Source: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=814&showfr=1
Timestamp: 2018-12-12 23:14:39
Document Index: 178665390

Matched Legal Cases: ['arts 812', 'art 20', 'art 58', 'art 56', 'art 50', 'art 71', 'art 71', 'art 820', 'art 801', 'art 809', 'art 58', 'art 56', 'art 50', 'art 58', 'art 56', 'art 50', 'art 16', 'art 16', 'art 16', 'art 16']

(c) This part applies to any class III medical device, unless exempt under section 520(g) of the act, that:
(1) Was not on the market (introduced or delivered for introduction into commerce for commercial distribution) before May 28, 1976, and is not substantially equivalent to a device on the market before May 28, 1976, or to a device first marketed on, or after that date, which has been classified into class I or class II; or
(2) Is required to have an approved premarket approval application (PMA) or a declared completed product development protocol under a regulation issued under section 515(b) of the act; or
(3) Was regulated by FDA as a new drug or antibiotic drug before May 28, 1976, and therefore is governed by section 520(1) of the act.
(d) This part amends the conditions to approval for any PMA approved before the effective date of this part. Any condition to approval for an approved PMA that is inconsistent with this part is revoked. Any condition to approval for an approved PMA that is consistent with this part remains in effect.
[51 FR 26364, July 22, 1986, as amended at 79 FR 1740, Jan. 10, 2014]
The purpose of this part is to establish an efficient and thorough device review process--
(a) To facilitate the approval of PMA's for devices that have been shown to be safe and effective and that otherwise meet the statutory criteria for approval; and
(b) To ensure the disapproval of PMA's for devices that have not been shown to be safe and effective or that do not otherwise meet the statutory criteria for approval. This part shall be construed in light of these objectives.
(a) Act means the Federal Food, Drug, and Cosmetic Act (sections 201-902, 52 Stat. 1040 et seq., as amended (21 U.S.C. 321-392)).
(b) FDA means the Food and Drug Administration.
(c) IDE means an approved or considered approved investigational device exemption under section 520(g) of the act and parts 812 and 813.
(d) Master file means a reference source that a person submits to FDA. A master file may contain detailed information on a specific manufacturing facility, process, methodology, or component used in the manufacture, processing, or packaging of a medical device.
(e) PMA means any premarket approval application for a class III medical device, including all information submitted with or incorporated by reference therein. "PMA" includes a new drug application for a device under section 520(1) of the act.
(f) PMA amendment means information an applicant submits to FDA to modify a pending PMA or a pending PMA supplement.
(g) PMA supplement means a supplemental application to an approved PMA for approval of a change or modification in a class III medical device, including all information submitted with or incorporated by reference therein.
(h) Person includes any individual, partnership, corporation, association, scientific or academic establishment, Government agency, or organizational unit thereof, or any other legal entity.
(i) Statement of material fact means a representation that tends to show that the safety or effectiveness of a device is more probable than it would be in the absence of such a representation. A false affirmation or silence or an omission that would lead a reasonable person to draw a particular conclusion as to the safety or effectiveness of a device also may be a false statement of material fact, even if the statement was not intended by the person making it to be misleading or to have any probative effect.
(j) 30-day PMA supplement means a supplemental application to an approved PMA in accordance with 814.39(e).
(k) Reasonable probability means that it is more likely than not that an event will occur.
(l) Serious, adverse health consequences means any significant adverse experience, including those which may be either life-threatening or involve permanent or long term injuries, but excluding injuries that are nonlife-threatening and that are temporary and reasonably reversible.
(n) HUD (humanitarian use device ) means a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year.
(o) Newly acquired information means data, analyses, or other information not previously submitted to the agency, which may include (but are not limited to) data derived from new clinical studies, reports of adverse events, or new analyses of previously submitted data (e.g., meta-analyses) if the studies, events or analyses reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA.
(p) Human cell, tissue, or cellular or tissue-based product (HCT/P) regulated as a device means an HCT/P as defined in 1271.3(d) of this chapter that does not meet the criteria in 1271.10(a) and that is also regulated as a device.
(q) Unique device identifier (UDI) means an identifier that adequately identifies a device through its distribution and use by meeting the requirements of 830.20 of this chapter. A unique device identifier is composed of:
(r) Universal product code (UPC) means the product identifier used to identify an item sold at retail in the United States.
[51 FR 26364, July 22, 1986, as amended at 61 FR 15190, Apr. 5, 1996; 61 FR 33244, June 26, 1996; 73 FR 49610, Aug. 22, 2008; 78 FR 55821, Sept. 24, 2013; 79 FR 1740, Jan. 10, 2014; 82 FR 26349, June 7, 2017]
(a) A "PMA file" includes all data and information submitted with or incorporated by reference in the PMA, any IDE incorporated into the PMA, any PMA supplement, any report under 814.82, any master file, or any other related submission. Any record in the PMA file will be available for public disclosure in accordance with the provisions of this section and part 20. The confidentiality of information in a color additive petition submitted as part of a PMA is governed by 71.15.
(b) The existence of a PMA file may not be disclosed by FDA before an approval order is issued to the applicant unless it previously has been publicly disclosed or acknowledged.
(c) If the existence of a PMA file has not been publicly disclosed or acknowledged, data or information in the PMA file are not available for public disclosure.
(d)(1) If the existence of a PMA file has been publicly disclosed or acknowledged before an order approving, or an order denying approval of the PMA is issued, data or information contained in the file are not available for public disclosure before such order issues. FDA may, however, disclose a summary of portions of the safety and effectiveness data before an approval order or an order denying approval of the PMA issues if disclosure is relevant to public consideration of a specific pending issue.
(2) Notwithstanding paragraph (d)(1) of this section, FDA will make available to the public upon request the information in the IDE that was required to be filed in Docket Number 95S-0158 in the Division of Dockets Management (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857, for investigations involving an exception from informed consent under 50.24 of this chapter. Persons wishing to request this information shall submit a request under the Freedom of Information Act.
(e) Upon issuance of an order approving, or an order denying approval of any PMA, FDA will make available to the public the fact of the existence of the PMA and a detailed summary of information submitted to FDA respecting the safety and effectiveness of the device that is the subject of the PMA and that is the basis for the order.
(f) After FDA issues an order approving, or an order denying approval of any PMA, the following data and information in the PMA file are immediately available for public disclosure:
(1) All safety and effectiveness data and information previously disclosed to the public, as such disclosure is defined in 20.81.
(2) Any protocol for a test or study unless the protocol is shown to constitute trade secret or confidential commercial or financial information under 20.61.
(3) Any adverse reaction report, product experience report, consumer complaint, and other similar data and information, after deletion of:
(i) Any information that constitutes trade secret or confidential commercial or financial information under 20.61; and
(ii) Any personnel, medical, and similar information disclosure of which would constitute a clearly unwarranted invasion of personal privacy under 20.63; provided, however, that except for the information that constitutes trade secret or confidential commercial or financial information under 20.61, FDA will disclose to a patient who requests a report all the information in the report concerning that patient.
(4) A list of components previously disclosed to the public, as such disclosure is defined in 20.81.
(5) An assay method or other analytical method, unless it does not serve any regulatory purpose and is shown to fall within the exemption in 20.61 for trade secret or confidential commercial or financial information.
(6) All correspondence and written summaries of oral discussions relating to the PMA file, in accordance with the provisions of 20.103 and 20.104.
(g) All safety and effectiveness data and other information not previously disclosed to the public are available for public disclosure if any one of the following events occurs and the data and information do not constitute trade secret or confidential commercial or financial information under 20.61:
(1) The PMA has been abandoned. FDA will consider a PMA abandoned if:
(i)(A) The applicant fails to respond to a request for additional information within 180 days after the date FDA issues the request or
(B) Other circumstances indicate that further work is not being undertaken with respect to it, and
(ii) The applicant fails to communicate with FDA within 7 days after the date on which FDA notifies the applicant that the PMA appears to have been abandoned.
(2) An order denying approval of the PMA has issued, and all legal appeals have been exhausted.
(3) An order withdrawing approval of the PMA has issued, and all legal appeals have been exhausted.
(4) The device has been reclassified.
(5) The device has been found to be substantially equivalent to a class I or class II device.
(6) The PMA is considered voluntarily withdrawn under 814.44(g).
(h) The following data and information in a PMA file are not available for public disclosure unless they have been previously disclosed to the public, as such disclosure is defined in 20.81, or they relate to a device for which a PMA has been abandoned and they no longer represent a trade secret or confidential commercial or financial information as defined in 20.61:
(2) Production, sales, distribution, and similar data and information, except that any compilation of such data and information aggregated and prepared in a way that does not reveal data or information which are not available for public disclosure under this provision is available for public disclosure.
[51 FR 26364, July 22, 1986, as amended at 61 FR 51531, Oct. 2, 1996]
(a) Data to support PMA. If data from clinical investigations conducted outside the United States are submitted to support a PMA, the applicant shall comply with the provisions in 812.28 of this chapter, as applicable.
(b) As sole basis for marketing approval. A PMA based solely on foreign clinical data and otherwise meeting the criteria for approval under this part may be approved if:
(1) The foreign data are applicable to the U.S. population and U.S. medical practice;
(2) The studies have been performed by clinical investigators of recognized competence; and
(3) The data may be considered valid without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA can validate the data through an on-site inspection or other appropriate means.
(c) Consultation between FDA and applicants. Applicants are encouraged to meet with FDA officials in a "presubmission" meeting when approval based solely on foreign data will be sought.
[51 FR 26364, July 22, 1986; 51 FR 40415, Nov. 7, 1986, as amended at 51 FR 43344, Dec. 2, 1986; 83 FR 7387, Feb. 21, 2018]
(a) The applicant or an authorized representative shall sign the PMA. If the applicant does not reside or have a place of business within the United States, the PMA shall be countersigned by an authorized representative residing or maintaining a place of business in the United States and shall identify the representative's name and address.
(b) Unless the applicant justifies an omission in accordance with paragraph (d) of this section, a PMA shall include:
(2) A table of contents that specifies the volume and page number for each item referred to in the table. A PMA shall include separate sections on nonclinical laboratory studies and on clinical investigations involving human subjects. A PMA shall be submitted in six copies each bound in one or more numbered volumes of reasonable size. The applicant shall include information that it believes to be trade secret or confidential commercial or financial information in all copies of the PMA and identify in at least one copy the information that it believes to be trade secret or confidential commercial or financial information.
(3) A summary in sufficient detail that the reader may gain a general understanding of the data and information in the application. The summary shall contain the following information:
(i) Indications for use. A general description of the disease or condition the device will diagnose, treat, prevent, cure, or mitigate, including a description of the patient population for which the device is intended.
(ii) Device description. An explanation of how the device functions, the basic scientific concepts that form the basis for the device, and the significant physical and performance characteristics of the device. A brief description of the manufacturing process should be included if it will significantly enhance the reader's understanding of the device. The generic name of the device as well as any proprietary name or trade name should be included.
(iii) Alternative practices and procedures. A description of existing alternative practices or procedures for diagnosing, treating, preventing, curing, or mitigating the disease or condition for which the device is intended.
(iv) Marketing history. A brief description of the foreign and U.S. marketing history, if any, of the device, including a list of all countries in which the device has been marketed and a list of all countries in which the device has been withdrawn from marketing for any reason related to the safety or effectiveness of the device. The description shall include the history of the marketing of the device by the applicant and, if known, the history of the marketing of the device by any other person.
(v) Summary of studies. An abstract of any information or report described in the PMA under paragraph (b)(8)(ii) of this section and a summary of the results of technical data submitted under paragraph (b)(6) of this section. Such summary shall include a description of the objective of the study, a description of the experimental design of the study, a brief description of how the data were collected and analyzed, and a brief description of the results, whether positive, negative, or inconclusive. This section shall include the following:
(A) A summary of the nonclinical laboratory studies submitted in the application;
(B) A summary of the clinical investigations involving human subjects submitted in the application including a discussion of subject selection and exclusion criteria, study population, study period, safety and effectiveness data, adverse reactions and complications, patient discontinuation, patient complaints, device failures and replacements, results of statistical analyses of the clinical investigations, contraindications and precautions for use of the device, and other information from the clinical investigations as appropriate (any investigation conducted under an IDE shall be identified as such).
(vi) Conclusions drawn from the studies. A discussion demonstrating that the data and information in the application constitute valid scientific evidence within the meaning of 860.7 and provide reasonable assurance that the device is safe and effective for its intended use. A concluding discussion shall present benefit and risk considerations related to the device including a discussion of any adverse effects of the device on health and any proposed additional studies or surveillance the applicant intends to conduct following approval of the PMA.
(4) A complete description of:
(i) The device, including pictorial representations;
(ii) Each of the functional components or ingredients of the device if the device consists of more than one physical component or ingredient;
(iii) The properties of the device relevant to the diagnosis, treatment, prevention, cure, or mitigation of a disease or condition;
(iv) The principles of operation of the device; and
(v) The methods used in, and the facilities and controls used for, the manufacture, processing, packing, storage, and, where appropriate, installation of the device, in sufficient detail so that a person generally familiar with current good manufacturing practice can make a knowledgeable judgment about the quality control used in the manufacture of the device.
(5) Reference to any performance standard under section 514 of the act or under section 534 of Subchapter C--Electronic Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for Health and Safety Act of 1968) in effect or proposed at the time of the submission and to any voluntary standard that is relevant to any aspect of the safety or effectiveness of the device and that is known to or that should reasonably be known to the applicant. The applicant shall--
(6) The following technical sections which shall contain data and information in sufficient detail to permit FDA to determine whether to approve or deny approval of the application:
(i) A section containing results of the nonclinical laboratory studies with the device including microbiological, toxicological, immunological, biocompatibility, stress, wear, shelf life, and other laboratory or animal tests as appropriate. Information on nonclinical laboratory studies shall include a statement that each such study was conducted in compliance with part 58, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
(ii) A section containing results of the clinical investigations involving human subjects with the device including clinical protocols, number of investigators and subjects per investigator, subject selection and exclusion criteria, study population, study period, safety and effectiveness data, adverse reactions and complications, patient discontinuation, patient complaints, device failures and replacements, tabulations of data from all individual subject report forms and copies of such forms for each subject who died during a clinical investigation or who did not complete the investigation, results of statistical analyses of the clinical investigations, device failures and replacements, contraindications and precautions for use of the device, and any other appropriate information from the clinical investigations. Any investigation conducted under an IDE shall be identified as such. Information on clinical investigations involving human subjects shall include the following:
(A) For clinical investigations conducted in the United States, a statement with respect to each investigation that it either was conducted in compliance with the institutional review board regulations in part 56 of this chapter, or was not subject to the regulations under 56.104 or 56.105, and that it was conducted in compliance with the informed consent regulations in part 50 of this chapter; or if the investigation was not conducted in compliance with those regulations, a brief statement of the reason for the noncompliance. Failure or inability to comply with these requirements does not justify failure to provide information on a relevant clinical investigation.
(C) For clinical investigations conducted outside the United States that are intended to support the PMA, the requirements under 812.28 of this chapter apply. If any such investigation was not conducted in accordance with good clinical practice (GCP) as described in 812.28(a), include either a waiver request in accordance with 812.28(c) or a brief statement of the reason for not conducting the investigation in accordance with GCP and a description of steps taken to ensure that the data and results are credible and accurate and that the rights, safety, and well-being of subjects have been adequately protected. Failure or inability to comply with these requirements does not justify failure to provide information on a relevant clinical investigation.
(7) For a PMA supported solely by data from one investigation, a justification showing that data and other information from a single investigator are sufficient to demonstrate the safety and effectiveness of the device and to ensure reproducibility of test results.
(8)(i) A bibliography of all published reports not submitted under paragraph (b)(6) of this section, whether adverse or supportive, known to or that should reasonably be known to the applicant and that concern the safety or effectiveness of the device.
(ii) An identification, discussion, and analysis of any other data, information, or report relevant to an evaluation of the safety and effectiveness of the device known to or that should reasonably be known to the applicant from any source, foreign or domestic, including information derived from investigations other than those proposed in the application and from commercial marketing experience.
(iii) Copies of such published reports or unpublished information in the possession of or reasonably obtainable by the applicant if an FDA advisory committee or FDA requests.
(9) One or more samples of the device and its components, if requested by FDA. If it is impractical to submit a requested sample of the device, the applicant shall name the location at which FDA may examine and test one or more devices.
(10) Copies of all proposed labeling for the device. Such labeling may include, e.g., instructions for installation and any information, literature, or advertising that constitutes labeling under section 201(m) of the act.
(11) An environmental assessment under 25.20(n) prepared in the applicable format in 25.40, unless the action qualifies for exclusion under 25.30 or 25.34. If the applicant believes that the action qualifies for exclusion, the PMA shall under 25.15(a) and (d) provide information that establishes to FDA's satisfaction that the action requested is included within the excluded category and meets the criteria for the applicable exclusion.
(14) Such other information as FDA may request. If necessary, FDA will obtain the concurrence of the appropriate FDA advisory committee before requesting additional information.
(c) Pertinent information in FDA files specifically referred to by an applicant may be incorporated into a PMA by reference. Information in a master file or other information submitted to FDA by a person other than the applicant will not be considered part of a PMA unless such reference is authorized in writing by the person who submitted the information or the master file. If a master file is not referenced within 5 years after the date that it is submitted to FDA, FDA will return the master file to the person who submitted it.
(d) If the applicant believes that certain information required under paragraph (b) of this section to be in a PMA is not applicable to the device that is the subject of the PMA, and omits any such information from its PMA, the applicant shall submit a statement that identifies the omitted information and justifies the omission. The statement shall be submitted as a separate section in the PMA and identified in the table of contents. If the justification for the omission is not accepted by the agency, FDA will so notify the applicant.
(e) The applicant shall periodically update its pending application with new safety and effectiveness information learned about the device from ongoing or completed studies that may reasonably affect an evaluation of the safety or effectiveness of the device or that may reasonably affect the statement of contraindications, warnings, precautions, and adverse reactions in the draft labeling. The update report shall be consistent with the data reporting provisions of the protocol. The applicant shall submit three copies of any update report and shall include in the report the number assigned by FDA to the PMA. These updates are considered to be amendments to the PMA. The time frame for review of a PMA will not be extended due to the submission of an update report unless the update is a major amendment under 814.37(c)(1). The applicant shall submit these reports--
(1) 3 months after the filing date,
(2) Following receipt of an approvable letter, and
(3) At any other time as requested by FDA.
(f) If a color additive subject to section 721 of the act is used in or on the device and has not previously been listed for such use, then, in lieu of submitting a color additive petition under part 71, at the option of the applicant, the information required to be submitted under part 71 may be submitted as part of the PMA. When submitted as part of the PMA, the information shall be submitted in three copies each bound in one or more numbered volumes of reasonable size. A PMA for a device that contains a color additive that is subject to section 721 of the act will not be approved until the color additive is listed for use in or on the device.
(g) Additional information on FDA policies and procedures, as well as links to PMA guidance documents, is available on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketApprovalPMA/default.htm.
(h) If you are sending a PMA, PMA amendment, PMA supplement, or correspondence with respect to a PMA, you must send the submission to the appropriate address as follows:
[51 FR 26364, July 22, 1986; 51 FR 40415, Nov. 7, 1986, as amended at 51 FR 43344, Dec. 2, 1986; 55 FR 11169, Mar. 27, 1990; 62 FR 40600, July 29, 1997; 63 FR 5253, Feb. 2, 1998; 65 FR 17137, Mar. 31, 2000; 65 FR 56480, Sept. 19, 2000; 67 FR 9587, Mar. 4, 2002; 71 FR 42048, July 25, 2006; 72 FR 17399, Apr. 9, 2007; 73 FR 34859, June 19, 2008; 74 FR 14478, Mar. 31, 2009; 75 FR 20915, Apr. 22, 2010; 78 FR 18233, Mar. 26, 2013; 79 FR 1740, Jan. 10, 2014; 80 FR 18094, Apr. 3, 2015; 83 FR 7387, Feb. 21, 2018]
(a) An applicant may amend a pending PMA or PMA supplement to revise existing information or provide additional information.
(c) A PMA amendment submitted to FDA shall include the PMA or PMA supplement number assigned to the original submission and, if submitted on the applicant's own initiative, the reason for submitting the amendment. FDA may extend the time required for its review of the PMA, or PMA supplement, as follows:
(1) If the applicant on its own initiative or at FDA's request submits a major PMA amendment (e.g., an amendment that contains significant new data from a previously unreported study, significant updated data from a previously reported study, detailed new analyses of previously submitted data, or significant required information previously omitted), the review period may be extended up to 180 days.
(2) If an applicant declines to submit a major amendment requested by FDA, the review period may be extended for the number of days that elapse between the date of such request and the date that FDA receives the written response declining to submit the requested amendment.
(d) An applicant may on its own initiative withdraw a PMA or PMA supplement. If FDA requests an applicant to submit a PMA amendment and a written response to FDA's request is not received within 180 days of the date of the request, FDA will consider the pending PMA or PMA supplement to be withdrawn voluntarily by the applicant.
(e) An applicant may resubmit a PMA or PMA supplement after withdrawing it or after it is considered withdrawn under paragraph (d) of this section, or after FDA has refused to accept it for filing, or has denied approval of the PMA or PMA supplement. A resubmitted PMA or PMA supplement shall comply with the requirements of 814.20 or 814.39, respectively, and shall include the PMA number assigned to the original submission and the applicant's reasons for resubmission of the PMA or PMA supplement.
(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)(1) 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.
(i) Information concerning pediatric uses as required under 814.20(b)(13).
(ii) If information concerning the device that is the subject of the supplement was previously submitted under 814.20(b)(13) or under this section in a previous supplement, that information may be included by referencing a previous application or submission that contains the information. However, if additional information required under 814.20(b)(13) has become readily available to the applicant since the previous submission, the applicant must submit that information as part of the supplement.
(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:
(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; 79 FR 1740, Jan. 10, 2014]
(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 of the Center for Biologics Evaluation and Research, or the Director of the Center for Drug Evaluation and Research, as applicable. 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.
[51 FR 26364, July 22, 1986, as amended at 63 FR 5254, Feb. 2, 1998; 73 FR 49942, Aug. 25, 2008]
(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 of this chapter or informed consent regulations in part 50 of this chapter or GCP referenced in 814.15(a) and described in 812.28(a) of this chapter, was not conducted in compliance with those regulations such that the rights or safety of human subjects were not adequately protected or the supporting data were determined to be otherwise unreliable.
(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)(4) 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's address listed on the Agency's Web site at http://www.fda.gov.
(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
(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; 73 FR 34859, June 19, 2008; 76 FR 31470, June 1, 2011; 79 FR 68115, Nov. 14, 2014; 83 FR 7387, Feb. 21, 2018]
(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 of this chapter or informed consent regulations in part 50 of this chapter or GCP referenced in 814.15(a) and described in 812.28(a) of this chapter, was not conducted in compliance with those regulations such that the rights or safety of human subjects were not adequately protected or the supporting data were determined to be otherwise unreliable.
(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.
[51 FR 26364, July 22, 1986, as amended at 83 FR 7387, Feb. 21, 2018]
(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 PMA.
(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 public health, the agency may, in accordance with 16.60(h) of this chapter, waive, suspend, or modify any part 16 procedure pursuant to 10.19 of this chapter.
(3) FDA shall deem the PMA holder's failure to request a hearing within the timeframe specified by FDA in the notice of opportunity for hearing to be a waiver.
(c) Temporary suspension order. If the PMA holder does not request a regulatory hearing or if, after the hearing, and after consideration of the administrative record of the hearing, FDA determines that there is a reasonable probability that the continued distribution of a device under an approved PMA would cause serious, adverse health consequences or death, the agency shall, under the authority of section 515(e)(3) of the act, issue an order to the PMA holder temporarily suspending approval of the PMA.
(d) Permanent withdrawal of approval of the PMA. If FDA issues an order temporarily suspending approval of a PMA, the agency shall proceed expeditiously, but within 60 days, to hold a hearing on whether to permanently withdraw approval of the PMA in accordance with section 515(e)(1) of the act and the procedures set out in 814.46.
[61 FR 15190, Apr. 5, 1996]
(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.
[51 FR 26364, July 22, 1986, as amended at 51 FR 43344, Dec. 2, 1986; 67 FR 9587, Mar. 4, 2002; 72 FR 73602, Dec. 28, 2007; 78 FR 58822, Sept. 24, 2013]
(i) In lieu of the summaries, conclusions, and results from clinical investigations required under 814.20(b)(3)(v)(B), (b)(3)(vi), and the introductory text of (b)(6)(ii), the applicant shall include the summaries, conclusions, and results of all clinical experience or investigations (whether adverse or supportive) reasonably obtainable by the applicant that are relevant to an assessment of the risks and probable benefits of the device and to the extent the applicant includes data from clinical investigations, the applicant shall include the statements described in 814.20(b)(6)(ii)(A) and (B) with respect to clinical investigations conducted in the United States and the information described in 814.20(b)(6)(ii)(C) with respect to clinical investigations conducted outside the United States; and
[61 FR 33244, June 26, 1996, as amended at 63 FR 59220, Nov. 3, 1998; 73 FR 49942, Aug. 25, 2008; 75 FR 20915, Apr. 22, 2010; 79 FR 1740, Jan. 10, 2014; 80 FR 18094, Apr. 3, 2015; 83 FR 7388, Feb. 21, 2018]