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This is an example of a "model" 510(k) submission for a Blood Gas/Blood pH Analyzer that is intended for use in a point-of-care or bedside environment. The 510(k) included the following elements:

Content and Format of a 510(k) Submission as specified under 21 CFR 807.90:

1. Submitter's Name
   Address
   Telephone and Fax Number
   Contact Person
   Establishment Registration Number: XXXXXX
   
   
2. Identification of the Device:
   

   	Device Name:	XXXXXX
   	Proprietary/Trade name:	XXXXXX
   	Common Name:	Blood gas analyzer
   	Classification Name:	Blood gases and (PCO2, PO2) and blood pH test system
   	Device Classification:	II
   	Regulation Number:	21 CFR § 862.1120
   	Panel:	Chemistry (75)
   	Product Code:	CHL

   
   

3. Identification of the Predicate Device:
   Predicate Device Name
   Manufacturer
   510(k) Number or Clearance Information
   Predicate Device Labeling
   
   
4. Description of the Device and reason for the submission.
   
   
5. Intended Use and Indications for Use of the subject device.
   
   
6. Substantial Equivalence
   
   

   A discussion of how the device is substantially equivalent to the claimed predicate device. Relevant topics include a descriptive comparison of the following items: methodology, test principle, sample requirements, physical dimensions, throughput, analysis time, software support, calibration requirements, etc.
   

   Technological Characteristics of the Device
   

   A discussion of information concerning the operation, function, methodology, and principles of the subject device.
   

   Performance Characteristics and Data

   A discussion of the performance data that was generated in support of the device including protocols, raw data points, graphical representation, and analyses or conclusions for the following parameters as applicable:
   

   Specific Performance Characteristics and Data
   Method Comparison - a method comparison for each sample or matrix claimed for analysis, e.g., whole blood, capillary whole blood, serum, plasma, urine, etc.	¨ slope ¨ intercept ¨ range of samples ¨ correlation ¨ standard error est. ¨ bias plot ¨ number (n=) ¨ sample comparability
   Precision - precision information using quality control materials or patient pools for each matrix claimed for analysis.	¨ within-run (assay), and ¨ between-run (assay), or ¨ total ¨ calculated CV's & SD's ¨ mean ¨ number (n=)
   Linearity	¨ recovery/dilution/parallelism, other, etc. ¨ linear range study
   Sensitivity	¨ min. detection limit, or ¨ analytical sensitivity
   Interferences	¨ bilirubin ¨ hemoglobin ¨ lipids (triglycerides) ¨ other, drugs, anticoagulants, etc.
   Clinical Studies for Near Patient or Bedside Use	¨ location of studies (3 sites) ¨ investigators ¨ site precision ¨ site comparison
   Software	¨ validation/certification information
   Expected Values	¨ literature references, or ¨ population study

   Labeling/Promotional Materials

   Provide a copy of the labeling in draft. Labeling should be conformance to the format and order of 21 CFR 809.10(b) (see below). An explanation should be provided for each element that is either absent or not applicable.

   21 CFR § 809.10 Labeling for In Vitro DiagnosticDevices

   21 CFR § 809.10(b) - labeling accompanying each product (package insert) shall bear...in the format and order specified below except where not applicable:
   (1)	Proprietary & Established Names
   (2)	Intended Use(s) Conditions for Use* 21 CFR § 801.5 (a)	- state the analyte to be measured - state if the test is quantitative or qualitative - state the specimen type(s) - state any special instrument requirements - state a concise claim of clinical utility - "For Professional Use Only" - state any special condition for use statement(s)
   (3)	Summary & Explanation
   (4)	Test Principle
   (5)	Reagents	- quantity, proportion, or concentration - biological material (source/measure of activity) - precautions, warnings - "For In Vitro Diagnostic Use" - instructions for reconstitution, mixing, or dilution - storage instructions (opened/unopened)
   (6)	For Instruments:	Operation Manual - name - use/function - installation requirements - principles of operation - performance characteristics/specifications - operating instructions - calibration procedures - precautions/limitations - hazards - service/maintenance requirements
   (7)	Specimen Collection & Preparation	- any special precautions or patient preparation - any specimen additives, preservatives - any known interferences - storage, handling requirements
   (8)	Procedure	- a list of materials provided - a list of materials required but not provided - step by step instructions - a description of the stability of the final reaction - details of calibration - details of quality control
   (9)	Results	- sample calculation or formula - description of the results
   (10)	Limitations	- interferences - additional testing requirements
   (11)	Expected Values	- stated range(s) - literature references - population characterization
   (12)	Specific Performance Characteristics	- accuracy (method comparison) - precision - specificity (cross-reactivity, etc.) - sensitivity (lower detection limit) - dilution/recovery/linearity - sample comparability - high dose hook effect
   (13)	Bibliography
   (14)	Name/place of manufacturer, packer, or distributor
   (15)	Date of last labeling revision

   Other: For a multi-purpose instrument used for diagnostic purposes...may bear the information in (b) (1), (2), (6), (14), and (15).
   
   

7. Summary of Safety and Effectiveness in the format specified under 21 CFR 807.92 or 510(k) Statement in the content and format specified under 21 CFR 807.93

8. Truthful and Accurate Statement

9. Indications for Use Form

Sample 1 - Substantially Equivalent

CLIA-SE
CLASSIFIED AND NOT CLASSIFIED
TO BE USED FOR 510(k)s K960001 AND AFTER
[CONTACT PERSON]
[COMPANY]
[ADDRESS]
[CITY, STATE, ZIP CODE]

Re: [510(k) NUMBER]
Trade Name: [               ]
Regulatory Class:
Product Code: [               ]
Dated:
Received:

Dear [ADDRESSEE]:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the

Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice on FDA's labeling regulations (21 CFR Part 801 and §809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4591. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained by contacting the Division of Small Manufacturers Assistance by phone at 800-638­2041, 301-443­6597, or by fax at 301-443-8818.

	Sincerely yours,
	[DIVISION DIRECTOR]
	Division of Clinical
	Laboratory Devices
	Office of Device Evaluation
	Center for Devices and
	Radiological Health

Enclosure

[510(k) HOLDER, COMPANY NAME]
[C/O COMPANY REPRESENTATIVE, THIRD PARTY, OR CONSULTANT (IF ANY)]
[COMPANY REPRESENTATIVE, THIRD PARTY, OR CONSULTANT ADDRESS]
[CITY, STATE, ZIP CODE]


Re: [510(k) NUMBER]
Trade Name: [               ]
Regulatory Class: III
Dated:
Received:

Dear [ADDRESSEE]:

We have reviewed your Section 510(k) notification of intent to market the device referenced above. We have determined the device is not substantially equivalent to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to any device which has been reclassified into class I (General Controls) or class II (Special Controls). This decision is based on the fact that [SEE END OF LETTER FOR SUGGESTED WORDING].

Therefore, this device is classified by statute into class III (Premarket Approval), under Section 513(f) of the Federal Food, Drug, and Cosmetic Act (Act).

Section 515(a)(2) of the Act requires a class III device to have an approved premarket approval application (PMA) before it can be legally marketed, unless the device is reclassified.

Any commercial distribution of this device prior to approval of a PMA, or the effective date of any order by the Food and Drug Administration re-classifying this device into class I or II, would be a violation of the Act. Clinical investigations of this device must be conducted in accordance with the investigational device exemptions (IDE) regulations.

If you wish to pursue the marketing of this device and need information or assistance for preparing PMA, IDE, or reclassification submissions, please contact the Division of Small Manufacturers Assistance by phone at 800-638-2041, 301-443-6597, or by fax at 301-443-8818.

	Sincerely yours,
	[DIVISION DIRECTOR]
	Division of Clinical
	Laboratory Devices
	Office of Device Evaluation
	Center for Devices and
	Radiological Health

Reasons for Not Substantially Equivalent Decisions

1. This decision is based on the fact that we are not aware of a legally marketed preamendments device labeled or promoted for [specify indication]. (This relates to the indication of any type device for the use -- not the technology.)

2. This decision is based on the fact that your device has a new indication [specify] that alters the therapeutic/diagnostic effect [choose one or the other], impacting safety and effectiveness, and is therefore a new intended use.

3. This decision is based on the fact that your device has new technological characteristics, that could affect safety and effectiveness, and raises a new type[s] safety and effectiveness question [specify new question].

4. This decision is based on the fact that the performance data you have provided did not demonstrate your device to be as safe and effective as legally marketed devices [specifically a device marketed prior to May 28, 1976 or a device which has been reclassified from class III to class II or I (the predicate), or a device found to be substantially equivalent through the 510(k) process].

1. Purpose
   
   The purpose of this document is to assist prospective manufacturers, producers, and marketers (hereinafter called manufacturers) of home-use in vitro diagnostic devices (IVDs) in complying with existing labeling regulations, e.g., 21 CFR 801 and 809.10; premarket clearance requirements e.g., Sections 510(k) and 515 of the Federal Food, Drug, and Cosmetic Act (the Act); and other regulations, including 21 CFR 814.
   
   CDRH believes that both prospective manufacturers of home-use IVDs and CDRH reviewers will be better able to evaluate the safety and effectiveness of these devices when supporting information based on the following considerations is submitted to CDRH in an appropriate premarket submission. Moreover, CDRH believes that as a result of these considerations the general public health will be better served by the availability of meaningful and reliable home-use IVDs.
   
   
2. Background
   
   In vitro diagnostic devices (IVDs) as defines in 21 CFR 809.3(a) are those reagents, instruments, and systems intended for use in the 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 sequelae. These products are intended for use in the collection, preparation, and examination of specimens taken from the human body. This document, therefore, addresses home-use testing kits as well as home-use mail-in specimen collection kits.
   
   Traditionally, IVDs have been used primarily by hospitals, clinical laboratories and physicians' offices. In recent years, however, there has been increasing interest in home-use IVDs. Because of this growing interest, FDA's Center for Devices and Radiological health (CDRH) anticipates receiving an increasing number of premarket product submissions, i.e., premarket notifications of premarket approval applications, for these devices. Consequently, CDRH believes that uniform evaluation criteria for home-use IVDs are needed to better ensure that these devices are regulated in a consistent fashion and that consumers are provided with reliable, useful, and adequately labeled products. To this end, CDRH, over the past year, has solicited views from various industry, consumer, and health professional organizations to help identify the issues to be resolved by CDRH in developing evaluation criteria for home-use IVDs. In addition, on September 9, 1985, CDRH convened a public meeting of the chairpersons, the consumer representatives, and the industry representatives of the Immunology Devices Panel, the Microbiology Devices Panel, the Hematology and Pathology Devices Panel. The purpose of this meeting was to solicit the views of these individuals and other interested persons regarding general issues of the safety and effectiveness of home-use IVDs.
   
   The present document reflects CDRH's views on key points to be considered by prospective manufacturers of home-use IVDs in establishing the safe and effective use of home-use IVDs. These views are significantly based on the input CDRH has received from the aforementioned outreach activities.
   
   
3. Factors CDRH Will Consider in Evaluating the Safety and Effectiveness of Home-Use IVDs
   1. Risk/Benefit Considerations
      
      In terms of function, home-use-IVDs are essentially the same as other clinical laboratory devices in that they are intended to detect and/or measure particular analytes, e.g., antigens, antibodies, hormones, or drugs, in human specimens. The significance of the test results will depend on the analyte's relationship to other medical patient data. Home-use IVDs are different from clinical laboratory devices in three important ways: (1) the person performing the test likely lacks the necessary medical training to evaluate other related medical information, such as pertinent personal or family medical history, other analyte levels, and the results of a complete physical examination; (2) the person performing the test may lack the technical training of laboratory technologists who usually perform laboratory tests, and may not interpret directions carefully; and (3) the person performing the test may or may not carry out necessary follow up actions on the basis of test results. Hence, a major factor CDRH must consider in evaluating the safety and effectiveness of home-use IVDs is the probable health benefit(s) to be gained by lay persons in the use of such devices compared to the probable risks associated with their use. Consequently, CDRH will consider the following questions relative to assessing risk/benefit factors:
      
      Benefits
      1. What is the clinical benefit of the test to the patient or society (public health) in terms of screening, diagnosing, or monitoring a particular disease, condition, or risk factor?
         
      2. What are the benefits to the patient or society of having the test available for home-use as opposed to having the test performed by health care professionals?

      Risks

      1. What is the impact on the user or to society of a false-positive or false-negative test result, e.g., in terms of user follow up of adverse medical conditions?
         
      2. What are the risks to the user or society in terms of delay in obtaining a professional examination if a proposed home-use IVD that is intended for use on symptomatic subjects gives a false or equivocal result?

      CDRH encourages prospective manufacturers of home-use IVDs to assist CDRH in assessing risk/benefit factors by addressing the above questions in an appropriate premarketing submission.

      CDRH recognizes that, for evaluation purposes, responses to these questions can vary based on the type of product being considered. Hence, an acceptable risk/benefit ratio is not based on uniform answers to the questions posed.

   2. Performance Considerations
      
      Another key factor CDRH must consider in assessing the safety and effectiveness (risk/benefit) of home-use IVDs is test performance. Because the great majority of proposed home-use IVDs are likely to be derived from professional use IVDs, it is expected that there will be a clear and established relationship between the analyte to be tested using the home-use IVD and a specific medical disorder or condition. Because home-use IVDs function essentially the same as professional-use IVDs, their performance characteristics can be defined in terms of traditional performance parameters such as sensitivity, specificity, accuracy, and reproducibility of test results. Nevertheless, the performance of the device in the hands of skilled users may not reflect the device's performance in the hands of lay users. Consequently, CDRH recommends that manufacturers of home-use IVDs focus their attention on the following performance considerations:
      1. For a given intended use, home-use IVDs should perform as well as their professional-use IVD equivalents, i.e., the ability of the home-use IVD to detect and/or measure a particular analyte of interest (analytical performance) should compare favorably with IVDs used in clinical settings that are intended for the same purpose;

      2. Home-use IVDs should be designed with a view to ensuring that the device's performance will not be appreciably affected by anticipated variation in user technique; and

      3. Home-use IVDs should include a simple method by which the user can reasonably verify that the product's performance meets its design specifications throughout the shelf-life of the product. That is, a user quality control test should be provided or "built into" each home-use IVD (see 21 CFR 809.10(a)(b)(6).) Omission of such a test should be justified based on scientific merit.

   3. Labeling Considerations
      
      Acceptability of home-use IVD labeling will depend upon whether such labeling meets the criteria for "adequate directions for use" as provided for in section 502(F)(1) of the Act and 21 CFR 801.5. In addition, 21 CFR 801.119 provides that all IVDs (including home-use IVDs) shall be deemed to be in compliance with the requirements for adequate directions for use if they meet the requirements of 21 CFR 809.10-Labeling for In Vitro Diagnostic Products.
      
      Inherent in the concept of "adequate directions for use" is the need for the labeling of home-use IVDs to be simple, concise, easy to understand, make liberal use of illustrations and drawings, use bold print or other methods to highlight warnings and precautions, and provide color coding of reagent containers whenever practicable.
      
      Although CDRH believes that the labeling requirements as provided for in 21 CFR 809.10 are generally adequate for home-use IVDs, these regulations have been promulgated primarily to address professional-use IVDs and some qualification of these requirements for home-use IVDs may be useful as follows:
      

      Labeling information must comply with the requirements of 21 CFR Part 801, subpart C - Labeling requirements for over-the-counter devices and 21 CFR Part 809, Subpart B, section 809.10 - Labeling for In Vitro Diagnostic Products unless specifically addressed by the following:
      

      Section 809.10(a)

      1. The intended use statement (section 809.10(a)(2)) should clearly indicate on the outside packaging container the type of procedure that is offered, i.e., screening, monitoring, or diagnostic, and the specific disorder, condition, or risk factor of interest for which the test is intended. In addition, a statement also should be presented indicating who should use the test and the conditions for its use, followed by a contraindication statement(s), if necessary.

      2. The quantity, proportion, concentration, or activity of each reactive ingredient included with the test kit need only be presented as specified by section 809.13(a)(3) when information is necessary for proper lay use of the test.

      Section 809.10(b)

      The order and scope of the information specified by this section should be as follows:

      1. The intended use statement should reiterate the information required under section 809.10(a).

      2. Section 809.10(b)(3), summary and explanation of the test, may be combined with section 809.10(b)(4), principles of the procedure. This combined section should include a discussion of both the medical benefits and limitations of the test with respect to its intended use in addition to providing a simple explanation of how the test works. Presentation of chemical reactions or formulas is not necessary, but they may be referenced in the bibliography (section 809.10(b)(13)).

      3. A separate information section, interpretation of test results, should be presented and should include information specified by section 809.10(b)(10), limitations of the procedure. Thus, this section should indicate the significance of the test results in light of the test's intended use and provide specific information as to what appropriate follow-up action should be taken by the user. Additionally, this section should explain the meaning of false-positive and false-negative test results and cite possible sources and implications of false results.

      4. A separate information section should be presented which discusses/lists any foods, medications, or other possible interfering substances that would affect test results. Such information should specify what substances should be avoided and for how long prior to testing.

      5. Information specified in sections 809.10(b)(5),(6),(7), and (8) may be combined into a single information section, i.e., test procedure. All information specified by these individual sections should be presented in the combined section if applicable, in addition to the following:
         1. As previously stated, the quantity, proportion, concentration, or activity of each reactive ingredient included in the test kit need not be presented unless this information is necessary for proper use of the test. However, such information should be presented elsewhere in a premarket submission for CDRH review.
         2. Discussion of specimen collection, preparation, and analysis steps should be enhanced by the use of pictures and illustrations, preferably in color.
      6. Information specified by section 809.10(b)(9), test results, should be presented. This section also should include troubleshooting information.

      7. Information specified by sections 809.10(b)(11) and (12) may be combined into a single information section, i.e., test performance characteristics. This section should summarize the data (separately) from both the laboratory evaluation and the consumer field evaluation (see III above) and should include a concise discussion and/or presentation of data relative to the test's accuracy should be presented and should include false-positive and false-negative levels. Such information should be presented for both the laboratory and the consumer field evaluations.

      8. Sections 809.10(b)(13), (14) and (15) should be addressed in the same manner as other IVDs.
         
         In addition, CDRH recommends that manufacturers provide users with a toll-free telephone number or an address to write to should questions occur concerning the use of the device.
         
         Finally, CDRH is concerned that consumers be aware of significant changes in home-use IVD labeling, particularly labeling accompanying frequently used devices such as home-use glucose test devices. CDRH advises manufacturers to alert consumers of significant labeling changes by including special inserts with device packaging which highlight key labeling changes. Moreover, CDRH advises manufacturers that labeling changes that significantly impact on a device's safe and effective use may require premarket review and clearance by CDRH before commercial distribution of devices bearing such labeling.

   4. Premarket Evaluation Considerations
      
      Given the above considerations, CDRH recommends that prospective manufactures of home-use IVDs conduct the following performance studies and submit results to CDRH for review in an appropriate premarket submission:
      1. A laboratory evaluation of the analytical performance of the device, e.g., analytical sensitivity, analytical specificity, accuracy, and reproducibility, should be done by performing standard laboratory measurements using appropriate reference tests. The purpose of this evaluation is to establish the "true" performance characteristics of the device as determined under controlled laboratory conditions. Also,

      2. A consumer field evaluation of the device should be conducted to determine the device's performance when used by lay users, unassisted, following instructions provided in the labeling.
         
         CDRH places considerable importance on the outcome of the consumer field evaluation (item 2 above) in assessing the safety and effectiveness of home-use IVDs. Consequently, the following additional suggestions are offered with respect to the goals, conduct, and analysis of such studies.
         1. The primary goal of the consumer field evaluation should be to establish comparable levels of test performance for a particular home-use IVD when comparison-tested by both intended users and trained laboratory personnel. It is suggested that split clinical samples be tested by both lay users and trained laboratory personnel with both groups using the home-use IVD. Such testing will simultaneously validate the technical performance characteristics of the device and the device's labeling based on user experience.

         2. In order to assess the ability of lay users to properly perform and interpret test results, CDRH recommends that manufacturers provide simple questionnaires to study participants as part of the consumer field evaluation to determine if lay users can read and understand the labeling. For example, a questionnaire could be used to determine if the user understands the purpose of the test, the conditions for its use, the test's limitations, the meaning of the results and appropriate follow up.
            
            It is recommended that samples of such questionnaires be included in a premarket submission, as well as a tabulation of all study participants' responses to each question.

         3. Lay users selected for the study should be representative of target users for which a test is intended. A representative study population may require the selection of individuals of varies background, education levels, and age groups. Consequently, subjects should be selected for testing based on carefully developed selection criteria. The basis for establishing the selection criteria should be submitted to CDRH along with the study protocol and test results.

         4. The number of subjects selected for testing should be sufficient to substantiate that all targeted lay user populations can perform and interpret the test. It is highly recommended that the number of subjects selected for study be based on a statistically valid sampling of relevant lay users and should take into account appropriate demographic factors. Moreover, test results should be analyzed using appropriate statistical methods to demonstrate correlation between lay users and trained technologists performing the test.

         5. To avoid potential problems of bias during data collection and evaluation, the consumer field study, ideally, should have double blind design. However, in studies where such a design is impossible or impractical, a single blind approach and other measures to reduce potential bias may be acceptable.

The Division of Small Manufacturers Assistance (DSMA)was mandated by the 1976 medical device legislation to provide technical assistance and regulatory guidance to manufacturers to help them comply with Food and Drug Administration (FDA) requirements for medical devices. DSMA is located in the Center for Devices and Radiological Health (CDRH) within FDA.

To contact DSMA staff for technical or regulatory assistance; call 800.638.2041 or 301.443.6597, fax 301.443.8818, E-mail DSMA@CDRH.FDA.GOV or write to the Division of Small Manufacturers Assistance (HFZ-220), Food and Drug Administration, 1350 Piccard Drive, Rockville, MD 20850-4307.

Manufacturers and others who are interested in the regulatory requirements for marketing medical devices and radiation-emitting electronic products can quickly obtain the latest information on operating policies and procedures through one of the following CDRH/DSMA document retrieval systems:

CDRH Facts-On-Demand - This automated system allows anyone to obtain CDRH information, 24 hours a day, 7 days a week by calling 800.899.0381 or 301.827.0111 from a touch-tone telephone. Using the telephone keypad and following the voice prompts, the caller can access the DSMA Facts section of CDRH Facts-On-Demand and request a DSMA Facts index or enter the three or four digit Shelf number for the document(s) they want. The DSMA Facts index & documents that are less than 30 pages are put in queue to be automatically faxed to the fax number provided by the requester. Documents that are greater than 29 pages are faxed after normal business hours.

World Wide Web ­ FDA/CDRH maintains an entry on the World Wide Web for easy access to information. Information includes text, graphics, and files that may be downloaded to a PC with access to the Web. Updated on a regular basis, the CDRH Home Page includes device safety alerts, Federal Register reprints, information on pre­market submissions (including lists of approved applications and manufacturers' addresses), small manufactures' assistance, information on video conferencing and electronic submissions, mammography matters, and other device­oriented information. The home page may be accessed via FDA's home page at http://www.fda.gov or directly at http://www.fda.gov/cdrh/index.html

A text­only version of the World Wide Web is also available from a computer or VT­100 compatible terminal by dialing 800­222­0185 (terminal settings are 8/1/N). Once the modem answers, press Enter several times and then select menu choice 1: FDA BULLETIN BOARD SERVICE. From there follow instructions for logging in, and at the BBS TOPICS PAGE, arrow down to the FDA Home Page (do not select the first CDRH entry). Then select Medical Devices and Radiological Health. From there select CENTER FOR DEVICES AND RADIOLOGICAL HEALTH for general information, or arrow down for specific topics.

DSMADOCs - Fax a request for the documents available in paper copy by mail to Gene Allen at 301.443.8818. Include the Shelf_# of the documents and your mailing address. Two separate complete indexes are available; 1. through CDRH Facts-On-Demand, or 2. by Fax order, as noted in the table below.

Index Sort / Source	DSMA Facts	Fax Order
Alphabetically on Title	3913	3913
Shelf_#	4913	4913
Document Date	5913	5913
Date logged into DSMADOC	6913	6913

Revised: 8-20-93

K ____________      Date DMC Received ____________

Device Trade Name: _____________________________________

Reason for 510(k) _____________________________________

Division/Branch: _____________________________________

Administrative Reviewer Signature: ____________________ Date ___________

Supervisory Signature ____________________ Date ____________________

Did the firm request expedited review? ____________________

Did we grant expedited review: ____________________

_______          _____________

accepted          refuse to
                        accept

Yes Present Omission Justified

Yes Inadequate Omitted

I.     Critical Elements:
Is the product a device?	o	o
Is the device exempt from 510(k) by regulation or policy?	o	o
Is device subject to review by CDRH?	o	o
(I) Are you aware that this device has been the subject of a previous NSE decision? (ii) If yes, does this new 510(k) address the NSE issue(s) (e.g., performance data)?	o	o
(I) Are you aware of the submitter being the subject of an integrity investigation? If yes, consult ODE Integrity Officer.	o	o
Has the ODE Integrity Officer given permission to proceed with the review? (Blue Book Memo #I91-2 and Federal Register 90N-0332, September 10, 1991.)	o	o
Does the submission contain the information required under Sections 510(k), 513(f), and 513(I) of the Federal Food, Drug, and Cosmetic Act (the Act) and Subpart E of Part 807 in Title 21 of the Code of Federal Regulations?:
Device trade or proprietary name	o	o
Device common or usual name or classification name	o	o
Establishment registration number (only applies if establishment is registered)	o	o
Class into which the device is classified under (21 CFR Parts 862 to 982)	o	o
Classification Panel	o	o
Action taken to comply with Section 514 of the Act	o	o
Proposed labels, labeling and advertisements (if available) that describe the device, its intended use, and directions for use (Blue Book Memo #G91-1)	o	o
A 510(k) summary of safety and effectiveness or a 510(k) statement that safety and effectiveness information will be made available to any person upon request.	o	o
For class III devices only, a class III certification and a class III summary	o	o
Photographs of the device	o	o
Engineering drawings for the device with dimensions and tolerance	o	o
The marketed device(s) to which equivalence is claimed including labeling and description of the device	o	o
Statement of similarities and/or differences with marketed device(s)	o	o
Data to show consequences and effects of a modified device(s)	o	o
III.     Additional Information that is necessary under 21 CFR 807.87(h):
Submitter's name and address	o	o
Contact person, telephone number and fax number	o	o
Representative/Consultant if applicable	o	o
Table of Contents with pagination	o	o
Address of manufacturing facility/facilities and, if appropriate, sterilization site(s)	o	o
III.     Additional information that may be necessary under 21 CFR 807.87(h):
Comparison table of the new device to the marketed device(s)	o	o
Action taken to comply with voluntary standards	o	o
Performance data:
marketed device:
bench testing	o	o
animal testing	o	o
clinical data	o	o
new device:
bench testing	o	o
animal testing	o	o
clinical data	o	o
Sterilization information	o	o
Software information	o	o
Hardware information	o	o
If this 510(k) is for a kit, has the kit certification statement been provided?	o	o
Is this device subject to issues that have been addressed in specific guidance document(s)?	o	o
If yes, continue review with checklist from any appropriate guidance documents.	o	o
If no, is 510(k) sufficiently complete to allow substantive review?	o	o
Other (specify)	o	o

POINTS TO CONSIDER FOR REVIEW OF CALIBRATION AND QUALITY CONTROL LABELING FOR IN VITRO DIAGNOSTIC DEVICES     DRAFT 2/1/96

Objectives of This Document

This draft document provides FDA's guidance for calibration and quality control (QC) recommendations and labeling in support of premarketing notification 510(k) in vitro diagnostic (IVD) device submissions. The intent is to provide both manufacturers and Division of Clinical Laboratory Device (DCLD) reviewers with a basis for improved review consistency. Review criteria for individual submissions for calibration or quality control materials are not included in the scope of this document.

Background

Calibration and quality control are key requirements of FDA review, as noted in the labeling regulations for in vitro devices [(21 CFR 809.10(b)(8)(v and vi)]. As a result FDA routinely reviews details of calibration and the kinds of quality control procedures and materials required as part of its product review.

The other major regulatory program that affects laboratories is the Clinical Laboratory Improvement Act of 1988 (CLIA 88) which currently mandates that all clinical laboratories follow quality control procedures as published in regulations (CFR Part 493, Subpart K).

FDA's Labeling Regulation

FDA's labeling regulations contain provisions to deal with both device accuracy and precision.

CFR 809.10(b)(8)(v) reads: "Details of calibration: Identify reference material. Describe preparation of reference samples(s), use of blanks, preparation of the standard curve, etc. The description of the range of calibration should include the highest and lowest values measurable by the procedure."

FDA currently requires information on calibrationprocedures performed both to support data collection as part of the submission and to provide users with information on the appropriate routine operation of the device. Whenever possible we encourage traceability of device performance to a reference method or material. Recommended calibration frequencies should be included as part of each submission with appropriate supporting data.

CFR 809.10(b)(8)(vi) reads: "Details of kinds of quality control procedures and materials required. If there is need for both positive and negative controls, this should be stated. State what are considered satisfactory limits of performance."

FDA currently requires that the package inserts of all devices contain information on the quality control materials appropriate for a test system. In addition any internal, electronic, reagent, or process control which is an integral component of the device must be clearly described and the nature of the information provided by its use explained. Recommended QC specific rules including run frequencies to be followed for assessing quality are left to the discretion of the individual laboratory.

The intent of the above review is to ensure that users clearly understand the operating characteristics of QC systems so that they can make informed choices about minimal QC requirements for a particular system and setting.

Calibration Procedures

Calibration procedures refer to the methods used to translate a device response measurement into a concentration, activity, or other outcome measurement. Calibration usually involves measurement of the device response in relation to special samples of known values called calibrators. Proper calibration and maintenanceof calibration impacts on both the accuracy and precision of test results.

Calibration Categories

Calibration is most commonly performed using calibrators specifically prepared to set up a standard curve or cut-off point for an assay. In some instances calibration may be based on a rigid determination of the operating characteristics of a system and its known performance parameters (e.g. enzymes) and in some instances selected patient samples or other samples are used to correlate accuracy between a reference method to a working method.

Requirements for Method Calibration

Requirements for method calibration are outlined in 21 CFR 809.10(b)(8)(v) and include:

1. identification of reference material

2. a description of the preparation of reference sample(s)

3. a description of preparation of the standard curve (if applicable)

4. a description of the range of calibration
   

Quality Control Procedures

Quality control procedures are the set of laboratory materials and analytical processes used to:

1. monitor the performance of laboratory analytical systems (reagents, instruments, and/or operators).
   

2. monitor the precision and accuracy of a test procedure.
   

3. ensure that proper testing conditions and instructions have been met.

All in vitro devices which result in generation of test results must include information on quality control to comply with the labeling requirements noted above.

Quality Control Categories

Quality control of in vitro devices may be composed of two different components:

1. External quality control samples: These are external samples which are run in parallel with patient samples to assess the analytical reliability of the total analytical test system. Ideally these are handled in exactly the same manner as the patient samples and are in an identical matrix. Results generated through use of QC samples optimally could be used to evaluate all components of the analytical system from specimen preparation through generation of test results.
   

2. Device quality control components (so-called procedureal controls): These are device components which can complement or augment external quality control samples. Quality control components include a wide variety of methods or mechanisms internal to a device which can be used to evaluate parts of the system including (but not limited to) the following examples:
   
   1. the operating integrity of the instrument system (internal electronic calibration or system checks)
      

   2. the integrity of reagents and sample (internal components used to check for volume flow, integrity of antibody/antigen, or the activity of important reaction ingredients) and/or
      

   3. proper procedures (internal design components to monitor that reagents have been added in the proper order.)
      

Appropriate control limits can be established for both external quality control samples and device quality control components and these mechanisms can be used together to monitor and assess devices and components involved and to predict analytical failure.

Requirements for Quality Control

External samples for use in QC. External samples for use in QC evaluation of a device may be included as part of a diagnostic test system or may be purchased as an accessory. If the QC material is included as a part of the device under review, performance information and labeling should follow that of the FDA Points to Consider for Quality Control Materials. Whatever the recommended source for QC materials, package inserts should include information on what types of QC material should be obtained, where they may be obtained, and why they must be used in support of device performance.

At a minimum, labeling should indicate the types of QC samples recommended including appropriate levels and matrices to be used. QC recommendations should be chosen to adequately assess ongoing test performance at key performance intervals or medical decision points. For qualitative tests it is recommended that positive and negative cut-offs be carefully identified and that controls be provided which adequately challenge performance at these levels.

Device quality control components (procedural controls). All device quality control components which contribute to evaluation of testing should be clearly identified and the actions and limitations of each of these components should be addressed. For example, devices which include a color control line as part of a visual read-out should clearly indicate what development of the colored line means; does it assess for proper fluid uptake alone; does it test reactivity of antibody; does it evaluate addition of reagents in a proper order, etc? The procedural instructions for the assay should specify the acceptability of: temperature and time variation, instrument maintenance, and functionality. Well established ranges for these areas of the procedure reflect on the adequacy of the assay's QC.

In most instances the frequency of quality control testing will depend on a variety of laboratory specific factors including testing volume, testing frequency, and the nature of the laboratory's operational quality control and quality assurance programs. In some instances minimal quality control specifications may be required by FDA. These are directed at control of the medical device alone and are not intended to establish parameters for laboratory practice or accreditation. Consequently, these recommendations should be accompanied by a clear disclaimer indicating that quality control requirements should be performed in conformance with local, state, and/or Federal regulations or accreditation requirments.

LETTER TO ALL MANUFACTURERS OF IN-VITRO DIAGNOSTIC (IVD) DEVICES SIGNED BY DR. STEVE GUTMAN, DIRECTOR, DCLD - 5/31/96

This letter describes revisions in the Tier/Triage Program for premarket submissions that are about to be implemented by the Division of Clinical Laboratory Devices (DCLD) in the Office of Device Evaluation (ODE).

The tier/triage program is an ODE initiative introduced in 1993 as part of a comprehensive management action plan for improving the efficiency of its administrative work process. This program is designed to allow levels of review of premarket submissions to be adjusted according to device risk. The lowest risk devices are assigned the lowest intensity of review, tier 1 review, and the highest risk devices the highest level of review, tier 3 review. Products of moderate risk are assigned tier 2 review.

When implemented by ODE in 1993, DCLD made the decision to limit assignment of tier 1 category to those devices for which review of standard performance characteristics (accuracy, precision, analytical sensitivity and specificity, etc.) would not be necessary. As a result only a handful of devices were reassigned to this low level review category and the workload impact of the program was minimal. In 1995 the Health Industry Manufacturers Association (HIMA) provided the agency with a proposal to expand the menu of devices assigned to the tier 1 category using a series of flowcharts incorporating a variety of device features including classification, analyte, matrix, methodology, technology, familiarity, and intended use. This flowchart approach was evaluated by DCLD and a simplified version taken to an FDA sponsored Tier/Triage workshop on October 1995. FDA staff, representatives of the IVD industry, academia, the clinical laboratory community, clinicians, and other HHS agencies all provided useful comments during this open public meeting.

The revised DCLD Tier/Triage Program consists of the following elements:

• FDA will pilot the DCLD tier/triage program for one year using the DCLD flow chart (Enclosure-1) proposed at the November 1995 Tier/Triage Workshop; starting date: June 1, 1996.

• DCLD has prepared a checklist for use in making the tier/ triage decision (Enclosure-2). Manufacturers have the option of including a suggested tier determination in their 510(k) submission using the DCLD tier decision chart and checklist. The manufacturer's tier determination will be taken into consideration by DCLD when assigning the tier level of review for each individual product submission.

• All IVD premarket submissions will have an up-front tier/triage by the branch chief of the DCLD branch to which the submission is assigned.

• Tier 1 review will consist of a submission completeness evaluation and a labeling review by the scientific reviewer to whom the submission is assigned. The review will consist of checking the labeling for conformity to 21 CFR 809.10. If the labeling content is the expected for a specific type of device, 510(k) clearance will be performed as a tier 1 review. If a deviation/omission from the usual labeling content for a specific type of device is noted, the level of review will be upgraded to tier 2. This will initiate a formal review of the data supporting the submission.

• Tier 2 review will be performed by a scientific reviewer and will consist of a labeling review similar to the one applied to the tier 1 review plus scientific evaluation of the data generated by the manufacturer to substantiate product labeling claims.

• Tier 3 review like the tier 2 review will consist of both a labeling review and a scientific evaluation of the data generated by the manufacturer to substantiate product labeling claims. Because these products are associated with high risk to the patient or with novel technical features, this review will be conducted by a team of scientific reviewers and will frequently require advisory panel review and comment either through "home work" assignments or through formal panel meetings.

• The IVD manufacturers have the option of including a suggested tier determination in their 510(k) submission using the DCLD tier decision chart. The manufacturer's tier determination will be taken into consideration by DCLD when assigning the tier level of review for each individual product submission. However, the final tier determination will be made by DCLD. All submissions regardless of their proposed tier status should include supporting information and data within the submission for all labeling claims.

• Tier 1 submissions will be reviewed in a unique review queue.

• In order to assess the appropriateness of the tier 1 review, for a limited period of time, a subset of the tier 1 IVD devices (about 10%) will be subject, randomly, to a tier 2 review.

• DCLD managers have identified which IVD devices would be subject to tier 1 review based solely on the last criterion described in the DCLD decision chart Ä major determinant in diagnosis and treatment (Enclosure-3). The ability to triage a product into the tier 1 category according to this risk assessment is predicated on the finding that the device meets all previous criteria of the decision flowchart, i.e., it involves a familiar analyte, methodology, and technology, is used in a clinical laboratory setting, and FDA has knowledge and experience in review of similar devices.

• The tier/triage program will be evaluated after one year by comparing the average overall review time following implementation of the tier triage program with the current average overall review time. Analysis will include evaluation of review times for each tier and will allow the division to assess the impact of the program on workload and on the submission turnaround time. In addition, results of the internal audit of tier 1 products will be evaluated to determine the impact of this program on the assessment of device performance and substantial equivalence to its predicate.

• The evaluation of the tier/triage program will be discussed in an open forum, similar to the one provided during the tier/ triage workshop. At this time, interested parties will have an opportunity to comment on the results of the program.

We believe that this revised program will thus streamline the review of premarket submissions and will bring more consistency and predictability to the IVD review process. If you have questions related to the content of this letter, please contact me or Clara A. Sliva at (301) 594-3084.

   

	Sincerely yours,
	Steve Gutman, MD, MBA
	Director
	Division of Clinical Laboratory Devices
	Office of Device Evaluation

Enclosures

INTERPRETATION OF THE DCLD'S TIER TRIAGE DECISION CHART AND DEFINITION OF TERMS

• The first three criteria in the chart are taken from the ODE decision tree which is routinely used to determine whether a device can be reviewed as a 510(k) or whether the device must be reviewed as a premarket approval application (PMA). The same interpretation of terms used for the ODE 510(k) chart applies to the DCLD Tier Triage Chart.

• Criterion #1 determines if there is a legally marketed predicate device. In the absence of such a predicate, the device is automatically a class III device and is subject to a PMA.

• Criterion #2 is an assessment of whether the new device has the same intended use or indications for use as the predicate device. If the intended use and/or indications for use are the same as the predicate, the device qualifies for a 510(k) review. If different the impact of the differences must be assessed.

• Criterion #3 assess whether differences in the intended use or indications for use alter the intended therapeutic/diagnostic effect. If there is a potential impact on the safety and effectiveness (new issues raised), a PMA is required. If such an impact is not expected, the device qualifies for a 510(k) review.

• Criterion #4 determines the novelty of the product in terms of analyte, matrix, methodology and/or technology. If the issues of safety and effectiveness are not new but require high level scrutiny, then a tier 3 review is warranted.
  
  New Analyte - a type of device that has not been previously cleared by FDA but with the same intended use as the predicate. Example: troponin for the diagnosis of acute myocardial infarction (with creatine kinase as the predicate device) is a tier 3 review. The first four of a kind will be considered under "new analytes" for the purpose of tier triage.
  
  New Matrix - the device uses a type of clinical specimen not previously used in the same type of IVDs cleared by FDA. Example: sweat patches for drugs of abuse (with urine drugs of abuse as the predicate device) is a tier 3 review. The first four of a kind will be considered under "new matrices" for the purpose of tier triage.
  
  New Methodology/Technology - the device's performance depends on a methodology/technology that has not been previously used in an IVD cleared by FDA. Example: nucleic acid amplification for the direct detection of certain infectious agents provided a predicate exists. The first four of a kind for each methodology/technology will be considered under "new methodology/technology" for the purpose of tier triage.
  
  
• Criterion #6 identifies the level of professional training of the person for whom the test is intended. Since DCLD requires device performance data in the hands of persons with minimal clinical laboratory training when the test is intended for use in physician office laboratories (POLs) and point-of-care settings, these types of devices would be subject minimally to a tier 2 review. The same rationale applies for IVD tests intended for over-the-counter use. For over the counter tests for which there is little information available on how lay users may handle test results, a tier 3 review is generally necessary.
  
  Clinical Laboratory Professionals - laboratory technologists or persons with clinical laboratory training employed by a clinical laboratory.

• Criterion #8 takes into account the FDA experience in reviewing similar devices. As a rule, the first four IVD tests of the same type will be subject to tier 3 review.

• Criterion #9 takes into account the risk associated with the clinical use of the product. An IVD product which serves as a major determinant of diagnosis, therapy, or prognosis will be subject to tier 2 review because of its likelihood to lead to clinical decision making and significant medical intervention.
  
  Major Determinant - an IVD test that will provide a result that is likely to make or cause change in diagnosis, therapy, or prognosis when used by itself or as a key element in conjunction with other tests.

Enclosure 2 - TIER/TRIAGE CHECKLIST

1. Is there a legally marketed predicate device?
   

   YES   _____

   NO    _____
   

2. Does the new device have the same intended use or indications for use of the predicate device?
   

   YES   _____

   NO    _____

3. If the answer to question #2 is NO, do differences in intended use or indications for use between the new device and the predicate alter the intended therapeutic/diagnostic effect of the new device (consider impact on safety and effectiveness)?
   

   YES   _____

   NO    _____
   

4. If the new device has the same intended use or indications for use as the predicate device, or if it does not, and if the differences do not alter the intended therapeutic/diagnostic effect,
   
   • Is it a new analyte?     YES   _____     NO   _____

   • Does it utilize novel matrix?     YES   _____     NO   _____
     

   • Does it utilize novel methodology?     YES   _____     NO   _____

   • Does it utilize novel technology?     YES   _____     NO   _____

5. If the answer to one of the elements of question #4 is YES, could the change raise new issues of safety and effectiveness?
   

   YES   _____

   NO    _____

6. If the answer to all elements of question #4 is NO, is the device intended to be used in:
   • Traditional Clinical laboratories?     YES   _____     NO   _____

   • Point of Care?     YES   _____     NO   _____

   • Physician Office Laboratory?     YES   _____     NO   _____

   • Over-the-counter?     YES   _____     NO   _____

7. If the device is intended for over-the-counter-use, is the use of the test results well established in lay hands?

   YES   _____

   NO    _____

8. If the device is intended for commercial clinical laboratories, does FDA have knowledge/experience with similar devices?

   YES   _____

   NO    _____

9. If the FDA has knowledge/experience with similar devices, is the use of the device in clinical practice the major determinant in diagnosis or treatment?

   YES   _____

   NO    _____

RATIONALE FOR THE DCLD DECISION CHART

The decision chart is based on an assessment of risk to the patient associated with the use of the device. If the risk of device use is low and predictable, a low level of premarket review may be required for clearance. If the risk is high or unknown, more data is required and a more intense review of the data is necessary.

The first four criteria in the decision chart deal with WHAT is the device, i.e., what it measures, what matrix it uses, what methodology it utilizes, and what technology it employs, and with WHY is the device indicated for use in the clinical setting. If we do not have a clear understanding of what is the device, its clinical relevance and its role in clinical practice, the risk to the patient associated with the use of the device is unknown.

Next, the DCLD decision chart deals with WHO will use the device. The risk to the patient associated with the use of the device will be directly related to the amount of clinical laboratory training and experience of the person performing the test. As user training and experience increases, device risk tends to become lower and more predictable allowing for a lower level of premarket review. Special attention is needed for products intended for use in lay hands; in these settings premarket review may require evaluation of both technical use of the product and use and interpretation of the information generated from over-the -counter testing.

The repeated exposure of FDA reviewers to a specific type of device will lead to a better understanding of the risks to the patient associated with the use of the device. The better understanding of risks will result from the larger number of known studies available with a particular device and from the higher probability of learning about possible device failures through the medical device adverse event reporting program.

Finally, of importance is HOW will the device be used in clinical practice. This question takes into account the importance of the results of the test in patient management. IVD devices that are a major determinant of diagnosis, treatment, or prognosis are associated with high risk to the patient from using the device and require a more stringent level of data review.

Several workshop panelists commented that this item should be placed earlier on in the decision chart. In reality, what impacts on the tier decision is not where in the chart this element is placed, but how major determinant is defiend. If major determinant is defined as the test that is the major determinant or the sole determinant of diagnosis more IVD products will be placed in tier 1 review. If we define major determinant as proposed, i.e., a major deteminant in diagnosis, therapy, or prognosis, then fewer IVD products will receive tier 1 review.

IVD DEVICES SUBJECT TO TIER 1 REVIEW

Panel		Product Code		Common Name		Class		Regulation
IM		DCF		ALBUMIN, ANTIGEN, ANTISERUM, CONTROL		II		866.5040
IM		JZJ		PREALBUMIN, ANTIGEN, ANTISERUM, CONTROL		I		866.5060
IM		DDE		CARBONIC ANHYDRASE C, ANTIGEN, ANTISERUM, CONTROL		I		866.5200
IM		DDH		CARBONIC ANHYDRASE B, ANTIGEN, ANTISERUM, CONTROL		I		866.5200
IM		KTK		REAGENT, IMMUNOASSAY, CARBONIC ANHYDRASE B AND C		I		866.5200
IM		DCK		C-REACTIVE PROTEIN, ANTIGEN, ANTISERUM, AND CONTROL		II		866.5270
IM		JZH		FACTOR B, ANTIGEN, ANTISERUM, CONTROL		II		866.5320
IM		DBF		FERRITIN, ANTIGEN, ANTISERUM, CONTROL		II		866.5340
IM		DCO		ALPHA-GLOBULIN, ANTIGEN, ANTISERUM, CONTROL		I		866.5400
IM		DAW		ALPHA-2-AP-GLYCOPROTEIN, ANTIGEN, ANTISERUM, CONTROL		I		866.5425
IM		DBC		ALPHA 2, 2N-GLYCOPROTEIN, ANTIGEN, ANTISERUM, CONTROL		I		866.5425
IM		DEF		ALPHA-2-HS-GLYCOPROTEIN, ANTIGEN, ANTISERUM, CONTROL		I		866.5425
IM		DEJ		ALPHA-2-GLYCOPROTEINS, ANTIGEN, ANTISERUM, CONTROL		I		866.5425
IM		DDN		BETA-2-GLYCOPROTEIN I, ANTIGEN, ANTISERUM, CONTROL		I		866.5430
IM		DDK		BETA-2-GLYCOPROTEIN III, ANTIGEN, ANTISERUM, CONTROL		I		866.5440
IM		DAD		HAPTOGLOBIN, ANTIGEN, ANTISERUM, CONTROL		II		866.5460
IM		DDG		TRANSFERRIN, ANTIGEN, ANTISERUM, CONTROL		II		866.5880
IM		CZO		INTER-ALPHA TRYPSIN INHIBITOR, ANTIGEN, ANTISERUM, CONTROL		I		866.5890
CH		CIX		BROMCRESOL GREEN DYE­BINDING, ALBUMIN		II		862.1035
CH		CJW		BROMCRESOL PURPLE DYE­BINDING, ALBUMIN		II		862.1035
CH		CJZ		ACID, HYDROXYAZOBENZENE­BENZOIC, ALBUMIN		II		862.1035
CH		CJF		TETRABROMOPHENOLPHTHALEIN, ALBUMIN		II		862.1035
CH		CJQ		RADIAL IMMUNODIFFUSION, ALBUMIN		II		862.1035
CH		CJG		TETRABROMO­M­CRESOLSULFONPHTHALEIN, ALBUMIN		II		862.1035
CH		CJC		FRUCTOSE­1, 6­DIPHOSPHATE AND NADH (U.V.), ALDOLASE		I		862.1040
CH		CJT		HYDRAZONE COLORIMETRY, ALDOLASE		I		862.1040
CH		JKL		ACID, DELTA­AMINOLEVULINIC, ION­EXCHANGE COLUMNS WITH COLORIMETRY		I		862.1060
CH		JID		PHOTOMETRIC METHOD, AMMONIA		I		862.1065
CH		JIF		ENZYMATIC METHOD, AMMONIA		I		862.1065
CH		JIG		ELECTRODE, ION­SPECIFIC METHOD, AMMONIA		I		862.1065
CH		JIE		METHOD, ION­EXCHANGE, AMMONIA		I		862.1065
CH		CIZ		RADIOIMMUNOASSAY, ANDROSTENEDIONE		I		862.1075
CH		CIY		RADIOIMMUNOASSAY, ANDROSTERONE		I		862.1080
CH		JMA		ACID, ASCORBIC, 2,4­DINITROPHENYLHYDRAZINE (SPECTROPHOTOMETRIC)		I		862.1095
CH		CIS		HYDRAZONE COLORIMETRY, AST/SGOT		II		862.1100
CH		CIT		NADH OXIDATION/NAD REDUCTION, AST/SGOT		II		862.1100
CH		CIQ		DIAZO, AST/SGOT		II		862.1100
CH		CIF		VANILLIN PYRUVATE, AST/SGOT		II		862.1100
CH		JJB		AZO­DYES, COLORIMETRIC, BILIRUBIN & ITS CONJUGATES (URINARY, NON­QUANT.)		I		862.1115
CH		JKW		N­ACETYL­L­TYROSINE ETHYL ESTER (U.V.), CHYMOTRYPSIN		I		862.1180
CH		JKX		N­BENZOYL­L­TYROSINE ETHYL ESTER (U.V.), CHYMOTRYPSIN		I		862.1180
CH		CHE		RADIOIMMUNOASSAY, CORTICOIDS		I		862.1195
CH		JKC		RADIOIMMUNOASSAY, DEHYDROEPIANDROSTERONE (FREE AND SULFATE)		I		862.1245
CH		CGN		ACID, FOLIC, RADIOIMMUNOASSAY		II		862.1295
CH		JGE		TURBIDIMETRIC METHOD, GLOBULIN		I		862.1330
CH		JGD		NEPHELOMETRIC METHOD, GLOBULIN		I		862.1330
CH		JGC		TRYPTOPHAN MEASUREMENT (COLORIMETRIC), GLOBULIN		I		862.1330
CH		CGH		ELECTROPHORETIC, GLOBULIN		I		862.1330
CH		JPZ		COLORIMETRIC METHOD, GAMMA­GLUTAMYL TRANSPEPTIDASE		I		862.1360
CH		JQA		ELECTROPHORETIC, GAMMA­GLUTAMYL TRANSPEPTIDASE ISOENZYMES		I		862.1360
CH		JQB		KINETIC METHOD, GAMMA­GLUTAMYL TRANSPEPTIDASE		I		862.1360
CH		CCZ		ZIMMERMAN/NORYMBERSKI, 17­KETOGENIC STEROIDS		I		862.1385
CH		JHE		RADIOASSAY, 17­HYDROXYCORTICOSTEROIDS		I		862.1385
CH		CDB		PORTER SILBER HYDRAZONE, 17­HYDROXYCORTICOSTEROIDS		I		862.1385
CH		JHD		FLUOROMETRIC METHOD, 17­HYDROXYCORTICOSTEROIDS		I		862.1385
CH		JIZ		ATOMIC ABSORPTION, IRON (NON­HEME)		I		862.1410
CH		JJA		RADIO­LABELED IRON METHOD, IRON (NON­HEME)		I		862.1410
CH		JIY		PHOTOMETRIC METHOD, IRON (NON­HEME)		I		862.1410
CH		CFM		BATHOPHENANTHROLINE, COLORIMETRY, IRON (NON­HEME)		I		862.1410
CH		JQF		BATHOPHENANTHROLINE, IRON BINDING CAPACITY		I		862.1415
CH		JMO		FERROZINE (COLORIMETRIC) IRON BINDING CAPACITY		I		862.1415
CH		JQD		RESIN, ION­EXCHANGE, THIOGLYCOLIC ACID, COLORIMETRY, IRON BINDING CAPACITY		I		862.1415
CH		JQE		RESIN, ION­EXCHANGE, ASCORBIC ACID, COLORIMETRY, IRON BINDING CAPACITY		I		862.1415
CH		JQG		RADIOMETRIC, FE59, IRON BINDING CAPACITY		I		862.1415
CH		CCY		ZIMMERMAN (SPECTROPHOTOMETRIC), 17­KETOSTEROIDS		I		862.1430
CH		CFH		TETRAZOLIUM INT DYE­DIAPHORASE, LACTATE DEHYDROGENASE		II		862.1440
CH		CER		2,4­DINITROPHENYLHYDRAZINE, LACTATE DEHYDROGENASE		II		862.1440
CH		CFJ		NAD REDUCTION/NADH OXIDATION, LACTATE DEHYDROGENASE		II		862.1440
CH		JGG		L­LEUCINE­4­NITROANILIDE (COLORIMETRIC), LEUCINE ARYLAMIDASE		I		862.1460
CH		CDC		L­LEUCYL B­NAPHTHYLAMIDE, LEUCINE AMINOPEPTIDASE		I		862.1460
CH		JMS		ACID, OXALACETIC AND NADH OXIDATION (U.V.), MALIC DEHYDROGENASE		I		862.1500
CH		JQN		COLORIMETRIC, MUCOPOLYSACCHARIDES		I		862.1505
CH		LPW		SYSTEM, TEST, OXALATE		I		862.1542
CH		CEO		PHOSPHOMOLYBDATE (COLORIMETRIC), INORGANIC PHOSPHORUS		I		862.1580
CH		JGR		REFRACTOMETRIC, TOTAL PROTEIN		II		862.1635
CH		JGQ		TURBIDIMETRIC, TOTAL PROTEIN		II		862.1635
CH		JGP		LOWRY (COLORIMETRIC), TOTAL PROTEIN		II		862.1635
CH		CEK		BIURET (COLORIMETRIC), TOTAL PROTEIN		II		862.1635
CH		JIR		INDICATOR METHOD, PROTEIN OR ALBUMIN (URINARY, NON­QUANT.)		I		862.1645
CH		JIQ		TURBIDIMETRIC METHOD, PROTEIN OR ALBUMIN (URINARY, NON­QUANT.)		I		862.1645
CH		JJS		CONTROLS FOR BLOOD­GASES, (ASSAYED AND UNASSAYED)		I		862.1660
CH		JJW		URINALYSIS CONTROLS (ASSAYED AND UNASSAYED)		I		862.1660
CH		JJT		ENZYME CONTROLS (ASSAYED AND UNASSAYED)		I		862.1660
CH		JJX		SINGLE (SPECIFIED) ANALYTE CONTROLS (ASSAYED AND UNASSAYED)		I		862.1660
CH		JJR		ELECTROLYTE CONTROLS (ASSAYED AND UNASSAYED)		I		862.1660
CH		JJY		MULTI­ANALYTE CONTROLS, ALL KINDS (ASSAYED AND UNASSAYED)		I		862.1660
CH		JNO		N­BENZOYL­L­ARGININE ETHYL ESTER (U.V.), TRYPSIN		I		862.1725
CH		JNN		P­TOLUENESULPHONYL­L­ARGININE METHYL ESTER (U.V.), TRYPSIN		I		862.1725
CH		JNP		INFRARED SPECTROSCOPY MEASUREMENT, URINARY CALCULI (STONE)		I		862.1780
CH		JNQ		QUALITATIVE CHEMICAL REACTIONS, URINARY CALCULI (STONE)		I		862.1780
TX		DKO		ADSORBENTS, ION­EXCHANGE		I		862.2230
TX		DMG		PAPERS, ION		I		862.2230
TX		KEA		RESINS, ION­EXCHANGE		I		862.2230
TX		DMS		GASES, GLC		I		862.2250
TX		DJA		COLUMN SUPPORTS, GLC		I		862.2250
TX		DLG		COATING, LIQUID, GLC		I		862.2250
TX		LEQ		DETECTORS, ELECTROCHEMICAL, LIQUID CHROMATOGRAPHY		I		862.2260
TX		DMZ		LIQUID CHROMATOGRAPHY, ADSORBENT		I		862.2260
TX		DNH		RESINS, ION­EXCHANGE, LIQUID CHROMATOGRAPHY		I		862.2260
TX		DPA		APPARATUS, GENERAL USE, THIN LAYER CHROMATOGRAPHY		I		862.2270
TX		DLY		PLATE, ALUMINA, TLC		I		862.2270
TX		DLC		ATOMIZER, TLC		I		862.2270
TX		DLO		INDICATOR, SILICA GEL FLUORESCENT, TLC		I		862.2270
TX		DJO		INDICATOR, CELLULOSE FLUORESCENT, TLC		I		862.2270
TX		DJS		U.V. LIGHT, TLC		I		862.2270
TX		DKG		PLATE, CELLULOSE, TLC		I		862.2270
TX		DKK		TANKS, DEVELOPING, TLC		I		862.2270
TX		DKS		PLATE, SILICA GEL, TLC		I		862.2270
TX		DKY		INDICATOR, ALUMINA FLUORESCENT, TLC		I		862.2270
TX		DIF		DRUG MIXTURE CONTROL MATERIALS		I		862.3280
TX		DIE		HEAVY METALS CONTROL MATERIALS		I		862.3280
TX		LAX		LIDOCAINE CONTROL MATERIALS		I		862.3280
TX		LAW		THEOPHYLLINE CONTROL MATERIALS		I		862.3280
TX		LAZ		N­ACETYLPROCAINAMIDE CONTROL MATERIALS		I		862.3280
TX		LAY		METHOTREXATE CONTROL MATERIALS		I		862.3280
TX		LAS		DRUG SPECIFIC CONTROL MATERIALS		I		862.3280
TX		DMP		DIGOXIN CONTROL SERUM, RIA		I		862.3280
TX		DKC		ALCOHOL CONTROL MATERIALS		I		862.3280
TX		DJK		DIGITOXIN CONTROL SERUM, RIA		I		862.3280
TX		LBA		PROCAINAMIDE CONTROL MATERIALS		I		862.3280
HE		GHK		CENTRIFUGE, MICROSEDIMENTATION		I		864.5350
HE		GIO		TUBE, COLLECTION, CAPILLARY BLOOD		I		864.6150
HE		JIO		BLOOD, OCCULT, COLORIMETRIC, IN URINE		II		864.6550
HE		JIP		BLOOD, OCCULT, ENZYMATIC METHOD, IN URINE		II		864.6550
MI		JTY		CULTURE MEDIA, FOR ISOLATION OF PATHOGENIC NEISSERIA		II		866.2410
MI		JSP		KIT, ANAEROBIC IDENTIFICATION		I		866.2660
MI		JSR		KIT, IDENTIFICATION, DERMATOPHYTE		I		866.2660
MI		JSS		KIT, IDENTIFICATION, ENTEROBACTERIACEAE		I		866.2660
MI		JSW		KIT, IDENTIFICATION, GLUCOSE NONFERMENTER		I		866.2660
MI		JSZ		KIT, IDENTIFICATION, PSEUDOMONAS		I		866.2660
MI		JTO		DISCS, STRIPS AND REAGENTS, MICROORGANISM DIFFERENTIATION		I		866.2660
MI		LIB		DEVICE, GENERAL PURPOSE, MICROBIOLOGY, DIAGNOSTIC		I		866.2660
MI		LJG		QUALITY CONTROL SLIDES		I		866.2660
MI		LQL		GRAM POSITIVE IDENTIFICATION PANEL		I		866.2660
MI		LQM		GRAM NEGATIVE IDENTIFICATION PANEL		I		866.2660
MI		LKS		DEVICE, PARASITE CONCENTRATION		I		866.2900
MI		JWT		ANTIGEN, CF, ASPERGILLUS SPP.		I		866.3040
MI		GSN		ANTISERUM, POSITIVE AND NEGATIVE FEBRILE ANTIGEN CONTROL SERUM		II		866.3085
MI		GSO		ANTIGENS (FEBRILE), AGGLUTINATION, BRUCELLA SPP.		II		866.3085
MI		GMG		ANTIGEN, LATEX AGGLUTINATION, COCCIDIOIDES IMMITIS		II		866.3135
MI		GMI		ANTIGEN, CF AND/OR ID, COCCIDIOIDES IMMITIS		II		866.3135
MI		GOP		ANTISERA, C. ACNES (553, 605)		I		866.3140
MI		KLH		ANTISERA, C. ACNES		I		866.3140
MI		GNG		ANTIGENS, CF (INCLUDING CF CONTROL), COXSACKIEVIRUS A 1­24, B 1­6		I		866.3145
MI		GNN		ANTISERA, NEUTRALIZATION, COXSACKIEVIRUS A 1­24, B 1­6		I		866.3145
MI		GNO		ANTISERA, CF, COXSACKIEVIRUS A 1­24, B 1­6		I		866.3145
MI		GQH		ANTIGEN, CF (INCLUDING CF CONTROL), CYTOMEGALOVIRUS		II		866.3175
MI		GQI		ANTISERUM, CF, CYTOMEGALOVIRUS		II		866.3175
MI		LJO		ANTIGEN, IHA, CYTOMEGALOVIRUS		II		866.3175
MI		GNQ		ANTIGEN, CF (INCLUDING CF CONTROL), EPSTEIN­BARR VIRUS		I		866.3235
MI		GQC		ANTISERA, CF, EQUINE ENCEPHALITIS VIRUS, EEE, WEE		I		866.3240
MI		GQD		ANTIGENS, CF (INCLUDING CF CONTROL), EQUINE ENCEPHALITIS VIRUS, EEE, WEE		I		866.3240
MI		GQN		ANTIGEN, CF (INCLUDING CF CONTROL), HERPESVIRUS HOMINIS 1,2		III		866.3305
MI		GQO		ANTISERA, CF, HERPESVIRUS HOMINIS 1,2		III		866.3305
MI		LKC		ANTIGENS, INDIRECT HEMAGGLUTINATION (IHA) HERPES SIMPLEX VIRUS		III		866.3305
MI		GQJ		ANTISERUM, CF, LYMPHOCYTIC CHORIOMENINGITIS VIRUS		I		866.3360
MI		GQK		ANTIGEN, CF, LYMPHOCYTIC CHORIOMENINGITIS VIRUS		I		866.3360
MI		GSB		ANTIGENS, CF, ALL, MYCOPLASMA SPP.		I		866.3375
MI		GQY		ANTIGEN, HA (INCLUDING HA CONTROL), MUMPS VIRUS		I		866.3380
MI		GQZ		ANTISERUM, NEUTRALIZATION, MUMPS VIRUS		I		866.3380
MI		GRB		ANTISERUM, CF, MUMPS VIRUS		I		866.3380
MI		GRC		ANTIGEN, CF (INCLUDING CF CONTROL), MUMPS VIRUS		I		866.3380
MI		GRD		ANTISERUM, HAI, MUMPS VIRUS		I		866.3380
MI		GOG		ANTISERA, CF, POLIOVIRUS 1­3		I		866.3405
MI		GOH		ANTIGENS, CF (INCLUDING CF CONTROL), POLIOVIRUS 1­3		I		866.3405
MI		GQG		ANTIGEN, CF (INCLUDING CF CONTROLS), RESPIRATORY SYNCYTIAL VIRUS		I		866.3480
MI		GPO		ANTIGEN, CF, TYPHUS FEVER GROUP		I		866.3500
MI		GPQ		ANTIGEN, CF, SPOTTED FEVER GROUP		I		866.3500
MI		GPR		ANTISERUM, CF, Q FEVER		I		866.3500
MI		GPS		ANTIGEN, CF, Q FEVER		I		866.3500
MI		GOK		ANTISERA, HAI (INCLUDING HAI CONTROL), RUBELLA		III		866.3510
MI		GOL		ANTIGEN, HA (INCLUDING HA CONTROL), RUBELLA		III		866.3510
MI		GOM		ANTISERA, CF, RUBELLA		III		866.3510
MI		GON		ANTIGEN, CF (INCLUDING CF CONTROL), RUBELLA		III		866.3510
MI		GNC		ANTIGENS, FEBRILE, SLIDE AND TUBE, ALL GROUPS, SLAMONELLA SPP.		II		866.3550
MI		GOO		ANTISERA, FLUORESCENT, ALL GLOBULINS, SALMONELLA SPP.		II		866.3550
MI		GRL		ANTIGENS, ALL GROUPS, SALMONELLA SPP.		II		866.3550
MI		GRM		ANTISERA, ALL GROUPS, SALMONELLA SPP.		II		866.3550
MI		GLZ		ANTIGENS, IF, TOXOPLASMA GONDII		II		866.3780
MI		GMM		ANTIGENS, IHA, TOXOPLASMA GONDII		II		866.3780
MI		GMN		ANTIGENS, CF, TOXOPLASMA GONDII		II		866.3780
MI		GND		ANTIGEN, IHA, T. CRUZI		I		866.3870
MI		GNF		ANTIGEN, CF, T. CRUZI		I		866.3870
MI		GQW		ANTIGEN, CF, (INCLUDING CF CONTROL), VARICELLA­ZOSTER		II		866.3900
MI		GQX		ANTISERUM, CF, VARICELLA­ZOSTER		II		866.3900

21 CFR PART 807 SUBPART E

Subpart E--Premarket Notification Procedures

§ 807.81 When a premarket notification submission is required.

(a) Except as provided in paragraph (b) of this section, each person who is required to register his establishment pursuant to § 807.20 must submit a premarket notification submission to the Food and Drug Administration at least 90 days before he proposes to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of a device intended for human use which meets any of the following criteria:

(1) The device is being introduced into commercial distribution for the first time; that is, the device is not of the same type as, or is not substantially equivalent to, (i) a device in commercial distribution before May 28, 1976, or (ii) a device introduced for commercial distribution after May 28, 1976, that has subsequently been reclassified into class I or II.

(2) The device is being introduced into commercial distribution for the first time by a person required to register, whether or not the device meets the criteria in paragraph (a)(1) of this section.

(3) The device is one that the person currently has in commercial distribution or is reintroducing into commercial distribution, but that is about to be significantly changed or modified in design, components, method of manufacture, or intended use. The following constitute significant changes or modifications that require a premarket notification:

(i) A change or modification in the device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design,material, chemical composition, energy source, or manufacturing process.

(ii) A major change or modification in the intended use of the device.

(b) A premarket notification under this subpart is not required for a device for which a premarket approval application under section 515 of the act, or for which a petition to reclassify under section 513(f)(2) of the act, is pending before the Food and Drug Administration.

(c) In addition to complying with the requirements of this part, owners or operators of device establishments that manufacture radiation-emitting electronic products, as defined in § 1000.3 of this chapter, shall comply with the reporting requirements of Part 1002 of this chapter.

§ 807.85 Exemption from premarket notification.

(a) A device is exempt from the premarket notification requirements of this subpart if the device intended for introduction into commercial distribution is not generally available in finished form for purchase and is not offered through labeling or advertising by the manufacturer, importer, or distributor thereof for commercial distribution, and the device meets one of the following conditions:

(1) It is intended for use by a patient named in the order of the physician or dentist (or other specially qualified person); or

(2) It is intended solely for use by a physician or dentist (or other specially qualified person) and is not generally available to, or generally used by, other physicians or dentists (or other specially qualified persons).

(b) A distributor who places a device into commercial distribution for the first time under his own name and a repackager who places his own name on a device and does not change any other labeling or otherwise affect the device shall be exempted from the premarket notification requirements of this subpart if:

(1) The device was in commercial distribution before May 28, 1976; or

(2) A premarket notification submission was filed by another person.

§ 807.87 Information required in a premarket notification submission.

Each premarket notification submission shall contain the following information:

(a) The device name, including both the trade or proprietary name and the common or usual name or classification name of the device.

(b) The establishment registration number, if applicable, of the owner or operator submitting the premarket notification submission.

(c) The class in which the device has been put under section 513 of the act and, if known, its appropriate panel; or, if the owner or operator determines that the device has not been classified under such section, a statement of that determination and the basis for the person's determination that the device is not so classified.

(d) Action taken by the person required to register to comply with the requirements of the act under section 514 for performance standards.

(e) Proposed labels, labeling, and advertisements sufficient to describe the device, its intended use, and the directions for its use. Where applicable, photographs or engineering drawings should be supplied.

(f) A statement indicating the device is similar to and/or different from other products of comparable type in commercial distribution, accompanied by data to support the statement. This information may include an identification of similar products, materials, design considerations, energy expected to be used or delivered by the device, and a description of the operational principles of the device.

(g) Where a person required to register intends to introduce into commercial distribution a device that has undergone a significant change or modification that could significantly affect the safety or effectiveness of the device, or the device is to be marketed for a new or different indication for use, the premarket notification submission must include appropriate supporting data to show that the manufacturer has considered what consequences and effects the change or modification or new use might have on the safety and effectiveness of the device.

(h) A 510(k) summary as described in § 807.92 or a 510(k) statement as described in § 807.93.

(i) For submissions claiming substantial equivalence to a device which has been classified into class III under section 513(b) of the act:

(1) Which was introduced or delivered for introduction into interstate commerce for commercial distribution before December 1, 1990; and

(2) For which no final regulation requiring premarket approval has been issued under section 515(b) of the act, a summary of the types of safety and effectiveness problems associated with the type of devices being compared and a citation to the information upon which the summary is based (class III summary). The 510(k) submitter shall also certify that a reasonable search of all information known or otherwise available about the class III device and other similar legally marketed devices has been conducted (class III certification), as described in § 807.94. This information does not refer to information that already has been submitted to the Food and Drug Administration (FDA) under section 519 of the act. FDA may require the submission of the adverse safety and effectiveness data described in the class III summary or citation.

(j) A statement that the submitter believes, to the best of his or her knowledge, that all data and information submitted in the premarket notification are truthful and accurate and that no material fact has been omitted.

(k) Any additional information regarding the device requested by the Commissioner that is necessary for the Commissioner to make a finding as to whether or not the device is substantially equivalent to a device in commercial distribution A request for additional information will advise the owner or operator that there is insufficient information contained in the original premarket notification submission for the Commissioner to make this determination and that the owner or operator may either submit the requested data or a new premarket notification containing the requested information at least 90 days before the owner or operator intends to market the device, or submit a premarket approval application in accordance with section 515 of the act. If the additional information is not submitted within 30 days following the date of the request, the Commissioner will consider the premarket notification to be withdrawn.

(Information collection requirements in this section were approved by the Office of Management and Budget (OMB) and assigned OMB control number 0910-0281)

§ 807.90 Format of a premarket notification submission.

Each premarket notification submission pursuant to this part shall be submitted in accordance with this section. Each submission shall:

(a)(1) For devices regulated by the Center for Devices and Radiological Health, be addressed to the Food and Drug Administration, Center for Devices and Radiological Health (HFZ-401), 1390* Piccard Dr., Rockville, MD 20850.

(2) For devices regulated by the Center for Biologics Evaluation and Research, be addressed to the Food and Drug Administration, Center for Biologics Evaluation and Research, Division of Product Certification (HFB-240), 8800 Rockville Pike, Bethesda, MD 20892.

(3) All inquiries regarding a premarket notification submission should be in writing and sent to one of the addresses above.

(b) Be bound into a volume or volumes, where necessary.

(c) Be submitted in duplicate on standard size paper, including the original and two copies of the cover letter.

(d) Be submitted separately for each product the manufacturer intends to market.

(e) Designated "510(k) Notification" in the cover letter.

§ 807.92 Content and format of a 510(k) summary.

(a) A 510(k) summary shall be in sufficient detail to provide an understanding of the basis for a determination of substantial equivalence. FDA will accept summaries as well as amendments thereto until such time as FDA issues a determination of substantial equivalence. All 510(k) summaries shall contain the following information:

* Correct address is: 9200 Corporate Blvd.

(1) The submitter's name, address, telephone number, a contact person, and the date the summary was prepared;

(2) The name of the device, including the trade or proprietary name if applicable, the common or usual name, and the classification name, if known;

(3) An identification of the legally marketed device to which the submitter claims equivalence. A legally marketed device to which a new device may be compared for a determination regarding substantial equivalence is a device that was legally marketed prior to May 28, 1976, or a device which has been reclassified from class III to class II or I (the predicate), or a device which has been found to be substantially equivalent through the 510(k) premarket notification process;

(4) A description of the device that is the subject of the premarket notification submission, such as might be found in the labeling or promotional material for the device, including an explanation of how the device functions, the scientificconcepts that form the basis for the device, and the significant physical and performance characteristics of the device, such as device design, material used, and physical properties;

(5) A statement of the intended use of the device that is the subject of the premarket notification submission, including a general description of the diseases or conditions that the device will diagnose, treat, prevent, cure, or mitigate, including a description, where appropriate, of the patient population for which the device is intended. If the indication statements are different from those of the legally marketed device identified in paragraph (a)(3) of this section, the 510(k) summary shall contain an explanation as to why the differences are not critical to the intended therapeutic, diagnostic, prosthetic, or surgical use of the device, and why the differences do not affect the safety and effectiveness of the device when used as labeled; and

(6) If the device has the same technological characteristics (i.e., design, material, chemical composition, energy source) as the predicate device identified in paragraph (a)(3) of this section, a summary of the technological characteristics of the new device in comparison to those of the predicate device. If the device has different technological characteristics from the predicate device, a summary of how the technological characteristics of the device compare to a legally marketed device identified in paragraph (a)(3) of this section.

(b) 510(k) summaries for those premarket submissions in which a determination of substantial equivalence is also based on an assessment of performance data shall contain the following information:

(1) A brief discussion of the nonclinical tests submitted, referenced, or relied on in the premarket notification submission for a determination of substantial equivalence;

(2) A brief discussion of the clinical tests submitted, referenced, or relied on in the premarket notification submission for a determination of substantial equivalence. This discussion shall include, where applicable, a description of the subjects upon whom the device was tested, a discussion of the safety or effectiveness data obtained from the testing, with specific reference to adverse effects and complications, and any other information from the clinical testing relevant to a determination of substantial equivalence; and

(3) The conclusions drawn from the nonclinical and clinical tests that demonstrate that the device is as safe, as effective, and performs as well as or better than the legally marketed device identified in paragraph (a)(3) of this section.

(c) The summary should be in a separate section of the submission, beginning on a new page and ending on a page not shared with any other section of the premarket notification submission, and should be clearly identified as a "510(k) summary."

(d) Any other information reasonably deemed necessary by the agency.

§ 807.93 Content and format of a 510(k) statement.

(a)(1) A 510(k) statement submitted as part of a premarket notification shall state as follows:

I certify that, in my capacity as (the position held in company by person required to submit the premarket notification, preferably the official correspondent in the firm), of (company name), I will make available all information included in this premarket notification on safety and effectiveness within 30 days of request by any person if the device described in the premarket notification submission is determined to be substantially equivalent. The information I agree to make available will be a duplicate of the premarket notification submission, including any adverse safety and effectiveness information, but excluding all patient identifiers, and trade secret and confidential commercial information, as defined in 21 CFR 20.61.

(2) The statement in paragraph (a)(1) of this section should be signed by the certifier, made on a separate page of the premarket notification submission, and clearly identified as "510(k) statement."

(b) All requests for information included in paragraph (a) of this section shall be made in writing to the certifier, whose name will be published by FDA on the list of premarket notification submissions for which substantial equivalence of determinations have been made.

(c) The information provided to requestors will be a duplicate of the premarket notification submission, including any adverse information, but excluding all patient identifiers, and trade secret and confidential commercial information as defined in §20.61 of this chapter.

§ 807.94 Format of a class III certification.

(a) A class III certification submitted as part of a premarket notification shall state as follows:

I certify, in my capacity as (position held in company), of (company name), that I have conducted a reasonable search of all information known or otherwise available about the types and causes of safety or effectiveness problems that have been reported for the (type of device). I further certify that I am aware of the types of problems to which the (type of device) is susceptible and that, to the best of my knowledge, the following summary of the types and causes of safety or effectiveness problems about the (type of device) is complete and accurate.

(b) The statement in paragraph (a) of this section should be signed by the certifier, clearly identified as "class III certification," and included at the beginning of the section of the premarket notification submission that sets forth the class III summary.

§ 807.95 Confidentiality of information.

(a) The Food and Drug Administration will disclose publicly whether there exists a premarket notification submission under this part:

(1) Where the device is on the market, i.e., introduced or delivered for introduction into interstate commerce for commercial distribution;

(2) Where the person submitting the premarket notification submission has disclosed, through advertising or any other manner, his intent to market the device to scientists, market analysts, exporters, or other individuals who are not employees of, or paid consultants to, the establishment and who are not in an advertising or law firm pursuant to commercial arrangements with appropriate safeguards for secrecy; or

(3) Where the device is not on the market and the intent to market the device has not been so disclosed, except where the submission is subject to an exception under paragraph (b) or (c) of this section.

(b) The Food and Drug Administration will not disclose publicly the existence of a premarket notification submission for a device that is not on the market and where the intent to market the device has not been disclosed for 90 days from the date of receipt of the submission, if:

(1) The person submitting the premarket notification submission requests in the submission that the Food and Drug Administration hold as confidential commercial information the intent to market the device and submits a written certification to the Commissioner:

(i) That the person considers his intent to market the device to be confidential commercial information;

(ii) That neither the person nor, to the best of his knowledge, anyone else, has disclosed through advertising or any other manner, his intent to market the device to scientists, market analysts, exporters, or other individuals, except employees of, or paid consultants to, the establishment or individuals in an advertising or law firm pursuant to commercial arrangements with appropriate safeguards for secrecy;

(iii) That the person will immediately notify the Food and Drug Administration if he discloses the intent to market the device to anyone, except employees of, or paid consultants to, the establishment or individuals in an advertising or law firm pursuant to commercial arrangements for appropriate safeguards for secrecy;

(iv) That the person has taken precautions to protect the confidentiality of the intent to market the device; and

(v) That the person understands that the submission to the government of false information is prohibited by 18 U.S.C. 1001 and 21 U.S.C. 331(q); and

(2) The Commissioner agrees that the intent to market the device is confidential commercial information.

(c) Where the Commissioner determines that the person has complied with the procedures described in paragraph (b) of this section with respect to a device that is not on the market and where the intent to market the device has not been disclosed, and the Commissioner agrees that the intent to market the device is confidential commercial information, the Commissioner will not disclose the existence of the submission for 90 days from the date of its receipt by the agency. In addition, the Commissioner will continue not to disclose the existence of such a submission for the device for an additional time when any of the following occurs:

(1) The Commissioner requests in writing additional information regarding the device pursuant to § 807.87(h), in which case the Commissioner will not disclose the existence of the submission until 90 days after the Food and Drug Administration's receipt of a complete premarket notification submission;

(2) The Commissioner determines that the device intended to be introduced is a class III device and cannot be marketed without premarket approval or reclassification, in which case the Commissioner will not disclose the existence of the submission unless a petition for reclassification is submitted under section 513(f)(2) of the act and its existence can be disclosed under § 860.5(d) of this chapter; or

(3) The person has requested in the premarket notification submission that the Commissioner protect the confidentiality of the intent to market a device for more than 90 days from the date of receipt of the premarket notification submission by the Food and Drug Administration, and the Commissioner determines that the person has reason to believe that the actual introduction of the device to the market may take longer than 90 days, and the person agrees in a written certification to provide the Commissioner with written notification immediately if the device is put on the market or the intent to market is disclosed. In this case the Commissioner will not disclose the existence of the submission until the Food and Drug Administration's receipt of notification by the person that the device has been put on the market or that the intent to market the device has been disclosed.

(d) FDA will make a 510(k) summary of the safety and effectiveness data available to the public within 30 days of the issuance of a determination that the device is substantially equivalent to another device. Accordingly, even when a 510(k) submitter has complied with the conditions set forth in paragraphs (b) and (c) of this section, confidentiality for a premarket notification submission cannot be granted beyond 30 days after FDA issues a determination of equivalency.

§ 807.97 Misbranding by reference to premarket notification.

Submission of a premarket notification in accordance with this subpart, and a subsequent determination by the Commissioner that the device intended for introduction into commercial distribution is substantially equivalent to a device in commercial distribution before May 28, 1976, or is substantially equivalent to a device introduced into commercial distribution after May 28, 1976, that has subsequently been reclassified into class I or II, does not in any way denote official approval of the device. Any representation that creates an impression of official approval of a device because of complying with the premarket notification regulations is misleading and constitutes misbranding.

§ 807.100 FDA action on a premarket notification.

(a) After review of a premarket notification, FDA will:

(1) Issue an order declaring the device to be substantially equivalent to a legally marketed predicate device;

(2) Issue an order declaring the device to be not substantially equivalent to any legally marketed predicate device;

(3) Request additional information; or

(4) Advise the applicant that the premarket notification is not required. Until the applicant receives an order declaring a device substantially equivalent, the applicant may not proceed to market the device.

(b) FDA will determine that a device is substantially equivalent to a predicate device using the following criteria:

(1) The device has the same intended use as the predicate device; and

(2) The device:

(i) Has the same technological characteristics as the predicate device; or

(ii)(A) Has different technological characteristics, such as a significant change in the materials, design, energy source, or other features of the device from those of the predicate device;

(B) The data submitted establishes that the device is substantially equivalent to the predicate device and contains information, including clinical data if deemed necessary by the Commissioner, that demonstrates that the device is as safe and effective as a legally marketed device; and

(C) Does not raise different questions of safety and effectiveness than the predicate device.

(3) The predicate device has not been removed from the market at the initiative of the Commissioner of Food and Drugs or has not been determined to be misbranded or adulterated by a judicial order.

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