N02CM77007-98_Amendment_Two.pdf

RFP Number : N02CM77007-98 Amendment 2

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OFFICE OF ACQUISITIONS

NATIONAL CANCER INSTITUTE

REQUEST FOR PROPOSAL NUMBER: N02CM77007-98

Amendment No.: 2

Date of Issuance: 03/23/2017

The above numbered Request For Proposal (RFP) is amended as set forth below. The hour and date specified for receipt of Offers remains unchanged.

Offerors MUST acknowledge receipt of the amendment prior to the hour and the date specified in the solicitation or as amended, by separate letter, telegram, or Electronic Mail which includes a reference to the RFP and Amendment number(s). For your convenience, the Proposal Intent Response Form is provided in SECTION J - List of Attachments of this RFP, for this purpose.

FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERORS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER.

This Amendment revises the RFP as stated below:

1. Section M item 3 "Mandatory Qualification Criteria" is updated as follows:

Listed below are mandatory qualification criteria. THE OFFEROR SHALL INCLUDE ALL INFORMATION

WHICH DOCUMENTS AND/OR SUPPORTS THE QUALIFICATION CRITERIA IN ONE CLEARLY MARKED

SECTION OF ITS TECHNICAL PROPOSAL. The qualification criteria establishes conditions that must be met at the time of receipt of Final Proposal Revisions (FPRs) by the Contracting Officer in order for your proposal to be considered any further for award.

The offeror shall document the following mandatory qualification criteria in the proposal.

(1) The facilities shall meet United States Food and Drug Administration (FDA) standards in accordance with the current Good Manufacturing Practices (cGMP) guidelines. The offeror should show documented proof of the most recent routine FDA inspection(s). Moreover, the offeror must be in compliance with FDA requirements during the entire course of the contract period.

(2) The facilities shall also conform to the applicable regulations of the U. S. Environmental Protection Agency (EPA), Occupational Safety and Health Administration (OSHA), U. S. Department of Transportation (DOT) and those of state and local regulatory agencies. The proposal shall include documentation of registration for all mandatory requirements.

2. Section M item 5 "Technical Evaluation Factors" is updated as follows:

A. PERSONNEL Weight 35

A Project Director (PD) will be responsible for the overall implementation of the project and will be the organization's key contact for technical aspects of the program. His/her proposed duties and the area or phase for which he/she will be responsible should be discussed.

(1) The PD responsible for overseeing the project should be named and possess at least five years of experiences in the conception and execution of chemical syntheses, scale up and synthetic process

- 2 -development in the laboratory, pilot plant and technical management levels. This individual shall have attained doctorate level educational status in organic or medicinal chemistry or closely related discipline and have demonstrated ability to lead a multi-disciplinary team of scientists which shall include synthetic chemists, analytical chemists and process chemists. The PD should be assigned to the project 25% of the time for this contract and a minimum of 10% of the PD's time should be used for hands-on technical synthetic work. A resume for the proposed PD should be provided which indicates his/her education, background, recent hand-on process chemistry and managerial experience, and specific scientific accomplishments. Suitability and adequacy of the PD training, recent hands-on experience in process/scale-up chemistry, scientific accomplishments, qualifications for leading this project, and availability for assignment.

Since this work is predominantly scale-up and process development, publication records are less important than practical experience and demonstration of practical performance in large-scale chemical production.

Communication between the Contract Officer Representative (COR) and the contractor is essential during the performance of projects and the PD will be a primary contact for technical discussions. The PD should be familiar with the FDA regulations/guidelines regarding cGMP bulk production.

(2) All other professional personnel should be named, indicating their present responsibilities, and availability to the project. The percent of total time and the number of hours per year that each will devote to the contract must be shown in a table according to the "H. Estimate of Effort". Evidence should be provided to demonstrate that the proposed personnel are capable of functioning as a team.

Current resumes for all proposed technical personnel should be provided which include education, background, recent hand-on experience, and specific scientific or technical accomplishments. A bibliography listing publications relevant to the project should be included for each individual proposed. Suitability and adequacy of the training, experience, qualifications, and scientific accomplishments of the entire proposed team members in the following areas:

• Synthetic organic or medicinal chemistry

• Scale-up and process optimization of existing methods

• Development of new and cost-effective processes

• Large-scale and/or pilot plant operations

• Analytical chemistry including QA/QC functions

• FDA regulations for cGMP bulk production

• Handling of potentially hazardous substances

• Laboratory or industrial-scale bulk synthesis, and/or chemical analysis (e.g., HPLC, NMR, UV, IR, etc.).

(3) Availability of the proposed team members, evidence and potential to perform as a team.

(4) Unrelated data or resumes of individuals not assigned to or not expected to be involved with the team are not necessary and will be considered excessive.

(5) Offerors should assure that the PD, 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.

(6) It is desirable to maintain as much work and expertise as is possible in one location in order to keep adequate communication and control over changes in priorities of work and delivery schedules. If subcontractors or consultants are proposed, they should be identified. Letter(s) of commitment from the proposed subcontractor(s) or consultant(s) and documents demonstrating their qualifications to perform in these capacities should be provided.

B. FACILITIES AND EQUIPMENT Weight 30 Adequacy and availability of all the proposed facilities and equipment to perform the functions of this contract including:

(1) Availability of large scale and/or pilot plant facilities, at least one (20-100 gallons) glass-lined reactor and

- 3 -several glass reaction vessels (50 and 100 L) with the necessary supporting equipment (heat exchangers-condensers, stirrers, holding tanks, large filters, transfer pumps, drying ovens, etc.), and modern, well-equipped laboratory facilities for organic/medicinal synthesis and pre-pilot plant process development.

(2) Laboratory space and equipment for:

• Organic/medicinal chemistry synthesis

• Purification and structure determination of intermediates and target material

• Analytical-quality control to comply with QA/QC requirements

• Library and/or other comparable information facilities (e.g. computing, software and electronic information)

• Unique and "back-up" equipment(s)

• Special facilities for the handling of hazardous and toxic reactions and disposal of waste

• Either in-house capabilities or easy and unlimited access to essential analytical instrumentation such as IR, UV, NMR, polarimeter, TLC, GC, and HPLC are essential. Ready access to sophisticated NMR and MS should be available.

• All major equipment including analytical and instrumental equipment essential to and available for contract use should be listed. Include make, model number and year of manufacture of each. Provide a statement indicating the location of each major equipment, whether or not it is under the direction of proposed personnel, and if not, who has responsibility for each and the time they are available for use in the contract. Include a breakdown by square feet of laboratory space which will be assigned to the contract.

• Identify all items, facilities and services which may be shared and show the priority and percentage of utilization for this contract work.

• Provide a legible floor plan or other means which clearly depict the locations of synthesis, analytical and instrument laboratories, pilot plant set ups, and toxic waste storage areas and relationships of these facilities directly to other facilities of your organization.

C. UNDERSTANDING OF PROBLEM AND TECHNICAL APPROACH Weight 25 Recent examples of three (3) large-scale (10 gm to multi-kilogram, at least four or more steps synthesis) cGMP bulk drug preparations should be described in detail as part of previous experiences of the PM and the proposed team. Within that description the following points should be included and discussed as much as possible:

• Scale-up issues should be discussed in your examples when a process is developed including your considerations on rapid scale-up

• Potential problems/concerns and resolution approach during yield optimization/process development and scale up

• Understanding of the approach to the scale up syntheses of bulk drugs for which only literature information is available but it is not practical for large scale

• Issues on FDA regulatory concerns

• Efforts on acquiring starting material or advanced intermediates from various vendors in terms of effectiveness of timeline and cost

• Issues on estimated timeline and cost of project and actual outcome

• Handling of toxic materials and approach to handle toxic materials

• Names of team members and their roles, including role of the proposed PD, in the provided examples

• Discuss how you would proceed with a laboratory scale synthetic process which does not lend itself to direct scale up and modify it for sub-pilot plant or pilot plant work?

• What are the problems from scale-up and regulatory perspectives?

• What changes in techniques or approach would you attempt to apply and what problems might you encounter?

• What would you do to simplify a synthesis process?

• What would you do to improve the cost effectiveness of an expensive or labor intensive synthetic process and why?

D. ORGANIZATIONAL SUPPORT/EXPERIENCE/SAFETY/SECURITY Weight 10

• Provide organizational charts or other means depicting organizational structure

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Provide a statement of general organizational background, experience, and qualifications in the operation of synthesis laboratories and pilot plant facility

• Provide information about accomplishments in the past and recently completed projects performed in the organization or by the proposed team that support your approach to this RFP. Describe one or two contributions to solve challenging problem(s) in a pertinent or related field to demonstrate the capability of the organization.

Include the chemistry involved, major problems and solutions, synthetic and purification procedures, scale up procedures, production methods, etc. Also include names of personnel involved, the staff hours spent and total cost (including labor, materials, indirect costs, etc.). Cite patents and publications, if any.

• Any similar or related projects performed in the past or currently being performed for the Government documenting the applicable agencies, contract numbers, title of the project(s), name(s) of the technical COR and years of performance.

• Flexibility of personnel duty assignments in your organization should be discussed when the number of assigned projects is variable.

• Demonstrated organizational experience in process development, scale-up of synthetic organic/medicinal compounds, and QA/QC

• Organization's ability to provide appropriate personnel and resources for the project and to give priority to the NCI project

• Relevance of examples cited to support the organization's ability to manage and operate synthesis laboratories and production facilities.

• Ability of the organization to handle varying levels of assigned work, including concurrent projects or periods with no active projects.

• Adequacy of the safety and security procedures to be used in conducting the proposed work

• Highlight of the safety policy is desirable. Summarize your organization's policy on safety and security which is relevant to this contract. Discuss the possible hazards inherent in this work and how your organization's safety policies are applicable

• Describe laboratory safety controls and procedures for the handling and disposal of carcinogenic and toxic waste materials proposed for this project. Describe procedures used to minimize contamination during laboratory operations.

• Describe your standard and any special housekeeping and inspection procedures. Describe procedures used for the cleaning and inspection of laboratory and large scale/pilot plant equipment including accidental spills.

• Describe how the proposed work area is designed to minimize contamination of chemicals with dust, debris, vapors, and other chemicals.

• Offerors shall comply with all pertinent security and safety requirements prescribed by the Project Officer or required by applicable Government regulations at the Federal, state and local levels. Documents that show compliance of the regulations should be provided.

• Offerors should document registration with the FDA as a manufacturer of bulk drugs.

TOTAL 100