The United States is the region that conducts most clinical trials in the world and is the flag bearer for most clinical research studies requires considering many factors and areas. In the first part of this series of articles for clinical trials in the United States, we have seen the regulatory situation, clinical sites, and investigators. In this article, we will understand the regulatory aspects of medical devices and other aspects of clinical trials in the USA.
Starting with some salient points on Clinical trials in United States.
Salient features of Clinical trials in the United States
- Language for a clinical trial application: English
- Process of regulatory & EC approval: Parallel
- Clinical trial registration: Required
- Studies on minors: Age is determined at the state level
- Export of specimens: Allowed
Regulatory for medical devices Clinical trials in the United States
What are regulatory bodies for medical devices in the USA?
FDA’s Center for Devices and Radiological Health (CDRH) is responsible for regulating firms that manufacture, repackage, relabel, and/or import medical devices sold in the United States.
CDRH regulates radiation-emitting electronic products (medical and non-medical) such as lasers, x-ray systems, ultrasound equipment, microwave ovens, and color televisions.
- Medical devices are classified into Class I, II, & III, and the regulatory control increases from Class I to Class III.
- The device classification regulation defines the regulatory requirements for a general device type.
- Class-I devices are exempt from premarket notification.
- Class-II devices require premarket notification.
- Class-III devices require premarket approval.
Which regulations apply to the clinical investigation of a medical device?
The regulations in clinical studies of medical devices must comply with
- FDA’s human subject protection requirements,
- Institutional Review Board (IRB) requirements,
- Investigational Device Exemptions (IDE) requirements,
- Financial Disclosure for Clinical Investigators requirements, as well as
- Any other applicable regulations, including pertinent regulations.
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Regulatory changes in IRB Requirements for medical device clinical trials in the United States
The organization that plans to conduct the particular type of clinical trials may rely on central rather than for reviews required by the US Food and Drug Administration.
- The FDA’s Center for Devices and Radiological Health (CDRH) has issued a technical amendment allowing sponsors to conduct clinical studies for Humanitarian Device.
- Exemption (HDE) devices to utilize central IRBs to review their activities; previously, clinical trial sponsors and sites were required to undergo such reviews by local IRBs.
- The allowance for central IRB review applies to Investigational Device Exemption (IDE) studies and multi-site clinical studies.
- This change is to bring drug and device regulations more closely in line with one another, according to the FDA.
When the regulations doesn’t apply ?
- An FDA-approved device to test a physiologic principle where no data is collected about the device,
- An FDA approved device to address a research question and no data is collected about the device, or
- Using an FDA-approved device for clinical purposes (e.g., monitor a side effect, measure treatment progress),
- As long as there is no intent to collect safety or effectiveness data or develop the device for marketing. (use of an MRI to measure a clinical outcome in a study that has nothing to do with the MRI itself).
The approval process for the medical device clinical trials in the United States
Various types of drug applications
Investigational New Drug (IND)
As per Federal Law, a drug requires marketing approval before transportation and distribution across the state lines.
- New Drug Application (NDA),
- Abbreviated New Drug Application (ANDA),
- Biologic License Application (BLA).
What is the submission process?
- In the United States, the sponsor should submit an investigational new drug application (IND) for the FDA review and authorization.
- Whether a drug requires an IND or not before marketing primarily depends on the intent of the investigation and the degree of risk associated with the use of the drug.
- Institutional ethics committee (EC) review of the clinical investigation may be conducted in parallel with the FDA review of the IND. However, EC approval must be obtained before the sponsor being permitted to initiate the clinical trial.
Clinical trial registry
- Either the sponsor or the principal investigator (PI) designated by the sponsor should register electronically with the Clinicaltrials.gov databank.
- The sponsor/PI must register 21 calendar days after the first human participant is enrolled in a trial.
Electronic regulatory submission and review
The Electronic Common Technical Document (eCTD) is the standard, accepted electronic format for the following submission types:
- Investigational New Drug Application (IND)
- New Drug Application (NDA)
- Abbreviated New Drug Application (ANDA)
- Biologics License Application (BLA)
- Master files: Drug Master File (DMF) and Biologics Master File (BMF)
- Emergency Use Authorization (EUA)
If the applicant submits the data electronically, it is easier for FDA to review data, approve new drugs, and monitor drugs after they go on the market.
When a clinical trial can get FDA assistance?
Drug developers can seek help from FDA at any point during the drug development process, including
- Pre-IND application, to review FDA guidance documents and get answers to questions that may help enhance their research.
- After Phase 2, to obtain guidance on the design of broad Phase 3 studies.
- Any time during the process for assessment of the IND application.
Regulations for import and export of medicinal products for clinical trials in the United States
The Centre for Drug Evaluation and Research (CDER) regulates import and export of medicinal products.
- Foreign drug manufacturers who wish to import drugs into the United States must register with the FDA.
- The Federal Food, Drug, and Cosmetic Act prohibit the import or export of unapproved new drugs, meaning any drug that has not been manufactured with FDA approval.
- Imported drug products are subject to inspection by the US Bureau of Customs and Border Protection, so the FDA may refuse admission of any drug that appears to be unapproved, misbranded, or adulterated.
When to initiate a trial?
Applicant can initiate the clinical trials immediately after the 30-day approval, after receiving IND and Ethics committee approval. The sponsor or the Principal investigator designated by the sponsor should register the Clinical Trials with clinicaltrial.gov.
What are the reporting and disclosure requirements?
Food and Drug Administration requires all applicable clinical trials to register and report results on a government-administered website (www.clinicaltrials.gov). If a clinical trial involves Phase I studies of a drug, then the results submission is not required.
FDA obligations with respect to clinical trial subjects
The FDA requires that clinical trial subjects be given adequate information and time to make an informed decision on whether to participate in a clinical trial and ask questions and have those questions answered.
Insurance requirements for clinical trials
- In the United States, human clinical trial liability insurance is not mandatory. But the multi-country trials are likely to require multiple insurance policies.
- Hence it is recommended that companies consider brokers and lawyers familiar with jurisdictional requirements to enter into sponsorship agreements.
What are the data protection concerns?
Data protection issues considered while conducting clinical trials
Most clinical trials today are designed according to International Conference on Harmonisation (ICH) guidelines with multiple jurisdictions in mind.
We can consider the data protection into two basic categories
- Data integrity and retention, and
- Patient privacy.
With regard to data integrity and retention, the FDA periodically issues guidance for industry documents on its website, which should be constantly monitored for updates.
Why USA is preferred destination for clinical trials, in numbers?
The country contributes the most clinical trial participants in the world. The USA (0.35) makes up a little more than 4% of the world population.
- Trial participants of US (31%) versus Non-US trial participants (69%).
- In the year, 2016 the total number of participants in the United States was 11,060 (42.64%), and the rest of the world participants were 14,881 (57.36%).
- Most clinical trials in 2016 were on Infectious disease (3,057), Dermatology (2,860), Ophthalmology (2,249), and Pulmonary diseases (724).
- In 2017, the most clinical trials were on Immune system disease (7,351), Psychotic Disorders (6,448), Infectious disease (6,059), and Oncology (6,001).
- The total number of male participants is (53,143), and the number of female participants is (56,181).
Click here for more information to Conduct Clinical Trials in the U.S.? Here’s what you need to know – Part 1
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