May 30, 2024

Investigational New Drug (IND) Pharmaceutical Regulatory Science Notes

Investigational New Drug (IND) Pharmaceutical Regulatory Science Notes


For small-molecule drugs, the path to a marketed drug involves a long and exhaustive journey through basic research, discovery of the medicine, pre-clinical development tests, increasingly complicated clinical trials with humans and regulatory approval by the Regulatory Authority.

Several years (usually 10 to 15) and hundreds of millions of dollars later, under the best of circumstances, a new drug will be approved for marketing. Because of its complexity, drug discovery and development are widely recognized as one of the most financially risky endeavours in all of science and a major challenge for the pharmaceutical industry.

Much of this cost comes from failures, which account for 75 percent of the total research and development costs. Although these failures are disappointing and costly, they still contribute to the body of knowledge on disease processes.


It’s an application filed to the FDA in order to start clinical trials in humans if the drug was found to be safe from the reports of Preclinical trials. The Federal Food, Drug and Cosmetics act regulated through Title 21 of U.S. Code of federal Regulations, requires a new drug to be approved by FDA before legally getting introduced into the market.

An investigational New Drug is defined under 21 CFR 312.3(b) as, “A new drug or biological drug that is used in clinical investigation.”

The term also includes a biological product used in-vitro for diagnostic purposes. After pre-clinical investigations when the new molecule has been screened for pharmacological activity and acute toxicity potential in animals the sponsor requires permission from FDA for its clinical trials in humans.

The sponsor submits the application for conduct of human clinical trials called Investigational New Drug (IND) application to FDA.

Once IND application is submitted, the sponsor must wait for 30 days before initiating any clinical trial.

Clinical trials in humans can begin only after IND is reviewed by the FDA and a local institutional review board (IRB).

IRBs approve clinical trial protocol, informed consent of all participants and appropriate steps to prevent subjects from harm.

If the FDA accepts the IND request within 30 days of submission, clinical testing of the new molecule on human may begin by the investigator.

At this point, the molecule under the legal status of FDA becomes a new drug subject to specific requirements of drug regulatory system.  If at any time during clinical testing, the data furnished to FDA indicate the Investigational Product (IP) to be toxic under the criterion of FDA’s Benefit/Risk ratio, FDA can terminate clinical trial and its actions are not subject to any judicial review.

Types of lND’s

A. Commercial INDs:

These are applications that are submitted primarily by the companies to obtain marketing approval for a new product.

B. Non-commercial (Research) INDs:

These INDs are filed for non- commercial research. These are:

Investigator’s IND:

It is submitted by a physician who both initiates and conducts an investigation and who also administers and dispenses the Investigational Product. A physician might submit a research IND to propose studying an unapproved drug or an approved drug for new indications or in new patient population.

Emergency Use IND:

This IND allows FDA to allow the use of an experimental drug in an emergency situation that does not allow submission of an IND in accordance with 21 CFR Sec 312.23 or Sec 312.34. It can also be used for patients who do not meet the criteria of an existing study protocol or if an approved study protocol does not exist.

Treatment IND

Also called Expanded Access IND. This 1ND may be submitted for experimental drugs showing promise in clinical testing of serious and immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place (21 CFR 312.34).

IND application Information

The IND application must contain Information In 3 broad areas:

1. Animal Pharmacology and toxicology studies: Preclinical data to assess if the product is reasonably safe for initial testing in humans.

2. Manufacturing Information: Information pertaining to composition, manufacturer, stability and controls used for manufacturing drug product to ensure that the company can adequately produce and supply consistent batches.

3. Clinical protocol and investigator information: Detailed Protocols for proposed clinical studies to make sure subjects are not exposed to undue risk. Also, information on the qualifications of the investigators (chiefly physicians) if they fulfill their clinical duties.

Finally, commitments to obtain informed consent from all research subjects, to obtain review of the study by an IRB and to adhere to the investigational new drug regulations. An IND must also include The Investigator’s brochure

Criteria for IND Application

A clinical study is required for an IND if it is intended to support

  • A new indication.
  • Change in the approved route of administration or dosage level.
  • Change in the approved patient population (vulnerable subjects, for e.g. pediatrics. elderly, HIV, immunocompromised).
  • A significant change in the promotion of an approved drug.

Codes of Federal Regulations (CFR):

  • 21 CFR PART 312: Investigational new drug application.
  • 21CFR PART 314: INDA and NDA for FDA approval to market a new drug.
  • 21CFR PART 316: Orphan drugs.
  • 21CFR PART 50: Protection of human subjects.
  • 21CFR PART 54: Financial disclosure by the clinical investigator.
  • 21CFR PART 56: Institutional review boards.
  • 21CFR PART 58: Good lab practice for Non-clinical laboratory (animal) studies.
  • 21CFR PART 201: Drug labelling.

Format and Content of IND

1. Cover sheet (Form FDA1571).

2. Table of contents.

3. Introductory statement and General Investigational Plan.

4. Investigator’s Brochure. 5. Protocols.

6. Chemistry, Manufacturing and Control information.

7. Pharmacology and Toxicology Information.

8. Previous human experience with IP.

9 Additional information.

Withdrawal of an IND

At any time, a sponsor can withdraw an effective IND. In such a case, FDA and IRS shall be so notified with reasons for withdrawal, all clinical studies ended, all current investigators and subjects notified, and all stocks of drug returned to the sponsor or otherwise disposed of on request of the sponsor in accordance with 312.59.

Final Year B Pharm Notes, Syllabus, Books, PDF Subjectwise/Topicwise

Final Year B Pharm Sem VIIBP701T Instrumental Methods of Analysis Theory
BP702T Industrial Pharmacy TheoryBP703T Pharmacy Practice Theory
BP704T Novel Drug Delivery System TheoryBP705 P Instrumental Methods of Analysis Practical
Final Year B Pharm Sem VIIBP801T Biostatistics and Research Methodology Theory
BP802T Social and Preventive Pharmacy TheoryBP803ET Pharmaceutical Marketing Theory
BP804ET Pharmaceutical Regulatory Science TheoryBP805ET Pharmacovigilance Theory
BP806ET Quality Control and Standardization of Herbals TheoryBP807ET Computer-Aided Drug Design Theory
BP808ET Cell and Molecular Biology TheoryBP809ET Cosmetic Science Theory
BP810ET Experimental Pharmacology TheoryBP811ET Advanced Instrumentation Techniques Theory
BP812ET Dietary supplements and NutraceuticalsPharmaceutical Product Development

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