Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems.

Plants have been proposed as an attractive alternative for pharmaceutical protein production to current mammalian or microbial cell-based systems. Eukaryotic protein processing coupled with reduced production costs and low risk for mammalian pathogen contamination and other impurities have led many to predict that agricultural systems may offer the next wave for pharmaceutical product production. However, for this to become a reality, the quality of products produced at a relevant scale must equal or exceed the predetermined release criteria of identity, purity, potency and safety as required by pharmaceutical regulatory agencies. In this article, the ability of transient plant virus expression systems to produce a wide range of products at high purity and activity is reviewed. The production of different recombinant proteins is described along with comparisons with established standards, including high purity, specific activity and promising preclinical outcomes. Adaptation of transient plant virus systems to large-scale manufacturing formats required development of virus particle and Agrobacterium inoculation methods. One transient plant system case study illustrates the properties of greenhouse and field-produced recombinant aprotinin compared with an US Food and Drug Administration-approved pharmaceutical product and found them to be highly comparable in all properties evaluated. A second transient plant system case study demonstrates a fully functional monoclonal antibody conforming to release specifications. In conclusion, the production capacity of large quantities of recombinant protein offered by transient plant expression systems, coupled with robust downstream purification approaches, offers a promising solution to recombinant protein production that compares favourably to cell-based systems in scale, cost and quality.

Prevalence and impact of manic traits in depressed patients initiating interferon therapy for chronic hepatitis C infection.

GOALS: To evaluate the impact of manic traits on adverse events in depressed hepatitis C patients initiating interferon therapy. BACKGROUND: Interferon alpha therapy for hepatitis C can exacerbate preexisting depression. Bipolar disorder frequently presents as depressive symptoms that are indistinguishable from or misdiagnosed as major depressive disorder. The impact of bipolar disorder on adverse psychiatric events during therapy is unknown. STUDY: A retrospective study was performed on consecutive patients initiating interferon therapy in the Hepatology clinic at a tertiary-care center between December 2004 and October 2007. All patients completed the Physicians Health Questionnaire (PHQ-9), a validated survey for major depressive disorder. Patients with a positive PHQ screen completed the Mood Disorders Questionnaire (MDQ), a validated screening tool for manic traits. Patients with a negative PHQ served as controls. All adverse psychiatric events were documented through retrospective record review for 6 months after interferon initiation. RESULTS: A total of 165 patients were treated with interferon alpha. One hundred thirty-two (80%) had a negative PHQ (controls) and 33 had a positive PHQ. Forty-one (30%) of the control patients had adverse psychiatric events. Psychiatric events occurred in 8 of 22 (36%) patients with positive PHQ but negative MDQ; 8 of 11 (73%) with positive PHQ and positive MDQ had psychiatric adverse events. This finding was statistically significant compared with the control group (P=0.007). The overall sustained viral response rate was 58% and was not statistically significant among groups. CONCLUSIONS: Baseline manic traits, as detected by the MDQ, were associated with high rates of adverse psychiatric events among individuals receiving antiviral therapy.