of approval will be published in the FEDERAL REGISTER and will state that a detailed summary of information respecting the safety and effectiveness of the device which was the basis for the order approving the PMA, including information about any adverse effects of the device on health, has been placed on public display and that copies are available upon request. When a notice of approval is published, data and information in the PMA file will be available for public disclosure in accordance with §814.9.

(e) FDA will send the applicant an approvable letter if the application substantially meets the requirements of this part and the agency believes it can approve the application if specific additional information is submitted or specific conditions are agreed to by the applicant.

(1) 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:

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

(ii) An FDA inspection that finds the manufacturing facilities, methods, and controls in compliance with Part 820 and, if applicable, that verifies records pertinent to the PMA;

(iii) Restrictions imposed on the device under section 515(d)(1)(B)(ii) or 520(e) of the act;

(iv) Postapproval requirements as described in Subpart E of this part.

(2) In response to an approvable letter the applicant may:

(i) Amend the PMA as requested in the approvable letter; or

(ii) Consider the approvable letter to be a denial of approval of the PMA under §814.45 and request administrative review under section 515(d)(3) of the act by filing a petition in the form of a petition for reconsideration under § 10.33; or

(iii) Withdraw the PMA.

(f) 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 §814.45(a). The not approvable

letter will describe the deficiencies in the application, including each applicable ground for denial under section 515(d)(2) (A) (E) of the act, and, where practical, will identify measures required to place the PMA in approvable form. In response to a not approvable letter, the applicant may:

(1) Amend the PMA as requested in the not approvable letter (such an amendment will be considered a major amendment under §814.37(c)(1)); or

(2) Consider the not approvable letter to be a denial of approval of the PMA under §814.45 and request administrative review under section 515(d)(3) of the act by filing a petition in the form of a petition for reconsideration under §10.33; or

(3) Withdraw the PMA.

(g) FDA will consider a PMA to have been withdrawn voluntarily if:

(1) The applicant fails to respond in writing to a written request for an amendment within 180 days after the date FDA issues such request;

(2) The applicant fails to respond in writing to an approvable or not approvable letter within 180 days after the date FDA issues such letter; or

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

[51 FR 26364, July 22, 1986, as amended at 57 FR 58403, Dec. 10, 1992]

§814.45 Denial of approval of a PMA.

(a) FDA may issue an order denying approval of a PMA if the applicant fails to follow the requirements of this part or if, upon the basis of the information submitted in the PMA or any other information before the agency, FDA determines that any of the grounds for denying approval of a PMA specified in section 515(d)(2) (A)–(E) of the act applies. In addition, FDA may deny approval of a PMA for any of the following reasons:

(1) The PMA contains a false statement of material fact;

(2) The device's proposed labeling does not comply with the requirements in Part 801 or Part 809;

(3) The applicant does not permit an authorized FDA employee an opportunity to inspect at a reasonable time and in a reasonable manner the facilities, controls, and to have access to

and to copy and verify all records pertinent to the application;

(4) A nonclinical laboratory study that is described in the PMA 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 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; or

(5) Any clinical investigation involving human subjects described in the PMA, subject to the institutional review board regulations in Part 56 or informed consent regulations in Part 50, was not conducted in compliance with those regulations such that the rights or safety of human subjects were not adequately protected.

(b) FDA will issue any order denying approval of the PMA in accordance with §814.17. The order will inform the applicant of the deficiencies in the PMA, including each applicable ground for denial under section 515(d)(2) of the act and the regulations under this part, and, where practical, will identify measures required to place the PMA in approvable form. The order will include a notice of an opportunity to request review under section 515(d)(3) of the act.

(c) FDA will use the criteria specified in §860.7 to determine the safety and effectiveness of a device in deciding whether to approve or deny approval of a PMA. FDA may use information other than that submitted by the applicant in making such determination.

(d) FDA will give the public notice of an order denying approval of the PMA. The notice will be published in the FEDERAL REGISTER and will state that a detailed summary of information respecting the safety and effectiveness of the device, including information about any adverse effects of the device on health, has been placed on public display and that copies are available upon request. When a notice of denial of approval is made publicly available, data and information in the PMA file

will be available for public disclosure in accordance with §814.9.

(e) FDA will issue an order denying approval of a PMA 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 section 515(d)(2) of the act still applies; or

(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.

§814.46 Withdrawal of approval of a PMA.

(a) FDA may issue an order withdrawing approval of a PMA if, from any information available to the agency, FDA determines that:

(1) Any of the grounds under section 515(e)(1) (A)-(G) of the act applies.

(2) Any postapproval requirement imposed by the PMA approval order or by regulation has not been met.

(3) A nonclinical laboratory study that is described in the PMA 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 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.

(4) Any clinical investigation involving human subjects described in the PMA, subject to the institutional review board regulations in Part 56 or informed consent regulations in Part 50, was not conducted in compliance with those regulations such that the rights or safety of human subjects were not adequately protected.

(b)(1) FDA may seek advice on scientific matters from any appropriate FDA advisory committee in deciding whether to withdraw approval of a PMA.

(2) FDA may use information other than that submitted by the applicant

in deciding whether to withdraw approval of a PMA.

(c) Before issuing an order withdrawing approval of a PMA, FDA will issue the holder of the approved application a notice of opportunity for an informal hearing under Part 16.

(d) If the applicant does not request a hearing or if after the Part 16 hearing is held the agency decides to proceed with the withdrawal, FDA will issue to the holder of the approved application an order withdrawing approval of the application. The order will be issued under §814.17, will state each ground for withdrawing approval, and will include a notice of an opportunity for administrative review under section 515(e)(2) of the act.

(e) FDA will give the public notice of an order withdrawing approval of a PMA. The notice will be published in the FEDERAL REGISTER and will state that a detailed summary of information respecting the safety and effectiveness of the device, including information about any adverse effects of the device on health, has been placed on public display and that copies are available upon request. When a notice of withdrawal of approval is published, data and information in the PMA file will be available for public disclosure in accordance with §814.9.

Subpart D-Administrative Review (Reserved)

Subpart E-Postapproval
Requirements

$814.80 General.

A device may not be manufactured, packaged, stored, labeled, distributed, or advertised in a manner that is inconsistent with any conditions to approval specified in the PMA approval order for the device.

(814.82 Postapproval requirements.

(a) FDA may impose postapproval requirements in a PMA approval order or by regulation at the time of approval of the PMA or by regulation subsequent to approval. Postapproval requirements may include as a condition to approval of the device:

(1) Restriction of the sale, distribution, or use of the device as provided by section 515(d)(1)(B)(ii) or 520(e) of the act.

(2) Continuing evaluation and periodic reporting on the safety, effectiveness, and reliability of the device for its intended use. FDA will state in the PMA approval order the reason or purpose for such requirement and the number of patients to be evaluated and the reports required to be submitted.

(3) Prominent display in the labeling of a device and in the advertising of any restricted device of warnings, hazards, or precautions important for the device's safe and effective use, including patient information, e.g., information provided to the patient on alternative modes of therapy and on risks and benefits associated with the use of the device.

(4) Inclusion of identification codes on the device or its labeling, or in the case of an implant, on cards given to patients if necessary to protect the public health.

(5) Maintenance of records that will enable the applicant to submit to FDA information needed to trace patients if such information is necessary to protect the public health. Under section 519(a)(4) of the act, FDA will require that the identity of any patient be disclosed in records maintained under this paragraph only to the extent required for the medical welfare of the individual, to determine the safety or effectiveness of the device, or to verify a record, report, or information submitted to the agency.

(6) Maintenance of records for specified periods of time and organization and indexing of records into identifiable files to enable FDA to determine whether there is reasonable assurance of the continued safety and effectiveness of the device.

(7) Submission to FDA at intervals specified in the approval order of periodic reports containing the information required by §814.84(b).

(8) Batch testing of the device. (9) Such other requirements as FDA determines are necessary to provide reasonable assurance, or continued reasonable assurance, of the safety and effectiveness of the device.

(b) An applicant shall grant to FDA access to any records and reports required under the provisions of this part, and shall permit authorized FDA employees to copy and verify such records and reports and to inspect at a reasonable time and in a reasonable manner all manufacturing facilities to verify that the device is being manufactured, stored, labeled, and shipped under approved conditions.

(c) Failure to comply with any postapproval requirement constitutes a ground for withdrawal of approval of a PMA.

(Approved by the Office of Management and Budget under control number 0910-0231)

[51 FR 26364, July 22, 1986, as amended at 51 FR 43344, Dec. 2, 1986]

$814.84 Reports.

(a) The holder of an approved PMA shall comply with the requirements of Part 803 and with any other requirements applicable to the device by other regulations in this subchapter or by order approving the device.

(b) Unless FDA specifies otherwise, any periodic report shall:

(1) Identify changes described in §814.39(a) and changes required to be reported to FDA under § 814.39(b).

(2) Contain a summary and bibliography of the following information not previously submitted as part of the PMA:

(i) Unpublished reports of data from any clinical investigations or nonclinical laboratory studies involving the device or related devices and known to or that reasonably should be known to the applicant.

(ii) Reports in the scientific literature concerning the device and known to or that reasonably should be known to the applicant. If, after reviewing the summary and bibliography, FDA concludes that the agency needs a copy of the unpublished or published reports, FDA will notify the applicant that copies of such reports shall be submitted.

(Approved by the Office of Management and Budget under control number 0910-0231)

[51 FR 26364, July 22, 1986, as amended at 51 FR 43344, Dec. 2, 1986]

The regulation set forth in this part describes current good manufacturing practices for methods used in, and the facilities and controls used for, the manufacture, packing, storage, and installation of all finished devices intended for human use. The regulation is intended to assure that such devices will be safe and effective and otherwise in compliance with the Federal Food, Drug, and Cosmetic Act. Part 820 establishes basic requirements applicable to finished devices, including additional requirements for critical devices. This regulation is not intended to apply to manufacturers of components or parts of finished devices, but such manufacturers are encouraged to use appropriate provisions of this reguElation as guidelines. Manufacturers of human blood and blood components are not subject to this part, but are subject to Part 606 of this chapter.

(a) Authority. This Part 820 is established and promulgated under authority of sections 501, 502, 518, 519, 520(f), and 701(a) of the act (21 U.S.C. 351, 352, 360h, 3601, 360j(f), and 371(a)). The failure to comply with any applicable provisions in Part 820 in the manufacture, packing, storage, or installation of a device renders the device adulterated under section 501(h) of the act. Such a device, as well as the person responsible for the failure to comply, is subject to regulatory action.

(b) Limitations. The current good manufacturing practice regulation in

Part 820 supplements regulations in other parts of this chapter except where explicitly stated otherwise. In the event it is impossible to comply with 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 regulations.

(c) Applicability. The provisions of Part 820 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.

(d) Exemptions or variances. Any person who wishes to petition for an exemption or variance from any device good manufacturing practice 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 Food and Drug Administration's administrative procedures. Guidance is available from the Center for Devices and Radiological Health, Division of Compliance Programs, Manufacturing Quality Assurance Branch (HFZ-332), 1390 Piccard Dr., Rockville, MD 20850; telephone 301427-1128.

[43 FR 31508, July 21, 1978, as amended at 44 FR 75628, Dec. 21, 1979; 53 FR 11253, Apr. 6, 1988; 55 FR 11169, Mar. 27, 1990]

§ 820.3 Definitions.

(a) Act means the Federal Food, Drug, and Cosmetic Act, as amended (secs. 201-902, 52 Stat. 1040 et seq., as amended (21 U.S.C. 321–392)).

(b) Audit means a documented activity performed in accordance with written procedures on a periodic basis to verify, by examination and evaluation of objective evidence, compliance with those elements of the quality assurance program under review. "Audit" does not include surveillance or inspection activities performed for the purpose of conducting a quality assurance program or undertaking complaint investigations or failure analyses of a device.

(c) Component means any material, substance, piece, part, or assembly used during device manufacture which