Comprehensive manipulation of glycosylation profiles across development scales.

The extent and pattern of glycosylation on therapeutic antibodies can influence their circulatory half-life, engagement of effector functions, and immunogenicity, with direct consequences to efficacy and patient safety. Hence, controlling glycosylation patterns is central to any drug development program, yet poses a formidable challenge to the bio-manufacturing industry. Process changes, which can affect glycosylation patterns, range from manufacturing at different scales or sites, to switching production process mode, all the way to using alternative host cell lines. In the emerging space of biosimilars development, often times all of these aspects apply. Gaining a deep understanding of the direction and extent to which glycosylation quality attributes can be modulated is key for efficient fine-tuning of glycan profiles in a stage appropriate manner, but establishment of such platform knowledge is time consuming and resource intensive. Here we report an inexpensive and highly adaptable screening system for comprehensive modulation of glycans on antibodies expressed in CHO cells. We characterize 10 media additives in univariable studies and in combination, using a design of experiments approach to map the design space for tuning glycosylation profile attributes. We introduce a robust workflow that does not require automation, yet enables rapid process optimization. We demonstrate scalability across deep wells, shake flasks, AMBR-15 cell culture system, and 2 L single-use bioreactors. Further, we show that it is broadly applicable to different molecules and host cell lineages. This universal approach permits fine-tuned modulation of glycan product quality, reduces development costs, and enables agile implementation of process changes throughout the product lifecycle.

Dermatology Medical Education: A Multicenter Survey Study of the Undergraduate Perspective of the Dermatology Clinical Clerkship.

BACKGROUND/AIMS: Limited data are available regarding the undergraduate dermatology clinical clerkship curriculum in the United States. Our primaryaim is to assess medical students' perspectives of the dermatology clinical clerkship. METHODS: A multicenter survey study was conducted, which included four California dermatology academic programs. A 17-item questionnaire was designed to investigate medical student perception with regard tothe overall educational value of the various teaching aspects of the dermatology clinical clerkship. RESULTS: A total of 152 medical student surveys were completed. Over half of the medical students felt proficient in diagnosing the most commondermatologic conditions. Eighty-seven percent of medical students were very satisfied with the dermatology clerkship. Ninety-one percent of students felt the length of the clerkship was appropriate. CONCLUSIONS: The vast majority of medical students reported a high level of proficiency in the treatment and diagnosis of common skin disorders. In contrast, our findings suggest that medical students may not begaining sufficient hands-on experience in conducting certain dermatologic procedures following the dermatology clerkship. Overall, medical studentperception of the dermatology clinical clerkship was mostly positive.

Erythrokeratoderma variabilis successfully treated with topical tazarotene.

Erythrokeratoderma variabilis, also known as Mendes da Costa syndrome, is a genodermatosis belonging to the group of diseases known as the erythrokeratodermias. Erythrokeratoderma variabilis is characterized by two distinctive manifestations: well-demarcated, variable, transient, figurate patches of erythema, and localized or generalized hyperkeratotic plaques. Treatments include topical retinoic acid, salicylic acid, and alpha-hydroxy acid in petrolatum, but all have been reported to have limited, variable success rates. We report a child with erythrokeratoderma variabilis with no family history of this entity, successfully treated with topical tazarotene.

Topical tacrolimus treatment of atopic eyelid disease.

PURPOSE: To describe the effects of topical tacrolimus treatment of severe atopic eyelid disease. DESIGN: Interventional consecutive case series. METHODS: A description of clinical findings and therapeutic response for five consecutive adult patients (mean age, 56.2 years; range 44-62) treated with topical tacrolimus for severe atopic eyelid disease at one institution. RESULTS: Five patients with bilateral atopic eyelid disease that was refractory to treatment with topical corticosteroids were treated with tacrolimus 0.03% ointment, applied to the affected eyelid skin of both eyes twice daily. Eyelid induration, erythema, and eczematous changes were substantially improved within 1 to 3 weeks after initiation of topical tacrolimus treatment in all patients. There was an associated decrease in ocular surface irritation and inflammatory signs in each of four patients who also had atopic keratoconjunctivitis. No adverse effect associated with tacrolimus treatment was noted during continued treatment for 5 to 14 months. All patients were able to discontinue longstanding use of topical corticosteroid drugs. CONCLUSIONS: Application of topical tacrolimus on eyelid skin may be effective for treatment of severe atopic dermatitis of the eyelids, and may have secondary benefits for atopic keratoconjunctivitis. Topical tacrolimus may be used for at least 1 year without apparent adverse reaction in some patients, although the rate of adverse reaction cannot be determined from this small series.