Product stability needs to be tested before and after storage at various times, temperatures, and humidity. Stability-indicating
parameters include pH, color, clarity, protein concentration determined by UV spectroscopy or enzyme-linked immunosorbent
assays (ELISAs) for vapor transmission; protein bioactivity bioassays; the presence of protein fragments and aggregates by
gel chromatography; and percent of deamidation by tryptic mapping. Other tests can be performed on container-closure integrity,
preservative efficacy, changes from upright or inverted handling, package or stopper extractables, in-use tests, and test
product remaining after in-use periods. Global climate zones and regulatory conditions require that therapeutics planned for
other countries anticipate region-specific registration requirements.
Campaign manufacturing is a critical economic concept that allows sequential manufacturing of different products in the same
facility so that common facilities and equipment can be used for multiple products. Because of economies of scale, lower unit
costs result from larger volumes, and smaller-volume products will have a lower cost of goods if they are produced in a shared
or multiuse facility. Expenses in production include facilities, utilities, validation, containment, raw materials, labor,
royalties, depreciation, insurance, and rent.
Multiproduct facilities can be subject to operations congestion, process equipment contamination, airborne contamination,
increased staff activities, and increased regulatory caution. Factors involved in economic multiproduct finishing and filling
include facility siting, operational efficiency, dedicated equipment, validation contingencies, flow separation, materials
storage, product transfers, personnel access, and gowning and pass-through air locks. Such working environment considerations
as flooring, walls, ceiling, and fixed furniture must be considered. Cell banking, seed preparation laboratories, fermentation
media and preparatory formulation, harvest product recovery, purification, buffer preparation, product formulation rooms,
product filling, lyophilization, labeling and packaging, quality laboratories, instrument calibration, routine maintenance
work space, and equipment washing are all factors in product validation.
Freezing and lyophilization provide a cost savings by allowing product to be pooled into larger and fewer lots. Production-scale bulk can be frozen and
thawed multiple times and sampled at intervals to extend its expiration date with adequate testing. Shipping and storing at
subzero temperatures may not be technically or economically feasible in many markets — Europe does not guarantee refrigerated
delivery, so lyophilization may be the most cost-effective choice for global distribution to a wider market. The goal is to
design the fastest and most robust cycle possible, consuming the least amount of energy without affecting product quality.
BFS is an attractive economic alternative to glass vials because the process is streamlined and usually requires no preservatives
or antimicrobials. Capital costs may be less than those for equipment and facilities needed to sterilize components and the
processes to fill, stopper, and cap glass vials. BFS machines can form, fill, and seal a set of containers in 12 seconds.
Scale-up is accomplished by increasing the number of mold cavities used. Quality control testing for a filled vial (not including
quality control of the bulk product) is estimated to be 12-20% of the total cost of goods.
Packaging and labeling. Many product recalls are due to mislabeling. They can devastate a company financially in terms of consumer confidence and
in the reputation of both the company and the biopharmaceutical industry as a whole. Although biopharmaceuticals are not yet
competing against generics, a recent consumer network survey suggested that seven of ten consumers would change a purchasing
decision based on improved drug packaging. u