Miryala Aishwarya et al / Int. J. of Allied Med. Sci. and Clin.

Research 11(4) 2023 [398-404]

International Journal of Allied Medical Sciences

and Clinical Research (IJAMSCR)
IJAMSCR |Vol.11 | Issue 4 | Oct - Dec -2023
www.ijamscr.com
ISSN: 2347-6567 DOI : https://doi.org/10.61096/ijamscr.v11.iss4.2023.398-404

Research

Regulatory strategy for filing NDA/ANDA

Miryala Aishwarya*, Unnam Subamoorthy1
Department Of Regulatory Affairs, Sree Dattha Institute Of Pharmacy, Nagarjuna Sagar Road Sheriguda,
Ibrahimpatnam Rangareddy - 501510.

*Author for Correspondence: Miryala Aishwarya

Email: [email protected]

Abstract
In Pharmaceutical Industry, Regulatory Affairs Department makes an
Published on: 13 Oct 2023 interface between the regulatory authorities and pharmaceutical industry. The
Regulatory Affairs department is an important part of the organizational structure
of pharmaceutical companies. Internally it liaises at the inter phase of drug
Published by: development, manufacturing, marketing and clinical research. Externally it is the
DrSriram Publications key interface between the company and the regulatory authorities. Regulatory
Affairs is involved in the development of new medicinal products from early on, by
integrating regulatory principles and by preparing and submitting the relevant
2023| All rights reserved. regulatory dossiers to health authorities. Regulatory Affairs is actively involved in
every stage of development of a new medicine and in the post-marketing activities
with authorized medicinal products. This professional can play a key role in guiding
Creative Commons drug development strategy in an increasingly global environment and has an
Attribution 4.0 important role for submitting the newly discovered drug products approval
International License. documents to the US FDA regulatory authorities and to carry out all the practices
required for obtaining the drug products approval. This article mainly focuses on
the US FDA drug approval strategies. These strategies playing core job in the
pharmaceutical industry. These strategies having all the guidelines which are
indispensable part of the IND, NDA and ANDA drug approval applications. It plays
a significant role in sequence for registration of newly exposed products and also
providing the guidelines which is helpful preparing the registration documents to
regulatory authorities.

Keywords: IND, NDA, ANDA, CDER,\

INTRODUCTION
The Center for Drug Evaluation and Research (CDER, pronounced "see'-der") is a division of the U.S.
Food and Drug Administration (FDA) that monitors most drugs as defined in the Food, Drug, and Cosmetic Act.
Some biological products are also legally considered drugs, but they are covered by the Center for Biologics
Evaluation and Research. The center reviews applications for brand name, generic, and over the counter
pharmaceuticals, manages US current Good Manufacturing Practice (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.

398
 Miryala Aishwarya et al / Int. J. of Allied Med. Sci. and Clin. Research 11(4) 2023 [398-404]

CDER reviews New Drug Applications to ensure that the drugs are safe and effective. Its primary objective is to
ensure that all prescription and over-the-counter (OTC) medications are safe and effective when used as directed.
The FDA requires a four phased series of clinical trials for testing drugs. Phase I involves testing new
drugs on healthy volunteers in small groups to determine the maximum safe dosage. Phase II trials involve patients
with the condition the drug is intended to treat to test for safety and minimal efficacy in a somewhat larger group
of people. Phase III trials involve one to five thousand patients to determine whether the drug is effective in
treating the condition it is intended to be used for. After this stage, a new drug application is submitted. If the drug
is approved, stage IV trials are conducted after marketing to ensure there are no adverse effects or long term
effects of the drug that were not previously discovered.

Fig 1: CDER

With the rapid advancement of biologically-derived treatments, the FDA has stated that it is working to
modernize the process of approval for new drugs. In 2017, Commissioner Scott Gottlieb estimated that they have
more than 600 active applications for gene and cell based therapies. 1
The Center for Drug Evaluation and Research (CDER) performs an essential public health task by
making sure that safe and effective drugs are available to improve the health of people in the United States. As
part of the U.S. Food and Drug Administration (FDA), CDER regulates over-the-counter and prescription drugs,
including biological therapeutics and generic drugs. This work covers more than just medicines. For example,
fluoride toothpaste, antiperspirants, dandruff shampoos and sunscreens are all considered drugs. 2 The mission of
FDA's Center for Drug Evaluation and Research (CDER) is to ensure that drugs marketed in this country are safe
and effective. CDER does not test drugs, although the Center's Office of Testing and Research does conduct
limited research in the areas of drug quality, safety, and effectiveness. It has responsibility for both prescription
and nonprescription or over-the-counter (OTC) drugs. Some companies submit a new drug application (NDA) to
introduce a new drug product into the U.S. Market. It is the responsibility of the company seeking to market a
drug to test it and submit evidence that it is safe and effective. A team of CDER physicians, statisticians, chemists,
pharmacologists, and other scientists reviews the sponsor's NDA containing the data and proposed labeling.

AIM AND OBJECTIVES

 New Drug Application (NDA) is the application process through which pharmaceutical drugs for human use
are approved by the United States Food and Drug Administration (US FDA).
 All ANDA submissions MUST be in eCTD format. eCTD submission sizes 10 GB or less must use the FDA
Electronic Submission Gateway (ESG). If an eCTD submission is greater than 10 GB, it may be submitted
via physical media (DVD/USB Drive) to the CDER Document Room or via ESG.
 Filing review is conducted to determine whether the application is sufficiently complete to permit a
substantive review and these strategies plays a significant role in sequence for registration of newly exposed

399
 Miryala Aishwarya et al / Int. J. of Allied Med. Sci. and Clin. Research 11(4) 2023 [398-404]

products and also providing the guidelines which is helpful preparing the registration documents to
regulatory authorities.

Types of Applications3
 Investigational New Drug (IND)
 New Drug Application (NDA)
 Abbreviated New Drug Application (ANDA)
 Over-the-Counter Drugs (OTC)
 Biologic License Application (BLA)

Fig 2: New Drug Approval Process and strategy

Investigational New Drug (IND)4

An Investigational New Drug Application (IND) is a request from a clinical study sponsor to obtain
authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological
product to humans. Clinical studies are often conducted to collect safety and effectiveness information in support
of marketing applications for biologic and drug products. Unless exempted, the sponsor for a clinical study must
obtain authorization from FDA for conducting the study by submitting an IND Application. Such authorization
must be secured prior to interstate shipment and administration of any new drug or biological product that is not
the subject of an approved New Drug Application or Biologics Product License Application.
Expanded access to a product in an investigational stage can be granted by FDA as a compassion measure. These
INDs are used for patients with serious diseases outside of clinical trials when no comparable or satisfactory
alternative therapy options are available and are requested by the treating licensed physicians who determine
whether the benefit outweighs the probable risk.
Clinical studies must follow a set of laws and regulations, which are intended to protect the right, safety,
and welfare of human subjects participating in human trials, ensure the quality, validity, and integrity of the
clinical trial data, and promote the availability of new medical products to the public. These laws and regulations
define the roles and responsibilities of entities, such as sponsors, clinical investigators, and institutional review
boards. In addition, various guidance documents and standard operating procedures are available to clarify
policies and procedures for the IND process.

400
 Miryala Aishwarya et al / Int. J. of Allied Med. Sci. and Clin. Research 11(4) 2023 [398-404]

Laws, Regulations, Policies and Procedures

Code of Federal Regulations (CFR)
The following regulations apply to the IND application process;
21CFR Part 312 Investigational New Drug Application
21CFR Part 314 INDA and NDA Applications for FDA Approval to Market a New Drug
21CFR Part 316 Orphan Drugs
21CFR Part 58 Good Lab Practice for Nonclinical Laboratory [Animal] Studies
21CFR Part 50 Protection of Human Subjects
21CFR Part 56 Institutional Review Boards
21CFR Part 201 Drug Labeling
21CFR Part 54 Financial Disclosure by Clinical Investigators

Content of an initial IND

1. Cover Sheet (Form FDA 1571)
2. Table of Contents
3. Introductory Statement & General investigational plan
4. Investigator’s Brochure
5. Protocols
6. Chemistry, Manufacturing & Control Information
7. Previous Human Experience with the Investigational Drug
8. Additional Information

Fig 3: IND Review Process

The drug sponsor formally asks the FDA to approve a drug for marketing in the United States by
submitting an NDA. An NDA includes all animal and human data, the analyses of that data, information about
how the drug behaves in the body, and a description of how it is manufactured.
After an NDA is received, the FDA has 60 days to decide whether the application is complete enough
to go through formal review. If it is not, the FDA asks the sponsor for more information, and sometimes even
more studies. Once the FDA finds the application to be sufficient, an FDA review team is assigned to evaluate
the research on the drug’s safety and effectiveness. The review timeline varies, depending on several factors:

401
 Miryala Aishwarya et al / Int. J. of Allied Med. Sci. and Clin. Research 11(4) 2023 [398-404]

whether other, similar drugs are already in the market; whether the drug treats a condition that is lacking
sufficient treatments; whether the drug is the first of its kind, scientifically; and so forth.5

Fig 4: NDA Review Process

The NDA is the vehicle through which drug sponsors (pharmacy companies) formally propose that the
FDA approve a new pharmaceutical for sale and marketing inthe U.S. The data gathered during the animal studies
and human clinical trials of an Investigational New Drug (IND) become part of the NDA.
In simple terms “It is an application filed with USFDA to get approval for marketing a new pharmaceutical for
sale in the U.S.” Since 1938, every new drug has been the subject of an approved NDA before U.S.
commercialization.
The goals of the NDA are to provide enough information to permit FDA reviewer to reach the following key
decisions:
 Is the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the
risks.
 Is the drug's proposed labeling (package insert) is appropriate, and what it should contain?

402
 Miryala Aishwarya et al / Int. J. of Allied Med. Sci. and Clin. Research 11(4) 2023 [398-404]

 Are the methods used in manufacturing the drug and the controls used to maintain the drug's quality are
adequate to preserve the drug's identity, strength, quality, and purity

Resources for NDA Submissions

The following resources have been gathered to provide you with the legal requirements of a new drug
application, assistance from CDER to help you meet those requirements, and internal NDA review principles,
policies and procedures.

Guidance Documents for NDAs

Guidance documents represent the Agency's current thinking on a particular subject. These documents
are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and
evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated
products. They also establish policies intended to achieve consistency in the Agency's regulatory approach and
establish inspection and enforcement procedures. Because guidances are not regulations or laws, they are not
enforceable, either through administrative actions or through the courts. An alternative approach may be used if
such approach satisfies the requirements of the applicable statute, regulations, or both. For information on a
specific guidance document, please contact the originating office.
For the complete list of CDER guidances, please see the Guidance Index. For information on a specific guidance
document, please contact the originating office.

Guidance documents to help prepare NDAs

 Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs and General Considerations
 Changes to an Approved NDA or ANDA
 Changes to an Approved NDA or ANDA: Questions and Answers
 Container Closure Systems for Packaging Human Drugs and Biologics
 Format and Content of the Microbiology Section of an Application,
 Format and Content of the Clinical and Statistical Sections of an Application
 Summary for New Drug and Antibiotic Applications--Format and Content of the Summary for New Drug
and Antibiotic Applications
 Formatting, Assembling and Submitting New Drug and Antibiotic Applications,
 Guideline For Submitting Supporting Documentation In Drug Applications For The Manufacture Of Drug
Products
 NDAs: Impurities in Drug Substances
 Format and Content of the Human Pharmacokinetics and Bioavailability Section of an Application
 Format and Content of the Nonclinical Pharmacology/Toxicology Section of an Application
 Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products
 Drug Master Files: Guidelines
 FDA IND, NDA, ANDA, or Drug Master File Binders
 PET Drug Applications - Content and Format for NDAs and ANDAs — 2011

Laws, Regulations, Policies and Procedures

The mission of FDA is to enforce laws enacted by the U.S. Congress and regulations established by the
Agency to protect the consumer's health, safety, and pocketbook. The Federal Food, Drug, and Cosmetic Act is
the basic food and drug law of the U.S. With numerous amendments, it is the most extensive law of its kind in the
world. The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced
under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are
safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not
deceptive.

Code Of Federal Regulations (CFR)

The final regulations published in the Federal Register (daily published record of proposed rules, final rules,
meeting notices, etc.) are collected in the CFR. The CFR is divided into 50 titles which represent broad areas
subject to Federal regulations. The FDA's portion of the CFR interprets the Federal Food, Drug and Cosmetic
Act and related statutes. Section 21 of the CFR contains all regulations pertaining to food and drugs. The
regulations document all actions of all drug sponsors that are required under Federal law.
 21CFR Part 314 - Applications for FDA Approval to Market a New Drug or an Antibiotic Drug.

403
 Miryala Aishwarya et al / Int. J. of Allied Med. Sci. and Clin. Research 11(4) 2023 [398-404]

CONCLUSION
A regulatory strategy is a science-driven assessment of a product's development options, key consider-
actions and likely regulatory outcome. It should span the earliest development stages through further
modifications planned post authorization.
Regulatory Strategies describes how the pharmaceutical companies communicate about the approval for
drug products. It is necessary to understand the various steps for drug approval. Deciding on a suitable regulatory
strategy plays a vital role in gaining time on the market authorization of a drug product.
Pharmaceutical regulations, or medicines regulations, have been defined as the combination of legal,
administrative, and technical measures that governments take to ensure the safety, efficacy, and quality of
medicines, as well as the relevance and accuracy of product information.
The drug regulatory authority is “the agency that develops and implements most of the legislation and
regulations on pharmaceuticals. Its main task is to ensure the quality, safety and efficacy of drugs, and the accuracy
of product information. This is done by making certain that the manufacture, procurement, import, export,
distribution, supply and sale of drugs, product promotion and advertising, and clinical trials are carried out
according to specified standards. Several of these functions also contribute to efforts to promote rational drug use.

АCKNOWLEDGEMENT

Thе Authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе nеcеssary facilitiеs for thе
rеsеarch work.

REFERENCES
1. Burton, Thomas M. (7 September 2017). "FDA Modernizing Evaluations as Gene, Cell Therapy Fields
Grow". Wall Street Journal – via www.wsj.com.
2. https://www.fda.gov/about-fda/fda-organization/center-drug-evaluation-and-research-cder.
3. https://en.wikipedia.org/wiki/New_drug_application
4. https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/investigational-
new-drug-applications-inds-cber-regulated
products#:~:text=An%20Investigational%20New%20Drug%20Application,or%20biological%20produ
ct%20to%20humans.
5. https://blogs.perficient.com/2017/07/24/what-happens-during-nda-review-in-the-fda-drug-approval-
process.
6. https://www.fda.gov/drugs/types-applications/new-drug-application-nda.
7. https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda.
8. “IND, NDA, ANDA, Concept of Para I to IV, Exclusivity: Content, Format & Application”
http://pharmaquest.weebly.com/uploads/9/9/4/2/994291 6/3.pdf.
9. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/Appr
ovalApplications/InvestigationalNewDrugINDApplication/default.htm.
10. https://www.contractpharma.com/issues/2020-03-01/view_fda-watch/the-art-of-filing-ndaanda-post-
approval-changes-to-the-fda.
11. http://www.jpsbr.org/index_htm_files/JPSBR14RS4027.pdf
12. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/Appr
ovalApplications/NewDrugApplicationNDA
13. https://en.wikipedia.org/wiki/New_drug_application
14. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/Appr
ovalApplications/NewDrugApplicationNDA/
15. http://www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/newdrugapplication
sndas/default.htm
16. http://www.investopedia.com/terms/n/new-drug-application-nda.asp
17. http://www.jpsbr.org/index_htm_files/JPSBR14RS4027.pdf
18. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3555014/
19. http://www.asq509.org/ht/a/GetDocumentAction/i/86200
20. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformatin/
guidances/ucm400630.pdf

404