N02CN75008-10.pdf

Pre-Solicitation Notice: N02CN75008-10

Contracting Office Address

Department of Health and Human Services National Institutes of Health (NIH) National Cancer Institute (NCI) Office of Acquisitions 9609 Medical Center Drive, MSC 9705 Bethesda, MD 20892-9705

Note: This synopsis follows a Small Business Sources Sought notice that was released on April 12, 2017 under HHS-NIH-NCI-SBSS-PCPSB-75008-10

THIS IS A NOTICE OF INTENT, NOT A REQUEST FOR PROPOSAL. A SOLICITATION WILL BE

ISSUED ON A LATER DATE.

Title: Regulatory Support for Cancer Prevention Agent Development

Description:

The purpose of the acquisition (re-competition) is to provide regulatory services and technical support to the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI). Technical Support is required to gather, interpret and summarize the vast amount of preclinical and clinical data associated with potential cancer preventive agents. This data is generated by the scientific community and NCI contract labs. Much of this data is used to prepare required reports for FDA review. This contract will prepare and maintain documents required by the Food and Drug Administration (FDA) and other regulatory bodies for clinical trials of investigational agents.

Background:

The National Cancer Institute (NCI), Division of Cancer Prevention (DCP) has over 40 active clinical trials, 15 trials in development and is the sponsor for approximately 35 INDs (Investigational New Drug Applications). DCPs INDs are located in six Divisions at the FDA. The mission of DCP is to plan and direct cancer prevention research, including testing promising agents in human clinical trials as part of a drug development program. Such testing falls under the purview of regulatory agencies such as the FDA and requires certain documentation for the use of the investigational agent. The collection, preparation, submission and continual update of this documentation is the focus of this acquisition. The current contractor for this acquisition is CCS Associates Inc., 1923 Landings Dr. Mountain View, CA 94043.

Technical and Contractual Requirement:

The proposed acquisition will involve the following type of activities, further defined in the attached Statement of Work (Attachment 1):

1) Provide regulatory submissions to support the DCP's chemoprevention agent development and clinical research program.

2) Prepare, review, maintain, and track correspondence related to regulatory submission.

3) Provide regulatory support for safety data (adverse event) review, processing, and submission to regulatory agencies and investigators.

4) Maintain electronic and paper files of agreement documents and other documents from pharmaceutical companies.

5) Assist in scheduling, facilitating, and attending meetings to support DCP's regulatory affairs, agent development, and clinical research programs.

6) Manage regulatory documents such as Investigational New Drug Applications (INDs) and Drug

Master Files (DMFs) in accordance with regulations, laws, and guidance.

7) Perform regulatory and safety reviews, reporting and advisory activities.

8) Prepare, process and establish a written plan for quality assurance and quality control of all data and procedures.

9) Maintain and enhance standard procedures for information management to support DCP's regulatory affairs.

10) Assist in the transition of the existing contract to the successor contractor.

This acquisition will be a total small business set-aside. The Government anticipates that one (1) contract will be awarded with a base period of one year and four one-year option periods. The Product Service Code is R499 and the NAICs Code is 541690; the size standard for this acquisition is $15,000,000.

The RFP will be available electronically on or about March 2018 and may be accessed through the FedBizOpps at www.fbo.gov. WE ENCOURAGE ALL RESPONSIBLE SMALL BUSINESS

SOURCES, TO SUBMIT A PROPOSAL, WHICH WILL BE CONSIDERED BY THE

AGENCY. This notice does not commit the Government to award a contract. No collect calls will be accepted. No facsimile or email transmissions will be accepted. IT IS THE OFFEROR’S

RESPONSIBILITY TO MONITOR THE ABOVE-MENTIONED SITE FOR THE RELEASE OF THE

SOLICITATION AND ANY AMENDMENTS.

Contracting Office Address:

9609 Medical Center Drive Bethesda, Maryland 20852

Primary Point of Contact:

Yifan Yang Contracting Officer yifan.yang@nih.gov Phone: 240-276-5282

Secondary Point of Contact:

Sara McLaurin Contracting Officer mclaurinsm@mail.nih.gov Phone: 240-276-5488 http://www.fbo.gov/ mailto:yifan.yang@nih.gov mailto:mclaurinsm@mail.nih.gov

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N02CN75008-10

Statement of Work The Contractor shall furnish services, qualified personnel, material, equipment compatible with NCI systems, and facilities, not otherwise provided by the Government under the terms of this contract, as needed to perform the support tasks set forth below.

TASK AREA I: Regulatory Submissions The Contractor shall be responsible for regulatory submissions to support the Government’s chemoprevention agent development and clinical research program. The regulatory contactor shall develop and implement procedures for accessing, reviewing, and compiling scientific, safety, and clinical data for possible inclusion in Investigational New Drug Applications (INDs) and other regulatory submissions. The Government shall provide the scientific background and current information on all of the chemopreventive agents. Regulatory submissions shall be made in accordance with U.S. Food and Drug Administration (FDA) regulations, ICH (International Committee on Harmonization) guidelines, and National Institutes of Health (NIH), National Cancer Institute (NCI), and Division of Cancer Prevention (DCP) requirements and other relevant regulations, laws, and guidelines.

Primarily this task will involve the preparation and submission of INDs to the FDA. Submissions will also include Drug Master Files (DMFs), New Drug Applications (NDAs), providing adverse event data for development of the Investigator's Brochures by the Technical Support contractor, Common Technical Documents, and other documents required by FDA regulations. For multinational research efforts supported by DCP, the Contractor may be directed to prepare submissions to international regulatory bodies. It is estimated that the Contractor shall prepare 5-6 lNDs per year. The DMFs shall be updated yearly.

The Contractor shall plan and implement a transition to an electronic process for managing content and transmitting regulatory submissions to regulatory agencies. Content used for regulatory submissions comes in a variety of formats and from several sources and systems. Data types and sources include: protocol information from the DCP Enterprise System Knowledgebase (DESK), clinical data from research sites via Oracle Clinical Remote Data Capture, preclinical data from the DCP's agent development program, and chemistry and manufacturing information from DCP's agent repository. Therefore, the regulatory Contractor shall interface with other systems and coordinate with DCP staff, monitoring contractor, scientific information technical support contractor, agent repository, pharmaceutical collaborators, and other organizations supporting DCP's chemoprevention program. The Contractor shall perform the following activities under this task:

A. IND submissions

1) The Contractor shall compile and submit IND applications as required by FDA. A portion of this information will come from the DCP databases. This includes protocols, protocol amendments, Serious Adverse Event (SAE) reports, Annual Reports, FDA forms 1571, additional chemistry and manufacturing information, and toxicology information.

2) The Contractor shall prepare all amendments to DCP-sponsored INDs in addition to the initial IND submission.

3) The Contractor shall ensure the accuracy and completeness of supporting regulatory documents collected from the clinical institutions to DCP. These may include the FDA 1572, investigator biosketches, IRB approval documentation, and other documents required for submission to regulatory agencies and/or needed for DCP to authorize the shipment of investigational agents to research sites. In addition, the Contractor shall track

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Office for Human Research Protection (OHRP) assurances, human subjects protection training, certificates of confidentiality and other documentation as required by DHHS Regulations and NIH policies.

4) The Contractor shall prepare Annual Reports to the FDA on all active INDs (between 15- 25/yr) in accordance with 21 CFR.312.33. These Annual Reports must be provided to the FDA no later than 30 days past the anniversary date of the IND submission to the FDA.

The Contractor shall notify DCP if a delay in submitting the Annual Report to the FDA is anticipated.

5) In the instance where there is a collaborating pharmaceutical company, the Contractor may be requested to provide information regarding regulatory submissions to that company.

6) The Contractor shall coordinate IND cross-filing activities as needed.

7) The Contractor shall file IND documents in electronic Common Technical Format (eCTD) to the FDA and utilize such software and licenses necessary to fulfill this requirement.

B Drug Master File (DMF) The Contractor shall review and update the DCP Drug Master File (DMF) on the anniversary date of this contract. The Contractor shall submit draft DMF to DCP for review and approval. Along with the standard required material, this file will include internal DCP standard operating procedures (SOPS) for such areas as Protocol and Safety Review, Agent Development, content of biomarker/assay methods validation, etc. In addition the Contractor shall:

1) Edit, index, and format data in conformance with FDA requirements.

2) Prepare correspondence noting the DMF filing and withdrawals.

TASK AREA 2: Regulatory correspondence and administrative tracking

a. The Contractor shall prepare, review, maintain, and track correspondence related to regulatory submissions. These regulatory submissions, include but are not necessarily limited to: correspondence to accompany all IND filings, inactivations, and withdrawals;

letters to investigators arising from FDA review of INDs and protocols; and responses to FDA requests based on DCP and investigator comments. All regulatory submissions and correspondence among the FDA, DCP, investigators, and pharmaceutical collaborators shall be tracked electronically within DESK.

b. The Contractor shall maintain in DESK data on persons, organizations, and contact information for FDA contacts, pharmaceutical collaborators, and other entities with which DCP interacts to carry out its regulatory activities.

TASK AREA 3: Safety Activities The Contractor shall provide regulatory support for safety data (adverse event) review, processing, and submission to regulatory agencies and investigators. Specifically:

a. The Contractor shall establish a 24-hour/7-day notification system for the prompt reporting of serious adverse events (or other serious matters) at the study sites. This system shall include the notification of the Contractor for tracking and monitoring purposes. The Contractor shall in turn notify the study’s medical monitor.

b. The Contractor shall receive, perform a regulatory review of and organize adverse event

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(AE) data and serious adverse event (SAE) data to submit to FDA and other regulatory bodies in accordance with regulations and DCP instructions. AE data and SAE data are obtained by several different mechanisms that include but are not limited to: reports from clinical investigators, legacy Access databases, legacy DESK (DCP Enterprise System Knowledgebase) Investigator Technical Progress Reporting (ITPR) System, Oracle Clinical Remote Data Capture, and the SAE reporting system(s). The Contractor shall manage and integrate data from these sources as required for reporting adverse events.

c. The Contractor shall perform regulatory review of SAE reports.

d. The Contractor shall provide support for adverse event coding. The Contractor shall have expertise in the use of (MedDRA) and a working knowledge of other vocabularies used in regulatory activities, (including but not necessarily limited to COSTART, WhoART, and NCI's CTCAE (Common Terminology Criteria for Adverse Events) ). The Contractor shall obtain the appropriate licenses needed to use such vocabularies.

e. The Contractor shall provide AE data and SAE data to collaborating pharmaceutical companies as directed by DCP.

f. The Contractor shall assist DCP staff and scientific technical contractors in the development of expected adverse event lists for DCP-sponsored agents.

TASK AREA 4: Maintenance of collaborating research agreement records To carry out its chemoprevention agent development and clinical research mission, DCP collaborates with pharmaceutical companies through the use of agreements such as CRADAs (Cooperative Research and Development Agreement), Clinical Trial Agreements (CTAs), Confidential Disclosure Agreements (CDAs), and Material Transfer Agreements (MTAs).

a. The Contractor shall maintain all files of agreement documents and other documents from pharmaceutical companies.

b. The Contractor shall create and maintain data about the status and nature of the collaborative agreement documents. This shall include correspondence between DCP and potential and actual collaborators, and tracking of special requirements for research activities conducted under collaborating research agreements. At the direction of the Contracting Officer’s Representative, these requirements shall include sharing clinical data with the collaborator or restrictions on the type of trials for which a collaborator will supply drug. These data shall be available to DCP so trials can be planned and conducted in accordance with the collaborative research agreements.

c. Data about collaborators and investigational agents may be sensitive and proprietary.

Therefore, the Contractor shall establish appropriate security mechanisms to maintain confidentiality of these data.

TASK AREA 5: Coordination and Documentation of Regulatory Meetings DCP meets with regulatory agencies, pharmaceutical companies, and preclinical and clinical researchers involved in the conduct of DCP- sponsored clinical trials to discuss scientific study results, drug development plans, and data sharing. At the request of the Contracting Officer’s Representative, the Contractor shall assist in scheduling, facilitating, and attending meetings to support DCP's regulatory affairs, agent development, and clinical research programs. The Contractor shall prepare detailed minutes and summaries of these meetings.

These minutes shall provide substantive content for future FDA correspondence.

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TASK AREA 6: Document Management The Contractor shall manage regulatory documents (such as INDs and DMFs) in accordance with regulations, laws, and guidance. The Contractor shall develop and implement a document management system that will:

a. Maintain, store, and provide to DCP all regulatory submissions, supporting documents, and essential site documents. Documents include but are not limited to: Annual Reports, active and inactive IND applications, amendments to the IND applications, and CTAs.

b. Handle document version control and review tracking.

c. Provide safe and secure electronic and physical storage conditions.

d. Allow all active and archived materials to be readily retrievable and available to DCP staff within twenty-four hours from the time of a request.

e. Store electronic copies of reports prepared in mandated electronic formats and provide electronic delivery of these data upon request.

f. Archive records in accordance with regulatory and other requirements.

TASK AREA 7: Regulatory review, reporting, and advisory activities

Under this task, the Contractor shall:

a. Perform regulatory and safety reviews of chemoprevention protocols and amendments as directed by DCP Protocol Information Office (PIO). Provide staff member to present comments at DCP's protocol review meetings.

b. Prepare slides and other briefing materials regarding DCP regulatory procedures and activities for presentation upon request by the DCP Contracting Officer’s Representative

(COR).

c. Participate as subject matter experts in DCP and NCI informatics design and development activities, as directed by the COR. This includes but is not limited to attending knowledge acquisition sessions to define requirements and data model reviews, and participating in user testing efforts for DESK enhancements and other systems.

d. Participate in regular conference calls between DCP staff and other contractors as needed to discuss specific issues and shall be available for routine information sharing as needed.

e. Stay abreast of emerging regulatory guidelines and other developments that could affect DCP regulatory affairs.

f. Advise DCP on regulatory issues, as requested by DCP program staff. From a regulatory perspective, the Contractor shall review draft DCP guidelines and procedures for agent development and clinical research activities. The Contractor shall also assist in the development of DCP guidelines and procedures for activities governed by FDA, ICH and OHRP (Office of Human Research Protection) Regulations.

g. Provide information to the DCP, scientific technical support contractor, and investigators that is relevant to agent development (e.g. Adverse event data) at the direction of the

COR.

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TASK AREA 8: Process and Quality Assurance/Quality Control SOPs The Contractor shall prepare and submit draft SOPs for all functions described in the SOW and submit to DCP for review and approval within 120 days of contract award. SOPs shall be updated as needed and submitted to DCP. The Contractor shall establish a written plan for quality assurance and quality control of all data and procedures described in this SOW. This plan shall include:

a. Defining parameters for the security of paper and electronic records;

b. Verification of accuracy of data entry in information management systems, including the reconciliation of data discrepancies from different sources (such as, between legacy systems and current systems);

c. Ensuring the accuracy of all information in the regulatory submissions including Annual Reports, letters, and INDs; and

d. Ensuring documents and their copies are complete and free of grammatical and typographical errors.

TASK AREA 9: Information Management System The Contractor shall maintain and enhance standard procedures for information management to support DCP's regulatory affairs.

a. The Contractor shall integrate its and DCP’s current and future information management systems (IMSs).

b. The Contractor shall ensure that its IMSs are fully interfaced with the DCP’s IMSs, to the extent possible, and that the IMSs have remote access capability for DCP and its designees. Data shall be shared between the system and DESK (or other comparable DCP applications) in an automated, labor-free process. The process shall not involve duplicate storage of the same data in both systems. Data sharing with DESK (or other comparable DCP applications) shall not require a manual reconciliation process.

c. The Contractor shall ensure, to the extent possible, that the systems use the presentation layer and user interface that is standard across all DCP IMS applications.

d. The Contractor shall ensure that its IMSs provide designated DCP personnel the capability to perform ad-hoc queries of information.

e. The Contractor shall maintain and update/upgrade/enhance standard procedures for information management for chemopreventive agents and test results. The Contractor shall ensure that its IMSs conform and integrate with appropriate industry standards and NCI technology infrastructure.

f. The Contractor shall ensure that all messages between the regulatory system and external systems are based on current interoperability standard.

g. The Contractor shall ensure that data used by the regulatory system complies with the National Cancer Institute's Cancer Data Standards Repository (caDSR) metadata standards and compliance standards, and that all data are represented as Common Data Element approved by DCP. The data shall be integrated with the caDSR, or other comparable applications, so that Common Data Element metadata may be accessed directly wherever appropriate.

h. The Contractor shall ensure that the IMSs contain a complete audit trail of all changes to

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i. The Contractor shall ensure that the IMS applications are web-enabled and capable of accommodating the anticipated concurrent user base (up to 100) . Performance response level shall be reasonable and mutually agreed upon with COR.

j. The Contractor shall have appropriate, experienced database management, programming and other technical personnel on its staff to provide support and maintenance of the system. The Contractor shall have the appropriate licensure within 30 calendar days of contract award.

k. The Contractor shall utilize TestTrack Pro or a comparable tool to track bugs, issues and change requests. Remote web access to the tool and its contents should be provided to NCI-designated representatives.

l. Changes to the system will require approval by the DCP Change and Configuration Group (CCG). The Contractor shall provide a representative to participate on the CCG.

The Contractor shall participate in other DCP IT status meetings and other activities as requested by the COR.

m. The Contractor shall ensure that the system complies with 21 Code of Federal Regulations Part 11, the FDA regulations regarding electronic records and signatures, as well as other applicable regulations and laws. 21 CFR 11 and current guidance are found at http://www.fda.gov/ora/cornpliance ref/part11

TASK AREA 10: Transition The Contractor shall assist in the transition of the existing contract to a successor contract.

The transition period shall consist of the final 60 calendar days of the contract. The following shall apply only to a transition wherein the contractor is not the recipient of the successor award.

a. The Contractor shall provide the successor contractor with detailed briefing regarding the policies and procedures for managing all aspects of the project. As part of these detailed briefings, the Contractor shall provide the successor contractor with the Procedures Manual for regulatory support. The Manual provided shall be complete, with all procedures detailed and current as of the date of the initial briefing.

b. The Contractor shall provide instruction to the successor contractor in the policies and procedures utilized in the performance of the contract.

c. The Contractor shall submit a plan for the transfer of all materials and data stored 90 days before completion of the contract.

Travel:

The Contractor shall be available to travel to NCI and FDA facilities, as needed in coordination with the COR, to accomplish any IND specific or other regulatory goal required by DCP.

http://www.fda.gov/ora/cornpliance%20ref/part11