Scale-Up → Elements of Scale-Up

A contract manufacturing organization (CMO) will often work with the pharmaceutical company in the scale-up process. CMOs are hired by companies in the pharmaceutical industry on a contract basis to provide comprehensive drug services such as formulation development, method development, scale-up, etc. CMOs take on aspects of the business involved with scalability, so that pharmaceutical companies can focus on drug discovery and marketing.

Before scale-up, the product profile and critical quality attributes (CQA) of the drug must be defined. CQA are the physical, chemical, biological, and microbiological attributes of a drug that must be monitored for appropriate range, limit, or distribution throughout the scale-up process to ensure desired product quality. Regulatory CQAs include composition and strength (pH, excipients, concentration, osmolarity), or adventitious agents (viruses, endotoxin, mycoplasma). CQAs should be identified based on severity of harm to a patient resulting from failure to meet that quality attribute.

Once CQAs are well defined, the appropriate manufacturing process can be designed. If a pharmaceutical company decides to change components of drug composition, the site of manufacture, the scale of manufacture, manufacturing equipment and/or the manufacturing process of a drug during the post approval period, the company should refer to the FDA’s scale-up and post-approval changes (SUPAC) guidelines to ensure the drug maintains a consistent quality.