In Vitro Diagnostics Submissions and Compliance (Ch. 7) Flashcards
What FDA centers have oversight of IVDs?
CDRH and CBER
(CDRH: Center for Devices and Radiological Health
CBER: Center for Biologics Evaluation and Research?)
What is the role of CDRH for IVD regulations?
Assigned the lead role for policy development, procedural regulations, regulating all IVDs not assigned to CBER, small business programs, registration and listing, GMP, and medical device reporting
What is the role of CBER for IVD regulations?
Assigned the lead role in regulating all IVDs for screening or confirmatory laboratory tests associated with blood banking operations, as well as devices intended to be used for collecting, processing, storing or administering blood products and their components
TRUE/FALSE: CDRH is responsible for surveillance activities and compliance actions (issue guidances/performance standards, review submissions).
FALSE! Both CDRH and CBER have authority for these activities
What does OBRR stand for?
OBRR: Office of Blood Research and Review (CBER)
What does OIR stand for?
Office of In Vitro Diagnostics and Radiological Health
What office administers complexity categorization and waiver determinations under CLIA?
OIR: Office of In Vitro Diagnostics and Radiological Health
What does CLIA stand for?
CLIA: Clinical Laboratory Improvement Amendments (1988)
What is the definition of an IVD?
IVD:
Products that are those reagents, instruments, and systems intended for use in 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 sequalae.
(Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body)
TRUE/FALSE: An IVD is both a device and also may be a biologic.
TRUE!
An IVD is both a device and also may be a biologic.
What are the 4 types of IVDs?
- Research Use Only (RUO)
- Investigational Use Only (IUO)
- General Purpose Reagent (GPR)
- Analyte Specific Reagent (ASR)
What is a Research Use Only (RUO) IVD?
Research Use Only (RUO):
IVD products in the laboratory research phase of development and not represented as effective IVDs
***being studied to evaluate design, etc.
What is an Investigational Use Only (IUO) IVD?
Investigational Use Only (IUO):
An IVD shipped/delivered for product testing prior to full commercial marketing
***being used in a clinical investigation/research to determine the device’s safety and effectiveness
What are General Purpose Reagent (GPR) IVDs?
General Purpose Reagent (GPR):
Chemical reagents with a general laboratory application, used to collect, prepare, and examine specimens from the human body for diagnostic purposes, and are not labeled or otherwise intended for a specific diagnostic application
What are Analyte Specific Reagent (ASR) IVDs?
Analyte Specific Reagent (ASR):
Antibodies (both polyclonal and monoclonal), specific receptor proteins, ligands, nucleic acid sequences and similar reagents that, through specific binding or chemical reaction with substances in a specimen, are intended for use in a diagnostic application for identifying and quantifying an individual chemical substance or ligand in biological specimens
What types of IVDs are NOT approved/cleared?
RUOs and IUOs
(RUO: Research Use Only
IUO: Investigational Use Only)
What statement must be labeled on RUOs?
RUO:
“For Research Use Only. Not for use in diagnostic procedures.”
What statement must be labeled on IUOs?
IUO:
“For Investigational Use Only. The performance characteristics of this product have not been established.”
What statement must be labeled on GPRs?
GPR:
“For Laboratory Use”
Also must be labeled with basic identifying information, storage conditions, and warnings/precautions
What statement must be labeled on ASRs?
ASR Class I: “Analyte Specific Reagent. Analytical and performance characteristics are not established.”
ASR Class II or III: “Analyte Specific Reagent. Except as a component of the approved/cleared test [test name], analytical and performance characteristics of this ASR are not established.”
IVDs are regulated according to a risk-based classification system based on what factors?
Intended use, indications for use, types of specimens to be tested, and the consequences of a false test result
What is the definition of intended use?
Intended Use:
The device’s general purpose of function and encompasses the indications for use
What is the definition of indications for use?
Indications for Use:
The disease or condition the device will diagnose, treat, prevent, cure, or mitigate, including a description of the patient population for which the device is intended
TRUE/FALSE: The level of control required to ensure devices are reasonably safe and effective when they are placed on the market determines the IVD class.
TRUE
Class 1 IVDs must comply with General Controls, which include…
Establishment registration and device listing, GMPs, Labeling
What are examples of Class 1 IVDs?
Class 1 IVDs:
clinical chemistry tests for urine pH, reagents and kits for immunohistochemistry stains
What is the regulatory pathway for most Class 2 IVDs?
General controls + special controls
510(k) submission for marketing clearance that includes evidence for a determination of substantial equivalence to a similar product already on the market (predicate device)
What are examples of Class 2 IVDs?
Class 2 IVDs:
microbiology tests for pathogenic organisms that cause diseases, newborn screening for metabolic disorders
What is the regulatory pathway for most Class 3 IVDs?
General controls + special controls
PMA application
What are examples of Class 3 IVDs?
Class 3 IVDs:
screening for cancers, tests screening for infectious agents in blood
What is the purpose of CLIA?
CLIA:
Regulates laboratory testing and requires clinical laboratories to obtain a certificate before accepting materials derived from the human body to provide information for the diagnosis, prevention, or treatment of any disease
TRUE/FALSE: The CLIA certificate type depends on the size of the laboratory.
FALSE! The CLIA certificate type depends on the laboratory tests’ complexity.
What are the 3 test complexity levels?
- Waived tests
- Moderate complexity tests
- High complexity tests
Requests for complexity categorization are submitted to what FDA center?
CDRH
When is CLIA categorization determined?
At the time a 510(k) or PMA is submitted; FDA will notify the manufacturer of the CLIA within 2 weeks of device clearance/approval
What is a presubmission?
Presubmission:
A formal written request from an applicant/sponsor to the FDA for feedback (either written response or a meeting)
What is premarket notification (510(k))?
Premarket Notification (510(k)): A premarket submission made to FDA at least 90 days prior to placing a device on the market, to demonstrate the device is as safe and effective (substantially equivalent) as a legally marketed predicate device (not subject to a PMA)
TRUE/FALSE: A clinical study is typically required for a PMA.
True
What does SSED stand for?
SSED: Summary of Safety and Effectiveness Data
When is an IDE required?
An IDE is required for significant risk IVDs
TRUE/FALSE: IVDs are typically exempt from IDE regulations.
True
What is the purpose of a de novo classification?
To classify a Class III device (auto-classified due to no predicate) as a Class I or II:
For devices that don’t have a predicate, but for which special controls will be appropriate for controlling risks and ensuring devices are reasonably safe and effective
What law created the requirement for eCopy submissions?
FDASIA
What are the three levels of concern of software?
- Major - failure could result directly in death or serious injury (includes incorrect/delayed information)
- Moderate - failure could result directly in minor injury (includes incorrect/delayed information)
- Minor - failure is unlikely to cause any injury
What is a device hazard analysis?
Includes the hardware and software hazards identified during design and development, and an assessment of the severity and the mitigations implemented to control them
What is the purpose of cybersecurity management?
To reduce patient risk by decreasing the likelihood that device functionality is intentionally or unintentionally compromised by inadequate cybersecurity
What is a companion diagnostic?
Companion diagnostic (aka in vitro companion diagnostic device): An in vitro diagnostic device that provides information essential for the safe and effective use of a corresponding therapeutic product
What are situations where companion diagnostics would be used?
- Identify patients that are most likely to benefit from the therapeutic product
- Identify patients likely to be at an increased risk for serious adverse reactions as a result of treatment
- Monitor response to treatment with the therapeutic product for the purpose of adjusting treatment
TRUE/FALSE: The FDA reviews each IVD companion diagnostic device submission within the context of its corresponding therapeutic product.
TRUE! IVD companion diagnostics are approved/cleared with the corresponding therapeutic product’s approval
What is a Laboratory Developed Test (LDT)?
Laboratory Developed Test (LDT):
Intended for clinical use and is designed, manufactured, and used within a single laboratory
TRUE/FALSE: LDT regulatory oversight is currently unclear.
TRUE - The FDA has allowed LDT commercialization without premarket review in the past. However, this is becoming an issue
