# Presentation: 736840

## Classification of HLA DevicesFDA Introduction & Background 

- Sheryl A. Kochman
- CBER/OBRR/DBA

## Objectives

- Provide an overview of the current regulatory status of HLA devices
- Provide background regarding medical device classification
- Provide an overview of the Third Party Review Program

## What are “HLA Devices”?

- In vitro diagnostic reagents and kits for use in determining the HLA phenotype or genotype of an individual or for detecting and identifying antibodies to HLA antigens

## What are “HLA Devices”? (cont’d)

- characterized polyclonal or monoclonal antibodies for determination of phenotype
- analogous to Blood Grouping Reagents
- (CBER licensed IVD)
- DNA-based assays for determination of genotype
- characterized leukocytes for detection and identification of antibodies
- analogous to Reagent Red Blood Cells
- (CBER licensed IVD)

## What are NOT “HLA Devices”?

- In vitro diagnostic reagents or kits used to predict disease
- Anti-HLA-B27 to detect HLA-B27 antigen as a marker for ankylosing spondylitis
- regulated by Center for Devices and Radiological Health (CDRH)

## Regulatory History

- First product license for Leukocyte Typing Serum issued December 1974
- FDA Guidelines for Production, Testing, and Lot Release of Leukocyte Typing Sera issued December 1977
- FDA Proposed Rule recommending that additional standards for Leukocyte Typing Serum be revoked issued August 1, 1980
- FDA Final Rule revoking additional standards for Leukocyte Typing Serum issued August 10, 1982

## Effect of Proposed and Final Rules

- Expanded control authority under the Medical Device Amendments to the FD&C Act
- adulteration §501
- misbranding §502
- registration §510
- classification §513
- banned devices §516
- notifications & other remedies §518
- records & reports §519
- restrictions on sale, distribution, or use §520(e)
- good manufacturing practice §520(f)

## Effect of Proposed and Final Rules

- All manufacturers (previously licensed and new unlicensed) to register and list under 21 CFR 807
- New manufacturers to submit premarket notification submission (510(k)) per          21 CFR 807
- Labeling to conform to 21 CFR 809.10
- Manufacturing to conform to 21 CFR 820 (cGMP) (currently QSR)
- Classification to follow

## Subsequent Regulatory Process

- CBER received, reviewed, and cleared a number of 510(k) submissions (~65)
- letters variably refer to device as Class I and Class II despite lack of formal classification
- current letters list device as unclassified

## Basis for Confusion

- Proposed rule clearly states a request for classification has been made and will be published upon receipt.
- Also states:
- If this proposal is published in final form, the device shall be subject to the general controls provisions
- The agency believes that these and other general controls applicable to medical devices are sufficient
- The appropriate regulatory status of the product will be considered in the course of classification

## Problems Associated With Lack  of Classification

- Confusion in industry about which standards apply
- Confusion in CBER about what review criteria apply
- Erroneous belief in industry that registration, listing, and 510(k) submission are not needed
- Confusion in ORA about whether or not to inspect and what standards to apply during an inspection
- Inability to proceed with initiatives pertaining to FDAMA, e.g., Third Party Review

## Device ClassificationPreamendments Devices

- Preamendments devices are those which were on the market prior to enactment of the Medical Device Amendments of 1976
- Three Classes
- Class I
- Class II
- Class III

## Class I 

- General controls alone are sufficient to provide reasonable assurance of safety and effectiveness  _**OR**_
- It is unclear if general controls alone are sufficient to provide reasonable assurance of safety and effectiveness but the device is not life-supporting, life-sustaining, or of substantial importance in preventing impairment of human health.

## General Controls

- Establishment registration
- Product listing
- Conformance to QSR (formerly GMP)
- Conformance to device labeling requirements
- Submission of a 510(k) (if applicable)
- Others in the act

## Class I

- Most Class I devices are now exempt from the requirement to submit a 510(k)
- Those that are not, are designated as “reserved”
- Most Class I devices are not subject to the design control provisions of the QSR
- Some Class I devices are exempt from other requirements of the QSR
**Least stringent regulatory category**
- EXAMPLE:  Blood grouping view box

## Class II

- General controls alone are insufficient to provide reasonable assurance of safety and effectiveness and there is sufficient information to establish special controls

## Special Controls

- Performance standards
- Special labeling requirements
- Guidance documents
- Recommendations
- Patient registries
- Post-market surveillance
- “Other actions deemed appropriate by the Commissioner”
**In addition to General Controls**

## Class II

- Generally moderate-risk devices
- May be life-supporting or life-sustaining
- Some have been exempted from the requirement to submit a 510(k)
- EXAMPLE: Automated blood grouping and antibody test system

## Class III

- There is insufficient information that general or special controls will provide reasonable assurance of safety and effective  _**AND**_
- The device is:
- life-supporting, life-sustaining, or of substantial importance in preventing impairment of human health  **OR**
- presents a potential unreasonable risk of illness or injury

## Premarket Approval

- Manufacturer must submit a premarket approval application (PMA)
- scientific and regulatory review ensure the safety and effectiveness of the device

## Class III

- High risk device
- Most stringent regulatory category
- General Controls also apply
- EXAMPLE: Electromagnetic blood and plasma warming device

## Device ClassificationPostamendments Devices

- Postamendments devices are those which are introduced to the market after  enactment of the Medical Device Amendments of 1976
- Two routes to classification
- same regulatory class as the device to which it is deemed substantially equivalent
- Class III if not substantially equivalent to a device already legally on the market

## Substantial Equivalence

- The device has the same intended use as the predicate device  _**AND**_
- The device has the same technological characteristics as the predicate device **OR**
- The device has different technological characteristics but does not raise new concerns of safety and effectiveness.