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11 August 2009
[Federal Register: August 11, 2009 (Volume 74, Number 153)][Notices] [Page 40189-40199] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr11au09-82] ======================================================================= ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES The National Biodefense Science Board (NBSB), a Federal Advisory Committee to the Secretary; Request for Public Comment AGENCY: Department of Health and Human Services, Office of the Secretary. ACTION: Request for public comment. ----------------------------------------------------------------------- SUMMARY: The U.S. Department of Health and Human Services is hereby giving notice that the National Biodefense Science Board (NBSB) Medical Countermeasure Markets and Sustainability Working Group is requesting public comment to their working document, ``Inventory of Issues Constraining or Enabling Industry Involvement in Medical Countermeasure Efforts''. The inventory (or grid) includes factors that may discourage industry involvement or partnering with the U.S. Government in medical countermeasure development efforts, reported constraints to industry involvement, and potential solutions for relief from a particular constraint. The inventory has been catalogued by financial, legislative, scientific, human capital, regulatory, and societal elements. The Working Group wishes to solicit comment, feedback, and guidance from members of industry, other government agencies, and the public at large for consideration by the Working Group to strengthen and refine the document prior to its public presentation to the NBSB at the scheduled Fall 2009 public meeting of the Board. DATES: The public is asked to submit comments by October 30, 2009, to the NBSB e-mail box (NBSB@hhs.gov) in order to be considered by the Working Group in preparing the final document. [[Page 40190]] ADDRESSES: Availability of Materials: Requests for a copy of the Inventory and accompanying ``Comment Revision Form'' should be made to the NBSB's e- mail box at NBSB@hhs.gov with ``M&S-WG Inventory Request'' in the subject line. All comments and/or recommendations for improvement to the Inventory should be made on the ``Comment Revision Form'' enclosed with the inventory document. Procedures for Providing Public Input: Interested members of the public may submit written comments and/or suggestions, using the ``Comment Revision Form,'' to the NBSB's e-mail box at NBSB@hhs.gov, with ``M&S-WG Inventory Comments'' in the subject line and should be received no later than October 30, 2009. Individuals providing comment or suggestions will be asked to provide their name, title, and organization. All comments received will be posted without change to http://www.hhs.gov/aspr/omsph/nbsb/, including any personal or commercial information provided. FOR FURTHER INFORMATION, CONTACT: Donald Malinowski, M.Sc., HHS/ASPR/ NBSB, 330 C St., SW.,5118, Washington, DC 20201, 202-205- 4761, donald.malinowski@hhs.gov. SUPPLEMENTARY INFORMATION: Pursuant to section 319M of the Public Health Service Act (42 U.S.C. 247d-7f) and section 222 of the Public Health Service Act (42 U.S.C. 217a), the Department of Health and Human Services established the National Biodefense Science Board. The Board shall provide expert advice and guidance to the Secretary on scientific, technical, and other matters of special interest to the Department of Health and Human Services regarding current and future chemical, biological, nuclear, and radiological agents, whether naturally occurring, accidental, or deliberate. The Board may also provide advice and guidance to the Secretary on other matters related to public health emergency preparedness and response. Dated: July 29, 2009. Nicole Lurie, Assistant Secretary for Preparedness and Response, Rear Admiral, U.S. Public Health Service. National Biodefense Science Board Markets & Sustainability Working Group Working Document ``Inventory of Issues Constraining or Enabling Industrial Involvement With Medical Countermeasure Development'' Request for Public Comment Published in Federal Register June 1, 2009. Inventory of Issues Constraining or Enabling Industrial Involvement with Medical Countermeasure Development Introduction: The National Biodefense Science Board (NBSB) Medical Countermeasure Markets and Sustainability Working Group (M&S-WG) has posted a request for public comment in the Federal Register to solicit comment, feedback, and guidance from members of industry, other government agencies, and the public at large on their working document, ``Inventory of Issues Constraining or Enabling Industry Involvement in Medical Countermeasure Efforts.'' Posting of the working document in the Federal Register will serve to solicit and obtain public comment for consideration by the Working Group to strengthen and refine the document. The Working Group plans to present the document to the NBSB at the scheduled Fall 2009 public meeting of the Board. Background: There exists a variety of limitations and barriers to biotechnology and pharmaceutical companies'' involvement in the biosecurity and biodefense efforts of the U.S. Government (USG), most notably medical countermeasure advanced research and development programs coordinated by the Department of Defense (DoD) and the Department of Health and Human Services (DHHS). Make-up of the medical countermeasure development efforts has been called fragmented, with confusing approaches used. To delineate and simplify the complexities of USG endeavors in medical countermeasure development, and the interactions between government agencies and private industry, the NBSB Markets & Sustainability Working Group (M&S-WG) assembled the enclosed inventory (or grid) of issues. This inventory includes factors that may discourage industry involvement or partnering with the USG in medical countermeasure development efforts, reported constraints to industry involvement, and potential solutions for relief from a particular constraint. The inventory has been catalogued by financial, legislative, scientific, human capital, regulatory, and societal elements. The public is encouraged to consider submitting comments and/or recommendations on the content of this inventory. Requests for a copy of the inventory and accompanying Comment Revision Form should be sent to the NBSB's e-mail box at NBSB@hhs.gov with ``M&S-WG Inventory Request'' in the subject line. All comments and/or recommendations for improvement to the inventory grid should be made on the Comment Revision Form enclosed with the inventory document. Comments and/or recommendations are to be submitted to the NBSB's e-mail box at NBSB@hhs.gov with ``M&S-WG Inventory Comments'' in the subject line and should be received no later than October 30, 2009. NBSB Markets & Sustainability Work Group 18 May 09 Observations, Adapted From June 08 NBSB Meeting Business Planning: [mshbox] Contracting with some portions of the USG can be slow, unwieldy, expensive, and opaque. [mshbox] Lack of clarity increases industry risk. [mshbox] Procurement size, warm-base requirements, length of review, etc. [mshbox] Lack of transparency increases industry risk. [mshbox] Contract review process, rate of issuance of new proposals, requirement generation. [mshbox] With a contract in place, situation improves. [mshbox] HHS viewed as cooperative, helpful, responsible and responsive. [mshbox] Perceived lack of coordination between development activities and regulatory responsibilities remains a concern to industry. Regulatory: [mshbox] Lack of clarity regarding usable product definitions, seeming differences in FDA approaches to providing guidance to industry. [mshbox] Industry reliance upon USG for key components of licensure submissions can lead to lack of accountability. [mshbox] Disease studies, toxicology reports, etc. Funding, Stability, Reliability, Predictability: [mshbox] Advanced Development needs more dedicated funding, separate from BioShield funding. [mshbox] BioShield remains a funded procurement device, not an advanced-development mechanism. [[Page 40191]] [mshbox] Advanced development efforts would benefit from contracting flexibility. [mshbox] Cost-plus-fee contracting flexibility is appropriate for advanced development and would reduce risk. [mshbox] Multiyear funding. [mshbox] Drug development and corporate investment/planning is long-term process, multiyear funding with carry-over authority, with multi-year contracting authority would signal USG commitment and increase industry sense of long-term stability. [mshbox] Project BioShield expires in 2013 and will need to be reauthorized and funded. [mshbox] Five years not a long time in drug-development process. [mshbox] BioShield funds should not be diverted to fund other initiatives. [mshbox] Inadequate funding delays the journey to MCM licensure. [mshbox] Initiate additional program against emerging diseases, modeled after pandemic program. Next Steps for WG : [mshbox] Continue to identify obstacles to greater industry participation in MCM development. [mshbox] Make recommendations where appropriate. [mshbox] Identify incentives to encourage greater industry participation in MCM development. [mshbox] Make recommendations where appropriate. [mshbox] Consider alternative models for MCM development. [mshbox] Do other models ensure national and public-health security while more efficiently using limited resources? Barriers Hindering Partnership: Opportunity cost (distractions from commercial business), economics (e.g. margins, volumes), product liability, uncertainty over sustained funding, ambiguous governance, competing public-health alternatives (e.g., needs of developing world), finite human capital, complexity of working with USG, obligations during crisis. Incentives Encouraging Partnership: Reliable access to excess capacity (e.g., for redundant capacity or developing-world projects), tax credits, patent-term extensions, grants, priority-review vouchers, preferred customer/vendor status with USG, product licensing rights, larger pool of scientists and engineers, public good, long-term contracts, intellectual-property development. Inventory of Issues Constraining or Enabling Industrial Involvement With Medical Countermeasure Development 18 May 09 ---------------------------------------------------------------------------------------------------------------- Approach/ advantages/ Row Problem/category Potential solution action Problem/limitation Column 1..... Column 2..... Column 3..... Column 4 ---------------------------------------------------------------------------------------------------------------- Financial Elements ---------------------------------------------------------------------------------------------------------------- 1................ Row 1; Column 1....... Row 1; Column 2....... Row 1; Column 3....... Row 1; Column 4. Capital requirements Increase financial Increased federal Risk of distraction to establish safety, return after risking funding for advanced of large industry efficacy, validated capital to industry- development, in the partners from manufacture. standard rates. form of cost- commercial mission Reduce requirement for reimbursement or dilution of private capital for contracts and effort [potential advanced development. rewarding private- conflict with capital investments fiduciary with milestone responsibility to payments and at shareholders of procurement. publicly traded companies]. ---------------------------------------------------------------------------------------------------------------- 2................ Row 2; Column 1....... Row 2; Column 2a...... Row 2; Column 3a...... Row 2; Column 4. Risk of technical Decentralized Reimbursement of Lack of interest, failure of vaccine discovery/centralized development costs at given opportunity development effort. development and cost +15%, with costs Congressional manufacture. return-on-working- tolerance for capital at 22%, and anticipatable cost-of-money-for- frustrations is capital at 15%. unknown. Row 2; Column 2b...... Row 2; Column 3b...... Evaluation of whether Provides support early indirect-cost in process. reimbursement greater than 100% may be appropriate. Assistance with calculating indirect cost rates (for companies that have never done so before).. ---------------------------------------------------------------------------------------------------------------- 3................ Row 3; Column 1....... Row 3; Column 2a...... Row 3; Column 3a...... Tax incentives........ Enhance current Currently, 20% for incremental R&D tax qualified R&D credit (increase, expenses and 50% for make refundable). clinical-trial expenses. Row 3; Column 2b...... Row 3; Column 3b...... Row 3; Column 4. New investment tax Enhance net revenue... Not yet authorized. credit (20%) for construction of new R&D and manufacturing facilities for biosecurity and emerging-infectious disease purposes (with refundable and/ or transferable provisions). ---------------------------------------------------------------------------------------------------------------- 4................ Row 4; Column 1....... Row 4; Column 2....... Row 4; Column 3....... Row 4; Column 4. [[Page 40192]] Revenue enhancements Enhance current Current statutory Note: Orphan drug tax based on Intellectual product or use patent- formula: Patent credit applies to Property. term restoration and/ extension vaccines only if or extension (revise supplemented by [\1/ less than 200,000 formula). 2\ time from IND to vaccinated Allow full patent-term filing BLA + full recipients extension for time from BLA filing anticipated. licensed products to FDA approval/ that gain CBRN or licensure]. emerging disease Currently, 5 years of application (akin to market exclusivity is adding pediatric provided to New indication). Chemical Entities Allow transfer of (NCEs) but not patent-term extension biologicals via Hatch- to another product or Waxman Act and 7 company years of market (``wildcard''). exclusivity is Market exclusivity: provided via Orphan Increase term of Drug Act. market exclusivity to ~ 12-15 years and extend it to biologicals (as does Orphan Drug Act). ---------------------------------------------------------------------------------------------------------------- 5................ Row 5; Column 1....... Row 5; Column 2....... Row 5; Column 3....... Row 5; Column 4. Priority-Review Make applicable to A PRV is a tradable Predictability: Would Vouchers (PRV). biosecurity products. certificate awarded a priority-review to a developer of a voucher simply treatment for a accelerate a ``no'' neglected tropical or ``not yet'' disease that gains response? licensure from FDA. 2007 law: Text at: It entitles holder to http://www.bvgh.org/ a priority review (a documents/HR3580- speedier review time) CompromiseFDA- for a future product PDUFABill.pdf Draft of their choosing, FDA guidance: http:// potentially www.fda.gov/cber/ shortening the review gdlns/ process by 6 to 12 tropicaldisease.htm. months. First PRV awarded to Novartis for Coartem malaria treatment (artemether and lumefantrine) in Apr 09. ---------------------------------------------------------------------------------------------------------------- 6................ Row 6; Column 1....... Row 6; Column 2a...... Row 6; Column 3a...... Row 6; Column 4a. Limited market size Acquisition RFPs Publication of Requirements are not (development costs >> should state minimum requirements along static and can be market potential). quantities (total and with advanced- expected to change to each successful development RFPs. It based on threat awardee) to increase may be possible to assessments and market certainty to more widely describe discoveries during potential bidders and procurement product development. their investors. requirements, in Requirements may contrast to the more signal USG threat sensitive value of recognition, so may treatment not be appropriate requirements. for public release. Row 6; Column 2b...... Row 6; Column 3b...... Row 6; Column 4b. Contract terms Treaty allies Allies have not made allowing represent additional substantial manufacturers access markets. independent to allied foreign purchases to date. governments and other Some may hope/expect authorized customers USG to share outside the US, as stockpile when well as civilian attack occurs. first responders, hospitals, and travel- vaccine providers within the US. Row 6; Column 2c...... Row 6; Column 4c. Add biodefense and Currently only drugs, other adult vaccines antidotes, and to Standardized various treatments Equipment List (SEL) are covered, but not and Authorized vaccines for Equipment List (AEL), prophylaxis in the so state and local first place. first-responders can use federal (DHS) grant funds to pay for vaccinations. ---------------------------------------------------------------------------------------------------------------- 7................ Row 7; Column 1....... Row 7; Column 2....... Row 7; Column 3....... Row 7; Column 4. [[Page 40193]] Surge issues.......... Compensation if Define Potential commercial product(s) ``compensation'' in compensation may displaced during initial contract or need to include emergencies (e.g., agree to a dispute- delay of a new lost sales, market resolution mechanism. product or loss of share, delayed market share to a licensing). competitor. Level difficult to determine a priori. ---------------------------------------------------------------------------------------------------------------- Legislative Elements ---------------------------------------------------------------------------------------------------------------- 8................ Row 8; Column 1....... Row 8; Column 2a...... Row 8; Column 3a...... Row 8; Column 4a. Predictability, Increase annual NIAID Multi-year contracting Limited track record. consistency adequacy appropriation authority (for large Partial analogies: of Congressional increases for early- molecules, due to Aerospace industry in appropriations. stage MCM development complex manufacturing early 1940s. to offset flat and limited use) and Consistent funding since 2001 multi-year funding procurement of anthrax attacks. with carry-over aircraft carriers Insufficient funds authority for R&D and since 1940s. now allocated for procurement advanced development initiatives. for CBRN. Increase BARDA Manage funding as a Congressional long- appropriations for ``national term recognition of advanced development portfolio'' that threat (natural and of CBRN MCMs and mitigates risk by a malicious) and continued long-term broad set of target tolerance for MCM funding for both CBRN products, with technical failure and pandemic multiple MCMs per unknown. countermeasues, to disease. offset recent funding Base metrics on shortfalls. portfolio performance, rather than individual candidate countermeasures. Long-term funding and ongoing government procurement (10 years or longer) is essential to maintain warm-base MCM manufacturing and surge capacity. Row 8; Column 2b...... Row 8; Column 3b...... Need significantly Solution: a blend of expanded federal indefinite mandatory funding under funding authority BioShield for with caveats to advanced development assure good-faith and procurement performance and activities (BioShield sufficient ongoing reauthorization and discretionary funding). appropriations. Stop and reverse Congressional diversion of BioShield Reserve Fund for other initiatives ($412M in FY09 = $137M for pandemic + $275M for PAHPA implementation), Need long-term funding for acquisition of FDA-approved/licensed MCMs for Strategic National Stockpile. ---------------------------------------------------------------------------------------------------------------- 9................ Row 9; Column 1....... Row 9; Column 3....... Row 9; Column 3....... Row 9; Column 4. Funding stream........ Provide for greater PAHPA (2006) Would likely require flexibility in authorized $1B to BARDA to use Other milestone-driven BARDA for advanced Transaction payment schedules development of MCMs, Authority (OTA) (not under PAHPA and in addition to used to date). BioShield, to account BioShield Reserve for the Fund. unpredictability of Avoids rPA102 scenario vaccine R&D technical (risk of repayment difficulties and upon cancellation). progress. ---------------------------------------------------------------------------------------------------------------- 10............... Row 10; Column 1...... Row 10; Column 2...... Row 10; Column 3...... [[Page 40194]] Untrodden development Cooperative R&D Enhanced recognition pathways. Agreements (CRADAs) that changes in allow collaboration product requirements with respect for can be expected to intellectual property. increase the cost and US Gov't and sponsor time required to agree on defined achieve a useable development pathway product. at early stages to Requires enhanced achieve a target integration of product profile. efforts by each USG entity (notably BARDA, NIAID, CDC, FDA, DoD, InterAgency Board). ---------------------------------------------------------------------------------------------------------------- 11............... Row 11; Column 1...... Row 11; Column 2...... Row 11; Column 3...... Row 11; Column 4. Facilitating Streamline process to Offer innovator an Milestone payments technology transfer support integration option of (a) a could be used on a from basic to of disciplines needed milestone payment multiple of private advanced development. for successful scale- (``prize'') as a paid-in capital up of manufacturing single fee to license (variable) or a processes. the intellectual fixed amount per Increase U.S. Gov't property for further drug. funding for applied development or (b) bioscience, material continue involvement sciences and in development in biopharmaceutical exchange for the processes. possibility of royalties after FDA licensure achieved. ---------------------------------------------------------------------------------------------------------------- Human Capital Elements ---------------------------------------------------------------------------------------------------------------- 12............... Row 12; Column 1...... Row 12; Column 2...... Row 12; Column 3...... Row 12; Column 4 Human capital within Grow the pool of Increased range of Additional industry. science and scientific programs flexibility needed engineering talent offers additional in USG agency pool within industry career-development authority to provide needed to develop and for industrial competitive manufacture MCMs scientists and compensation to within the US. engineers. critical employees. DARPA model assumes industry-standard compensation rates. Congress authorized large increases for NIH grants for researcher awards, but a long-term approach is needed to sustain the industrial base.. ---------------------------------------------------------------------------------------------------------------- 13............... Row 13; Column 1...... Row 13; Column 2a..... Row 13; Column 3a..... Complex, evolving Clarify expectations Spill-over benefits to regulatory early in product commercial sphere via requirements. development and enhanced dialog with minimize changes in FDA. expectations in application review (e.g., requirements under ``animal rule''). Row 13; Column 2b..... Row 13; Column 3b..... Row 13; Column 4b. Implement best Partner with Companies with practices for quality/ experienced biopharma extensive FDA regulatory systems organization to gain experience not for biosecurity access to either currently engaged products. staff or quality with MCM development systems. or manufacture. Row 13; Column 2c..... Row 13; Column 3c..... Collaboration with FDA Centralized advanced to meet evolving development and (more stringent) manufacturing to standards for facilitate cross- development, product learning and manufacture, clinical system development. trials, and ``animal- rule'' pathways. Row 13; Column 2d..... Accelerated FDA review ---------------------------------------------------------------------------------------------------------------- 14............... Row 14; Column 1...... Row 14; Column 2...... Row 14; Column 3...... Row 14; Column 4 Administrative Contracting reform to Waive nonessential Familiarity with requirements to relieve the accounting Federal Acquisition comply with USG regulatory and requirements and Regulations (FAR) contracts. reporting burden. other components of (or relief from the Federal them). Acquisition Regulation (FAR). [[Page 40195]] BARDA should identify opportunities to use Other Transaction Authority (OTA) to enhance R&D contracts (akin to DARPA).. Explore Cooperative R&D Agreement (CRADA) approaches. ---------------------------------------------------------------------------------------------------------------- 15............... Row 15; Column 1...... Row 15; Column 2...... Row 15; Column 3...... Adequacy of review and Increase More medical reviewers consultation appropriations to needed, plus research resources at FDA. enhance FDA review and assay development and consultation. within FDA. Increase percentage of personnel eligible for enhanced bonus payments or super- grades. ---------------------------------------------------------------------------------------------------------------- Societal Elements ---------------------------------------------------------------------------------------------------------------- 16............... Row 16; Column 1...... Row 16; Column 2...... Row 16; Column 3...... Row 16; Column 4 Contribution to Exploration of Enhanced corporate Increased public national security.. biosecurity MCMs is reputation.. attention during likely to have spill- crisis. over benefits to ``natural'' infectious diseases as well. ---------------------------------------------------------------------------------------------------------------- Legal Elements ---------------------------------------------------------------------------------------------------------------- 17............... Row 17; Column 1...... Row 17; Column 2...... Row 17; Column 3...... Row 17; Column 4. Product liability..... Expand coverage of Indemnification via Not tested in PREP Act to Public Readiness & practice or additional MCMs for Emergency litigated. http:// which Material Threat Preparedness (PREP) www.pandemicflu.gov/ Assessments (MTAs) Act of 2005 (PL 109- plan/federal/prep-- exist. 148, Dec 30, 2005). act.html Public Law 109-148. PHS Act Section 319(f)(3). 42 U.S.C. 247d-6d. [See also Support Antiterrorism by Fostering Effective Technologies (SAFE- T) Act of 2002 [within Homeland Security Act, Pub. L. 107-296].] ---------------------------------------------------------------------------------------------------------------- 18............... Row 18; Column 1...... Row 18; Column 2...... Row 18; Column 3...... Antitrust Provisions.. Assess need for, plan, Need ability to and implement develop contingency antitrust waiver plans and preliminary authority under PAHPA communication and 2006 for R&D and technical preparedness consultation. activities to allow Continue and expand nominally competing efforts such as those parties to underway with collaborate during a pandemic influenza public health vaccine and adjuvant emergency or to ``mix-and-match'' conduct contingency studies to assess exercises before a safety and efficacy. public-health emergency. Involve DoJ and Attorney General in supervisory/ compliance role. ---------------------------------------------------------------------------------------------------------------- Corollary Elements ---------------------------------------------------------------------------------------------------------------- 19............... Row 19; Column 1...... Row 19; Column 2...... Row 19; Column 3...... [[Page 40196]] Attractiveness of Implement national Consolidate Medicare commercial vaccine policies to provide coverage of all market for support of adequate vaccines within Part future R&D and reimbursement for B (not Part D). manufacturing. vaccines and their administration in both the public and private sectors, to help underwrite and sustain the industrial base needed for biosecurity and global-health products. Increase administration reimbursement rates under Medicaid and Vaccines for Children (VFC) beneficiaries with federal subsidies to offset increased State costs. Third-party payers to provide first-dollar coverage for FDA- licensed vaccines and their administration under healthcare reform. ---------------------------------------------------------------------------------------------------------------- 20............... Row 20; Column 1...... Row 20; Column 2...... Row 20; Column 3...... Approaches suitable Advanced Market Examples: Guarantee a for developing-world Commitments (AMC) market in developing situations (perhaps separately for countries for useful by analogy). existing vaccines and pneumococcal vaccines global health to prevent deadly vaccines at R&D stage. respiratory infections in children and as an incentive for development of vaccines that currently do not exist against infectious disease threats in those countries, but which may be imported into the U.S. or threaten global security. ---------------------------------------------------------------------------------------------------------------- Other Benefits to Involvement With Biosecurity Initiative ---------------------------------------------------------------------------------------------------------------- 21............... Row 21; Column 1...... Row 21; Column 2...... Row 21; Column 3...... Competitive situation. Don't put all eggs in Participation by one basket, allow manufacturer with multiple technologies U.S. Gov't withholds and product scientific, candidates to financial, and human- progress capital benefit to simultaneously competitors. through development pathways. ---------------------------------------------------------------------------------------------------------------- 22............... Row 22; Column 1...... Row 22; Column 3...... Row 22; Column 4. New intellectual IP developed in course U.S. Gov't has step- property. of government in rights if patent contract remains with arising from federal discoverer. government-funded research not exploited [Bayh-Dole Act of 1980 (or University & Small Business Patent Procedures Act), codified in 35 U.S.C. 200-212[1], implemented by 37 CFR 401[2]]. ---------------------------------------------------------------------------------------------------------------- 23............... Row 23; Column 1...... Row 23; Column 3...... Row 23; Column 4. Staying abreast of Access to state-of-art Need to understand advancing sciences. process analytics for exclusivity of wide variety of access. biological products. ---------------------------------------------------------------------------------------------------------------- Citations: Project BioShield Act of 2004: Public Law 108-276, http:// frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=108_cong_ public_laws&docid=f:publ276.108.pdf. BioShield II (2005): PAHPA, PL 109-417, Dec 19, 2006. Bibliography: Matheny J, Mair M, Mulcahy A, Smith BT. Incentives for biodefense countermeasure [[Page 40197]] development. Biosecur Bioterror 2007 Sep;5(3):228-38. Animal Rule = U.S. Food and Drug Administration. New drug and biological drug products; evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. Final rule. FR 2002 May 31;67(105):37988-98. http://frwebgate5.access.gpo.gov/cgi-bin/ PDFgate.cgi?WAISdocID=483712496781+5+2+0&WAISaction=retrieve. BILLING CODE 4150-37-C [[Page 40198]] [GRAPHIC] [TIFF OMITTED] TN11AU09.038 [[Page 40199]] [FR Doc. E9-19199 Filed 8-10-09; 8:45 am] BILLING CODE 4150-37-C