that
there must be included adequate data to assure the
biologic availability of the drug, and the preparations
claiming sustained action, such data should show that
the drug is available at a rate of release that will be
safe and effective.
Goals of ANDA:
To reduce the price of the drug.
To reduce the time development.
Increase the bioavailability of the drug in comparison to
references list drug.
Using bioequivalence as the basis for approving generic
copies of drug products was established by the "“Drug
Price Competition and patent Term restoration Act of
1984”,also known as the Waxman-Hatch Act.
This Act expedites the availability of less costly generic
drugs by permitting FDA to approve applications to
market generic versions of brand-name drugs without
conducting costly and duplicative clinical trials.
Waxman-Hatch Act – contd
At the same time, it provides a mechanism to grant drug
companies up to 5 years additional patent protection for
new drugs to compensate for some of the years of
patent life lost as a result of the time consuming testing
required by the FDA.
Under this provision, patent office, working in
collaboration with FDA, can grant up to 5 years
additional time of patent protection to certain new
pharmaceutical entities depending on the length of time
for which these entities were required to go through the
regulatory review process.
Waxman-Hatch Act – contd
The FDA, which will not grant any additional time for
delays caused by the neglect or mistakes of the
Brand-name drugs are subject to the same
bioequivalence tests as generics upon reformulation.
Conditions which must be fulfilled in order to
ask for an extension are:
1. The patent must not have expired at the time of filing
the request for extension.
2. The patent must never have been extended.
3. The product must have been subjected to examination
by the FDA.
4. The request for extension must have been filed within
60 days of the granting of the NDA.
5. The request for extension must have been filed, at the
latest during the last three months of the life of the
6. A fee of $750 must be paid.
Patent Certification condition for
Brand drug applicants are to provide the FDA with the
identity and expiration date of any patent that claims
the drug for which FDA approval is required.
ANDA’s must certify that:
i. No Such patents have been identified by the original
brand drug applicant.
ii. The identified patents have expired.
iii. The date the patents will expire.
iv. The patents are invalid or will not be infringed by the
marking, use or sale of the generic drug.
If the first (i) and second (ii) certifications are made,
approval can be immediate.
If the third (iii) certification is made approval is delayed
until the patents expire.
If the applicant makes the fourth (iv) certification, the
generic applicant must apply the original brand drug
applicant a detailed statement supporting the assertion
non-infringement or invalidity.
(Reviewed by CDER)
Center for Drug Evaluation and
Research – (CDER)
The center reviews applications for new and generic
pharmaceuticals, manages US cGMP regulations for
pharmaceutical manufacturing, determines which
medications require a medical prescription, monitors
advertising of approved medications, and collects and
analyzes safety data about pharmaceuticals that are
already on the market.
CDER reviews New drug Applications to ensure that the
drugs are safe and effective. It is one of the Centers at the
FDA. Its primary objective is to ensure that all prescription
and over-the-counter(OTC) medications are safe and
effective when used as directed.
NDA vs. ANDA Review Process
(NDA) Requirements (ANDA) Requirements
1. Labeling 1. Labeling
2. Pharm/Tox 2. Pharm/Tox
3. Chemistry 3. Chemistry
4. Manufacturing 4. Manufacturing
5. Controls 5. Controls
6. Microbiology 6. Microbiology
7. Inspection 7. Inspection
8. Testing 8. Testing
9. Animal Studies
10. Clinical Studies 9. Bioequivalence
How is Generic Drug Quality
First 8 steps of review process identical to NDA
Bioequivalence requirements for ANDA’s same as
FDA has experience with the product
Product is known to be safe
Scientific literature published
Post-approval product surveys
“Same” information as brand name labeling
May delete portions of labeling protected by patent or
exclusivity (i.e., an indication, strength)
May differ in excipients and product description (i.e.,
Pharm / Tox :
All inactive ingredients must be approved in either the
reference listed drug or similar NDA in same or higher
levels. (FDA publishes the ingredient and highest
Chemistry, Manufacturing and
Components and composition
Manufacturing and Controls
Batch formulation and records
Description of facilities
Specifications and testing
Includes for anti infective drug products.
requires the following technical information and data:-
A complete description of the biochemical basis of the
drug action on microbial physiology
The drugs antimicrobial spectrum
Describe any known mechanism of resistance to the drug
and provide information/data of any known epidemiologic
studies demonstrating prevalence to resistance factor
Clinical microbiology laboratory methods
Assure the sterility of the product through the
manufacturing process – especially important with
injectable drug products.
Assure manufacturing facilities are in compliance with
current good manufacturing practices (cGMPs)
Assure bioequivalence sites are in compliance with
current good clinical practices (cGCPs)
Conducted primarily by Field/Office of Regulatory
Affairs with support from Center (Office of Compliance)
and assigned geographically
Labs are in the Office of Regulatory Affairs and the
A generic drug is considered to be bioequivalent to
the brand name drug if:
The rate and extent of absorption do not show a
significant difference from listed drug, or
The extent of absorption does not show a
significant difference and any difference in rate
is intentional or not medically significant.
Bioequivalence – contd:
Original Abbreviated New Drug Application
(ANDA) Approvals: July 2010
andFDA Appl. #
TRIAMCINOLONE ACETONIDTER(IAANMDCAIN #O 0L4O0N77E1 )
Prescription LYNE 07/01/2010
(ANDA # 078890)
(ANDA # 090402)
TACROLIMUS Prescription WATSON LABS 07/01/2010
(ANDA # 090855)
DOXYCYCLINE Prescription MYLAN 07/01/2010
(ANDA # 091314)
ADAPALENE Prescription GLENMARK
Applicable for new drug Applicable for generic drug
Take longer time ( 12-15
Compare to NDA less time
More expenditure of money Comparatively less
Cost of drugs are more Cost of drugs are less
Nonclinical studies and
clinical investigations are
Nonclinical studies and clinical
investigations are nonessential
except bioavailability and
Modern pharmaceutics 4th edition by Banker and Rhodes.
Burgers Medicinal Chemistry and drug discovery – Vol-II.
A Text Book of Pharmaceutical medicine 5th Edition by
John p.Griffin and John O’Grady.
Comprehensive Medicinal chemistry by Hansch,
The Theory and Practice of Industrial Pharmacy by Leon