10606.1 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.

10606.2 Unless the applicant justifies an omission in accordance with § 10606.4, a PMA shall include:

1. (a) The name and address of the applicant;
2. (b) 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 (6) copies each bound in one (1) or more numbered volumes of reasonable size. The applicant shall include information that it believes to be a trade secret or confidential commercial or financial information in all copies of the PMA and identify in at least one (1) copy the information that it believes to be trade secret or confidential commercial or financial information;
3. (c) 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:
4. (1) 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;
5. (2) 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;
6. (3) 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;
7. (4) 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a list of all countries in which the device has been marketed and a list of all countries in which the device has been withdrawn from marketing for any reason related to the safety or effectiveness of the device.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;

(5) An abstract of any information or report described in the PMA and a summary of the results of technical data. 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 was 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; and

(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); and

(6) A discussion demonstrating that the data and information in the application constitute valid scientific evidence 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;

(d) A complete description of:

(1) The device, including pictorial representations;

(2) Each of the functional components or ingredients of the device if the device consists of more than one (1) physical component or ingredient;

(3) The properties of the device relevant to the diagnosis, treatment, prevention, cure, or mitigation of a disease or condition;

(4) The principles of operation of the device; and

(5) 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;

(e) Reference to any performance standard under 21 U.S.C. § 360d or under 21 U.S.C. § 360hh 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:

(1) Provide adequate information to demonstrate how the device meets, or justify any deviation from, any performance standard established under 21 U.S.C. § 360d or under 21 U.S.C. § 360kk; and

(2) Explain any deviation from a voluntary standard;

(f) The following technical sections which shall contain data and information in sufficient detail to permit the Department to determine whether to approve or deny approval of the application:

(1) 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 21 C.F.R. part 58, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance;

(2) 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 following:

(A) A statement with respect to each study that it either was conducted in compliance with the institutional review board regulations in 21 C.F.R. part 56, or was not subject to the regulations under 21 C.F.R. § 56.104 or 21 C.F.R. § 56.105, and that it was conducted in compliance with the informed consent regulations in 21 C.F.R., part 50; or if the study was not conducted in compliance with those regulations, a brief statement of the reason for the noncompliance; or

(B) A statement that each study was conducted in compliance with Chapter 109 of this subtitle concerning sponsors of clinical investigations and clinical investigators, or if the study was not conducted in compliance, a brief statement of the reason for the noncompliance.

(g) For a PMA supported solely by data from one (1) 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;

(h) A bibliography of all published reports not submitted under § 10606.2(f), 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;

(i) 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;

1. (j) Copies of such published reports or unpublished information in the possession of or reasonably obtainable by the applicant if a Department advisory committee or the Department requests;
2. (k) One or more samples of the device and its components, if requested by the Department. If it is impractical to submit a requested sample of the device, the applicant shall name the location at which the Department may examine and test one or more devices;
3. (l) Copies of all proposed labeling for the device. Such labeling may include (for example, instructions for installation and any information, literature, or advertising that constitutes labeling under 21 U.S.C. § 321(m));
4. (m) An environmental assessment prepared in the applicable format in § 10606.2(m)(1), unless the action qualifies for exclusion under § 10606.2(m)(2). If the applicant believes that the action qualifies for exclusion, the PMA shall provide information that establishes to the Department's satisfaction that the action requested is included within the excluded category and meets the criteria for the applicable exclusion;
5. (1) The following shall apply to environmental assessments:
   1. (A) An environmental assessment (EA) is a concise public document that serves to provide sufficient evidence and analysis for an agency to determine whether to prepare an environmental impact statement (EIS) or a finding of no significant impact (FONSI). The EA shall include brief discussions of the need for the proposal, of alternatives, of the environmental impacts of the proposed action and alternatives, and a listing of agencies and persons consulted. An EA shall be prepared for each action not categorically excluded. The EA shall focus on relevant environmental issues relating to the use and disposal from use of Department-regulated articles and shall be a concise, objective, and well-balanced document that allows the public to understand the agency's decision. If potentially adverse environmental impacts are identified for an action or a group of related actions, the EA shall discuss any reasonable alternative course of action that offers less environmental risk or that is environmentally preferable to the proposed action. The use of a scientifically justified tiered testing approach, in which testing may be stopped

when the results suggest that no significant impact will occur, is an acceptable approach;

1. (B) Generally, the Department requires an applicant to prepare an EA and make necessary corrections to it. Ultimately, the Department is responsible for the scope and content of EAs and may include additional information in environmental documents when warranted;
2. (C) Information concerning the nature and scope of information that an applicant or petitioner shall submit in an EA may be obtained from the center or other office of the agency having responsibility for the action that is the subject of the environmental evaluation. Applicants and petitioners are encouraged to submit proposed protocols for environmental studies for technical review by agency staff. Applicants and petitioners also are encouraged to consult applicable Department EA guidance documents, which provide additional advice on how to comply with Department regulations;
3. (D) EAs may incorporate by reference information presented in other documents that are available to the Department and to the public; and
4. (E) The Department evaluates the information contained in an EA and any public input to determine whether it is accurate and objective, whether the proposed action may significantly affect the quality of the human environment, and whether an EIS or a FONSI will be prepared. The Department examines the environmental risks of the proposed action and the alternative courses of action, selects a course of action, and ensures that any necessary mitigating measures are implemented as a condition for approving the selected course of action; and(2) The classes of actions listed below are categorically excluded and, therefore, ordinarily do not require the preparation of an EA or EIS:- (A) Action on a device premarket notification submission under Chapter 105 of this subtitle;

5. (B) Classifications or reclassifications of a device;

6. (C) Issuance, amendment, or repeal of a standard for a class II medical device or an electronic product, and issuance of exemptions or variances from such a standard;

7. (D) Approval of a PMA or a notice of completion of a PDP or amended or supplemental applications or notices for a class III medical device if the device is of the same type and for the same use as a previously approved device;
8. (E) Changes in the PMA or a notice of completion of a PDP for a class III medical device that do not require submission of an amended or supplemental application or notice;
9. (F) Issuance of a restricted device regulation if it will not result in increases in the existing levels of use or changes in the intended uses of the product or its substitutes;
10. (G) Action on an application for an IDE or an authorization to commence a clinical investigation under an approved PDP; and
11. (H) Issuance of a regulation exempting from preemption a requirement of a State or political subdivision concerning a device, or a denial of an application for such exemption.- (n) A financial certification, disclosure statement, or both; and
12. (o) If necessary, the Department will obtain the concurrence of the appropriate Department advisory committee before requesting additional information.10606.3 Pertinent information in Department 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 the Department 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 five (5) years after the date that it is submitted to the Department, the Department will return the master file to the person who submitted it.10606.4 If the applicant believes that certain information required under § 10606.2(m) 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. The Department will notify the applicant if it does not accept their justification for omission.

10606.5 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 (3) copies of any update report and shall include in the report that number that the Department assigns to the PMA. These updates are considered to be amendments to the PMA. The timeframe for reviewing the PMA will not be extended due to the submission of an update report unless the update is a major amendment under 21 C.F.R. § 814.37(c)(1). The applicant shall submit these reports:

(a) Three (3) months after the filing date;

(b) Following receipt of an approvable letter; and

(c) At any other time as requested by the Department.

10606.6 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, submitting a color additive petition under 21 CFR, part 71, at the option of the applicant, the information may be submitted under 21 CFR, part 71 as part of the PMA. When submitted as part of the PMA, the information shall be submitted in three (3) 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.

10606.7 If you are sending a PMA, PMA amendment, PMA supplement, or correspondence with respect to a PMA, you must send the submission to the Department.

SOURCE: Final Rulemaking published at 60 DCR 10252 (July 12, 2013).