SOW_060724.pdf

Statement of Work (SOW) – Tangential Flow Filtration Unit

Part I: General Information

A. Introduction This SOW details the procurement of a Tangential Flow Filtration Unit (TFF) to be used jointly between the Sung and Marklein Labs in the Cellular and Tissue Therapies Branch (CTTB). The Sung lab acquired two KR1 pumps from Repligen in FY23, and now requires a compatible base TFF system that will complement the existing pumps in the lab.

B. Background The Marklein and Sung laboratories in DCT1/OCTHT devote significant research effort to investigating the effects of manufacturing on cell-derived extracellular vesicle (EV) quality. EVs are collected from the conditioned medium of cultured cells and considerable downstream processing is necessary to purify and concentrate EVs for further characterization. Currently, our labs use ultracentrifugation, but this approach is very low throughput, takes a considerable amount of time, and is very difficult to standardize. To improve our ability to manufacture EVs at larger scales (more relevant to industry sponsors), we are proposing acquisition of a TFF unit.

TFFs ability to use tangential flow significantly increases the scale of our EV production (from 100’s of mLs to several liters) while also being significantly faster than ultracentrifugation. In terms of purity, TFF minimizes membrane fouling that is a major challenge with other ultrafiltration approaches for EV collection. The TFF is a widely used piece of equipment for large scale EV manufacturing and therefore using this approach will allow us to better understand the critical aspects of manufacturing relevant to the products we regulate. Finally, manufacturing larger batches of more consistent EVs will enable us to make strides in standardization as the same single batch of EV can be stored and used by multiple labs both within our branch, as well as with external collaborators. Having large quantities of EVs will enable comprehensive profiling of the EV cargo/identity and the therapeutic potential in our labs’ already well-established bioactivity assays. Our TFF unit could also be readily used by other CBER researchers outside our division that may have needs to purify and concentrate large quantities of sub-micron particles (e.g. bacteria derived vesicles, viruses, etc.)

C. Scope To obtain a Tangential Flow Filtration Unit that meets all specified technical requirements at the lowest possible price.

Part II: Work Requirements

A. Technical Requirements for TFF unit

Must be compatible with two KR1 pumps from Repligen

1. Shall have a capacity as low as 25 mL and as high as 15 L.2.

2. Shall allow for interchangeable filters that enable different cell-types and allow for media preparations that's used without cross-contamination.

3. The settings shall be automated and programmable with a integrated

LCD touchscreen monitor.

4. The system shall have large scale capabilities 100+ L with the possibility for a larger scale in future.

B. Deliverables

0001 One KR2i Tangential Flow Filtration Unit with scale.

0002 One Factory Warranty +1yr extended warranty 0003 One Install, Test, & Basic User Traning

Part III: Supporting Information

Part IV: Evaluation Criteria

Ability to meet all technical criteria Price

Market Research

- KR2I TFF system – KF COMM 2- with scale ($33,913.00)

- This TFF system is the only one available in the market that is compatible with existing pump systems.

A. Security Point of contact is Kyung Sung (240-402-7994) kyung.sung@fda.hhs.gov

B. Place of Performance Shall be delivered to:

10903 New Hampshire Ave WO 52/72, Room 3240 Silver Spring, MD 20993 Kyung Sung Phone: (240) 402-7994

C. Period of Performance 9/29/2024 - 9/28/2025

D. Special Considerations None.