Abbreviated New Drug Applications (ANDA)

PRESENTED BY:Ramneet Kaur

M.Pharm – PharmaceuticsAmity institute of pharmacy

• Contains data submitted to FDA's Center for Drug Evaluation and Research

• Office of Generic Drugs - Review and final approval for Generic drug

• Manufacturers of generic drugs receive approval to market an off patent drug in the United States of America

• Once approved - Generic drug product can be manufactured and marketed

ABBREVIATED NEW DRUG APPLICATIONS (ANDA)1

Goals of ANDA1

Tool for facilitating the approval of a generic drug

To reduce:- Drug price- Development time

Availability in a cost effective manner

Market demand increases

ANDA 1 NDA 2

Applicable for generic drug Applicable for new drug

Compared to NDA less time taken (1-2 years)

Takes longer time ( 12-15 years)

Bioequivalence studies

Nonclinical studies and clinical investigations are essential

Lesser expenditure of money More expenditure

Cost of drugs is less It is more

Generic Drugs1

Bioequivalent and comparable to a reference listed drug in dosage form, strength, route of administration, identity, purity, quality, performance and intended use

Also known as copycat drugs and sold at low price

Manufactured under the same strict standards of FDA's Good Manufacturing Practice (GMP) regulations required for innovator products

Can be over-the-counter (OTC) drugs or prescription drugs• Ibuprofen - Advil ( OTC analgesic )• Fluoxetine - Prozac (prescription drug)

Not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness - Termed as Abbreviated

Drug Price Competition and Patent Term Restoration Act - 1984

To control drug price Brand-name companies can apply for up to five additional years

patent protection while their products are going through FDA's approval process

Allows generic drug manufacturers to "challenge" an existing patent by filing an ANDA prior to expiration of patent

Established bioequivalence as the basis for approving generic drug products

Hatch-Waxman Act1

DATA BASES FOR FILING AN ANDA

Electronic Orange BookDrugs @ FDA NDC (National Drug Code) Directory Dissolution Method Database IIG (Inactive ingredient guide) Database Drug product Bioequivalence database Freedom of Information

Electronic Orange Book3,4

o Also known as Approved Drug Products with Therapeutic Equivalence Evaluations

o Managed by FDA

o Orange colored cover

o Its list first appeared as a print publication in 1980

o Appropriate starting place for :• Identification of patents claiming an approved drug• Formulations of the approved drug• Therapeutic uses of the drug

EXAMPLEEXAMPLE

o Patents are subsequently published in the Orange Book

oOrange Book Search added to the FDA website - October 31, 1997 o Can search by active ingredient, proprietary name, applicant, or application number

Appl No TE Code

RLD Active Ingredient Dosage Form Route Strength Proprietary Name

Applicant

N011210 AA Yes BENZONATATE

CAPSULE ORAL 100MG TESSALON FOREST LABS

N011210 AA Yes BENZONATATE

CAPSULE ORAL 200MG TESSALON FOREST LABS

Drugs @ FDA5

Contains official information about FDA approved branded, generic drugs and therapeutic biological products

Search by - drug name, active ingredient or application number

Used to find:- Label information for approved drug products- Generic drug products for a brand name drug product- All drugs with the specific active ingredient- Approval history of a drug

NDC (National Drug Code) Directory6,7

Similar to the Bar Coding system

Upto 11 digits in length

Separated by hyphens (-) into three segments• First segment - Labeler code - identify the manufacturer of the

drug (4-5 characters)• Second segment – Product code - identifies the strength, dosage

form and formulation (3-4 characters)• Third segment - Package code - identifies package size (1-

2character)

Unique product identifier for drugs

Appears on all drug labels

Searchable database with download facility

Drug products are identified and reported using NDC

Dissolution Method Database8

o Searchable database containing FDA recommended dissolution methods for approved drug products

o Main challenges for dissolution studies includes:• To select a suitable dissolution method for development • Profile matching of Test & Innovator in official media for

all strengths• Select a discriminatory media (by varying media, speed or

volume)• Matching Innovator dissolution profile in discriminatory

media

o Has information regarding innovator product:

• USP dissolution apparatus used

• Speed of dissolution to be carried out

• Medium to be taken for carrying out dissolution

• Recommended sampling times

IIG (Inactive ingredient guide) Database9

Searchable database - available with USFDA

Contains information about inactive ingredients used in FDA approved drug products

One can vary the inactive ingredients from that of the innovator

Maximum dose/day for a particular excipients can be calculated

Updated quarterly- by tenth working day of April, July, October, and January

Drug product Bioequivalence database10

Generic drug product needs to be bioequivalent with the innovator product

Contains FDA recommendations for carrying out bioequivalence studies

Updated regularly

Freedom of Information11

India - Right to InformationUnited States - Freedom of information act (FOIA)Using the FOIA information about • Approval letter• Package insert• Labeling• FDA final reviews• Summary Basis of Approval (SBOA) for an NDA and

ANDA

Submission Requirements1

o Model Bioequivalence Data Summary Tables• Developed by - Division of Bioequivalence • Purpose - Data can be submitted to the Office of

Generic Drugs in a concise format

o Common Technical Document (CTD)  - Set of specification for application dossier for registration of Medicines• Quality, Safety and Efficacy

o Completed tables and Bioequivalence submissions of ANDA are required to be sent

ANDA Filings13

Generic manufacturer is required to identify the necessary patent holders affected by the early ANDA filing

Identification is set out in the ANDA application itself where the filer chooses between four alternative certifications or paragraphs

Described in section 505(j)(2)(A)(vii) of the Act Paragraph I    Drug has not been patented Approval effective after OGD scientific determination

Paragraph II   Patent already expired Approval effective after OGD scientific determination

Paragraph III        Date on which the patent will expire Tentative approval after OGD determination, final approval when patent

expires Paragraph IV         Patent Challenge

Tentative approval after OGD determination, final approval when challenge won

Paragraph IV certification13

According to section 505(j)(2)(B)(i), 2157 CFRANDA applicant must provide appropriate notice of a paragraph

IV certification to each owner of the patent and to the holder of the approved NDA to which the ANDA refers

And by Section 505(j)(5)(B)(iv)180-day period of marketing exclusivity is provided as an

incentive for generic manufacturers to file paragraph IV certifications and to challenge listed patents

180-Day Exclusivity Period13

Awarded to first ANDA holder to file a complete application with patent challenge

Protection from other generic competition – blocks approval of subsequent ANDAs

Guidance Documents for ANDAs1

Represent the Agency's current thinking on a particular subject

Prepared for FDA review staff and applicants

Establish policies intended to achieve uniformity in the agency's regulatory approach and to establish inspections

These are not regulations or laws and are not enforceable either through administrative actions or through courts

o Generics Procedural Draft1

• Distributed for comment purposes only• Applications Covered by Section 505(b)(2) 

o Biopharmaceutics1

• Bioavailability and Bioequivalence Studies for Drug Products • Useful for applicants - planning to conduct bioavailability and

bioequivalence studies

o Drug Master Files1

• Submit to FDA • Provide confidential detailed information about facilities, processes, or

articles used in the manufacturing, processing, packaging, and storing of one or more human drugs

MaPPs  (Manual of Policies and Procedures)1

• Provide official instructions for internal practices and procedures followed by CDER staff

• Help to standardize the drug review process and other activities (both internal and external) 

  • Available for the public to review to get a better understanding of

office policies, definitions, staff responsibilities  and procedures 

• Help prepare ANDAs

• Listed together on CDER's Manual of Policies and Procedures webpage

• Chapter 5200 – Explains Generic Drugs

Electronic Submissions 1

ANDA Checklist for Completeness and Acceptability

Office of Generic Drugs revised the regulatory filing checklist to enhance the ANDA review process

Regulatory filing checklist reviewed on a quarterly basis (calendar year) and updated on an as needed basis 

CDER Office of Generic Drugs developed a guidance document entitled Providing Regulatory Submissions in Electronic Format

To assist applicants making regulatory submissions in electronic format

Sun Pharma gets USFDA for anti-cough drug12

USFDA granted approval to market a generic version of Forest Labs Tessalon Benzonatate capsules

Sun Pharmaceutical Industries received marketing approval for the ANDA of its generic version of anti-cough drug Benzonatate

Benzonatate capsules available in the market in two strengths of 100mg and 200mg

Used to relieve cough due to the common cold, bronchitis, pneumonia and other lung infections

REFERENCES1. http://www.fda.gov/drugs/developmentapprovalprocess/

howdrugsaredevelopedandapproved/approvalapplications/abbreviatednewdrugapplicationandagenerics/default.htm

2. http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/newdrugapplicationNDA/default.htm

3. http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm

4. http://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm

5. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm

6. http://hayajneh.org/g/2010/12/national-drug-code-ndc

7. http://www.accessdata.fda.gov/scripts/cder/ndc/default.cfm

8.http://www.accessdata.fda.gov/scripts/cder/dissolution/disclaimer.cfm

9. http://www.fda.gov/Drugs/InformationOnDrugs/ucm080123.htm

10.http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm075207.htm

11. http://www.state.gov/m/a/ips

12. http://articles.economictimes.indiatimes.com/2008-03-21/news/28421188_1_usfda-nod-100mg-generic-version-- 2011-08-31

13. Office of Generic Drugs, http://www.fda.gov/cder/ogd

THANK YOUTHANK YOU