PDA Journal of Pharmaceutical Science and Technology最新文献

Chimeric antigen receptor (CAR) T cell therapies have transformed the treatment of hematologic malignancies, providing meaningful clinical outcomes for patients with limited therapeutic options. However, the complexity of these therapies presents significant manufacturing challenges that could affect cost, scalability, and accessibility. Early CAR T production relied on highly manual, variable processes developed in academic settings, while current commercial manufacturing has moved toward more structured and standardized platforms. This review examines how that transition unfolded, with particular attention to changes in process design, analytical control strategies, and quality systems that support more robust manufacturing operations. Rather than individual technologies, the literature emphasizes increased levels of maturity in process controls as the defining feature of progress in manufacturing. Improvements in unit operations have helped enable more predictable scale-out of therapies, reinforcing the role of manufacturing in translating scientific innovation into consistent clinical delivery.

The bacterial endotoxin method uses amoebocyte lysate reagents from the horseshoe crab (Limulus polyphemus or Tachypleus tridentatus) to detect and quantify bacterial endotoxin in injectable medications and medical devices. Two types of recombinant reagents have been introduced by various manufacturers, and the equivalency of these results to natural Limulus Amoebocyte Lysate (LAL) reagents has been recently assessed by the United States, European, and Japanese Pharmacopoeia. Recombinant reagents and amoebocyte lysate reagents appear to be highly comparable, according to several investigations.Limulus Amoebocyte Lysate assays are currently the gold standard. LAL is used in vitro for the precise detection of endotoxins and is based on the endotoxin-activated Factor C-mediated clotting cascade. In our quality control laboratory, we tested several categories of drug samples using different compendial methods for detection of bacterial endotoxin method that provides reliable and consistent results. Since 2024, a bacterial endotoxin test based on recombinant cascade reagent (rCR), the endotoxin sensor recombinant factor C, factor B, and pro-clotting enzyme inside of LAL, has been used as an animal-free alternative to LAL. The non-animal derived reagents rCR, which uses cloned genes from the genome of the Limulus polyphemus horseshoe crab to detect and measure bacterial endotoxins.In addition to providing ethical and environmental benefits over traditional LAL assays, rCR eliminates interfering Horseshoe Crab blood components, allowing for extremely specific endotoxin detection. For rCR test performance in routine setting, a comparative study was conducted of compendial bacterial endotoxin testing by LAL with alternates animal-free reagents rCR and summarize the evidence presented by using analysis of different categories of pharmaceutical products. According to the compendial endotoxin testing requirements, all results were acceptable. When the rCR assay was applied rather of the LAL test, no interference was seen in certain samples. In this study, that rCR and LAL are equivalent and comparable.

Nitrosamines are classified as probable (IARC Group 2A) or possible (IARC Group 2B) human carcinogens, capable of inducing tumors even at very low concentrations (nanogram per liter levels). Regulatory considerations specifically affect Large Volume Parenteral (LVP) products due to the high application volume combined with very low allowable intake limits. These compounds have already attracted significant attention for elastomer materials like rubber. A recent FDA communication highlighted the particular importance of infusion bags, given their unique nature. In this study, over 300 batches of plastic materials, used for LVP packaging, were tested and trace levels of nitrosamines at ng/L scale were detected in several plastic granules and films. These results indicated the importance of nitrosamine profiling during raw material qualifications for LVP products.

Background Prefilled syringes (PFS) are commonly used for self-administered injectable drugs, particularly for chronic conditions. A critical design factor is the injection force needed to depress the plunger, which varies by drug viscosity and syringe mechanics. This is especially important for patients with potential strength limitations. Human factors studies help evaluate these physical demands to ensure PFS can be used safely and effectively across diverse users. Assessing both maximum force capabilities and endurance provides key insights for optimizing syringe design and minimizing patient discomfort.Objectives This study evaluated Chronic Obstructive Pulmonary Disease (COPD) patients' experience with PFS samples of varying injectability (injection force and duration) and measured pinch force endurance-an indicator for PFS physical demand. Those insights aimed to guide PFS design for users with strength limitations.Methods 42 COPD patients performed simulated injections using three PFS samples (28N, 38N, 47N force) and rated perceived demand. They also gripped a surrogate PFS device at 28N and maximum force to measure endurance. Data predicted the 5th percentile pinch force endurance for COPD patients.Results The estimated COPD patients' 5th percentile pinch force endurance at 28N was 16 seconds, while their maximum pinch force endurance was around 4.4 seconds. Males pinched and held 28N longer than females, but no gender difference was observed at the maximum force. Endurance decreased as required force approached maximum capacity (consistent with Rohmert's Curve).Conclusions PFS usage can be challenging for users with strength limitations. A 28N force was sustainable for 16 seconds for 95% of COPD patients. Developers should minimize injection force where possible and accommodate varied injection styles-lower forces improve endurance, aiding users with reduced strength. These findings support designing accessible PFS for diverse populations.

The answer to this question is yes, and yes. The two subjects co-exist within pharmaceutical manufacturing in aseptic and sterile environments. This poster will highlight how environmental monitoring and disinfection provide continuous trending, process improvement, and final product evaluations. The processes need to be designed to identify outliers (biological and numerical) and objectionable organisms and assess cleaning protocols based on data collected. The information acquired through environmental monitoring and disinfectant efficacy studies helps to determine effective Root Cause Analysis and Corrective Action when issues with contamination are encountered. The processes, when performed and evaluated consistently will ensure that manufacturing environments are in a state of control and the products manufactured in sterile and aseptic environments are pure, safe, and effective.

The Mango system was evaluated by spiking Fluid A with seven different microorganisms: Clostridium sporogenes ATCC 11437, Cutibacterium acnes ATCC 6919, Staphylococcus aureus ATCC 6538, Bacillus spizizenii ATCC 6633, Aspergillus brasiliensis ATCC 16404, Pseudomonas paraeruginosa ATCC 9027, and Candida albicans ATCC 10231. For each microorganism, two replicates were prepared on spread plates, Oasis TSA cartridges, and Mango Cartridges. Each microorganism was tested three times by three different analysts. The inoculated control plates (Oasis and spread plates onto TSA medium) were incubated at 30-35°C for 24h to 7 days. The Mango test plates were incubated for 16-160h.The study provides comparative data on the time to detection and recovery rates for the tested microorganisms. The results indicated that the Mango system consistently showed faster time to detection for aerobic organisms than traditional methods, however incubation time and conditions were microorganism-dependent, particularly for anaerobic bacteria such as C. sporogenes and C. acnes. In addition, this study showed that the rates of recovery between the Mango and traditional systems were equivalent and provides data on the filterability of different matrices. The findings indicate that the Mango system has potential to rapidly and consistently recovery microorganisms from biopharmaceutical samples.

Bacterial endospores represent a significant challenge to the pharmaceutical industry due to their presence in the environment, resistance to many commonly used inactivation procedures, and difficulty in culturing using traditional plating methods. This may result in the inadvertent release of contaminated products that may present health concerns for the patient. As a result, the use of a bio-fluorescent particle counter (BFPC) may prove advantageous for the detection of both water-borne and air-borne spores as their detection is not dependent on traditional culturing methods. In this study, we investigate the ability of an online water bioburden analyzer (OWBA), a specific class of BFPC, to detect Bacillus subtilis spores in pharmaceutical-grade water and present the results as auto-fluorescence units (AFU's) per B. subtilis spore. The spores were a commercial grade spore preparation and were previously quantified per manufacture recommendations. The results show that the OWBA can detect B. subtilis spores with an accuracy of 1.25 AFU per spore. The limit of detection was determined to be 1 spore/mL with a linearity greater than 0.9025 up to a concentration of 100 spores/mL. This data shows that OWBA's are a rapid and effective tool for the detection of bacterial endospores in pharmaceutical waters.

EU GMP Annex I, Section 4.36 specifically states that "Cleaning programs should effectively remove disinfectant residues". Although residue in controlled environments, and disinfectant residue in particular, has been around since the advent of cleanroom disinfection, there is currently an increased sensitivity towards understanding and mitigating cleanroom residues.This talk will focus on the science and microbiology of scientific residues including potential impact on rotational sporicides, the likelihood of trapping microorganisms and best practices for addressing residue in the cleanroom. The active ingredients and surfactants that make up disinfectant residue are not inherently bad, but instead key components of a complex formulation. By understanding the nature of disinfectant residue and their impacts, continuous improvements can be made to optimize an overall cleaning and disinfection program.

Roche has implemented an automated endotoxin system (Lonza PyroTec® PRO) in commercial Quality Control microbiology.The key drivers for the implementation were to reduce ergonomic risk, save time and resources, increase data integrity, simplify training, digitalization, digital data flow and increase the right-first-time rate.The strategic approach to implementation and conclusions from routine testing shall be shared and discussed.