In Vitro Diagnostic Development

In vitro diagnostic (IVD) is one of my direct therapeutic specialties as I worked as a Clinical Research Associate (CRA) for an in vitro diagnostic sponsor company for 3.5 years. Below is a summary of what I know about in-vitro diagnostic clinical trial.

In Vitro Diagnostics

So what are in vitro diagnostics (IVDs)? An in vitro diagnostic is a way to test for certain property or result outside the human body. Some example of in vitro diagnostic tests include testing blood for infectious pathogens, testing urine for pregnancy, and testing finger stick for blood glucose. FDA defines IVDs as (21 CFR 809.3(a)):

In vitro diagnostic products are those 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 or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body. These products are devices as defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (the act), and may also be biological products subject to section 351 of the Public Health Service Act.

IVDs are regulated under the definition of medical device and fall under requirement of medical device regulation, 21 CFR 812. Thus, they are categorized into the 3 classes of medical devices.

Class I devices are those that general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device. This is the lowest risk category. General controls include establishment registration, device listing, good manufacturing practices, labeling, and premarket notification. Class I devices are exempt from the IDE process and premarket review.

Class II devices are those that pose a moderate risk to patients and are subjected to special controls in addition to general controls. Special controls may include additional labeling requirements, specific performance standards, and post market surveillance. Most class II IVDs need to go through premarket notification (510(k)) process. 510(k) approval may or may not require clinical trials.

Class III devices are those with the highest risk to the patients. They are subject to investigational device exemption (IDE) application and premarket approval (PMA) requirements. PMA application usually requires clinical trials.

In Vitro Diagnostic Clinical Trial

Because in vitro diagnostic tests are done outside human body, samples such as blood, urine, or tissue are collected for the test. This allows clinical trials for in vitro diagnostic to be much simpler (although not necessary easier) to conduct when compared to drug or medical devices. Below are some unique aspects of clinical trials for IVDs.

Number of Clinical Sites Required

In general, FDA required clinical trials to evaluate the performance of an IVD to be evaluated at 3 or more clinical sites. One of these sites can be at the manufacturer. Compared to drug clinical trials where number of sites can be 10 or more, IVD clinical trials are done in quiet fewer number of sites.

Informed Consent Waiver for Some In Vitro Diagnostic Clinical Trials

Specifically, FDA allows some in vitro diagnostic trial to be conducted without the need for informed consent if the samples meet the following criteria (from Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable, Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff –

  1. In vitro diagnostic test does not need IDE submission (see 21 CFR 812.2(c))
  2. Leftover specimens will be used (specimens for routine clinical care that would have been discarded)
  3. Specimens are not individually identifiable
  4. Individual caring for the patients are different from those conducting the clinical trial
  5. Specimens are provided to the investigator(s) without identifiers that can identify patient information
  6. Clinical trial is overseen by an IRB following 21 CFR 56

Type of clinical evaluation needed

The type of clinical evaluation needed for IVDs can vary depending on the intended use and the target specimen from patients. However, there are some common tests that are usually required for IVD performance evaluation. This may include precision, reproducibility, interference from other substance, measuring interval (range and cutoff), expected clinical performance characteristics (e.g. sensitivity, specificity).

Level of on-site monitoring needed

IVD clinical trials are tests that give results. As procedures for conducting an IVD test are set for clinical trials, the results of the test can usually be monitored remotely via email or fax. Thus, the number of monitoring visits normally conducted by the clinical trial monitor (Clinical Research Associate) for an IVD trial can be a lot less for IVD trial compared to drug or medical device trial.

6. Clinical Trial Basics-IVD-Differences2


Post author

Ernie Sakchalathorn

Polachai Ernie Sakchalathorn is the founder of and has been in clinical research since 2007. While he is no longer affiliated with the website or benefits financially from site operations, he still remains a professional in the clinical research space and currently serves as a Clinical Affairs Manager at a medical device company.

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