(d) of this section, or an order denying approval of the application under § 814.118(a).

(b) Approval order. FDA will issue to the applicant an order approving an HDE if none of the reasons in §814.118 for denying approval of the application applies. FDA will approve an application on the basis of draft final labeling if the only deficiencies in the application concern editorial or similar minor deficiencies in the draft final labeling. Such approval will be conditioned upon the applicant incorporating the specified labeling changes exactly as directed and upon the applicant submitting to FDA a copy of the final printed labeling before marketing. The notice of approval of an HDE will be published in the FEDERAL REGISTER in accordance with the rules and policies applicable to PMA's submitted under § 814.20. Following the issuance of an approval order, data and information in the HDE file will be available for public disclosure in accordance with § 814.9(b) through (h), as applicable.

(c) Approvable letter. FDA will send the applicant an approvable letter if the application substantially meets the requirements of this subpart and the agency believes it can approve the application if specific additional information is submitted or specific conditions are agreed to by the applicant. The approvable letter will describe the information FDA requires to be provided by the applicant or the conditions the applicant is required to meet to obtain approval. For example, FDA may require as a condition to approval:

(1) The submission of certain information identified in the approvable letter, e.g., final labeling;

(2) Restrictions imposed on the device under section 520(e) of the act;

(3) Postapproval requirements as described in subpart E of this part; and

(4) An FDA inspection that finds the manufacturing facilities, methods, and controls in compliance with part 820 of this chapter and, if applicable, that verifies records pertinent to the HDE.

(d) Not approvable letter. FDA will send the applicant a not approvable letter if the agency believes that the application may not be approved for one or more of the reasons given in § 814.118. The not approvable letter will

describe the deficiencies in the application and, where practical, will identify measures required to place the HDE in approvable form. The applicant may respond to the not approvable letter in the same manner as permitted for not approvable letters for PMA's under §814.44(f), with the exception that if a major HDE amendment is submitted, the review period may be extended up to 75 days.

(e) FDA will consider an HDE to have been withdrawn voluntarily if:

(1) The applicant fails to respond in writing to a written request for an amendment within 75 days after the date FDA issues such request;

(2) The applicant fails to respond in writing to an approvable or not approvable letter within 75 days after the date FDA issues such letter; or

(3) The applicant submits a written notice to FDA that the HDE has been withdrawn.

[61 FR 33244, June 26, 1996, as amended at 63 FR 59221, Nov. 3, 1998]

§ 814.118 Denial of approval or withdrawal of approval of an HDE.

(a) FDA may deny approval or withdraw approval of an application if the applicant fails to meet the requirements of section 520(m) of the act or of this part, or of any condition of approval imposed by an IRB or by FDA, or any postapproval requirements imposed under §814.126. In addition, FDA may deny approval or withdraw approval of an application if, upon the basis of the information submitted in the HDE or any other information before the agency, FDA determines that:

(1) There is a lack of a showing of reasonable assurance that the device is safe under the conditions of use prescribed, recommended, or suggested in the labeling thereof;

(2) The device is ineffective under the conditions of use prescribed, recommended, or suggested in the labeling thereof;

(3) The applicant has not demonstrated that there is a reasonable basis from which to conclude that the probable benefit to health from the use of the device outweighs the risk of injury or illness, taking into account the probable risks and benefits of currently

available devices or alternative forms of treatment;

(4) The application or a report submitted by or on behalf of the applicant contains an untrue statement of material fact, or omits material information;

(5) The device's labeling does not comply with the requirements in part 801 or part 809 of this chapter;

(6) A nonclinical laboratory study that is described in the HDE and that is essential to show that the device is safe for use under the conditions prescribed, recommended, or suggested in its proposed labeling, was not conducted in compliance with the good laboratory practice regulations in part 58 of this chapter and no reason for the noncompliance is provided or, if it is, the differences between the practices used in conducting the study and the good laboratory practice regulations do not support the validity of the study;

(7) Any clinical investigation involving human subjects described in the HDE, subject to the institutional review board regulations in part 56 of this chapter or the informed consent regulations in part 50 of this chapter, was not conducted in compliance with those regulations such that the rights or safety of human subjects were not adequately protected;

(8) The applicant does not permit an authorized FDA employee an opportunity to inspect at a reasonable time and in a reasonable manner the facilities and controls, and to have access to and to copy and verify all records pertinent to the application; or

(9) The device's HUD designation should be revoked in accordance with § 814.102(c).

(b) If FDA issues an order denying approval of an application, the agency will comply with the same notice and disclosure provisions required for PMA's under §814.45(b) and (d), as applicable.

(c) FDA will issue an order denying approval of an HDE after an approvable or not approvable letter has been sent and the applicant:

(1) Submits a requested amendment but any ground for denying approval of the application under §814.118(a) still applies;

(2) Notifies FDA in writing that the requested amendment will not be submitted; or

(3) Petitions for review under section 515(d)(3) of the act by filing a petition in the form of a petition for reconsideration under § 10.33 of this chapter.

(d) Before issuing an order withdrawing approval of an HDE, FDA will provide the applicant with notice and an opportunity for a hearing as required for PMA's under §814.46(c) and (d), and will provide the public with notice in accordance with §814.46(e), as applicable.

[61 FR 33244, June 26, 1996, as amended at 63 FR 59221, Nov. 3, 1998]

§ 814.120 Temporary suspension of approval of an HDĚ.

An HDE or HDE supplement may be temporarily suspended for the same reasons and in the same manner as prescribed for PMA's in §814.47.

[63 FR 59221, Nov. 3, 1998]

§ 814.122 Confidentiality of data and

information.

(a) Requirement for disclosure. The "HDE file" includes all data and information submitted with or referenced in the HDE, any IDE incorporated into the HDE, any HDE amendment or supplement, any report submitted under §814.126, any master file, or any other related submission. Any record in the HDE file will be available for public disclosure in accordance with the provisions of this section and part 20 of this chapter.

(b) Extent of disclosure. Disclosure by FDA of the existence and contents of an HDE file shall be subject to the same rules that pertain to PMA's under §814.9(b) through (h), as applicable.

§ 814.124 Institutional Review Board

requirements.

(a) IRB approval. The HDE holder is responsible for ensuring that a HUD approved under this subpart is administered only in facilities having an Institutional Review Board (IRB) constituted and acting pursuant to part 56 of this chapter, including continuing review of use of the device. In addition. a HUD may be administered only if

such use has been approved by the IRB located at the facility or by a similarly constituted IRB that has agreed to oversee such use and to which the local IRB has deferred in a letter to the HDE holder, signed by the IRB chair or an authorized designee. If, however, a physician in an emergency situation determines that approval from an IRB cannot be obtained in time to prevent serious harm or death to a patient, a HUD may be administered without prior approval by the IRB located at the facility or by a similarly constituted IRB that has agreed to oversee such use. In such an emergency situation, the physician shall, within 5 days after the use of the device, provide written notification to the chairman of the IRB of such use. Such written notification shall include the identification of the patient involved, the date on which the device was used, and the reason for the use.

(b) Withdrawal of IRB approval. A holder of an approved HDE shall notify FDA of any withdrawal of approval for the use of a HUD by a reviewing IRB within 5 working days after being notified of the withdrawal of approval.

[61 FR 33244, June 26, 1996, as amended at 63 FR 59221, Nov. 3, 1998]

(a) An HDE approved under this subpart H shall be subject to the postapproval requirements and reports set forth under subpart E of this part, as applicable, with the exception of § 814.82(a)(7). In addition, medical device reports submitted to FDA in compliance with the requirements of part 803 of this chapter shall also be submitted to the IRB of record.

(b) In addition to the reports identified in paragraph (a) of this section, the holder of an approved HDE shall prepare and submit the following complete, accurate, and timely reports:

(1) Periodic reports. An HDE applicant is required to submit reports in accordance with the approval order. Unless FDA specifies otherwise, any periodic report shall include:

(i) An update of the information required under §814.102(a) in a separately bound volume;

(ii) An update of the information required under § 814.104(b)(2), (b)(3), and (b)(5);

(iii) The number of devices that have been shipped or sold since initial marketing approval under this subpart H and, if the number shipped or sold exceeds 4,000, an explanation and estimate of the number of devices used per patient. If a single device is used on multiple patients, the applicant shall submit an estimate of the number of patients treated or diagnosed using the device together with an explanation of the basis for the estimate;

(iv) Information describing the applicant's clinical experience with the device since the HDE was initially approved. This information shall include safety information that is known or reasonably should be known to the applicant, medical device reports made under part 8dd of this chapter, any data generated from the postmarketing studies, and information (whether published or unpublished) that is known or reasonably expected to be known by the applicant that may affect an evaluation of the safety of the device or that may affect the statement of contraindications, warnings, precautions, and adverse reactions in the device's labeling; and

(v) A summary of any changes made to the device in accordance with supplements submitted under §814.108. If information provided in the periodic reports, or any other information in the possession of FDA, gives the agency reason to believe that a device raises public health concerns or that the criteria for exemption are no longer met, the agency may require the HDE holder to submit additional information to demonstrate continued compliance with the HDE requirements.

(2) Other. An HDE holder shall maintain records of the names and addresses of the facilities to which the HUD has been shipped, correspondence with reviewing IRB's, as well as any other information requested by a reviewing IRB or FDA. Such records shall be maintained in accordance with the HDE approval order.

[61 FR 33244, June 26, 1996, as amended at 63 FR 59221, Nov. 3, 1998]

820.170 Installation.

Subpart M-Records

820.180 General requirements. 820.181 Device master record. 820.184 Device history record. 820.186 Quality system record. 820.198 Complaint files.

Subpart N-Servicing

820.200 Servicing.

Subpart O-Statistical Techniques

820.250 Statistical techniques.

AUTHORITY: 21 U.S.C. 351, 352, 360, 360c, 360d, 360e, 360h, 3601, 360j, 3601, 371, 374, 381, 383.

SOURCE: 61 FR 52654, Oct. 7, 1996, unless otherwise noted.

Subpart A-General Provisions § 820.1 Scope.

(a) Applicability. (1) Current good manufacturing practice (CGMP) requirements are set forth in this quality system regulation. The requirements in this part govern the methods used in, and the facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished devices intended for human use. The requirements in this part are intended to ensure that finished devices will be safe and effective and otherwise in compliance with the Federal Food, Drug, and Cosmetic Act (the act). This part establishes basic requirements applicable to manufacturers of finished medical devices. If a manufacturer engages in only some operations subject to the requirements in this part, and not in others, that manufacturer need only comply with those requirements applicable to the operations in which it is engaged. With respect to class I devices, design controls apply only to those devices listed in § 820.30(a)(2). This regulation does not apply to manufacturers of components or parts of finished devices, but such manufacturers are encouraged to use appropriate provisions of this regulation as guidance. Manufacturers of human blood and blood components are not subject to this part, but are subject to part 606 of this chapter.

(2) The provisions of this part shall be applicable to any finished device as defined in this part, intended for human use, that is manufactured, imported, or offered for import in any State or Territory of the United States, the District of Columbia, or the Commonwealth of Puerto Rico.

(3) In this regulation the term "where appropriate" is used several times. When a requirement is qualified by "where appropriate," it is deemed to be "appropriate" unless the manufacturer can document justification otherwise. A requirement is "appropriate" if nonimplementation could reasonably be expected to result in the product not meeting its specified requirements or the manufacturer not being able to carry out any necessary corrective action.

(b) Limitations. The quality system regulation in this part supplements regulations in other parts of this chapter except where explicitly stated otherwise. In the event that it is impossible to comply with all applicable regulations, both in this part and in other parts of this chapter, the regulations specifically applicable to the device in question shall supersede any other generally applicable requirements.

(c) Authority. Part 820 is established and issued under authority of sections 501, 502, 510, 513, 514, 515, 518, 519, 520, 522, 701, 704, 801, 803 of the act (21 U.S.C. 351, 352, 360, 360c, 360d, 360e, 360h, 360i, 360j, 3601, 371, 374, 381, 383). The failure to comply with any applicable provision in this part renders a device adulterated under section 501(h) of the act. Such a device, as well as any person responsible for the failure to comply, is subject to regulatory action.

(d) Foreign manufacturers. If a manufacturer who offers devices for import into the United States refuses to permit or allow the completion of a Food and Drug Administration (FDA) inspection of the foreign facility for the purpose of determining compliance with this part, it shall appear for purposes of section 801(a) of the act, that the methods used in, and the facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, or servicing of any devices produced at such facility that are offered for import into the United States

do not conform to the requirements of section 520(f) of the act and this part and that the devices manufactured at that facility are adulterated under section 501(h) of the act.

(e) Exemptions or variances. (1) Any person who wishes to petition for an exemption or variance from any device quality system requirement is subject to the requirements of section 520(f)(2) of the act. Petitions for an exemption or variance shall be submitted according to the procedures set forth in § 10.30 of this chapter, the FDA's administrative procedures. Guidance is available from the Center for Devices and Radiological Health, Division of Small Manufacturers Assistance (HFZ-220), 1350 Piccard Dr., Rockville, MD 20850, U.S.A., telephone 1-800-638-2041 or 1301-443-6597, FAX 301-443-8818.

(2) FDA may initiate and grant a variance from any device quality system requirement when the agency determines that such variance is in the best interest of the public health. Such variance will remain in effect only so long as there remains a public health need for the device and the device would not likely be made sufficiently available without the variance.

[61 FR 52654, Oct. 7, 1996, as amended at 65 FR 17136, Mar. 31, 2000; 65 FR 66636, Nov. 7, 2000] § 820.3 Definitions.

(a) Act means the Federal Food, Drug, and Cosmetic Act, as amended (secs. 201-903, 52 Stat. 1040 et seq., as amended (21 U.S.C. 321-394)). All definitions in section 201 of the act shall apply to the regulations in this part.

(b) Complaint means any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is released for distribution.

(c) Component means any raw material, substance, piece, part, software, firmware, labeling, or assembly which is intended to be included as part of the finished, packaged, and labeled device.

(d) Control number means any distinctive symbols, such as a distinctive combination of letters or numbers, or both, from which the history of the manufacturing, packaging, labeling,