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(d) of this section, or an order denying describe the deficiencies in the applicaapproval of the application under tion and, where practical, will identify $814.118(a).

measures required to place the HDE in (b) Approval order. FDA will issue to approvable form. The applicant may the applicant an order approving an respond to the not approvable letter in HDE if none of the reasons in $814.118 the same manner as permitted for not for denying approval of the application approvable letters for PMA's under applies. FDA will approve an applica- $814.44(f), with the exception that if a tion on the basis of draft final labeling major HDE amendment is submitted, if the only deficiencies in the applica- the review period may be extended up tion concern editorial or similar minor to 75 days. deficiencies in the draft final labeling. (e) FDA will consider an HDE to have Such approval will be conditioned upon been withdrawn voluntarily if: the applicant incorporating the speci- (1) The applicant fails to respond in fied labeling changes exactly as di- writing to a written request for an rected and upon the applicant submit- amendment within 75 days after the ting to FDA a copy of the final printed date FDA issues such request; labeling before marketing. The notice (2) The applicant fails to respond in of approval of an HDE will be published

writing to an approvable or not approvin the FEDERAL REGISTER in accord- able letter within 75 days after the date ance with the rules and policies appli- FDA issues such letter; or cable to PMA's submitted under

(3) The applicant submits a written $814.20. Following the issuance of an notice to FDA that the HDE has been approval order, data and information

withdrawn. in the HDE file will be available for public disclosure in accordance with

[61 FR 33244, June 26, 1996, as amended at 63 $814.9(b) through (h), as applicable.

FR 59221, Nov. 3, 1998] (c) Approvable letter. FDA will send the applicant an approvable letter if

8814.118 Denial of approval or with

drawal of approval of an HDE. the application substantially meets the requirements of this subpart and the (a) FDA may deny approval or withagency believes it can approve the ap- draw approval of an application if the plication if specific additional informa- applicant fails to meet the requiretion is submitted or specific conditions

ments of section 520(m) of the act or of are agreed to by the applicant. The ap

this part, or of any condition of approvable letter will describe the infor- proval imposed by an IRB or by FDA, mation FDA requires to be provided by or any postapproval requirements imthe applicant or the conditions the ap

posed under $814.126. In addition, FDA plicant is required to meet to obtain may deny approval or withdraw apapproval. For example, FDA may re

proval of an application if, upon the quire as a condition to approval:

basis of the information submitted in (1) The submission of certain infor- the HDE or any other information bemation identified in the approvable let- fore the agency, FDA determines that: ter, e.g., final labeling;

(1) There is a lack of a showing of (2) Restrictions imposed on the de- reasonable assurance that the device is vice under section 520(e) of the act; safe under the conditions of use pre

(3) Postapproval requirements as de- scribed, recommended, or suggested in scribed in subpart E of this part; and the labeling thereof;

(4) An FDA inspection that finds the (2) The device is ineffective under the manufacturing facilities, methods, and conditions of prescribed, reccontrols in compliance with part 820 of ommended, or suggested in the labeling this chapter and, if applicable, that thereof; verifies records pertinent to the HDE. (3) The applicant has not dem

(d) Not approvable letter. FDA will onstrated that there is a reasonable send the applicant a not approvable basis from which to conclude that the letter if the agency believes that the probable benefit to health from the use application may not be approved for of the device outweighs the risk of inone or more of the reasons given in jury or illness, taking into account the $814.118. The not approvable letter will probable risks and benefits of currently


(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 ap

proval of an HDĖ. 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]

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) Anonclinical 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;

8814.122 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.

8814.124 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)

(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 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.


8814.126 Postapproval requirements

and reports. (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;

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

[blocks in formation]

820.50 Purchasing controls.

Subpart F-Identification and Traceability 820.60 Identification. 820.65 Traceability.

Subpart G-Production and Process

Controls 820.70 Production and process controls. 820.72 Inspection, measuring, and test

equipment. 820.75 Process validation.

Subpart H-Acceptance Activities

820.80 Receiving, in-process, and finished

device acceptance. 820.86 Acceptance status.

Subpart |--Noncontorming Product 820.90 Nonconforming product. Subpart 1-Corrective and Preventive


8820.1 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.

820.100 Corrective and preventive action.

Subpart K-Labeling and Packaging

Control 820.120 Device labeling. 820.130 Device packaging.

Subpart L-Handling, Storage, Distribution,

and Installation

820.140 Handling. 820.150 Storage. 820.160 Distribution.

(2) The provisions of this part shall do not conform to the requirements of be applicable to any finished device as section 520(f) of the act and this part defined in this part, intended for and that the devices manufactured at human use, that is manufactured, im- that facility are adulterated under secported, or offered for import in any tion 501(h) of the act. State or Territory of the United (e) Exemptions of variances. (1) Any States, the District of Columbia, or the person who wishes to petition for an Commonwealth of Puerto Rico.

exemption or variance from any device (3) In this regulation the term quality system requirement is subject "where appropriate" is used several to the requirements of section 520(1)(2) times. When a requirement is qualified of the act. Petitions for an exemption by "where appropriate,” it is deemed or variance shall be submitted accordto be “appropriate" unless the manu- ing to the procedures set forth in $ 10.30 facturer can document justification of this chapter, the FDA's administraotherwise. A requirement is "appro- tive procedures. Guidance is available priate" if nonimplementation could from the Center for Devices and Radioreasonably be expected to result in the logical Health, Division of Small Manproduct not meeting its specified re- ufacturers Assistance (HFZ-220), 1350 quirements or the manufacturer not Piccard Dr., Rockville, MD 20850, being able to carry out any necessary U.S.A., telephone 1-800-638–2041 or 1corrective action.

301-443-6597, FAX 301-443-8818. (b) Limitations. The quality system (2) FDA may initiate and grant a regulation in this part supplements variance from any device quality sysregulations in other parts of this chap- tem requirement when the agency deter except where explicitly stated oth- termines that such variance is in the erwise. In the event that it is impos- best interest of the public health. Such sible to comply with all applicable reg- variance will remain in effect only so ulations, both in this part and in other long as there remains a public health parts of this chapter, the regulations need for the device and the device specifically applicable to the device in would not likely be made sufficiently question shall supersede any other gen- available without the variance. erally applicable requirements. (c) Authority. Part 820 is established

[61 FR 52654, Oct. 7, 1996, as amended at 65 FR and issued under authority of sections

17136, Mar. 31, 2000; 65 FR 66636, Nov. 7, 2000) 501, 502, 510, 513, 514, 515, 518, 519, 520,

8820.3 Definitions. 522, 701, 704, 801, 803 of the act (21 U.S.C. 351, 352, 360, 3600, 3600, 360e, 360h, 360i, (a) Act means the Federal Food, 3600, 3601, 371, 374, 381, 383). The failure Drug, and Cosmetic Act, as amended to comply with any applicable provi

(secs. 201-903, 52 Stat. 1040 et seq., as sion in this part renders a device adul- amended (21 U.S.C. 321-394)). All definiterated under section 501(h) of the act.

tions in section 201 of the act shall Such a device, as well as any person re

apply to the regulations in this part. sponsible for the failure to comply, is (b) Complaint means any written, subject to regulatory action.

electronic, or oral communication that (d) Foreign manufacturers. If a manu- alleges deficiencies related to the idenfacturer who offers devices for import tity, quality, durability, reliability, into the United States refuses to per- safety, effectiveness, or performance of mit or allow the completion of a Food a device after it is released for disand Drug Administration (FDA) inspec- tribution. tion of the foreign facility for the pur- (c) Component means any raw matepose of determining compliance with rial, substance, piece, part, software, this part, it shall appear for purposes firmware, labeling, or assembly which of section 801(a) of the act, that the is intended to be included as part of the methods used in, and the facilities and finished, packaged, and labeled device. controls used for, the design, manufac- (d) Control number means any distincture, packaging, labeling, storage, in- tive symbols, such as a distinctive stallation, or servicing of any devices combination of letters or numbers, or produced at such facility that are of- both, from which the history of the fered for import into the United States manufacturing, packaging, labeling,

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