Applying Quality by Design to the manufacture of drug product for biopharmaceuticals

QBD is a term that is often spoken with respect to the production of biopharmaceuticals.  However, despite the issuance of guidance documents on this topic, it is still relatively poorly understood. 

This discussion seeks to demystify the concept of quality by design as it applies to fill/finish of drug product.  This serves also as a reminder that not all drug products are the same in the world of biotherapeutics. 

Critical Quality Attributes are dependent not just on the chemical and basic biophysical properties of the product, but also on higher order structural elements.  The right instruments must be applied at all stages of drug product development to minimize the probability of unwanted visible and subvisible particles in product that will ultimately be injected into patients. These stages include formulation development, selection of primary containers for drug product, and the evaluation of drug product filling equipment option (pumping studies).

The combination of orthogonal methods, such as Nanoparticle Tracking Analysis (Nanosight) in conjunction with Resonant Mass Measurement (Archimedes) provides an opportunity to both enumerate and understand the structure and types of subvisible particles present in drug product solution that may be formed during the different stages of production. This knowledge enables the development of an effective control strategy to support patient safety.