(1) The labeling of the device complies with the requirements of § 813.5 (a) and (b) and bears the following additional statement: CAUTION-DEVICE FOR INVESTIGATIONAL USE ONLY IN LABORATORY ANIMALS (2) The person who ships the device under this subpart uses due diligence to assure that the consignee is regularly engaged in conducting tests in animals used only for laboratory research, or similar for in vitro or other mechanical tests or tests that do not involve use of human subjects and that the shipment of the investigational device will actually be used only in such tests. (3) The person who ships the device under this subpart maintains adequate records showing the name and address of the consignee to whom the device is shipped, date, quantity, and batch or code mark of each shipment for a period of 2 years after such shipment and, upon the request of a properly authorized employee of the Department at reasonable times, make such records available for inspection and copying or submits such records to the Food and Drug Administration. (b) This subpart does not apply to any use of an investigational device that involves use of human subjects. [42 FR 58889, Nov. 11, 1977, as amended at 53 FR 11253, Apr. 6, 1988] § 813.170 Termination of exemption. (a) The commissioner shall terminate an exemption under this subpart if he makes either of the following findings: (1) The person shipping an investigational device under this subpart has failed to comply with any of the conditions for the exemption under this subpart. (2) Any of the grounds for withdrawal of an investigational device exemption under § 813.35 apply. (b) The Commissioner shall notify the sponsor of the termination of an exemption under this subpart with a full statement of the reasons for such termination and shall afford an opportunity for a regulatory hearing under (b) References in this part to regulatory sections of the Code of Federal Regulations are to Chapter I of Title 21, unless otherwise noted. (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. (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). § 814.9 Confidentiality of data and information in a premarket approval application (PMA) file. (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 disclo sure. (d) 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. (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: (1) Manufacturing methods or processes, including quality control procedures. (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. (3) Quantitative or semiquantitative formulas. § 814.15 Research conducted outside the United States. (a) A study conducted outside the United States submitted in support of a PMA and conducted under an IDE shall comply with Part 812. A study conducted outside the United States submitted in support of a PMA and not conducted under an IDE shall comply with the provisions in paragraph (b) or (c) of this section, as applicable. (b) Research begun on or after effective date. FDA will accept studies submitted in support of a PMA which have been conducted outside the United States and begun on or after November 19, 1986, if the data are valid and the investigator has conducted the studies in conformance with the "Declaration of Helsinki" or the laws and regulations of the country in which the research is conducted, whichever accords greater protection to the human subjects. If the standards of the country are used, the applicant shall state in detail any differences between those standards and the "Declaration of Helsinki” and explain why they offer greater protection to the human subjects. (c) Research begun before effective date. FDA will accept studies submitted in support of a PMA which have been conducted outside the United States and begun before November 19, 1986, if FDA is satisfied that the data are scientifically valid and that the rights, safety, and welfare of human subjects have not been violated. (d) 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 onsite inspection or other appropriate means. (e) 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. (Approved by the Office of Management and Budget under control no. 0910-0231) [51 FR 26364, July 22, 1986; 51 FR 40415, Nov. 7, 1986, as amended at 51 FR 43344, Dec. 2, 1986] § 814.17 Service of orders. Orders issued under this part will be served in person by a designated officer or employee of FDA on, or by registered mail to, the applicant or the designated agent at the applicant's or designated agent's last known address in FDA's records. § 814.19 Product development protocol (PDP). A class III device for which a product development protocol has been declared completed by FDA under this chapter will be considered to have an approved PMA. Subpart B-Premarket Approval § 814.20 Application. (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: (1) The name and address of the applicant. (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 de scription 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 |