Guidelines investigation and technical considerations of virus safety during investigational new drug application of innovative monoclonal antibody products / 药学学报

With the development of antibody manufacturing technology and improvement of new drug research in domestic industry, more innovative monoclonal antibody products submitted investigational new drug (IND) application. At the same time, monoclonal antibody products from abroad which have been approved marketing authorization and/or conducted clinical trials submitted IND applications in China. The National Medical Products Administration (NMPA) issued the "Guideline of Investigational New Drug Application" (No. 16, 2018) which emphasized the chemical, manufacturing, and control (CMC) regulatory, and dossier requirements in IND application, greatly promoted the application quality of innovative biological products. However, compared to the Food and Drug Administration (FDA) and European Medicines Agency (EMA), our particular guidelines are insufficient, such as guideline on virus safety evaluation of biotechnological investigational medicinal products. This review investigated the questions raised by sponsors from 2018 to 2020, including the end of production cell (EOPC) and/or unprocessed bulk (UPB) testing and virus removal or inactivation validation. Meanwhile, sponsors submitted different dossiers due to differences in understanding of stage requirements of guidelines from domestic and abroad. Based on the guidelines of virus safety from NMPA, FDA, and EMA, and the technical considerations, this review puts forward personal suggestions on the adventitious agents testing and virus removal or inactivation validation in manufacturing process, aim to ensure virus safety of innovative monoclonal antibody products in clinical trials.

Preparation and properties of thermosensitive in situ gel for ophthalmic formulation containing pearl hydrolyzate / 药学学报

The study was designed to generate an ophthalmic thermosensitive in situ gel with improved mechanical and mucoadhesive properties that may prolong the retention time to enhance the bioavalability of pearl hydrolyzate. The gene was comprised of poloxamer 407, poloxamer188 and Carbopol 934, which were optimized by central composite design and response surface methodology. The rheological properties, transcorneal permeability, retention time and in vitro release behaviors of the optimal gel formulation were investigated. The gel was Newtonian liquid at 25℃ and performed as a semisolid gel with non-Newtonian liquid property with a gelation time of 13 s at 35℃. Compared with a conventional eye drops, the ophthalmic in situ gel exhibited a sevenfold increase in retention with a sustained release behavior, which was observed with suitable permeability coefficient at 5.58 cm·s-1. In conclusion, the new gel of pearl hydrolyzate prolonged the release duration of drug, which may decrease the frequency of administration of pearl hydrolyzate. kilometers with ecological similarity between 20% and 40%, mainly in Yunnan, Guangxi, Guangdong, Guizhou, Hainan, Sichuan, Fujian and Chongqing. The climate factors mainly affecting the distribution of Panax notoginseng (Burk.) F. H. Chen were precipitation of warmest quarter, SD of temperature seasonality, altitude, isothermality, coefficient of variation of precipitation seasonality, mean temperature of monthly, precipitation of driest month, reference bulk density of soil and soil texture.

Determination of contact angle of pharmaceutical excipients and regulating effect of surfactants on their wettability / 药学学报

To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose <magnesium stearate. In addition, surfactants both in droplets and mixed in excipients significantly reduced the contact angle of excipients, and their abilities to lower contact angle varied. The results of the present study offer a guideline in the formulation design of tablets.

Long term follow-up and prognostic analysis of 85 cases with primary gastrointestinal diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics, prognostic factors in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL).</p><p><b>METHODS</b>Long term follow-up of 85 patients with PGI-DLBCL was carried out and the patients clinical data were retrospectively evaluated. The risk factors for survival rate were analyzed by univariate and multivariate Cox regression analysis.</p><p><b>RESULTS</b>The median age of 85 patients was 61 years old (18-87), and male: female ratio was 1.83:1 (55/30). The stomach origin accounted for 63.5% (54/85), intestine origin for 35.3% (30/85) and multiple GI involvements for 1.2% (1/85). Bone marrow involvement accounted for 16.4% (11/64), Helicobacter pylori (HP) infection for 51.4% (19/37). The 5-year overall survival (OS) rates of all patients were 63.9%. The 5-year OS of patients in stomach and intestinal groups were 75.3% and 44.1%, respectively (P=0.005). The 5-year OS of germinal center B cell-like (GCB) group and non-GCB groups were 64.7% and 62.4%, respectively (P = 0.610). Univariated analysis revealed that the factors affecting OS of patients included age, lesion site, tumor size, gastrointestinal clinical Lugano staging system, IPI score (all P values < 0.05). Multivariate Cox regression analysis revealed that IPI score was independent prognosis risk factor affecting OS (RR = 3.609, 95 CI 2.034-6.404, P < 0.01).</p><p><b>CONCLUSION</b>IPI score was independent prognosis risk factor affecting OS of PGI-DLBCL patients.</p>

Clinical and prognostic analysis of 101 cases of primary gastrointestinal non-Hodgkin's lymphoma / 中国实验血液学杂志

This study was purposed to analyze the clinical characteristics and prognostic factors in patients with primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL). The pathological data of 101 PGI-NHL patients admitted in our hospital in the past 15 years were analyzed retrospectively. The results showed that 101 patients with PGI-NHL accounted for 14.49% of NHL in the same period, there were 64 males, 37 females, the range of ages was from 18 to 87 years old, median age was 61 years old; in disease distribution, the stomach PGI-NHL accounted for 58.42%, intestine PGI-NHL accounted for 39.60%, multiple GI involvements (MGI) accounted for 1.98%; in pathological type, diffuse large B cell lymphoma (DLBCL) accounted for 66.34%, mucosa-associated lymphoid tissue (MALT) lymphoma accounted for 17.82%, mantle cell lymphoma (MCL) accounted for 3.96%, enteropathy-associated T cell lymphoma (EATL) accounted for 7.92%, extra-nodal nasal type NK/T cell lymphoma accounted for 1.98%, follicular lymphoma (FL) accounted for 0.99%, small lymphocyte lymphoma (SLL) accounted for 0.99%. Eighty-nine out of 101 patients were followed up (49 cases live, 40 cases dead), data of the 12 patients were lost; the median survival time was 29 months (1 - 173). The three-year OS and five-year OS were 58.4% and 52.6% respectively. Univariate analysis revealed that the factors affecting OS included sex (P = 0.004), lesion site (P = 0.002), tumor size (P = 0.011), clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma (P = 0.003), IPI score (P = 0.000), pathological cell phenotype (P = 0.001), and pathological type (P = 0.006), their differences were statistically significant (P < 0.05). Multivariate Cox regression analysis indicated that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score, pathological type were independent prognostic risk factors affecting OS. It is concluded that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score and pathological type are independent risk factors affecting OS.