Quality by design and process analytical technology for sterile products--where are we now?

Quality by design (QbD) and process analytical technology (PAT) have become priorities for the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA). Numerous recent initiatives within CDER and FDA have had the objective of encouraging the pharmaceutical industry to utilize QbD and PAT in their product development and manufacturing processes. Although sterile products may be a minority compared to non-sterile dosage forms (e.g., solid orals), their absolute requirement for sterility make design and control of the manufacturing processes extremely critical. This emphasis on the manufacturing process makes the sterile drug product an obvious target for QbD and PAT. Although the FDA encourages QbD submissions, the utilization of QbD and PAT for sterile products so far is still limited. This paper will examine the present state of QbD and PAT for sterile products and review some examples currently in use. Additional potential applications of QbD and PAT for sterile product development and manufacturing will also be discussed.