Issue link: https://www.e-digitaleditions.com/i/1052795
Pharmaceutical Technology LABORATORY BEST PRACTICES 2018 39 tious agent contamination. Raw materials of ani- mal origin bring a risk to the manufacture of bio- logicals, and this risk is applicable to historic cell banks and seed viruses as well as to the finished products. Residual DNA or host cell DNA can be a contaminant present in biologicals that are co-purified with drug substances. These types of DNA can have a negative effect, therefore, manu- facturers of biologicals must ensure that the final products derived from continuous mammalian cell lines contain acceptable levels of host cell DNA. Foehr (Pacific BioLabs): Poor quality raw materials can impact biological drug production in many ways. Poor production yields, minor or major changes in the quality attributes of the biologic, and costly delays or failed lots are just a few of the perils. Cells can be very sensitive to small changes in growth conditions. The growth media, serum source, growth factors, cytokines, and other addi- tives should be tested to ensure lot-to-lot consis- tency. The testing may involve simple assessments, such as physical appearance, pH, and osmolality, or may include more complex analysis, such as po- tency tests, immunoblot, mass spectrometry, and chromatography-based impurity analysis. Changes in raw materials can cause slower growth of cells, low production rates of the bio- therapeutic, and changes in characteristics of the protein, such as post-translational processing and potency. These changes may impact the quality attributes and cause shifts to the product speci- fications over time. In the worst situation, a pro- duction lot may fail specifications and need to be repeated, causing costly delays. Raw material variability PharmTech: Is raw material variability an issue, and if so, how do biomanufacturers address this challenge? Bulpin (MilliporeSigma): The production of a bio- logic drug requires raw materials ranging in com- plexity from mammalian cell lines that produce a biologic and media and media components used to 'feed' the production, to filters and gels used in the purification process. In addition, when consid- ering that manufacturing of biologics happens at different sites around the world and contingencies for backups are needed for each, the number of suppliers and the number of raw material prod- ucts can seem overwhelming. Each of these raw materials can have lot-to-lot quality differences. Testing of each component used in drug produc- tion and monitoring products of each phase during production and lot release testing for a variety of attributes informs the production teams of any is- sues that should be addressed. Foehr (Pacific BioLabs): Good quality, reputable vendors of raw materials have tight controls over production and low variability lot-to-lot. However, sometimes different vendors are used, products are discontinued and supply chains are disrupted, or lower-cost substitutes are introduced to the raw "Raw materials of animal origin bring a risk to the manufacture of biologicals, and this risk is applicable to historic cell banks and seed viruses as well as to the finished products." —Bulpin, MilliporeSigma