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(6) For a reagent, a means by which which are packaged within an outer the user may be assured that the prod- container from which they are removed uct meets appropriate standards of for use, the information required by identity, strength, quality and purity paragraphs (a) (2), (3), (4), (5), (6) (ii), at the time of use. This shall be pro- (iii) and (7) of this section may appear vided, both for the product as provided in the outer container labeling only. and for any resultant reconstituted or (ii) In any case in which the presence mixed product, by including on the of this information on the immediate label one or more of the following: container will interfere with the test,

(i) An expiration date based upon the the information may appear on the stated storage instructions.

outside container or wrapper rather (ii) A statement of an observable in- than on the immediate container label. dication of an alteration of the prod- (b) Labeling accompanying each act, e.g., turbidity, color change, pre- product, e.g., a package insert, shall cipitate, beyond its appropriate stand- state in one place the following inforards.

mation in the format and order speci(iii) Instructions for a simple method fied below, except where such informaby which the user can reasonably de- tion is not applicable, or as specified in termine that the product meets its ap- a standard for a particular product propriate standards.

class. The labeling for a multiple-pur(7) For a reagent, a declaration of the pose instrument used for diagnostic net quantity of contents, expressed in purposes, and not committed to speterms of weight or volume, numerical cific diagnostic procedures or systems, count, or any combination of these or may bear only the information indiother terms which accurately reflect cated in paragraphs (b) (1), (2), (6), (14), the contents of the package. The use of and (15) of this section. The labeling for metric designations is encouraged, a reagent intended for use as a replacewherever appropriate. If more than a ment in a diagnostic system may be single determination may be performed limited to that information necessary using the product, any statement of to identify the reagent adequately and the number of tests shall be consistent to describe its proper use in the syswith instructions for use and amount tem. of material provided.

(1) The proprietary name and estab(8) Name and place of business of lished name, i.e., common or usual manufacturer, packer, or distributor. name, if any.

(9) A lot or control number, identi- (2) The intended use or uses of the fied as such, from which it is possible product and the type of procedure, e.g., to determine the complete manufac- qualitative or quantitative. turing history of the product.

(3) Summary and explanation of the (i) If it is a multiple unit product, the test. Include a short history of the lot or control number shall permit methodology, with pertinent references tracing the identity of the individual and a balanced statement of the special units.

merits and limitations of this method (ii) For an instrument, the lot or con- or product. If the product labeling retrol number shall permit tracing the fers to any other procedure, approidentity of all functional subassem- priate literature citations shall be inblies.

cluded and the labeling shall explain (iii) For multiple unit products which the nature of any differences from the require the use of included units to- original and their effect on the results. gether as a system, all units should (4) The chemical, physical, physiobear the same lot or control number, if logical, or biological principles of the appropriate, or other suitable uniform procedure. Explain conciselywith identification should be used.

chemical reactions and techniques in(10) Except that for items in para- volved, if applicable. graphs (a) (1) through (9) of this sec- (5) Reagents: tion: (i) In the case of immediate con- (i) A declaration of the established tainers too small or otherwise unable name (common or usual name), if any, to accommodate a label with sufficient and quantity, proportion or concentraspace to bear all such information and tion or each reactive ingredient; and for biological material, the source and (i) Special precautions regarding a measure of its activity. The quantity, specimen collection including special proportion, concentration or activity preparation of the patient as it bears shall be stated in the system generally on the validity of the test. used and recognized by the intended (ii) Additives, preservatives, etc.. user, e.g., metric, international units, necessary to maintain the integrity of etc. A statement indicating the pres- the specimen. ence of and characterizing any cata- (iii) Known interfering substances. lytic or nonreactive ingredients, e.g., (iv) Recommended storage, handling buffers, preservatives, stabilizers.

or shipping instructions for the protec(ii) A statement of warnings or pre- tion and maintenance of stability of cautions for users as established in the the specimen. regulations contained in 16 CFR part (8) Procedure: A step-by-step outline 1500 and any other warnings appro- of recommended procedures from repriate to the hazard presented by the ception of the specimen to obtaining product; and a statement “For In Vitro results. List any points that may be Diagnostic Use” and any other limiting useful in improving precision and accustatements appropriate to the intended racy. . use of the product.

(i) A list of all materials provided, (iii) Adequate instructions for recon- e.g., reagents, instruments and equipstitution, mixing, dilution, etc.

ment, with instructions for their use. (iv) Appropriate storage instructions (ii) A list of all materials required adequate to protect the stability of the but not provided. Include such details product. When applicable, these in- as sizes, numbers, types, and quality. structions shall include such informa- (iii) A description of the amounts of tion as conditions of temperature, reagents necessary, times required for light, humidity, and other pertinent specific steps, proper temperatures, factors. For products requiring manip- wavelengths, etc. ulation, such as reconstitution and/or (iv) A statement describing the stamixing before use, appropriate storage bility of the final reaction material to instructions shall be provided for the be measured and the time within which reconstituted or mixed product. The it shall be measured to assure accurate basis for such instructions shall be de- results. termined by reliable, meaningful, and (v) Details of calibration; Identify specific test methods such as those de- reference material. Describe preparascribed in $211.166 of this chapter.

tion of reference sample(s), use of (v) A statement of any purification blanks, preparation of the standard or treatment required for use.

curve, etc. The description of the range (vi) Physical, biological, or chemical of calibration should include the highindications of instability or deteriora- est and the lowest values measurable tion.

by the procedure. (6) Instruments:

(vi) Details of kinds of quality con(i) Use or function.

trol procedures and materials required. (ii) Installation procedures and spe- If there is need for both positive and cial requirements.

negative controls, this should be stat(iii) Principles of operation.

ed. State what are considered satisfac(iv) Performance characteristics and tory limits of performance. specifications.

(9) Results: Explain the procedure for (v) Operating instructions.

calculating the value of the unknown. (vi) Calibration procedures including Give an explanation for each compomaterials and/or equipment to be used. nent of the formula used for the cal

(vii) Operational precautions and culation of the unknown. Include a limitations.

sample calculation, step-by-step, ex(viii) Hazards.

plaining the answer. The values shall (ix) Service and maintenance infor- be expressed to the appropriate number mation.

of significant figures. If the test pro(7) Specimen collection and prepara- vides other than quantitative results, tion for analysis, including a descrip- provide an adequate description of extion of:

pected results.

(10) Limitation of the procedure: Include a statement of limitations of the procedure. State known extrinsic factors or interfering substances affecting results. If further testing, either more specific or more sensitive, is indicated in all cases where certain results are obtained, the need for the additional test shall be stated.

(11) Expected values: State the range(s) of expected values as obtained with the product from studies of various populations. Indicate how the range(s) was established and identify the population(s) on which it was established.

(12) Specific performance characteristics: Include, as appropriate, information describing such things as accuracy, precision, specificity, and sensitivity. These shall be related to a generally accepted method using biological specimens from normal and abnormal populations. Include a statement summarizing the data upon which the specific performance characteristics are based.

(13) Bibliography: Include pertinent references keyed to the text.

(14) Name and place of business of manufacturer, packer, or distributor.

(15) Date of issuance of the last revision of the labeling identified as such.

(c) A shipment or other delivery of an in vitro diagnostic product shall be exempt from the requirements of paragraphs (a) and (b) of this section and from a standard promulgated under part 861 provided that the following conditions are met:

(1) In the case of a shipment or delivery for an investigation subject to part 812, if there has been compliance with part 812; or

(2) In the case of a shipment or delivery for an investigation that is not subject to part 812 (see $812.2(c)), if the following conditions are met:

(i) For a product in the laboratory research phase of development, and not represented as an effective in vitro diagnostic product, all labeling bears the statement, prominently placed: “For Research Use Only. Not for use in diagnostic procedures."

(ii) For a product being shipped or delivered for product testing prior to full commercial marketing (for example, for use on specimens derived from hu

mans to compare the usefulness of the product with other products or procedures which are in current use or recognized as useful), all labeling bears the statement, prominently placed: “For Investigational Use Only. The performance characteristics of this product have not been established.”

(d) The labeling of general purpose laboratory reagents (e.g., hydrochloric acid) and equipment (e.g., test tubes and pipettes) whose uses are generally known by persons trained in their use need not bear the directions for use required by $ 809.10(a) and (b), if their labeling meets the requirements of this paragraph.

(1) The label of a reagent shall bear the following information:

(i) The proprietary name and established name (common or usual name), if any, of the reagent.

(ii) A declaration of the established name (common or usual name), if any, and quantity, proportion or concentration of the reagent ingredient (e.g., hydrochloric acid: Formula weight 36.46, assay 37.9 percent, specific gravity 1.192 at 60 °F); and for a reagent derived from biological material, the source and where applicable a measure of its activity. The quantity, proportion, concentration or activity shall be stated in the system generally used and recognized by the intended user, e.g., metric, international units, etc.

(iii) A statement of the purity and quality of the reagent, including a quantitative declaration of any impurities present. The requirement for this information may be met by a statement of conformity with a generally recognized and generally available standard which contains the same information, e.g., those established by the American Chemical Society, U.S. Pharmacopeia, National Formulary, National Research Council.

(iv) A statement of warnings or precautions for users as established in the regulations contained in 16 CFR part 1500 and any other warnings appropriate to the hazard presented by the product; and a statement "For Laboratory Use."

(v) Appropriate storage instructions adequate to protect the stability of the

194-069 D-01--4

product. When applicable, these in- (iv) A statement of the purity and structions shall include such informa- quality of the reagent, including a tion as conditions of temperature, quantitative declaration of any impurilight, humidity, and other pertinent ties present and method of analysis or factors. The basis for such information characterization. The requirement for shall be determined by reliable, mean- this information may be met by a ingful, and specific test methods such statement of conformity with a genas those described in $211.166 of this erally recognized and generally availchapter.

able standard that contains the same (vi) A declaration of the net quantity information, e.g., those established by of contents, expressed in terms of the American Chemical Society, U.S. weight or volume, numerical count, or Pharmacopeia, National Formulary, any combination of these or other and National Research Council. The laterms which accurately reflect the con- beling may also include information tents of the package. The use of metric concerning chemical/molecular comdesignations is encouraged, wherever position, nucleic acid sequence, binding appropriate.

affinity, cross-reactivities, and inter(vii) Name and place of business of action with substances of known clinmanufacturer, packer, or distributor. ical significance;

(viii) A lot or control number, identi- (v) A statement of warnings or prefied as such, from which it is possible cautions for users as established in the to determine the complete manufac- regulations contained in 16 CFR part turing history of the product.

1500 and any other warnings appro(ix) In the case of immediate con- priate to the hazard presented by the tainers too small or otherwise unable product; to accommodate a label with sufficient (vi) The date of manufacture and apspace to bear all such information, and propriate storage instructions adewhich are packaged within an outer quate to protect the stability of the container from which they are removed product. When applicable, these infor use, the information required by structions shall include such informaparagraphs (d)(1)(ii), (iii), (iv), (v), and tion as conditions of temperature, (vi) of this section may appear in the light, humidity, date of expiration, and outer container labeling only.

other pertinent factors. The basis for (2) The label of general purpose lab- such instructions shall be determined oratory equipment, e.g., a beaker or a by reliable, meaningful, and specific pipette, shall bear a statement ade- test methods, such as those described quately describing the product, its in 8211.166 of this chapter; composition, and physical characteris- (vii) A declaration of the net quantics if necessary for its proper use. tity of contents, expressed in terms of

(e)(1) The labeling for analyte spe- weight or volume, numerical count, or cific reagents (e.g., monoclonal anti- any combination of these or other bodies, deoxyribonucleic acid (DNA) terms that accurately reflect the conprobes, viral antigens, ligands) shall tents of the package. The use of metric bear the following information:

designations is encouraged, wherever (i) The proprietary name and estab- appropriate; lished name (common or usual name), (viii) The name and place of business if any, of the reagent;

of manufacturer, packer, dis(ii) A declaration of the established tributor; name (common or usual name), if any; (ix) A lot or control number, identi

(iii) The quantity, proportion, or con- fied as such, from which it is possible centration of the reagent ingredient; to determine the complete manufacand for a reagent derived from biologi- turing history of the product; cal material, the source and where ap- (x) For class I exempt ASR's, the plicable, a measure of its activity. The statement: "Analyte Specific Reagent. quantity, proportion, concentration, or Analytical and performance characteractivity shall be stated in the system istics are not established”; and generally used and recognized by the (xi) For class II and III ASR's, the intended user,

e.g.,

metric, inter- statement: “Analyte Specific Reagent. national units, etc.;

Except as a component of the approved

or

well as how to contact a trained health professional if additional information on interpretation of test results from the laboratory or followup counseling is desired.

(7) Name and place of business of the manufacturer, packer, or distributor.

Subpart C-Requirements for Manufacturers and Producers

cleared test (Name of approved/cleared test), analytical and performance characteristics of this ASR are not established.”

(2) In the case of immediate containers too small or otherwise unable to accommodate a label with sufficient space to bear all such information, and which are packaged within an outer container from which they are removed for use, the information required by paragraphs (e)(1) through (e)(6) of this section may appear in the outer container labeling only. [41 FR 6903, Feb. 13, 1976, as amended at 45 FR 3750, Jan. 18, 1980; 45 FR 7484, Feb. 1, 1980; 47 FR 41107, Sept. 17, 1982; 47 FR 51109, Nov. 12, 1982; 48 FR 34470, July 29, 1983; 62 FR 62259, Nov. 21, 1997)

EFFECTIVE DATE NOTE: At 65 FR 18234, Apr. 7, 2000, $ 809.10 was amended by adding paragraph (), effective Apr. 9, 2001. At 66 FR 17359, Mar. 3, 2001, the effective date was delayed until June 8, 2001. For the convenience of the user, the added text is set forth as follows: $ 809.10 Labeling for in vitro diagnostic

products.

$ 809.20 General requirements for

manufacturers and producers of in

vitro diagnostic products. (a) [Reserved]

(b) Compliance with good manufacturing practices. In vitro diagnostic products shall be manufactured in accordance with the good manufacturing practices requirements found in part 820 of this chapter. (41 FR 6903, Feb. 13, 1976, as amended at 42 FR 42530, Aug. 23, 1977; 43 FR 31527, July 21, 1978]

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(1) The labeling for over-the-counter (OTC) test sample collection systems for drugs of abuse testing shall bear the following information in language appropriate for the intended users:

(1) Adequate instructions for specimen collection and handling, and for preparation and mailing of the specimen to the laboratory for testing.

(2) An identification system to ensure that specimens are not mixed up or otherwise misidentified at the laboratory, and that user anonymity is maintained.

(3) The intended use or uses of the product, including what drugs are to be identified in the specimen, a quantitative description of the performance characteristics for those drugs (e.g., sensitivity and specificity) in terms understandable to lay users, and the detection period.

(4) A statement that confirmatory testing will be conducted on all samples that initially test positive.

(5) A statement of warnings or precautions for users as established in the regulations contained in 16 CFR part 1500 and any other warnings appropriate to the hazard presented by the product.

(6) Adequate instructions on how to obtain test results from a person who can explain their meaning, including the probability of false positive and false negative results, as

8809.30 Restrictions on the sale, dis

tribution and use of analyte specific

reagents. (a) Analyte specific reagents (ASR's) (8 864.4020 of this chapter) are restricted devices under section 520(e) of the Federal Food, Drugs, and Cosmetic Act (the act) subject to the restrictions set forth in this section.

(b) ASR's may only be sold to: (1) In vitro diagnostic manufacturers;

(2) Clinical laboratories regulated under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), as qualified to perform high complexity testing under 42 CFR part 493 or clinical laboratories regulated under VHA Directive 1106 (available from Department of Veterans Affairs, Veterans Health Administration, Washington, DC 20420); and

(3) Organizations that use the reagents to make tests for purposes other than providing diagnostic information to patients and practitioners, e.g., forensic, academic, research, and other nonclinical laboratories.

(c) ASR's must be labeled in accordance with 8 809.10(e).

(d) Advertising and promotional materials for ASR's:

(1) Shall include the identity and purity (including source and method of acquisition) of the analyte specific reagent and the identity of the analyte;

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