20190621_-_2019-31170_-_Statement_of_Work_(SOW).pdf

Section C – Description/Specification/Work Statement

C.1 Project Identification & Purpose

The Centers for Disease Control & Prevention (CDC) urgently needs additional real-time PCR kits to meet projected Laboratory Response Network (LRN) testing requirements over the next several years. The Government needs to replace used and expired kits to assure the nation’s ability to respond to a real BT event and develop improved assays for enhanced detection capability.

The CDC, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Preparedness and Emerging Infections (DPEI), Laboratory Preparedness and Response Branch (LPRB), as part of national preparedness, supplies PCR kits to the LRN network. This nationwide program is comprised of over 100 LRN laboratories that have the capability to detect potential biothreat and emerging infectious disease agents. LRN reagents are used by state and local public health, FDA, USDA, EPA, DOD, and neighboring international laboratories.

Additionally, LPRB supplies PCR kits to the laboratory component of BioWatch, a program of the Department of Homeland Security, whose mission is intensive environmental surveillance in major U.S. cities. Select laboratories in the LRN also serve as BioWatch laboratories. They evaluate air samples using real-time PCR primer and probes. This extensive environmental sampling and testing program will improve the speed and probability of detecting a covert aerosol event and enable a more rapid response.

This LRN requirement currently includes production of up to thirty-three different PCR kit types.

The Blanket Purchase Agreement (BPA) provides significant flexibility relative to the total number of kits which may be purchased. The lower (minimum) quantities provide for simple routine detection capabilities. The larger (maximum) quantities allow for surge capacity and for remediation at a national level. A five year BPA is needed because no suitable, equivalent technology is expected to replace the real-time PCR kits during this period and allows for inventory planning.

C.2 Background and Need

The LRN’s purpose is the detection, analysis, and reporting of biothreat agents and biological agents causing any emergency public health problem. Because of the rapid and successful growth of the LRN, the amount of reagents required to supply and sustain the member laboratories to conduct testing has increased. If we are unable to purchase these proprietary reagents, the Government’s ability to respond to a biothreat or emerging infectious disease will be severely impaired. Failure to procure these will compromise response capability of agencies such as the EPA, USDA, FBI, DHS, and others depending on LRN capacity to accomplish their own preparedness and response missions.

Real-time PCR assays are very high confidence assays. PCR assays offer high levels of sensitivity and specificity, easily detecting agent DNA that other assay types might not detect. PCR reagents are relatively stable when compared to many other reagent types. PCR reagents are relatively inexpensive when compared to many other reagent types. PCR reagents provide very rapid detection capability providing results within hours.

The Agency’s public health mission depends upon these real-time PCR reagents to detect potential biothreats and/or emerging infectious diseases.

C.3 Project Objective

The objective of this Blanket Purchase Agreement (BPA) is to obtain real-time PCR primers and probes in a dried/lyophilized format. The Government has defined specification for the production of up to 33 different types of kits that are needed. Actual order quantities will depend upon Government policy decisions, funding, and actual usage/demand.

Rapid delivery of reagents with proven quality is a critical need. Manufacturer shall have proven capability to produce and deliver real-time high quality PCR primer and probe kits using Black Hole Quencher (BHQ1) and FAM reporter technology. Manufacturer shall meet the minimal quality standards defined by FDA in 21 CFR820 for the production of in vitro diagnostic devices. Refer to Section C.4.1 Technical Requirements for additional information.

C.4 Scope of Work

C.4.1 Technical Requirements

The Contractor shall perform the following tasks.

C.4.1.1 Ensure by documentation that primer and probe sequences remain confidential and proprietary information and as the exclusive and secure property of the Government.

Primer and probe sequences for the different markers will be provided two (2) weeks after the contract is awarded or as mutually agreed upon by the Government and Contractor.

C.4.1.2 Assure by documentation that primer and probe sequence information never leaves the manufacturing facility, is never shared with a third party, and that the information remains secure within the Contractor’s facility.

C.4.1.3 Assure by documentation and written notification to the Government that sequence information is destroyed upon completion of the contract(s). Destruction of all documentation and materials will be requested by the Government in writing at the end of the Period of Performance, or when the Government deems necessary.

C.4.1.4 Provide all raw materials and labor to produce kits.

C.4.1.5 Provide packaging materials and pay shipping to the Government.

C.4.1.6 Produce and submit pilot batches of 6 kits for each kit type. Pilots will be evaluated within three (3) weeks by Bioterrorism Rapid Response and Advanced Technology Laboratory (BRRATL) at CDC. Delivery schedule will be included in each delivery order issued under this BPA.

C.4.1.7 Supply completed batch (the order quantity) after pilot approval by BRRATL and receipt of authorization to ship. Delivery schedule will be included in each delivery order issued under this BPA.

C.4.1.8 Make deliveries FOB Destination (at Contractor’s expense) to the address stated in the Contact Information for Shipment of approved finished goods.

C.4.1.9 Allow all lots to be Quality Control (QC) tested/inspected by the Government prior to acceptance and payment.

C.4.1.10 Package and ship finished goods in compliance with Government requirements and/or shipping/packaging instructions.

C.4.1.11 Contractor may be allowed by the Government to hold a small number of finished samples (kits) for stability/retention purposes. The number of samples to be held by Contractor must be approved by the Government and will be destroyed upon the Government’s request.

C.4.1.12 Allow the Government to perform on site visits and/or audits.

C.4.2 Technical Requirements

The Government will perform the following tasks.

C.4.2.1 Provide confidential sequence information for the primers and probes after award of contract.

C.4.2.2 Specify order in which primer/probe types are to be manufactured and supplied.

C.4.2.3 Perform QC testing of pilot kits (samples) to check formulation prior to full scale production.

C.4.2.3 Notify Contractor with approval/disapproval within three (3) weeks after receipt of pilot samples.

C.4.2.4 Provide label information and requirements.

C.4.2.5 Provide product information and requirements.

C.4.2.6 Perform QC of finished goods at the Government prior to final acceptance by the Government.

C.4.2.7 Purchase approved finished goods upon receipt and in accordance to the terms specified in contract.

C.4.2.8 Review and approve all labeling components prior to use with product.

C.5 Detailed Technical Requirements

C.5.1 In process QC analysis, the Contractor shall perform the following tasks.

C.5.1.1 A check of crude OD’s and HPLC is run to check the concentration and purity after Cleavage and De-protection.

C.5.1.2 A qualitative HPLC analyzes purity while Mass Spectroscopy identifies molecular weight after Purification.

C.5.1.3 Total yield is determined using Beer’s law with a molar absorptivity at 260nm during OSs.

C.5.1.4 Concentration checks are measured in the same fashion as yield.

C.5.1.5 Volume checks are measured in volumetric pipettes after Normalization.

C.5.1.6 Pilot Kit QC consists of a small scale assembly of kits from bulk reagent components. The entire finished product QC: Volume QC, Dry Down, MS AX HPLC, RP HPLC, and concentration checks are performed before sending pilot kits to the Government for testing.

C.5.1.7 Once the Government approval has been provided to Contractor, bulk reagent remaining components of kits are released to final kit assembly.

C.5.1.8 Perform volume QC checks following dispensing.

C.5.1.9 Visual inspection of the product is conducted after dry down.

C.5.1.10 Finished product Quality Assurance (QA)/QC consists of analysis of recommended reagents by MS, AX HPLC, RP HPLC, and concentration checks.

C.5.1.11 Kit inspections include kit, tubes, label, data analysis, certificates of analysis verification.

C.5.2 The Contractor shall perform the following labeling, filling and lyophilization tasks.

C.5.2.1 Label approved vials with Government-approved labels. Vial size shall be provided per Government product specification. All labels shall be pre-approved by the Government.

C.5.2.2 For all PCR kits dispense quantity of primer and probe provided per Government product specification

C.5.2.3 Dispense specified nmole quantity of forward primer per vial into an approved vial.

C.5.2.4 Dispense specified nmole of reverse primer per vial into an approved vial.

C.5.2.5 Dispense specified nmole probe per vial into an approved vial.

C.5.2.6 Lyophilize primers and probes. Cap vials.

C.5.2.7 Prior to assembly of kits, labeled vials shall be stored in sealed containers/bags at 2-8oC in the dark.

C.5.3 Kit Assembly

C.5.3.1 The Contractor shall perform the following kit assembly tasks.

C.5.3.1.1 The Government must review and approve all inserts and labels prior to kit assembly.

C.5.3.1.2 Each target signature has a labeled vial of each: 1) a forward primer, 2) a reverse primer and 3) a probe.

C.5.3.1.3 Each signature shall be placed (three (3) labeled vials) into a labeled 2.5″ x 3.5″ Government-approved foam envelope.

C.5.3.1.4 Each kit shall contain a one-page product insert.

C.5.3.1.5 One to five (1–5) envelope(s), with the primer and probe vials, and product insert are placed into an appropriate sized sealed, resealable plastic bag (Ziploc brand or equivalent).

C.5.3.1.6 Each sealed, resealable plastic bag (Ziploc brand or equivalent) has an outer label.

C.5.3.1.7 Product branding: “Distributed by CDC for the Laboratory Response Network (LRN)”.

C.5.4 QC Evaluation

C.5.4.1 The Contractor shall perform the following QC evaluation tasks.

C.5.4.1.1 Assuring kits shall have been assembled in compliance with Government requirements.

C.5.4.1.2 Assuring labels and inserts meet Government requirements.

C.5.4.1.3 Primers, shall be greater than 90% full length.

C.5.4.1.4 Probes, shall be greater than 90% full length.

C.5.4.1.5 Probes, shall be greater than 90% contain both FAM reporter and BHQ1 quencher.

C.5.5 QA Specifications

C.5.5.1 The Contractor shall perform the following QA tasks.

C.5.5.1.1 Product shall be manufactured in compliance with Federal Drug Administration (FDA) Quality Systems Requirements (QSR) as defined by 21 CFR 820.

C.5.5.1.2 Manufacturer shall notify the Government of any deficiencies encountered during manufacture and storage of each product. The Government will review the deviation to determine whether it will interfere with the product performance.

C.5.5.1.3 Final QA testing of kits must demonstrate specificity/sensitivity within expected limits.

C.5.5.1.4 Final payment is contingent on QC testing and approval of final product by the Government.

C.5.5.1.5 Contractor shall permit site visits and quality audits to be performed by the Government.

C.5.5.1.6 Changes to the BPA or specifications contained within shall be submitted to the Contracting Officer for review and approval prior to implementation.

C.5.6 QC Specifications

C.5.6.1 The Contractor shall meet the following QC Specifications.

C.5.6.1.1 The finished product will be analyzed by HPLC with the following QA/QC criteria:

C.5.6.1.2 Anion exchange HPLC (AX-HPLC) on primers to ensure 90% or greater full length product.

C.5.6.1.3 Anion exchange HPLC on probes to ensure 90% or greater full length product.

C.5.6.1.4 Reverse Phase HPLC (RP- HPLC) and Photo Diode Array (PDA) analyses on probes to ensure 90% or greater of probes contain FAM and BHQ1.

C.5.6.2 The finished product shall be analyzed by Electro Spray Ionization Mass Spectroscopy (ESI-MS) with the following QA/QC criteria:

C.5.6.2.1 ESI-MS analysis on primers and probes to ensure molecular weights of primer and probe shall be within 0.1% of theoretical molecular weights.

C.5.6.3 Concentration checks on bulk primer and probe solutions before dispensing to ensure that concentration is within +/- 5% of target values.

C.5.6.4 Volume check of aliquoted probes to ensure that dispensed volume is within +/-10% of target volumes.

C.5.6.5 Volume check of aliquoted primers to ensure that dispensed volume is within +/-5% of target volumes.

C.5.6.6 Inspections of vials prior to dry down to ensure liquid has been dispensed to each vial and label is appropriate.

C.5.6.7 Visual inspection of the dried down vials to ensure completeness of drying and capping.

C.5.6.8 AX-HPLC, RP- HPLC and ESI-MS on buffer reconstituted by vacuum evaporated primers and probes to ensure product integrity was maintained during dry down.

C.5.6.9 Concentration checks on reconstituted primers and probes to ensure post-dry down quality is within +/- 10% of target quality.

C.5.6.10 Visual inspection of each kit to ensure correct assembly. At least 5% of the assembled kits shall be manually inspected.

C.5.6.11 Supply the Government with Certificate of Analysis (COA) stating QC conformity with product specifications and compliance with 21 CFR820 production.

C.6 Reporting Schedule

C.6.1 Contractor shall coordinate the production and delivery schedule with the Government

COR.

C.6.2 All shipments to the Government shall be pre-authorized by the Government; refer to individual delivery orders issued under this BPA for delivery requirements.

C.6.3 Contractor shall notify the Government COR within two (2) business days of potential production and/or delivery delays.