During these various phases, cell line selections, cell culture processing, harvesting, and purification are all studied and
optimized. GMP regulations require that these processes be validated. Therefore, assays must be developed and large amounts
of data must be collected on critical parameters such as purity, contamination, degradation, etc.
Cleaning validations may also be carried out on equipment, surfaces, etc., to check for residual detergents, product, or microorganisms.
In many cases, a simple, nonspecific assay such as total organic carbon (TOC) can be used. However, in other situations, specific
analyses (one that can determine the concentration of a specific chemical) are performed using HPLC. Moreover, an increasing
number of applications that use single-use or disposables, such as filters, tubing, and bags for biopharmaceuticals can introduce
unwanted extractables into the final product. The qualification and quality control of all components coming into contact
with the drug formulation has become an integral part of any FDA application process.
Process validation is a legal requirement in the industry to demonstrate through appropriate testing and documentation that
the finished biopharmaceutical produced by a specified process meets all release requirements for quality. Successful process
validation requires thorough process development, identification of controlled and critical parameters, and establishment
of specifications throughout the process. A minimum of three consecutive lots of product meeting the established quality specifications
is necessary to validate a process. Many of the tests described here are used during process validation. These validations
may entail collection and testing of large volumes of samples.
Stability and Release
Once the drug is approved there will be ongoing testing to support stability and release of the product. This typically covers
critical parameters such as characterization, identity, concentration, purity, excipient testing, potency, sterility, and
safety. An example of a specific testing matrix is shown in Table 4.
Table 4. Ongoing stability and release tests like these are conducted after drug approval.
In conclusion, an enormous amount of analytical testing is required to support a biopharmaceutical product throughout its
lifecycle, from discovery and early development through stability and release testing. Due to their complexity, an extensive
number of methods are required to fully characterize them. Many biopharmaceutical organizations may need to consider outsourcing
portions of their analytical testing to remain competitive.
Jon S. Kauffman, PhD, is the director of Method Development and Validation and Biopharmaceutical Services at Lancaster Laboratories, Lancaster,
PA, 717.656.2300, firstname.lastname@example.org