FDA Home Page | CDRH Home Page | Search | A-Z Index | ||
Please note: as of October 1, 2002, FDA charges fees for review of Premarket Notification 510(k)s and Premarket Approvals
Application Contents*NEW* Required Elements (§814.20) There is no preprinted form for a PMA Application. Unless an omission is justified by the applicant [§814.20(d)], a PMA must include all of the following:
The summary section must contain the following information: Indications for use. Give a general description of the disease
or condition that the device will diagnose, treat, prevent, cure, or
mitigate and include a description of the patient population for which
the device is intended. Tip: Include a statement such as "other commercially available devices" if similar class III products are available. Do not include any treatment practices or procedures that are considered investigational. Marketing history. Give a brief description of the foreign and U.S. marketing history, if any, of the device known to the applicant. At a minimum, include a list of all countries in which the device has been marketed and a list of all countries in which the device has been withdrawn from marketing for any reason related to the safety or effectiveness of the device. Tip: It would be appropriate to include dates of introduction into each country, information about the quantity of product distributed in each country, a brief description of any experience reporting mechanism, a summary of any adverse experiences reported, and information about any withdrawals for any reason related to the safety or effectiveness. Withdrawals because of poor sales or physician disfavor should not be included. A U.S. marketing history may occur if the device is marketed under 510(k) for a different intended use. The description must 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. Summary of studies. This section must contain a summary of the results of technical data (nonclinical and clinical studies) under §814.20(b)(6) and an abstract of any other data, information, or report described in the PMA under §814.20(b)(8)(ii). The summary must include a description of the objective of each study, a description of the experimental design of the study (or hypothesis tested), a brief discussion of how the data were collected and analyzed, and a brief description of the findings and conclusions, whether positive, negative or inconclusive. The summary must include a summary of nonclinical laboratory studies submitted in the application and a summary of the clinical investigations involving human subjects. The summary of the clinical investiations should include a discussion of subject selection and exclusion criteria, study population demographics, study period, safety and effectiveness data, adverse reactions and complications, patient discontinuation, device failures and replacements, tabulations of data from all individual subject reporting 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, contraindications and precautions for use of the device, and other information from the clinical investigations, as appropriate. Any investigation conducted under an IDE must be identified. Conclusions drawn from the studies. Discuss how the data and information in the application constitute valid scientific evidence within the meaning of 21 CFR 860.7, Determination of Safety and Effectiveness, and provide reasonable assurance that the device is safe and effective for its intended use. A concluding discussion must 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 that the applicant intends to conduct following approval of the PMA. Tip: The applicant`s summary section should objectively link the medical claim(s) for the device to the hypotheses tested and conclusions drawn from the findings of all studies and investigations. Biased presentation of the study data and inclusion of promotional claims are to be avoided. When preparing the summary section, the applicant should be able to detect and correct any accountability discrepancies, incomplete reporting and study design deficiencies which an in-depth scientific review would discover. A properly developed summary section by the applicant can serve as the basis for FDA`s Summary of Safety and Effectiveness Data and will facilitate the FDA and panel review process. A full and explicit account of the clinical investigations and supporting data is needed to meet the legal requirements imposed by the FD&C Act. For a more detailed discussion of how to design, document, and present a clinical investigation to demonstrate safety and effectiveness, see "Statistical Guidance for Clinical Trials for Non-diagnostic Medical Devices" .
Other information. Pertinent information already in FDA files
and specifically referred to by an applicant may be incorporated into
a PMA by reference. Information in a master file (see "Master Files"
http://www.fda.gov/cdrh/dsma/pmaman/appdxc.html#P7_2
) 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.
Omissions. If an applicant believes that certain required information under §814.20(b) is not applicable to the device and omits any such information from their PMA, the applicant must submit a statement that identifies the omitted information and justifies the omission. The statement must be submitted as a separate section in the PMA and identified in the table of contents. If FDA does not accept the justification for the omission, FDA will notify the applicant. Tip: An applicant may request a waiver for the manufacturing information to be submitted later in the application process. Any delayed submission of the manufacturing information may cause a delay in the Quality System inspection process. Updates. An applicant must periodically update its pending application with any new safety and effectiveness information learned about the device from ongoing or completed studies that may affect an evaluation of the safety and effectiveness of the device or that may affect the statement of contraindications, warnings, precautions, and adverse reactions in the draft labeling. The updated report must be consistent with the data-reporting provisions of the protocol. The applicant must submit three copies of any updated report and must include in the report the PMA number assigned by FDA. These updates are considered to be amendments to the pending PMA. The timeframe for review of a PMA will not be extended due to the submission of an update report unless the update is a major amendment [§814.37(c)(1)]. An applicant must submit these reports three months after the filing date, following receipt of an approvable letter, and at any other time as requested by FDA. Note: This periodic updating is limited to studies sponsored by the applicant or to which the applicant has reasonable access. Color additive. A color additive used in or on the device is subject to Part 721 of the FD&C Act and must be listed for such use by FDA. If the color additive has not previously been listed by FDA for such use, an applicant may request FDA to list the color additive by submitting a color additive petition under 21 CFR 71 to the Center for Food Safety and Applied Nutrition (CFSAN). Alternatively, the request may be submitted to CDRH as part of as the PMA. If the request is submitted in the PMA, three copies of the color additive petition information must be included, 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 Part 721 of the FD&C Act will not be approved until a color additive is listed by FDA for use in or on the device. See "Color Additives for Medical Devices" http://www.fda.gov/cdrh/dsma/pmaman/appdxe.html#P7_2 for further information. Premarket Submissions Coversheet The completion of this Premarket Submission Coversheet is voluntary and will not affect any Food and Drug Administration (FDA) decision concerning your submission, but will help FDA`s Center for Devices and Radiological Health process your submission more efficiently by placing administrative data elements in a consistent format for data entry purposes. The coversheet was developed to reduce the number of administrative deficiencies common in many submissions. The information provided should apply only to a single accompanying submission; please do not send cover sheets for any previous submissions. When submitting an amendment or supplement, identify the document number and type of submission, and then complete only the information which has changed since your most recent cover sheet relating to the same submission. The coversheet should be used only for submissions that are referenced in the coversheet. Premarket Submissions Coversheet An applicant`s cover letter should accurately identify the type of PMA submission, i.e., an original PMA, PMA supplement, PMA amendment to a pending PMA or PMA supplement, periodic report, etc. and include information needed for FDA tracking purposes. To expedite its processing, the following suggestions and formats have been prepared. General Suggestions
Suggested Formats The full format of the cover letter for an original PMA appears below. For other types of PMA submissions, only the subject section and opening sentence(s) are provided. In several instances, alternative opening statements are included to address specific situations. Original PMA Cover Letter [Date] Document Mail Center (HFZ-401) Center for Devices and Radiological Health Food and Drug Administration 9200 Corporate Blvd. Rockville, MD 20850 SUBJECT: Original PMA for [device trade name and model number if applicable] To Whom It May Concern: [Applicant`s name] is submitting this original premarket approval application for the [device trade name], [device generic name] intended for use in [indication for use]. Clinical studies of the above device were initiated on [date] and [were/were not] conducted under an approved investigational device exemption [give IDE number if a significant risk device]. [If applicable, include the FDA reference number for any premarket notification, reclassification petition, or color additive petition submitted for this device]. [Include a paragraph providing the name and address of each facility involved in the manufacture of the device and indicate whether the facility is prepared for an FDA inspection. If not prepared, provide an expected date when the facility will be ready for inspection. If a waiver of the QS information is requested, provide an anticipated date that the information will be provided.] If another document is incorporated by reference, e.g., a master file, please include the original letter of authorization as an attachment to this cover letter. The existence of this PMA and the data and other information that it contains are confidential, and the protection afforded to such confidential information by 18 USC 1905, 21 USC 331(j), 5 USC 552, and other applicable laws is hereby claimed. [Tip: confidentiality claims cannot be made unless the applicant has complied with the applicable requirements. If there are questions regarding this submission, [name] may be contacted at [give telephone number including area code]. Sincerely yours,
[signature] [Name and title of applicant`s representative] Amendment to Original PMA SUBJECT: Amendment to [original PMA or PMA supplement reference number] for [device trade name] Unsolicited submission of additional information [Applicant`s name] is submitting this amendment to its [premarket approval application] [original PMA reference number] for the [device trade name] to provide [identify the additional information being provided]. In order to facilitate FDA`s handling of PMA applications, the following recommendations are offered:
The following information should be submitted in separate volumes:
A PMA or PMA supplement, if applicable, is required by §814.20(b)(6)(ii) to include copies of individual subject report forms for each subject who died during a clinical investigation or who did not complete the investigation. Before submitting the PMA, the applicant should consult with the ODE reviewing division to determine the information to be included in these report forms, how many copies are required, and whether these report forms will be required for other subjects enrolled in the study (e.g., subjects experiencing specified adverse effects or complications). A PMA must be signed by the applicant or an authorized U.S. representative. If the applicant does not reside or have a place of business within the U.S., the PMA must be countersigned by an authorized representative who does. The applicant must also provide the representative`s name and address. Send 6 copies of an original PMA, clearly identified as such, to: Document Mail Center (HFZ-401) Summary of Safety and Effectiveness Data (§814.44) Overview The FD&C Act requires that FDA prepare a detailed summary of the safety and effectiveness data on which the approval or denial decision is based. Authority The Summary of Safety and Effectiveness Data (SSED) is a document mandated by 520(h)(1)(A) of the FD&C Act (the act). It is to be publicly available upon issuance of an order approving or denying approval of a premarket approval application (PMA). When required Approval/denial decisions for original PMA applications must include an SSED. An SSED is also prepared for submissions designated by CDRH as panel-track supplements. An abbreviated SSED is required for approval of a PMA based on a licensing agreement. The abbreviated SSED is acceptable because the scientific data on which the PMA relies were previously described in the SSED for the application which is being licensed. Purpose The SSED is an FDA document (originally submitted by the applicant and modified by FDA) which is intended to present a reasoned, objective, and balanced critique of the scientific evidence which served as the basis of the decision to approve or deny the PMA . The SSED documents that there was reasonable assurance of safety and effectiveness for the device as labeled based on the nonclinical and clinical studies described in the PMA. The SSED is a summation of both the positive and negative aspects of the PMA. the scientific evidence. For a PMA to be approved, potential risks versus possible benefits assessment must favor this action. The SSED summarizes these judgments. SSED preparation Initially FDA intended drafting the publicly releasable SSED, which is based on the SSED the applicant is required to submit under 21 CFR 814.20. If FDA must substantially rewrite the applicant`s SSED, FDA will often go back to the applicant and request that they make another attempt at writing the publicly releasable SSED. Unfortunately, the applicant SSED too often differs from FDA`s objective, i.e., it contains only the positive aspects of the device, it contains marketing language, etc. Consequently, an edit-rewrite exercise often results. Since minor variations in SSED formats are possible, it is best to consult previously released SSEDs (preferably recent ones for similar devices) for guidance. Since the SSED deals with scientific/technical data and will be read by many non-professionals, it is best to keep the format clear by grouping study objective(s), study methods, results, interpretation(s), and conclusion(s) for each study or substudy. An overall statement/conclusion integrating the individual study outcomes in the light of safety and effectiveness and risk versus benefits and your conclusions can then be written. Level of comprehension The SSED should be written for the comprehension of a college graduate, but not necessarily a science graduate or professional in the device specific area. Medical and scientific terms should be used whenever needed, but it is preferred that simpler, generally recognized terminology be used (provided it can be used without suffering loss of meaning). Format for Summary of Safety and Effectiveness Data The following is the format of the summary of safety and effectiveness data prepared by FDA. PMA applicants can facilitate this step of the PMA process by following this format in preparing the summary of safety and effectiveness data required under §814.20(b)(3).
Tip: Include any information concerning actual or potential adverse effects that the device may have on health (e.g. if an implanted device, discuss the fate of the device in the body) Laboratory studies Study design Risk/benefit analysis The PMA Review Statistical Checklist lists the required elements of the statistical aspects of the PMA submission. This list is used to screen all PMA applications before in-depth review by the Division of Biostatistics. The absence of any of these elements may be sufficient to reject an in-depth statistical review. It is essential, therefore, that the applicant check to determine that the statistical reports in the submission are complete. Additional guidance on statistical evaluation of medical devices can be found in "Statistical Aspects of Submissions to FDA: A Medical Device Perspective." http://www.fda.gov/cdrh/osb/guidance/fod537.pdf (This guidance also includes "Observed Uses and Abuses of Statistical Procedures in Medical Device Submissions.") PMA Review Statistical Checklist The checklist referenced below is used by PMA reviewers to determine the completeness of a PMA and is a part of the Blue Book Memo, PMA Refuse to File Procedures 5/2/94 (P94-1). PMA applicants may also wish to use the checklist to assure the completeness of the application. Premarket Approval Application Filing Review Premarket Approval Application Filing Review Quality System Information for Certain Premarket Application Reviews Guidance for the Content of Premarket Submissions for Software Contained
in Medical Devices Off-The-Shelf Software Use in Medical Devices Statistical Aspects of Submissions to FDA: A Medical Device Perspective
(also includes as Appendix the article Observed Uses and Abuses of Statistical
Procedures in Medical Device Submissions PMA Review Statistical Checklist Master Files Updated 01/30/2008
|
CDRH Home Page | CDRH A-Z Index | Contact CDRH | Accessibility | Disclaimer
FDA Home Page | Search FDA Site | FDA A-Z Index | Contact FDA | HHS Home Page
Center for Devices and Radiological Health / CDRH