Why have Potency Lot Release Testing?

The US FDA requires that licensed products pass critical analysis before release by the manufacturer for clinical use. These include potency, sterility, purity and identity. Potency is used to ensure consistency and efficacy in the manufacturer’s product used for stability and lot release.

The goal for the potency assay is to represent the mechanism of action for the intended therapeutic activity. However, many new therapies use different modalities of activity (e.g. gene therapy requires transfer of genetic sequence into a cell and biological effect of this sequence). The traditional approach is to develop a quantitative biological assay (e.g. cell based/bioassay) that measures the specific intended activity with regards to the amount of drug. A surrogate assay (e.g. ELISA binding assay) can be used only if the measurement and biological activity is well established.

In summary, potency assays will allow for product characterization and understanding of what affects the quality, potency, lot to lot consistency and stability over time. These assays should be initiated early during the development and pre-clinical stages in order to establish a baseline knowledge of the drug.

Marin Bio has developed hundreds of potency assays over the past 25 years and can assist you in the identifying an appropriate assay specific for your drug. Some of the assays we developed have been for small molecules, antibodies, bispecific constructs, Fab products, antibody-drug conjugates, DNA and RNA, antisense moieties, recombinant proteins and stem cells. Let our scientist guide you to find the appropriate potency assay.

What Methods Can be Used to Measure Potency?

The bioassay or cell-based assay is the traditional approach whereupon the targeted mechanism of action is employed in the assay readout (e.g. synthesis of a cytokine or cell death or proliferation). The assay should be specific so that it is not affected by degraded drug, or inactive ingredients (e.g. matrix). At clinical Phase III and BLA / NDA stage, linearity, robustness (including at least two operators), and documentation of acceptable range of critical parameters and parallelism showing qualitative equivalence of the test sample and Standard, are required.

Early phase studies, Phase 1 or 2, the assay criteria will have wider acceptance criteria than later phase investigations. In Phase 3, pivotal studies, the acceptance criteria will be narrower to support efficacy and assure lot-to-lot drug preparations are biologically active and consistently manufactured.

Development and Validation of Potency Assays

The strategy for development of Potency Assays is to ensure that the assay will be accurate and robust through validation and reproducible in subsequent use. Potency of a new lot of drug is determined by Relative Potency (RP), comparing the new lot to a Reference Standard also titrated in the same assay.

The MarinBio supporting technology for these areas are:

Issues to be investigated:

  • Precision (Repeatability, Intermediate Precision), each assay must be shown to give a precise RP with a small 95% confidence interval
  • Accuracy, the method must be shown to measure a lot accurately, target within 10% at the BLA stage
  • Specificity, not affected by interference, (e.g. drug incipient, drug degradants, or other drugs in the manufacturing pipeline) should have negligible response
  • Linearity Range, and Accurate Concentrations, the method should be shown to have a linear dose response (e.g. 70% to 130% of the nominal 100% value)
  • Stability indicating, the method should be able to distinguish purposefully degraded material
  • Parallelism, a new lot should have a dose response curve that parallels the Reference Standard, to demonstrate that it is quantitatively the same as the Reference Standard
  • System Suitability, from the above criteria, a set of system suitability criteria are developed to demonstrate that the assay passes
  • Robustness, from the above criteria, the assay should be reproducible from operator to operator, laboratory to laboratory, time to time

Marin Bio has validated many different kinds of Potency Assays which are used for drug release and stability studies over many years. Let our scientists help you with your Potency Assay design, development, qualification/validation and implementation throughout your drug’s life cycle.

QUICK READS

From the beginning and ongoing, your assay is a critical component of the life cycle of your current or eventual product. That is precisely why you want experience and expertise at the earliest possible stage of your development.

When you require an assay to prove your science and there is no commercial kit available, you need a custom assay. MarinBio’s extensive expertise enables rapid and methodical development of your assay for eventual validation. Typically, a custom assay can be developed from the inception to a completed bioassay in 5 or less experiments, while minimizing any effects of the matrix.

MarinBio expert at preparing and validating GMP/GLP or research level cell banks. The banks could include primary cells or cell lines for specific bioassays, as well as cell bank uses for production, isolation and characterization of genetically defined clonal cell populations and small-scale manufacturing of biologic products.

MarinBio professionals have vast experience with improving cell culture growth, freezing, serum-free culture, cloning for client bioassays, as well as transfection with DNA or RNA and/or liposomes (lipofection) for genetically variant cell lines as well as for gene or protein expression bioassays.

Our scientists have developed over 200 custom bioassays involving growth, toxicity, transfection, cell surface, cytokine or gene expression. We are your scientists; MarinBio will make your GMP potency lot release assay or drug screening assay.

Many companies planning an IND submission or in Phase I/II may only require a well-qualified assay, rather than a fully validated assay. You may or may not need GLP/GMP stringency and auditability. The expert MarinBio scientific team works with your scientists to qualify your assay for reproducibility, appropriate precision and accuracy, with validation in mind for the future.

To validate an assay, the precision, linearity, accuracy, robustness, system suitability and repeatability is measured to meet acceptance criteria. We in-source your assay or fully develop and validate an assay to meet the FDA GLP or GMP requirements.

When patient samples or drug product samples need analysis, MarinBio will map out a timeline and follow through with sample receipts, meeting your regulatory needs at all points. We perform your assay as a developed, qualified or validated bioassay, and promptly communicate the results and/or provide a Certificate of Testing for any or all of your pre-clinical or clinical phases.

Knowing the importance to the FDA of lot release potency testing data, our professional scientific team tests every manufactured lot with your assay and provides Certificates of Testing.

In order to determine shelf-life for a particular drug substance, stability tests are performed at pre-determined calendar intervals. MarinBio’s expert project coordinators communicate closely with you to anticipate the arrival of samples in order to be prepared for timely analysis and the submittal of data and Certificates of Testing.

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