Attachment SOW.pdf

75F401F25R00066 Statement of Work, Biorelevant characterization system for subcutaneous injections

Statement of Work (SOW)

Biorelevant characterization system for subcutaneous injections Scope of Work The scope is to purchase and install an in vitro biorelevant characterization system for subcutaneous injections at the injection site in an artificial extracellular matrix (ECM) with integrated camera and turbidity sensors, inline fiber optic probes, pH monitors, and an automated sample fraction collector for unattended operation and media refill after sampling.

The aim is to expand and augment the capacity and capability of CDER/OPQ/OPQR to ensure quality, safety and efficacy of pharmaceutical products. In particular, this in vitro system will offer the capability for investigating the release performance of subcutaneous formulations under simulated physiological conditions. It assesses the critical drug attributes, risk and performance of subcutaneously administered drugs including biologics, peptides and small molecules.

Background Subcutaneous injections are formulations injected to the subcutaneous space. After injection, along with drug release, the formulation may undergo solvent exchange, aggregation and precipitation, liquid to solid phase transition, depot migration and matrix degradation. Some subcutaneous injections are associated with an initial burst in drug release right after the injection. An integrated biorelevant in vitro investigation platform that can monitor the formulation continuously is necessary to investigate the relationship between in vitro critical drug attributes and in vivo drug performance.

1) Technical Requirements The instrumentation shall meet the following salient characteristics.

The integrated system must consist of a main unit for the drug release in artificial extracellular matrix (ECM) with integrated camera and turbidity sensors, inline fiber optic probes, pH monitors, and an automated sample fraction collector for unattended operation and media refill after sampling.

(1) Shall contain a main unit that holds the chambers and cartridges for the drug release in artificial extracellular matrix (ECM) simulating the subcutaneous space,

(2) The ECM shall be a viscous liquid that contains hyaluronic acid with a complex viscosity between 1.3 – 2.3 Pa·s,

(3) Shall be able to run at least 3 independent assays simultaneously,

(4) Shall be configured with at least 3 chamber assemblies (60 mL or 300 mL), cartridge holder, LED light source and detectors, temperature probe, and pH electrodes for the cartridge and chamber,

a. Shall provide multiple selectable stirring speeds ranging from 100 rpm to 300 rpm,

b. LED wavelength shall be 504 nm or equivalent,

(5) Shall include at least 3 Cartridge Packs in total, which enough consumables for a total of 15 experimental runs. Each pack must minimally contain:

a. 5 x 5ml syringes of artificial ECM

b. 5 x 5ml cartridges

(6) Shall include automated sample fraction collector for unattended operation, with programmable sampling volumes from 50 µL to 1000 µL, programmable sampling times with minimum timeframe between samples of no more than 5 minutes, no less than 240 vial capacity, and media refill after sampling,

(7) Shall include integrated camera and turbidity sensors for effective detection of turbidity at 504 nm and assessment of precipitation or dissolution of particles in suspension,

(8) Shall include integrated fiber optic probe port for use with UV/Vis monitor to generate concentration profiles in real-time,

(9) Shall include integrated temperature and pH control system for the assay chamber,

(10) Shall be able to maintain physiologically relevant temperatures and buffer environments during assays,

a. Shall be able to measure pH withing +/- 0.05 pH accuracy in a range of no less than pH 4-10,

b. Shall be able to maintain physiological pH (pH 7.40) in bicarbonate buffer within +/- 0.1 pH units,

c. Shall be able to maintain chamber temperature at 34°C (typical); adjustable over 30 – 40°C

i. Stability +/- 1.0°C degrees over 24 hours

ii. Temperature equilibration time, < 1 hour

(11) Shall be able to monitor pH and temperature changes upon injection in the ECM,

(12) Shall include integrated camera assembly one per chamber, which allows photography at multiple timepoints,

(13) Camera image capture shall be no less than 2 images/minute,

(14) Shall include integrated sampling pump,

a. Pump flow rate: > 25 mL/minute,

b. Fluid transit time (chamber to sampling port): <30 seconds

(15) Shall include at least one flow through vial per chamber for aliquot collection and an external rack for manual sampling and electrode storage,

(16) Shall include an external fraction collector configurable with the system for automatic sampling,

(17) Shall include an external auto-injector for automatic injection,

(18) The following items shall be included for training and familiarization:

a. Three Training Packs (Each training pack comprises 1 x Caffeine standard solution, 1 x Bromophenol Blue Standard Solution, 6 x 1mL syringe with needle (25G 16x 0.5mm), 3 x cartridges and 3 x syringes of ECM). In total, allowing for up to 9 individual experiments,

b. Electrode Storage and pH buffer solutions (pH 4 and pH 10 standards),

c. Twenty-five Pipette tips for Auto-Injector

(19) The ECM cartridge shall withstand testing of a 0.5 mL organic solvent-containing formulation (including dimethylsulfoxide (DMSO) and N-methyl-2-pyrrolidone (NMP)) for 24 hours or longer.

2) Service Requirements

(1) The vendor must perform and document IQ/OQ including installation and testing.

(2) The vendor must include software / hardware familiarization and on-site training course at place of performance.

(3) Free unlimited technical support for the life of the instrument: phone AND internet.

(4) The instrument must be a newly manufactured unit, not used and refurbished or previously used for demonstration. CDER must be able to reasonable expect service and technical support from the vendor during its lifecycle.

(5) The entire system must be warranted for parts and labour for 12 months from the date of installation. The vendor shall provide a copy and pricing for any available extended warranties and service contracts. The vendor must also be capable of servicing the instrument through the extended warranty or service contract. This information shall not obligate CDER to purchase an extended warranty.

3) Optional service agreement For years 1-4 following warranty end, contractor shall provide service agreement including but not limited to preventative maintenance, corrective maintenance (repair) and software updates for purchased system with costs including all applicable certified original equipment manufacturer (OEM) parts, labor, and travel to be performed by licensed technical specialists.

DELIVERABLE TABLE

Deliverable Description Quantity/Media Date Completed

A biorelevant characterization system for subcutaneous injections as outlined in “Minimum Salient Requirements”

1 180 days after contract award.

2 Installation, instrument qualification and training 1 180 days after contract award.

3 Manufacturer's Warranty - 12 months.

Following equipment installation

4 Option Period 1, One-Year Post Warranty Service Agreement 1 Following warranty expiry

Deliverable Description Quantity/Media Date Completed

5 Option Period 2, One-Year Post Warranty Service Agreement 1 Following Option

Period 1

6 Option Period 3, One-Year Post Warranty Service Agreement 1 Following Option

Period 2

7 Option Period 4, One-Year Post Warranty Service Agreement 1 Following Option

Period 3

REPORTING REQUIREMENT AND DELIVERABLES

The contractor shall provide 30-day notice prior to shipping. All reports for installation and qualification shall be provided (electronic format preferred). Acceptance will be made by the government within 30 days following completion of instrument installation and qualification.

DELIVERY ADDRESS

The contractor shall be responsible for the delivery to the CDER location in St. Louis, MO.

FDA/CDER/OPQ/OPQR

645 S Newstead Ave., St. Louis, MO 63110

INSPECTION AND ACEPTANCE

Requirements for inspection and acceptance are as follows:

Partial acceptance is made upon delivery of all the parts. Full acceptance is made after completion of Installation and Operational Qualification (IQ/OQ) by the contractor that the system meets all the specifications and requirements.

The COR will inspect and accept the services/products provided to ensure they meet the requirements of the SOW. Inspection and acceptance will occur within thirty (30) business days of the deliverable.

The Government will:

• Provide written notification of acceptance or rejection within five (5) business days;

o Inspection will include testing of the deliverables to ensure that they perform adequately;

• Accept goods, reports, and services only if they conform to all terms and conditions of the SOW, and satisfy the performance standards developed under this SOW; and

• Reject non-conforming products and services.

The Contractor shall:

• Correct any deficiencies within five (5) business days of when the Government issues the rejection notice; and

• Immediately notify the COR of the reason for the delay and provide a proposed corrective action plan within three (3) business days if the Contractor cannot correct the deficiencies within this time frame.

PERIOD OF PERFORMANCE

This contract shall include a base year of 180 days for delivery/installation and 12 months of support from date of installation and four (4) twelve (12) month option years. The delivery of the entire system with accessories as outlined in the SOW should be completed within 180 days of award. Instrument installation and qualification should be completed within 180 days of award.

Instrument familiarization and training should be completed on the day of installation.

SECURITY

Supervision of install engineer upon arrival at DCDA will be required. All software required must be approved on FDA’s Master Approved Technology (MAT) list and comply with OIMT requirements. Software not already on the FDA MAT list may be considered but must be approved on MAT list prior to award.

CONTRACT TYPE

This will be a Firm Fixed Price (FFP) contract.

CONTRACTING OFFICERS AUTHORITY

The Contracting Officer (CO) is the only person with authority to act as agent of the Government under this contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in the RFP; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor any costs incurred during the performance of this contract; or (5) otherwise change any terms and conditions of this contract. No statement, whether oral or written, by anyone other than the Contracting Officer, shall be interpreted as modifying the terms and conditions of this award. It is the Contractor’s responsibility to contact the CO immediately if there is even the appearance of any technical direction that is or may be outside the scope of the award. The Government will not reimburse the Contractor for any work not authorized by the Contracting Officer, including work outside the scope of the award.

The Contracting Officer’s Representative (COR) is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the contract and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance.

ORDER OF PRECEDENCE

The Contractor shall follow the terms and conditions of this contract. Should the Contractor include any additional terms and conditions resulting in conflicts between this document and the Contractor’s document, the Order of Precedence shall be as specified in FAR Clause 52.212-4.

The Contractor shall not auto-renew any subscriptions, licenses, maintenances and services not authorized under this contract. Any auto-renewals are at the risk of the Contractor, and the Government will not reimburse the Contractor.

In the event of any inconsistencies between any licensing agreement incorporated into this order as an attachment and the FAR and HHSAR Clauses incorporated into this order, the FAR or HHSAR Clauses shall take precedence.

CONTRACT ADMINISTRATION

The points of contact for Contract administration are as follows:

Contract Specialist (CS):

Erika Crawford

Email: Erika.Crawford@fda.hhs.gov

Contracting Officer Representative (COR):

Changning Guo

Email: changning.guo@fda.hhs.gov

Contracting Officer (CO):

Maria Finan

Email: Maria.Finan@fda.hhs.gov mailto:Erika.Crawford@fda.hhs.gov mailto:changning.guo@fda.hhs.gov mailto:changning.guo@fda.hhs.gov mailto:Maria.Finan@fda.hhs.gov