The process of developing a new drug is very complicated and regulated so we can be sure that the drug is going to be safe and work properly in the patient population. The first step in the IND application process is to submit an IND application.
After a company has completed enough lab/safety testing and animal studies, the IND will allow them to conduct their clinical trials in people for research purposes, as well as providing a mechanism for the regulatory body of the IND to approve the IND application for investigational use of drugs on patients.
The U.S. FDA and comparable organizations in other countries (such as EMA in Europe and CDSCO in India) have established regulations for submitting IND applications. Therefore, all persons involved with Developing Drugs (including Drug Developers, Clinical Research and Drug Regulatory Affairs) need an understanding of submitting an IND application.
In addition to providing ethical guidelines for conducting research on human subjects, IND also provides state and federal governments with information related to the drug including:
- Preclinical studies
- Manufacturing
- Protocols for conducting clinical studies
- Qualifications of Principal Investigational Staff
When submitting the IND application, the manufacturer is requesting permission from regulatory agencies to conduct human trials of this drug.
These studies can determine:
It will contain:
Key elements contained in this section include:
This information shall include:
Usually, the FDA has a 30 day period after submission to review an IND application.
Multiple actions can occur during the Regulatory Authority’s review period:
1. Approve an IND and allow clinical trials to begin.
2. Request additional information for sufficient review.
3. Place the clinical trial on clinical hold due to safety.
Once there are no objections made during the review period, the sponsor may begin the clinical trial phase of the drug development.
Phase I- Assess safety through testing in small groups of healthy participants.
Phase II- Evaluate efficacy (how well the drug works) in an appropriate patient population. The safety and side effects are also assessed.
Phase III- Assess efficacy in large-scale clinical trials. Compare the drug to available treatments.
Once the IND application has been successfully completed and all clinical trial data is collected, the sponsor can submit a New Drug Application (NDA) to receive FDA marketing approval.
The essential format of reporting includes:
Common types of issues experienced when preparing IND applications are:
If there were no regulatory framework in place for approving a drug as a candidate for clinical trial:
The IND application is an essential component of the pharmaceutical development process involving all investigational drugs; it provides patients with assurance that therapeutic products have been subject to rigorous scientific analysis prior to their exposure to humans as part of clinical trials.
The detailed submission of the development history and status of investigational drug candidates; manufacturing processes; preclinical evaluation of safety, efficacy, etc.; and clinical protocols constitute the IND system that protects patients from harm while stimulating innovative advances in medicines.
Knowledge of the IND process is essential for all organizations engaged in developing new therapies for progression through the pharmaceutical drug development "life cycle" from the laboratory into clinical practice and on to the patient population that will benefit from them.
The U.S. FDA and comparable organizations in other countries (such as EMA in Europe and CDSCO in India) have established regulations for submitting IND applications. Therefore, all persons involved with Developing Drugs (including Drug Developers, Clinical Research and Drug Regulatory Affairs) need an understanding of submitting an IND application.
What is an Investigational New Drug (IND) Application?
The IND application permits the pharmaceutical company to apply to the appropriate regulatory entity for permission to commence the clinical testing of a drug not previously approved by the FDA. After demonstrating through pre-clinical studies that the drug appears to be safe enough for use in humans as part of a clinical trial, the drug developer must prepare and submit the IND application to the appropriate regulatory entity (e.g., the FDA or EMA).In addition to providing ethical guidelines for conducting research on human subjects, IND also provides state and federal governments with information related to the drug including:
- Preclinical studies
- Manufacturing
- Protocols for conducting clinical studies
- Qualifications of Principal Investigational Staff
When submitting the IND application, the manufacturer is requesting permission from regulatory agencies to conduct human trials of this drug.
Types of IND Applications
IND Applications that fall within one of four major types based on the intended purpose of the clinical study.1. Commercial INDs
A Commercial IND is submitted by a sponsor (e.g., pharmaceutical company) that intends to manufacture and sell the drug after successful completion of the clinical study; therefore, this is the most common type of IND application submitted to the FDA.2. Investigator INDs
An Investigator IND is submitted by the principal investigator who is both sponsoring and conducting the clinical study. An investigator submitting an IND will be responsible for all regulatory compliance as the sponsor.3. Emergency Use INDs
Emergency Use INDs (EINDs) permit the use of investigational drugs to treat patients with a life-threatening illness in which no adequate alternative therapies exist. EIND allows for rapid access to potentially life-saving therapies for patients in otherwise unavailable circumstances.4. Treatment INDs
A Treatment IND permits the use of investigational drugs in the treatment of patients who have a serious disease or condition and who otherwise would not qualify for participation in the ongoing clinical study of the investigational drug. Treatment IND may be used primarily for patients who have serious and/or life-threatening diseases (e.g., cancer, certain rare genetic disorders).Key Components of an IND Application
As an IND submission to the FDA, it has several important, distinct sections to ensure that the FDA has a complete understanding of the investigational drug.1. Preclinical Study Data
Taxes must be assessed via laboratory/animal studies before any human studies take place.These studies can determine:
- Toxicity
- Pharmacological behavior
- Dosing and metabolism of the drug
- Safe dosage limit for a drug
2. Chemistry, Manufacturing and Control (CMC)
The CMC section of your entity’s application will describe how the entity has manufactured, tested and retained appropriate controls over the drug.It will contain:
- Information on the drug’s composition
- A description of the drug manufacture
- Data demonstrating the drug’s stability
- A description of the quality controls used in the manufacture of the drug
3. Clinical Protocols
Clinical protocols describe how the study will be performed.Key elements contained in this section include:
- Study design
- Patient eligibility criteria
- Plan of dosage
- Plan of monitoring
- Designating safety endpoints
4. Investigator Information
Sponsors will be required to submit information about the clinical investigators that will be involved in the trial.This information shall include:
- Qualifications
- Clinical experience
- Review and approval by IRB
Review Process for Investigational New Drug
A regulatory authority will review and assess an IND application to be able to determine whether to proceed with clinical trials.Usually, the FDA has a 30 day period after submission to review an IND application.
Multiple actions can occur during the Regulatory Authority’s review period:
1. Approve an IND and allow clinical trials to begin.
2. Request additional information for sufficient review.
3. Place the clinical trial on clinical hold due to safety.
Once there are no objections made during the review period, the sponsor may begin the clinical trial phase of the drug development.
Phases of Clinical Trials Post IND Approval
Clinical trials are conducted in phases when the IND becomes effective.Phase I- Assess safety through testing in small groups of healthy participants.
Phase II- Evaluate efficacy (how well the drug works) in an appropriate patient population. The safety and side effects are also assessed.
Phase III- Assess efficacy in large-scale clinical trials. Compare the drug to available treatments.
Once the IND application has been successfully completed and all clinical trial data is collected, the sponsor can submit a New Drug Application (NDA) to receive FDA marketing approval.
IND Safety Reporting Requirements
It is essential for sponsors to consistently keep track of the safety of their subjects during their clinical trials.The essential format of reporting includes:
- Adverse Event Reports.
- Annual Progress Reports.
- Protocol Amendments.
- Safety Updates.
Challenges in IND Preparation
There are many scientific and regulatory challenges that need to be overcome in order to prepare a successful IND application.Common types of issues experienced when preparing IND applications are:
- Some Sponsors do not submit the appropriate amount of Preclinical Data.
- Variations in Manufacturing Processes.
- Poor clinical protocol design.
- Insufficient Amount of Safety Data.
Importance of IND in Drug Development
The IND application is an essential step in the transition from laboratory study of potential new medicines to using them in human subject research.If there were no regulatory framework in place for approving a drug as a candidate for clinical trial:
- The safety of patients participating in those trials may be jeopardized.
- Quality of the drug may not be adequately monitored.
- There may be no assurance that scientific validity or integrity will be upheld during the trial.
The IND application is an essential component of the pharmaceutical development process involving all investigational drugs; it provides patients with assurance that therapeutic products have been subject to rigorous scientific analysis prior to their exposure to humans as part of clinical trials.
The detailed submission of the development history and status of investigational drug candidates; manufacturing processes; preclinical evaluation of safety, efficacy, etc.; and clinical protocols constitute the IND system that protects patients from harm while stimulating innovative advances in medicines.
Knowledge of the IND process is essential for all organizations engaged in developing new therapies for progression through the pharmaceutical drug development "life cycle" from the laboratory into clinical practice and on to the patient population that will benefit from them.
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