Guidance for Industry and FDA 

Staff 

Commercially Distributed 

Analyte Specific Reagents (ASRs): 

Frequently Asked Questions 

Document issued on: September 14, 2007 

The draft of this guidance document was released on September 7, 

2006. 

 

For questions regarding this document contact Courtney Harper at 240-276-0694 

(courtney.harper@fda.hhs.gov). For questions regarding this document as applied to 

devices regulated by CBER contact Martin Ruta at 301-827-3518 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Devices and Radiological Health 

Office of In Vitro Diagnostic Device Evaluation and Safety 

 Center for Biologic Evaluation and Research 
Contains Non-Binding Recommendations

Preface 

Comments 

Written comments and suggestions may be submitted at any time for Agency 

consideration to the Division of Dockets Management (HFA-305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Alternatively, 

electronic comments may be submitted to http://www.fda.gov/dockets/ecomments . All 

comments should be identified with the docket number 2006D-0336. 

For questions regarding this document contact Courtney Harper at 240-276-0694 

Additional Copies 

Additional copies are available from the Internet at: 

http://www.fda.gov/cdrh/oivd/guidance/1590.pdf or 

http://www.fda.gov/cber/guidelines.htm. You may also send an e-mail request to 

dsmica@fda.hhs.gov to receive an electronic copy of the guidance or send a fax request 

to 240-276-3151 to receive a hard copy. Please use the document number (1590) to 

identify the guidance you are requesting. Copies of the guidance are also available from: 

Office of Communication, Training and Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research 

Food and Drug Administration 

1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448 

Phone: 800-835-4709 or 301-827-1800 

 

 

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Guidance for Industry and FDA Staff 

Commercially Distributed Analyte 

Specific Reagents (ASRs): Frequently 

Asked Questions

This guidance represents the Food and Drug Administration's (FDA's) current 

thinking on this topic. It does not create or confer any rights for or on any person 

and does not operate to bind FDA or the public. You can use an alternative 

approach if the approach satisfies the requirements of the applicable statutes and 

regulations. If you want to discuss an alternative approach, contact the FDA staff 

responsible for implementing this guidance. If you cannot identify the appropriate 

FDA staff, call the appropriate number listed on the title page of this guidance. 

INTRODUCTION 

This guidance document is intended to clarify the regulations regarding commercially 

distributed analyte specific reagents (ASRs) (21 CFR 809.10(e), 809.30, and 864.4020), 

and the role and responsibilities of ASR manufacturers. This document is not intended 

to provide guidance on the role of clinical laboratories in the development of laboratory 

developed tests (LDTs). The guidance follows the substance, spirit, and meaning of the 

ASR regulations already in place. 

The guidance addresses some frequently asked questions about how ASRs may be 

marketed, and provides FDA’s Office of In Vitro Diagnostic Device Evaluation and 

Safety’s (OIVD’s) and the Center for Biologics Evaluation and Research’s (CBER’s) 

responses to those questions. Except where otherwise indicated, the use of the term

"ASR" in this guidance document refers to commercially distributed ASRs and the term 

"manufacturer" refers to manufacturers of commercially distributed ASRs. 

FDA is providing this guidance in order to eliminate confusion regarding particular 

marketing practices among ASR manufacturers. As noted in this guidance document, 

ASRs are building blocks of LDTs. (See section II of this guidance.) ASRs are 

defined and classified in a rule codified at 21 CFR 864.4020. With this guidance 

document, FDA seeks to advise ASR manufacturers that it views the following practices 

as being inconsistent with the marketing of an ASR, as defined under 21 CFR 864.4020: 

 

• Combining, or promoting for use, a single ASR with another product such as 

other ASRs, general purpose reagents, controls, designated laboratory 

instrument(s), software, etc. 

• Promoting an ASR with specific analytical or clinical performance claims, 

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instructions for use in a particular test, or instructions for validation of a specific 

test using the ASR. 

Some manufacturers have believed that when they combine a Class I ASR, which is 

exempt from premarket notification requirements under section 510(l) of the Federal 

Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 360(l), with other products, or with 

instructions for use in a specific test, the product remains exempt because of the presence 

of an ASR. However, as explained in this guidance, when an ASR is marketed in the 

ways described above, FDA views the product as no longer being an ASR within the 

meaning of 21 CFR 860.4020 and instead views it as another type of in vitro diagnostic 

device (IVD) or device component not covered by the ASR regulations and, therefore, 

not necessarily exempt from premarket notification. 

FDA's guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the Agency's current thinking on a topic 

and should be viewed only as recommendations, unless specific regulatory or statutory 

requirements are cited. The use of the word should in Agency guidances means that 

something is suggested or recommended, but not required. 

The Least Burdensome Approach 

The issues identified in this guidance document represent those that we believe need to be 

addressed before your device can be marketed. In developing the guidance, we 

carefully considered the relevant statutory criteria for Agency decision-making. We 

also considered the burden that may be incurred in your attempt to follow the statutory 

and regulatory criteria in the manner suggested by the guidance and in your attempt to 

address the issues we have identified. We believe that we have considered the least 

burdensome approach to resolving the issues presented in the guidance document. If, 

however, you believe that there is a less burdensome way to address the issues, you 

should follow the procedures outlined in the document, “A Suggested Approach to 

Resolving Least Burdensome Issues.” It is available on our Center web page at: 

http://www.fda.gov/cdrh/modact/leastburdensome.html. 

 

FREQUENTLY ASKED QUESTIONS 

I. The ASR Rule 

1. What is the definition of an ASR? 

ASRs are defined as “antibodies, both polyclonal and monoclonal, specific receptor 

proteins, ligands, nucleic acid sequences, and similar reagents which, through specific 

binding or chemical reactions with substances in a specimen, are intended for use in a 

diagnostic application for identification and quantification of an individual chemical 

substance or ligand in biological specimens." 21 CFR 864.4020(a). ASRs are medical 

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devices that are regulated by FDA. They are subject to general controls, including 

current Good Manufacturing Practices (cGMPs), 21 CFR Part 820, as well as the specific 

provisions of the ASR regulations (21 CFR 809.10(e), 809.30, 864.4020). 

 

2. What is the ASR rule? 

This guidance document refers to three regulations as "the ASR rule." Published in 

1997, the regulations define and classify ASRs (21 CFR 864.4020), impose restrictions 

on the sale, distribution, and use of ASRs (21 CFR 809.30), and establish requirements 

for ASR labeling (21 CFR 809.10(e)). 

 

3. What was the objective of the ASR rule? 

The ASR rule was designed to accomplish several policy objectives. One of the 

primary goals of the rule was to ensure the quality of the primary, active reagents of 

finished IVDs or LDTs. Another focus of the rule is the requirement for appropriate 

labeling to be appended to test results when ASRs are used by clinical laboratories in 

LDTs, so that healthcare users can understand when tests are being developed and 

validated by the laboratory and have not undergone FDA clearance or approval. 62 FR 

62244. FDA adopted the approach of regulating most ASRs by means of general 

controls and exempting them from premarket notification requirements as the least 

burdensome approach. This approach relies primarily on cGMPs, medical device 

reporting, and labeling requirements to adequately control the risks associated with these 

devices. In addition, laboratories that develop tests using ASRs must be in compliance 

with the Clinical Laboratory Improvement Amendments (CLIA), 42 U.S.C. 263a 62 FR 

62252. 

 

4. What does the ASR rule require? 

The rule classifies most ASRs as Class I devices subject to general controls under section 

513(a)(1)(A) of the Act, but exempt from premarket notification. The general controls 

require ASR manufacturers to register and list their devices, 21 CFR 807.20(a), submit 

medical device reports (21 CFR Part 803), follow labeling requirements, 21 CFR 

809.10(e), and follow cGMPs, 21 CFR 809.20(b). The rule also restricts the sale, use, 

distribution, labeling, advertising and promotion of ASRs. 21 CFR 809.30. One of 

these restrictions allows only physicians and other persons authorized by applicable State 

law to order LDTs that are developed using ASRs. 21 CFR 809.30(f). Another 

restriction requires the laboratory that develops an LDT using an ASR to add a statement 

disclosing that the laboratory developed the test and it has not been cleared or approved 

by FDA when reporting the test result to the practitioner. 21 CFR 809.30(e). 

 

The restrictions also prohibit advertising and promotional materials for ASRs from 

making any claims for clinical or analytical performance. 21 CFR 809.30(d)(4). 

Consistent with this restriction, the labeling for Class I, exempt ASRs must bear the 

statement, "Analyte Specific Reagent. Analytical and performance characteristics are 

not established." 21 CFR 809.10(e)(1)(x). Manufacturers who wish to make 

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analytical and/or clinical performance claims for a product should submit an application 

to FDA for premarket review rather than marketing the product as an ASR. For 

example, performance claims might include statements such as, "This ASR can be used 

for quantification of [an analyte] to determine [a diagnosis]”. 

 

5. Are some ASRs Class II or Class III, requiring a premarket submission? 

Yes. Although most ASRs are Class I, there are some ASRs that are Class II and Class 

III and that must be cleared or approved by FDA before they can be marketed in the 

United States. 21 CFR 864.4020. FDA classifies medical devices, including 

diagnostic devices such as ASRs, into Class I, II, or III according to the level of 

regulatory control that is necessary to provide a reasonable assurance of safety and 

effectiveness. These classifications include consideration of the level of risk associated 

with the device. 21 U.S.C. 360c. The classification of an ASR determines the 

appropriate premarket process. 

 

An ASR is a Class II device if the reagent is used as a component in a blood banking test 

of a type that has been classified as a Class II device (e.g., certain cytomegalovirus 

serological and treponema pallidum nontreponemal test reagents). 21 CFR 

864.4020(b)(2). 

 

An ASR is a Class III device if the reagent is intended as a component in tests intended 

either: 

 

• to diagnose a contagious condition that is highly likely to result in a fatal 

outcome and prompt, accurate diagnosis offers the opportunity to mitigate the 

public health impact of the condition (e.g., human immunodeficiency virus 

(HIV/AIDS) or tuberculosis (TB)); or 

• for use in donor screening for conditions for which FDA has recommended or 

required testing in order to safeguard the blood supply or establish the safe use 

of blood and blood products (e.g., tests for hepatitis or for identifying blood 

groups). 21 CFR 864.4020(b)(3). 

FDA considers ASRs intended to be used as a component in tests for diagnosis of HIV 

(including monitoring for viral load or HIV drug resistance mutations) to be Class III 

ASRs. 

6. How does a manufacturer know whether its device is an ASR? 

We recommend that ASR manufacturers consult this document for guidance on whether 

their product is or is not within the scope of the ASR rule. Manufacturers should 

contact FDA if they are unsure about the classification of their device to discuss any 

applicable regulatory requirements. Manufacturers who wish to obtain FDA advice on 

this matter in advance of marketing may consult with OIVD, or, with CBER for 

questions about HIV ASRs or ASRs for blood or cellular and tissue products. 

 

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II. What Meets the ASR Definition? 

 

There has been some confusion about which products fall within and outside the 

definition of an ASR. Some of this confusion relates to a misunderstanding that a 

product is an ASR if it is labeled as one, even if the product contains analytical or clinical 

performance claims and does not meet the definition of an ASR. 

 

In the preamble to the ASR rule, FDA stated that ASRs are the "active ingredients" of 

tests that are used to identify one specific disease or condition. ASRs are purchased by 

manufacturers who use them as components of tests that are cleared or approved by FDA 

and also by clinical laboratories that use the ASRs to develop LDTs used exclusively by 

that laboratory. 62 FR 62243, 62244. This is in contrast to what the preamble referred 

to as a "kit or system for 'in vitro diagnostic use'" that has a proposed intended use, 

indications for use, instructions for use, and performance characteristics. 62 FR 62243, 

62250. 

The ASR rule was intended to require that ASR manufacturers take certain actions, such 

as following cGMPs, to help ensure the quality of these reagents so that IVD 

manufacturers and laboratories who purchase them can produce tests that are safe and 

effective. A premise underlying the rule, however, is that laboratories and IVD 

manufacturers, rather than ASR manufacturers, design and develop the test in which the 

ASR is used, using their judgment and knowledge, and provide all necessary verification 

and validation. 

 

Based upon this description, together with the ASR definition, FDA views an ASR as 

having the following characteristics: 

 

• used to detect a single ligand or target (e.g., protein, single nucleotide change, 

epitope); 

• not labeled with instructions for use or performance claims; and 

• not promoted for use on specific designated instruments or in specific tests. 

7. What are some examples of entities that FDA considers to be ASRs? 

 

Examples of entities that are ASRs include: 

• a single antibody (e.g., an anti-troponin I polyclonal or monoclonal antibody, 

whether untagged or tagged, e.g., conjugated to horseradish peroxidase), 

• a single forward/reverse oligonucleotide primer1 pair (e.g., a primer pair for 

amplification of a single amplicon, such as for amplification of the ΔF508 locus 

of the gene encoding the cystic fibrosis transmembrane regulator (CFTR)), or 

single forward or reverse primer individually, 

 

1

 For the purposes of this guidance, a primer is defined as a nucleic acid sequence that is intended to initiate 

amplification by binding selectively to a complementary sequence in a large nucleic acid polymer.

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• a nucleic acid probe2 (whether untagged or tagged, e.g., conjugated to biotin or 

CyTM3) intended to bind a single complementary amplified or unamplified 

nucleic acid sequence, 

• a single purified protein or peptide (e.g., purified B-type natriuretic peptide). 

The above-listed examples would not be considered ASRs if they are marketed with 

clinical or analytical performance claims (e.g., quantification of an infectious agent, 

assessment of cardiac risk). 

In addition to the examples listed here, there may be other products that can be 

appropriately marketed as ASRs provided they meet the criteria listed above, i.e., the 

ASR is used to detect a single ligand or target (e.g., protein, single nucleotide change, 

epitope), is not labeled with instructions for use or performance claims, and is not 

promoted for use on specific designated instruments or in specific tests. In the future, 

with the development of novel technologies, there may be products that meet the 

definition of an ASR (21 CFR 864.4020) that are dissimilar to the examples listed above. 

In those cases, ASR manufacturers should contact FDA with questions about specific 

products. 

8. What are some examples of entities that FDA does not consider to be ASRs? 

 

• Multiple individual ASRs (e.g., antibodies, probes, primer pairs) bundled 

together in a single pre-configured or optimized mixture so that they must be 

used together in the resulting LDT. For example, a set of 5 primer pairs 

combined in a single tube that are used to detect 5 different viral genotypes 

requires that all of these pairs be used together, and that they work together to 

accurately detect all five genotypes. This is an analytical claim for the product, 

and FDA does not consider this type of product to be an ASR. 

• Products that include or require more than a single ASR (i.e., the product 

includes some or all of the products needed to conduct a particular test such as 

more than one ASR, general reagents, controls, equipment, software, etc.) 

and/or has instructions for use. FDA does not consider such a product to be an 

ASR but rather an IVD or IVD component not covered by the ASR rule. 

• Reagents that are designed to require use in a specific assay or on a designated 

instrument (e.g., arrayed on beads). The requirement for reagents and 

designated instruments to be used together constitutes a performance claim that 

they will work properly when used in combination, since those specific reagents 

are intended for use with that specific instrument. FDA does not consider such 

a product to be an ASR but rather an IVD or IVD component not covered by the 

ASR rule. 

When manufacturers have assembled ingredients towards the development of a 

test, such as in the examples listed above, the product is no longer an ASR. A 

 

2

 For the purposes of this guidance, a probe is defined as a molecule that is intended to isolate, bind, or 

identify a specific target or ligand. 

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laboratory cannot validate that the way those individual ASRs and other 

components are combined by the manufacturer (e.g., the identity, concentration, 

purity) is appropriate for meeting the intended use and specifications of their 

in-house test. However, laboratories themselves are not precluded by the ASR 

rule from selecting and combining individual ASRs and other components in the 

development of their own in-house tests. 

Other types of devices that do not meet the definition of an ASR include: 

• Control material or calibrators. 

• Products that have specific performance claims, or procedural instructions, or 

interpretations for use. 

• Reagents offered with software for interpretation of results. 

• Software for interpretation of assay results. 

• Microarrays. 

Manufacturers who wish to market a product in a fashion that is similar to the examples 

listed above should discuss the classification of their product with FDA prior to 

marketing. 

 

9. How do General Purpose Reagents compare to ASRs? 

A General Purpose Reagent (GPR) is “a chemical reagent that has general laboratory 

application, that is used to collect, prepare, and examine specimens from the human body 

for diagnostic purposes, and that is not labeled or otherwise intended for a specific 

diagnostic application.” 21 CFR 864.4010(a). Like ASRs, GPRs are not labeled for 

a specific clinical or diagnostic use. Because GPRs are not analyte-specific, they should 

have the potential to be combined with, or used in conjunction with more than one type 

of ASR by the laboratory or IVD manufacturer that develops the finished test. In 

contrast, as stated above, an ASR is a specific chemical component, probe, or antibody 

that by its design determines which individual chemical substance or ligand can be 

detected. 

 

III. Manufacturer Marketing Practices 

10. To whom can manufacturers sell ASRs? 

 

ASRs may only be sold to: 

 

• in vitro diagnostic manufacturers; 

• clinical laboratories regulated under the Clinical Laboratory Improvement 

Amendments of 1988 (CLIA), as qualified to perform high complexity testing, 

or clinical laboratories regulated under VHA Directive 1106; and 

• organizations that use the reagents to make tests for purposes other than 

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providing diagnostic information to patients and practitioners, e.g., forensic, 

academic, research and other nonclinical laboratories. 21 CFR 809.30 (b). 

11. Can a manufacturer or distributor promote specific ASRs and GPRs for use 

together in developing a test? 

 

No. As explained above, ASRs are considered specific individual “building blocks” of 

LDTs and finished IVDs tests, while GPRs are not intended for any specific diagnostic 

application. 21 CFR 864.4010, 864.4020. A product that is promoted for use with an 

ASR is intended for a specific diagnostic use with that ASR and therefore would not 

meet the GPR definition of being for "general laboratory application." Similarly, a 

product that is promoted for use with a specific GPR is intended for a particular intended 

use rather than as an ASR, which is a building block of LDTs. Therefore, a 

manufacturer who wishes to market its products as GPRs or ASRs should not promote or 

sell them together, including in finished or partial IVD test configurations. 

We recommend that manufacturers who wish to market multiple different products as 

ASRs, e.g. multiple ASR primer sets to amplify different mutation loci in a single gene, 

rather than as IVDs or IVD components, avoid marketing the ASRs in a manner that 

suggests that use of particular ASRs together will provide a particular effect, or that these 

devices should be used together for a specific purpose. 

12. Can the manufacturer include instructions with an ASR? 

ASR manufacturers should not provide instructions for developing or performing an 

assay with an ASR. As explained above, FDA does not view reagents that are sold with 

instructions for developing or performing a test as ASRs because ASRs are intended to 

be building blocks for tests and are intended to be used to develop a test for which the 

developer must establish instructions for use and performance claims. 21 CFR 

809.10(e)(1)(x), 809.30(d)(4). Instructions for use of an ASR in a particular test would 

constitute a claim that, when used as directed, the ASR will perform to detect a particular 

chemical substance or ligand. 

 

On the other hand, instructions for proper storage and handling of an ASR must be 

provided. 21 CFR 809.10(e)(1)(vi). In addition, scientific information may be 

included on chemical/molecular composition, concentration or mass, nucleic acid 

sequence, binding affinity, cross-reactivities, known mutations associated with the 

sequence, and interaction with substances of known clinical significance. 21 CFR 

809.10(e)(1)(iv). 

 

13. Can a manufacturer or distributor tell a laboratory which ASRs are useful 

for a particular application, for example, which monoclonal antibodies or 

probes are useful for leukemia or lymphoma testing? 

ASR manufacturers and distributors should not make claims to physicians or laboratories 

regarding analytical or clinical performance for ASRs. The laboratories, not the ASR 

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manufacturers or distributors, are responsible for the design and performance of the test. 

21 CFR 809.30(d)(4). 

ASR labeling may indicate the affinity of the reagent, such as "anti-estrogen receptor 

antibody” or “ΔF508 CFTR nucleic acid probe." Other similar information, such as the 

affinity, target, or sequence of a DNA probe or a protein sequence, may also be provided 

because it describes the ligand to which the ASR is specific but does not claim to 

produce a particular clinical or analytical result. But a name such as “Cardiac Risk 

ASR” describes a specific clinical use for the product and FDA, therefore, would not 

consider such a product to be an ASR. 

 

14. Can an ASR manufacturer supply quality control materials/reagents that 

can be used with an ASR? 

 

Yes, but these materials should be promoted independently of specific ASRs. 

Marketing such materials for use with an ASR would indicate that the ASR manufacturer 

is actually marketing a product which could trigger premarket review requirements. 

Quality control materials should be promoted and sold using existing FDA classifications 

for quality control material (e.g., 21 CFR 862.1660, 862.3280, 864.8625). 

 

15. Can a manufacturer or distributor market software for use with an ASR? 

If an ASR manufacturer chooses to market software for use with its product, then the 

products together would not be considered an ASR. Software does not meet the 

definition of an ASR. FDA views marketing practices that directly suggest or state that 

particular software is needed to achieve a function of an ASR to cause the ASR part of 

the combination to fall outside of the ASR definition because the ASR would now be 

intended for use with the software. As a result, FDA’s view is that ASR manufacturers 

should not promote, sell, or otherwise distribute software for use with a particular ASR. 

 

16. What types of instrumentation can manufacturers promote for use with 

LDTs? 

ASRs are intended to be sold as building blocks for use in design of a diagnostic test by 

the test developer. If an ASR is promoted as being intended for use with a particular 

instrument, FDA would not view the promoted product as an ASR. Use of the ASR 

with the particular instrument would be a design choice by the ASR manufacturer and not 

by the test developer. As a result, manufacturers should not promote specific laboratory 

instruments for use in conjunction with particular ASRs. 

 

In contrast, open instruments that have user-defined capabilities, which allow the user to 

select an instrument and an ASR independently, and define, optimize, and validate the 

test performance characteristics and interpretation criteria, may be promoted for use 

generally in LDTs (e.g., spectrophotometers, HPLC). If instrumentation is used for an 

ASR-based test, the laboratory should be able to select the instrumentation and validate 

the performance of the LDT on that instrument. 

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17. Can the manufacturer of an ASR help with the validation and verification of 

performance specifications of a test that utilizes its ASR? 

 

If a manufacturer or distributor wishes to market its product as an ASR, it should not 

assist with the development or validation of an LDT using its specific ASR. Under the 

CLIA regulations, the laboratory must conduct validation and verification of test 

performance specifications. 42 CFR 493.1213. This validation by the laboratory is 

the minimum requirement under CLIA for the laboratory to generate clinical results for 

tests of high complexity. 

 

18. What type of information about a particular ASR can an ASR manufacturer 

provide to a laboratory? 

 

An ASR manufacturer may provide laboratories with information, including 

peer-reviewed and published/presented literature, that establishes characteristics of the 

ASR itself, such as information describing the single ligand or target the ASR detects. 

Such information may not, however, describe the use of an ASR in a specific test, 

including information regarding an ASR's clinical utility and clinical performance as well 

as specific instructions-for-use and validation protocols. 21 CFR 809.30, 864.4020. 

When coupled with such information, the product would fall outside the definition of an 

ASR. See Section II, "What Meets the ASR Definition?". 

 

IV. Research and Investigational Use of ASRs 

 

19. Can ASRs be used for research? 

Yes, ASRs can be used for research applications. The ASR requirements, including the 

need for the laboratory report disclaimer, apply only to clinical diagnostic use of these 

products and not to research applications. 21 CFR 864.4020(a)(2). 

 

20. How is the ASR rule related to in vitro diagnostic products labeled for 

research or investigational use? 

Products labeled for research use only (RUO) or investigational use only (IUO) are IVDs 

in different stages of development. 

 

• FDA considers RUO products to be products that are in the laboratory research 

phase of development, that is, either basic research or the initial search for 

potential clinical utility, and not represented as an effective in vitro diagnostic 

product. During this phase, the focus of manufacturer-initiated studies is 

typically to evaluate limited-scale performance and potential clinical or 

informational usefulness of the test. These products must be labeled “For 

Research Use Only. Not for use in diagnostic procedures.” as required under 21 

CFR 809.10 (c)(2)(i). 

• FDA considers IUO products to be products that are in the clinical investigation 

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phase of development. They may be exempt from the investigational device 

(IDE) requirements of 21 CFR Part 812 (21 CFR 812.2(c)), or may be regulated 

under 21 CFR Part 812 as either a non-significant risk device or a significant risk 

device. Diagnostic devices exempt from IDE requirements cannot be used for 

human clinical diagnosis unless the diagnosis is being confirmed by another, 

medically-established diagnostic product or procedure (21 CFR 812.2(c)(3)(iv)). 

During this phase, the safety and effectiveness of the product are being studied; 

i.e., the clinical performance characteristics and expected values are being 

determined in the intended patient population(s). These products must be 

labeled, "For Investigational Use Only. The performance characteristics of this 

product have not been established.” 21 CFR 809.10(c)(2)(ii). 

21. What is the difference in GMP requirements for manufacturers of an ASR 

versus an RUO reagent? 

Manufacturers establish and follow cGMPs, as established in the quality system 

regulation, to help ensure that their products are manufactured under controlled 

conditions that assure the devices meet consistent specifications across lots and over time. 

ASRs must be manufactured following cGMPs. 21 CFR 809.20. FDA does not 

expect RUO reagents to be manufactured in compliance with cGMPs because products 

labeled as RUO reagents cannot be used as clinical diagnostic products. 21 CFR 

809.10(c)(2)(i). 

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