Lot Release Testing

When it comes to ensuring a biologic is ready for market launch, one of the greatest challenges a drug manufacturer faces is gathering and reporting the appropriate data to the relevant regulatory bodies.  The selection, qualification and validation of appropriate lot release methods  form a critical part of this required data, reflecting what developers have deemed important to the manufacturing of their product.

During the drug manufacturing process, bulk harvest samples are taken from the end of the production process, prior to downstream activities, to assess the safety profile by thoroughly testing for the detection of any contaminants of the production process.

Once contamination has been ruled out, further processing to generate the drug substance and final drug product can continue. Release testing at these final stages is a regulatory requirement for all marketed products to confirm the identity, purity and potency of the drug substance and final drug product.

Support for Your Program, From Preclinical to Commercial Phase

Sartorius’ unique set of integrated services allows us to support your biologic development program from cell line development to commercial batch release.  We have developed a suite of early-phase characterization assays to anticipate any future qualification and validation needs in mind. This is how we future-proof your analytical development to avoid costly delays at a later phase. We can advise on the suitability of a method for lot release and perform phase appropriate GMP qualification and validation. Combined with our comprehensive, fully compliant biosafety assay portfolio, Sartorius helps generate the data needed to establish specifications and support the efficient release of product.


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Bulk Harvest Testing is a critical step in the manufacture of biologics. It is the ideal time to test samples for process-related contaminants before downstream purification. The specific tests that take place at this stage depend on product and regulatory guidelines, but the standard required testing for bulk harvest includes:

  • Sterility testing 

  • Mycoplasma testing 

  • In vivo assays 

  • In vitro assays 

  • Retrovirus assays 

  • Bovine and porcine assays 

  • Electron microscopy 

  • Species-specific assays 

The results of the bulk harvest testing may define what viral clearance studies should be undertaken and if additional testing should be carried out on the drug substance.

Fast turnaround is critical, as production is essentially on hold until these tests show the  batch is contamination free.

To support expedited testing, Sartorius offers methods for streamlined reporting of results and, when appropriate, can suggest alternative assays that meet all regulatory requirements in less time. In many cases, Sartorius can deliver bulk harvest test results within 16 days of receiving samples instead of the industry standard 8 to 9 weeks.

Drug substance (unformulated active ingredient) and drug product (formulated drug) need to undergo testing to confirm the identity, purity and potency of the product. Sartorius offers a broad array of analytical testing methods to establish identity, purity and potency:

Testing for the identity depends on the nature of the product, but can include specific PCR tests, sequencing analysis, SDS-PAGE, and restriction enzyme analysis: 

  • Intact mass (deglycosylated) 

  • N-terminal sequencing 

  • Peptide mapping 

Purity and impurity tests confirm the absence of product- and process-related impurities. Orthogonal methods should be used where possible to give an extensive picture of the product-related impurities, including: 

  • CE-SDS 

  • SEC 

  • cIEF

  • IEX 

Process related impurities should be minimized through well-controlled manufacturing processes and monitored through a series of tests including: 

  • Residual host cell protein ELISA 

  • Residual host cell DNA PCR 

  • Residual impurities ELISAs 

Potency testing involves a quantitative measurement of biological activity based on the attribute of the product, calibrated against  a reference standard.  Potency assays are custom for the product by their nature and should address the mechanism(s) of action of the product. Assay types include: 

  • Neutralization 

  • Proliferation 

  • Apoptosis/cell death 

  • Production of mediators and more 

Where possible a cell-based bioassay should be employed to determine batch potency, however, with appropriate supporting data, it is possible to use an ELISA or SPR based assay. 
Sartorius also offers the following tests designed to fully characterize the final drug product:  

  • Sterility testing 

  • Appearance 

  • pH 

  • Osmolality 

  • Titer determination for viral- based products 

  • Endotoxin 

  • Extractable volume

The development, qualification and validation of analytical assays is fundamental to producing the highest quality products and bringing them to market efficiently.

Qualification studies are used to understand the limits of an assay, establishing parameters that indicate whether an assay has worked. There are no pre-determined acceptance criteria, just performance capability requirements based on the intended application.  Assays can be qualified to GMP or non-GMP based on your phase and needs. A GMP qualification is usually required for phase 1 clinical batch release. 

Validation of an assay is always GMP, and it demonstrates that the performance of the assay consistently meets the criteria and parameters established through qualification. Every validation run must meet the criteria to pass. If any run fails, root cause for the failure must be investigated and resolved before the method can be considered fully validated.

Sartorius understands the complexities related to qualifying and validating analytical methods and we will tailor your study to meet the appropriate regulatory guidelines and phase of your development. This includes cGMP-qualified assays required for clinical batch release or fully validated assays required during Phase III and final regulatory submission.

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