`
`Code of Federal Regulations
`Title 21. Food and Drugs
`Chapter I. Food and Drug Administration, Department of Health and Human Services (Refs & Annos)
`Subchapter H. Medical Devices
`Part 814. Premarket Approval of Medical Devices (Refs & Annos)
`Subpart B. Premarket Approval Application (Pma)
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`21 C.F.R. § 814.20
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`§ 814.20 Application.
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`Effective: April 3, 2015
`Currentness
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`(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.
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`(b) Unless the applicant justifies an omission in accordance with paragraph (d) of this section, a PMA shall include:
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`(1) The name and address of the applicant.
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`(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.
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`(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:
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`(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.
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`(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.
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`(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.
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` © 2015 Thomson Reuters. No claim to original U.S. Government Works.
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`1
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`Ex. 2030-0001
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`§ 814.20 Application., 21 C.F.R. § 814.20
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`(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.
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`(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:
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`(A) A summary of the nonclinical laboratory studies submitted in the application;
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`(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).
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`(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.
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`(4) A complete description of:
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`(i) The device, including pictorial representations;
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`(ii) Each of the functional components or ingredients of the device if the device consists of more than one physical
`component or ingredient;
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`(iii) The properties of the device relevant to the diagnosis, treatment, prevention, cure, or mitigation of a disease or
`condition;
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`(iv) The principles of operation of the device; and
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`(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
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` © 2015 Thomson Reuters. No claim to original U.S. Government Works.
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`2
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`Ex. 2030-0002
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`§ 814.20 Application., 21 C.F.R. § 814.20
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`manufacturing practice can make a knowledgeable judgment about the quality control used in the manufacture of the
`device.
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`(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—
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`(i) Provide adequate information to demonstrate how the device meets, or justify any deviation from, any performance
`standard established 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),
`and
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`(ii) Explain any deviation from a voluntary standard.
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`(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:
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`(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.
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`(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:
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`(A) A statement with respect to each study that it either was conducted in compliance with the institutional review
`board regulations in part 56, 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; or if the study was not conducted in compliance with
`those regulations, a brief statement of the reason for the noncompliance.
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`(B) A statement that each study was conducted in compliance with part 812 or part 813 concerning sponsors of clinical
`investigations and clinical investigators, or if the study was not conducted in compliance with those regulations, a
`brief statement of the reason for the noncompliance.
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` © 2015 Thomson Reuters. No claim to original U.S. Government Works.
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`3
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`Ex. 2030-0003
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`§ 814.20 Application., 21 C.F.R. § 814.20
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`(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.
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`(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.
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`(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.
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`(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.
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`(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.
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`(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.
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`(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.
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`(12) A financial certification or disclosure statement or both as required by part 54 of this chapter.
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`(13) Information concerning uses in pediatric patients. The application must include the following information, if readily
`available:
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`(i) A description of any pediatric subpopulations (neonates, infants, children, adolescents) that suffer from the disease or
`condition that the device is intended to treat, diagnose, or cure; and
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`(ii) The number of affected pediatric patients.
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`(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.
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` © 2015 Thomson Reuters. No claim to original U.S. Government Works.
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`4
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`Ex. 2030-0004
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`§ 814.20 Application., 21 C.F.R. § 814.20
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`(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.
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`(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.
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`(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—
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`(1) 3 months after the filing date,
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`(2) Following receipt of an approvable letter, and
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`(3) At any other time as requested by FDA.
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`(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.
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`(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.
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`(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:
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` © 2015 Thomson Reuters. No claim to original U.S. Government Works.
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`5
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`Ex. 2030-0005
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`§ 814.20 Application., 21 C.F.R. § 814.20
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`(1) For devices regulated by the Center for Devices and Radiological Health, Food and Drug Administration, Center for
`Devices and Radiological Health, Document Mail Center, 10903 New Hampshire Ave., Bldg. 66, rm. G609, Silver Spring,
`MD 20993–0002.
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`(2) For devices regulated by the Center for Biologics Evaluation and Research, send it to: Food and Drug Administration,
`Center for Biologics Evaluation and Research, Document Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm.
`G112, Silver Spring, MD 20993–0002.
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`(3) For devices regulated by the Center for Drug Evaluation and Research, send it to: Central Document Control Room,
`Center for Drug Evaluation and Research, Food and Drug Administration, 5901–B Ammendale Rd., Beltsville, MD 20705–
`1266.
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`Credits
`[51 FR 40415, Nov. 7, 1986; 51 FR 43344, Dec. 2, 1986; 55 FR 11169, March 27, 1990; 62 FR 40600, July 29, 1997; 63 FR
`5253, Feb. 2, 1998; 65 FR 17137, March 31, 2000; 65 FR 56480, Sept. 19, 2000; 67 FR 9587, March 4, 2002; 71 FR 42048,
`July 25, 2006; 72 FR 17399, April 9, 2007; 73 FR 34859, June 19, 2008; 74 FR 14478, March 31, 2009; 75 FR 16351, April
`1, 2010; 75 FR 20915, April 22, 2010; 75 FR 41986, July 20, 2010; 78 FR 18233, March 26, 2013; 79 FR 1740, Jan. 10, 2014;
`80 FR 18094, April 3, 2015]
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`SOURCE: 51 FR 26364, July 22, 1986; 51 FR 43344, Dec. 2, 1986; 54 FR 39641, Sept. 27, 1989; 61 FR 51531, Nov. 1, 1996;
`62 FR 51520, Oct. 1, 1997, unless otherwise noted.
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`AUTHORITY: 21 U.S.C. 351, 352, 353, 360, 360c–360j, 371, 372, 373, 374, 375, 379, 379e, 381.
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`Notes of Decisions (116)
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`Current through Dec. 3, 2015; 80 FR 75638.
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`End of Document
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`© 2015 Thomson Reuters. No claim to original U.S. Government Works.
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` © 2015 Thomson Reuters. No claim to original U.S. Government Works.
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`6
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`Ex. 2030-0006