Lot Release Testing for Biologics

Bulk harvest testing is a critical step in biologics manufacturing. It provides an opportunity to test samples for process-related contaminants before downstream purification. The specific tests performed at this stage depend on product and regulatory guidelines. 

Bulk harvest testing results may define which viral clearance studies should be undertaken and whether 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 can offer streamlined reporting of results and, when appropriate, suggest alternative assays that meet regulatory requirements in less time. 

The table below shows a representative testing package for bulk harvest, including standard and accelerated approaches.

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 support these requirements.

Identity testing 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 provide a comprehensive picture of the product-related impurities. Methods include:

• 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 (ELISA)

Potency testing involves a quantitative measurement of biological activity based on the attributes of the product, calibrated against a reference standard. Potency assays are customized 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

Analytical assay development, qualification, and validation are essential for ensuring high product quality and efficient market entry.

Qualification defines an assay’s performance limits and parameters based on its intended use, without fixed acceptance criteria. Assays may be qualified as GMP or non-GMP depending on the development phase and specific needs, with GMP qualification typically required for Phase 1 clinical batch release.

Key aspects of qualification:

• Focuses on performance capability rather than strict pass | fail acceptance criteria
• Establishes parameters that indicate whether an assay has worked as intended
• Can be aligned to GMP or non-GMP standards based on program phase

Validation is always performed under GMP and confirms that an assay consistently meets the criteria established during qualification. Every validation run must pass these criteria; if any run fails, the root cause must be investigated and resolved before the method is considered fully validated. 

Sartorius supports you by:

• Designing assay qualification and validation strategies tailored to your phase and regulatory needs
• Providing cGMP-qualified assays for clinical batch release
• Delivering fully validated assays for Phase III and final regulatory submissions