Brewing Up Quality and Compliance in Biopharmaceuticals

At first glance, the production of protein-based drugs resembles the brewing of beer. Performed in computer-controlled vats, it's a tricky fermentation process that uses living organisms to transform various inputs into products consumed by humans. As a biological process, it's also susceptible to impurities. In beer, impurities can merely ruin the flavor and aroma of the brew. In protein-based drugs, however, impurities can be life threatening if they decrease drug efficacy or cause adverse immune reactions in patients.

Minimizing the potential for adverse reactions is one reason for the strict regulation of biopharmaceuticals, especially during clinical trials and in volume production, where product quality is monitored very closely. Maintaining regulatory compliance and achieving high quality provides important safeguards for consumers. Of course, biopharmaceutical companies bear the costs and complications, and their lab and production personnel must handle the additional work. However, automated analytical tools that perform standardized, repeatable protein analysis can reduce the workload while also improving quality and supporting compliance.

Enhancing protein analysis

In the parallel pursuit of quality and compliance for protein-based drugs (e.g., antibodies), lab and production personnel rely on four essential procedures:

• Protein identification to detect unwanted proteins that may cause side effects or be ineffective
• Protein quantitation to characterize production yields
• Purity monitoring to ensure drug tolerance and efficacy
• Stability testing to define appropriate storage conditions and shelf life

To achieve compliance, all of these procedures must be standardized and reproducible. They should also meet good laboratory practice (GLP), good manufacturing practice (GMP) and 21 CFR Part 11 requirements.

Although protein analysis methods are advancing quickly, many researchers still rely on traditional approaches such as denaturing gel electrophoresis. Also called SDS-PAGE, this method has changed very little since the 1970s. It is very labor intensive, time consuming and difficult to standardize—a major problem in compliance and quality control (QC) applications, which require thorough documentation.

One emerging alternative is automated protein analysis on a microfluidic chip. This approach integrates several experimental procedures into a single workflow: sample handling, separation, staining and destaining, and data analysis. When compared to SDS-PAGE, the chip-based method delivers equal sizing accuracy and precision, better quantitation, and much better reproducibility.

Examining a new solution

Agilent's microfluidic solution for protein analysis is based on three key products: the Agilent 2100 bioanalyzer, the Protein 200 Plus LabChip^® kit and the Protein 50 LabChip kit. This powerful solution unites fast, standardized methods with automated and detailed data analysis. It can analyze 10 protein samples in less than 30 minutes, and can handle proteins from 5 to 200kDa with resolution of 10% or better throughout the size range. In addition, the system software conforms to GLP and GMP requirements and will soon have a security pack that provides the features required to support full 21 CFR Part 11 compliance. Agilent also addresses the needs of quality control labs by offering installation qualification (IQ) and operational qualification (OQ) services.

The Agilent 2100 bioanalyzer unites fast, standardized methods with automated data analysis

The application note "Quality control of antibodies using the 2100 bioanalyzer and the Protein 200 Plus assay" describes use of the system to evaluate stress-stability tests of two different antibodies. In the examples, standard and stress-test samples were analyzed under reducing conditions on the Agilent 2100 bioanalyzer using a Protein 200 Plus LabChip kit and the dedicated Protein 200 Plus software assay.

Gaining an advantage

The Agilent solution performs data analysis automatically and in real time. To facilitate documentation, it stores and archives results in digital form. What's more, all reagents and microfluidic chips are standardized and are shipped with declarations of conformity.

In the delicate—and tightly regulated—production of biopharmaceuticals, companies need every advantage. Achieving and maintaining compliance can prevent regulatory failures that may result in large fines and costly delays in product launches or shipments. Achieving high quality can maximize production yields and prevent shortages of high-demand medications. Most important of all, high quality also minimizes the risk of impurities and maximizes drug tolerance and efficacy.

For more information

To learn more about our wide range of solutions, please see the Drug Manufacturing/QA/QC and Protein Solutions pages, or sign up for an E-seminar. For additional information about these and other Agilent life sciences products and resources, please visit the Life Sciences/Chemical Analysis main page.

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