[Federal Register Volume 77, Number 224 (Tuesday, November 20, 2012)]
[Notices]
[Pages 69637-69638]
[FR Doc No: 2012-28197]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0974]

Development of Prioritized Therapeutic Area Data Standards;
Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the
intent to prioritize and develop therapeutic area data standards to
facilitate the conduct of clinical research and the regulatory review
of medical products. Therapeutic area disease and domain specific data
standards should enable and enhance the ability to integrate, analyze,
report, and share regulatory information. FDA has developed a roadmap
that provides its current thinking on therapeutic area priorities and
has posted it on the FDA Web site. FDA is actively participating with
regulated industry, the Clinical Data Interchange Standards Consortium
(CDISC), the Critical Path Institute, Health Level 7's (HL7) Clinical
Interoperability Council, and other stakeholders to support the
development of these therapeutic area standards. The therapeutic area
standards will be developed collaboratively based on open, consensus-
based data standards development methodology.

DATES: To ensure that the Agency considers your comments, submit either
electronic or written comments by January 22, 2013.

ADDRESSES: Submit written requests for a copy of the roadmap to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm.
2201, Silver Spring, MD 20993-0002, or the Office of Communication,
Outreach and Development (HFM-40), Center for Biologics Evaluation and
Research, Food and Drug Administration, 1401 Rockville Pike, Rockville,
MD 20852-1448. Send one self-addressed adhesive label to assist that
office in processing your requests.
    Submit electronic comments on FDA's objective to develop
prioritized therapeutic area data standards or on the roadmap to http://www.regulations.gov. Submit written comments to the Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, Rm. 1061, Rockville, MD 20852. See the SUPPLEMENTARY
INFORMATION section for electronic access to the roadmap.

FOR FURTHER INFORMATION CONTACT:

Ron Fitzmartin, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 1160, Silver
Spring, MD 20993-0002<EMAIL_ADDRESS>or
Amy Malla, Center for Biologics Evaluation and Research (HFM-25), 1401
Rockville Pike, Suite 200N, Rockville, MD 20852-1448,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    Traditionally, clinical study data submitted to FDA is in a format
that is unique to each individual sponsor; furthermore the data quality
varies. This has created inefficiencies in the review process and
impeded efforts to analyze the data across applications when such
analyses could be beneficial to detect trends in safety or efficacy or
for other reasons. Sponsor adoption of available clinical trial data
standards (CDISC/SDTM) for the submission of product applications have
helped to improve the quality and standardization of submitted data.
However, such a voluntary approach has proved insufficient to support
both the current business requirements as well as efforts to modernize
the review environment.
    In 2011, the Center for Drug Evaluation and Research (CDER)
identified a set of disease and therapeutic areas that could benefit
from further standardization. These content area standards are
primarily intended to support the efficient evaluation of medical
products as noted previously in this document. Several factors were
considered in the identification of these areas: (1) Areas of
particular need, (2) areas with existing data standardization projects
underway, and (3) areas with greater drug development pipeline
activity. The initial prioritization was based on the number of active
investigational new drug applications (or INDs) and input from review
divisions, as well as from industry. The three tiers of priority were
assembled into a roadmap and posted on the FDA Web site at http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm287408.htm. The
roadmap sets out a sequence of standardization efforts to achieve
significant results by December 2017. CDER established a small grants
program to fund projects that develop

disease and domain-specific therapeutic area data standards.
    On July 9, 2012, President Obama signed into law the Food and Drug
Administration Safety and Innovation Act of 2012, which includes the
reauthorization of the Prescription Drug User Fee Act (PDUFA V). Under
section XII of the PDUFA V performance goals, FDA agreed to create a
plan for distinct therapeutic area data standards and to prioritize and
develop the data standards in collaboration with CDISC and other open
standards organizations. FDA is seeking public comment on the roadmap
and will consider the comments as the Agency develops its proposed
project plan which is due to be issued for review and comment by June
30, 2013. In addition, FDA will publish notices soliciting input on,
and engagement in, standards development activities, and will
periodically issue guidances specifying the completed data standards,
formats, and terminologies that sponsors should use to submit data in
applications.

II. Comments

    Interested persons may submit either written comments regarding the
roadmap, as well as recommendations on how the therapeutic area data
standards development effort could be accomplished more rapidly, to the
Division of Dockets Management (see ADDRESSES) or electronic comments
to http://www.regulations.gov. It is only necessary to send one set of
comments. Identify comments 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, and will be posted to the docket at http://www.regulations.gov.

III. Electronic Access

    Persons with access to the Internet may obtain the roadmap at
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm287408.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm, or http://www.regulations.gov.

    Dated: November 15, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-28197 Filed 11-19-12; 8:45 am]
BILLING CODE 4160-01-P


U. S. Environmental Protection Agency Meeting Summary August 1, 2003 Enforceable Consent Agreement Development for Perfluorooctanoic Acid ( PFOA) and Fluorinated Telomers Summary of July 10, 2003 Public Plenary Meeting Ninety nine people attended the second public enforceable consent agreement ( ECA) Plenary session meeting on PFOA and fluorinated telomers at EPA Headquarters in Washington, DC on Thursday July 10, 2003 from noon to 3: 30 PM. The meeting participants represented registered interested parties, observers, and EPA staff. Copies of the attendance list, the meeting agenda, and the four summary presentations made by the PFOA ECA Technical Workgroups can be found in the electronic docket at OPPT 2003 0012 0148. The next plenary meeting was tentatively scheduled for the week of October 20, 2003, in Washington, DC.

I. Introduction EPA welcomed the participants to the plenary session and presented a brief review of the current state of affairs. EPA summarized the agreements reached at the June 6, 2003 plenary meeting, and described the subsequent technical workgroup meetings held on June 23, June 24, July 9, and July 10, 2003.

A general overview of the tasks assigned by the June 6, 2003 Plenary to the 4 workgroups was stated as follows: ° The Communications Workgroup was tasked with focusing on CBI issues and working toward obtaining a means for industry to make publicly available non CBI market and production volume information that would meet the needs of interested parties. ° The Monitoring Technical Workgroup was to address technical details of data needs involving environmental sampling and monitoring in the vicinity of fluoropolymer and telomer manufacturing and use facilities, the selection and adaptation of monitoring protocols, and the development of sampling methodologies. ° The Fluoropolymer Technical Workgroup was to investigate physical/ chemical properties, the presence of PFOA in fluoropolymer treated articles during both normal use and aged conditions, and incineration analysis. ° The Telomer Technical Workgroup was to assess the full set of data needs expressed in the EPA Framework with regard to telomers and telomer related products, with the exception of PFOA and PFOA precursors as related to fire fighting foam.

Issues identified at the outset that remained to be addressed by the Plenary due to lack of agreement at the previous Plenary included fluoropolymer biodegradation and the potential for release of and exposure to PFOA and PFOA precursors from fire fighting foam. U. S. Environmental Protection Agency Meeting Summary August 1, 2003 2 Copies of the workgroup summaries from the June 23 and June 24 meetings were available at the meeting and in the public docket at OPPT 2003 0012 0132 through 0135.

II. Summary of Workgroup Activities Fluoropolymers Workgroup Greg Fritz of EPA presented a summary of events from the Fluoropolymer Technical Workgroup session. The presentation began with a summary of Fluoropolymer Manufacturers Group ( FMG) commitments under the LOI, including Product Stewardship, physical chemical properties, and articles of commerce testing. FMG committed to providing information on specific chemical use and production volume; submitting additional physical chemical properties data on selected polymers; continuing to discuss fate and biodegradation information; and developing a timeline for ECA developments in two technical expert subgroups. EPA agreed to review FMG's product selection criteria and to determine whether additional applications would need to be tested. EPA indicated that the analysis of aged products was an area where additional work would be needed, including the selection of articles for testing; simulation of aging process; determining sampling adequacy and product coverage; and adequacy and validation of testing methodologies. EPA provided an ECA incineration proposal for consideration by the group which discussed selecting potential test substances, establishing appropriate test conditions, and analyzing for the C8 acid as well as possible analogs. The EPA proposal contemplated a tiered approach for additional testing. The Workgroup concluded that many items from the ECA Preliminary Framework document have been addressed through the LOI commitments. The Workgroup formed two technical expert subgroups to develop ECA proposals for incineration and aged articles testing.

Discussion/ Questions: None Conclusions:

° Certain items from the EPA Preliminary Framework have been or may be adequately met by the LOI commitments, including items 1 ( product characterization and market information); 2 ( p chem data); and 6 ( articles analysis). ° Recommendation for formation of expert technical subgroups in the areas of aged articles and incineration for identification of LOI commitments, testing protocols, and ECA development. ° Additional degradation information is expected in the future. This issue will remain in the large Technical Workgroup until a later date. ° Additional material balance information is forthcoming. ° Agreement on adequacy of Product Stewardship efforts. ° The Plenary group agreed in principal with the Workgroup's conclusions and proposed path forward. U. S. Environmental Protection Agency Meeting Summary August 1, 2003 3 Communications Workgroup Harry Lewis of EPA presented a summary of events from the Communication Workgroup. The goal of the Communication Workgroup was to develop a roadmap to meaningfully communicate, within the PFOA ECA process, information regarding marketing data, test substance( s), and article identity in a way that preserves proprietary information ( CBI) and satisfies the needs of EPA and the interested parties. CBI was defined as any information that can provide a commercial advantage and which meets the regulatory criteria. CBI claims must be based on regulatory criteria and involve commercial advantage, with an emphasis on demonstrating that public disclosure is likely to cause " substantial harm" to competitive position. TSCA Section 14( b) was referenced, stating that health and safety information can only be claimed CBI for process and mixture proportion information, and that all CBI claims are closely reviewed. EPA's task is to balance the need of the industry to maintain legitimate proprietary information with the need of the public for protection. Public interest groups expressed an interest in obtaining CAS number and chemical structure information in order to be able to identify consumer products of concern. Groups questioned whether generic information would be sufficient for determining representative test samples and which products consumers may encounter. Industry emphasized that strategic decisions regarding market and product development are very sensitive and must be treated as confidential, and that they are prepared to validate all CBI claims as necessary. TRP stated that telomer products are unique by end use and by company. FMG noted that it has provided the CAS numbers of approximately 95% of the products representing FMG's markets. The Workgroup concluded that in a generic setting, parties were unable to agree about specific information that would be necessary for determining exposure. The parties remanded specific determinations of information needed for ECAs to the individual technical workgroups. The Communications Workgroup will reconvene if specific CBI issues raised within other workgroups are not resolved there. The Workgroup noted that an ombudsman may be requested to mediate should that be necessary.

Discussion/ Questions: None Conclusions:

° Suggestion to hold off meeting again until such time as issues or needs emerge for broader discussion. Discussion of CBI issues will take place within the Technical Fluoropolymer and Telomer Workgroups. ° The Plenary group agreed in principal with the Workgroup's conclusions and proposed path forward.

Telomers Workgroup David Lynch of EPA reported on the progress made in the Telomer Workgroup. The Workgroup noted that the industry effort to gather marketing information is largely complete and will be used by EPA to inform the selection of representative test chemicals. Because much of U. S. Environmental Protection Agency Meeting Summary August 1, 2003 4 this information is claimed as CBI, it is not available to the public, although other federal agencies, including CPSC and FDA, may have access to it. The Workgroup suggested the formation of a technical subcommittee where experts will convene to develop an approach for biodegradation testing of representative telomers and telomer based products. Group discussions included information being developed by the Telomer Research Program ( TRP) under the LOI in the areas of fate and exposures. EPA presented views on additional data that may be considered for ECA development beyond the LOI commitments of TRP. The Workgroup suggested the formation of another technical subcommittee to work on further development of a proposed incineration ECA for telomers and telomer based products and articles. TRP committed to document their product stewardship activities.

Discussion/ Questions: None Conclusions:

° According to EPA, the market information submitted under the LOI is largely complete. Because this information is claimed as CBI, it is not available to the public, although other federal agencies, including CPSC and FDA, may have access to it. ° Recommendation for formation of expert technical subgroups in the areas of degradation and incineration for identification of LOI commitments, testing protocols, and ECA development. ° Other items identified for more discussion include information soon to be provided by companies on physical/ chemical properties, the presence of PFOA and PFOA precursors in products and articles, aging studies and product stewardship. ° The Plenary group agreed in principal with the Workgroup's conclusions and proposed path forward.

Monitoring Workgroup Phil Oshida of EPA reported on the progress made in the Monitoring Workgroup. The Workgroup activities included EPA and industry presentations characterizing and clarifying FMG, 3M, and TRP environmental monitoring programs under the LOI. Workgroup participants raised many questions and were involved in much discussion on the need for a mutual understanding and a better focus. EPA defined the overall objective of the ECA activity as the determination of how PFOA and PFOA precursors are released into the environment, their fate and transport upon release, and the routes and levels of human and environmental exposure. Within this overall objective, the objective of the monitoring program and the role of environmental monitoring must be decided, including what questions must be answered by monitoring. The Workgroup participants concluded a technical subgroup was necessary to consider telomer and fluoropolymer monitoring issues separately; to review all data submitted to date; to arrive at a common understanding of the goal and objective of environmental monitoring within the context of the overall investigation of PFOA; to formulate questions specifically to be answered by monitoring; and to bring those goals and questions back to the main Workgroup. U. S. Environmental Protection Agency Meeting Summary August 1, 2003 5 EPA committed to the development of a timeline for the subgroup activities to be circulated to interested parties. Interested parties wishing to participate will identify themselves to EPA. The subgroup( s) will convene at least once prior to the next Workgroup meeting in September. The Workgroup participants suggested that the next full Workgroup meeting be scheduled for an entire day as many issues need discussion and the previous Workgroup meetings were not adequate to accomplish significant progress. One additional issue identified by interested parties but not addressed by the Workgroup was the expressed need for human blood sampling in the vicinity of manufacturing facilities to determine the existence of " hot spots" with higher blood levels than those found in the general population. EPA noted that blood sampling was not within the purview of this current ECA process.

Discussion/ Questions:

Interested parties expressed concerns regarding the absence of human biomonitoring in the ECA process. These parties stated their belief that EPA is not making this a major goal of the ECA process and wanted clarification of this issue. EPA stated that the current ECA framework is to understand areas of exposure in the environment and that it does not intend to pursue this issue under the current framework. EPA recognized the importance of the PFOA levels in human blood, but observed that the approach is to gather information from other sources prior to seeking any ECA commitment for blood monitoring.

One party asked who would handle human biomonitoring. EPA responded that it has proposed that the Centers for Disease Control and Prevention ( CDC) undertake biomonitoring for PFOS/ PFOA materials via the National Health and Nutrition Examination Survey ( NHANES). EPA indicated that, although no final decision has yet been made, EPA anticipates that CDC will agree.

One area of particular concern to interested parties was the possible transfer of PFOA to humans. Parties questioned whether EPA should explore the penetration and skin migration of PFOA through contact with articles such as carpet and clothing. EPA stated that the industry has responded to that question in part through the submission of pharmacokinetic research. FMG specifically expressed their willingness to share information that they believe will clarify this issue. DuPont also expressed knowledge of testing that shows no skin migration of TRP products. EPA requested that the specific docket submission information in the Administrative Record be provided for interested party review.

Public interest groups expressed concerns regarding the formation of technical subgroups due to the difficulty in interested party participation and lack of access to the discussions. EPA responded that the ECA structure is designed to funnel detailed work into smaller technical subgroups, but that those subgroups report back to the Technical Workgroups and to the Plenary at a level where all interested parties can appreciate and comment on what was discussed. U. S. Environmental Protection Agency Meeting Summary August 1, 2003 6 Conclusions:

° Recognize the strong positions regarding human blood monitoring to understand PFOA issues. EPA is not prepared to address at this time, but is open to addressing in the future. ° Recommendation for formation of expert technical subgroup( s) to formulate goals and key questions on the objective of the monitoring work under the ECA. ° The Plenary group agreed in principal with the Workgroup's conclusions and proposed path forward.

III. Discussion of Topics Remaining in Plenary Session Two issues identified in the previous Plenary session that required further discussion were fluoropolymer fate data and fire fighting foam data. EPA noted that it has come to understand that fire fighting foam is principally C6, not C8, but the interest is clear and there is a continued desire for information.

Representatives from FMG announced that additional fate data for fluoropolymers had been submitted for review on July 3, 2003. FMG requested that the information be reviewed by the Agency and moved into the fluoropolymer workgroup as an item for further discussion. The group agreed with the proposal.

A Fire Fighting Foam Coalition ( FFFC) representative spoke regarding the issue of fire fighting foam data. He stated that an unpublished report of groundwater analysis of 3 Department of Defense fire fighting sites had been submitted to EPA on July 3, 2003 for review ( OPPT 2003 0012 0143 and 0144). The information cannot be distributed to the public due to pending publication in a scientific journal, but a copy is available in the reading room for interested parties to review. The FFFC representative suggested the information be reviewed by the Agency and discussed at the next Telomer Workgroup meeting. The FFFC would participate in the discussion and return the issue to the next Plenary meeting for further discussion. The group agreed with this proposal.

One commenter suggested that EPA enter into an ECA with Department of Defense, Department of Transportation/ Federal Aviation Administration and the Department of Homeland Security since those are the agencies that mandate the use of fire fighting foams. A copy of a 1974 1976 bioassay of Air Force FC 206 was submitted to the public record ( OPPT 2003 0012 0152). EPA responded that an ECA is not the appropriate legal tool for an agreement between agencies, but EPA noted that it has been in contact with these agencies to coordinate with them as the ECA activities progress. The Agency is open to inviting other agencies to the technical discussions. U. S. Environmental Protection Agency Meeting Summary August 1, 2003 7 IV. Next Steps Fluoropolymers Workgroup ° Development of separate aged products and incineration technical expert subgroups to meet at least once prior to the full Workgroup meeting in mid September. FMG will provide a timeline within two weeks. ° The Fluoropolymers Technical Workgroup will convene during the week of Sept 15, 2003.

Monitoring Workgroup ° Development of separate technical subgroups for fluoropolymers and telomers to meet at least once before the full Monitoring Workgroup meets in mid September. EPA will provide a timeline for subgroup activities within two weeks. ° The Monitoring Technical Workgroup will convene during the week of Sept 15, 2003.

Telomers Workgroup ° Development of separate degradation and incineration technical expert subgroups to meet at least once before the full Telomer Workgroup meets in mid September. EPA will provide a timeline for subgroup activities within two weeks. ° Suggestion that the information provided by the FFFC be reviewed by the Agency and discussed at the next Telomer Workgroup meeting. The FFFC would participate in the discussion and return the issue to the next Plenary meeting for further discussion. ° The Telomer Technical Workgroup will convene during the week of Sept 15, 2003.

Plenary Session ° The next Plenary meeting will tentatively convene the week of Oct 20, 2003. ° The Workgroups will have the option of convening prior to the Plenary session.

V. Public Comments None at this time.

VI. Closing Remarks EPA thanked the members of the plenary session for their participation and attendance.