Support for FDA Regulatory Compliance

The Office of Regulatory Support (ORS) offers services to support clinical and translational research investigators with the navigation of and compliance with specific FDA-regulated processes, including research involving experimental drugs and devices, as well as pre-clinical laboratory studies.

Investigational New Drugs (IND)

ORS provides a variety of services to support development of IND application submission, and provides guidance and assistance throughout the life cycle of IND-regulated studies.

An IND Training Module, designed to provide local requirements for filing an IND application as the Regulatory Sponsor and to educate on FDA requirements, is offered through Blackboard. This training will take less than an hour, and is required for any investigator who will be submitting (or who currently holds) an active IND and optional (but strongly recommended) for study coordinators and research staff involved with the submission and maintenance of an IND. Access the training.

Applications will be filed with the Center for Drug Evaluation and Research (CDER) if the product is a drug and to the Center for Biologics Evaluation and Research (CBER) if the product is a biologic or a vaccine.

Determination of Need

An IND application must be filed with the FDA for any clinical research that proposes the use of an unapproved drug or when clinical studies propose to use an approved drug for an off-label indication or at alternative doses.

The Office of Regulatory Support will assist you in determining if you need to file an IND.

Exemptions:

Some clinical trials are exempt from submitting an IND.

A study may be exempt if it complies with all of the following criteria:

  • it is not intended to be reported to the FDA in support of a new indication for use or to support any other significant change in the labeling or advertising for the drug; and
  • it does not involve a change in the route of administration or dosage level, use in a subject population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product; and
  • it is conducted in compliance with the requirements for IRB review and does not intend to invoke exemption from informed consent; and
  • it is conducted in compliance with the requirements concerning the promotion and sale of drugs.

Guidance for pre-IND discussions with FDA

Often, the preparation of an IND application and the planning of a Study Protocol can be aided by some early advice from the FDA, in the form of a pre-IND consultation.

ORS assists in identifying any outstanding questions which would benefit from an audience with the FDA. ORS works with the researcher to assemble the pre-IND package and by participating in communications with the Regulatory Agency, as needed.

Submission of a request for a pre-IND consultation also provides an excellent opportunity to verify that the Division within the FDA to which you have chosen to submit an IND application is the best choice for a timely review of your study.

Assistance with submission of IND to FDA

The FDA has specified a format that the IND application should follow. ORS offers support for determining what content should be included in your IND package, and how to best map this to the FDA requirements.

Once the IND has been filed, the FDA acknowledges an official receipt date and assigns an IND number. The study cannot start until 30 days after the FDA receipt of the application, unless written notice from the FDA is given earlier that the study may begin. The FDA may request that the study not begin until additional information has been submitted to the Agency. In some cases, if the FDA feels like significant safety concerns remain, they may place the study on “Clinical Hold” until all issues have been addressed.

Assistance with filing annual reports and amendments to the FDA

As the study progresses, the sponsor is responsible for seeing that the study is conducted according to the current approved protocol. Changes to the protocol can be made by submitting amendments to both the IRB and the FDA. Our office can assist in the assembly of amendments for making such changes.

Even if no protocol changes are made, regulations require that reports be submitted to the Agency on an annual basis, at a minimum. Our office will assist with both reminding you about reporting milestones and in the preparation of the reports.

Adverse Event reporting is also critical to the continued operation of any clinical trial and our office will assist researchers in abiding by the proper reporting procedures. There are several categories of adverse events and they have varying timelines for submission of the reports based on severity.

Investigational Device Exemptions (IDE)

The IDE application, which is submitted to the FDA, allows for the conduct of a clinical study using a significant risk device which is either new, or has not yet been approved for that requested use.

A Devices and IDE Training Module, designed to provide an introduction to the field of Medical Devices, provide training in the process of filing an IDE as the Regulatory Sponsor and to educate on FDA requirements, is offered through Blackboard. This training lasts approximately one and a half hours, and is required for any investigator who will be submitting (or who currently holds) an active IDE with the FDA and optional (but strongly recommended) for study coordinators and research staff involved with the submission and maintenance of an IDE. Access the Device and IDE Access the training.

Navigation of the FDA-regulated device processes involves a series of decisions including assessment of the potential risk posed by the device. Research studies performed under IDE regulation are subject to differing levels of regulatory control – depending on the level of risk. The regulations differ between ‘significant risk’ and ‘non-significant risk’ device studies. Approval procedures for these differ accordingly and some studies are even exempt from IDE regulations.

Classification of Medical Devices

The FDA has established classifications and 16 groups for current medical devices [21 CFR 862-892]. Every device is assigned to one of three regulatory classes based on the level of control necessary to assure the safety and effectiveness of the device. The classes are Class I, Class II and Class III and differing requirements apply to each class.

Determination of Need

An IDE [21 CFR 812] is filed with the Center for Devices and Radiological Health (CDRH) to use a medical device for investigational purposes in a clinical study in order to collect safety and effectiveness data required to support a future marketing submission to the FDA. If the device is determined to be a ‘significant risk device’, then an IDE will likely need to be submitted to the FDA. If it is determined to be a ‘non-significant risk device’, then an abbreviated IDE might be all that is required to be submitted to the IRB, who would then function as the overseer of the device trial.

The Office of Regulatory Support will assist the researcher in determining if an IDE submission to the FDA is required. We can also assist with preparations of an abbreviated IDE to the IRB if necessary.

Guidance for pre-IDE discussions with FDA

If it is determined that an IDE is necessary, the FDA encourages new sponsors to obtain further device guidance prior to the submission of an IDE application. Submission of a pre-IDE increases the sponsor’s understanding of FDA requirements, regulations and guidance documents. ORS can assist researchers with setting up a pre-IDE meeting with the FDA and with the content of the pre-IDE package for submission.

Assistance with submission of an IDE to FDA

The format which the FDA requires for the IDE can be found at the CDRH IDE policies and procedures website. The required documents include a cover letter, monitoring procedures, investigator information, and information about the device. Support for the investigator during the application process will be to assist in the assembly of the submission.

Assistance with filing annual reports and amendments to the FDA

After the 30-day period for the FDA to request more information has elapsed, or once the IRB has determined that the non-significant risk device trial may proceed, the study may begin. Regulations require that reports be submitted to the Agency on an annual basis, at a minimum, but also if key changes take place in the format or structure of the study. Our office will assist with both reminding you about reporting milestones and in preparation of the reports.

Unanticipated adverse device effect (UADE) reporting is also critical to the continued operation of any clinical trial and our office will assist researchers in abiding by the proper reporting procedures. Reports of UADE must be submitted to the IRB and FDA within 10 days of the event.

Special considerations for in-vitro diagnostics

In-vitro diagnostics (IVDs) are reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body. IVD’s are devices, but may also be classified as biological products in some circumstances. Generally, IVDs are submitted to the US FDA through the CDRH [21 CFR § 809.3].

Exemptions:

Some in-vitro diagnostics may be exempt from IDE requirements if all of the following conditions are met:

  • The sponsor has labeled the device properly
  • The testing is non-invasive
  • The testing does not require an invasive sampling procedure that presents significant risk
  • The testing does not, by design or intention, introduce energy into a participant; and
  • The testing is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically-established diagnostic product or procedure.

Good Laboratory Practice (GLP)

Good Laboratory Practice (GLP) [21 CFR 58] deals with the organization, process and conditions under which laboratory studies are planned, performed, monitored, recorded and reported. These practices are intended to promote the quality and validity of test data. Preclinical studies should be performed under GLP conditions if they are intended to support applications for research or marketing permits to the FDA.

A properly designed and documented GLP study should make it possible to answer the following questions both during the study, for the researchers, and after the study, for FDA auditing, as well as 10 years or more later:

  • Who performed the study?
  • How was the experiment carried out?
  • Which procedures were used?
  • Were there any problems?
  • How were problems solved?

A list of frequently asked questions concerning work is available at the FDA webpage for GLP Guidance for Industry. This provides answers to some of the basic queries surrounding GLP nonclinical studies.

Support for developing a GLP-compliant laboratory system

Our office provides initial consultation about GLP regulations and expectations. This assesses the status of the laboratory and determines what practices will need to be implemented in order to bring the lab into full GLP compliance, including aspects of the infrastructure such as facilities, training, equipment, personnel and standard operating procedures (SOPs). We offer training for the laboratory staff on a variety of GLP topics including: documentation of results; tracking of samples; calibration of equipment; preparation of procedures; study protocols; and reports.

Courtesy Review of SOPs

A GLP-compliant laboratory can only run as smoothly as is directed by its SOPs. Correct format, proper amount of detail and the appropriate level of sign-offs are a few of the critical SOP issues. We provide training in writing SOPs and provide courtesy reviews of the SOPs.

Quality Assurance Oversight

The Quality Assurance Unit (QAU) is housed within the Office of Regulatory Support and serves as the regulation-guided entity which audits adherence to GLP-compliant SOPs in the labs. Once a lab has determined that they will be conducting GLP-compliant studies and have reached a level of GLP compliance in their infrastructure, we provide an initial System Audit prior to the start of any Study Protocol. This allows the QAU to do a formal assessment of the level of GLP compliance and provides the lab with feedback of any final changes which should be implemented before the Study Protocol begins.

The QAU will archive an executed copy of every Study Protocol which will be performed under GLP regulations.

Joint discussions between the QAU and the Study Director will determine the Critical Phases of Study Protocols. Critical phase inspections will then be scheduled and performed by the QAU, and reports to the Study Director will complete the feedback loop.

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