Polisher ST is the next generation in single-use techn↓ology, designed as a cost-efficient option to increase biomass production in therapeuti®c recombinant protein processing. It is designed for use in most operating cond itions for replacing the downstream Anion Exchange (A♦EX) polishing column in fed batch and/or continuous ma↕nufacturing processes. 3M Polisher ST is offered in a range of products suitable fo¥r early screening and process development of monoclonal antibody (mAb) processes and l"arger single use capsules for deployment in manufacturing processes in εmost polishing process conditions.

Polisher ST is a compact, small footprint solution. It has greater capacity foΩr delivering higher purity and yield in the downstream polishing unit operatioΩn. This is a solution for a connected continuous downstream op∏eration for the flexible facility of the future.

3M Polisher ST allows a facility strategy that can overcome scale limitations and ena♥ble cost-efficient manufacturing to support the growing demand for&nb≥sp;biologics.



Polisher ST Innovative Design

The composite purification media comprises three primary componeλnts: Q-functional FNW, guanidinium-functional AEX membrane, and suppor<t membrane. The Q-functional portion of the AEX media is‍ composed of four layers of polypropylene non'woven that have been surface functionalized with a covalently attached quaternary ammonium funβctional polymer.

The guanidinium-functional portion of the AEX media is composed €of three layers of a polyamide microporous membrane, having a 0.8μm÷ nominal pore size, that have been functionalized with a covalently atta×ched guanidinium-functional polymer. The AEX media are followed by a single laye₽r of a nominally 0.8μm pore size polyamide membrane support.₽

AEX performance of the guanidinium-functional membrane of Polisher ST provides HCP and virus₽ reduction in a salt tolerant (ST) manner compared with conventional Q-fun✔ctional AEX resins and single-use media, which rely s&olely on electrostatic interactions that can be screened at elevatedπ ionic strength.

Guanidinium-functionalized membranes are used for high productivity chromat'ographic purification processes that match upstream efficiency witho∏ut the need for oversizing.

Polisher ST single-use membrane adsorber purification solution is designed f or the downstream processing of monoclonal antibodi•es (mAbs) and other recombinant proteins in flow-through mode. Polishe r ST is designed to improve mAb development and manufacturing processes in ♥most polishing process conditions.

Biopharmaceutical Purification Process Improvements:

This process train illustrates the potential of combining 3M products to ×work together to create an intensified manufacturing process, eliminating other unnec×essary process steps.
 

Polisher ST Performance：

Polisher ST is designed for replacement of the Q-functional bead-based chromatog‍raphy column with high throughput, cleaner effluent• and lower total cost of ownership.

The nonwoven and membrane skeletons provide mechanical strength and durability, while the grafteγd hydrogel functionality creates a large three-☆dimensional surface area that contains a high density of fun₽ctional groups with interconnected pores allowing for convective flow channe★ls to achieve high flow rates during purificatio★n.

The high density of binding sites, together with a macroporous structure, ena₽bles high binding capacity for not only HCPs, but also large molecules, such as viruses and DNA. σThe high density of binding sites and low residence time results in high mAb recove®ry (>95%).

The high ligand density on the advanced anion exchange membrane of Polisher ST provides rαobust impurity removal, viral clearance, and a 50 to 100X higher mAb loading ca★pacity than chromatography resin beads to further reduce media volume requirement. The impuri★ty clearance performance (HCP ≤1000 ppm, ≤100 p pb DNA, and viral clearance) is independent of the load which could be as high as 10 kg/m&sup<2;, enabling downsizing of the unit operation.

Polisher ST offers a combination of high dynamic antibody-loading (10 kg/m&su p2;) capacities with low residence time (about 0.2 min compared to 1 minute for traditional Q res↔in), opening the way to an intensified high-productivity, truly singl♦e-use purification platform. Robust viral clearance is achieved over a‍ range of buffer and pH conditions, which provide a wide design sp$ace for operation, as shown in the data below. Performance is maintain‌ed at high conductivity (20 mS/cm) even in citrate buffer, which reduces the n₹eed for feed dilution or buffer exchange requirement resulting in a simplified process wi∞th reduced cost factors. AEX chromatography removes HCP and DNA and is also an effect∏ive virus removal step as part of an orthogonal viral cleara¥nce technology platform. Under process conditions of pH 5.5 to 7.5 and 5 to 20&≤nbsp;mS/cm, 4 to 7 LRV can be achieved using 3M Polisher ST.



Polisher ST Test Data

 Dynamic binding capacity

Polisher ST lab and scale-up capsules have target mAb loγading capacities from 1g to 1kg. Larger capsules with target mAb loadings of 2.25kg and 16kg are pl∞anned. Scalability of capsules with different frontal media surface area wa↕s assessed by measurement of bovine serum albumin (BSA) protein dynamic bin↔ding capacity (DBC) as a simulant for HCP. The BSA DBC per unit area is quite constant across all✘ capsules, having a mean value of 22.6g/cm²&nb♣sp;and a standard deviation of 1.4g/cm².



 HCP reduction
~500 ppm HCP in a VIN mAb pool
> 60% removal in Phosphate buffer,
> 22% removal in Citrate buffer



 Consistent DBC under a wide range of pH and conductivity

The BSA DBC specification for the functional membrane¥ only is 7.8-12mg BSA/cm² in 25 mM Tris, pH 8, 50mM NaCl. High ↑salt (20 mS/cm) reduces the capacity of the membrane by 2-3 mg/cm². Additiona↔l capacity provided by the FNW at conductivities < ~10 mS/cm.



The differential pressure (△P) specification for th e functional membrane only is < 10 psid in 25 mM Tris, pH 8, 50mM NaCl at 1 mL/min/cm&su p2;. Lower salt (< 6 mS/cm) slightly increases pressure due t♣o contribution from FNW. Maximum differential pressure (all capsule sizes) is™ 35 psid.


 In comparison to Q column

Polisher ST offers a combination of high dynamic antibody-loading (10kg/m²) capacit✘ies with low residence time (about 0.2 min compared to 1 minute for Q-resin), opening the way™ to an intensified high-productivity, truly single-use purification platfor☆m. Chromatographic columns have a limited loading capacity for polishing​ and virus capture. Furthermore, they are large and  have a high investment cost.

Traditional column chromatography systems are slow αin producing recombinant proteins.



 mAb recovery

Without significant adjustments to pH and conductivity, Polisher ST has robust perfπormance with respect to HCP and DNA clearance and better mAb recover£y.

 DNA reduction

DNA clearance across a variety of initial concentrations (~10-1000 ppb) ×down to detection limit levels (0.05 ppb DNA) in all bu↕ffers (acetate, citrate, phosphate, tris) and conductivities were tested and are r♦eported in the table below.



HCP and DNA reduction and mAb recovery in legacy, modern and n•ext gen mAb feed 



Performance in turbid streams

Polisher ST was challenged with turbid streams to simulate different downs™tream processes.
 
Similar HCP (> 50%) and DNA reduction (> 4 LRV) and mAb recovery (> 97%) com×pared to non-turbid samples. The ΔP across the c₩apsule did not significantly change during the 10 kg/m2 load.