(a) After FDA's approval of a PMA, an applicant shall submit a PMA supplement for review and approval by FDA before making a change affecting the safety or effectiveness of the device for which the applicant has an approved PMA, unless the change is of a type for which FDA, under paragraph (e) of this section, has advised that an alternate submission is permitted or is of a type which, under section 515(d)(6)(A) of the act and paragraph (f) of this section, does not require a PMA supplement under this paragraph. While the burden for determining whether a supplement is required is primarily on the PMA holder, changes for which an applicant shall submit a PMA supplement include, but are not limited to, the following types of changes if they affect the safety or effectiveness of the device:
(1) New indications for use of the device.
(2) Labeling changes.
(3) The use of a different facility or establishment to manufacture, process, or package the device.
(4) Changes in sterilization procedures.
(5) Changes in packaging.
(6) Changes in the performance or design specifications, circuits, components, ingredients, principle of operation, or physical layout of the device.
(7) Extension of the expiration date of the device based on data obtained under a new or revised stability or sterility testing protocol that has not been approved by FDA. If the protocol has been approved, the change shall be reported to FDA under paragraph (b) of this section.
(b) An applicant may make a change in a device after FDA's approval of a PMA for the device without submitting a PMA supplement if the change does not affect the device's safety or effectiveness and the change is reported to FDA in postapproval periodic reports required as a condition to approval of the device, e.g., an editorial change in labeling which does not affect the safety or effectiveness of the device.
(c) All procedures and actions that apply to an application under 814.20 also apply to PMA supplements except that the information required in a supplement is limited to that needed to support the change. A summary under 814.20(b)(3) is required for only a supplement submitted for new indications for use of the device, significant changes in the performance or design specifications, circuits, components, ingredients, principles of operation, or physical layout of the device, or when otherwise required by FDA. The applicant shall submit three copies of a PMA supplement and shall include information relevant to the proposed changes in the device. A PMA supplement shall include a separate section that identifies each change for which approval is being requested and explains the reason for each such change. The applicant shall submit additional copies and additional information if requested by FDA. The time frames for review of, and FDA action on, a PMA supplement are the same as those provided in 814.40 for a PMA.
(d)(1) After FDA approves a PMA, any change described in paragraph (d)(2) of this section to reflect newly acquired information that enhances the safety of the device or the safety in the use of the device may be placed into effect by the applicant prior to the receipt under 814.17 of a written FDA order approving the PMA supplement provided that:
(i) The PMA supplement and its mailing cover are plainly marked "Special PMA Supplement--Changes Being Effected";
(ii) The PMA supplement provides a full explanation of the basis for the changes;
(iii) The applicant has received acknowledgement from FDA of receipt of the supplement; and
(iv) The PMA supplement specifically identifies the date that such changes are being effected.
(2) The following changes are permitted by paragraph (d)(1) of this section:
(i) Labeling changes that add or strengthen a contraindication, warning, precaution, or information about an adverse reaction for which there is reasonable evidence of a causal association.
(ii) Labeling changes that add or strengthen an instruction that is intended to enhance the safe use of the device.
(iii) Labeling changes that delete misleading, false, or unsupported indications.
(iv) Changes in quality controls or manufacturing process that add a new specification or test method, or otherwise provide additional assurance of purity, identity, strength, or reliability of the device.
(e)(1) FDA will identify a change to a device for which an applicant has an approved PMA and for which a PMA supplement under paragraph (a) is not required. FDA will identify such a change in an advisory opinion under 10.85, if the change applies to a generic type of device, or in correspondence to the applicant, if the change applies only to the applicant's device. FDA will require that a change for which a PMA supplement under paragraph (a) is not required be reported to FDA in:
(i) A periodic report under 814.84 or
(ii) A 30-day PMA supplement under this paragraph.
(2) 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, informs 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 be deemed approved 30 days after receipt.
(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.
(g) The submission and grant of a written request for an exception or alternative under 801.128 or 809.11 of this chapter satisfies the requirement in paragraph (a) of this section.
[51 FR 26364, July 22, 1986, as amended at 51 FR 43344, Dec. 2, 1986; 63 FR 54044, Oct. 8, 1998; 67 FR 9587, Mar. 4, 2002; 69 FR 11313, Mar. 10, 2004; 72 FR 73602, Dec. 28, 2007; 73 FR 49610, Aug. 22, 2008]