The U.S. represents the largest continental pharma market worldwide and holds around 45% of the global market The US pharmaceutical market is projected to increase from $354bn in 2015 to $497bn by 2020, according to a report.

Though markets like china and Indian have shown a great leap in the pharma market, the United States and Europe are still the key players in the pharmaceutical industry.

The United States has the world’s most stringent standards for approving new drugs and Drug approval standards in the United States are considered by many regulators in the world.

Which is the drug regulatory body in the USA?

The Food and Drug Administration (FDA) is responsible for protecting and promoting public health. 

The Center for Drug Evaluation and Research (CDER) 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.

FDA’s new drug approval process is also accomplished in two phases

  • IND for Clinical Trials (CT) and
  • New Drug Application (NDA) approval

FDA approval process begins only after the submission of the Investigational New Drug (IND) application.

Who can submit IND, NDA & NDA 505(b)(2)?

  • The applicant, or the applicant’s attorney, agent, or authorized official must sign the NDA. 
  • If the person signing the NDA does not reside or conduct business within the United States, the NDA is required to contain the name and address of, and be countersigned by, an attorney, agent, or an authorized official who resides or maintains a place of business within the United States.

What is the process for IND approval?

An Investigational New Drug (IND) application is filed with the FDA to start clinical trials in humans if the drug was found to be safe in Preclinical trials and the sponsor is responsible for submitting the IND application

A Pre – IND assessment can be organized with the FDA to deliberate multiple issues such as:  

  • The design of animal research, which is required to lend support to the clinical studies  
  • The intended protocol for conducting the clinical trial  
  • The chemistry, manufacturing, and control of the investigational drug.

Requirements for IND

  • Required Forms
    • Form FDA 1571 Investigational New Drug Application
    • Form FDA 1572 Statement of Investigator
    • Form FDA 3674 Certification of Compliance, under 42 U.S.C. 282(j)(5)(B), with 207 Requirements of Data Bank
  • Table of Contents
  • Introductory Statement and General Investigational Plan Investigator’s Brochure
  • Protocols
  • Chemistry, Manufacturing, and Control Information
  • Pharmacology and Toxicology Information
  • Previous Human Experience With the Investigational Drug
  • Other Important Information
  • Relevant Information

Process for IND

  • An applicant with all the required information applies to FDA
  • On receiving the application, FDA forwards to the review team
  • Within 30 days after the IND sealing date, the review team provides its positive or no response where the sponsor can start clinical trials 
  • Within 60 days from announcing the IND, the sponsor shall submit the reports of clinical trials. A meeting shall be conducted before one month of ending phase II trials. 
  • Once the sponsor has completed phase III trials successfully the sponsor shall initiate pre-NDA from 9 – 12 months before NDA submission

Process flow


Generally, approval of an NDA is granted within two years, however, this timeline may from several months to years due to several reasons 

What is the approval process for NDA?

A New Drug Application (NDA) can be filed only when the drug successfully passes all three phases of clinical trials and comprises all animal and human data, analyses data, the pharmacokinetics of the drug, and its manufacturing and anticipated label.

The preclinical, clinical reports and risk-benefit analysis are studied at the Centre for Drug Evaluation and Research

FDA’s new drug approval process is also considered in two phases: 

  • Clinical trials (CT) and 
  • New Drug Application (NDA) approval

Requirements for NDA submission

Two copies of the application are

  • Archival copy and
  • Review copy.

Archival Copy: It serves as a reference source for FDA reviewers to locate information not contained in the review copy, and it contains copies of tabulations and clinical study case report forms. It contains the following elements:

  • Application form FDA 356
  • Index
  • Summary
  • Technical sections: further typed to1. Chemistry, manufacturing and controls section
    • Non-clinical pharmacology and toxicology section
    • Human pharmacokinetics and bioavailability section
    • Microbiology section
    • Clinical data section
    • Statistical section
    • Pediatric use section
  • Samples and labeling
  • Case report forms 

Review Copy: Each technical section is separately bound in each folder. Each technical section should contain:

  1. Index
  2. Copy of FDA Form 356 h
  3. Copy of cover letter
  4. Letters of authorization
  5. Copy of application summary


  • Pre-NDA Meeting
    • The pre-NDA meeting addresses the submission of the NDA including issues such as format and content, data presentations, methods of statistical analyses, electronic submission, whether standard or priority review and other issues as needed. 
  • NDA submission and review 
    • The FDA has 60 days to decide whether to accept the file to review. 
    • FDA forwards this file to CDER for review and CDER will evaluate the eligibility for filing. If found eligible accepts the application and forwards to FDA reviewer team
    • The review team evaluates whether the studies the sponsor submitted show that the drug is safe and effective for its proposed use. Each reviewer prepares a written evaluation containing conclusions and recommendations about the application. 
  • Reviews for drug labeling 
    • The drug labeling is reviewed by the FDA for the following information:  
    • Adequate information such as  indications, effects, dosages, routes, methods, and frequency and duration of administration and any relevant warnings, hazards, contraindications, side effects, and precautions, and  
    • The same information concerning the ingredients of the drug appears on the label and labeling on or within the package from which the drug is to be dispensed.
  • FDA inspection 
    • The Food and Drug Administration (FDA) conducts inspections of regulated facilities to determine a firm’s compliance with applicable laws and regulations, such as the Food, Drug, and Cosmetic Act and related Acts.
    • Within 180 days the reviewer team submits the report to CDER
    • If the review result is positive, FDA issues marketing authorization to the sponsor 
  • Drug Approval

Process flow

What is NDA 505(b)(2)?

A 505(b)(2) application is one for which one or more of the investigations relied upon by the applicant for approval which was not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.

An example of 505(b)(2) applications:

Route of administration: An application for a change in the route of administration, such as a change from an intravenous to an intrathecal route.

New chemical entity (NCE)/new molecular entity (NME)

A 505(b)(2) application may be submitted for an NCE when some part of the data necessary for approval is derived from studies not conducted by or for the applicant and to which the applicant has not obtained a right of reference.

For an NCE, this data is likely to be derived from published studies, rather than FDA’s previous finding of safety and effectiveness of a drug.

Changes to previously approved drugs

  • An application may rely on the agency’s finding of safety and effectiveness of the previously approved product, along with the information needed to support the change from the approved product. 
  • This use of section 505(b)(2) was intended to encourage innovation without creating duplicate work and reflects the same principle as the 505(j) application.

Approval procedure

Same as NDA approval above


The FDA’s Center for Drug Evaluation and Research (CDER) expects to review and act on at least 90 percent of NDAs for standard drugs no later than 10 months after the applications are received.

What is the regulatory for generic drugs/ANDA?

The Office of Generic Drugs (OGD) ensures, through a scientific and regulatory process, that the generic drugs are safe, effective, and high-quality.

FDA-approved generic drugs account for about 90 percent of prescriptions filled in the United States. 

It’s an application made for approval of Generic Drugs. Here the sponsor is not required to reproduce the clinical studies that were done previously for the original, brand name product. Instead, generic drug manufacturers must demonstrate that their product is the same as, and bioequivalent to, a previously approved brand name product


  • Application for ANDA is made to FDA under section 505(j) 
  • A filing review is conducted to determine whether the application is sufficiently complete to permit a substantive review.
  • Acceptance/Refuse to Receive (RTR) letter is issued based on the completeness of the Abbreviated New Drug Application (ANDA).
  • The regulatory filing checklist is updated on a quarterly basis and on an as-needed basis. 
  • Review process 
    • Bioequivalence study shall evaluate the following areas:
      • Clinical area (treatment) 
      • Analysis (biological fluid analysis) 
      • Statistics (bioequivalence)
    • Chemistry/Microbiology Review
    • Labeling Review
  • Inspection – cGMP/Compliance (click here for guidance document)
    • All facilities used for manufacturing, testing, packaging/storing drug substance and drug product are subject for inspections and must be in compliance at the time of approval.
  • If all the information is acceptable, OGD of CDER issues market approval
  • ANDA Approval 
    • There are two types of ANDA approval: 
      • Full Approval: all valid patents and exclusivities for the reference listed drug (RLD) are expired or any legal issues that may block approval of the ANDA are settled. 
      • Tentative Approval – there exist unexpired patents and exclusivities for the RLD.

Process flow


The initial review cycle may be adjusted by mutual agreement between the FDA and an applicant as the result of a major amendment.

Patent and exclusivity

Patent and exclusivity in 505(b)(2) application 

  • A 505(b)(2) application may itself be granted 3 years of Hatch-Waxman exclusivity if one or more of the clinical investigations, other than BA/BE studies was essential to approval of the application and is conducted or sponsored by the applicant. 
  • The 505(b)(2) application may also be granted for 5 years of exclusivity if it is for a new chemical entity.

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