When a drug or biological product is approved and enters the market, the product is introduced to a larger patient population in settings different from clinical trials. New information generated during the postmarketing period offers further insight into the benefits and risks of the product, and evaluation of this information is important to ensure the safe use of these products.

FDA receives information regarding postmarketing adverse drug experiences 1 from safety reports submitted to the agency. For nearly 35 years, FDA has received these postmarketing safety reports on paper. In recent years, many companies have voluntarily submitted these reports to the agency in electronic format.

Data from both electronic and paper reports are entered into FDA's Adverse Event Reporting System (AERS) database. AERS is a computerized information database designed to support FDA's postmarketing safety surveillance program for drug and biological products. The AERS database is used to store and analyze data received in postmarketing safety reports. Safety reporting data submitted on paper must first be converted into an electronic format before being entered into AERS. 2

FDA is proposing to require use of an electronic format for the submission of postmarketing safety reports (see section II of this document), which would be an important step toward improving the agency's systems for collecting and analyzing these reports. The proposal would:

• Eliminate the time and costs associated with submitting paper reports (for industry) and converting data from paper reports into electronic format for review and analysis (for the agency),

• Expedite the agency's access to safety information and provide data to the agency in a format that would support more efficient and comprehensive reviews, and

• Enhance our ability to rapidly communicate information about suspected problems to health care providers, consumers, applicants, and sponsors within the United States and internationally in support of FDA's public health mission.

The proposed rule would require that postmarketing safety reports be submitted to us in an electronic format that we can process, review, and archive. Consistent with FDA's current practice for firms that already submit these reports in electronic format voluntarily, technical specifications referenced in FDA guidance documents will describe how to submit such reports to the agency. 3 As necessary, the agency will revise the technical specifications referenced in FDA guidance documents to address changing technical specifications or any additional specifications that may be needed for mandatory electronic safety reporting. Using guidance documents to communicate these technical specifications will permit FDA to be more responsive to rapidly occurring changes in the technological environment.

Currently, the technical specifications referenced in guidance documents rely upon and adopt certain safety reporting and transmission standards recommended by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). ICH was formed to facilitate the harmonization of technical requirements for the registration of pharmaceutical products among the three ICH regions: The European Union, Japan, and the United States. In this proposed rule, we reaffirm our intention to continue to rely on these ICH-recommended standards, in addition to providing other options (see section II.D.1 of this document). We believe the continued use of ICH standards will promote harmonization of safety reporting among regulatory agencies and facilitate the international exchange of postmarketing safety information. Accordingly, this proposed rule is consistent with ongoing agency initiatives to encourage the widest possible use of electronic technology and to promote international harmonization of safety reporting for human drug and biological products through reliance on ICH standards. (See section II.C.3 of this document for additional discussion of ICH.).

In this document, we provide background information on the current status of FDA's postmarketing safety reporting requirements (current regulations and previously proposed revisions) (sections II.A and II.B of this document). We also discuss the rationale for proposing this rule (section II.C of this document). Additionally, we describe electronic postmarketing safety reporting initiatives (section II.D of this document), including an advanced notice of proposed rulemaking (ANPRM) that we issued in 1998. Finally, we describe the proposed rule (section III of this document).

The current postmarketing safety reporting requirements for drug and biological products are summarized below. The proposed electronic reporting amendments would leave the substantive aspects of these requirements largely unchanged.

Under existing regulations in part 310, 314, and 600 (21 CFR part 310, 314, and 600), specifically §§ 310.305, 314.80, 314.98, and 600.80, manufacturers, packers, distributors, 4 and applicants 5 with approved new drug applications (NDAs), abbreviated new drug applications (ANDAs), and biological license applications (BLAs) and those that market prescription drugs for human use without an approved application are required to submit postmarketing safety reports of adverse drug experiences to FDA. These safety reports include individual case safety reports (ICSRs), and other related documents (ICSR attachments 6 ) for each adverse drug experience. An ICSR is a description of the adverse drug experience that includes the basic elements, or facts, of each reportable event for an individual patient or subject. Under the current regulations, persons who submit safety reports on paper must use the approved reporting form for ICSRs—either the FDA Form 3500A or an equivalent form as discussed below. Although current regulations do not use the term ICSR, the term is used in FDA and ICH guidances to refer to the adverse drug experience information supplied on the FDA Form 3500A or other approved forms, including those currently submitted in electronic format. 7 Accordingly, we will refer throughout this document to the description of each adverse drug experience related to an individual patient or subject using human drug or biological products as an ICSR. As discussed in section III.E of this document, consistent with the proposed change to a mandatory electronic format for safety reports, we propose to delete most references to the paper forms (e.g., FDA Form 3500A) from FDA postmarketing safety reporting regulations and to add: (1) A definition of ICSR for drugs and biologics and (2) a statement of the information required to be reported in an ICSR.

a. 15-day Alert reports . FDA regulations require manufacturers, packers, distributors, and applicants to submit an ICSR on FDA Form 3500A, or its equivalent, for each postmarketing adverse drug experience that is both serious and unexpected to the agency within 15 calendar days of initial receipt of information about the adverse drug experience (15-day “Alert reports”). An unexpected adverse drug experience is any adverse drug experience that is not listed in the current labeling for the product (§§ 310.305(b), 314.80(a), and 600.80(a)). Followup reports are required to be submitted within 15 calendar days of receipt of new information or as requested by FDA, and are also submitted on an FDA Form 3500A or on an equivalent form. In addition to the ICSR, 15-day Alert reports frequently include related documents, such as medical records, hospital discharge summaries, or other documentation related to the event (ICSR attachments).

To avoid duplication of reports, nonapplicant manufacturers, packers, and distributors of drug and biological products having an approved application may, under §§ 314.80 and 600.80, submit all reports of serious adverse drug experiences to the applicant within 5 calendar days of receipt of the report instead of to FDA. Similarly, packers and distributors of prescription drug products marketed without an approved application may meet their postmarketing 15-day safety reporting obligations under § 310.305 by submitting all reports of serious adverse drug experiences to the manufacturer within 5 calendar days of the receipt of the information instead of to FDA. Applicants/manufacturers receiving such data must then, in turn, submit a 15-day Alert report to FDA.

b. Periodic reports . In addition to 15-day Alert reports, applicants are also required to submit postmarketing periodic safety reports to FDA. For each approved application, applicants are required under §§ 314.80 and 600.80 to submit a periodic report quarterly or annually, depending on how long the drug or biological product has been approved. Upon written notice, the agency can require that an applicant submit these reports to FDA at different times than those stated. These reports contain the following information: (1) A narrative summary and analysis of the information in the report, (2) an analysis of all of the 15-day Alert reports submitted during the reporting interval, (3) an ICSR (and ICSR attachments, if applicable) for each adverse drug experience not previously reported (i.e., reports of all serious, expected (labeled) and nonserious events) 8 , and (4) a history of actions taken since the last periodic report because of the reports of adverse drug experiences. The descriptive information portions of a postmarketing periodic safety report (report summary, analysis of 15-day Alert reports, and history of actions) are submitted to the agency in a narrative format accompanied by the ICSRs and any ICSR attachments for all serious, expected and nonserious adverse drug experiences that occurred during the reporting period. Manufacturers of drugs marketed without an approved application (e.g., NDA, ANDA) are not required to submit postmarketing periodic safety reports to FDA.

c. Distribution reports . In addition to periodic reports, under § 600.81, applicants with approved BLAs are also required to submit distribution reports to the agency every 6 months or at other intervals that the agency may specify with written notice. These reports contain information about the quantity of biological product distributed under the BLA, including the quantity distributed to distributors.

d. Nonprescription human drug products marketed without an approved application . Public Law 109-462, enacted on December 22, 2006, amended the Federal Food, Drug, and Cosmetic Act (the act) to create a new section 760 (21 U.S.C. 379aa), entitled “Serious Adverse Event Reporting for Nonprescription Drugs.” Section 760 of the act requires manufacturers, packers, or distributors whose name appears on the label of nonprescription human drug products marketed without an approved application to report serious adverse events associated with their products. Effective December 22, 2007, section 760 of the act requires these reports to be submitted to FDA within 15 business days. As required by section 2(e)(3) of Public Law 109-462, FDA issued a draft guidance for industry entitled “Postmarketing Adverse Event Reporting for Nonprescription Human Drug Products Marketed without an Approved Application” (72 FR 58316, October 15, 2007). The draft guidance describes the minimum data elements and the relevant policies and procedures for making these reports under section 760 of the act. It provides, among other things, that the reports be submitted on paper on FDA Form 3500A or in the electronic format described in the guidance.

This proposed rule does not contain language that would require that safety reports under section 760 of the act for nonprescription human drug products marketed without an approved application be submitted to FDA in electronic format. However, we are soliciting public comment on whether the final rule should require the use of electronic format for these reports. We expect that any electronic format requirements for these section 760 reports would be quite similar to the requirements for other categories of drug products addressed by this rule. Any decision whether to include section 760 reports will be informed by the public comments submitted in response to this proposal and the agency's experience since submission of serious adverse event reports for nonprescription human drug products marketed without an approved application became mandatory in December 2007.

Finally, note that nonprescription drugs that are marketed under approved applications (NDAs or ANDAs) are not covered under section 760 of the act. Such products are subject to reporting under current §§ 314.80 and 314.81. Reports submitted to FDA under those sections would be subject to the mandatory electronic format requirements proposed in this rule as described elsewhere in this document.

a. Drug and biological products . FDA currently accepts all postmarketing ICSRs in either a paper format or an electronic format. Sections 310.305(d), 314.80(f), and 600.80(f) authorize use of a paper FDA Form 3500A for reporting of single cases of adverse drug experiences for human drug and biological products. The regulations also permit use of the form introduced by the World Health Organization's (WHO's) Council for International Organizations of Medical Sciences (CIOMS) Working Group I for reporting single cases of foreign adverse drug experiences that are serious and unexpected (CIOMS I form).

Section 11.2(b)(2) currently provides that regulatory submissions may be voluntarily provided to the agency in electronic form 9 if the submissions are identified by FDA in its electronic submissions public docket as submissions the agency will accept in electronic form. 10 Postmarketing safety reports for drug and nonvaccine biological products have been identified in the docket as submissions the agency can accept in electronic format. See Memorandums 23 and 28 in FDA's electronic submissions public docket. If the reporter elects to file the safety report in electronic format rather than on paper, current §§ 310.305(d), 314.80(f), and 600.80(f) require that the ICSRs in the electronic report include the same information as the paper FDA Form 3500A or CIOMS I form.

Accordingly, under current regulations, an ICSR submission can take the form of a paper FDA Form 3500A, a paper CIOMS I form, or comparable information submitted in electronic format. (See section II.D.1 of this document). Each of these is a different method of transmitting to FDA the same basic elements of the ICSR, whether on paper or in electronic format. As described in section II.D.1.a of this document, ICSR attachments and the descriptive information portions of periodic safety reports may also be submitted electronically.

b. Vaccine products . Adverse experience reporting for vaccine products may be submitted to the Vaccine Adverse Event Reporting System (VAERS). VAERS is a computerized information database designed to support the Centers for Disease Control and Prevention's (CDC's) and FDA's postmarketing surveillance program for vaccine products. Postmarketing ICSRs for vaccines can be submitted on a VAERS paper form 11 or reported on-line using the VAERS secure web-based system 12 . Each of these is a different method of transmitting to CDC/FDA the same basic elements of the ICSR. Currently, VAERS does not have the capability to receive electronic ICSRs submitted through the FDA's electronic submissions gateway. However, developments are underway to implement this submission capability.

In the Federal Register of March 14, 2003 (68 FR 12406), FDA published a proposed rule to amend its safety reporting requirements for human drug and biological products (Safety Reporting Proposed Rule). The agency proposed new definitions and reporting formats and standards for pre- and postmarketing safety reporting as recommended by ICH (see section II.C.3 of this document) and by CIOMS. Some of the proposed amendments were based on the recommendations of ICH, while others were proposed by the agency on its own initiative. With regard to coding of postmarketing ICSRs to standardize safety reports for comparison and analysis, the agency proposed use of the Medical Dictionary for Regulatory Activities (MedDRA) terminology developed by ICH 13 . The agency also proposed to require the submission of new types of postmarketing safety reports to FDA. FDA is currently considering the comments that it has received on the Safety Reporting Proposed Rule. Any new postmarketing safety reports that are required by a safety reporting final rule would be required to be submitted electronically in accordance with this rulemaking, if adopted as final.

As explained more below, the agency proposes to require that all postmarketing safety reports for human drugs and biological products be submitted in electronic format. By requiring submission of these reports in electronic format, FDA would expedite access to safety information and facilitate international harmonization and exchange of this information. This, in turn, would lead to more efficient reviews of safety data and enhance our ability to rapidly disseminate safety information to health care providers, consumers, applicants, sponsors, and other regulatory authorities in support of FDA's public health mission. In addition, the agency would recognize a significant cost savings by converting the safety reporting system from a paper submission process to an all electronic system that would increase the accuracy of information and reduce the need for manual data entry.

Establishment and maintenance of efficient risk management programs (where appropriate) is an agency priority (see FDA's January 2007 response to the Institute of Medicine (IOM) report on drug safety entitled “The Future of Drug Safety: Promoting and Protecting the Health of the Public,” FDA's March 2005 guidance for industry entitled “Development and Use of Risk Minimization Action Plans,” and FDA's 2007 Strategic Action Plan). 14 The changes proposed in this rule, if adopted, would improve the agency's management of risks from human drug and biological products by expediting the postmarketing identification and communication of emerging safety information for these products.

Requiring that postmarketing ICSRs be submitted in electronic format would result in reducing the time required for FDA to enter information from a paper safety report into a database for evaluation and analysis. Currently, approximately 60 percent of all ICSRs (i.e., 15-day Alert reports and ICSRs associated with periodic reports 15 ) are submitted to FDA on paper for input into the AERS database (approximately 30,000/month). With regard to 15-day Alert reports, approximately one-third are submitted on paper (approximately 8,000/month) to FDA. Fifteen-day Alert reports that are submitted on paper generally reach FDA's data entry contractor within the required 15 days following the adverse drug experience, but then the ICSRs must be manually entered into the AERS database. These ICSRs are entered into the FDA AERS database on a priority basis because they may indicate a new, previously unidentified risk. The time required for data entry, validation, and quality control processes, however, adds an additional 2 weeks before the ICSRs are actually available for assessment by FDA's safety evaluators. With regard to periodic ICSRs, approximately 80 percent are submitted on paper (approximately 22,000/month). 16 Periodic ICSRs, which are submitted on paper, may not be available for review by safety evaluators for up to 2 months after submission to the agency because of their volume and because ICSRs in 15-day Alert reports must take first priority.

In contrast, the ICSRs in both 15-day Alert and periodic reports submitted in electronic format are processed and available for safety evaluator review much more quickly because there is no need for data entry and the associated quality control and validation processes are faster. Instead of 2 months for periodic ICSRs or 2 weeks for 15-day Alert ICSRs that are submitted in a paper format, ICSRs submitted in electronic format are, generally, available to reviewers within 2 days of their receipt by FDA. The requirement for electronic safety reports is expected to result in faster processing and this will permit FDA to more quickly identify emerging safety issues and rapidly disseminate significant safety information to the medical community and the public with corresponding benefits to the public health.

The proposed electronic formatting requirements for postmarketing safety reports would enhance operations for both industry and FDA. Electronic reporting can benefit industry by eliminating the costs associated with collating, copying, storing, retrieving, and mailing paper copies. In addition, FDA would benefit from the elimination of data entry processes and significant reduction in physical storage requirements. When data are provided only on paper, the information must be converted manually into an electronic form to review and analyze. This process is time consuming, costly, and creates an opportunity for data entry error to occur.

FDA expects to provide two options for submitting electronically formatted ICSRs. Reporters would be able to submit ICSRs by using either an ICH-compatible electronic transmission system, or a Web-based form similar to those used for commercial transactions, such as retail purchases, on the Internet. (These options, as well as those for submission of ICSR attachments in electronic form, are discussed in more detail in section II.D.1 of this document.) For companies that submit large numbers of ICSRs, use of the ICH-compatible system for electronic transmission would be cost effective because the information from the ICSRs will be transmitted directly from the company's database to FDA without needing additional administrative support for manual entry of the information. For companies that submit a small number of ICSRs, use of the Web-based form may be more cost effective than using the ICH-compatible system.

FDA has worked with industry on electronic submission of postmarketing ICSRs since 1998. In 2001, FDA announced through public docket number 92S-0251 that the agency would accept voluntary electronic submissions of ICSRs for 15-day Alert and periodic safety reports in lieu of a paper submission (see section II.A.2 of this document). Currently, over 40 pharmaceutical companies are voluntarily using electronic format to submit to FDA ICSRs for both 15-day Alert and periodic reports for human drug and biologics, with more than 500,000 ICSRs submitted to date. This experience has shown that electronic data submissions to the AERS database reduce the cost of data entry and facilitate the review process. It currently costs FDA approximately $35 to process a report submitted on paper. In comparison, a report submitted in an electronic format costs approximately $12 to process.

In developing this proposal, FDA considered the international standards developed by ICH for the submission of safety information. The other ICH regions (the European Union (EU) and Japan) are also implementing the standards recommended by ICH for the electronic submission of safety reports. The procedures for the electronic submission of postmarketing safety reports in this proposed rule would, therefore, reduce costs to industry associated with maintaining multiple electronic systems designed to meet the needs of different regulatory authorities. The proposed electronic safety reporting regulations would also encourage better communication between FDA and the industry, as well as with other regulators, nationally and abroad, while reducing the costs associated with reporting. Moreover, the industry would be able to rely on one form of electronic reporting, which would reduce the administrative costs of compliance.

a. Status of electronic submissions in the EU . The European Commission drafted guidance on adverse event reporting, including Volume 9 of “The Rules Governing Medicinal Products in the European Union” (the EU rules), which contains a specific emphasis on pharmacovigilance. The EU rules require the electronic submission of adverse event reports (effective November 2005) and incorporate international guidelines reached within the framework of the ICH. The EU rules specify that the electronic transmission and management of safety reports will be carried out according to the guidelines and specifications contained in ICH guidance on safety reporting and electronic standards.

b. Status of electronic submissions in Japan . On October 27, 2003, the Japanese Ministry of Health, Labour, and Welfare mandated that ICH guidance E2BM 17 compliant ICSRs be submitted in electronic format either by the Internet or by physical media.

c. Global impact of a standard electronic submission . FDA collaborates with many international regulatory counterparts on drug safety issues. Frequently, FDA sends to and receives from other regulators paper copies of ICSRs for further clinical analysis of specific drug safety issues. FDA envisions that regulatory partners participating in ICH, and other regulators that choose to implement the same standards, will be able to electronically exchange specific ICSRs in real time as safety issues emerge. As a result, regulatory partners would be assured that they are making regulatory decisions based on a full complement of available information.

a. Voluntary electronic submissions . In the Federal Register of March 20, 1997 (62 FR 13430), FDA published a regulation on electronic records and electronic signatures (21 CFR part 11). In August 2003, FDA issued guidance for industry entitled “Part 11, Electronic Records; Electronic Signatures—Scope and Application,” describing the agency's thinking regarding part 11. Part 11 generally provides that in instances where records are submitted to the agency, such records may be submitted in electronic format instead of paper format, provided that FDA has identified the submission in FDA's electronic submissions public docket as the type of submission that FDA can accept in electronic format. Postmarketing safety reports have been identified in FDA's electronic submissions public docket as submissions that FDA may accept in electronic format 18 .

Presently, FDA allows applicants, manufacturers, packers, and distributors to submit postmarketing safety reports (both 15-day Alert and periodic reports) in electronic format by sending the reports to FDA either: (1) Through FDA's Electronic Submission Gateway (ESG) or (2) on physical media, e.g., CD-ROM, digital tape, or floppy disk (sent by mail). 19 These electronic submissions may include ICSRs, any ICSR attachments, and descriptive information. The data elements and electronic transport formats that FDA can accept for electronic ICSRs are described in technical specifications referenced in FDA guidance documents. 20 Currently, FDA can accept attachments to ICSRs and the descriptive information of periodic reports in an electronic form as portable document format (PDF) files, which may be sent through the FDA's ESG or mailed to FDA on physical media. 21 To send these reports by FDA's ESG, a manufacturer/applicant must initially contact FDA's AERS electronic submission coordinator 22 to establish an ESG connection with FDA's network.

b. ICH standards . FDA codes and analyzes electronic submissions of safety information received via the ESG or on physical media based on ICH standards. 23 ICH has developed international standards for the electronic submission of safety information that include: (1) Standardized common data elements for transmission of ICSRs (ICH E2B guidance), and (2) electronic standard transmission procedures (ICH M2 24 ). ICH E2B guidance provides standardized common data elements for the transmission of ICSRs by identifying and defining the data elements for the transmission of all types of ICSRs, regardless of source and destination. The ICH format for ICSRs includes provisions for transmitting all the relevant data elements useful to assess an individual adverse drug reaction or adverse event report. The common data elements are sufficiently comprehensive to cover complex reports from most sources, different data sets, and different transmission requirements.

c. FDA Web-based submission portal . In addition to submission of ICSRs through the ESG, FDA is developing a Web-based electronic submission portal to collect and process safety information for all FDA-regulated products that will be consistent with ICH standards and may be used as another method for reporting adverse drug experiences to the agency. 25 FDA's Web-based portal will allow for the secure electronic submission of postmarketing ICSRs directly into FDA's AERS database once information is typed into a Web-based electronic form. Users will receive electronic confirmation that their submissions have been received by FDA. Any person who is subject to FDA's postmarketing safety reporting requirements and has Internet access will be able to use the Web-based form to submit ICSRs to the agency. The Web-based submission function will assist entities that submit a small number of safety reports by creating a simpler and more efficient mechanism for reporting that does not require them to have an internal database that is compatible with the ICH-based system. However, because some administrative support would be needed to manually enter the information for the ICSRs onto a form on the Web, this Web-based electronic reporting format will be less cost effective than direct submission through the ESG (or submitting the information on physical media) for companies with large numbers of safety reports. As soon as FDA can accept submissions using this Web-based form, information in docket 92S-0251, and the guidance documents described in this section will be updated to reflect this option.

In this proposal, we provide background information on the current status of FDA's medical device reporting requirements, explain the revisions we are proposing here, and describe our approach to electronic medical device reporting.

For over 20 years, FDA has received postmarket MDRs in a paper format. This proposed rule to require the electronic submission to FDA of most MDRs is an important step towards improving the agency's systems for collecting and analyzing postmarket MDRs. The proposed rule includes reports of deaths, serious injuries, and malfunctions that must be reported to FDA in initial 5-day, 10-day, or 30-day individual MDRs or in supplemental reports. We believe this proposed rule would have the following benefits:

• Reduce industry's time and costs associated with transcribing data from internal data management systems to paper and mailing the paper reports to the agency,

• Eliminate the agency's transcription errors, time, and costs associated with receiving paper reports and transcribing data to electronic format for review and analysis,

• Expedite the agency's access to safety information in a format that would support more efficient and comprehensive data analysis and reviews, and

• Enhance the agency's ability to rapidly communicate information about suspected problems to the medical device industry, health care providers, consumers, and other government agencies.

In addition, this proposed rule is consistent with the Government Paperwork Elimination Act (Public Law 105-277) requirement that Federal agencies allow individuals or entities to submit information or transact business with the agency electronically.

The requirements of current medical device reporting regulations are summarized in sections I.A.1 to I.A.3 of this document. In addition, we address changes to these regulations to be effected outside of this proposed rule.

Current MDR regulations (part 803 (21 CFR part 803)) require manufacturers and importers of marketed medical devices, and user facilities, to submit postmarket reports of individual medical device adverse events to FDA on the FDA Form 3500A.

The current MDR regulation requires that manufacturers of medical devices submit a postmarket MDR of an individual adverse event no later than 30 calendar days after becoming aware of information that a device the manufacturer markets may have caused or contributed to a death, serious injury, or malfunction (§ 803.50). This report must be submitted on the FDA Form 3500A, (§ 803.20), and contain information described in § 803.52.

In addition, the regulation requires manufacturers to provide supplemental information about such events, on an FDA Form 3500A, within 30 calendar days of obtaining information should such information become available after the initial MDR was filed with FDA (§ 803.56). In instances where the medical device adverse event resulted in remedial action to prevent an unreasonable risk of substantial harm to the public health, or at the discretion of the agency, the regulation requires the manufacturer to submit an MDR to the agency no later than 5 working days after becoming aware of the information (§ 803.53).

Title II, section 227, of the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Public Law 110-85), amended section 519 of the Federal Food, Drug, and Cosmetic Act (the act) to require that FDA establish criteria for manufacturer reports of malfunctions for most class I and certain class II devices that include requiring those reports to be in summary form and made on a quarterly basis. The types of events required to be reported are unchanged. FDA intends to address changes necessitated by this statutory change separately from this proposed rule, and will address requirements for submission of those new summary malfunction reports at that time. However, some individual malfunction reports will continue to be required even after the FDAAA-related changes, and as explained below, the rule proposed here does address submission of individual malfunction reports to the agency.

The MDR regulation requires that importers of medical devices submit a postmarket MDR to the agency and the manufacturer no later than 30 calendar days after becoming aware of information that reasonably suggests that one of the importer's marketed devices may have caused or contributed to a death or serious injury (§ 803.40(a)). Importers must submit reports to the manufacturer no later than 30 calendar days after becoming aware of information that reasonably suggests that one of the importer's marketed devices has malfunctioned and that this device or a similar device marketed by the importer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur (§ 803.40(b)). These reports must be submitted on the FDA Form 3500A (see § 803.20) and contain the information specified in § 803.42.

The MDR regulation requires that user facilities submit a postmarket MDR of death to the agency and an MDR of death or serious injury to the device manufacturer within 10 working days of becoming aware of information that reasonably suggests that a device has or may have caused or contributed to the death or a serious injury of a patient of the facility. (§ 803.30(a)). The regulation requires that user facilities submit postmarket reports of serious injury to the agency within 10 working days if the manufacturer of the device is unknown or cannot be identified (§ 803.30(a)(2)). These reports must be submitted on the FDA Form 3500A (see § 803.20(a)), and include the information described in § 803.32.

In addition, user facilities are required to submit to the agency an annual summary of the reports they sent to manufacturers and the FDA, using FDA Form 3419 (§ 803.33). The proposal to require submission of reports to FDA in an electronic format does not apply to user facility annual reports made under § 803.33, although other changes to § 803.33 are proposed as explained in section I.B of this document.

Current regulations at § 803.20(a) require that user facilities, importers, and manufacturers use the FDA Form 3500A to submit mandatory reports about FDA-regulated devices. This requirement took effect July 31, 1996 (see 60 FR 63578, December 11, 1995; 61 FR 16043, April 11, 1996).

Certain blocks of the FDA Form 3500A are required only for user facilities, while others are required only for manufacturers (see § 803.20(a)(2)).

Subsequent to its initial adoption, FDA revised the Form 3500A and its instructions, adding elements including the premarket approval application (PMA) or 510(k) number for the device, and two questions regarding reprocessed single-use devices. The agency was required to revise the form to include the questions regarding reprocessed single-use devices under section 303 of the Medical Device User Fee and Modernization Act of 2002 (Public Law 107-250). The revised FDA Form 3500A is approved under the PRA, under OMB control number 0910-0291.

FDA Form 3500A has been routinely completed on paper and transmitted to FDA by mail, requiring FDA to manually input information from those reports into its internal electronic systems before it can be reviewed and analyzed. This process is extremely time consuming, costly, and susceptible to data entry errors. Because FDA regulations at § 803.14 provide for the possibility of voluntary electronic submission of MDRs, with agency permission, several regulations in part 803 refer to submission of reports using the FDA Form 3500A “or an electronic equivalent approved under section 803.14.” (See, e.g., §§ 803.30, 803.40, and 803.53.) However, reporters have not made use of section 803.14 to pursue voluntary electronic submission of MDRs, and FDA's legacy systems were not in general designed to accept submission of MDRs in electronic format.

When a medical device has been cleared for marketing and enters the market, the product is introduced to a larger patient population in settings different from clinical trials. New information generated during the postmarketing period offers further insight into the benefits or risks of the product, and evaluation of this information is important for all products to ensure their safe use. Historically, FDA has received almost all postmarket MDRs on paper through the mail. When data elements are provided to FDA on only paper, the information must be entered by hand into an electronic format for review and analysis. This process is extremely time consuming, costly, and susceptible to data entry errors.

The electronic submission of medical device reports would lead to more efficient reviews, enhancing our ability to rapidly disseminate significant information to the medical device industry, health care providers, and consumers, in support of FDA's public health mission.

Electronic submissions would also improve the speed and efficiency of both industry and agency operations. Electronic reporting can benefit industry by reducing the costs associated with collating, copying, storing, retrieving, and mailing paper medical device reports to the agency on FDA Form 3500A. In addition, the agency benefits from the elimination of manual data entry processes and reductions in physical storage for paper copies of the FDA Form 3500A. Based on low rates of participation in prior pilot voluntary electronic MDR submission programs, FDA believes that without a regulation requiring electronic submission of MDRs a large number of medical device firms and user facilities would resist changing their procedures for a long period of time. This delay would hinder our achieving the benefits of standardized formats and quicker access to MDR data.

FDA's Center for Devices and Radiological Health (CDRH) has established its MDR databases currently to support two options for electronic submission of MDRs: One designed for low volume reporting and one designed for high volume reporting. Both options make use of the FDA Electronic Submission Gateway (FDA ESG), a secure electronic portal described further in this document, for transmission of reports to FDA. In accordance with 21 CFR 11.2(b), CDRH is now accepting on a voluntary basis, in lieu of paper, MDRs prepared and transmitted in accordance with these options. More information on electronic submission of MDRs is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/ReportingAdverseEvents/ucm127932.htm.

For low-volume medical device reporting (few or infrequent MDRs), the current approach developed by the agency uses the CDRH eSubmitter (CeSub) software. The CeSub software allows for the submission of one MDR at a time. The software provides the following tools:

• Save address and contact information,

• Search for a Product Code,

• Search to locate a patient or Device Problem Code,

• Search to find manufacturer evaluation codes (method, result, and conclusion),

• Attach documents when additional information needs to be provided,

• Produce a “missing data report” to help ensure that all required information is supplied before submission to FDA.

Once the MDR is completed, the file is “packaged for submission.” The package generates an electronic version of the FDA Form 3500A, which can be submitted to FDA using the FDA ESG. The final CeSub-generated report can also be saved or printed, for recordkeeping or to provide reports to manufacturers or other entities outside of FDA. The CeSub software and instructions for installation are free and available at: http://www.fda.gov/ForIndustry/FDAeSubmitter/ucm107903.htm . We may sometimes update or change our methodology, approach or software to improve the low-volume reporting experience.

Reporters with large volumes of MDRs may prefer the second option, called the Health Level 7 Individual Case Safety Report (HL7 ICSR). The HL7 ICSR was developed in conjunction with the HL7 standards organization to support the exchange of electronic data. This option allows for the extraction directly from the reporter's database of information to populate an MDR, production of the appropriate data output, and transmission of the MDRs to the FDA ESG. The HL7 ICSR supports the batch submission of more than one individual MDR at a time. Reporters developing applications using the HL7 ICSR standard may also build functions for saving or printing those reports.

The draft guidance document announced elsewhere in this Federal Register provides information on both options for electronic submission of MDRs.

The FDA ESG is the entry point for all electronic submissions to the agency. The FDA ESG is available 24 hours a day, 7 days a week. Information on the FDA ESG is available at http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/default.htm . To use the FDA ESG, reporters need to have a digital certificate. A digital certificate is an attachment to an electronic message that allows the recipient to authenticate the identity of the sender via third party verification from an independent certificate authority. Digital certificates are used to identify encryption and decryption codes between message senders and recipients. Information on digital certificates can be found at http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/ucm113223.htm .

FDA's electronic submission processing system sends the submitter three different acknowledgments (messages) for each submission. Acknowledgment 1 comes from the ESG and indicates your submission was received. Acknowledgment 2 is sent by the ESG and indicates the submission reached CDRH. CDRH sends Acknowledgment 3 and notifies you whether your submission was successfully loaded into CDRH's adverse event database or the submission contained errors (specified in the acknowledgment) during validation and loading. If your submission contained errors, the errors need to be corrected and the corrected reports resent.

This rule would revise § 803.12 to require that manufacturers, importers, and user facilities submit postmarket MDRs to the agency in an electronic format that FDA can process, review, and archive. Under the proposal, FDA will periodically issue information on file formats, preparation and organization of files, media, method of transmission, and other relevant technological specifications for providing reports in an electronic format that FDA can process, review, and archive. Proposed new § 803.23 would direct reporters to the agency's Web site to find the most updated relevant information. Reports between manufacturers, importers, and user facilities would not be subject to the requirement of submission in electronic format, and may be in any format the recipient can read.

The rule would make conforming changes throughout part 803 to reflect the proposed requirement to submit reports to FDA in electronic format. These changes include removing § 803.11, which currently addresses obtaining paper forms, and removing § 803.14, which currently provides for voluntary electronic submission of reports with FDA consent. The proposal would amend § 803.19, which already addresses exemptions or variances from any of the requirements of part 803, to specifically address exemption or variance from the requirement to submit reports to FDA in electronic format. Other changes include removing references to “electronic equivalent[s] approved under § 803.14” from §§ 803.13, 803.30, 803.33, 803.40, and 803.53, and updating wording in § 803.20 and 803.56 to be more consistent with the fact that reports will not be submitted on paper (and thus, for example, would no longer have a front and back).

If this proposed rule becomes final, manufacturers, importers, and user facilities would be required to begin submitting medical device reports to the agency in electronic format no later than 1 year from the date of publication of a final rule. After the effective date, the agency would not accept MDRs submitted on paper copies of the FDA Form 3500A, or in electronic formats other than those identified as ones that FDA can process, review, and archive in information provided in conjunction with this rule, unless the agency had granted an exemption or variance as provided for in § 803.19.

The rule would amend §§ 803.50(a), 803.53, and 803.56 to require submission of information required by §§ 803.52, 803.53, and 803.56 in electronic format in accordance with § 803.12(a).

The proposed rule amends § 803.40(a) to require submission to FDA of information required by § 803.42 in electronic format in accordance with § 803.12(a). The proposed electronic format requirement does not extend to importer reports submitted to device manufacturers, which may be in any format that the recipient can read.

The proposed rule amends § 803.30(a) to require submission to FDA of information required by § 803.32 in electronic format in accordance with § 803.12(a). The amendment does not impose mandatory electronic format requirements on user facility reports submitted to device manufacturers, which may be provided in any format the recipient can read.

The proposed rule also makes certain changes to § 803.33, addressing user facility annual reports. Under the proposed rule, user facilities will continue to submit annual reports on the paper FDA Form 3419. Because the proposal to require submission of individual adverse events reports in electronic format calls for amendments to § 803.12 and for removal of §§ 803.11 (indicating how to obtain paper forms) and 803.14 (addressing voluntary electronic submissions), FDA is proposing to amend § 803.33 to specify where to obtain the FDA Form 3419, where to submit completed reports under that section, and to remove references to § 803.14.

Section 803.18 of the regulation addresses requirements for establishing and maintaining MDR files or records for manufacturers, user facilities, and importers. FDA is proposing to amend § 803.18(b)(ii) to require that MDR files contain copies of all reports submitted under part 803, whether paper or electronic. As under the current regulations, under the proposal, regulated entities may choose to maintain required records either in hard copy, by printing out reports submitted in electronic format, or in electronic form. (For information regarding FDA's current thinking and enforcement policy with regard to requirements for maintaining electronic records, see 21 CFR part 11 and the agency guidance document, “Guidance for Industry: Part 11, Electronic Records; Electronic Signatures—Scope and Application,” available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072322.pdf5667fnl.pdf .). FDA is also proposing to add § 803.18(b)(1)(iii) to require the retention of all acknowledgments FDA sends the manufacturer, importer, or user facility when reports are submitted in electronic format, which will indicate the timing and success of submission.

As noted previously, if the proposed rule is finalized, manufacturers, importers, and user facilities will be required to submit most MDRs to the agency in an electronic format that FDA can process, review, and archive. In order to best accommodate technological changes, FDA expects to issue information on how to prepare and submit MDRs to the agency in a way that would satisfy the requirements of this proposed rule. The most specific and updated information about how to create, format, and transmit reports, using the CeSub software (designed for low volume reporting) or the HL7 ICSR (designed for high volume reporting), is provided on the agency's Web site, at the address provided in proposed § 803.23. The agency will make every effort to maintain backwards compatibility when implementing changes to the systems and formats for electronic submission. When backwards compatibility is not possible, the agency will provide public notice with a duration commensurate with the complexity of the change.

Under proposed § 803.19, a manufacturer, importer, or user facility may submit a written request to FDA seeking a variance of the § 803.12 requirement to submit reports to the agency in an electronic format that the agency can process, review, and archive. Written requests must contain the reason(s) why the reporting entity requires a variance and for how long the variance is needed. FDA anticipates receiving few variance requests because of the availability of the Internet and the commercial availability of digital certificates as well as FDA's free CeSub Internet software. Under the proposal, if FDA grants a variance, the manufacturer, importer, or user facility would be required to submit MDRs as specified by FDA in the letter authorizing the variance.

The proposed rule would also codify the following modifications:

1. FDA proposes to remove the definition of “Five-day report” in § 803.3, which merely referred to a report submitted under § 803.53 (the only provision of the regulation in which the term appears), using the FDA Form 3500A or “an electronic equivalent approved under § 803.14.” Because this definition is not necessary, FDA proposes to remove it.

2. FDA proposes to amend §§ 803.32, 803.42, and 803.52 to make minor wording changes and corrections to these sections to reflect modifications already made to FDA Form 3500A and its instructions, with OMB approval under the PRA. For example, section 303 of the Medical Device User Fee and Modernization Act of 2002 (Public Law 107-250) required FDA to modify the forms to facilitate reporting of MDRs involving single-use devices that have been reprocessed for reuse (see 69 FR 7491, February 17, 2004). FDA is proposing to amend §§ 803.32, 803.42, and 803.52 to reflect the addition to the FDA Form 3500A of these two questions concerning whether the device is a single use device that has been reprocessed and reused on a patient and the name and address of the reprocessor.

FDA is also proposing to change §§ 803.32(b)(4), 803.42(b)(4), and 803.52(b)(4) from “date of report by the initial reporter” to “date of this report.” This change would make part 803 consistent with the way that other FDA Centers interpret FDA Form 3500A, Block B4 and how Block B4 appears on FDA Form 3500A. Finally, FDA is also proposing to make other minor updates to §§ 803.32(c), 803.42(c), and 803.52(c) and (e) to reflect the changes already made to the forms and instructions, including a reference to the product code and PMA/510(k) number.

FDA proposes that any final rule that issues based on this proposal become effective 1 year after the date the final rule publishes in the Federal Register .

FDA's legal authority to amend its regulations governing the submission of postmarket medical device adverse event reports for medical devices derives from 21 U.S.C. 352, 360, 360i, 360j, 371, and 374.

The agency has determined under 21 CFR 25.30(h) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required.

FDA has examined the impacts of the proposed rule under Executive Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive Order 12866 directs agencies to assess all costs and benefits of available regulatory alternatives and, when regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety, and other advantages; distributive impacts; and equity). This proposed rule has been determined to be a significant regulatory action.

The Regulatory Flexibility Act requires agencies to analyze regulatory options that would minimize any significant impact of a rule on small entities. Because we lack information on the electronic submission capabilities of all the firms potentially affected by this proposed rule we have not proposed to certify that the proposed rule would not have a significant economic impact on a substantial number of small entities. We request commenters to submit such information in their comments.

Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires that agencies prepare a written statement, which includes an assessment of anticipated costs and benefits, before proposing “any rule that includes any Federal mandate that may result in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any one year.” The current threshold after adjustment for inflation is $133 million, using the most current (2008) Implicit Price Deflator for the Gross Domestic Product. FDA does not expect this proposed rule to result in any 1-year expenditure that will meet or exceed this amount.

The purpose of this proposed rule is to require the submission of MDRs in an electronic format the agency can process, review, and archive. It would affect all persons subject to medical device reporting under part 803, which includes medical device manufacturers, device importers, and user facilities.

The proposed rule is part of a greater agency initiative to adopt electronic technologies to improve the quality of our operations and increase the efficiency of our resources. The rule would reduce FDA's current costs associated with processing medical device reports (or MDRs) that are received on the paper FDA Form 3500A. By receiving MDRs electronically, FDA would be able to access the adverse event information more quickly and also eliminate potential data entry errors that could occur during input transcription of the information from the paper FDA Form 3500A reports into our electronic medical device adverse event reporting database.

After considering various alternatives, FDA determined that without this regulation, the agency will need to maintain adequate resources to continue to convert paper 3500A MDRs to electronic MDR records until all manufacturers, importers, and user facilities voluntarily adopted the proposed electronic submission format, possibly years in the future.

The major benefit of this proposed rule would be to public health because the agency would have quicker access to the medical device adverse event reports information and thus could more quickly identify and act on any medical device problems. Currently, FDA receives 100,000 initial MDRs annually on the paper FDA Form 3500A, which are manually entered into the FDA database. FDA receives an additional 110,000 supplemental reports each year that are also submitted on the paper FDA Form 3500A and need to be processed and entered into the FDA database. It can take from 3 days to more than 6 months before an MDR submitted on a paper copy of the FDA Form 3500A may be available for analysis in the Manufacturer and User Device Experience database (MAUDE). With a standardized electronic format, medical device reports would become available for analysis as soon as they are processed into MAUDE. With a reduction in the time to manually enter the MDRs into the MAUDE database, analysis and action, including feedback to manufacturers and consumers, could be taken sooner with a corresponding benefit to public health.

The public health benefits would be supplemented with operating cost reductions within FDA. Assuming the number of MDRs remains fairly constant over time, electronic reporting would save the agency about $1.25 million annually in data entry costs, which is about one-half of our current data entry contract.

There are about 18,000 medical device manufacturers and importers identified in FDA's medical device registration database and approximately 38,500 user facilities identified in the 2002 U.S. Economic Census that would be affected by the proposed rule (for a total of 56,500 manufacturers, importers, and user facilities) (Census, 2002). Table 1 shows the estimated numbers of firms and establishments in the affected industries.

One-time costs would be the sum of the costs of:

• Rewriting standard operating procedures (SOPs) and training the appropriate personnel,

• Installing and validating either the installation of CDRH's CeSub Web interface software or the programming and configuration of a computer system to transmit reports directly to the FDA ESG using the HL7 ICSR, and

• Acquiring the electronic digital certificate required by the FDA ESG.

a. Rewriting SOPs and training personnel . All entities affected would need to update their SOPs to include the electronic submission requirement. For medical device manufacturers, importers, and hospitals, we estimate that it would require about 10 hours to make the modifications and train the appropriate people on the new procedures. For the other user facilities, we assume that the corporate or regional offices would have the major responsibility for medical device reporting and thus the SOPs for these individual entities would require less time to modify. For this analysis we estimated that 55 percent of the other user facilities would require about 10 hours to modify their SOPs and the remaining 45 percent would require about 2 hours. 1 The estimated one-time incremental cost for updating SOPs, assuming an average wage rate of $52 per hour, 2 (Bureau of Labor Statistics (BLS), 2006) is about $34.1 million [((18,000 medical device manufacturers and importers + 6,300 hospitals) x 10 hours) + ((0.45 x 2 hours + 0.55 x 10 hours) x 64,500 other user facilities) x $52/hour].

b. Setting up systems for submission . MDRs would be submitted through the FDA ESG using one of two methods: The CDRH CeSub software or the HL7 ICSR. Because most entities are small and submit few if any MDRs annually, we assume they would probably use the CDRH CeSub software, which allows for the submission of one MDR at a time. To comply using this submission method, manufacturers, importers, and user facilities would need high-speed Internet connections and would have to download and install up to three free software programs, validate the installation, and train the appropriate personnel on the new procedures. Entities that have dedicated information technology (IT) staff would be able to install and validate the installation themselves. Smaller manufacturers, importers, and user entities would probably choose to hire an outside contractor for the installation and its validation.

We do not have data on the amount of time required to install and validate the installation of the software or the percentage of entities that might need to contract out the installation. For this analysis, we assumed it would take an entity 8 to 16 hours to install and validate the installation of CDRH's CeSub software and install, if necessary, Java Runtime Edition software and Java security policy files for their Internet browser. This estimate also includes the time required to notify FDA, run a test submission through the FDA ESG, and to train the appropriate staff to use the new program. We are also assuming that almost all medical device manufacturers, importers, and all user facilities would use this method to submit MDRs. Using an average wage of $46.50 for computer and mathematical occupations 3 (BLS 2006), we estimate the cost to install and use the software to be between $21.0 million and $41.7 million [(8 hours x $46.50 wage) x (38,500 user facilities + 18,000 manufacturers and importers) to (16 hours x $46.50 wage) x (38,500 user facilities + 18,000 manufacturers and importers)].

Entities that submit a large number of MDRs each year may choose to use the HL7 ICSR method to submit the reports. This method allows for the batch submission of multiple MDRs at faster transmission rates. We do not know at what threshold of reporting it becomes cost effective for an entity to submit medical device reports using this method. An analysis of FDA submission data for a 6-year period indicated that about 20 large medical device manufacturers submit 500 or more MDRs each year and about 85 submit close to 100 medical device reports per year. We assumed that the actual number of entities using the HL7 ICSR would fall somewhere within this range (20 to 85). We also assumed that only entities that have existing infrastructure to support HL7 ICSR transmissions would choose this method to submit MDRs. We estimated that it would take about 50 hours to set up their gateway to be compatible with the agency's system. Using the wage $46.50, the one-time cost for establishing HL7 ICSR submission capabilities would range between $50 thousand and $200 thousand [($46.50 x 50 hours) x 20 entities) and ($46.50 x 50 hours) x 85 entities)].

c. Electronic certificates . All entities would need an electronic certificate to submit any electronic regulatory document to the FDA ESG. The electronic certificate identifies the sender and serves as an electronic signature. Entities that have not submitted any electronic documents to the agency would incur a one-time cost to acquire the certificate and recurring costs to keep the certificate active as a result of this proposed rule. The certificates cost about $20 and are valid for 1 year. We assume that the search and transactions costs involved in the initial acquisition of the certificate doubles the cost of the certificate to a total of $40 for the first year, half of which would be setup costs. If all entities needed to acquire electronic certificates, the one-time search and acquisition costs would be $1.1 million ($20 acquisition cost x 56,500 entities).

In addition to the costs we have estimated, manufacturers, importers, and user facilities affected by this proposed rule may have to hire outside expertise to install and validate the software installation to comply with the proposed requirements.

Table 2 summarizes the estimated one-time costs by type of cost for this proposed rule by cost and type of manufacturers, importers, and user entities. The estimate of the total one-time costs for all manufacturers, importers, and user facilities ranges from $58.6 million to $79.7 million. Much of the cost involves acquiring the electronic certificate for the capability to submit any regulatory document to the FDA, including installation and validation of the CeSub software or to establish HL7 ICSR capabilities. Therefore, manufacturers, importers, and user facilities that are not already making electronic submissions of any kind to the agency if this proposed rule becomes final would incur these total costs.

The annual costs of this proposed rule would include the costs of:

• Maintaining certificates and

• High-speed Internet access.

a. Maintaining electronic certificates . Manufacturers, importers, and user facilities would bear the cost to maintain the electronic certificate that identifies the sender. In addition to having to renew the certificate on a regular basis, those entities who have not submitted MDRs would also have to ensure they are capable of transmitting electronic MDRs to FDA should such a report submission be necessary. To add these costs to the cost of the certificate itself, we assume that entities would incur an additional annually recurring cost equal to one-half the price of the certificate ($10), for a total annually recurring cost of $30. If all manufacturers, importers, and user facilities need to acquire electronic certificates, the annual cost would be $1.7 million ($30 acquisition certificate renewal and acquisition cost x 56,500 entities).

b. High-speed Internet access . Entities would also need high-speed Internet access to use either of the submission methods. A 2004 study of small businesses sponsored by the Small Business Administration (SBA) found that essentially all small firms had Internet access and about 50 percent had high-speed Internet access (Pociask, 2004). The average cost of high speed access was about $40 per month more than dial-up access. Because the average cost of Internet access has been going down over time, we estimate that by the time this proposed rule would be made final, about 75 percent of device and user facilities would have high speed access. The average annual recurring increase in cost for high speed Internet access for the remaining 25 percent of the entities would be $6.8 million (($40 x 12 months) x (0.25 x (18,000 manufacturers and importers + 38,500 user facilities))).

Table 3 shows the annual costs of the proposed rule. As with the one-time costs, only entities not making electronic regulatory document submissions of any kind to the agency if this proposed rule becomes final would incur all these costs. There would be no change in the actual time required to research and prepare the MDRs, nor would there be any additional reporting requirements as a result of this proposed rule. Manufacturers, importers, and user facilities that maintain paper FDA Form 3500A records for their internal MDR files own use could still do so under the proposed rule.

Cost savings: We estimate a modest industry savings of about $3.2 million annually because electronic submission should reduce the time it takes to submit documents. It should be noted that the savings accumulate to firms submitting MDRs; firms that submit very few or no MDRs would not realize any savings.

The principal benefit of this proposed rule would be the public health benefits associated with more rapid processing and analysis of the 100,000 initial individual MDRs currently submitted to FDA on a paper FDA Form 3500A. In addition, requiring electronic submission of MDRs is expected to reduce FDA annual operating costs by $1.25 million and generate industry savings of about $3.2 million.

The total one-time cost for modifying SOPs and establishing electronic submission capabilities is estimated to range from $58.6 million to $79.7 million. Annually recurring costs totaled $8.5 million and include maintenance of electronic submission capabilities, including renewing the electronic certificate, and for some entities the incremental cost to maintain high-speed Internet access. The total annualized cost of the proposed rule, assuming a 7-percent discount rate over 10 years, would be from $16.8 million to $19.9 million ($15.4 million to $17.8 million at a 3-percent discount rate). We request comment on the accuracy and completeness of the assumptions used to estimate the costs of this proposed rule. For example, we invite comment on our use of a 10-year time horizon and whether a shorter or a longer horizon would be more appropriate to express the social costs of this proposed rule.

During the development of this proposed rule, we considered a number of alternative approaches. The first was to allow manufacturers, importers, and user facilities to voluntarily submit MDRs electronically. Because our experience has shown that a number of medical device firms and user facilities would resist changing their procedures for a long period of time, we would not attain the benefits of standardized formats and quicker access to medical device adverse event data. The FDA, for example, would have to maintain contracts to handle the input of information from both written and electronic MDRs. A voluntary system, therefore, would fail to achieve the goals of this proposed rule.

Another alternative was to allow small entities more time to comply with the electronic submission requirements. This alternative would allow small entities to delay compliance. Under this alternative, we would not receive the full data-entry savings from requiring electronic submissions or all the benefits of quicker access to these reports. Because so many device companies are small entities, this approach would significantly postpone the benefits the rule is intended to confer. Moreover, as shown in the following section, the estimated incremental costs per small entity from the proposed rule are small, so the cost reduction per small entity from delayed compliance would also be small.

The SBA defines a small medical device manufacturer as having fewer than 500 employees. Based on data from U.S. Census, about 98 percent of device firms affected by this proposed rule are considered small entities, and have an average value of shipments of about $9.0 million. 4 Businesses in the health care industry are classified as small if their revenues are below a certain level. Hospitals are small if their total revenue falls below $25 million and the other user facilities are considered small if their revenues are below $10 million. U.S. Census data indicates that about 87 percent of the user facilities are classified as small and have a weighted average revenue of about $3.3 million. 5 However, very few user facilities submit MDRs in any given year. While this proposed rule will now require those reports submitted to the agency to be in electronic format, the content of a report is not being changed from that already addressed on the current FDA Form 3500A. The average costs for these manufacturers, importers, and user facilities are listed in table 4. The average total annualized cost per small entity, assuming a 7-percent discount rate over 10 years, would range from $581 to $693; at a 3-percent discount rate, average annualized costs would range from $568 to $661. These costs represent less than 0.1 percent of revenues for medical device firms and less than 0.1 percent of revenues for user facilities.

We considered two possible alternatives for regulatory relief for small businesses. As described above, one regulatory alternative would be longer compliance times for small entities. We would not receive the full data-entry savings from requiring electronic submissions or all the benefits of quicker access to these reports. Because so many device companies are small entities, this approach would significantly postpone the benefits the rule is intended to confer. Moreover, as shown above, the estimated incremental costs per small entity from the proposed rule are small, so the cost reduction per small entity from delayed compliance would also be small.

In addition, we considered proposing a waiver to the electronic submission requirement for small firms that can demonstrate an economic hardship. Because the estimated incremental costs per small entity from the proposed rule are small, the cost reduction per small entity from a waiver would also be small.

We ask for comments on both of these options for regulatory relief for small entities.

While the estimated costs per affected entity are low, FDA does not have adequate information on the electronic capabilities of all of the firms affected by this proposed rule and has made many assumptions to derive these estimate used in this analysis, therefore we do not propose to certify that this proposed rule would not have a significant economic impact on a substantial number of small entities. FDA requests comment on this issue.

This proposed rule contains information collection provisions that are subject to review by OMB under the PRA (44 U.S.C. 3501-3520). A description of these provisions is given in this document with an estimate of the annual reporting and recordkeeping burden. Included in the estimate is the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing each collection of information.

FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

Title : Medical Device Reporting

Description : In accordance with the proposed Medical Device Reporting regulation, medical device manufacturers, importers, and user facilities would be required to submit MDRs to FDA, to maintain records, and may also seek exemption or variance from these requirements. FDA is also proposing to amend §§ 803.32, 803.42, and 803.52 to make minor wording changes and corrections to these sections to reflect modifications already made to FDA Form 3500A and its instructions. Manufacturers, importer, and user facilities are currently submitting paper MDR reports on FDA Form 3500A. The existing information collection for part 803 is approved under OMB control number 0910-0437. The changes to the burden associated with this proposed rule are described below and have been sent to OMB as a revision to OMB control number 0910-0437 for review under section 307(d) of the PRA.

Section 519(a)(1) of the act (21 U.S.C. 360i(a)(1)) requires every manufacturer or importer to report “whenever the manufacturer or importer receives or otherwise becomes aware of information that reasonably suggests that one of its marketed devices—

(A) may have caused or contributed to a death or serious injury, or

(B) has malfunctioned and that such device or a similar device marketed by the manufacturer or importer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur * * *”

Section 519(b)(1)(A) of the act requires “whenever a device user facility receives or otherwise becomes aware of information that reasonably suggests that a device has or may have caused or contributed to the death of a patient of the facility, the facility shall, as soon as practicable but not later than 10 working days after becoming aware of the information, report the information to the Secretary and, if the identity of the manufacturer is known, to the manufacturer of the device.”

Section 519(b)(1)(B) of the act requires “whenever a device user facility receives or otherwise becomes aware of: (i) information that reasonably suggests that a device has or may have caused or contributed to the serious illness of, or serious injury to, a patient of the facility * * *, shall, as soon as practicable but not later than 10 working days after becoming aware of the information, report the information to the manufacturer of the device or to the Secretary if the identity of the manufacturer is not known.”

Complete, accurate, and timely adverse event information is necessary for the identification of emerging device problems so the agency can protect the public health under section 519 of the act. FDA is requesting approval for the information collection requirements contained in part 803.

Description of Respondents : Manufacturers and importers of medical devices and device user facilities. Device user facility means a hospital, ambulatory surgical facility, nursing home, outpatient diagnostic facility, or outpatient treatment facility as defined in § 803.3, which is not a physician's office (also defined in § 803.3).

The total annual estimated burden imposed by this collection of information is 21,525 hours annually.

The approved MDR reporting and recordkeeping burden for paper submissions is 138,271 hours. This proposed rule reporting and recordkeeping burden for electronic submissions is 21,525 hours, a decrease of 123,071 hours. Based on an average wage rate of $46.50 per hour, the total cost to respondents associated with these reporting and recordkeeping burdens is $1,000,913. An explanation for the burden decrease is provided below.

The number of respondents for each Code of Federal Regulations (CFR) section in table 5 is based upon the number of respondents entered into FDA's internal databases. FDA estimates that electronic submission will decrease the burden associated with §§ 803.19, 803.30, 803.32, 803.40, 803.50, 803.52, and 803.56. We believe electronic submission will neither increase nor decrease burden associated with § 803.33, which we estimate will take 1 hour. We believe § 803.19 will take 1 hour, while §§ 803.30, 803.32, 803.40, and 803.42 will take 20 minutes. Sections 803.50 and 803.52 will take 7 minutes. Section 803.56 will take 6 minutes. The following table summarizes our burden estimates and how we believe they will change due to electronic submission.

As previously described, there are two reporting options. The first one is CeSub for low volume reporters and the second one is HL7 ICSR for high volume reporters. We are basing our hours per response for both systems on FDA's experience using the two options.

The number of respondents for each CFR section in table 6 is based upon the number of respondents entered into FDA's internal databases. The agency believes that the majority of manufacturers, user facilities, and importers have already established written procedures to document complaints and information to meet the MDR requirements as part of their internal quality control system. The following table summarizes our burden estimates and how we believe they will change due to electronic submission.

As stated earlier, the cost to respondents for these reporting and recordkeeping requirements is $1,000,913. In addition, the conversion from paper to electronic submissions will result in capital costs, both one-time costs as well as annual costs, as discussed earlier in this proposed rule in the economic analysis. One-time capital costs include the cost to modify reporting systems, installing and validating CeSub software, installing gateway to gateway submission capabilities, and acquiring e-certificates and have been estimated to range from a low of $58.6 million to a high of $79.7 million. Once the procedures have been modified, there is an operating and maintenance cost to renew the digital certificate and maintain high-speed internet access, which have been estimated cost $8.5 million each year. Burden estimates are based on reports processed between July 1, 2005, and June 30, 2006, with the existing medical device adverse event reporting program.

In compliance with the PRA, the agency has submitted the information collection provisions of this proposed rule to OMB for review. Interested persons are requested to send comments regarding information collection to OMB (see the DATES and ADDRESSES sections of this document).

FDA has analyzed this proposed rule in accordance with the principles set forth in Executive Order 13132. FDA has determined that this rule does not contain policies that have federalism implications as defined in the order and, consequently, a federalism summary impact statement is not required.

Interested persons may submit to the Division of Dockets Management (see ADDRESSES ) written or electronic comments regarding this document. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

The following references have been placed on display in the Division of Dockets Management (see ADDRESSES ) and may be seen by interested persons between 9 a.m. and 4 p.m., Monday through Friday. (FDA has verified the Web site addresses, but is not responsible for any subsequent changes to the Web site after this document publishes in the Federal Register .)

Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, FDA proposes to amend part 803 to read as follows:

In accordance with the provisions of the CSA (21 U.S.C. 811(a)), this action is a formal rulemaking “on the record after opportunity for a hearing.” Such proceedings are conducted pursuant to the provisions of the Administrative Procedure Act (5 U.S.C. 556 and 557). All persons are invited to submit their comments or objections with regard to this proposal. Requests for a hearing may be submitted by interested persons and must conform to the requirements of 21 CFR 1308.44 and 1316.47. The request should state, with particularity, the issues concerning which the person desires to be heard and the requestor's interest in the proceeding. Only interested persons, defined in the regulations as those “adversely affected or aggrieved by any rule or proposed rule issuable pursuant to section 201 of the Act (21 U.S.C. 811),” may request a hearing.

Please note that all comments received are considered part of the public record and made available for public inspection online at http://www.regulations.gov and in the Drug Enforcement Administration's public docket. Such information includes personal identifying information (such as your name, address, etc.) voluntarily submitted by the commenter.

If you want to submit personal identifying information (such as your name, address, etc.) as part of your comment, but do not want it to be posted online or made available in the public docket, you must include the phrase “PERSONAL IDENTIFYING INFORMATION” in the first paragraph of your comment. You must also place all the personal identifying information you do not want posted online or made available in the public docket in the first paragraph of your comment and identify what information you want redacted.

If you want to submit confidential business information as part of your comment, but do not want it to be posted online or made available in the public docket, you must include the phrase “CONFIDENTIAL BUSINESS INFORMATION” in the first paragraph of your comment. You must also prominently identify confidential business information to be redacted within the comment. If a comment has so much confidential business information that it cannot be effectively redacted, all or part of that comment may not be posted online or made available in the public docket.

Personal identifying information and confidential business information identified and located as set forth above will be redacted and the comment, in redacted form, will be posted online and placed in the Drug Enforcement Administration's public docket file. Please note that the Freedom of Information Act applies to all comments received. If you wish to inspect the agency's public docket file in person by appointment, please see the FOR FURTHER INFORMATION CONTACT paragraph.

5-MeO-DMT is related to the schedule I hallucinogen, N,N-dimethyltryptamine (DMT), in its chemical structure and pharmacological properties. 5-MeO-DMT also shares pharmacological similarities with several other schedule I hallucinogens such as 2,5-dimethoxy-4-methylamphetamine (DOM), lysergic acid diethylamide (LSD) and mescaline. In animal drug discrimination studies, DOM, LSD, mescaline, DMT, and alpha-methyltryptamine (AMT) fully substitute for the discriminative stimulus cue of 5-MeO-DMT. In in vitro receptor binding studies, 5-MeO-DMT, similar to DMT and other schedule I hallucinogens, binds to central serotonin 2 (5-HT 2 ) receptors.

Studies show that the potencies of hallucinogens in humans correlate with their drug affinities for the 5-HT 2 receptor and discriminative stimulus potencies. Accordingly, 5-MeO-DMT produces psychoactive effects in humans following inhalation (~6-20 mg), intravenous injection (~0.7-3.1 mg), sublingual (~10 mg), intranasal insufflation (~10 mg) and oral (~30 mg) (if encapsulated or taken with a monoamine oxidase inhibitor) routes of administration. Anecdotal reports from humans who have used 5-MeO-DMT describe hallucinogenic effects similar to those produced by DMT. 5-MeO-DMT, however, is reported to be 4 to 5-fold more potent than DMT when administered by inhalation, sublingual or oral (if encapsulated) routes of administration.

Evidence of the abuse of 5-MeO-DMT was first reported in 1999 by federal law enforcement personnel. According to the System to Retrieve Information on Drug Evidence (STRIDE), a federal database for seized drug exhibits analyzed by DEA laboratories, from January 1999 to December 2008, law enforcement seized 33 drug exhibits and filed 23 cases pertaining to the trafficking, distribution and abuse of 5-MeO-DMT. The seized drug exhibits comprised 89 grams of powder and 10 milliliters of liquid containing 5-MeO-DMT. Since 2004, National Forensic Laboratory Information System (NFLIS), a database for drug cases analyzed by federal, state and local forensic laboratories, registered 23 state and local cases involving 27 analyzed items containing 5-MeO-DMT.

There is evidence of clandestine laboratory operations to synthesize 5-MeO-DMT. 5-MeO-DMT has been encountered in powder, capsule, and liquid forms. 5-MeO-DMT is typically abused either by smoking or insufflating the powder. Investigations by federal law enforcement indicate that individuals, especially youths and young adults, are purchasing 5-MeO-DMT from Internet-based chemical suppliers. In addition, there are several instances where 5-MeO-DMT was sold as a counterfeit of MDMA.

The risks to the public health associated with the abuse of 5-MeO-DMT are similar to the risks associated with those of schedule I hallucinogens. 5-MeO-DMT can pose serious health risks to the user and general public through its ability to induce hallucinogenic effects and other sensory distortions and impaired judgment. Self-reports that are posted on Internet Web sites describe the abuse of this substance in combination with other controlled drugs such as DMT, N,N-diethyltryptamine (DET), LSD, marijuana, ecstasy, or mushrooms (contains psilocybin and psilocin). This practice of drug abuse involving combinations can pose additional health risks to the users and the general public. These data show that the continued trafficking and abuse of 5-MeO-DMT pose hazards to the public health and safety. Indeed, there have been reports of emergency room admissions and death associated with the abuse of 5-MeO-DMT.

There are no FDA-approved drug products. 5-MeO-DMT has never been approved by the FDA for marketing as a human drug product in the United States and there are no recognized therapeutic uses of 5-MeO-DMT in the United States.

References to the above studies and data may be found in the Health and Human Services scheduling recommendation and DEA's independent analysis, both of which are available on the electronic docket associated with this rulemaking.

In accordance with 21 U.S.C. 811(b) of the CSA, DEA has gathered and reviewed the available information regarding the pharmacology, chemistry, trafficking, actual abuse, pattern of abuse, and the relative potential for abuse of 5-MeO-DMT. On February 21, 2007, the Deputy Administrator of the DEA submitted these data to the Acting Assistant Secretary for Health, Department of Health and Human Services. In accordance with 21 U.S.C. 811(b), the Deputy Administrator also requested a scientific and medical evaluation and a scheduling recommendation for 5-MeO-DMT from the Acting Assistant Secretary for Health. On December 18, 2008, the Principal Deputy Assistant Secretary for Health, Department of Health and Human Services (DHHS), sent the Deputy Administrator of the DEA a scientific and medical evaluation and a letter recommending that 5-MeO-DMT and its salts be placed into schedule I of the CSA. Enclosed with the letter was a document prepared by FDA entitled, “Basis for the Recommendation to Control 5-Methoxy-Dimethyltryptamine (5-MeO-DMT) in Schedule I of the Controlled Substances Act.” The document contained a review of the factors which the CSA requires the Secretary to consider (21 U.S.C. 811(b)). The factors considered by the Assistant Secretary of Health and DEA with respect to 5-MeO-DMT were:

(1) Actual or relative potential for abuse;

(2) Scientific evidence of its pharmacological effects, if known;

(3) The state of current scientific knowledge regarding the drug;

(4) History and current pattern of abuse;

(5) The scope, duration, and significance of abuse;

(6) What, if any, risk there is to the public health;

(7) Psychic or physiological dependence liability; and

(8) Whether the substance is an immediate precursor of a substance already controlled under the CSA.

Based on the recommendation of the Assistant Secretary for Health, received in accordance with section 201(b) of the Act (21 U.S.C. 811(b)), and the independent review of the available data by DEA, the Deputy Administrator finds that sufficient data exist to support the placement of 5-MeO-DMT into schedule I of the CSA pursuant to 21 U.S.C. 811(a). The specific findings required pursuant to 21 U.S.C. 811 and 812 for 5-MeO-DMT to be placed into schedule I are as follows:

(1) 5-MeO-DMT has a high potential for abuse.

(2)5-MeO-DMT has no currently accepted medical use in treatment in the United States.

(3) There is a lack of accepted safety for use of 5-MeO-DMT under medical supervision.

If this rule is finalized as proposed, 5-methoxy-N,N-dimethyltryptamine would be subject to regulatory controls and administrative, civil and criminal sanctions applicable to the manufacture, distribution, dispensing, importation and exportation of a schedule I controlled substance, including the following:

Registration. Any person who manufactures, distributes, dispenses, imports or exports 5-methoxy-N,N-dimethyltryptamine or who engages in research or conducts instructional activities with respect to 5-methoxy-N,N-dimethyltryptamine, or who proposes to engage in such activities, would be required to submit an application for schedule I registration in accordance with part 1301 of Title 21 of the Code of Federal Regulations.

Security. 5-methoxy-N,N-dimethyltryptamine would be subject to schedule I security requirements and must be manufactured, distributed and stored in accordance with §§ 1301.71; 1301.72(a), (c), and (d); 1301.73; 1301.74; 1301.75(a) and (c); and 1301.76 of Title 21 of the Code of Federal Regulations.

Labeling and Packaging. All labels and labeling for commercial containers of 5-methoxy-N,N-dimethyltryptamine which are distributed on or after the effective date of a Final Rule finalizing this regulation would be required to comply with requirements of §§ 1302.03 through 1302.07 of Title 21 of the Code of Federal Regulations.

Quotas. Quotas for 5-methoxy-N,N-dimethyltryptamine would be established pursuant to the requirements of part 1303 of Title 21 of the Code of Federal Regulations.

Inventory. Every registrant required to keep records and who possesses any quantity of 5-methoxy-N,N-dimethyltryptamine upon the effective date of any Final Rule finalizing these regulations would be required to keep an inventory of all stocks of the substance on hand pursuant to §§ 1304.03, 1304.04 and 1304.11 of Title 21 of the Code of Federal Regulations. Every registrant who desires registration in schedule I to handle 5-methoxy-N,N-dimethyltryptamine would be required to conduct an inventory of all stocks of the substance.

Records. All registrants who handle 5-methoxy-N,N-dimethyltryptamine would be required to keep records pursuant to §§ 1304.03, 1304.04 1304.21, 1304.22, and 1304.23 of Title 21 of the Code of Federal Regulations.

Reports. All registrants required to submit reports in accordance with § 1304.33 of Title 21 of the Code of Federal Regulations would be required to do so regarding 5-methoxy-N,N-dimethyltryptamine.

Order Forms. All registrants involved in the distribution of 5-methoxy-N,N-dimethyltryptamine would be required to comply with the order form requirements of part 1305 of Title 21 of the Code of Federal Regulations.

Importation and Exportation. All importation and exportation of 5-methoxy-N,N-dimethyltryptamine would be required to be in compliance with part 1312 of Title 21 of the Code of Federal Regulations.

Criminal Liability. Any activity with 5-methoxy-N,N-dimethyltryptamine not authorized by, or in violation of, the Controlled Substances Act or the Controlled Substances Import and Export Act occurring on or after the effective date of any Final Rule finalizing these regulations would be unlawful.

In accordance with the provisions of the CSA (21 U.S.C. 811(a)), this action is a formal rulemaking “on the record after opportunity for a hearing.” Such proceedings are conducted pursuant to the provisions of 5 U.S.C. 556 and 557 and, as such, are exempt from review by the Office of Management and Budget pursuant to Executive Order 12866, section 3(d)(1).

The Deputy Administrator, in accordance with the Regulatory Flexibility Act (5 U.S.C. 601-612), has reviewed this proposed rule and by approving it certifies that it will not have a significant economic impact on a substantial number of small entities. This proposed rule, if finalized, would place 5-methoxy-N,N-dimethyltryptamine into schedule I of the Controlled Substances Act.

This regulation meets the applicable standards set forth in Sections 3(a) and 3(b)(2) of Executive Order 12988 Civil Justice Reform.

This rulemaking does not preempt or modify any provision of State law; nor does it impose enforcement responsibilities on any State; nor does it diminish the power of any State to enforce its own laws. Accordingly, this rulemaking does not have federalism implications warranting the application of Executive Order 13132.

This rule will not result in the expenditure by State, local and tribal governments, in the aggregate, or by the private sector, of $120,000,000 or more (adjusted for inflation) in any one year, and will not significantly or uniquely affect small governments. Therefore, no actions were deemed necessary under provisions of the Unfunded Mandates Reform Act of 1995.

This rule is not a major rule as defined by § 804 of the Small Business Regulatory Enforcement Fairness Act of 1996 (Congressional Review Act). This rule will not result in an annual effect on the economy of $100,000,000 or more; a major increase in costs or prices: or significant adverse effects on competition, employment, investment, productivity, innovation, or on the ability of United States-based companies to compete with foreign based companies in domestic and export markets.

Under the authority vested in the Attorney General by section 201(a) of the CSA (21 U.S.C. 811(a)), and delegated to the Administrator of DEA by Department of Justice regulations (28 CFR 0.100), and redelegated to the Deputy Administrator pursuant to 28 CFR 0.104, the Deputy Administrator hereby proposes that 21 CFR part 1308 be amended as follows:

We encourage you to participate in this rulemaking by submitting comments and related materials. All comments received will be posted without change to http://www.regulations.gov and will include any personal information you have provided.

If you submit a comment, please include the docket number for this rulemaking (USCG-2009-0720), indicate the specific section of this document to which each comment applies, and provide a reason for each suggestion or recommendation. You may submit your comments and material online (via http://www.regulations.gov ) or by fax, mail, or hand delivery, but please use only one of these means. If you submit a comment online via http://www.regulations.gov, it will be considered received by the Coast Guard when you successfully transmit the comment. If you fax, hand deliver, or mail your comment, it will be considered as having been received by the Coast Guard when it is received at the Docket Management Facility. We recommend that you include your name and a mailing address, an e-mail address, or a telephone number in the body of your document so that we can contact you if we have questions regarding your submission.

To submit your comment online, go to http://www.regulations.gov, click on the “submit a comment” box, which will then become highlighted in blue. In the “Document Type” drop down menu, select “Notices” and insert “USCG-2009-0720” in the ”Keyword” box. Click “Search” then click on the balloon shape in the Actions column. If you submit your comments by mail or hand delivery, submit them in an unbound format, no larger than 8 1/2 ; by 11 inches, suitable for copying and electronic filing. If you submit comments by mail and would like to know that they reached the Facility, please enclose a stamped, self-addressed postcard or envelope. We will consider all comments and material received during the comment period and may change the rule based on your comments.

To view comments, as well as documents mentioned in this preamble as being available in the docket, go to http://www.regulations.gov, click on the “read comments” box, which will then become highlighted in blue. In the “Keyword” box, insert USCG-2009-0720 and click “Search.” Click the “Open Docket Folder” in the “Actions” column. You may also visit the Docket Management Facility in Room W12-140 on the ground floor of the Department of Transportation West Building, 1200 New Jersey Avenue, SE., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. We have an agreement with the Department of Transportation to use the Docket Management Facility.

Anyone can search the electronic form of comments received into any of our dockets by the name of the individual submitting the comment (or signing the comment, if submitted on behalf of an association, business, labor union, etc. ). You may review a Privacy Act notice regarding our public dockets in the January 17, 2008 issue of the Federal Register (73 FR 3316).

We do not now plan to hold a public meeting. But you may submit a request for one on or before August 18, 2009, using one of the four methods specified under ADDRESSES . Please explain why you believe a public meeting would be beneficial. If we determine that one would aid this rulemaking, we will hold one at a time and place announced by a later notice in the Federal Register.

On September 19-20, 2009, the Ocean City Business and Neighborhood Development INC will sponsor the Ocean City Beachfront Air Show. The event will consist of high performance jet aircraft performing low altitude aerial maneuvers over the waters of the Atlantic Ocean adjacent to Ocean City, New Jersey. A fleet of spectator vessels is expected to gather nearby to view the aerial demonstration. Due to the need for vessel control during the event, vessel traffic will be temporarily restricted to provide for the safety of spectators and transiting vessels.

The Coast Guard proposes to establish a temporary safety zone on the North Atlantic Ocean, immediately adjacent to the shoreline at Ocean City, New Jersey. Except for persons or vessels authorized by the Coast Guard Patrol Commander, no person or vessel may enter or remain in the regulated areas during the enforcement period. The Patrol Commander will notify the public of specific enforcement times by Marine Radio Safety Broadcast. This regulation will be enforced to prevent personal injury to mariners and damage to vessel traffic during the event.

The temporary safety zone includes all waters offshore from Ocean City, New Jersey, bounded within the following area: Beginning at latitude 39°16′28″ N, longitude 074°33′38″ W, thence southeasterly to latitude 39°16′20″ N, longitude 074°33′30″ W, thence southwesterly to latitude 39°15′38″ N, longitude 074°34′41″ W, thence northwesterly to latitude 39°15′47″ N, longitude 074°34′51″ W, thence returning northeasterly to latitude 39°16′28″ N, longitude 074°33′38″ W. All coordinates listed for the following safety zones reference Datum NAD 1983.

This temporary safety zone will be enforced from 1 p.m. to 3 p.m. on September 19, 2009, and from 12 p.m. (noon) to 4 p.m. on September 20, 2009.

We developed this proposed rule after considering numerous statutes and executive orders related to rulemaking. Below we summarize our analyses based on 13 of these statutes or executive orders.

This proposed rule is not a significant regulatory action under section 3(f) of Executive Order 12866, Regulatory Planning and Review, and does not require an assessment of potential costs and benefits under section 6(a)(3) of that Order. The Office of Management and Budget has not reviewed it under that Order.

We expect the economic impact of this proposed rule to be so minimal that a full Regulatory Assessment is unnecessary. Although this regulation restricts vessel traffic from transiting a small segment of coastal waters near Ocean City, New Jersey, the effect of this regulation will not be significant due to the limited duration that the regulated area will be in effect and the advance notifications that will be made to the maritime community via marine information broadcasts and area newspapers so mariners can adjust their plans accordingly.

Under the Regulatory Flexibility Act (5 U.S.C. 601-612), we have considered whether this proposed rule would have a significant economic impact on a substantial number of small entities. The term “small entities” comprises small businesses, not-for-profit organizations that are independently owned and operated and are not dominant in their fields, and governmental jurisdictions with populations of less than 50,000.

The Coast Guard certifies under 5 U.S.C. 605(b) that this proposed rule would not have a significant economic impact on a substantial number of small entities. This rule will affect the following entities, some of which may be small entities: The owners or operators of vessels intending to transit coastal waters in the vicinity of Ocean City, New Jersey during the event.

This safety zone will not have a significant economic impact on a substantial number of small entities for the following reasons. This rule will be in effect for only a short period, from 1 p.m. to 3 p.m. on September 19, 2009 and from 12 a.m. (noon) to 4 p.m. on September 20, 2009. Traffic will be allowed to pass through the zone with the permission of the Coast Guard patrol commander. Before the enforcement period, we will issue maritime advisories so mariners can adjust their plans accordingly.

If you think that your business, organization, or governmental jurisdiction qualifies as a small entity and that this rule would have a significant economic impact on it, please submit a comment (see ADDRESSES ) explaining why you think it qualifies and how and to what degree this rule would economically affect it.

Under section 213(a) of the Small Business Regulatory Enforcement Fairness Act of 1996 (Pub. L. 104-121), we want to assist small entities in understanding this proposed rule so that they can better evaluate its effects on them and participate in the rulemaking. If the rule would affect your small business, organization, or governmental jurisdiction and you have questions concerning its provisions or options for compliance, please contact Lieutenant Rebecca Walthour, Chief of Waterways Management Branch, Coast Guard Sector Delaware Bay, at 215-271-4889, or e-mail Rebecca.A.Walthour@uscg.mil. The Coast Guard will not retaliate against small entities that question or complain about this proposed rule or any policy or action of the Coast Guard.

This proposed rule would call for no new collection of information under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520.).

A rule has implications for federalism under Executive Order 13132, Federalism, if it has a substantial direct effect on State or local governments and would either preempt State law or impose a substantial direct cost of compliance on them. We have analyzed this proposed rule under that Order and have determined that it does not have implications for federalism.

The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538) requires Federal agencies to assess the effects of their discretionary regulatory actions. In particular, the Act addresses actions that may result in the expenditure by a State, local, or tribal government, in the aggregate, or by the private sector of $100,000,000 or more in any one year. Though this proposed rule would not result in such an expenditure, we do discuss the effects of this rule elsewhere in this preamble.

This proposed rule would not effect a taking of private property or otherwise have taking implications under Executive Order 12630, Governmental Actions and Interference with Constitutionally Protected Property Rights.

This proposed rule meets applicable standards in sections 3(a) and 3(b)(2) of Executive Order 12988, Civil Justice Reform, to minimize litigation, eliminate ambiguity, and reduce burden.

We have analyzed this proposed rule under Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and would not create an environmental risk to health or risk to safety that might disproportionately affect children.

This proposed rule does not have tribal implications under Executive Order 13175, Consultation and Coordination with Indian Tribal Governments, because it would not have a substantial direct effect on one or more Indian tribes, on the relationship between the Federal Government and Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes.

We have analyzed this proposed rule under Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use. We have determined that it is not a “significant energy action” under that order because it is not a “significant regulatory action” under Executive Order 12866 and is not likely to have a significant adverse effect on the supply, distribution, or use of energy. The Administrator of the Office of Information and Regulatory Affairs has not designated it as a significant energy action. Therefore, it does not require a Statement of Energy Effects under Executive Order 13211.

The National Technology Transfer and Advancement Act (NTTAA) (15 U.S.C. 272 note) directs agencies to use voluntary consensus standards in their regulatory activities unless the agency provides Congress, through the Office of Management and Budget, with an explanation of why using these standards would be inconsistent with applicable law or otherwise impractical. Voluntary consensus standards are technical standards ( e.g. , specifications of materials, performance, design, or operation; test methods; sampling procedures; and related management systems practices) that are developed or adopted by voluntary consensus standards bodies.

This proposed rule does not use technical standards. Therefore, we did not consider the use of voluntary consensus standards.

We have analyzed this proposed rule under Department of Homeland Security Management Directive 023-01 and Commandant Instruction M16475.lD, which guide the Coast Guard in complying with the National Environmental Policy Act of 1969 (NEPA) (42 U.S.C. 4321-4370f), and have made a preliminary determination that this action is one of a category of actions which do not individually or cumulatively have a significant effect on the human environment. A preliminary environmental analysis checklist supporting this determination is available in the docket where indicated under ADDRESSES . This proposed rule involves creating a temporary safety zone on the waters of the Atlantic Ocean offshore from Ocean City, New Jersey, which will restrict vessel movement due to a scheduled air show. We seek any comments or information that may lead to the discovery of a significant environmental impact from this proposed rule.

For the reasons discussed in the preamble, the Coast Guard proposes to amend 33 CFR part 165 as follows:

Extension of Comment Period: EPA received requests for an extension of the public comment period from various parties ranging from 60 to 90 days. After considering all of these comments, EPA has determined that an extension of an additional 60 days is an appropriate amount of time to provide the public for submission of meaningful comments on the proposed rule. Accordingly, the public comment period for the HPD proposed rulemaking is extended until November 4, 2009. EPA does not anticipate any further extension of the comment period at this time.

Reschedule of Public Hearing: EPA received requests for a public hearing. In view of the above extension of the comment period the EPA is establishing October 7, 2009 as the date for the public hearing that was originally scheduled for August 25, 2009. EPA believes that this postponement will provide adequate time for interested parties to develop their verbal comments and presentations.