Impact of fed-batch process intensification on the productivity and product quality of two CHO cell lines expressing unique novel molecular format proteins.

While monospecific antibodies have long been the foundational offering of protein therapeutics, recent advancements in antibody engineering have allowed for the development of far more complex antibody structures. Novel molecular format (NMF) proteins, such as bispecific antibodies (BsAbs), are structures capable of multispecific binding, allowing for expanded therapeutic functionality. As demand for NMF proteins continues to rise, biomanufacturers face the challenge of increasing bioreactor process productivity while simultaneously maintaining consistent product quality. This challenge is exacerbated when producing structurally complex proteins with asymmetric modalities, as seen in NMFs. In this study, the impact of a high inoculation density (HID) fed-batch process on the productivity and product quality attributes of two CHO cell lines expressing unique NMFs, a monospecific antibody with an Fc-fusion protein and a bispecific antibody, compared to low inoculation density (LID) platform fed-batch processes was evaluated. It was observed that an intensified platform fed-batch process increased product concentrations by 33 and 109% for the two uniquely structured complex proteins in a shorter culture duration while maintaining similar product quality attributes to traditional fed-batch processes.

Optimizing radiation safety in dentistry: Clinical recommendations and regulatory considerations.

BACKGROUND: The value of dental radiographs to oral health care decision making must be balanced with radiation safety to minimize patient exposure and occupational risk of oral health care providers. This review summarizes recommendations and regulatory guidance regarding dental radiography and cone-beam computed tomography. An expert panel presents recommendations on radiation safety, appropriate imaging practices, and reducing radiation exposure. TYPES OF STUDIES REVIEWED: A systematic search run in Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews identified relevant topical systematic reviews, organizational guidelines, and regulatory reviews published in the peer-reviewed literature since 2010. A supplemental search of the gray literature (eg, technical reports, standards, and regulations) identified topical nonindexed publications. Inclusion criteria required relevance to primary oral health care (ie, general or pediatric dentistry). RESULTS: A total of 95 articles, guidance documents, and regulations met the inclusion criteria. Resources were characterized as applicable to all modalities, operator and occupational protection, dose reduction and optimization, and quality assurance and control. PRACTICAL IMPLICATIONS: Understanding factors affecting imaging safety and applying fundamental principles of radiation protection consistent with federal, state, and local requirements are essential for limiting patient ionizing radiation exposure, in conjunction with implementing optimal imaging procedures to support prudent use of dental radiographs and cone-beam computed tomographic imaging. The regulatory guidance and best practice recommendations summarized in this article should be followed by dentists and other oral health care providers.

An automated high inoculation density fed-batch bioreactor, enabled through N-1 perfusion, accommodates clonal diversity and doubles titers.

An important consideration for biopharmaceutical processes is the cost of goods (CoGs) of biotherapeutics manufacturing. CoGs can be reduced by dramatically increasing the productivity of the bioreactor process. In this study, we demonstrate that an intensified process which couples a perfused N-1 seed reactor and a fully automated high inoculation density (HID) N stage reactor substantially increases the bioreactor productivity as compared to a low inoculation density (LID) control fed-batch process. A panel of six CHOK1SV GS-KO® CHO cell lines expressing three different monoclonal antibodies was evaluated in this intensified process, achieving an average 85% titer increase and 132% space-time yield (STY) increase was demonstrated when comparing the 12-day HID process to a 15-day LID control process. These productivity increases were enabled by automated nutrient feeding in both the N-1 and N stage bioreactors using in-line process analytical technologies (PAT) and feedback control. The N-1 bioreactor utilized in-line capacitance to automatically feed the bioreactor based on a capacitance-specific perfusion rate (CapSPR). The N-stage bioreactor utilized in-line Raman spectroscopy to estimate real-time concentrations of glucose, phenylalanine, and methionine, which are held to target set points using automatic feed additions. These automated feeding methodologies were shown to be generalizable across six cell lines with diverse feed requirements. We show this new process can accommodate clonal diversity and reproducibly achieve substantial titer uplifts compared to traditional cell culture processes, thereby establishing a baseline technology platform upon which further increases bioreactor productivity and CoGs reduction can be achieved.