FDA-RFP-1155964.docx

Page 18of 20 – FDA-RFP-1155964

PART 1: DESCRIPTION

Solicitation number FDA-RFP-1155964 is issue as a Request for Proposal (RFP).

All quotes and revisions shall be submitted to Linda Troutman via email at Linda.Troutman@fda.hhs.gov. Questions are due August 18, 2015, at 9:00 A.M. Eastern Time. Quotes and all revisions are due no later than August 27, 2014, at 4:30 P.M. Eastern Time. Offeror shall ensure the RFP number is visible in the subject line of the email. Faxed RFP not be accepted.

This is a combined synopsis/solicitation for commercial items prepared in accordance with 41 U.S.C. 253 (c)(5) and the format in Subpart 12.6, as supplemented with additional information from FAR Part 13. This announcement constitutes the only full and open competition solicitation. The resultant contract will include all applicable provisions and clauses in effect through the Federal Acquisition Circular 05-83. The NAICS code for this item is 541711, may fit multiple NAICS codes.

PART 2

SERVICES AND PRICES/COSTS

2.1. DESCRIPTION OF SERVICES

The U.S. Department of Health and Human Services, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER) requires a service contract to conduct a study on Pharmacokinetics Studies of Opioid Drug Product following Snorting of Milled Drug Products within the Office of Generic Drugs.

2.2 CONTRACT TYPE

The anticipated contract type is Firm Fixed Price Contract.

2.3 CONTRACT PERIOD OF PERFORMANCE

The period of performance will start on September 07, 2015 through September 06, 2017

2.4 PRICING/COSTS

PART 3

STATEMENT OF WORK

3. SCOPE OF WORK

The contractor shall furnish the personnel, services, facilities, except as provided in the schedule, required for or incident to the performance of the work as described below.

3.1 Technical Requirements:

Background

Misuse and abuse of prescription opioid drugs is a problem of public health concern. It is associated with increased adverse effects, emergency visits, and mortality due to overdose.1 There is also constant demand for prescription opioids as they are effective and necessary treatment of acute and chronic pain. Therefore, FDA encourages the development of abuse-deterrent formulation of prescription opioid drugs and is developing tools to evaluate the relative performance of a generic product to perform to its reference listed drug (RLD) with respect to properties relevant to deterrence of abuse.

One of the common ways to abuse a solid oral opioid drug product is to crush/mill the drug product to small particles for snorting. The milling process (e.g. tool, strength, duration) affects particle size distribution, morphology, amount of drug recovered from the milled product, the drug release kinetics of the manipulated products, and ultimately, bioavailability after snorting. A systemic evaluation of the effect of milling process on these in vitro and in vivo endpoints will help identifying critical parameters when designing in vitro and in vivo pharmacokinetics studies to compare deterrence of nasal abuse between a generic and RLD.

ACRONYMS: reference listed drug (RLD), Food and Drug Administration (FDA), Office for Human Research Protections (OHRP), pharmacokinetics (PK), Institutional Review Board (IRB), Good Manufacturing Practices (GMP), Good Laboratory Practices (GLP), Good Clinical Practice (GCP), Institutional Review Board (IRB), Research Involving Human Subjects Committee (RIHSC), Statement of Work (SOW), Contracting Officer Representative (COR), Principal Investigator (PI).

3.2 Objectives

The objective of this study is to investigate factors that affect bioavailability of opioid drug products following snorting of milled drug products. Factors to be evaluated include, but are not limited to milling procedure (e.g. tool, duration, strength), amount of milled material obtained from the drug product, particle size distribution, morphology, and in vitro dissolution of the milled product. Outcome of this study may help determining critical study design parameters when comparing deterrence of nasal abuse between a generic and its RLD

3.3. The contractor shall perform the follow task as follows:

3.3.1. Perform milling procedures on selected oral opioid drug products using at least three types of common household equipment at different rate, strength, and duration. The contractor shall record efforts of the milling processes.

3.3.2. Perform in vitro characterization on selected milled products including but not limited to the amount of drug recovered, particle size distribution, and morphology of milled products.

3.3.3. Determine the milled products to use in in vitro dissolution study. Particle size of the selected milled products should range from fine, medium, to coarse.

3.3.4. Determine the milled products for use in the in vivo pharmacokinetics (PK) study in healthy subjects.

3.3.5. Develop protocol for a 4-sequence, 4-period, 4-treatment, crossover in vivo PK study in healthy, recreational opioid users with intranasal abuse history to compare plasma PK of the drug substance. The protocol shall conform to all applicable Good Clinical Practice (GCP) regulations. The protocol shall include at a minimum: Informed Consent Form, Clinical and Analytical Site Identification, Key Personnel, Background Material, Demographics, Inclusion and Exclusion Criteria, Method of Subject Selection, Randomization Scheme, Study Design, Sample Size Determination, Fasting and Fed Conditions, Blood Sampling Times and Volume, Sample Storage, Potential Risks to the Subjects, Protection Against Risks, Potential Benefits to the Subjects and to Society, Risk/Benefit Assessment, Confidentiality of Subject Information, Data Safety Monitoring Plan, Subject Recruitment Oversight, Study Progress, and Adverse Event Reporting Plan. The protocol developed by the Contractor shall comply with the requirements of FDA’s IRB, the Research Involving Human Subjects Committee (RIHSC) in addition to the Contractor’s local IRB. The contractor shall submit to FDA a protocol that follows RIHSC guidelines for format and content.

3.3.6. Begin the study within 15 calendar days from the date the Contractor obtains both RIHSC approval and local IRB approval.

3.3.7. The contractor shall measure and record “hold time” of the snorted milled products and the amount of drug being snorted.

3.3.8. Perform the bioanalytical study according to Good Laboratory Practice (GLP) regulations. Document and justify any deviations from these regulations. Bioanalytical method validation includes all the procedures that demonstrate that a particular method used for quantitative measurement of analytes in a given biological matrix such as blood, plasma, serum is reliable and reproducible for the intended use. The fundamental parameters for this validation include (a) accuracy, (b) precision, (c) selectivity, (d) sensitivity, (e) reproducibility and (f) stability. Incurred sample reanalysis should be performed.

3.3.9. Monitor and record any side effects or adverse reactions during the in vivo PK study.

3.3.10. Conduct appropriate statistical analyses of study outcome. Use appropriate statistical analysis software to evaluate relative bioavailability and compare PK parameters between treatments.

3.3.11. Generate study report on the evaluation of PK profiles and on safety outcome of the study.

3.3.12. Be responsible for subject recruitment, supplies, equipment, data collection, and computational software.

3.3.13. Adhere to all relevant FDA guidance documents.

References

3.4.1. http://www.cdc.gov/drugoverdose/pdf/hhs_prescription_drug_abuse_report_09.2013.pdf

Research Involving Human Subjects

All research conducted, supported, or regulated by any U.S. Government Agency is subject to certain uniform requirements of the Federal Policy for the Protection of Human Subjects including Institutional Review Board (IRB) membership, IRB review and approval criteria, IRB operations and record keeping, and informed consent. The Contractor agrees that the rights and welfare of human subjects involved in research under this contract shall be protected in accordance with 45 CFR Part 46 and with the Contractor’s current Assurance of Compliance on file with the Office for Human Research Protections (OHRP), Department of Health and Human Services.

The Institutional Review Board (IRB) specified in the Contractor’s Assurance of Compliance, hereafter referred to as "the local IRB," shall review the proposed research protocol. A letter from the local IRB stating that the proposed research protocol adequately protects the rights and welfare of human subjects involved, or a letter stating that the proposed research is exempt under 45 CFR 46.101(b) and shall be submitted to the FDA Contracting Officer’s Representative (COR).

The Contractor further agrees that research involving human subjects and funded by the FDA shall receive approval from FDA’s Research Involving Human Subjects Committee (RIHSC) prior to enrolling human subjects. The Contractor shall submit its proposed research protocol and all related documents (including but not limited to the informed consent form, recruitment material, telephone script, questionnaire, and Investigator’s brochure or package insert of study drug(s) as appropriate) through the FDA COR to the FDA’s Research Involving Human Subjects Committee (RIHSC).

The Contractor shall understand and comply with ethical principles and regulatory requirements involving human subjects research as specified in the Federal regulations for the Protection of Human Subjects, 45 CFR 46. The Contractor shall remain in compliance with the Health and Human Services (HHS) policies and procedures that concern the conduct of human subjects research.

The Contractor shall bear full responsibility for the performance of all work and services involving the use of human subjects under this contract in a proper manner and as safely as is feasible. Nothing in this contract shall be deemed to constitute the Contractor or any sub-Contractor, agent or employee of the Contractor, or any other person, organization, institution, or group of any kind whatsoever, as the agent or employee of FDA. The Contractor agrees that it has entered into this contract and will discharge its obligations, duties, and undertakings and the work pursuant thereto, whether requiring professional judgment or otherwise, as an independent Contractor without imputing liability on the part of FDA for acts of the Contractor or its employees.

If at any time during performance of this contract, the Contracting Officer determines, in consultation with FDA’s RIHSC, that the Contractor is not in compliance with any of the requirements and/or standards stated in Section 3.5, the Contracting Officer may immediately suspend, in whole or in part, work and further payments under this contract until the Contractor corrects the noncompliance. Notice of the suspension may be communicated by telephone and confirmed in writing by the Contracting Officer. If the Contractor fails to complete the corrective action within the period of time designated in the Contracting Officer's written notice of suspension, the Contracting Officer may, in consultation with FDA’s RIHSC, terminate this contract in whole or in part, and the Contractor’s name may be removed from the list of those Contractors with approved Department of Health and Human Services Human Subject Assurances.

3.5.1. Compliance

The Contractor shall ensure compliance with the following requirements:

a. No FDA funds shall be expended to implement any part of the proposed research protocol funded in whole or part under this contract until approval is received from both the local IRB and RIHSC. Activities requiring approval include recruitment, enrollment, screening, records review or any other activity related to protocol implementation.

b. Should a portion of the FDA funds be applied to protocol development or other support activities conducted prior to protocol implementation, the Contractor shall provide an accounting of the use of these funds at the time of RIHSC review.

c. All consent forms shall comply with HHS and FDA regulations at 5 CFR 46.116 and 21 CFR 50.25 regarding the required elements of informed consent.

d. The FDA COR will serve as the responsible party for a trial which is determined to be an applicable clinical trial under Title VIII of FDAAA. The FDA COR or their delegate shall register and submit the results of the research study to ClinicalTrials.gov. https://clinicaltrials.gov/. For trials which do not meet the definition of an applicable clinical trial under Title VIII of FDAAA, the contractor may register and submit the results of the study with prior approval by the FDA COR. In such a case, the contractor is responsible for all matters relating to the ClinicalTrials.gov databank. The information on the registry can be found at the link above.

e. If FDA is providing partial funding for the research study, details of the expenses paid for with FDA funds shall be tracked separately.

f. Should funds support any salaries, information on what activities are being performed by each individual for that salary support must be tracked and reported to the FDA.

g. Any changes to the protocol, informed consent form, recruitment materials or any other documents related to the protocol implementation shall be reviewed and approved by RIHSC as well as the local IRB, prior to implementation.

h. Research approved by the local IRB and RIHSC may not continue beyond one year from the approval date unless a continuing review is conducted by both the local IRB and RIHSC and approved.

The RIHSC shall review the research protocol to assure that the rights and welfare of human subjects involved are adequately protected. The RIHSC shall also determine whether the proposed research is exempt under 45 CFR 46.l01 (b).

Research involving human subjects may commence immediately upon the Contractor’s receipt of RIHSC approval provided by the FDA COR and the local IRB approval.

If the Contractor fails to obtain RIHSC approval of its proposed research during RIHSC's initial review, the Contractor shall have the opportunity to correct the deficiencies identified during the RIHSC review and resubmit the proposed research protocol to RIHSC for a second review. The Contractor is to solicit the RIHSC's input during the resubmission process.

The Contractor must provide a risk-based monitoring plan in the protocol that describes the procedures and documentation that shall be used to monitor the clinical study. This includes resources available to the Contractor for oversight and quality assurance monitoring of the study (e.g. Quality Assurance Program, Human Subject Research Compliance Program).

The proposed research study protocol shall comply with ICHE6 Good Clinical Practice Consolidated Guidance which sets an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. All human subject research regulated by FDA may also be subject to FDA's regulations regarding the protection of human subjects (21 CFR parts 50 and 56).

3.5.2. Research Involving Human Subject Committee

Upon contract award, the Government will arrange a kickoff meeting with the Contractor to discuss requirements of the Research Involving Human Subjects Committee (RIHSC), the FDA’s Institutional Review Board (IRB) and the roles and responsibilities of Government personnel throughout the RIHSC review process.

Following the kickoff meeting, the Contractor shall submit the proposed study documents including the research protocol, informed consent form(s), participant information sheet (if applicable), and recruitment advertisements to the FDA COR. The FDA COR shall review the submission package to ensure completeness and will provide comments/suggestions. All final research documents shall be submitted to the FDA COR for review including CVs or resumes and appropriate training records of key personnel, a medical license of medically accountable officer, Investigator’s brochure or package insert of study drug(s) as appropriate, a federal wide assurance number of local IRB, and FDA form 1572. Following the review and sign off by the Center’s RIHSC Liaison, the submission package shall be submitted electronically to the RIHSC. The Contractor and the FDA COR will be copied on the email submission to the RIHSC.

If the Contractor has already received local IRB approval for the final study documents prior to submission to RIHSC, a copy of the approval letter from the local IRB must be included in the submission package to the FDA COR. The IRB approval letter must state that the proposed research study documents adequately protect the rights and welfare of human subjects. The Contractor may submit the research study documents to their IRB at the same time the Contractor submits its package to the FDA COR for RIHSC review. The Contractor is required to submit the approval letter from the local IRB to the FDA COR upon receipt of the letter. This requirement would include proposed research that is exempt from IRB approval.

Please note: Certification of local IRB review and approval must include the following: the PHS/HHS application number, title of the project, name of the program director/principal investigator, date of IRB approval, and appropriate signatures. The IRB must ensure that any corresponding protocol(s) are consistent with the specific application.

The RIHSC will review the research study documents to assure that the rights and welfare of human subjects involved are adequately protected. The RIHSC will also determine whether the proposed research is exempt under 45 CFR 46.101(b). The FDA COR will provide the Contractor with a copy of RIHSC’s letter of approval/approval with stipulations/disapproval. If RIHSC renders a decision other than approval of the proposed research study documents, the FDA COR will assist the Contractor in revising the research study documents for re-submission to RIHSC for review and approval.

The Contractor shall seek RIHSC approval and local IRB review and approval whenever modifications, amendments or other changes are made to the research study documents. Modifications and amendments include, but are not limited to, changes to the study protocol, consent form(s), recruitment materials, and the addition or deletion of key personnel/investigators. The Contractor shall submit modified/amended study documents to the FDA COR for RIHSC review and approval. The FDA COR will provide the Contractor with a copy of RIHSC’s letter of approval/approval with stipulations/disapproval. The Contractor shall also submit a copy of the local IRB approval of modifications/amendments to the FDA COR upon receipt.

Questions regarding FDA RIHSC shall be directed to Contracting Officer Representative.

3.5.3. Reporting

a. Changes/amendments to the protocol/informed consent document must promptly report to the RIHSC all proposed changes in the research activity including any modifications to the Study Protocol, and Informed Consent document

b. Non-compliance: the Contractor must report any alleged breaches of the protocol, such as breakdowns in the informed consent process, violations of confidentiality of data or privacy of a research subject, complaints by participants or their representatives, and any serious or continuing noncompliance with federal regulations by the investigators or research staff via FDA Sponsor

c. Adverse event reporting: the Contractor must report to the FDA Sponsor, any unanticipated problems involving risk to human subjects or others and anticipated adverse events may be reported to the RIHSC in the annual report for continuing review.

Annual Submissions Requirements: Contractor shall provide an approval letter from their local IRB, at least annually; stating that the research protocol performed under this contract has been reviewed and approved to continue for another year. This shall be submitted to the FDA COR for inclusion in the contract file. In return, the COR will provide a copy of the approval letter from RIHSC to the Contractor, at least annually, stating that the research protocol performed under this contract has been reviewed and approved to continue for another year.

3.5.4. Quality Assurance and Monitoring

The Government will perform quality assurance monitoring (either remotely or via on-site visits) to ensure human subject protections throughout the conduct of the study and document compliance with the regulations and the RIHSC requirements that govern the conduct of research involving human subjects. The CDER’s Extramural Clinical Studies Coordinator and/or the FDA COR will provide the Contractor with a report of all identified deviations and/or violations related to human subject protections. If violations are found, the Contractor shall provide responses to the corrective actions listed in the report to the CDER’s Extramural Clinical Studies Coordinator and the FDA COR within 2 weeks of receipt of the report/violation notice. If the Contractor has established a Steering Committee and/or a Monitoring Board (for monitoring quality assurance) for this contract, the Contractor shall submit the responses to the corrective actions of violations to the Steering Committee and/or Monitoring Board as established.

The Contractor must provide documentation of acknowledgement of the violations either by the local IRB and/or Steering Committee/Monitoring Board to the CDER’s Extramural Clinical Studies Coordinator and the FDA COR. This documentation will be forwarded to RIHSC for review and documentation of the review and any required actions will be provided to the Contractor.

PART4

Reporting Requirements and Deliverable Items

All deliverables shall be 508 compliant. All electronic and information technology (EIT) must met the applicable accessibility standards at 36 CFR 1194, unless an agency exception to this requirement exists. 36 CFR 1194 implements Section 508 of the Rehabilitation Act of 1973, as amended, and is viewable at:

http://www.access-board.gov/sec508/standards.htm.

Pursuant to the HHSAR clause 352.270-19, the Section 508 standards applicable to the prospective award are:

• § 1194.41 Information, documentation, and support

• § 1194.21 Software applications and operating systems

• § 1194.22 Web-based intranet and internet information and applications

Reports (i.e., monthly progress reports, and final report), containing the description of experiments and data analysis, will be provided to the FDA using FDA recommended format in both paper and electronic format. In addition, all of the raw data from the experiments will be provided to the FDA in electronic format, along with these reports.

No information furnished to or generated by the contractor in the performance of this contract will be released to the public until it has been reviewed by the Government Contracting Officer’s Representative for accuracy of factual data and interpretation. The Government will have sixty (60) calendar days after receipt of the manuscript or other written draft of the material to be released, to review, comment, and return to the contractor.

Scientific manuscripts/publications resulting from work conducted by the Contractor and Government site investigators will be prepared and published according to guidelines agreed upon at study initiation by the investigator team for that study. At study initiation, each study group shall determine the first and senior author positions. While the order of listing authors on each publication shall be determined on a case-by-case basis by mutual decision of all collaborative parties and shall reflect appropriately each author’s contribution to the project, it is likely that a Contractor employee will be offered the first author position for the primary manuscript arising from the study. However, the senior author position may be offered to any member of the study team who is willing to provide substantial input into study design, implementation, and manuscript preparation and oversight of all study procedures. Study Site Principal Investigator (PI) and Principal Investigators from the other sites, including FDA, will be listed as authors 2-x on the manuscripts, with ordering in these positions determined by consensus based on the amount of input into the actual production of the manuscript. All authors shall provide final approval of the manuscript as written. Even though the Contractor will likely be the first author on resulting publications, it is the Government’s discretion as to when the articles should be published. The Contractor shall not unduly delay publication or unilaterally decide that the data should not be published. This right is retained by the Government only.

PART 5

INSPECTION AND ACCEPTANCE

The Contracting Officer’s Representative (COR) will perform inspection and acceptance of materials and services to be provided.

5.1 Inspection and acceptance will be performed at; location identified in Part 6. Acceptance is communicated in writing unless otherwise indicated in writing by the Contracting Officer or the COR within 30 days of receipt

5.2 This contract incorporates one or more provisions by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at: www.acquisition.gov/far/index.html

PART 6

DELIVERIES OF PERFORMANCE

6.1 Deliveries

6.1.1 Satisfactory performance of this contract shall be deemed to occur upon performance of the work described in the Statement of Work in PART 3 of this contract and upon delivery and acceptance by the Contracting Officer, or the COR, of the services, plans and reports required at the dates specified within PART 3 of this contract.

6.1.2 Deliveries of the reports are to be sent via email to the COR's address listed at the time of award:

6.2 PLACE OF PERFORMANCE

The place of performance for this contract shall be at the contractor's site.

PART 7

CONTRACT ADMINISTRATION DATA

7.1 CONTRACTING OFFICER’S REPRESENTATICE (COR)

The following COR will represent the Government for the purpose of this contract (To be determined upon contract award)

7.1.1. The COR is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the Statement of Work and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance.

COR contact information shall be provided at time of award.

7.2 CONTRACT ADMINISTRATION

7.2.1 The Contracting Officer is the only person with authority to act as agent of the Government under this contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in the RFQ; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor any costs incurred during the performance of this contract; or (5) otherwise change any terms and conditions of this contract.

Linda Troutman Contract Specialist Linda.Troutman@fda.hhs.gov 404-253-1258

7.3 CONTRACTOR REPRESENTATIVE

The Contractor's representative shall act as the central point of contact with the FDA. The representative shall have full authority to act for the Contractor in all contractual matters.

Name: Shall be provided at time of award Email:

Telephone:

PART 8

SPECIAL CONTRACT REQUIREMENTS

8.1. HHSAR CLAUSES INCORPORATED BY REFERENCE

This contract incorporates one or more clauses by reference, noted in Title 48, Federal Acquisition Regulations System, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at: http://www.gpoaccess.gov/cfr/index.html.

and seminars to persons with disabilities

8.2 INVOICING INSTRUCTIONS

The Contractor shall submit invoices to the Contract Specialist and the COTR concurrently, via email (ref. Part 7). To constitute a proper invoice, the invoice must be submitted on company letterhead and include:

1. Name and address of the Contractor

2. Invoice date and invoice number

3. Contract number

4. Description, Quantity, Unit of Measure, Unit Price, and Extended Price of supplies delivered

5. Shipping number and date of shipment, including the bill of lading number and weight of shipment if shipped on Government bill of lading

6. Terms of any discount for prompt payment offered

7. Name and address of official to whom payment is to be sent (Must be the same as that in the delivery order or in a proper notice of assignment)

8. Name, title, and phone number of person to notify in event of defective invoice

9. Taxpayer identification number

10. Electronic Funds Transfer (EFT) banking information

11. Name and telephone number of the FDA COTR referenced on the delivery order

12. Any other information or documentation required by the delivery order

An electronic invoice is acceptable if submitted in adobe acrobat (PDF) format. All items listed in 1-12 of this clause must be included in the electronic invoice. Electronic invoices must be on company letterhead and must contain no ink changes and be legible for printing.

Questions relating to when payment will be received should be directed to the FDA payment office at 301.827-3742.

PART 9

CONTRACT CLAUSES

9.1 52.252-2 Clauses Incorporated by Reference (FEB 1998) This contract incorporates one of more clauses by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at http://www.acquisition.gov

Commercial Items

9.2 52.212-5 Contract Terms and Conditions Required to Implement Statutes or Executive Orders—Commercial Items (MAY 2011).

(a) The Contractor shall comply with the following Federal Acquisition Regulation (FAR) clauses, which are incorporated in this contract by reference, to implement provisions of law or Executive orders applicable to acquisitions of commercial items:

(1) 52.222-50, Combating Trafficking in Persons (Feb 2009) (22 U.S.C. 7104(g)).

___Alternate I (Aug 2007) of 52.222-50 (22 U.S.C. 7104(g)).

(2) 52.233-3, Protest After Award (AUG 1996) (31 U.S.C. 3553).

(3) 52.233-4, Applicable Law for Breach of Contract Claim (OCT 2004) (Pub. L. 108-77, 108-78).

(b) The Contractor shall comply with the FAR clauses in this paragraph (b) that the Contracting Officer has indicated as being incorporated in this contract by reference to implement provisions of law or Executive orders applicable to acquisitions of commercial items:

_x (1) 52.203-6, Restrictions on Subcontractor Sales to the Government (Sept 2006), with Alternate I (Oct 1995) (41 U.S.C. 253g and 10 U.S.C. 2402).

__ (2) 52.203-13, Contractor Code of Business Ethics and Conduct (Apr 2010) (Pub. L. 110-252, Title VI, Chapter 1 (41 U.S.C. 251 note)).

__ (3) 52.203-15, Whistleblower Protections under the American Recovery and Reinvestment Act of 2009 (June 2010) (Section 1553 of Pub. L. 111-5). (Applies to contracts funded by the American Recovery and Reinvestment Act of 2009.)

__ (4) 52.204-10, Reporting Executive Compensation and First-Tier Subcontract Awards (Jul 2010) (Pub. L. 109-282) (31 U.S.C. 6101 note).

__ (5) 52.204-11, American Recovery and Reinvestment Act—Reporting Requirements (Jul 2010) (Pub. L. 111-5).

__ (6) 52.209-6, Protecting the Government’s Interest When Subcontracting with Contractors Debarred, Suspended, or Proposed for Debarment (DEC 2010) (31 U.S.C. 6101 note). (Applies to contracts over $30,000). (Not applicable to subcontracts for the acquisition of commercially available off-the-shelf items).

__ (7) 52.219-3, Notice of Total HUBZone Set-Aside or Sole-Source Award (Jan 2011) (15 U.S.C. 657a).

__ (8) 52.219-4, Notice of Price Evaluation Preference for HUBZone Small Business Concerns (JAN 2011) (if the offeror elects to waive the preference, it shall so indicate in its offer) (15 U.S.C. 657a).

__ (9) [Reserved] _x (10)(i) 52.219-6, Notice of Total Small Business Set-Aside (June 2003) (15 U.S.C. 644).

__ (ii) Alternate I (Oct 1995) of 52.219-6.

__ (iii) Alternate II (Mar 2004) of 52.219-6.

__ (11)(i) 52.219-7, Notice of Partial Small Business Set-Aside (June 2003) (15 U.S.C. 644).

__ (ii) Alternate I (Oct 1995) of 52.219-7.

__ (iii) Alternate II (Mar 2004) of 52.219-7.

__ (12) 52.219-8, Utilization of Small Business Concerns (Jan 2011) (15 U.S.C. 637(d)(2) and (3)).

__ (13)(i) 52.219-9, Small Business Subcontracting Plan (Jan 2011) (15 U.S.C. 637(d)(4)).

__ (ii) Alternate I (Oct 2001) of 52.219-9.

__ (iii) Alternate II (Oct 2001) of 52.219-9.

__ (iv) Alternate III (Jul 2010) of 52.219-9.

__ (14) 52.219-14, Limitations on Subcontracting (Dec 1996) (15 U.S.C. 637(a)(14)).

__ (15) 52.219-16, Liquidated Damages—Subcontracting Plan (Jan 1999) (15 U.S.C. 637(d)(4)(F)(i)).

__ (16)(i) 52.219-23, Notice of Price Evaluation Adjustment for Small Disadvantaged Business Concerns (OCT 2008) (10 U.S.C. 2323) (if the offeror elects to waive the adjustment, it shall so indicate in its offer).

__ (ii) Alternate I (June 2003) of 52.219-23.

__ (17) 52.219-25, Small Disadvantaged Business Participation Program—Disadvantaged Status and Reporting (Dec 2010) (Pub. L. 103-355, section 7102, and 10 U.S.C. 2323).

__ (18) 52.219-26, Small Disadvantaged Business Participation Program— Incentive Subcontracting (Oct 2000) (Pub. L. 103-355, section 7102, and 10 U.S.C. 2323).

__ (19) 52.219-27, Notice of Total Service-Disabled Veteran-Owned Small Business Set-Aside (May 2004) (15 U.S.C. 657 f).

__ (20) 52.219-28, Post Award Small Business Program Representation (Apr 2009) (15 U.S.C. 632(a)(2)).

__ (21) 52.219-29 Notice of Total Set-Aside for Economically Disadvantaged Women-Owned Small Business (EDWOSB) Concerns (Apr 2011).

__ (22) 52.219-30 Notice of Total Set-Aside for Women-Owned Small Business (WOSB) Concerns Eligible Under the WOSB Program (Apr 2011).

_x (23) 52.222-3, Convict Labor (June 2003) (E.O. 11755).

_x (24) 52.222-19, Child Labor—Cooperation with Authorities and Remedies (Jul 2010) (E.O. 13126).

_x (25) 52.222-21, Prohibition of Segregated Facilities (Feb 1999).

_x (26) 52.222-26, Equal Opportunity (Mar 2007) (E.O. 11246).

_x (27) 52.222-35, Equal Opportunity for Veterans (Sep 2010)(38 U.S.C. 4212).

_x (28) 52.222-36, Affirmative Action for Workers with Disabilities (Oct 2010) (29 U.S.C. 793).

__ (29) 52.222-37, Employment Reports on Veterans (SEP 2010) (38 U.S.C. 4212).

__ (30) 52.222-40, Notification of Employee Rights Under the National Labor Relations Act (Dec 2010) (E.O. 13496).

__ (31) 52.222-54, Employment Eligibility Verification (JAN 2009). (Executive Order 12989). (Not applicable to the acquisition of commercially available off-the-shelf items or certain other types of commercial items as prescribed in 22.1803.)

__ (32)(i) 52.223-9, Estimate of Percentage of Recovered Material Content for EPA–Designated Items (May 2008) (42 U.S.C. 6962(c)(3)(A)(ii)). (Not applicable to the acquisition of commercially available off-the-shelf items.)

__ (ii) Alternate I (May 2008) of 52.223-9 (42 U.S.C. 6962(i)(2)(C)). (Not applicable to the acquisition of commercially available off-the-shelf items.)

__ (33) 52.223-15, Energy Efficiency in Energy-Consuming Products (DEC 2007) (42 U.S.C. 8259b).

__ (34)(i) 52.223-16, IEEE 1680 Standard for the Environmental Assessment of Personal Computer Products (DEC 2007) (E.O. 13423).

__ (ii) Alternate I (DEC 2007) of 52.223-16.

_x (35) 52.223-18, Contractor Policy to Ban Text Messaging While Driving (SEP 2010) (E.O. 13513).

_x (36) 52.225-1, Buy American Act—Supplies (Feb 2009) (41 U.S.C. 10a-10d).

__ (37)(i) 52.225-3, Buy American Act—Free Trade Agreements—Israeli Trade Act (June 2009) (41 U.S.C. 10a-10d, 19 U.S.C. 3301 note, 19 U.S.C. 2112 note, 19 U.S.C. 3805 note, Pub. L. 108-77, 108-78, 108-286, 108-302, 109-53, 109-169, 109-283, and 110-138).

__ (ii) Alternate I (Jan 2004) of 52.225-3.

__ (iii) Alternate II (Jan 2004) of 52.225-3.

__ (38) 52.225-5, Trade Agreements (AUG 2009) (19 U.S.C. 2501, et seq., 19 U.S.C. 3301 note).

__ (39) 52.225-13, Restrictions on Certain Foreign Purchases (June 2008) (E.O.’s, proclamations, and statutes administered by the Office of Foreign Assets Control of the Department of the Treasury).

__ (40) 52.226-4, Notice of Disaster or Emergency Area Set-Aside (Nov 2007) (42 U.S.C. 5150).

__ (41) 52.226-5, Restrictions on Subcontracting Outside Disaster or Emergency Area (Nov 2007) (42 U.S.C. 5150).

__ (42) 52.232-29, Terms for Financing of Purchases of Commercial Items (Feb 2002) (41 U.S.C. 255(f), 10 U.S.C. 2307(f)).

__ (43) 52.232-30, Installment Payments for Commercial Items (Oct 1995) (41 U.S.C. 255(f), 10 U.S.C. 2307(f)).

_x (44) 52.232-33, Payment by Electronic Funds Transfer—Central Contractor Registration (Oct 2003) (31 U.S.C. 3332).

__ (45) 52.232-34, Payment by Electronic Funds Transfer—Other than Central Contractor Registration (May 1999) (31 U.S.C. 3332).

__ (46) 52.232-36, Payment by Third Party (Feb 2010) (31 U.S.C. 3332).

__ (47) 52.239-1, Privacy or Security Safeguards (Aug 1996) (5 U.S.C. 552a).

__ (48)(i) 52.247-64, Preference for Privately Owned U.S.-Flag Commercial Vessels (Feb 2006) (46 U.S.C. Appx. 1241(b) and 10 U.S.C. 2631).

__ (ii) Alternate I (Apr 2003) of 52.247-64.

(c) The Contractor shall comply with the FAR clauses in this paragraph (c), applicable to commercial services, that the Contracting Officer has indicated as being incorporated in this contract by reference to implement provisions of law or Executive orders applicable to acquisitions of commercial items:

[Contracting Officer check as appropriate.] __ (1) 52.222-41, Service Contract Act of 1965 (Nov 2007) (41 U.S.C. 351, et seq.).

__ (2) 52.222-42, Statement of Equivalent Rates for Federal Hires (May 1989) (29 U.S.C. 206 and 41 U.S.C. 351, et seq.).

__ (3) 52.222-43, Fair Labor Standards Act and Service Contract Act—Price Adjustment (Multiple Year and Option Contracts) (Sep 2009) (29 U.S.C. 206 and 41 U.S.C. 351, et seq.).

__ (4) 52.222-44, Fair Labor Standards Act and Service Contract Act—Price Adjustment (Sep 2009) (29 U.S.C. 206 and 41 U.S.C. 351, et seq.).

__ (5) 52.222-51, Exemption from Application of the Service Contract Act to Contracts for Maintenance, Calibration, or Repair of Certain Equipment—Requirements (Nov 2007) (41 351, et seq.).

__ (6) 52.222-53, Exemption from Application of the Service Contract Act to Contracts for Certain Services—Requirements (Feb 2009) (41 U.S.C. 351, et seq.).

__ (7) 52.226-6, Promoting Excess Food Donation to Nonprofit Organizations (Mar 2009) (Pub. L. 110-247).

__ (8) 52.237-11, Accepting and Dispensing of $1 Coin (Sept 2008) (31 U.S.C. 5112(p)(1)).

(d) Comptroller General Examination of Record. The Contractor shall comply with the provisions of this paragraph (d) if this contract was awarded using other than sealed bid, is in excess of the simplified acquisition threshold, and does not contain the clause at 52.215-2, Audit and Records—Negotiation.

(1) The Comptroller General of the United States, or an authorized representative of the Comptroller General, shall have access to and right to examine any of the Contractor’s directly pertinent records involving transactions related to this contract.

(2) The Contractor shall make available at its offices at all reasonable times the records, materials, and other evidence for examination, audit, or reproduction, until 3 years after final payment under this contract or for any shorter period specified in FAR Subpart 4.7, Contractor Records Retention, of the other clauses of this contract. If this contract is completely or partially terminated, the records relating to the work terminated shall be made available for 3 years after any resulting final termination settlement. Records relating to appeals under the disputes clause or to litigation or the settlement of claims arising under or relating to this contract shall be made available until such appeals, litigation, or claims are finally resolved.

(3) As used in this clause, records include books, documents, accounting procedures and practices, and other data, regardless of type and regardless of form. This does not require the Contractor to create or maintain any record that the Contractor does not maintain in the ordinary course of business or pursuant to a provision of law.

(e)(1) Notwithstanding the requirements of the clauses in paragraphs (a), (b), (c), and (d) of this clause, the Contractor is not required to flow down any FAR clause, other than those in this paragraph (e)(1) in a subcontract for commercial items. Unless otherwise indicated below, the extent of the flow down shall be as required by the clause—

(i) 52.203-13, Contractor Code of Business Ethics and Conduct (Apr 2010) (Pub. L. 110-252, Title VI, Chapter 1 (41 U.S.C. 251 note)).

(ii) 52.219-8, Utilization of Small Business Concerns (Dec 2010) (15 U.S.C. 637(d)(2) and (3)), in all subcontracts that offer further subcontracting opportunities. If the subcontract (except subcontracts to small business concerns) exceeds $650,000 ($1.5 million for construction of any public facility), the subcontractor must include 52.219-8 in lower tier subcontracts that offer subcontracting opportunities.

(iii) [Reserved]

(iv) 52.222-26, Equal Opportunity (Mar 2007) (E.O. 11246).

(v) 52.222-35, Equal Opportunity for Veterans (Sep 2010) (38 U.S.C. 4212).

(vi) 52.222-36, Affirmative Action for Workers with Disabilities (Oct 2010) (29 U.S.C. 793).

(vii) 52.222-40, Notification of Employee Rights Under the National Labor Relations Act (Dec 2010) (E.O. 13496). Flow down required in accordance with paragraph (f) of FAR clause 52.222-40.

(viii) 52.222-41, Service Contract Act of 1965 (Nov 2007) (41 U.S.C. 351, et seq.).

(ix) 52.222-50, Combating Trafficking in Persons (Feb 2009) (22 U.S.C. 7104(g)).

___Alternate I (Aug 2007) of 52.222-50 (22 U.S.C. 7104(g)).

(x) 52.222-51, Exemption from Application of the Service Contract Act to Contracts for Maintenance, Calibration, or Repair of Certain Equipment-Requirements (Nov 2007) (41 U.S.C. 351, et seq.).

(xi) 52.222-53, Exemption from Application of the Service Contract Act to Contracts for Certain Services-Requirements (Feb 2009) (41 U.S.C. 351, et seq.).

(xii) 52.222-54, Employment Eligibility Verification (JAN 2009).

(xiii) 52.226-6, Promoting Excess Food Donation to Nonprofit Organizations (Mar 2009) (Pub. L. 110-247). Flow down required in accordance with paragraph (e) of FAR clause 52.226-6.

(xiv) 52.247-64, Preference for Privately Owned U.S.-Flag Commercial Vessels (Feb 2006) (46 U.S.C. Appx. 1241(b) and 10 U.S.C. 2631). Flow down required in accordance with paragraph (d) of FAR clause 52.247-64.

(2) While not required, the contractor may include in its subcontracts for commercial items a minimal number of additional clauses necessary to satisfy its contractual obligations.

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PART 12

INSTRUCTIONS, CONDITIONS, AND NOTICES TO OFFERORS OR RESPONDENTS

12.1 This contract incorporates one or more provisions by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at: www.acquisition.gov/far/index.html

The Government contemplates award of Firm Fixed Price Contract.

12.3 Response Instructions

All quotes and revisions shall be submitted to Linda Troutman via email at Linda.Troutman@fda.hhs.gov. Questions are due August 18, 2015, at 9:00 A.M. Eastern Time. Quotes and all revisions are due no later than August 27, 2014, at 4:30 P.M. Eastern Time. Offeror shall ensure the RFP number is visible in the subject line of the email. Faxed RFP not be accepted.

12.4 Format

12.4.1 The cover letter shall include; a POC (name and telephone number); a statement from the contractor verifying SAM Registered under NAICS code 541711; business size;

PER FAR PART 52.212-1 – Instructions to Offers – Commercial Items (JUN 2008)

12.5 Evaluation Criteria for Competitive Proposals

52.212‐2, Evaluation – Commercial Items (Jan 1999)

Evaluation of Offers (Single Award)

An offeror must offer on all items in this solicitation to be eligible for award.

The Government reserves the right to award a contract without discussions in accordance with FAR 52.212‐1; however if discussion become necessary a competitive range may be established with offerors that provide the most advantageous approach to the Government. After evaluating all proposals in accordance with 52.212‐1, the Government may determine that the number of most highly rated offers exceeds the number at which an efficient competition can be conducted. The Government reserves the right to exclude offers from further consideration of award and limit the number of offerors it will negotiate with to the greatest number that will permit an efficient competition.

Evaluation Criteria and Basis for Award (Best Value)

1. Basis for Award – The Government will award a single award contract resulting from this solicitation to the responsible offeror whose offer, conforming to this solicitation, is determined to be the best value to the Government, technical, price and other factors considered. The Government reserves the right to make an award to other than the lowest priced offeror.

1. General – In order to determine the offer providing the best value, the following factors will be considered:

FACTOR 1: Technical Understanding and Approach FACTOR 2: Relevant Past Performance FACTOR 3: Relevant Experience

FACTOR 4: PRICE

(1) The Technical Evaluation Factors (Factors 1 and 2) listed in descending order of importance. All weighted evaluation factors combined, are significantly more important than cost or price. As technical merit of an offeror’s proposals becomes equal, the evaluated price may become the determining factor. Factors 1 and 2 will be evaluated adjectivally and categorized as Excellent, Highly Acceptable, Acceptable, Marginal or Unacceptable.

Evaluation of Technical Proposal

Offerors evaluated based upon the following criteria:

FACTOR 1: Technical Understanding and Approach: The Government will evaluate the extent to which the Offeror’s proposal demonstrates an understanding of the SOW and its approach to conduct appropriate in vivo studies of generic drug products in healthy subjects or patients. A highly rated technical proposal is one that demonstrates full compliance with the technical requirements of this solicitation while demonstrating an understanding of the mitigation strategies for potential risks. The highly rated proposal will also demonstrate the availability of adequate equipment and facilities (i.e. number of patient beds/rooms) for conducting all phases of the proposed research as specified in the Statement of Work.

FACTOR 2: Relevant Past Performance: The Government will evaluate the extent to which the offeror’s proposal demonstrates the success of efforts on current and previous contracts, which are relevant to the Statement of Work in terms of scope…