CONVALESCENT PLASMA THERAPY FOR COVID-19 PATIENTS: REGULATORY GUIDANCE ON COLLECTION, TESTING, PROCESSING, STORAGE, DISTRIBUTION, AND CLINICAL TRIALS

Convalescent plasma can be transfused to patients suffering from the same infection or for preparing immunoglobulin concentrates. Plasma obtained from recovered patients can be a valuable alternative during the COVID-19 pandemic for supporting its treatment within a randomized or case-control clinical trials or observational studies of plasma transfusion and for preparing plasma-derived biological products. WHO Blood Regulators Network highlighted that a systematic approach for collecting convalescent plasma from patients recovered from COVID-19 could provide a useful intervention. Structured clinical trials can be used to assess safety and effectiveness of convalescent plasma. The convalescent plasma therapy is still in the experimental stage and is currently not included in the interim clinical guidelines of WHO. However, an emergency investigational new drug application (eIND) process has been induced to ensure the availability of COVID-19 convalescent plasma to the patients with severe or life-threatening COVID-19 conditions. USFDA is regularly amending its guidance as new results, and best practices are emerging. The write-up provides an overview of convalescent plasma, from a regulatory considerations viewpoint, systematic workflow protocol, and a cross-section of clinical trials underway.

Assessing Animal Models of Bacterial Pneumonia Used in Investigational New Drug Applications for the Treatment of Bacterial Pneumonia

ABSTRACT Animal models of bacterial infection have been widely used to explore the in vivo activity of antibacterial drugs. These data are often submitted to the U.S. Food and Drug Administration to support human use in an investigational new drug application (IND). To better understand the range and scientific use of animal models in regulatory submissions, a database was created surveying recent pneumonia models submitted as part of IND application packages. The IND studies were compared to animal models of bacterial pneumonia published in the scientific literature over the same period of time. In this review, we analyze the key experimental design elements, such as animal species, immune status, pathogens selected, and route of administration, and study endpoints.

Need and Recommendations for Universal Guidelines on Regulatory Status and Quality Control/Safety of Probiotic Products

Background: In today’s era, various health boosting products viz. probiotics, functional foods, dietary supplements and nutraceuticals are gaining great commercial interest. Although probiotics have traditional history of their use, their regulatory approval regimes across the globe are complicated and incoherent. Objective: The present article has been compiled to give an overview of the existing approval guidelines for the probiotic products across the globe along with their associated ambiguities. Furthermore, suggestive consolidations for harmonized approval process to be implemented in future are proposed on the basis of their intended use. Methods: The study was carried out by using secondary sources through literature survey from journals, market reports, proceedings, books and web pages of relevant regulatory authorities and a critical comparative study was conducted with respect to approval process of probiotics. Results: As per the comparative account of the current regulatory guidelines, it has been evidenced that different countries have adopted diverse approval process for probiotics and; lack of uniformity is of great concern. But due to rapid emergence of probiotics as drugs, a harmonized approval process similar to other drugs covering all aspects of Investigational New Drug Application (INDA) and New Drug Application (NDA) has been proposed in which organisms falling under Generally Recognized As Safe (GRAS) category are exempted from INDA submission whereas non GRAS, GRAE or new organisms are not exempted. After submission of NDA and getting approval from Food and Drug Administration (FDA), product should be manufactured and marketed. Conclusion: Regulatory bodies across the globe must ensure that probiotics based products should be regulated by lawful approval process in such a manner which will lead to maximal health benefits and minimal health risk for consumers.

A Native Human Monoclonal Antibody Targeting HCMV gB (AD-2 Site I)

Hyperimmune globulin (HIG) has shown efficacy against human cytomegalovirus (HCMV) for both transplant and congenital transmission indications. Replicating that activity with a monoclonal antibody (mAb) offers the potential for improved consistency in manufacturing, lower infusion volume, and improved pharmacokinetics, as well as reduced risk of off-target reactivity leading to toxicity. HCMV pathology is linked to its broad cell tropism. The glycoprotein B (gB) envelope protein is important for infections in all cell types. Within gB, the antigenic determinant (AD)-2 Site I is qualitatively more highly-conserved than any other region of the virus. TRL345, a high affinity (Kd = 50 pM) native human mAb to this site, has shown efficacy in neutralizing the infection of fibroblasts, endothelial and epithelial cells, as well as specialized placental cells including trophoblast progenitor cells. It has also been shown to block the infection of placental fragments grown ex vivo, and to reduce syncytial spread in fibroblasts in vitro. Manufacturing and toxicology preparation for filing an IND (investigational new drug) application with the US Food and Drug Administration (FDA) are expected to be completed in mid-2019.

DMF FILING IN US, EUROPE AND CANADA

A Drug Master File or DMF is a reference source that provides drug evaluator’s confidential information not available to drug product manufacturer about the specific process and components used in the manufacturing, processing and packaging of a drug meant for Human/Animal use. The submission of a DMF is not required by law or FDA regulation. A DMF is submitted solely at the discretion of the holder. The information contained in the DMF may be used to support an Investigational New Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA), another DMF, or amendments and supplements to any of these.