Diagnostic Kits/USA Regulation Review

This section will detail the current state of Federal and State regulations required by government agencies for genetic tests. At present, the U.S. Food and Drug Administration ("FDA") and the Centers for Medicare & Medicaid Services ("CMS") regulate certain aspects of genetic testing. Although the vast majority of regulatory efforts are overseen by Federal Agencies, there are certain State-imposed standards for genetic tests that vary in scope by State.

Regulatory Agencies

U.S. Government Regulatory Entities

Agency Name	Abbreviation	Agency Type	Scope of Regulatory Oversight	External Link to Websites
Food & Drug Administration	FDA	Federal		fda.gov
Centers for Medicare & Medicaid Services	CMS	Federal		cms.gov
Federal Trade Commission	FTC	Federal		ftc.gov
Various State Agencies	(varies per state)	State		insert website list

Federal Agencies

The scope of FDA requirements, such as pre-market regulatory approvals, that apply to companies offering genetic tests depend almost entirely on the nature of the genetic test offered. In some cases, manufacturers must meet stringent requirements before marketing a genetic test, whereas in others, there are little or no substantive requirements.

CMS requires certain laboratory standards for all laboratories that conduct testing for patients in the United States. The requirements imposed by this agency are still somewhat dependent on the nature of testing conducted on the premises. For certain complex tests, including some genetic testing, laboratories must be approved by CMS and may require certain levels of supervision by highly trained individuals conducting the testing. However, for simpler tests, laboratories may perform testing without stringent oversight

State Agencies

Certain states have become increasingly involved in administering genetic testing oversight. In some cases, where states have implemented their own regulatory schemes for laboratories, laboratories located within an applicable state have become exempt from the requirements imposed by CMS. In other cases, laboratories located in a state which have state-mandated regulations that apply to laboratories must also meet CMS regulations.

New York and the state of Washington are two primary examples of where laboratories are exempt from CMS regulation. New York requires any laboratory which conducts testing to be evaluated and approved by license by the New York Department of Health before any testing can be conducted. Interestingly, these requirements also apply to laboratories that obtain specimens from patients residing within the state. Some commentators believe many laboratories avoid offering genetic testing services to New York residents.

California is an example of a state where laboratories must be both state and CMS regulations for clinical laboratory testing. Laboratories must obtain an approval license issued by the state before conducting direct-to-consumer genetic testing.

For all states that impose additional licensing or approval requirements for laboratory testing, companies manufacturing and marketing genetic tests will still be subject to any applicable FDA regulations.

Types of Genetic Tests and Testing "Services"

As previously noted, the scope of certain Federal Regulations that apply to manufacturers, marketers, and laboratories depends on the how a particular genetic test is categorized. This section will explain some of the pertinent differences of consumer genetic tests.

Most genetic tests, whether sold as a commercial testing "kit" to a laboratory or developed and an in-house "Laboratory Developed Test", utilize Analyte Specific Reagents (or "ASRs") to develop or conduct a test. ASRs are both polyclonal and monoclonal molecules that serve as the active ingredients of a test. When used in the course of a genetic test, ASRs effect certain chemical reactions with a specimen which can be use to identify or quantify certain chemical substances and provide diagnostic information. These may be purchased from specific manufacturers or created in-house.

Genetic Testing "Kits"

Certain manufacturers of medical devices develop and sell genetic laboratory testing "kits" which include a set of test ASRs and instructions for conducting a test. It's best to think of a kit as a commercial test that is manufactured and sold to several laboratories who will administer the test pursuant to the instruction within the kit.

Lab Testing Online

Laboratory Developed Tests ("LDTs")

Some laboratories develop their own "in-house" genetic tests. These tests have become known as Laboratory Developed Tests (or "LDTs").

Laboratories who offer LDTs believe that LDTs are distinguishable from testing "kits" because they are not actual testing "devices", but rather testing proprietary testing "services" to be conducted only by the laboratory who developed the test. Laboratories base this distinction is based, in part, on the fact that LDTs are only used internally and are not sold to other entities.

Laboratories who offer LDTs may create their own set of ASRs necessary for conducting the test or purchase the ASRs from an external entity. LDTs are especially distinct from "kits" when the ASRs are created internally. For regulatory purposes, the a laboratory that is a distinguishable as a test "service provider" rather than a commercial test "manufacturer" when the ASRs are not sold or used beyond the confines of a proprietary lab test. This issue will be explored extensively in the follow section.

AACC LDT Explanation
How Laboratory Tests Get to Market

FDA Regulations

The FDA's primary source of authority over genetic tests comes from the Food, Drug, and Cosmetic Act. This act allows the FDA to regulate "medical devices" which are defined as "an instrument, apparatus, implement, machine, continuance, implant, in vitro agent, or similar or related articles, including any component, part or accessory" that is "intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, or treat or prevention of disease, in man or other animals." Under this statutory authority, the FDA created and implemented a series of regulatory definitions, which further clarify what items and services are considered "medical devices," as well as a classification system which subject "medical devices" to various requirements.The FDA regulations further defined medical devices as "in vitro diagnostic products" which consistent of "those reagents, instruments, and systems, intended for use in the diagnosis of disease or other conditions."

Classification System of "Medical Devices"

The FFDCA contains a classification system for all medical devices intended for human use. Under this system, manufacturers of medical devices must satisfy certain requirements in the course of developing and marketing a product. Primarily, whether a device falls into a lower classification (e.g., Class I) is dependent on the level of complexity and inherent risks present in the device. The more complex devices are classified as Class II and III devices and subject to much more stringent requirements under the FFDCA. The contrast between requirements in the classification system is quite sharp. Class I devices typically have to satisfy simple reporting requirements whereas Class III devices must meet extensive clinical trials and pre-market approval standards set by the FDA.

Considerations (860.7) for classification, (1) The persons for whose use the device is represented or intended (2) THe conditions of use for the device, including conditions of use prescribed, recommended, or suggested in the labeling or advertising of the device, and other intended conditions of use; (3) The probable benefit to health from the use of the device weighed against any probably injury or illness from such use; and (30 the reliability of the device

Submission of evidence and documentation to a panel that determines classification.

N.B. -- 21 C.F.R. § 860.3

Federal Food, Drug, and Cosmetic Act Classifications

Classification	Description of Classification	FDA Requirements Prior to Market Clearance
Class I	The device can reasonably safe and effective for its intended use with minimal supervision. The device is also not considered life-threatening, or life-sustaining or a substantially important in preventing impairment of human health, nor does use present a potential unreasonable risk of illness or injury.	Device and manufacturer must be registered and listed with FDA. The device must be: manufactured under a quality assurance program, suitable for its intended use, adequately packaged and labeled. Most Class I devices do not have to satisfy 510(k) Pre-Market Notification (PMN) requirements.
Class II	Heightened oversight into the process of manufacture and use of the device is necessary to provide reasonable assurance of safety and effectiveness of the device.	Class II devices must meet all the requirements of Class I devices. Class II devices may require special labeling, mandatory performance standards, and post-market surveillance. Many Class II device will require 510(k) Pre-Market Notification (PMN); however a small number of Class II devices are exempt from this requirement.
Class III	Class III devices are under the most stringently regulated category of medical devices. These devices usually support or sustain human life, or are of substantial importance in preventing the impairment of human health, or are those which may present a potential unreasonable risk of injury.	Most class III devices require Pre-Market approval (PMA) prior to being marketed. is or will be required. The review process consists of a administrative and limited scientific review, an in-depth scientific, regulatory, and quality system review, and review and recommendation by an FDA advisory committee.

More information on the classification system available at fda.gov website.

FTC

Regulatory role: oversee marketing aspects of test offerings.

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