Amendment_2_N02CM77004-16.pdf

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods:

(a) By completing items 8 and 15, and returning or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment your desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

E. IMPORTANT: Contractor is not, is required to sign this document and return copies to the issuing office.

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE

2. AMENDMENT/MODIFICATION NO. 3. EFFECTIVE DATE 4. REQUISITION/PURCHASE REQ. NO. 5. PROJECT NO. (If applicable)

7. ADMINISTERED BY (If other than Item 6) CODE

STANDARD FORM 30 (REV. 10-83)

Prescribed by GSA FAR (48 CFR) 53.243

FACILITY CODE

9A. AMENDMENT OF SOLICITATION

NO.

9B. DATED (SEE ITEM 11)

10A. MODIFICATION OF CONTRACT/ORDER NO.

10B. DATED (SEE ITEM 13)

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers is extended, is not extended.

12. ACCOUNTING AND APPROPRIATION DATA (If required) copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted;

13. THIS ITEM ONLY APPLIES TO MODIFICATION OF CONTRACTS/ORDERS.

IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

CHECK ONE A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER NO.

IN ITEM 10A.

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority)

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

15C. DATE SIGNED

15A. NAME AND TITLE OF SIGNER (Type or print)

16C. DATE SIGNED

16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

PAGE OF PAGES

6. ISSUED BY CODE

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP Code) (X)

CODE

15B. CONTRACTOR/OFFEROR

(Signature of person authorized to sign)

16B. UNITED STATES OF AMERICA

(Signature of Contracting Officer)

NSN 7540-01-152-8070

Previous edition unusable

IO-NCI

Nicole Belanger, Contracting Officer

Purpose: To replace Attachments 15 and 16 with corrected versions.

National Institutes of Health National Cancer Institute Frederick, MD 21701

TO ALL CONTRACTORS

N02CM77004-16

1 2

03/24/2017

Nicole M. Belanger -S Digitally signed by Nicole M. Belanger -S DN: c=US, o=U.S. Government, ou=HHS, ou=NIH, ou=People, 0.9.2342.19200300.100.1.1=0011203542, cn=Nicole M. Belanger -S Date: 2017.03.24 10:18:26 -04'00'

03/24/2017

Attachment 15 Additional Technical/Cost Proposal Instructions

As outlined in Section L- Instructions, Conditions, and Notices to Offerors, a technical proposal shall be submitted that addresses the Statement of Work (SOW), with a separate section for the Sample Task Order. The technical proposals shall address all information outlined below.

A detailed work plan must be submitted indicating how each aspect of the Statement of Work is to be accomplished. Your technical approach should be in as much detail as necessary to fully explain your proposed technical approach or method. The technical proposal should reflect a clear understanding of the nature of the work being undertaken. The technical proposal must include information on how the project is to be organized, staffed, and managed. Information should be provided which will demonstrate your understanding and ability to manage important events or tasks.

Mandatory Qualification Criteria

Offerors must include, in a separate section of the Technical Proposal, a discussion of how they meet the Mandatory Qualification Criteria required by Section M., Mandatory Qualification Criteria.

1. TECHNICAL DISCUSSIONS

The technical discussions included in the technical proposal should respond to the items set forth below:

a. Objectives and Scope of Work

A definitive statement of the proposed work to be done should be provided. The proposal should include: a statement of the overall objectives of the project, as envisaged by the offeror, and the specific accomplishments you hope to achieve for the entire period of performance; an outline of a program for implementing the work and the technical approach that would be used to achieve the objectives and fulfill the Government requirements; and, awareness of the important factors to be considered in the performance of the contract.

b. Personnel

Describe in detail the experience and qualifications of personnel who will be assigned for direct work on this program. Information is required which will show the composition of the task or work group, its general qualifications, and recent experience with similar equipment or programs. Special mention shall be made of direct technical supervisors and key technical personnel, and the approximate percentage of the total time each will be available for this program.

Contingency hires (i.e, employment offers that hinge on whether this contract is awarded) are not acceptable for this RFP. All proposed staff must be on the payroll at the time of proposal submission.

Offerors should assure that the Project Manager/Director (PM/D), and all other personnel proposed, shall not be committed on federal grants and contracts for more than a total of 100% of their time. if the situation arises where it is determined that a proposed employee is committed for more than 100% of his or her time, the government will require action on the part of the offeror to correct the time commitment.

1) The PM/D should be thoroughly familiar with the analysis of bulk pharmaceutical substances and clinical dosage forms. It is recommended that the PM/D commit not less than 10% of his/her time to this project.

The PM/D should be trained in Chemistry (Analytical, Pharmaceutical, Organic, etc.), preferably at the Ph.D. level from an accredited school and should be thoroughly familiar with the analysis and evaluation of bulk drug substances and clinical dosage forms. The PM/D should have at least three years of recent experience in the analysis of drug substances and drug products.

PM/D’s not trained at the Ph.D. level should have at least the following training and experience:

Masters level - The PM/D should have at least five years of recent experience in the analysis of drug substances. He/she should also have three years of recent experience in the analysis of clinical dosage forms.

Identify the PM/D by name and describe the background, training, recent experience and accomplishments that qualifies the individual to lead this Project. Also, include the PM/D’s updated curriculum vitae with a listing of scientific publications. Indicate this individual’s availability and proposed level of effort.

2) A Principal Assistant should also be assigned to this project. The Principal

Assistant should be an individual of extensive, relevant analytical experience capable of independently supervising and coordinating the actual laboratory work.

Identify the Principal Assistant by name and describe the background, training, recent experience and accomplishments that qualify the individual to lead this Project. Include the Principal Assistant’s updated curriculum vitae with a listing of scientific publications. Indicate this individual’s availability and proposed level of effort.

Offerors must present a clear, specific plan whereby either the PM/D or the Principal Assistant will be on the job managing the active Task Order(s), and available for consultation with the Government’s COR.

3) Additional Personnel: Identify these professional staff members (by name) and describe the background, training, recent experience and accomplishments that qualify each individual to perform in their area of responsibility. Include each individual’s updated resume. Indicate each individual’s availability and proposed level of effort. For all proposed personnel who are not currently members of the offeror’s staff, a letter of commitment or other evidence of availability is required. A resume does not meet this requirement. Commitment letters for use of consultants and other personnel to be hired must include:

a) The specific items or expertise they will provide;

b) Their availability to the project and the amount of time anticipated;

c) Willingness to act as a consultant;

d) And how rights to publications and patents will be handled;

Include each individual’s updated curriculum vitae.

Curricula Vitae: Curricula Vitae or resumes of all key personnel are required.

Each must indicate educational background, dates that academic degrees were received, recent experience, specific or technical accomplishments, scientific publications and dates that encompass each term of training or employment.

c. Facilities and Equipment

The Contractor should provide a complete, ongoing and fully operational facility including all necessary equipment and instrumentation for all aspects of the analytical assessment of bulk drug substances and formulated drug products. The analytical facility should have refrigeration and deep freeze storage available for the analytical samples and reference materials. The laboratories should have a dry box and fume hoods for the proper handling of materials.

The Contractor should provide adequate, up-to-date analytical instrumentation and equipment to perform the required analysis of bulk drug substances and formulated drug products. The following instrumentation and equipment shall be accessible and available for the immediate use of the personnel on this project:

1) Sufficient equipment to utilize the following chromatographic techniques:

a) Thin layer chromatography

b) Gas liquid chromatography (capillary capability desirable) with electron capture, flame ionization and thermal conductivity detectors

2) A sufficient number (at least 2) of High Pressure Liquid Chromatograph (HPLC) systems to meet the needs of this project.

3) A sufficient number of variable wavelength ultraviolet detectors (for HPLC) and at least one evaporative light scattering detector (ELSD) shall be provided.

4) An LC-MS (liquid chromatography-mass spectrometer) system to meet the needs of this project.

5) Chromatographic data system(s) compatible with HPLC units proposed.

6) Electrochemical instrumentation for non-aqueous titration and pH determination.

7) Instruments for spectroscopic determinations:

a) Research quality infrared grating spectrophotometer

b) Research quality scanning ultraviolet-visible spectrophotometer

The following equipment should be readily accessible to the project staff and should be available to the project when required:

a) Mass Spectrometer (with multiple ionization capability) and High Resolution

(TOF) Mass Spectrometer

b) Polarimeter with variable wavelength detection

c) High-Field Nuclear Magnetic Resonance Spectrometer (with multiple nuclei and two-dimensional experiment capability)

d) Equipment for Capillary Electrophoresis

e) Differential Scanning calorimeter

f) Thermogravimetric analyzer

The following services are required on a less frequent basis:

a) Elemental analysis

b) Particle size analysis

c) Residue on ignition analysis

d) Heavy metal trace analysis

All facilities and equipment which are required to be available for ‘immediate use’ shall be housed in close proximity to one another, preferably in the same building.

Describe in detail the facility that will be directly utilized and available for this project and provide a detailed floor plan, with dimensions, of the proposed facility. Such description and floor plan must be in sufficient detail to allow for proper evaluation of the proposed facility.

Discuss in detail the offeror’s awareness of the Food and Drug Administration (FDA) promulgated Current Good Manufacturing Practices (cGMP) and how these impact upon this contract work. Further, discuss the offeror’s approach to assure compliance with cGMP requirements as needed; and be aware that the facility may be subject to FDA inspection during the review of a New Drug Application.

Describe security arrangements available to safeguard Government owned materials to prevent theft, misuse or damage.

Note the exact location of the facility proposed for this contract.

Describe in detail the equipment, instruments, and facilities to be used in the analysis of bulk drug substances and clinical dosage forms. Equipment dedicated for the exclusive use on this project should be identified by manufacturer and model number. Back-up equipment should also be identified.

Describe the procedures for routine maintenance and repair of equipment and analytical instrumentation.

No government-owned equipment will be available for use on this project.

Describe the library facilities and information resources available for this project.

Discuss the adequacy and availability of these facilities and resources and their current holdings and literature search capabilities.

NOTE: In the laboratory space proposed, if more than one building or institution is involved, a clear description should be given of the location of all sites, distance, and travel time between them. It is expected that most of the equipment will be under the direct control of the PM/D, and special mention should be made when this is not the case. When equipment is only available on a shared basis, some evidence should be provided as to who is responsible for controlling access and how determination of priority of usage will be made (letter of commitment from department head, etc.)

d. Understanding of the Project and Technical Approach

Describe the awareness and understanding of problems associated with the analysis of bulk drug substances and clinical dosage forms. Discuss proposed approaches to the resolution of such problems.

Discuss approaches to analytical method development of a drug substance. Describe two (2) representative examples for drug substances that are technically challenging.

Discuss approaches to the definitive structural elucidation of a drug substance. Describe two (2) representative examples for drug substances of high structural complexity.

Indicate the systems and procedures to be used to ensure that the various activities will be scheduled according to their priority as determined by the COR, so that all assignments are performed at the appropriate times.

e. Organizational Support and Experience

Describe overall organizational experience in the analysis of bulk drug substances and clinical dosage forms.

Describe in detail organizational activities currently ongoing or recently completed that would indicate satisfactory experience and capabilities in the analysis of bulk drug substances and clinical dosage forms.

Discuss the organization’s overall ability to respond to work requirements. Describe possible interfering commitments which might cause delays in completion of the effort required. Indicate the priority to be placed on this project as compared to other existing commitments.

Indicate by chart and/or in narrative form how the various activities will be coordinated so as to demonstrate an awareness of organizational influences on project implementation and control. Include a clear description of relevant lines of authority and responsibility. Describe a management plan for implementing this project including provisions for backup technical support for the project team.

The substances under study should be considered to be toxic agents and, thus, should be handled accordingly. Describe fully your organization’s policy on safety and security.

Please submit an electronic copy of the organization’s safety manual. Describe laboratory safety controls and procedures available. Describe laboratory safety controls and procedures for the handling and disposal of carcinogenic and toxic materials now followed or proposed for this project. Describe procedures for the prevention of contamination during laboratory operations.

Additional Technical Proposal Information

Proposals which merely offer to conduct a program in accordance with the requirements of the Government’s scope of work will not be eligible for award. The offeror must submit an explanation of the proposed technical approach in conjunction with the tasks to be performed in achieving the project objectives.

The technical evaluation is conducted in accordance with the weighted technical evaluation criteria by an initial review panel. This evaluation produces a numerical score (points) which is based upon the information contained in the offeror’s proposal only.

Other Considerations

Record and discuss specific factors not included elsewhere which support your proposal.

Using specifically titled subparagraphs, items may include:

a) Any agreements and/or arrangements with subcontractors. Provide as much detail as necessary to explain how the statement of work will be accomplished within this working relationship.

b) Unique arrangements, equipment, etc., which none or very few organizations are likely to have which is advantageous for effective implementation of this project.

c) Equipment and unusual operating procedures established to protect personnel from hazards associate with this project.

d) Other factors you feel are important and support your proposed project.

e) Recommendations for changing reporting requirements if such changes would be more compatible with the offeror’s proposed schedules.

Attachment 16

Sample Task Order Compound #12

Instructions Sample Task Order: Analysis of Sample Compound #12

Utilizing the cited literature reference, discuss how you would proceed with the following characterization: “Developmental Studies of 2-CI-4’-T-dAdo (Compound 12)”

Objective: to perform complete physicochemical characterization (IR, UV, 1H-NMR, 13C-NMR, 2-D

NMR, MS, Optical rotation), HPLC method development and validation, 12-month bulk drug stability studies and release testing (2 GMP-grade bulk drug lots) of 2-Cl-4’-T-dAdo* (Compound 12).

*see Tiwari, K.N. et al., ‘Synthesis and Biological Activity of 4’-Thionucleosides of 2- Chloroadenine’, Nucleosides and Nucleotides, 13 (8), 1819-1828 (1994).

Compound 12: 2-chloro-2’-deoxy-4’-thioadenosine.

Use as many subparagraphs, appropriately titled, as needed to clearly outline the general plan of work.

Include literature examples where available and if more than one procedure is available justify your choice of approach with detailed discussion. Address problems that may be encountered. Discuss your proposed solutions to such problems. For HPLC method development, include prior first-hand experience from your laboratory and relevant literature examples to justify your choice of approach.

Further, describe in detail the technical approaches that you would take and indicate the time required to complete each portion of the work. Please provide a comprehensive cost analysis for each target

(inclusive of all charges such as overhead, G&A, fee etc.).

Note: The Sample Task Order is merely an example for the purpose of demonstrating your capabilities for this project and will not be the analysis that you will be asked to perform.

A separate technical proposal, along with supporting documentation for the price/cost estimate, shall also be submitted in response to the Statement of Work included in the Task Order Request for

Proposals for Sample Task Order Compound #12.