PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Something for Nothing.","authors":"James Agalloco","doi":"10.5731/pdajpst.2022.012736","DOIUrl":"https://doi.org/10.5731/pdajpst.2022.012736","url":null,"abstract":"<p><p>This article reviews the evolution of performance standards for aseptic processing as defined by regulatory, pharmacopoeial, and industry activities. The increasing rigor of the expectations for sterility testing, environmental monitoring, and process simulation have made for improvements in capability for sterile manufacturing. The document explains why contemporary requirements are such that satisfying them requires a shift in operating practice from manned clean rooms to isolation technology.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9978044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flexible Loading Pattern Approach in Overkill Steam Sterilization Based on the Physical Properties of Steam and Thermodynamics of Sterilization.","authors":"Arnan Ben-David","doi":"10.5731/pdajpst.2021.012708","DOIUrl":"https://doi.org/10.5731/pdajpst.2021.012708","url":null,"abstract":"<p><p>Because overkill steam sterilization processes in autoclaves are considered critical, they are highly scrutinized, and the use of autoclaves in fixed loading patterns is a common approach to the interpretation of regulatory requirements. Many such regulations are attributed to tradition and a buildup of restrictions that aim to improve the levels of assurance of the process and minimize risk. However, these measures complicate the operation and qualification of autoclaves, becoming cumbersome, time-consuming, and costly. In actuality, overkill sterilization is one of several processes in the pharmaceutical industry that provides the highest levels of sterility assurance. This method provides a minimum reduction of highly durable spore populations of 12 logs, achieving a probability of a nonsterile unit (PNSU) of 10^-6 Because these spores are far sturdier than the common microorganisms that can be found in pharmaceutical facilities, overkill sterilization effects significantly lower PNSU values for the latter. The physical properties of steam and the thermodynamics of steam sterilization constitute a predictable and repeatable process that can be monitored and verified. The high assurance level of overkill sterilization, combined with the properties of steam, actualizes a high safety margin that encompasses nearly every load type and load configuration when the cycle is performed under certain basic rules. The aim of this article is to present data that advocate and favor an approach that allows greater freedom and variability in arranging items in an autoclave when running overkill cycles, without the need to qualify each configuration.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9958700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CPV of the Future: AI-Powered Continued Process Verification for Bioreactor Processes.","authors":"Andrej Ondracka,&nbsp;Arnau Gasset,&nbsp;Xavier García-Ortega,&nbsp;David Hubmayr,&nbsp;Joeri B G van Wijngaarden,&nbsp;José Luis Montesinos-Seguí,&nbsp;Francisco Valero,&nbsp;Toni Manzano","doi":"10.5731/pdajpst.2021.012665","DOIUrl":"https://doi.org/10.5731/pdajpst.2021.012665","url":null,"abstract":"<p><p>According to the standard guidelines by the FDA, process validation in biopharma manufacturing encompasses a life cycle consisting of three stages: process design (PD), process qualification (PQ), and continued process verification (CPV). The validity and efficiency of the analytics methods employed during the CPV require extensive knowledge of the process. However, for new processes and new drugs, such knowledge is often not available from Process performance qualification and Validation (PPQV). In this work, the suitability of methods based on machine learning/artificial intelligence (ML/AI) for the CPV applied in bioprocess monitoring and cell physiological control of the yeast <i>Pichia pastoris (Komagataella phaffii)</i> was studied with limited historical data. In particular, the production of recombinant <i>Candida rugosa</i> lipase 1 (Crl1) under hypoxic conditions in fed-batch cultures was considered as a case study. Supervised and unsupervised machine learning models using data from fed-batch bioprocesses with different gene dosage clones under normoxic and hypoxic conditions were evaluated. Firstly, a multivariate anomaly detection (isolation forest) model was applied to the batch phase of the bioprocess. Secondly, a supervised random forest model for prediction of required operator's control actions during the semiautomated fed-batch phase under hypoxic conditions was assessed to maintain the respiratory quotient (RQ) within the desired range for maximizing the specific production rate (<i>q_P</i> ). The performance of these models was tested on historical data using independent evaluation of the process by the process control engineer (subject matter expert-SME), and on real-time data in the case of manual action prediction, where the model was implemented to guide the control of the bioprocess. The work presented here constitutes a proof-of-concept that multivariate analytics methods, based on machine learning, can be a valuable tool for real-time monitoring and control of biopharma manufacturing bioprocesses to improve its efficiency and to assure product quality.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9975418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panoramic Review on Progress and Development of Molecular Docking","authors":"Kiran Dudhat","doi":"10.11648/j.pst.20230701.11","DOIUrl":"https://doi.org/10.11648/j.pst.20230701.11","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82524510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating T_m Method Specificity Using Oligonucleotide Sequence Variants.","authors":"Alexandra H Heussner,&nbsp;Sarina Schuler,&nbsp;Gerd Berger,&nbsp;Melanie Zerulla-Wernitz","doi":"10.5731/pdajpst.2021.012694","DOIUrl":"https://doi.org/10.5731/pdajpst.2021.012694","url":null,"abstract":"<p><p>All starting materials and the active pharmaceutical ingredient (API) of a drug product must be subjected to analytical identity (ID) testing as part of the release prior to their introduction into the pharmaceutical manufacturing process. Generally, it is preferable for Quality Control (QC) laboratories to perform ID tests using a simple and fast to perform, yet highly specific, analytical method. This preference also applies to oligonucleotides, an emerging class of APIs, where a combined ID testing strategy should be applied, including intact mass determination and a sequence-specific method. Within this work, we investigated whether ultravioloet (UV)-spectrometric determination of the melting temperature (T_m) of oligonucleotides is a suitable sequence-specific ID test for these substances in the pharmaceutical routine QC. Therefore, this method was evaluated for its specificity toward deviating oligonucleotide sequences. For this, model oligonucleotide sequences and variants thereof were designed, synthesized, and analyzed, resulting in precise and specific data. Even single base exchanges or single nucleotide deletions and insertions in the sequences led to significant changes in the measured T_m of the corresponding oligonucleotide duplexes. These results indicate a generally high specificity of the method toward subtle changes in oligonucleotide sequences and confirm the applicability of the analytical method as part of the ID testing strategy for oligonucleotides in the pharmaceutical QC environment.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9407814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Design, Development, and Performance of a Mass-Flow Based, Open-Source Buffer Manufacturing System.","authors":"Natraj Ram,&nbsp;Jeff Johnson,&nbsp;Hiren Ardeshna,&nbsp;Joseph Camire,&nbsp;Ryan Campbell,&nbsp;Doan Chau,&nbsp;Sam Gardner,&nbsp;Kevin Gibson,&nbsp;Joey Norikane,&nbsp;Paul Randolph,&nbsp;Kelly Smith,&nbsp;Katherine Stafford,&nbsp;Rachel Swamy,&nbsp;Shana Usery,&nbsp;Kelvin H Lee","doi":"10.5731/pdajpst.2021.012660","DOIUrl":"https://doi.org/10.5731/pdajpst.2021.012660","url":null,"abstract":"<p><p>Buffer solutions are a critical component of the manufacturing process for therapeutic proteins and other biomolecules. The traditional way to make and use buffers is space and resource intensive, creating operational bottlenecks that impact efficiencies and costs. Here we describe a full-scale, current Good Manufacturing Practices (cGMP) capable buffer stock blending system that has an open-source, configurable design and that overcomes the challenges of traditional buffer preparation. The system comprises simplified control and operation using mass flow to provide on-demand supply of buffer solutions. The system also has self-cleaning capability and is amenable to be operated as a closed system. The data will demonstrate the excellent performance and capabilities of the system as well as illustrate its potential transformative impact on biomanufacturing.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9277746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Investigation into the Spatial Distribution of Moisture in Freeze-Dried Products Using NIR Spectroscopy and Chemical Imaging.","authors":"Azheruddin Mohammed,&nbsp;Antoine Cournoyer,&nbsp;Ryan Gosselin","doi":"10.5731/pdajpst.2020.012443","DOIUrl":"https://doi.org/10.5731/pdajpst.2020.012443","url":null,"abstract":"<p><p>Near-infrared (NIR) spectroscopy (NIRS) is a widely accepted method of measuring moisture in pharmaceutical freeze-dried products, both during the process and in the finished products. Multiple NIR measurement approaches have been introduced to monitor product moisture in freeze-dried vials. However, the spatial moisture gradients within a vial have not been investigated in depth. Like any other point-focused process analytical technology (PAT) tool, a spectrum produced by NIRS represents an average over a given area of the product vial. Implementing a point-focused NIR on any random position without proper understanding of spatial moisture variations within the vial may severely impact the reliability of the results. The present work focuses on understanding the moisture distribution within freeze-dried vials. We performed an investigation using NIR tools, NIR chemical imaging (NIR-CI), and NIRS to understand the spatial variations in moisture on the outer surface (i.e., periphery) of the freeze-dried vials. To achieve this, the moisture distribution within individual vials was mapped using NIR images. Then, NIRS was used to determine the necessity of using multiple measurement points to produce robust models quantifying the moisture inside freeze-dried products. Overall, the results show a simplified version of the phenomenon in which non-homogenous distribution of moisture, as well as the non-uniform drying front, occur within the vials. The findings from the NIRS-based partial least squares (PLS) models indicate that to achieve reliable product/process information, measurements must be drawn from multiple measurement points on the surface of the freeze-dried products.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9407819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New PDA President Says Hello to PDA Journal.","authors":"Glenn E Wright","doi":"10.5731/pdajpst.2023.001323","DOIUrl":"https://doi.org/10.5731/pdajpst.2023.001323","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9337155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Qualification of Visible Particle Load Analysis Methods for Injectable Drug Product Primary Packaging Components.","authors":"Robin Wagner,&nbsp;Peter Masatani,&nbsp;Dana Grace,&nbsp;Gianpiero Torraca,&nbsp;Stephanie Moore,&nbsp;David Semin","doi":"10.5731/pdajpst.2021.012710","DOIUrl":"https://doi.org/10.5731/pdajpst.2021.012710","url":null,"abstract":"<p><p>In the biopharmaceutical industry, the observation of a single particle in a vial or syringe may result in entire lots of drug product recalls. U.S. Pharmacopeia <787> and <788> describe light obscuration methods and particle collection (membrane filtration) followed by light microscopy for particle counting of filled drug products. However, there are no corresponding pharmacopeial methods for determining the particle levels of unfilled primary packaging components or their packaging materials (tubs, nests, bags, etc.). This article describes a quantification method to accurately assess the number of particles in primary containers and corresponding closures. As a microscopic method, the size ranges can be set by the user and are limited only by the optical properties of the microscope and analysis time. Particle load is a critical quality attribute that has a direct impact on product safety. Applying a standardized method to compare the effect of process changes on particle load can aid manufacturers in refining their processes to minimize particulates. Described herein are the critical parameters to develop physical rinse methods and the subsequent qualification results to measure the visible particle load of nonsiliconized and siliconized primary packaging systems.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9401599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIT CAACB Risk Assessment Case Study: Assessing Virus Cross-Contamination Risk between Two Simultaneous Processes in an Open Biomanufacturing Facility.","authors":"Andrea L Koenigsberg,&nbsp;Veronica Fowler,&nbsp;Reuben Domike,&nbsp;Audrey Brussel,&nbsp;Paul W Barone,&nbsp;Flora J Keumurian,&nbsp;James Leung,&nbsp;Michael E Wiebe,&nbsp;Michael T Brewer,&nbsp;Shawn Chan,&nbsp;Nicolas Dumey,&nbsp;Anne Fournillier,&nbsp;Marcella Goodnight,&nbsp;Johanna Kindermann,&nbsp;Richard Leavy,&nbsp;Buyoung Lee,&nbsp;Stefan Minning,&nbsp;Marie Murphy,&nbsp;Eric Myers,&nbsp;Armen Nahabedian,&nbsp;Kavita Nanda,&nbsp;Sandi Parriott,&nbsp;G K Raju,&nbsp;Ciaran Scallan,&nbsp;Stephanie Schoch,&nbsp;Joe Shiminsky,&nbsp;Bonnie Shum,&nbsp;Sebastian Teitz,&nbsp;Bernice Westrek,&nbsp;Stacy Springs","doi":"10.5731/pdajpst.2021.012691","DOIUrl":"https://doi.org/10.5731/pdajpst.2021.012691","url":null,"abstract":"<p><p>Some members of MIT's Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) previously published content on the \"Quality Risk Management in the Context of Viral Contamination\", which described tools, procedures, and methodologies for assessing and managing the risk of a potential virus contamination in cell culture processes. To address the growing industry interest in moving manufacturing toward open ballrooms with functionally closed systems and to demonstrate how the ideas of risk management can be leveraged to perform a risk assessment, CAACB conducted a case study exercise of these new manufacturing modalities. In the case study exercise, a cross-functional team composed of personnel from many of CAACB's industry membership collaboratively assessed the risks of viral cross-contamination between a human and non-human host cell system in an open manufacturing facility. This open manufacturing facility had no walls to provide architectural separation of two processes occurring simultaneously, specifically a recombinant protein perfusion cell culture process using the human cell line, HEK-293 (Process 1) and a downstream postviral filtration unit operation (Process 2) of a recombinant protein produced in CHO cells. This viral risk assessment focused on cross-contamination of the Process 2 filtration unit operation after the Process 1 perfusion bioreactor was contaminated with a virus that went undetected. The workflow for quality risk management that is recommended by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) was followed, which included identifying and mapping the manufacturing process, defining the risk question, risk evaluation, and risk control. The case study includes a completed Failure Mode and Effects Analysis (FMEA) to provide descriptions of the specific risks and corresponding recommended risk reduction actions.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9402302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}