Along with review by the IRB, research studies involving human subjects may require review by other departments or committees.  Ancillary reviews are reviews of human research projects by compliance groups or individuals and happen in addition to the IRB review.  These reviews vary, depending on the grant requirements and type of research performed and may be required by federal or state regulations, IRB policy, or institutional requirements.  There are different types of ancillary review.  The Quality Assurance program conducts ancillary reviews for studies using a potential investigational drug or device.  First, the Quality Assurance team will determine if the drug or device meets the FDA's definition.  Then, the Quality Assurance team will determine if the study also meets the FDA's definition of a clinical investigation.  If both conditions are met, the study will qualify as an Applicable Clinical Trial using either a drug or device and will therefore be subject to the corresponding regulations. 

Investigational Drugs

The definition of the term drug in section 201(g)(1) of the FD&C Act includes, among other things, “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease...” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.”  The FDA defines a drug as: 

• A substance recognized by an official pharmacopoeia or formulary. 
• A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. 
• A substance (other than food) intended to affect the structure or any function of the body. 
• A substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device. 
• Biological products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process versus biological process.) 

Investigational drugs are not only defined as experimental drugs, but can also include the use of food as a "drug" to address medical conditions. 

IND Applications

To determine if a study uses an investigational drug, the Quality Assurance team references HRP-306, which can be found in the CATS IRB Library.  Research using investigational drugs requires an Investigational New Drug Application (IND).  An Investigational New Drug Application (IND) is a request from a clinical study sponsor to obtain authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans.  Any drug that does not currently have FDA approval for marketing requires an IND before it can be administered as a part of a research study. In some cases an FDA-approved (marketed) drug must also be conducted under an IND. 

If a study is potentially using a food or dietary supplement as a drug, the IRB requires either an IND or a letter from the FDA indicating that an IND is not required.  For drugs that are potentially IND Exempt, the PI can provide their own justification for which IND exemption category they think the drug meets (following HRP-306).  The board will need to determine if they agree with the justification.  The Quailty Assurance team can assist researchers in drafting justifications for IND exemptions. 

Investigational Devices

The FDA defines a medical device as:

• "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part or accessory which is: recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,
• intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
• intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes" (see FDA.gov).

Medical devices range from simple tongue depressors and bedpans to complex programmable pacemakers, and closed loop artificial pancreas systems.  Medical devices also include medical mobile apps and the use of software as a medical device.  In the context of Penn State research at University Park, the most typical medical devices include apps, assistance devices, and diagnostic devices.

IDE Applications

To determine if a study is a device study and requires an Investigational Device Exemption (IDE), the Quality Assurance team references HRP-307 found in the CATS IRB Library. Device studies are "intended for use in diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease"  and the activity "evaluates the safety or effectiveness" of the device. 

Device studies may be exempt from the need to request an IDE, but are not exempt from FDA regulations.  The Quality Assurance team will help the IRB to make that determination.  If not exempt from an IDE, the IRB will use HRP-416 to determine if the study is significant or non-significant risk.  If the study is non-signficant risk, an IDE submission is not needed as the study will qualify for an Abbreviated IDE.  Studies deemed to be significant risk will require an IDE application, which the Quality Assurance team can assist to facilitate as needed.