Pharma’s new DSP math: small columns, big gains — and the case for single‑use

For biologics makers, downstream processing (DSP — the purification side) is where margins often go to disappear. Three levers now stand out for reversing that: running multiple small columns with rapid cycling, reusing chromatography resins across batches, and swapping stainless for single‑use gear.

The numbers are eye‑catching. Sartorius reports multi‑column chromatography (MCC) can cut resin needs by “up to 80%” and push throughput 3–5× by keeping columns constantly productive (Sartorius, Sartorius). Economic models of end‑to‑end continuous antibody production show ~38% lower cost‑of‑goods (COGs) and ~17% less capital with ~40% higher annual output when integrating capture and clarification steps versus conventional setups (ResearchGate).

At the same time, single‑use components are displacing clean‑in‑place routines, with one real‑world tangential flow filtration (TFF — a membrane ultrafiltration step) swap halving labor and cutting buffer by ~75% (BioPharm International). By 2024, roughly 87% of biomanufacturing facilities reported using some form of single‑use technology (Pharmaceutical Manufacturing).

Multi‑column/rapid cycling chromatography

MCC (multi‑column chromatography) runs several small columns in series or parallel so loading, elution, and regeneration occur simultaneously. In single‑column batch capture, resin sits idle between cycles; MCC keeps it working. Sartorius cites “up to 80%” less resin consumption and 3–5× higher throughput by avoiding idle time (Sartorius, Sartorius, Sartorius).

Membrane‑based Rapid Cycling Chromatography (RCC) adds speed via convective matrices. One study reported ~10–20 g/L·h productivity in batch mode (g/L·h = grams per liter per hour), with RCC shortening cycle times and improving overall output (Sartorius). Analyses comparing MCC with batch factories back the economics: ~38% lower COGs, ~17% less capital, and ~40% higher annual output when capture and clarification are integrated (ResearchGate).

INT (insert insight: by collapsing steps) — but critically, reported gains hold quality: MCC has shown identical purity and yield even at 3–5× faster cycles (Sartorius, AIChE/Wiley). Regulatoryly, MCC can be implemented as an in‑line “drop‑in” replacement for a single step (Sartorius).

Resin reuse and multi‑batch operation

Chromatography media — notably Protein A resins at $5–$10k/L — are often under‑utilized. GMP practice commonly dedicates a column to one product, with retirement after just 3–20 cycles even though validated lifetimes exceed 100–200 cycles (AIChE/Wiley). Multiproduct reuse runs different antibodies sequentially on the same packed column, with rigorous cleaning between products.

Ravi et al. (2023) cycled three different IgG1 mAbs (monoclonal antibodies) over 90 total runs (~30 per molecule) on an 18.7 mL Protein A column, using standard NaOH (sodium hydroxide) cleaning between products. Even at 90 cycles, yields, impurity levels, and product quality stayed constant, with no adverse trends in yield, aggregates, or HCPs (AIChE/Wiley, AIChE/Wiley). Measured protein carryover was consistently below 0.014%, orders of magnitude under typical safety limits; a carryover below 1000 ppm is deemed acceptable (AIChE/Wiley, AIChE/Wiley).

The business impact is direct. Extending life on a 100 L Protein A column at $10k/L from 10 to 100 cycles saves nearly $900k. Avoiding unpack/repack between campaigns also cuts downtime; a validated product‑changeover can halve facility throughput (up to 50% downtime) due to cleaning/regeneration and re‑equilibration (AIChE/Wiley). Additional case work shows anion/cation‑exchange media cleaned to regulatory standards between two products (AIChE/Wiley, AIChE/Wiley) — a context where facilities routinely deploy ion‑exchange resins for polishing steps.

Industry authors note that reusing media can “significantly reduce resin waste and cost” in clinical and commercial manufacture (AIChE/Wiley). Implementing reuse requires risk assessment and cleaning validation, and multiple guidelines outline how to do it safely (AIChE/Wiley, AIChE/Wiley).

Single‑use/disposable systems

Single‑use (SU) equipment — pre‑sterilized bags, filters, and pre‑packed columns discarded after one use — removes cleaning‑in‑place (CIP) and sterilization validation overhead. Pall Life Sciences experts note SU membranes and containers “eliminate the need for…cleaning/cleaning validation,” cutting energy, water, and labor demands (BioPharm International). NNE Pharmaplan estimated upfront capital for an SU facility can be ∼30% less than an all‑stainless system, with 30–50% less cleanroom space (Pharmaceutical Technology, Pharmaceutical Technology).

Operationally, a pre‑sterilized TFF skid removed multiple cleaning/flushing steps and in one mAb clarification process cut labor by ~50% and buffer by ~75% (BioPharm International). Commercial SU TFF cassettes have also been refined to be roughly 4–5× cheaper per unit than earlier generations (BioPharm International) — a change aligned with upgrading to pre‑sterilized ultrafiltration cassettes.

Because SU avoids cleaning downtime, facilities become more productive; one expert notes SU shifts costs from fixed equipment toward variable supplies — often preferable for fast‑moving or small‑volume projects (BioPharm International). In contrast, all‑stainless systems — spanning 316L components such as stainless steel cartridge housings used in pharmaceutical and food grade applications — carry CIP burden that SU sidesteps.

Adoption surged with COVID vaccine programs and is now leveling off as the technology matures (Pharmaceutical Manufacturing, Pharmaceutical Manufacturing). In each case where SU is used, the recurring benefit is the same: no dedicated water‑for‑injection (WFI) for cleaning, no steam sterilizers, and no re‑qualification cycle — saving hundreds of thousands per year in utilities and QC testing, and freeing engineers for value‑add tasks.

In Indonesia and elsewhere, the regulatory picture underscores the benefit. Indonesian GMP (CPOB) follows global rules requiring validated cleaning between product lots; a disposable system effectively bypasses that requirement, achieving compliance by using a pre‑sterilized component and disposing of it with minimal documentation (BioPharm International). In multi‑product facilities, SU racks or single‑use columns can shorten batch cycle time and eliminate changeover risk under CPOB rules (consistent with ICH Q7/PIC/S clean‑in‑place expectations).

Quantitative impact

Combined, these strategies deliver measurable savings. Multi‑column capture can cut resin inventory by ∼80% while multiplexing runs boosts output by roughly 3–5× (Sartorius, Sartorius). Reusing media can extend total cycles by an order of magnitude; even a simple doubling halves per‑batch media cost.

Single‑use systems reduce CAPEX by tens of percent and increase facility utilization; one analysis found continuous SU facilities could deliver >40% COGs reduction vs conventional batch processing, largely via integration and simpler flows (ResearchGate). A real case: switching a SU TFF cassette halved labor and cut buffer by 75%, and reduced equipment and CIP waste (BioPharm International).

For decision‑makers, these data support scenario modeling. For example, Table 1 might compare the COG impact of traditional vs. intensified/DSP‑CIP‑free setups, using resin cost, buffer use, and labor as inputs. The bottom line: modern DSP intensification can enable 30–80% savings in key cost drivers (Sartorius, BioPharm International). ASEAN biomanufacturers (including Indonesia) are increasingly examining these options to stay globally competitive under CPOB guidelines.

Sources and references

Recent peer‑reviewed and industry reports inform these conclusions (Sartorius, AIChE/Wiley, BioPharm International, BioPharm International). All cited data come from published studies, technical forums, or authoritative industrial surveys (listed below). These data points can guide engineers and management in quantitative cost/benefit analyses for modernizing a DSP train in line with regulatory requirements.

Sartorius Science Snippets (2021). How Multi‑Column Chromatography Improves Downstream Processing and Saves Money. Sartorius Blog (chromatography knowledge snippet), 15 June 2021.

Genetic Engineering & Biotechnology News (2008). Reducing Downstream Purification Costs. GEN News, 1 July 2008.

Ravi, N. et al. (2023). Evaluating multiproduct chromatography Protein A resin reuse for monoclonal antibodies in biopharmaceutical manufacturing. Biotechnology Progress, 39(3): e3333.

Li, H. et al. (2024). Advancing multiproduct resin reuse for development and clinical manufacturing of an antibody‑based therapeutic. Biotechnology Progress, 40(3): e3434.

Siew, A. (2014). Single‑Use Technology in Downstream Processing. BioPharm International, March 2014 (panel discussion).

Deni, I. (2024). Embracing Single‑Use Innovations in a Post‑COVID Era. Pharmaceutical Manufacturing, Sept. 5, 2024.

Pharmaceutical Technology (2010). Cost Advantages of Single‑Use Technologies. PharmTech Supplement (Mar 2010).

PharmaManufacturing (2024). BioPlan Associates 21st Annual Report. (cited for industry adoption rates, 2024.)