Downstream Processing in Biopharma

Ensuring Yield, Safety, and Quality of Large Molecule Therapeutics

Call for Quote

Downstream Processing Techniques
<center>Fig. 1</center>
Fig. 1
<center>Fig. 2</center>
Fig. 2
<center>Fig. 3</center>
Fig. 3
<center>Fig. 4</center>
Fig. 4
<center>Fig. 5</center>
Fig. 5
<center>Fig. 6</center>
Fig. 6
flocculation application support

Additional Resources

On-Demand Webinars

Related Products

<center>Downstream Bioprocessing Workstation: Automated lab reactor and PAT equipment</center>
Downstream Bioprocessing Workstation: Automated lab reactor and PAT equipment

Citations and References

Adjuvant Downstream Processing

More Information


What are the steps associated with downstream processing?

Depending on the nature of the product and method of synthesis, downstream processing (DSP) generally includes a combination of the following steps:

  1. Harvest and Filtration
    Harvest is the first step to separate product from bulk debris while optimizing retention of the product yield and quality

  2. Primary Capture
    Capture refers to holding onto the desired product while minimizing retention of impurities and by-products. It differs from 'Harvest' in that essentially all bulk debris will have already been removed.

  3. Buffer Exchange and Up-concentration
    Ultrafiltration (UF) concentrates a dilute product stream and separates molecules in solution based on the membrane pore size or molecular weight cutoff. Diafiltration (DF) exchanges products from an existing buffer into a new buffer for a following process or a final formulation buffer. Ultrafiltration (UF) and diafiltration (DF) together are the steps of buffer exchange.

  4. Purification (and Contaminant or Impurity Clearance)
    Purification removes residual impurities with each successive method employed, while also retaining as much product as possible. The goal is to achieve product purity while minimizing potential yield loss.

  5. Bioconjugation (Molecule Dependent)
    Bioconjugate molecules are a new class or generation of biologic molecules which are designed to have an increased efficacy enabled by the combined function of two or more different therapeutic types of molecules. Antibody-Drug Conjugates (ADC) are one of the more common bioconjugates and are synthesized by biochemically modifying an antibody and covalently linking it to another active pharmaceutical ingredient (API).

  6. Formulation
    Formulation is the process that transitions a drug substance (DS) into a formulated drug product (DP). Formulation brings the product molecule from an environment, solvent or other physical state into a form suitable for clinical administration.

What is downstream processing in biotechnology?

Downstream processing refers to the recovery and purification of biosynthetic products, such as pharmaceuticals, from natural sources. Its aim is to meet purity and quality requirements by processing cell mass from the upstream phase. 

What is the purpose of downstream processing?

Downstream processing is a crucial step in the recovery and purification of biosynthetic products, particularly pharmaceuticals, from natural sources like animal or plant tissue, or fermentation broth. Its purpose is to recycle salvageable components and dispose of waste properly. The end result is a purified product that is fit for a specific use and can be manufactured in marketable quantities. Besides its use in producing pharmaceuticals, downstream operations can also be applied in medical and agricultural fields.

What are benefits of PAT for Downstream Processing (DSP)?

  • Identify factors contributing to bottlenecks and impurity formation during bioprocess development
  • Understand how process conditions impact product concentration and yield
  • Minimize inaccuracies and time delays arising from traditional, less efficient production and analysis techniques
  • Monitor specific operations such as purification, chromatography, buffer exchange, up-concentration and formulation
  • Use data mining methods to fully characterize the relationship between the various downstream processing steps and using this actionable information to optimize performance of continuous processes
  • Implement an integrated Quality by Design (QbD)/process analytical technology (PAT) strategy