FBO_Synopsis-Solicitation_Req_1116088_130530_Final.doc

This is a combined synopsis/solicitation for commercial items prepared in accordance with the Federal Acquisition Regulation (FAR) format in Subpart 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued. This requirement is being issued in conjunction with FAR 13.5 Test Program for Certain Commercial Items, as applicable. The solicitation number is FDA_13-RFQ-1116088. This solicitation is issued as a Request for Quote (RFQ).

The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular (FAC) 2005-66, effective April 1, 2013.

The associated North American Industry Classification System (NAICS) Code is 541380-Testing Laboratories; which carries a Small Business Size Standard of $14 million. However, this requirement is NOT set-aside for small business. The requirement is being competed subject to full and open competition and any qualified, interested party may submit a quote.

Background Accurate prediction of in vivo performance for oral solid dosage forms will significantly reduce the length and cost of drug development including both innovation drugs and generic drugs. Various methods have been developed to predict in vivo performance for oral solid dosage forms, which mainly can be classified as empirical models and mechanistic models.

Empirical models are relatively mathematically simple, but have the limitations such as it is difficult to be extrapolated. For example, the empirical in vitro-in vivo correlation (IVIVC) models are difficult to be applied to other formulations with different release mechanisms. Mechanistic models have the merits that they integrate formulation properties and physiological properties to simulate the physical and chemical fate of the active ingredients in vivo. Unlike empirical IVIVC models, which require at least two formulations for model development, IVIVC based on mechanistic models can be applied to formulations with different release mechanisms in follow-on formulation development without developing additional formulations. It is expected that predictive mechanistic models will reduce the number of failed bioequivalence trials.

Even though mechanistic absorption models have been advanced and widely used over the past twenty years, there are still knowledge gaps that need to be filled to improve prediction of in vivo performance. These knowledge gaps can be classified into three categories: (1) Better understanding of gastrointestinal (GI) physiology under different conditions (fasting, fed, disease, etc.), such as GI lumen fluid volume and distribution, composition of GI luminal fluid, micro-environment pH, regional abundance of metabolic enzymes and transporters, and hydrodynamics of GI fluid, etc.; (2) Better tools (in vitro or in silico) that correlate well in vivo release of active pharmaceutical ingredients from formulations designed by different release mechanisms and that predict in vivo permeability; and (3) Better in silico tools that integrate GI physiology and in vitro results to predict in vivo performance for oral solid dosage forms. The purpose of this project is to address some of challenges and improve prediction of in vivo performance for oral solid dosage forms.

Objectives The objective of this requirement is to improve prediction of in vivo performance for oral solid dosage forms.

Minimum Performance Requirements The Contractor shall be required to perform an in vivo validation study under fasting condition measuring local concentration of the model drug in the gastrointestinal lumen and plasma concentration. The study will enroll at least 60 subjects for the initial study/model development, and at least 36 subjects in each additional validation study. The FDA shall identify the model drug product for the initial study at the time of award and the drug product(s) for the additional, validation studies if/when options are exercised.

Tasks 1-4 are tasks that shall be required of the Contractor during the two year base period of the contract. Requirements listed under Task 5 will be option line items in the contract that the Government may exercise unilaterally after the base year tasks have been completed.

Task 1:

Conduct an in vivo study to acquire human GI physiology data from 60 healthy subjects under fasting (30 subjects) and fed (30 subjects) conditions which are necessary for mechanistic model development. Human GI physiology data shall include at least the composition of GI luminal fluid such as buffer type and capacity, pH and microenvironmental pH of GI luminal fluid, volume of GI luminal fluid, hydrodynamics of GI luminal fluid, and motility of GI tract. Within-subject variability of those physiology parameters shall also be assessed, i.e. each subject will be measured at least twice.

Task 2:

Development of in vitro predictive dissolution methodologies that closely reflect in vivo conditions, including hydrodynamics, buffer type and capacity, pH, and volume of GI luminal fluid.

Task 3:

Development of computational models that simulate hydrodynamics in human GI lumen.

Task4:

Development of computational models that integrate in vivo physiology data acquired in this project, and in vitro dissolution measurements to predict in vivo performance for oral solid dosage forms.

Task 5:

Validation Studies: After the parameter characterization and model development, the model will be validated through the testing of 6 additional drug products. The selection of model drug products will be identified by the FDA. The 6 additional validation studies will be crossover in vivo bioequivalence (BE) studies with pharmacokinetic endpoints. At least 36 subjects will be enrolled in each of the 6 validation studies.

Task 5.a:

Option 1 will be comprised of two of the six additional validation studies. One is under fasting condition and one is under fed condition, the drug concentration in the different sites of GI lumen will be measured in addition to plasma concentration in order to validate the predictability of the model for GI local concentration.

Task 5.b:

The remaining four validation studies shall constitute Option 2. For these 4 studies, only regular BE studies measuring plasma concentration shall be performed.

Note: The contractor shall be responsible for subject recruitment, supplies, equipment, and computational software needed for all studies and model development.

References

· Dressman JB, Thelen K, Willmann S. An update on computational oral absorption simulation. Expert Opin Drug Metab Toxicol. 2011 Nov;7(11):1345-64.

· Yu L, Zhang X, Lionberger R. Modeling and mechanistic approaches for oral absorption: quality by design in action. Ther Deliv. 2012 Feb;3(2):147-50.

Deliverables

Quarterly Progress Report

30 days following the close of every third month from the contract award date.

Reports (i.e., quarterly progress reports, annual reports and final report), containing the description of experiments and data analysis, will be provided to the FDA in 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. The FDA will not be providing data to the contractor. The contractor shall be responsible for obtaining a new set of gastrointestinal physiology data from the study. The ideal is to make the final data available to the scientific community to contribute to the science and research in this area in addition to meeting (Office of Generic Drugs) OGD’s needs and advancing the regulatory science. Additionally, for the computation model, all the original code, input files, output files, geometries, and documents on the model development will be provided to the FDA in electronic format so that the model can be used by the FDA for future projects.

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 Technical 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.

Place of Performance The vast majority of the work is to be performed at the Contractor’s location. The exception is that the Contractor should anticipate one required trip per year to an FDA campus located in Rockville, MD in order to present the findings of the annual report.

Period of Performance Note: Performance Period start/end dates listed below are estimates only. Actual performance dates will be based on the actual award date of the contract and shall be identified in the contract award document.

The estimated performance dates could potentially be as follows:

Award of contract- 8/26/13 Base period: 8/26/13 – 8/25/15

Option 1: 8/26/15 – 8/25/16

Option 2: 8/26/16- 8/26/17 Schedule of Items:

1. Base Period: Tasks 1-4 as identified in “Minimum Performance Requirements” section.

Firm fixed price of $_____________.

2. Option 1:– Tasks 5.a. as identified in “Minimum Performance Requirements” section.

Firm fixed price of $____________per study x Max Qty (2) = $____________

3. Option 2:– Tasks 5.b. as identified in “Minimum Performance Requirements” section.

Firm fixed price of $____________per study x Max Qty (4) = $____________ Total Price (Base + Options): Firm fixed price of $____________

Contract clauses- The clause at 52.212-4, Contract Terms and Conditions-Commercial Items (FEB 2012), applies to this acquisition. The following addenda apply:

The supplies and/or services delivered hereunder shall be inspected and accepted at destination by the contracting officer’s representative (COR) specified at award. If the supplies or services are acceptable, the COR shall promptly forward a report of inspection and acceptance to the paying office. If the supplies or services are not acceptable, the COR shall document the nonconforming items/services and immediately notify the contracting officer.

Other Terms and Conditions

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 Technical 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 a Contractor employee 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 and shall not unilaterally decide that the data should not be published. These rights are retained by the Government only.

The following additional provisions and/or clauses, incorporated by reference, apply to this acquisition. FAR and HHSAR clauses and provisions can be obtained at http://www.acquisition.gov/far/ and http://www.hhs.gov/policies/hhsar/subpart352.html.

The following FAR and HHSAR clauses, incorporated by reference, and apply to this acquisition.

FAR Clause 52.204-4 Printed or Copied Double-Sided on Recycled Paper. (MAY 2011)

FAR Clause 52.225-8 Duty-Free Entry. (OCT 2010)

FAR Clause 52.217-9 Option to Extend the Term of the Contract (MAR 2000)

(a) … within 1 day of contract expiration; …. at least 15 days before the contract expires...

(c) …shall not exceed 5 years.

HHSAR Clause 352.201-70 Paperwork Reduction Act

JAN 2006

HHSAR Clause 352.202-1 Definitions

JAN 2006

HHSAR Clause 352.203-70 Anti-Lobbying

JAN 2006

HHSAR Clause 352.219-70 Mentor-protégé program

JAN 2010

HHSAR Clause 353.219-71 Mentor-protégé program reporting requirements

JAN 2010

HHSAR Clause 352.222-70 Contractor Cooperation in Equal Employment Opportunity Investigations

OCT 2009

HHSAR Clause 352.223-70 Safety and Health

JAN 2006

HHSAR Clause 352.224-70 Privacy Act

JAN 2006

HHSAR Clause 352.227-70 Publications and Publicity JAN 2006 HHSAR Clause 352.231-71 Pricing of Adjustments

JAN 2001

HHSAR Clause 352.242-71 Tobacco-Free Facilities

JAN 2006

HHSAR Clause 352.270-1 Accessibility of meetings, conferences, and seminars to persons with disabilities

JAN 2001

Contract Administration

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 statement of work;

(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.

The Contracting Officer for this order is:

Aaron A. Glazier, Contracting Officer

3900 NCTR Rd

HFT-320

Jefferson, AR. 72079

Phone: (870) 543-7577

Email: aaron.glazier@fda.hhs.gov 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.

The COR for this order is: to be completed at time of award.

Invoice Submission

Invoices shall be submitted to the attention of the designated Contract Specialist identified below and contain all necessary information per FAR 52.212-4 (g) in accordance with the following instructions.

I. An original and two (2) copies shall be submitted to:

3900 NCTR Road, HFT-320 Attn: Aaron Glazier Building 50, 4th floor, Room 417 Jefferson, AR 72079 Phone: (870) 543-7577 Fax 870-543-7224

An electronic invoice can be emailed to the following address:

aaron.glazier@fda.hhs.gov II. One copy to the Contracting Officer Representative (COR) or other program center/office designee, clearly marked “courtesy copy only”:

To be completed at time of award.

Questions regarding invoice payments should be directed to the FDA payment office at phone or email reference provided above.

Questions relating to when payment will be received should be directed to the FDA payment office at the email below or at (870) 543-7446 or (870) 543-7042. nctrinvoices@fda.hhs.gov.

The clause at FAR 52.212-5, Contract Terms and Conditions Required to Implement Statues or Executive Orders-Commercial Items (JAN 2013) applies to this acquisition. The following additional FAR clauses cited in this clause are applicable:

(b) 52.203-6 Alt I, 52.203-13, 52.204-10, 52.209-6, 52.209-9, 52.219-4, 52.219-8, 52.219-9, 52.219-16, 52.219-28, 52.222-3, 52.222-19, 52.222-21, 52.222-26, 52.222-35, 52.222-36, 52.222-37, 52.222-40, 52.222-54, 52.223-18, 52.225-13, and 52.232-33.

Solicitation provisions

Contract Type: Commercial Item-Firm Fixed Price.

The provision at FAR 52.212-1 Instructions to Offerors-Commercial Items (FEB 2012) applies to this solicitation. The following addenda apply:

Addendum to 52.212-1 (b) Submission of Offers

Offerors’ proposals shall be comprised of two separate volumes. Proposals shall be prepared in accordance with the instructions below. The volumes shall be as follows:

Volume I:

Technical Proposal

Volume II:

Business Proposal Each of the proposals shall be separate and complete in itself so that evaluation of one may be accomplished independently of, and concurrently with, evaluation of the other. The technical proposal must include direct cost and resources information, such as the number of proposed labor categories and number of hours, list of materials, subcontracts, etc., so that the Offeror's understanding of the project may be evaluated. However, the technical proposal should not include actual pricing information or total costs. The technical proposal should disclose your technical approach in accomplishing Tasks 1-5 in as much detail as possible. The technical proposal shall also include the requested Past Performance Information. The Offeror shall identify 2-3 other organizations for whom they have performed similar tasks. Descriptions shall include the degree of their involvement (prime or subcontractor), the size of the client’s organization, and other information to describe their expertise and performance in the subject areas, highlighting the organization’s demonstrated successes. For each project cited as relevant experience, the Offeror shall include a POC for the organization for whom the work was performed. Offerors may also include in their proposals performance recognition documents received within the last 3 years, such as awards, award fee determinations, customer letters of commendation, or any other relevant forms of performance recognition that may demonstrate successful pat performance.

Offerors shall ensure that the price (business) proposal is consistent with the technical proposal in all respects since the price proposal may be used as an aid to determine the Offeror's understanding of the technical requirements. Discrepancies may be viewed as a lack of understanding. The pricing structure provided in the business proposal shall easily tie back to the tasks and Contractor’s approach as described in the technical proposal.

Addendum to 52.212-1 (c) Period for acceptance of offers. The offeror shall state in its quote that the prices in its quote are valid through September 30, 2013.

FAR 52.212-2 Evaluation-Commercial Items (JAN 1999)

(a) The Government will award a contract resulting from this solicitation to the responsible offeror whose offer conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors, listed in descending order of importance, shall be used to evaluate offers: Technical Approach/Capability, Past Performance, and Price.

Technical Approach/Capability and past performance, when combined, are significantly more important than price. When making its best value determination, if the Government determines non-price factors to be essentially equal, price becomes more important as the discriminating factor.

(b) Options. The Government will evaluate offers for award purposes by adding the total price for all options to the total price for the basic requirement. The Government may determine that an offer is unacceptable if the option prices are significantly unbalanced. Evaluation of options shall not obligate the Government to exercise the option(s).

(c) A written notice of award or acceptance of an offer, mailed or otherwise furnished to the successful offeror within the time for acceptance specified in the offer, shall result in a binding contract without further action by either party. Before the offer’s specified expiration time, the Government may accept an offer (or part of an offer), whether or not there are negotiations after its receipt, unless a written notice of withdrawal is received before award.

The Government will award a contract resulting from this solicitation to the responsible offeror whose offer conforming to the solicitation will be the most advantageous to the Government, price and other factors considered.

Technical Approach/Capability Technical Approach/Capability will be determined by review of information submitted by the offeror which shall provide sufficient technical information necessary for the Government to conclusively determine that it is capable of performing Tasks 1-5 as described in the “Minimum Performance Requirements” Section. Offerors shall demonstrate that they have the knowledge and expertise to accomplish these tasks. Offerors shall specifically address each of the tasks and thoroughly demonstrate that they understand the task and show how they intend to accomplish it. This would include but not be limited to describing the technical approach, steps, methodologies, anticipated labor categories, individuals to perform the work. Offerors may also provide descriptive material, literature, brochures and other information which demonstrates the capabilities of the offeror. The Proposal shall be specific, detailed, and complete enough to clearly and fully demonstrate that the Contractor understands the requirements and the inherent problems associated with the objectives of this procurement. Stating that you understand and will comply with the specifications/tasks, or paraphrasing the specs/tasks is inadequate. Similarly, proposals with phrases such as: "Standard procedures will be employed" and "Well-known techniques will be used" will be determined to be non-responsive. The Proposal must address each Task and be sufficiently detailed so as to allow the government to evaluate the feasibility of how the Offeror proposes to comply with the applicable Performance Requirements including a full explanation of the techniques and procedures to be followed. The Offeror is urged to examine this solicitation in its entirety and to ensure that the submitted proposal contains all the necessary information and provides all required documentation and is complete in all respects. Evaluation of the proposal will be based on the actual material presented and not on the basis of what is implied.

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 tasks set forth in Section C in terms of type, scope, complexity, and size. The Government may telephone and/or email the POC’s for the Offeror’s cited projects in order to ascertain how well the Contractor performed.

Price

The Government will evaluate offers for award purposes by adding the total price for all options to the total price for the basic requirement. Offerors shall ensure that the price (business) proposal is consistent with the technical proposal in all respects since the price proposal may be used as an aid to determine the Offeror's understanding of the technical requirements. Discrepancies may be viewed as a lack of understanding. The pricing structure provided in the business proposal shall easily tie back to the tasks listed in the technical proposal.

A written notice of award or acceptance of an offer, mailed or otherwise furnished to the successful offeror within the time for acceptance specified in the offer, shall result in a binding contract without further action by either party. Before the offer’s specified expiration time, the Government may accept an offer (or part of an offer), whether or not there are negotiations after its receipt, unless a written notice of withdrawal is received before award.

The Provision at FAR 52.212-3, Offeror Representations and Certifications-Commercial Items (DEC 2012), applies to this acquisition. An offeror should complete only paragraph (b) of this provision if the offeror has completed the annual representations and certifications electronically at https://www.sam.gov/portal/public/SAM/ .

It is the offeror's responsibility to monitor http://www.fbo.gov for the release of any information related to this acquisition, e.g., questions and answers, amendments, award notice, etc.

Offerors that fail to complete the required representations and certifications, or reject the terms and conditions of the solicitation, may be excluded from consideration.

All responsible sources may submit a quote, which if timely received, shall be considered. The offer shall reference solicitation number FDA_13-RFQ-1116088. The offers are due in person, by postal mail or email to the point of contact listed below on or before 26 June, 2013 by 13:00 hours (local time in Jefferson, Arkansas) at the Food and Drug Administration, OO/OFBA/OAGS, Attn: Aaron A. Glazier, 3900 NCTR Road, HFT-320, Jefferson, AR 72079-9502.

For information regarding this solicitation, please contact Aaron Glazier at (870) 543-7577, FAX (870) 543-7990 or email aaron.glazier@fda.hhs.gov. Questions pertaining to the scope or solicitation submittal procedures shall be submitted by 13:00 hours (local time in Jefferson, Arkansas) 11 June 2013.