NIHAI2015035 _Amendment_No_1_with_attachments.pdf

Amendment 1 pg. 1 RFP No. NIAID-DAIDS-NIHAI2015035

Amendment No. 1

NIAID-DAIDS-NIHAI2015035

“NIAID Preclinical Development Support”

Solicitation Number: NIAID-DAIDS-NIHAI2015035

Amendment Number: One (1)

Amendment Issue Date: May 27, 2016

Proposal Due Date (Unchanged): Friday, June 10, 2016 at 3:00 PM, Local Time

Issued By: Michelle L. Scala

Contracting Officer

OA/DEA/NIAID/NIH/DHHS

5601 Fishers Lane, Room 3D10, MSC 9821 Bethesda, Maryland 20892-9821

Points of Contact: PRIMARY patelki@niaid.nih.gov Kishan Patel, Contracting Officer Phone: (240) 669-5157

SECONDARY

mscala@niaid.nih.gov Michelle L. Scala, Contracting Officer Phone: (240) 669-5156

Please note that we do NOT intend to extend the due date for submission of proposals as a result of this amendment. The date specified for receipt of proposals remains unchanged.

The purpose of this Amendment is to provide responses to questions from potential offerors regarding the solicitation and modify the Request for Proposal as follows:

Attachment 9, Sample Task Order F-1, Safety and Immunogenicity Testing, is revised to modify the Statement of Work to address concerns raised by potential offerors.

Attachment 10, Additional Technical Proposal Instructions, is revised to clarify the requirements regarding subcontractor/consultant identification.

mailto:patelki@niaid.nih.gov mailto:mscala@niaid.nih.gov

Amendment 1 pg. 2

Attachment 11, Additional Business Proposal Instructions and Uniform Cost Assumptions, is revised to address budget preparation questions regarding frequency and duration of Task Orders, and to questions about some of the Uniform Cost Assumptions.

Attachment 16 – Contract Proposals Vertebrate Animal Section Worksheet, is removed in its entirety and replaced with the attached document entitled, “Attachment 16 – Contract Proposals Vertebrate Animal Section Worksheet.” In addition, Section L - Instructions, Conditions, and Notices to Offerors paragraph 2., Instructions to Offerors, Subparagraph B., Technical Proposal Instructions, subparagraph 5., Research Involving Live Vertebrate Animals, is revised to remove bullet c., Information on the veterinary care of animals.

Attachment 18, Small Business Subcontracting Plan, is removed in its entirety and replaced by the attached updated document entitled, “Attachment 18 – Small Business Subcontracting Plan.”

Offerors must acknowledge receipt of this Amendment by identifying this amendment number and date of the amendment on each copy of the proposal submitted. Failure to receive your acknowledgement may result in the rejection of your proposal. Except as provided herein, all terms and conditions of the solicitation remain unchanged and in full force and effect.

Question 1:

Can you confirm that the Vertebrate Animal Section (VAS) no longer requires 5 sections, as requested in Section L.2.b.5.? NIH revised VAS requirements on 10/8/15 to specify only 4 sections are now required. Which format is required for this submission?

http://grants.nih.gov/grants/olaw/VAScontracts.pdf

Response to Question 1: The Government has updated Section L.2.b.5. and also Attachment 16 - Contract Proposals Vertebrate Animal Section Worksheet, of the RFP as stated above.

Question 2:

The business instructions in Attachment 11 for Sample Task Order F-1: Safety and Immunogenicity Testing call for two more doses than the technical instructions in Attachment 9.

How many doses should we base our costing and timeline against?

Response to Question 2: Please base the proposed budget and timeline against 4 doses.

Attachment 11, ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST ASSUMPTIONS, Section 3, Uniform Cost Assumptions, paragraph 1.D., Cost Proposals for Sample Task Orders, subparagraph 5), Sample Task Order F-1 for Safety and Immunogenicity Testing, first paragraph, is revised to read as follows:

Assume 3 Toxicity and Immunogenicity Testing projects per year during the 7 year base contract period. A typical study would be a four arm, 4 dose, rabbit repeat toxicity study with terminal and recovery groups. Assume dosing of DNA or protein vaccines at 3 week intervals and a 3 week recovery interval. One to three immunogens will be given http://grants.nih.gov/grants/olaw/VAScontracts.pdf

Amendment 1 pg. 3

IM at each time interval. Serum specimens will be collected at 3 time points during the study and saved for immunogenicity studies. The total duration for the study will be approximately one year.

Question 3:

Sub-contracts: In multiple places in Attachments 10 and 11 it is indicated that offerors should not propose or name subcontractors for the sample task orders. We anticipate the need to sub-contract various functions under the sample task orders. Please clarify how you expect the sub-contracted functions to be presented in the technical and business proposal responses for each sample task order. We understand the need to address a plan for identifying potential subcontractors with interest and the necessary capability and qualifications; however we are unclear regarding the requirement to identify actual subcontractors for the sample task orders.

This activity would require additional time to complete. At present, we are unclear as to how to present subcontracted functions and how to proceed with the respective budgets for these for each sample task orders.

Response to Question 3: It is very important that we understand the offeror’s process for identifying, selecting, and managing subcontractors/consultants to carry out the work in the Sample Task Orders. Therefore, we ask that you identify potential consultants and subcontractors who will be tasked to carry out the work. You should demonstrate that the subcontractor/consultant is capable of carrying out the proposed work and what previous experience you have had with the subcontractor. We do not expect you to enter into subcontract agreements or to obtain cost proposals from subcontractors for the Sample Task Orders.

However, you should propose costs for subcontracts/consultants based on experience with the potential subcontractors/consultants for previously performed work for similar tasks.

Attachment 10, Additional Technical Proposal Instructions, and Attachment 11, ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST ASSUMPTIONS, are attached and have been revised to clarify what information is to be included in your proposal regarding subcontracts.

Question 4:

Attachment 11 provides a table showing the anticipated number of task orders to be issued for each Task Area. Please clarify whether we are expected to budget for the anticipated number of task orders per year over the seven years of the contract. For example, for Task Area E, Process Development & CGMP Manufacturing, do you expect a budget for 4 task orders annually (each for an average duration of 3 years) over 7 years for a total of 28 task orders? If not, then do we follow the guidance on page 3 of Attachment 11 and budget for one task order (Sample Task Order E-1) for a period of 7 years? Please provide clarifications on how to budget for each task area.

Response to Question 4: You should provide a cost proposal for the total number of task orders per year over the 7 year period of the contract (as listed in the table in Attachment 11, Amendment 1 pg. 4

ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST

ASSUMPTIONS, Section 3, Uniform Cost Assumptions, Paragraph 1.B., Scope of Activities).

In regard to Sample Task Order E-1 for Process Development and CGMP Manufacturing, we are revising the cost proposal requirements so that the Year 1 estimate will be different than Years 2 through 7.

For Year 1, please assume the completion of upstream and downstream process development and cGMP Manufacture, fill, finish, labeling, release, and 4 year stability program of four HIV-1 gp120 protein (1 gram) for phase I human clinical trials. Total task length will be 7 years including the stability program. Also assume that 4 Task Orders will be issued in Year 1.

For Years 2 – 7, please assume the completion of upstream and downstream process development and cGMP Manufacture, fill, finish, labeling, release of four HIV-1 gp120 protein (1 gram) for phase I human clinical trials. Total task length will be 3 years. No stability program should be budgeted.

As a result of the response to this question, Attachment 11 - ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST ASSUMPTIONS, has been revised accordingly.

Question 5:

What is the turnaround time for NIAID to respond to questions under this RFP? Also, does NIAID plan to issue a complete list of Questions and Answers for this RFP?

Response to Question 5: NIAID requires approximately 7 business days to respond to any questions. That is why we encouraged the submission of questions by no later than May 20, 2016, so that we had adequate time to provide timely responses before proposals are due. A complete list of Questions and Answers will be provided by issuing an Amendment to the RFP and will be published through the FBO.gov website.

Task Area B – Feasibility Assessment Questions

Question 6:

The scope of the Feasibility Assessment narrates: ‘The purpose of this task area is to assess the status of products and materials for feasibility of design, development, manufacture, potency assay development, stability, and cost for the development of phase I‐III clinical trial materials’.

As feasibility assessment for a vaccine candidate is done, is it accurate to assume that vaccine production using transient transfection will not proceed beyond Phase I clinical evaluation and Phase II-III clinical trial material will be produced using stable CHO-lines?

Response to Question 6: Yes, it is accurate to assume that vaccine production using transient transfection will not proceed beyond Phase I clinical evaluation and Phase II-III clinical trial material will be produced using stable CHO-lines.

Amendment 1 pg. 5

Question 7:

Certain parts of the RFP text refers to “electroporation and other methods of transfection” and sometimes only “electroporation” is mentioned. Is it expected that various cell transient transfection methods be compared for each vaccine candidate?

Response to Question 7: No, different transient transfection methods are not expected to be compared although the possibility is not precluded. Electroporation is currently the preferred transfection method.

Question 8:

Is it expected that duration of all stability studies to be conducted as part of feasibility studies will be 48 months?

Response to Question 8: For budgeting proposes, assume the duration of all stability studies to be conducted as part of feasibility studies will be 48 months. As a result of the response to this question, Attachment 11 - ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST ASSUMPTIONS, has been revised accordingly.

Task Area C –Auditing:

Question 9:

The requirements for the contractor are stated as: “When requested by the COR, manage and conduct audits of foreign and domestic sites, for compliance with domestic and non‐domestic laws and regulations and FDA regulations and guidance, including those required to meet GLP, CGMP, and Good Clinical Practice (GCP) standards, NIAID policies, and the terms of the contract. Audits include facility audits and/or technical audits. Ensure that appropriate staff and all necessary records are available for audits.”

a. Please clarify the responsibilities for GCP and GCLP auditing to be conducted as part of Task order C (Auditing).

Response to Question 9.a.: It is not anticipated that the Contractor will be required to complete GCP and GCLP audits.

b. What are the specific responsibilities of the contractor with regard to audit of clinical laboratories during Phase I, II, and III trials, including immunology and safety testing (chemistry, hematology and urinalysis)? Is monitoring of EQA data in scope of the

RFA?

Response to Question 9.b.: It is not anticipated that the Contractor will be required to audit clinical laboratories or monitor EQA data.

Amendment 1 pg. 6

Task Area D – Regulatory Documentation

Question 10:

The scope of Task Order D includes: “The purpose of this task order is to develop, in consultation with the Contracting Officer’s Representative (COR), vaccine sponsors, and other contractors, all documentation needed for submission of an investigational New Drug Application (IND to CBER, FDA) for an HIV-Env protein vaccine. The Contractor shall prepare and submit a Pre-IND and an IND.”

a. Please clarify the responsibilities of the contractor in IND submission. Is the contractor responsible only for the preclinical documentation, or as implied, the CMC, preclinical, and regulatory (Module 1) sections of the IND/preIND?

Response to Question 10.a: The Contractor shall be responsible for ALL sections (as stated in Attachment 7 – Sample Task Order D-1, Regulatory Documentation, Section III, Technical Requirements, subsection A. paragraphs 1 through 6) in the IND submission.

b. If the Contractor is responsible for the final preparation of the pre IND/IND, please clarify if an eCTD document is the expected deliverable of Task order D?

Response to Question 10.b: The Contractor is responsible for the final preparation of the pre IND/IND as is indicated in the Sample Task Order. At this time, paper documents are delivered to the Food and Drug Administration. However, this will be transitioning to an electronic format at some time during the course of the contract. For the purpose of this sample Task Order, assume paper copies will be required. As a result of the response to this question, Attachment 11 - ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST ASSUMPTIONS, has been revised accordingly.

Task Area E - Process Development and cGMP Manufacturing Questions:

Question 11:

Is stable CHO-line generation out of scope of the contract for Phase I clinical material production?

Response to Question 11: This is out of scope for sample Task Order E-1, but not for Phase I clinical materials in general.

Question 12:

In Attachment 11, under ‘Storage and Shipping’, it is suggested that ‘current volumes are approximately 100 cubic feet at -80C, 50 cubic feet at -20C and 200cubic feet of biomaterials at room temperature’. However, based on the storage conditions cited (-80C, -20C, 2-6C), is the expectation to store ‘200 cubic feet volume’ of biomaterial at 2-6C and not ‘room temperature’?

Amendment 1 pg. 7

Response to Question 12: The 200 cubic feet volume is at room temperature as stated. Thus “room temperature” is hereby added to the list of storage temperatures cited in Attachment 11.

As a result of the response to this question, Attachment 11 - ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST ASSUMPTIONS, has been revised accordingly.

Question 13:

Based on the table below (from Attachment 11 of the RFP), and the assumption to conduct 1 cGMP manufacturing per year for 7 years, is there an expected average ‘timeline’ to complete feasibility assessment, process development, cGMP manufacturing, fill-finish and drug product release for a given candidate vaccine?

Response to Question 13: We did provide the average duration of each Sample Task Order noted in the Table above. No other timelines were provided since it may vary based on the vaccine product.

Please note that the assumption listed in the Table you refer to is to conduct 4 Process Development and cGMP Manufacturing each year during each year of the 7 year contract, not 1 per year as you have stated. The average duration for the Process Development & CGMP Manufacturing has been revised as noted above in Question 4.

As for Feasibility Assessments, as noted in the table, you should budget for 1 Feasibility Assessment per year during the 7 year period of the contract. As noted in the table, the average duration of each Task Order is 1 year.

As a result of the response to this question, Attachment 11 - ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM COST ASSUMPTIONS, has been revised accordingly.

Question 14:

Since most vaccine dosing in pre-clinical studies is typically done at low microgram levels (with the exception of mAbs), how critical is it under Task Area E to plan to produce “gram quantities” of vaccine candidates? What are the expectations for the quantities of viral vaccine candidates which are quantified by infectivity?

Amendment 1 pg. 8

Response to Question 14: It depends on the product. For Env protein products a typical yield might be 1 gram or more. Viral vaccines depend on many factors and are virus specific.

Task Area F - Safety and Immunogenicity Questions:

Question 15:

Should we present information about possible CROs given that the sample task order specifically states not to identify the subcontractors?

Response to Question 15: See our response to Question 3 above. Please present sufficient information so that the Government can evaluate how you identify, select and manage the subcontractors. Part of the identification and selection process would address how you determine whether a subcontractor is qualified to carry out the proposed work.

Question 16:

Should we obtain actual quotations from CRO(s) for this sample task order?

Response to Question 16: It is not necessary to provide actual quotations from CROs. Estimated costs for subcontractors, however, should be based on actual/historical cost experience for similar work.

Question 17:

For this sample task order, should we assume that:

a. the proposed clinical route of administration is intramuscular?

Response to Question 17.a: Yes, the proposed clinical route of administration is intramuscular.

b. the four (4) groups will be Control, High dose plus Alum, Low dose plus alum, High dose plus placebo? If not, please describe the groups.

Response to Question 17.b: The four treatment groups will be high, medium and low antigen doses plus placebo group.

c. an immunogenicity assay is available and could be transferred to a CRO? If not, please describe what method should be developed.

Response to Question 17.c: For this sample task assume that immunogenicity may be measured by standard commercially available EIA and western blot assays.

d. an analytical assay is available to be transferred to the CRO for test article confirmation

(CFR58.113)?

Amendment 1 pg. 9

Response to Question 17.d: Test article confirmation is not required for this sample Task Order.

e. the products will be provided ready for use or will dilution of the protein and mixture with alum or placebo be required to be performed at the CRO?

Response to Question 17.e: For this sample Task Order, assume Antigen and alum will be provided by the Government and must be mixed just prior to use

As a result of the responses to the questions above, Attachment 9 – Task Order F-1 Safety and Immunogenicity Testing, has been revised accordingly.

Question 18:

What do we do about contingencies? For example, if there is an unexpected finding in a toxicity study, additional investigations may be required to understand if the finding is a safety concern. This could involve additional time by the study monitor, toxicologist or supervisor or even additional studies. How should this be included in our response?

Response to Question 18: Please only budget for the study as it is presented in the Sample Task Order. If such contingencies arise during performance, these changes will be dealt with by modifying the Task Order to increase the duration and/or to provide additional funds.

END OF AMENDMENT #1

ATTACHMENT 9 – STATEMENT OF WORK FOR TASK

ORDER F-1, SAFETY AND IMMUNOGENICITY TESTING rev.

5/27/2016 Page 1 of 4

ATTACHMENT 9 – SAMPLE TASK ORDER F-1

PROJECT TITLE: NIAID PRECLINICAL DEVELOPMENT SUPPORT

SAMPLE TASK ORDER F-1

SAFETY AND IMMUNOGENICITY TESTING

Associated with Task Area F: Safety and Immunogenicity Testing

NOTE: The following Sample Task Order indicated in this Attachment is provided to assess the Offeror’s capabilities to conduct and fulfill the requirements of the Statement of Work for projects of similar scope and size to be issued under contracts awarded in response to this solicitation. Although the Sample Task Order will NOT be executed nor will awards be made for the Sample Task Order, Offerors are to include in their proposals a response that specifies the methods by which each Sample Task Order will be accomplished and the project management plan, with associated costs. Offerors should refer to the Additional Technical Proposal Instructions and Additional Business Proposal Instructions for guidance regarding preparation of their proposals.

SECTION B – SUPPLIES OR SERVICES AND PRICES/COSTS

There are no additional SECTION B clauses applicable to this Task Order beyond those in the base contract.

SECTION C – DESCRIPTION OF WORK/SPECIFICATIONS/WORK STATEMENT

ARTICLE C.1. STATEMENT OF WORK

I. BACKGROUND AND INTRODUCTION

Preclinical safety and immunogenicity testing is required for products to be used in human clinical trials. The results of testing are included in the IND submitted to the FDA. For HIV vaccines these safety studies usually include repeat dose studies in rabbits or other small animals designed to measure both local and systemic toxicity. For some novel vaccine products additional tests may be required in these or other species such as nonhuman primates. A comprehensive toxicology report will be required for each study.

I. SCOPE

The activity to be supported under this Task Order is for toxicity and immunogenicity testing of an HIV-Env protein vaccine as required for IND submission prior to initial clinical evaluation.

II. TECHNICAL REQUIREMENTS

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, products, reagents, specimens equipment, and facilities, not otherwise provided by the Government under the terms of the contract, as needed to perform the Statement of Work below:

Specifically, the Contractor shall:

A. Conduct an acute and chronic toxicity study in rabbits (10/sex/group x 4 groups). Rabbits shall be dosed intramuscularly with 4 doses of antigen (high, medium and low antigen doses plus placebo group) in alum, or placebo at 2 week intervals over a 42 day course and then euthanized on either day 43 or day 56.

Antigen and alum will be provided by the Government and must be mixed just prior to use. Analysis shall include gross pathology, histopathology, clinical chemistry, and hematology.

B. Perform all tests required to qualify a vaccine product for human administration. Such testing must also include all tests required for Investigational New Drug (IND) and Master file submission. All studies must be performed in accordance with Good Laboratory Practice (GLP) regulations (21 CFR 58) unless otherwise approved by the Contract Officer’s Representative (COR).

1. Preclinical safety evaluations shall include, but are not limited to the following:

5/27/2016 Page 2 of 4

a) Systemic toxicity

Preclinical studies shall include dose-ranging and dose escalation studies of systemic toxicity as well as toxicity to potential target organs, including hematopoietic and immune systems.

b) Local reactogenicity Local site reactivity studies include detailed clinical observations and histological evaluation of tissue of the injection site or other visible lesions from biopsies or term necropsy samples.

c) All other safety tests as may be required for this particular vaccine type

d) Immunogenicity tests including comparison of adjuvants versus placebo with protein

e) Immunogenicity may be measured by standard commercially available enzyme immunoassay and western blot assay.

f) Adjuvant testing

2. The use of adjuvants and/or facilitators for the administration of a vaccine shall necessitate specific preclinical evaluation procedures to ensure the safety of the candidate formulation to include but not limited to the evaluations listed in 1.a. above.

3. Provide to the COR and the Contracting Officer (CO) verification of OLAW approved Animal Assurance and Institutional Animal Care and Use Committee approval of the studies to be performed prior to commencing any work involving laboratory animals.

4. Provide all data, information and records required for the writing and submission of the Master file and all other documents related to IND submission to the COR or to a designated third party. This information shall be submitted within 30 calendar days from the time the COR makes the request.

5. Provide adequate facilities, equipment and resources necessary to accomplish these studies.

Maintain adequate animal facilities.

6. Meet with COR in person or by teleconference at periodic intervals to be scheduled after contract award. Provide to the COR action items for all meetings and meeting minutes (48 hours after completion of each meeting).

7. Participate in preparing the pre-IND package and be available as necessary for discussions with the

FDA during pre-IND and IND meetings held by telephone or in person.

8. Retain all records, samples, histopathological slides, etc. and make them available as indicated under

GLP guidelines.

9. Options - In addition to the services/quantities outlined above to be provided for the base requirement, Options(s) for additional services/quantities under the Task Order may be exercised at the discretion of the Government and are defined as follows:

Option 1 - 6: Additional Quantities: The Government may exercise options for additional quantities that may result from unanticipated increases in demand. Should the Government elect to exercise these options, the Contractor shall provide resources for the unanticipated increase in work volume for each option exercised.

10. Upon the completion of all required toxicity testing for the acute and chronic studies, the Contractor shall submit one (1) electronic copy of an unaudited Draft Toxicity Report to the COR for review and comment. The report shall be comprehensive and in sufficient detail to describe the results achieved and consist of the following:

a) Provide all products, procedures and outcomes achieved with summaries and conclusions

b) Graphs and tables of data obtained

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c) Histopathology reports

d) Pathology reports

e) Clinical pathology reports

f) In life physical measurements

g) Immunogenicity study reports

h) Additional information as directed by the COR

11. The Contractor shall submit one (1) electronic copy of the Final Audited Toxicity Report to the COR and one (1) electronic copy to the CO. The milestone report shall be comprehensive and in sufficient detail to describe the results achieved and shall be submitted no later than the Task Order completion date and consist of the following:

a) Provide all products, procedures and outcomes achieved with summaries and conclusions

b) Graphs and tables of data obtained

c) Histopathology reports

d) Pathology reports

e) Clinical pathology reports

f) In life physical measurements

g) Immunogenicity study reports

12. The Contractor shall deliver to the Government or its designee by the completion date of the Task

Order, the following items:

a) Provide all vaccine products, adjuvants, etc., remaining from these studies.

b) Provide all data, information and records required for the writing and submission of the Master file and all other documents related to IND submission to the COR or to a designated third party.

SECTION D – PACKAGING, MARKING, AND SHIPPING

There are no additional SECTION D clauses applicable to this Task Order beyond those in the base contract.

SECTION E – INSPECTION AND ACCEPTANCE

There are no additional SECTIOIN E clauses applicable to this Task Order beyond those in the base contract.

SECTION F – DELIVERIES OR PERFORMANCE

ARTICLE F.1. DELIVERIES

Satisfactory performance of the final contract shall be deemed to occur upon performance of the work described in the Statement of Work Article in SECTION C of this contract and upon delivery and acceptance by the Contracting Officer, or the duly authorized representative, of the following items in accordance with the stated delivery schedule:

a. The items specified below as described in the REPORTING REQUIREMENTS Article in SECTION C of this contract will be required to be delivered F.O.B. Destination as set forth in FAR 52.247-35, F.O.B. DESTINATION, WITHIN CONSIGNEES PREMISES (APRIL 1984), and in accordance with and by the date(s) specified below:

Technical Progress Reports

Item Reports Recipients Delivery Schedule

1. Unaudited draft toxicity reports

1 electronic copy to COR Within 30 calendar days after completion of chronic toxicity study

2. Final audited toxicity Report

1 electronic copy to COR and CO.

Within 60 calendar days after receiving all responses to the unaudited draft report

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Other Reports and Deliverables (Delivery Schedule)

Item Deliverables SOW Reference Recipient Delivery Schedule

3. Provide all vaccine products, adjuvants, etc. remaining from these studies

SOW paragraphs B.1, 2.a-b

Site designated by the COR

As produced or requested by the COR. Products shall be shipped by the completion of the TO.

4. Provide all data, information and records required for regulatory submissions

SOW paragraph B.4 1 elec. copy to COR Upon request of the COR.

Delivered within 30 calendar days.

b. If the Contractor becomes unable to deliver the reports or other deliverables here specified within the period of performance because of unforeseen difficulties, notwithstanding the exercise of good faith and diligent effort in performance of the work, the Contractor shall give the Contracting Officer immediate written notice of anticipated delays with reasons therefore, at the address given below in paragraph c.

c. Copies of the technical reports shall be submitted as follows:

Addressee No. of Copies Deliverable Item No.

Contracting Officer Office of Acquisitions, Division of Extramural Activities National Institute of Allergy and Infectious Diseases National Institutes of Health, DHHS 5601 Fishers Lane, Room 3D10, MSC 9821 Bethesda, MD 20892-9821 Email Address: TBD at time of award

1 2.

Contracting Officer’s Representative Vaccine Research Program, Division of AIDS National Institute of Allergy and Infectious Diseases National Institutes of Health, DHHS 5601 Fishers Lane, Room XXXX, MSC XXXX Bethesda, MD 20892-XXXX Email Address: TBD at time of award

1 1. through 4.

SECTION G – TASK ORDER ADMINISTRATION DATA

There are no additional SECTION G clauses applicable to this Task Order beyond those in the base contract.

SECTION H – SPECIAL CONTRACT REQUIREMENTS

There are no additional SECTION H clauses applicable to this Task Order beyond those in the base contract.

ATTACHMENT 10 – ADDITIONAL TECHNICAL PROPOSAL INSTRUCTIONS rev. 5/27/2016 Page 1 of 5

ATTACHMENT 10: ADDITIONAL TECHNICAL PROPOSAL INSTRUCTIONS,

FORMAT FOR TECHNICAL PROPOSAL, and TABLE OF CONTENTS

It is strongly recommended that offerors use the following template as the Table of Contents for the Technical Proposal. All information presented in the Technical Proposal should be presented in the order specified below.

These additional Technical Proposal instructions reflect the requirements of the solicitation and provide specific instructions and formatting for the Technical Proposal. While Section L of the solicitation provides a generic set of Technical Proposal instructions applicable to all NIH R&D solicitations, these instructions are tailored to the specific requirements of the RFP. The information requested in these instructions should be used to format and prepare the Technical Proposal, and should be used as a Table of Contents for your Technical Proposal. Offerors should follow the instructions in Section L of the solicitation, and include the information requested here.

Offerors are advised to give careful consideration to the Statement of Work, all reference materials, and attachments, the Technical Evaluation Criteria in Section M, and the solicitation as a whole in the development of their Technical Proposals.

Offerors proposing subcontracts to perform portions of the Statement of Work should clearly identify the specific tasks for which they plan to utilize subcontractors, as well as the method and level of integration/coordination between the prime Contractor and all proposed subcontractors, and the expected advantages of such an approach.

Offerors must refer to the solicitation Attachment entitled “Packaging and Delivery of the Proposal,” which details strict guidelines, including page limitations, formatting and layout of proposals, and prohibits the offerors use of links to internet web site addresses (URLs) to direct readers to alternate sources of information.

TECHNICAL PROPOSAL – TABLE OF CONTENTS

Offerors must submit responses within their proposal for Task Order A-1 and each sample Task Order B-1 through F-1 as stipulated in the Task Orders Statements of Work (Attachments 4 through 9)

Immediately, upon award of the contract, NIAID anticipates issuing a single Task Order for Task Area A-1, Essential Core Activities, which encompasses the following essential activities that will be performed on a regular basis: Project Management, Quality Assurance/Quality Control, Document Management, Personnel and Physical Infrastructure, Storage and Shipping, Transition, and Reporting Requirements/Deliverables.

SECTION 1:

1) PROPOSAL TITLE PAGE. Include RFP title and number, name of organization, DUNS number, and identify if the proposal is an original or a copy. Offerors that include in their proposals data that they do not want disclosed to the public for any purpose, or used by the Government, except for evaluation purposes, shall also include the legend regarding Restriction on Disclosure and Use of Data prescribed by FAR 52.215-1(e).

2) TABLE OF CONTENTS

SECTION 2: TECHNICAL PROPOSAL OVERVIEW (suggested 3-page maximum) Provide a brief overview of the Technical Proposal, including:

1) A brief description of the activities proposed by the offerors and all proposed subcontractors, including identification of all proposed potential subcontractors and a list of key personnel for the offerors and the proposed subcontractors with degrees, titles and role in the project.

ATTACHMENT 10 – ADDITIONAL TECHNICAL PROPOSAL INSTRUCTIONS rev. 5/27/2016 Page 2 of 5

2) By area of expertise, provide the total number of staff, the number available to be assigned to the contract for the offerors and all proposed subcontractors, and total number of additional staff to be hired and trained.

3) A brief description of the facilities and equipment to be made available by the offerors and all proposed subcontractors.

SECTION 3: TECHNICAL PLAN/APPROACH FOR EACH TASK AREA

In addition to the information provided in Section L, offerors should demonstrate their capabilities to fulfill the activities specified in Task Areas A through F indicated in the Statements of Work (SOW).

The capability of the Offerors to fulfill the requirements of the Statement of Work will be assessed based on the Offerors responses to Task Order A-1 (Essential Core Activities) and the five Sample Task Orders. The Offeror’s proposals should address the approach to the Essential Core Activities relative to the five Sample Task Orders. The Technical Approach should be organized to clearly identify the specific responses to each item in the Statement of Work for Task Order A-1, Essential Core Activities. Responses to the five Sample Task Orders should be well integrated; any area that is not relevant or applicable to the proposed effort should not be included. In cases where an Essential Core Activity effort has been described for another Sample Task Order, it is not necessary to reiterate the information for a subsequent Task Order.

The five Sample Task Orders requiring a response are:

Task Order B-1, Feasibility Assessment Task Order C-1, Auditing Task Order D-1, Regulatory Documentation Task Order E-1, Process Development and CGMP Manufacture Task Order F-1, Safety and Immunogenicity Testing

Below are areas/activities (A-F) included in each of the Task Area A-1 Essential Core Activities that the Offeror must address when describing their Technical Approach to the five Sample Task Orders B-1, C-1, D-1, E-1 and F-1.

A. Project Management

Describe in detail processes and procedures for Project Management including task organization, staffing, and management in relation to the planning, initiation, implementation, integration, conduct, and monitoring for completion of Sample Task Orders in the areas of Feasibility Assessments (Task Order B-1), Auditing (Task Order C-1), Regulatory Documentation (Task Order D-1), Process Development and CGMP Manufacture (Task Order E-1), and Safety and Immunogenicity Testing (Task Order F-1). Please note, effort associated with oversight/project management of individual Sample Task Orders in Task Areas B, C, D, E and F, should be included in the cost for that Task. Effort and costs associated with management and coordination of the overall contract should be included in Task Area A.

For Sample Task Orders B-1, C-1, D-1, E-1 and F-1, include the following:

• Responsibilities and effort for all proposed including proposed potential subcontractors and consultants

• the administrative and technical framework indicating clear lines of authority and responsibility for all proposed personnel

• If subcontractors are proposed, include a plan to manage, coordinate, and oversee the work performed by subcontractors.

• a chart of the proposed organizational/management structure for the project

• relevant organizational experience, including problems or obstacles encountered and approaches to their resolution or correction

1. Describe in detail the process and procedures for Subcontract Acquisition and Management including procedures for the soliciting, evaluating, negotiating, awarding, and managing of subcontractors for completion of Sample Task Orders in the areas of Feasibility Assessments (Task Order B-1), Auditing (Task Order C-1), Regulatory Documentation (Task Order D-1), Process Development and CGMP Manufacture (Task Order E-1), and Safety and Immunogenicity Testing (Task Order F-1)). Include the following aspects:

• criteria to qualify a subcontractor and how the Offeror identifies sources for services

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• proposed processes to ensure that subcontractor personnel, equipment and facilities are compliant with appropriate regulatory requirements

• experience in the acquisition and management of subcontracts under Federal contracts

• experience with identification and remediation of subcontractor performance problems or noncompliance with subcontract terms and conditions

2. Describe the project management systems that will be used to track activities and keep multiple activities on time and budget, including a description of the quality control methods that will be used to ensure the effective and efficient initiation, implementation, management, and oversight of contract requirements.

3. Outline how the PI (or Project Director) will communicate with the COR and Contracting Officer and how the PI (or Project Director) will communicate, monitor, and manage the project both internally and externally (at subcontractor facilities).

B. Quality Control/Quality Assurance Describe in detail the plans and operating procedures for implementing a QA/QC program for completion of Sample Task Orders in the areas of Feasibility Assessments (Task Order B-1), Auditing (Task Order C-1), Regulatory Documentation (Task Order D-1), Process Development and cGMP Manufacture (Task Order E-1), and Safety and Immunogenicity Testing (Task Order F-1). Include the following aspects:

• description of the personnel, resources and lines of authority for a Quality Assurance Unit (QAU)

• governing policies and procedures of the QAU

• description of the Quality System

• description of process to ensure the commitment of the contractor’s senior management support for the Quality Systems

• the plan for providing QA/QC oversight of all activities at the Contractor’s or subcontractor’s site

• the plan to conduct QA/QC of reagents and materials to define standard performance and ensure optimal quality, consistency, reproducibility, stability, and lot-to-lot comparability over time

• relevant organizational experience, including problems or obstacles encountered and approaches for their resolution or correction

C. Document Management

Provide a comprehensive plan for document writing, storage, transfer, maintenance and updating consistent with the needs for completion of Sample Task Orders in the areas of Feasibility Assessments (Task Order B-1), Auditing (Task Order C-1), Regulatory Documentation (Task Order D-1), Process Development and cGMP Manufacture (Task Order E-1), and Safety and Immunogenicity Testing (Task Order F-1). Include the following aspects:

• a list of documents to be produced

• plans for weekly transfer to the NIAID document management system and

• an IT Systems Security and data security plan

D. Staffing Plan

1. Sample Task Orders B-1, C-1, D-1, E-1, and F-1:

Provide a staffing plan for Sample Task Orders in the areas of Feasibility Assessments (Task Order B-1), Auditing (Task Order C-1), Regulatory Documentation (Task Order D-1), Process Development and cGMP Manufacture (Task Order E-1), and Safety and Immunogenicity Testing (Task Order F-1). Describe roles and level of effort of scientific and technical personnel, including proposed potential subcontractors/consultants. Do not name proposed potential subcontractors/consultants for the Sample Task Orders. It is very important that we understand the offeror’s process for identifying, selecting, and managing potential subcontractors/consultants to carry out the work in the Sample Task Orders. You should demonstrate that the subcontractor/consultant is capable of carrying out the proposed work and what previous experience you have had with the subcontractor.

2. Task Order A-1 Essential Core Activities:

Provide a staffing plan and describe all relevant information to document individual training, education, experience, qualifications and expertise necessary for the Essential Core Activities. Clearly identify Key Personnel (including subcontractors/consultants) for the Essential Core Activities effort. In the case of Task

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Order A-1, the subcontractor/consultant must be identified since this Task Order will be awarded immediately upon contract execution. Limit CVs to 2-3 pages and provide selected references for publications relevant to the scope of the RFP, and include experience with projects of similar scope, size and complexity carried out by the Offeror and any proposed subcontractors over the past 5 years.

a) Principal Investigator (PI): include experience and qualifications of the PI to plan, manage, and direct the activities to be carried out under this contract including contracts with similar scope and complexity.

b) Scientific and Technical Personnel: include experience and expertise with respect to conduct of the assays described in the SOW, analysis of results, and assay development including managing projects that deal with biological systems such as CGMP manufacturing or toxicological assessments, managing a QAU and establishment, implementation, maintenance, and monitoring of a Quality System conducting audits, and information technology such as document maintenance.

c) Describe plans and procedures for training and monitoring of personnel for exposure to infectious and other hazardous materials.

E. Storage and Shipping

Describe the proposed plans and procedures for the receipt, storage, retrieval, packaging, and shipping of products, materials, and specimens from domestic and international locations. Include a description of relevant organizational experience, problems or obstacles encountered and approaches implemented to resolve or correct identified problems for the successful completion of Sample Task Orders in the areas of Feasibility Assessments (Task Order B-1), Auditing (Task Order C-1), Regulatory Documentation (Task Order D- 1), Process Development and cGMP Manufacture (Task Order E-1), and Safety and Immunogenicity Testing (Task Order F-1).

F. Transition Plan

Describe in detail plans and operating procedures to ensure a smooth and timely transition including a description of transition activities, timelines, and assigned staff for all vaccine products, data, software, documentation, reagents, stored specimens, and Government-owned equipment for the successful completion of Sample Task Orders in the areas of Feasibility Assessments (Task Order B-1), Auditing (Task Order C-1), Regulatory Documentation (Task Order D-1), Process Development and CGMP Manufacture (Task Order E-1), and Safety and Immunogenicity Testing (Task Order F-1).

SECTION 4: SCIENTIFIC AND TECHNICAL PERSONNEL

Document individual training, experience, qualifications and expertise necessary for the successful completion of all Task Order requirements for Task Orders. Limit CVs to 2-3 pages and provide selected references for publications relevant to the scope of the Task Order.

1) Principal Investigator (PI): Describe the experience, training, expertise, and qualifications, and level of effort of the proposed Principal Investigator to lead and direct the activities to be carried out under this Solicitation.

2) Other Key Scientific and Technical Personnel: Describe the experience, training, expertise and qualifications, as well as the level of effort, for proposed key scientific and key technical personnel.

SECTION 5: FACILITIES, EQUIPMENT, AND OTHER RESOURCES

The Technical Proposal should document availability and adequacy of facilities, equipment, space and other resources necessary to carry out the Statement of Work, including:

1) Location and features of facilities including a floor plan and a list of equipment and resources dedicated to the project for the prime contractor and any proposed subcontractors (lease or ownership information should be provided).

2) Identification and description of ALL support resources (including Information Technology systems) that will be required to effectively complete the SOW.

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3) Describe resources for CGMP manufacturing including those required for recombinant protein manufactured by transient transfection with electroporation.

SECTION 6: TASK ORDER/SAMPLE TASK ORDER OPTIONS

Options should be presented as a separate part of the Technical Proposal for each Task Order and clearly identified as such.

Task Area A-1, Essential Core Activities

Options 1 through 6: Extend the Term of the Task Order

Discuss plans and procedures for continuing and providing the same services indicated in the Statement of Work beyond the Task Order base period. To address this option, offerors should describe the methods and procedures to maintain the operations specified in the Statement of Work beyond the base period, including retaining or recruiting necessary staff, and maintaining and/or acquiring required equipment and facility space.

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ATTACHMENT 11: ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS

AND UNIFORM COST ASSUMPTIONS

RFP NUMBER: NIAID-DAIDS-NIHAI2015035

In addition to the format requirements for the Business Proposal that are contained in Section L of the solicitation, the information presented in this section of the RFP is intended to provide uniform cost assumptions and business clarifications.

Offerors are advised to give careful consideration to the Statement of Work, all reference material provided as attachments, the Technical Evaluation Criteria, and, the RFP as a whole, in the development of your proposal.

The information requested in these instructions should be used as a guide for the development and formatting of your Business Proposal. Offerors should consider and include the information requested here, as well as any other information which will benefit the proposal.

BUSINESS PROPOSAL – TABLE OF CONTENTS

SECTION 1 – PROPOSAL COVER SHEET (use form NIH 2043 identified in Section J of the solicitation).

SECTION 2 – COST OR PRICE SUPPORT

Section L of the RFP specifies the minimum documentation requirements for cost data and all cost related support.

All related documentation should be included in the proposal in a clearly marked section of the proposal.

SECTION 3 – UNIFORM COST ASSUMPTIONS

1. Technical Cost Assumptions

A. Contract Value This contract will have a Minimum Guaranteed Award of $30,000 and a Maximum Potential Value of $318,500,000. The Maximum Potential Value is not guaranteed, but represents the potential for additional funding through Task Order awards under the contract during the ordering period, up to the Maximum Potential Value.

B. Scope of Activities

Upon award of the base contract, the Government anticipates awarding one Task Order in Task Area A (see Task Order A-1, Essential Core Activities. The Task Order will be a cost-reimbursement. Term (level of effort) type, with a base period of 12 months and Options to extend the term of the Task Order in 12 month increments for a total period of performance of seven years.

Task Orders to be issued for Task Areas A, B, C, D, E, and F will be issued as cost reimbursement, completion type. Task Orders will vary in complexity and may combine activities from different Task Areas. Below is a table showing the anticipated number of task orders to be issued per Task Area during the life of the base contract.

Task Area

Estimated Number of Task Orders to be Issued/Year

Average Duration of Each Task Order

A - Essential Core Activities 1 1 year B – Feasibility Assessments 1 1 year C – Auditing 4 6 months – 1 year D – Regulatory Documentation 1 2 years E – Process Development & CGMP Manufacturing 4 3 years* F – Safety & Immunogenicity Testing 3 1 year

*See Paragraph D, Cost Proposals for Sample Task Orders, subparagraph 5, below.

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Offerors should budget for…