(f) Under section 515(d) of the act, modifications to manufacturing procedures or methods of manufacture that affect the safety and effectiveness of a device subject to an approved PMA do not require submission of a PMA supplement under paragraph (a) of this section and are eligible to be the subject of a 30-day notice. A 30-day notice shall describe in detail the change, summarize the data or information supporting the change, and state that the change has been made in accordance with the requirements of part 820 of this chapter. The manufacturer may distribute the device 30 days after the date on which FDA receives the 30-day notice, unless FDA notifies the applicant within 30 days from receipt of the notice that the notice is not adequate. If the notice is not adequate, FDA shall inform the applicant in writing that a 135-day PMA supplement is needed and shall describe what further information or action is required for acceptance of such change. The number of days under review as a 30-day notice shall be deducted from the 135-day PMA supplement review period if the notice meets appropriate content requirements for a PMA supplement.

FDA will identify, in the advisory opinion or correspondence, the type of information that is to be included in the report or 30-day PMA supplement. If the change is required to be reported to FDA in a periodic report, the change may be made before it is reported to FDA. If the change is required to be reported in a 30-day PMA supplement, the change may be made 30 days after FDA files the 30-day PMA supplement unless FDA requires the PMA holder to provide additional information, forms the PMA holder that the supplement is not approvable, or disapproves the supplement. The 30-day PMA supplement shall follow the instructions in the correspondence or advisory opinion. Any 30-day PMA supplement that does not meet the requirements of the correspondence or advisory opinion will not be filed and, therefore, will not

in

be deemed approved 30 days after receipt.

(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; 63 FR 54044, Oct. 8, 1998]

Subpart C-FDA Action on a PMA

§ 814.40 Time frames for reviewing a PMA.

Within 180 days after receipt of an application that is accepted for filing and to which the applicant does not submit a major amendment, FDA will review the PMA and, after receiving the report and recommendation of the appropriate FDA advisory committee, send the applicant an approval order under §814.44(d), an approvable letter under § 814.44(e), a not approvable letter under §814.44(f), or an order denying approval under §814.45. The approvable letter and the not approvable letter will provide an opportunity for the applicant to amend or withdraw the application, or to consider the letter to be a denial of approval of the PMA under §814.45 and to request administrative review under section 515 (d)(3) and (g) of the act.

§ 814.42 Filing a PMA.

(a) The filing of an application means that FDA has made a threshold determination that the application is sufficiently complete to permit a substantive review. Within 45 days after a PMA is received by FDA, the agency will notify the applicant whether the application has been filed.

(b) If FDA does not find that any of the reasons in paragraph (e) of this section for refusing to file the PMA applies, the agency will file the PMA and will notify the applicant in writing of the filing. The notice will include the PMA reference number and the date FDA filed the PMA. The date of filing is the date that a PMA accepted for filing was received by the agency. The 180-day period for review of a PMA starts on the date of filing.

(c) If FDA refuses to file a PMA, the agency will notify the applicant of the reasons for the refusal. This notice will identify the deficiencies in the application that prevent filing and will include the PMA reference number.

(d) If FDA refuses to file the PMA, the applicant may:

(1) Resubmit the PMA with additional information necessary to comply with the requirements of section 515(c)(1) (A)-(G) of the act and §814.20. A resubmitted PMA shall include the PMA reference number of the original submission. If the resubmitted PMA is accepted for filing, the date of filing is the date FDA receives the resubmission;

(2) Request in writing within 10 working days of the date of receipt of the notice refusing to file the PMA, an informal conference with the Director of the Office of Device Evaluation to review FDA's decision not to file the PMA. FDA will hold the informal conference within 10 working days of its receipt of the request and will render its decision on filing within 5 working days after the informal conference. If, after the informal conference, FDA accepts the PMA for filing, the date of filing will be the date of the decision to accept the PMA for filing. If FDA does not reverse its decision not to file the PMA, the applicant may request reconsideration of the decision from the Director of the Center for Devices and Radiological Health. The Director's decision will constitute final administrative action for the purpose of judicial review.

(e) FDA may refuse to file a PMA if any of the following applies:

(1) The application is incomplete because it does not on its face contain all the information required under section 515(c)(1) (A)-(G) of the act;

(2) The PMA does not contain each of the items required under §814.20 and justification for omission of any item is inadequate;

(3) The applicant has a pending premarket notification under section 510(k) of the act with respect to the same device, and FDA has not determined whether the device falls within the scope of § 814.1(c).

(4) The PMA contains a false statement of material fact.

(5) The PMA is not accompanied by a statement of either certification or disclosure as required by part 54 of this chapter.

[51 FR 26364, July 22, 1986, as amended at 63 FR 5254, Feb. 2, 1998]

§ 814.44 Procedures for review of a PMA.

(a) FDA will begin substantive review of a PMA after the PMA is accepted for filing under §814.42. FDA may refer the PMA to a panel on its own initiative. and will do so upon request of an applicant, unless FDA determines that the application substantially duplicates information previously reviewed by a panel. If FDA refers an application to a panel, FDA will forward the PMA, or relevant portions thereof, to each member of the appropriate FDA panel for review. During the review process, FDA may communicate with the applicant as set forth under §814.37(b), or with a panel to respond to questions that may be posed by panel members or to provide additional information to the panel. FDA will maintain a record of all communications with the applicant and with the panel.

(b) The advisory committee shall submit a report to FDA which includes the committee's recommendation and the basis for such recommendation on the PMA. Before submission of this report, the committee shall hold a public meeting to review the PMA in accordance with part 14. This meeting may be held by a telephone conference under §14.22(g). The advisory committee report and recommendation may be in the form of a meeting transcript signed by the chairperson of the committee.

(c) FDA will complete its review of the PMA and the advisory committee report and recommendation and, within the later of 180 days from the date of filing of the PMA under §814.42 or the number of days after the date of filing as determined under §814.37(c), issue an approval order under paragraph (d) of this section, an approvable letter under paragraph (e) of this section, a not approvable letter under paragraph (f) of this section, or an order denying approval of the application under § 814.45(a).

(d)(1) FDA will issue to the applicant an order approving a PMA if none of

the reasons in §814.45 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. FDA will also give the public notice of the order, including notice of and opportunity for any interested persons to request review under section 515(d)(3) of the act. The notice of approval will be placed on FDA's home page on the Internet (http://www.fda.gov), and it 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, is available on the Internet and has been placed on public display, and that copies are available upon request. FDA will publish in the FEDERAL REGISTER after each quarter a list of the approvals announced in that quarter. 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.

(2) A request for copies of the current PMA approvals and denials document and for copies of summaries of safety and effectiveness shall be sent in writ

ing to the Dockets Management Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857.

(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:

an

(1) Amend the PMA as requested in the not approvable letter (such 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; 63 FR 4572, Jan. 30, 1998]

§ 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)(1) FDA will give the public notice of an order denying approval of the PMA. The notice will be placed on the FDA's home page on the Internet (http://www.fda.gov), and it 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, is available on the Internet and has been placed on public display and that copies are available upon request. FDA will publish in the FEDERAL REGISTER after each quarter a list of the denials announced in that quarter. 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.

(2) A request for copies of the current PMA approvals and denials document and copies of summaries of safety and effectiveness shall be sent in writing to the Freedom of Information Staff (HFI-35), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857.

(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.

[51 FR 26364, July 22, 1986, as amended at 63 FR 4572, Jan. 30, 1998]

§ 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.

§ 814.47 Temporary suspension of approval of a PMÅ.

(a) Scope. (1) This section describes the procedures that FDA will follow in exercising its authority under section 515(e)(3) of the act (21 U.S.C. 360e(e)(3)). This authority applies to the original PMA, as well as any PMA supplement(s), for a medical device.

(2) FDA will issue an order temporarily suspending approval of a PMA if FDA determines that there is a reasonable probability that continued distribution of the device would cause serious, adverse health consequences or death.

(b) Regulatory hearing. (1) If FDA believes that there is a reasonable probability that the continued distribution of a device subject to an approved PMA would cause serious, adverse health consequences or death, FDA may initiate and conduct a regulatory hearing to determine whether to issue an order temporarily suspending approval of the РМА.

(2) Any regulatory hearing to determine whether to issue an order temporarily suspending approval of a PMA shall be initiated and conducted by FDA pursuant to part 16 of this chapter. If FDA believes that immediate action to remove a dangerous device from the market is necessary to protect the