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Most industrial processes are composed of multiple subsequent steps. In this article, we provide a statistical approach to design experiments and to define the manufacturing design space of multi-step processes by taking into account the complex system of interactions among steps. We consider each intermediate outcome as an additional input factor in the next step and we plan experiments following a particular sequential structure. To encompass the potential deviations from the target levels of such input factors, designs are selected according to the D-optimality in average criterion and, in order to assess their prediction capabilities, a suitable extension of the fraction of design space technique has been proposed. The manufacturing design space of the process is then defined by combining the interconnected manufacturing design spaces of the process steps and by deriving the linear combination of the process inputs that ensures the required quality standard for the final outcome. Appealing properties of this approach are also shown by the application to a three-steps biochemical process of expression and purification of a recombinant protein in which 10 input factors are included in the design.

Background: The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). Methods: Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. Results: A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2–84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9–21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7–59.4). Conclusions: Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.