Statement of Work YF.docx

ITEM

NOT TO EXCEED

Large-scale Production and Manufacture of Yellow Fever YF MAC-HD Kits Period of Performance: 4/2/2020 – 7/31/2020

Large-scale Production and Manufacture of Yellow Fever YF MAC-HD Kits Period of Performance: 8/1/2020 -11/28/2021

Statement of Work

Large-scale Production and Manufacture of Yellow Fever YF MAC-HD Kits

SECTION 1 – BACKGROUND

The Arbovirus Diseases Branch (ADB) at the Centers for Disease Control and Prevention (CDC), National Center for Emerging Infectious and Zoonotic Diseases, is a Global Specialized Laboratory in the Yellow Fever Laboratory Network (GYFLN) of the World Health Organization (WHO). One of ADB’s responsibilities is to provide quality diagnostic testing materials and/or kits for serology methods to GYFLN members. The ADB has developed and produced a test kit, the yellow fever M-antibody capture-half day (YF MAC-HD) kit, to detect IgM antibodies to yellow fever virus (YFV). The kit is intended to improve the quality of disease surveillance in yellow fever (YF) endemic countries/regions. YF MAC-HD kits will be used in Central and South America, Africa, and other regions for rapid detection of this vaccine preventable disease and is expected to be approved for use in these regions by a WHO Expert Review Committee. This kit was developed to resist non-ideal transport temperatures and to provide low-resource National Labs with a sturdy diagnostic that is rugged enough to withstand fluctuations in storage environment. The production of the kits is labor-intensive and time-consuming for CDC.

YFV is an RNA virus that belongs to the genus Flavivirus. It is related to West Nile, St. Louis encephalitis, and Japanese encephalitis viruses. YFV is transmitted to people primarily through the bite of infected Aedes or Haemagogus species mosquitoes. Mosquitoes acquire the virus by feeding on infected primates (human or non-human) and then can transmit the virus to other primates (human or non-human). People infected with YFV are infectious to mosquitoes (referred to as being "viremic") shortly before the onset of fever and up to 5 days after onset. In December of 2015, the largest outbreak of YF in 30 years began in Angola, subsequently spreading to Democratic Republic of Congo.

The CDC has an obligation as a WHO collaborating center to provide reagents to the WHO for testing of human samples for YFV on a periodic basis and as the need arises for surveillance purposes. Test methods supported include the CDC MAC-ELISA, for which reagents are supplied as individual test components. This approach has inherent problems due to the technical difficulties of the test methodology, lack of training of laboratorians, different test protocols used across the African continent, reductions in viable suppliers, shipping difficulties, and lack of consistent storage facilities. The CDC-developed YF MAC-HD kit addresses these problems, and was validated in-house using samples primarily from YF-vaccinated individuals. The kit was trialed during the Angola outbreak during the first half of 2016, and was introduced to 9 key National Laboratories via a workshop in 2018. In 2019, the kit was further validated using samples from YF-endemic countries and a pilot phase production was introduced to 33 African National laboratories during collaborative workshops in Cameroon and Senegal in 2019. This Project will move production to full-scale manufacturing.

SECTION 2 – PURPOSE

The overall objective of this Purchase Order is to produce 250 YF MAC-HD kits. Production, quality control and storage will take place at the Contractor’s facility in accordance with the contractor’s SOPs which have been developed in collaboration with ADB. The Contractor will report the results of quality control testing to ADB in order to obtain clearance for lot release. Final lot release will be dependent on additional QC testing at ADB. The Contractor will be responsible for all aspects of quality control and successful production of Kits. ‘Successful’ production is defined as completion of Kits meeting all acceptable performance metrics and specifications. The benefit of the project to ADB is that ADB will no longer have to provide analyte-specific reagents to the WHO, much of which is wasted or used incorrectly. Instead, government employees in ADB can focus their efforts on training National Laboratories, enhancing the diagnostic platform, and providing feedback to participating laboratories in order to improve their performance.

SECTION 3 – SCOPE OF WORK

The Contractor will supply all materials and reagents to produce the kits, with the exceptions of CDC-provided non-infectious positive control material, negative control, non-infectious YF and normal antigens, and conjugate. The Contractor will also supply normal human serum to create non-infectious QC-testing panels for use at the Contractor facilities and at CDC, where the positive panel material will be provided by the CDC. The Contractor will supply facilities, and equipment (including but not limited to storage space, temperature-monitored -20°C, -70°C freezers, and 4°C refrigerator; biological safety cabinet, lyophilizer, 96-well manifold plate washer, calibrated plate reader, 28°C incubator, calibrated pipettes, controlled conditions for plate drying) to produce the kits. The Government will provide a one-time on-site training in the proper use of the kit to the QC department. QC operations will be separate from manufacturing operations and will require separate plate washing equipment.

The Contractor will produce manufacturing SOP’s following Government-provided protocols and will subsequently produce 250 Kits according to the Contractor’s SOP’s. The Contractor’s SOP’s will need to be approved by the Government prior to manufacturing.

The Contractor will produce quality control SOP’s following Government-provided protocols and will perform quality control testing of the kits. The Contractor’s SOP’s will need to be approved by the Government prior to manufacturing. The Contractor will report results of the quality control testing to the Contracting Officer’s Technical Representative. Prior to lot release, the Contractor will ship three or more kits to CDC for final lot release testing, plus at least two QC-testing panels for testing at CDC. Upon approval, the Contractor will release kits to approved logistics partners for use overseas or to CDC, dependent on the intended use.

This scope of work covers the activities requested by the CDC to further refine mass production and complete YF MAC-HD Kit manufacturing at scale. This work will be broken down into two (2) Tasks, with one being an option for a full-scale production:

SECTION 4 – TASKS TO BE PERFORMED

I. Production and Quality Control of YF MAC-HD kits

a. The Contractor will receive CDC-provided reagents and confirm that the shipment was received at the appropriate shipping temperature.

b. The Contractor will produce 5 kits any time that a new lot of plates is used for manufacturing. The 5 kits will be used to determine suitability of the plate lot for large-scale manufacturing.

c. The Contractor will produce 250 complete kits.

d. The Contractor will perform QC analysis on a minimum of 3 kits that show agreement with reference values generated at the CDC. The quality control criteria for lot release to CDC are, at a minimum for the controls, consistent with the test validity criteria contained within the YF MAC-HD package insert (protocol). In addition, values of 1.0-1.5 OD for the positive control reacted with YF antigen, and values of 0.02-0.15 OD for the negative control reacted with YF antigen should also be obtained. QC panel samples tested in triplicate should also maintain OD and P/N values consistent with those obtained at CDC using the same lot of kits. In addition, final lot release will require that results generated at CDC from kit testing using a serum panel, are consistent with results obtained using the CDC MAC-ELISA reference method. QC testing should be coordinated between the Contractor and CDC, and should be performed as soon as possible after the final kit components are produced.

e. The Contractor will perform stability testing following protocols generated in collaboration between the Contractor and the Government. The criteria for acceptable stability for the kits are measured by using the QC panel after two weeks of storage at room temperature (to be determined).

f. The Contractor will report all results of quality control and stability testing to the Contracting Officer’s Technical Representative for inspection and approval.

g. In case the panels fail the quality control or stability testing, the vendor will use scientific advice from the Contracting Officer’s Technical Representative to correct the problem. Only kits that pass the established criteria for quality and stability will be approved by the Government.

II. Packaging and Storage of kits

a. For Task 1, following approval of the Contracting Officer’s Technical Representative, the Contractor will prepare from 50 up to 200 kits for shipping to CDC for validation, quality control testing, and stability testing.

b. The Contractor will store 50 kits for backup and testing, and up to an additional 150 kits for shipping to alternate domestic or international locations if needed.

c. Remaining stored kits will be prepared for release.

d. Each kit will be packaged with a hardcopy of the YF MAC-HD instructions for use. Packaging will be in bulk format according to need.

e. The Contractor will bear the costs for all shipping and storage-related expenses.

f. For optional Task 2, following approval of Task 1, all kits will be stored by Contractor and the Contractor will bear the costs for all shipping and storage-related expenses.

Communication: The Contractor will discuss by email or in phone conferences the composition of the kits, any needed updates to protocols, any problems encountered during the manufacturing processes, and any manufacturing or quality control testing situations that require troubleshooting. The Contractor will share results of quality control and stability testing and will discuss results in a timely fashion with CDC before releasing kits.

QUALITY EXPECTATION:

The process activity in this scope of work will be performed using Good Documentation Practices (GDP). The material generated is not intended for Human or GMP-associated use and thus not subject to cGMP as regulated (through law, guidance’s, ICHs, practices, expectations or the like) by the US Food and Drug Administration (FDA), equivalent government agencies, and/or industry expectations for the production and/or release of an intermediate product, bulk product, BDS, Drug substance, Drug product or the like. The Contractor will provide quality control and batch release procedures and documentation to the Government.

The Contractor will seek eventual WHO prequalification for this product.

QUALITY MANAGEMENT SYSTEM

The Contractor will be required to

· have ISO 13485 certification in place

· furnish the Government with the most recent quality management system (QMS) audit report

· Provide the Government a copy of the quality manual

SECTION 5 – GOVERNMENT FURNISHED MATERIALS

The following Government-Furnished Materials will be provided to the Contractor at its facility by no later than the date for start of work:

a. Positive panel material for QC panels that will be diluted by the Contractor, for use by the Contractor and CDC.

b. For Task 1, the CDC will supply the positive control, negative control, YF antigen, Normal antigen, and conjugate; Contractor shall prepare the material and buffers for use in production and supply and prepare all commercially-available components for the kit, including the production of coated, stabilized microtiter plates.

c. Government agrees to provide copies of all documents necessary to complete the Key Process Steps and the Deliverables.

d. Government agrees to work with Contractor staff to interpret and/or develop the necessary information to complete Key Process Steps and the Deliverables.

SECTION 6 – PERIOD OF PERFORMANCE

Base Period: 4/2/2020 – 7/31/2020 Option Period One: 8/1/2020 -11/28/2021

SECTION 7 – DELIVERABLES/REPORTING SCHEDULE

Items

Description Quantity or No.

of Copies

Delivery Date

Deliver To

SECTION 8 – REFERENCE MATERIAL

The following documents will be provided by Government before start of Kit packaging:

--Package inserts for YF MAC-HD

SECTION 9 – CONTRACTING OFFICER’S REPRESENTATIVE

Contracting Officer’s Representative Chris Duggar, MPH, Senior Public Health Advisor Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Arboviral Diseases Branch 3156 Rampart Road Fort Collins, CO 80521 Phone: 970-221-6499 Email: cduggar@cdc.gov

SECTION 10 – PAYMENT TERMS

Contractor will be paid after completion of work.

SECTION 11 – MINIMUM VENDOR QUALIFICATIONS AND LEVEL OF EFFORT

The Contractor must have experience with the production, quality control testing and stability testing of Serology Elisa testing kits. The Contractor must adhere to good laboratory practice principles.

The Contractor will be required to have in place a Quality Management System (e.g. ISO accreditation) and to furnish the Government with evidence of this system.

SECTION 12: Security Compliance Stardard-7: Generic Information Technology Security and Privacy Language Safeguarding Information and Information Systems. In accordance with the Federal Information Processing Standards Publication (FIPS)199, Standards for Security Categorization of Federal Information and Information Systems, the Contractor (and/or any subcontractor) shall:

Controlled Unclassified Information (CUI). CUI is defined as “information that laws, regulations, or Government-wide policies require to have safeguarding or dissemination controls, excluding classified information.” The Contractor (and/or any subcontractor) must comply with Executive Order 13556, Controlled Unclassified Information, (implemented at 3 CFR, part 2002) when handling CUI. 32 C.F.R. 2002.4(aa) As implemented the term “handling” refers to “…any use of CUI, including but not limited to marking, safeguarding, transporting, disseminating, reusing, and disposing of the information.” 81 Fed. Reg. 63323. All sensitive information that has been identified as CUI by a regulation or statute, handled by this solicitation/contract, shall be:

Protection of Sensitive Information. For security purposes, information is or may be sensitive because it requires security to protect its confidentiality, integrity, and/or availability. The Contractor (and/or any subcontractor) shall protect all government information that is or may be sensitive in accordance with OMB Memorandum M-06-16, Protection of Sensitive Agency Information by securing it with a FIPS 140-2 validated solution.

Confidentiality and Nondisclosure of Information. Any information provided to the contractor (and/or any subcontractor) by HHS or collected by the contractor on behalf of HHS shall be used only for the purpose of carrying out the provisions of this contract and shall not be disclosed or made known in any manner to any persons except as may be necessary in the performance of the contract. The Contractor assumes responsibility for protection of the confidentiality of Government records and shall ensure that all work performed by its employees and subcontractors shall be under the supervision of the Contractor. Each Contractor employee or any of its subcontractors to whom any HHS records may be made available or disclosed shall be notified in writing by the Contractor that information disclosed to such employee or subcontractor can be used only for that purpose and to the extent authorized herein. The confidentiality, integrity, and availability of such information shall be protected in accordance with HHS and CDC policies. Unauthorized disclosure of information will be subject to the HHS/CDC sanction policies and/or governed by the following laws and regulations:

Standard for Encryption. The Contractor (and/or any subcontractor) shall:

Contractor Non-Disclosure Agreement (NDA). Each Contractor (and/or any subcontractor) employee having access to non-public government information under this contract shall complete the HHS/CDC non-disclosure agreement. A copy of each signed and witnessed NDA shall be submitted to the Contracting Officer (CO) and/or CO Representative (COR) prior to performing any work under this acquisition.

Incident Response. A privacy breach is a type of incident and is defined by Federal Information Security Modernization Act (FISMA) as the loss of control, compromise, unauthorized disclosure, unauthorized acquisition, or any similar occurrence where (1) a person other than an authorized user accesses or potentially accesses personally identifiable information (PII) or (2) an authorized user accesses or potentially accesses personally identifiable information for an other than authorized purpose. The HHS Policy for IT Security and Privacy Incident Reporting and Response further defines a breach as “a suspected or confirmed incident involving PII”.

In the event of a suspected or confirmed incident or breach, the Contractor (and/or any subcontractor) shall:

Sanitization of Government Files and Information. As part of contract closeout and at expiration of the contract, the Contractor (and/or any subcontractor) shall provide documentation or attestation to the CO and/or COR to certify that, at the government’s direction, all electronic and paper records are appropriately disposed of and all devices and media are sanitized in accordance with NIST SP 800-88, Guidelines for Media Sanitization.

Contractor Responsibilities Upon Physical Completion of the Contract. The contractor (and/or any subcontractors) shall return all government information and IT resources (i.e., government information in non-government-owned systems, media, and backup systems) acquired during the term of this contract to the CO and/or COR. Additionally, the Contractor shall provide a certification that all government information has been properly sanitized and purged from Contractor-owned systems, including backup systems and media used during contract performance, in accordance with HHS and/or CDC policies.

Information Technology Application Design, Development, or Support.

1) The Contractor (and/or any subcontractor) shall ensure IT applications designed and developed for end users (including mobile applications and software licenses) run in the standard user context without requiring elevated administrative privileges.

2) The Contractor (and/or any subcontractor) shall follow secure coding best practice requirements, as directed by United States Computer Emergency Readiness Team (US-CERT) specified standards and the Open Web Application Security Project (OWASP), that will limit system software vulnerability exploits.

3) The Contractor (and/or any subcontractor) shall ensure that computer software developed on behalf of HHS or tailored from an open-source product, is fully functional and operates correctly on systems configured in accordance with government policy and federal configuration standards. The contractor shall test applicable products and versions with all relevant and current updates and patches updated prior to installing in the HHS environment. No sensitive data shall be used during software testing.

4) The Contractor (and/or any subcontractor) shall protect information that is deemed sensitive from unauthorized disclosure to persons, organizations or subcontractors who do not have a need to know the information. Information which, either alone or when compared with other reasonably-available information, is deemed sensitive or proprietary by HHS shall be protected as instructed in accordance with the magnitude of the loss or harm that could result from inadvertent or deliberate disclosure, alteration, or destruction of the data. This language also applies to all subcontractors that are performing under this contract.

SECTION 13 – EVALUATION FACTORS

This award will be made as a result of "best value” source selection. Best value means that the Government will perform a price/technical trade-off analysis such that business judgment will be exercised in selecting the most advantageous alternative to the Government, considering both the price and technical merit of the proposals. The Government will assess the benefits of technically superior proposals against the price of obtaining those technical benefits.

The following criteria shall be utilized in evaluation of the technical proposal. The contractor should address each of these dimensions in the application in response to the Purchase Order.

Technical evaluation criteria for this SOW are as follows:

Technical Approach (25 Points Maximum) Contractors are to provide a discussion of their technical approach for providing the services required for this Purchase Order. This criterion will be evaluated according to the soundness, practicality, and feasibility of the Contractor’s technical approach for providing services required for this Purchase Order.

Staffing Plan (25 Points Maximum) Contractors are to provide a staffing plan that demonstrates their understanding of the labor requirements for this Purchase Order. The plan should address the proposed labor categories, descriptions of the services to be provided, estimated labor hours, etc. This criterion will be evaluated according to the soundness, practicality, and feasibility of the offeror’s staffing plan for this Purchase Order.

Experience of Personnel (25 Points Maximum) Provide information reflecting experience of assigned staff that is similar in complexity and size of the anticipated project. This information will be represented by the proposed staff/personnel Resumes. This criterion will be evaluated according to the qualification related to background and need and appropriate experience of assigned personnel.

Quality Assurance & Certification (25 Points Maximum) Contractors are to provide discussion of their quality assurance approach and related certifications for providing the services required for this Purchase Order. This criterion will be evaluated according to the Contractor’s existing certifications for production of diagnostic materials required for this Purchase Order.

Price Evaluation: The price proposals will not be assigned quantitative scores. The information contained in the proposals will be analyzed and evaluated to determine validity, realism and reasonableness of each price proposed.