To explore the internal factors affecting the quality of cefotiam hydrochloride for injection.

The routine quality items of cefotiam hydrochloride for injection products from different manufactures were evaluated, and the thermal stability was compared. The degradation impurities were analyzed using column switching LC-MS, the crystal forms of products with different manufactures were compared by powder X diffraction method, the particle size distribution of the products was determined by light scattering method, and TGA and near infrared spectroscopy were used to predict the binding mode of water.

The differences of the routine quality among the products from different manufacturers were small, but the thermal stability and internal quality showed significant differences.

The main internal factors affecting the thermal stability of cefotiam hydrochloride for injection were crystal size distribution and sodium carbonate content. The evaluation of product quality should start with its internal quality, so as to evaluate the advantages and disadvantages of the production process.

To establish the 10^th national standard for human chorionic gonadotrophin (HCG).

According to Chinese Pharmacopoeia (Volume Ⅳ, 2015 edition) 1209 Chorionic Gonadotrophin bioassay, the 5^th batch of international standard 07/364 was taken as reference, six laboratories collaboratively calibrated the biotiter of the 10^th HCG nation standard.

The 10^th batch of HCG national standard products was determined to have biological titer of 55 IU·per ampoule after collaborative calibration.

The candidate was established as the 10^th national standard for the determination of the titer of HCG API and preparations.

To analyze the information of clinical trial subjects who stopped taking drugs during the epidemic period, so as to provide guidance for the follow-up of clinical trial subjects under special events.

The data of subjects in clinical trials of melanoma who stopped treatment during the epidemic period from February 3, 2020 to May 29, 2020 were collected. SPSS 24.0 statistical analysis software was used to compare the general data and clinical trial information between patients with advanced disease and patients without disease progression.

A total of 32 subjects were included, including 15 progressive subjects and 17 non progressing subjects. Gender, primary site, enrollment test, previous treatment, recurrence and metastasis site, best evaluation during enrollment, and administration regimen were independent risk factors for disease-free progression (P<0.05). There was significant difference in the number of medication cycles between the two groups.

The previous best efficacy, medication regimen, and number of medication cycles have significant effects on the outcome of cancer clinical trials under special public health events.

To explore the clinical and pathological characteristics, treatment measures and clinical outcome of programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors-induced skin vasculitis.

Relevant domestic and foreign databases (up to November 30, 2020) were searched, case reports and clinical research papers on skin vasculitis caused by PD-1/PD-L1 inhibitors were collected, and the characteristics of PD-1/PD-L1 inhibitor-induced skin vasculitis was analyzed using descriptive statistics.

A total of 11 patients were included in the analysis. Patient medications included four cases of nivolumab, three cases of pembrolizumab, one case of duvaluzumab, one case of nivolumab combined with ipilimumab, and one case of pembrolizumab combined with ipilimumab. One patient did not provide the name of the drug. The time from the patients' start of using PD-1/PD-L1 inhibitor to the appearance of skin vasculitis was 1 to 28 weeks, with a median time of 8 weeks (3~13). The skin vasculitis manifested as skin purpura or skin necrosis, which may be accompanied by immune related adverse events of other systems, and skin biopsy showed perivascular neutrophil and lymphocyte infiltration with focal fibrinoid necrosis. Glucocorticoid therapy was the main treatment measure, and the prognosis was good. Most patients got remission. The recover time ranged from 2 to 60 days, with a median time of 30 (13~50) days.

Vasculitis is a rare adverse reaction of PD-1/PD-L1 inhibitors. Skin purpura is the main manifestation. Glucocorticoids can be used for treatment. The prognosis is good, but it may be combined with other serious adverse reactions, which should be paid attention to in clinical practice.

To develop quality control methods for recombinant anti-interleukin-23 monoclonal antibodies (anti-IL23 mAb).

Peptide map analysis by RP-HPLC was used for identification of an anti-IL-23 mAb. The purity was measured by reduced/non-reduced capillary electrophoresis-sodium dodecyl sulfonate (CE-SDS) and size exclusion-high performance liquid chromatography (SEC-HPLC). Charge heterogeneity was measured by imaging capillary isoelectric focusing electrophoresis (icIEF). LC isoAsp95 was measured by RP-HPLC. The biological activity was determined on U2OS IL23R/IL12RB1 dimerization cell. Other quality control items complied with corresponding requirements of “Chinese Pharmacopeia” 2015 edition and related guidelines.

Peptide mapping showed the specific spectrum of the anti-IL23 mAb, which could be adopted for the identification test. The area percentage of heavy chain, NGHC and light chain was (97.84±0.12)% as detected by reduced CE-SDS; the area percentage of main peak detected by non-reduced CE-SDS was (97.23±0.11)%. The area percentage of monomer peak and total aggregate peak detected by SEC-HPLC were (99.26±0.005)% and (0.71±0.005)%, respectively. The area percentage of main peak, acid peak and alkaline peak detected by icIEF were (73.83±0.29)%, (24.03±0.34)% and (2.10±0.09)%, respectively. The percentage of LC isoAsp95 was (3.37±0.52)%. The relative biological activity was (102.25±8.47)%.

A series of quality control methods for anti-IL23 mAbs has been established, which can be adaptable in ensuring the safety, effectiveness and quality controllability for similar biologics. The study is of great significance as a representative quality control reference for anti-IL23 mAbs.