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PDA Journal of Pharmaceutical Science... 2020This technology review, written by a small group of pharmaceutical microbiologists experienced in cell therapies, discussed a risk-based approach to microbiological... (Review)
Review
This technology review, written by a small group of pharmaceutical microbiologists experienced in cell therapies, discussed a risk-based approach to microbiological contamination detection and control during gene and cell therapy production. Topics discussed include a brief overview of cell therapies, a risk analysis related to donor selection, cell collection and infectious agent testing, cell transformation and expansion, packaging, storage, and administration, and cell therapy microbial contamination testing and release.
Topics: Cell- and Tissue-Based Therapy; Drug Contamination; Drug Packaging; Humans; Risk Assessment; Technology, Pharmaceutical
PubMed: 31941793
DOI: 10.5731/pdajpst.2019.010546 -
PDA Journal of Pharmaceutical Science... 2020Extractables and leachables (E&L) are identified and quantified so that their impact on patient safety can be established and assessed. The uncertainty in the impact... (Review)
Review
Extractables and leachables (E&L) are identified and quantified so that their impact on patient safety can be established and assessed. The uncertainty in the impact assessment is affected by the uncertainty in the substance's experimentally determined identity and concentration. Thus, these experimentally determined quantities must be reported not only in terms of their absolute result but also in terms of the uncertainty in the result, which is based on the amount and rigor of the information on which the result is based. In this way, the impact assessment can be tempered to account for the uncertainty in its input data. To facilitate the assignment and reporting of uncertainty, classification hierarchies are proposed and discussed for both identification and quantitation. Both hierarchies establish levels or degrees of identification and quantitation based on the uncertainty of the result and contain descriptions of the quality and quantity of information required to achieve a certain level within the hierarchy. The minimal levels that must be achieved to support impact assessment are also established.
Topics: Chemistry, Pharmaceutical; Drug Contamination; Drug Packaging; Humans; Patient Safety; Pharmaceutical Preparations
PubMed: 31420509
DOI: 10.5731/pdajpst.2019.010538 -
Briefings in Bioinformatics Jul 2023Human prescription drug labeling contains a summary of the essential scientific information needed for the safe and effective use of the drug and includes the...
Human prescription drug labeling contains a summary of the essential scientific information needed for the safe and effective use of the drug and includes the Prescribing Information, FDA-approved patient labeling (Medication Guides, Patient Package Inserts and/or Instructions for Use), and/or carton and container labeling. Drug labeling contains critical information about drug products, such as pharmacokinetics and adverse events. Automatic information extraction from drug labels may facilitate finding the adverse reaction of the drugs or finding the interaction of one drug with another drug. Natural language processing (NLP) techniques, especially recently developed Bidirectional Encoder Representations from Transformers (BERT), have exhibited exceptional merits in text-based information extraction. A common paradigm in training BERT is to pretrain the model on large unlabeled generic language corpora, so that the model learns the distribution of the words in the language, and then fine-tune on a downstream task. In this paper, first, we show the uniqueness of language used in drug labels, which therefore cannot be optimally handled by other BERT models. Then, we present the developed PharmBERT, which is a BERT model specifically pretrained on the drug labels (publicly available at Hugging Face). We demonstrate that our model outperforms the vanilla BERT, ClinicalBERT and BioBERT in multiple NLP tasks in the drug label domain. Moreover, how the domain-specific pretraining has contributed to the superior performance of PharmBERT is demonstrated by analyzing different layers of PharmBERT, and more insight into how it understands different linguistic aspects of the data is gained.
Topics: Humans; Drug Labeling; Information Storage and Retrieval; Learning; Natural Language Processing
PubMed: 37317617
DOI: 10.1093/bib/bbad226 -
Annals of Clinical Psychiatry :... Nov 2022
Topics: Humans; United States; Drug Labeling; Drug-Related Side Effects and Adverse Reactions
PubMed: 36331562
DOI: 10.12788/acp.0084 -
Dermatology (Basel, Switzerland) 2021Off-label drug use is associated with an increased risk of adverse drug reactions. It is common in pediatrics and in rare diseases, which are two characteristics...
BACKGROUND
Off-label drug use is associated with an increased risk of adverse drug reactions. It is common in pediatrics and in rare diseases, which are two characteristics applying to vascular anomalies (VA).
OBJECTIVES
The aim of this work was to quantify off-label drug use in VA and assess its safety.
METHODS
A review was conducted to extract a list of drugs used in VA management. A drug was considered to have significant safety concerns if a black box warning was present or if a serious adverse drug reaction (SADR) was reported in at least 1% of the patients (SADR is defined as a noxious and unintended response to a drug that occurs at any dose and results in hospitalization, prolongation of existing hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data.
RESULTS
We found that 98.9% of the inventoried drugs were used off-label or unlicensed for VA management. Only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas is approved. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs.
CONCLUSIONS
Off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is necessary to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients should be openly informed and involved in the decision-making process.
Topics: Blood Vessels; Congenital Abnormalities; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Humans; Off-Label Use; Pharmaceutical Preparations
PubMed: 33823514
DOI: 10.1159/000515980 -
Journal of Dairy Science Dec 2023The aim of this study was to evaluate the influence of different packaging materials [standard foil: BOPP (biaxially oriented polypropylene)/PET (polyester)/PE...
The aim of this study was to evaluate the influence of different packaging materials [standard foil: BOPP (biaxially oriented polypropylene)/PET (polyester)/PE (polyethylene) for upper layer, and APET (polyethylene terephthalate)/PE for bottom layer; foil 1: PP (polypropylene)/PET/PE/EVOH (ethylene-vinyl alcohol copolymer)/PE upper layer, and PP/PE/EVOH/PE bottom layer; foil 2: PP/PET/PE/EVOH/PE upper layer, and PA (polyamide)/EVOH/PE bottom layer; foil 3: PP/PET/PE upper layer, and PA/EVOH/PE bottom layer; foil 4: PP/PET/PE upper layer, and PA/PE bottom layer; foil 5: PP upper layer, and PP/PP bottom layer] on the quality of 3 different ripening rennet cheeses packed under different modified atmosphere (MAP) conditions as reflected in particular physicochemical, microbiological, and sensorial changes. The changes were monitored during a period of 90 d of storage at 2°C or 8°C. For Gouda cheese, CO content of the headspace of the packages was in the range 35% to 45%, whereas for Maasdamer and Sielski Klasyczny cheeses it was 55% to 65%. Three-way ANOVA showed that the foil type influenced the moisture content of Gouda cheese stored for 90 d at 2°C and for Sielski Klasyczny cheese at 8°C, whereas the moisture content was not dependent on MAP conditions during storage. Moreover, the foil type had a significant effect on free fatty acid changes for Gouda and Sielski Klasyczny cheeses stored at 2°C for 90 d. Sensory attributes changed significantly over storage time at 2°C for all studied cheeses as affected by foil type, whereas there was no effect of MAP conditions. In general, the cheeses packed in standard foil and foil 4 were characterized by the highest values of mean sensory attributes. Time was the most significant factor influencing most changes in physicochemical and sensory attributes of cheeses stored at 2°C and 8°C. The storage temperature did not affect the moisture of the samples during storage. In general, we found an increase in the pH value during storage regardless of storage temperature. It was possible to decrease the thickness of the packaging material from initial 103 and 250 µm (standard foil; lid and bottom, respectively) to 98 and 100 µm (foil 4) without affecting sensory attributes of the product.
Topics: Animals; Cheese; Polypropylenes; Food Packaging; Drug Packaging; Climate
PubMed: 37641356
DOI: 10.3168/jds.2022-22772 -
Toxicology and Industrial Health Dec 2022Silicon is one of the most monitored elements in extractables and leachables studies of pharmaceutical packaging systems and related components. There is a need to... (Review)
Review
Silicon is one of the most monitored elements in extractables and leachables studies of pharmaceutical packaging systems and related components. There is a need to review and evaluate toxicological thresholds of silicon because of its direct contact with drug products (DP) especially a liquid form of DP with the widely used pharmaceutical packaging systems made of silicon materials like glass and silicone. It is required by regulatory authorities to test silicon content in DP; however, there are no official guidelines on the toxicology of silicon that are currently available, yet the knowledge of toxicological thresholds of silicon is critical to justify the analytical limit of quantification (LOQ). Therefore, we reviewed the toxicity of silicon to derive a toxicological threshold by literature review of toxicity studies of both inorganic and organic silicon compounds. Oral toxicity is low for inorganic silicon like silicon dioxide or organic silicon polymers such as silicone tube/silicone oil (polydimethylsiloxane, or namely, PDMS as the major ingredient). In comparison, inhalational toxicity of silicon dioxide leads to pulmonary silicosis or even lung cancer. When orally administered, the toxicity of silicon dioxide, glass, polymers, or PDMS oligomers varies depending on their morphology, molecular weight (MW), and degrees of polymerization. PDMS with high MW has minimal toxic symptoms with non-detectable degradation/elimination by both intraperitoneal and subcutaneous administration routes, while exposure to either PDMS or small molecule dimethyl silicone compounds by the intravenous administration route may lead to death. We here determined a general parenteral permitted daily exposure (PDE) of 93 μg/day for inorganic silicon element and 100 μg/day for organic silicon element by reviewing toxicological data of both forms of silicon. In conclusion, this work provides evidence for pharmaceutical companies and regulatory agencies on the PDEs of silicon elements in pharmaceutical packaging and process components through a variety of administration routes.
Topics: Molecular Weight; Polymers; Silicon Dioxide; Silicones; Drug Packaging
PubMed: 36368686
DOI: 10.1177/07482337221123368 -
Yakugaku Zasshi : Journal of the... 2021Recent years, evidences for medical safety and efficacy are accelerated-developing using medical big data. Medical big data were adequate for analyzing 1) rare events... (Review)
Review
Recent years, evidences for medical safety and efficacy are accelerated-developing using medical big data. Medical big data were adequate for analyzing 1) rare events that difficult for finding in each hospital, 2) for comparison of bench marks obtained routine work between average data in large number of hospitals and specific hospital data and 3) prescription surveys etc. As so far, these analyses using medical big data were conducted by academia and/or researcher. However, in these days, evidences using medical big data were focused on hospital pharmacists little by little. In this review, we show 3 researches using large claims data such as 1) risk factors assessing for failed low-density lipoprotein level achievement in members of the working-age population, 2) prevalence of drug-drug interaction in atrial fibrillation patients and 3) assessment of "look-alike" packaging designs related to medication errors using information technology and large claims data. Medical big data such as large claims data analysis is useful and suitable for building evidences according to medical staffs-needs.
Topics: Atrial Fibrillation; Big Data; Drug Interactions; Drug Packaging; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins, LDL; Medication Errors; Pharmacists; Pharmacy Service, Hospital; Risk Factors; Safety; Treatment Outcome
PubMed: 33518636
DOI: 10.1248/yakushi.20-00196-3 -
Pharmaceutical Medicine Sep 2021Pharmaceutical development was at the forefront of efforts to prevent infection with the SARS-CoV-2 virus as well as to treat its often-devastating effects. Drug... (Review)
Review
Pharmaceutical development was at the forefront of efforts to prevent infection with the SARS-CoV-2 virus as well as to treat its often-devastating effects. Drug development, and its multifaceted and multi-disciplined activity toward effective vaccines and drugs, became part of everyday news. I review several key areas of vaccine and drug development that were brought into the public mainstream over the evolution of the pandemic. These include the unprecedented speed of vaccine discovery and development, issues uncovered from early clinical studies, and regulatory concepts that were highlighted throughout the development process. Among these was the importance of pharmacovigilance as each new agent was rapidly deployed to a mostly eager public. Critical challenges around production, packaging, and procurement of product for patient use were often centre stage. Finally, the ever-important need to transition not only from scientific concept to vaccine and drug, but from their authorized and approved use to their implementation in health systems to insure the intended effects both in individuals and populations.
Topics: Animals; COVID-19; COVID-19 Vaccines; Drug Approval; Drug Development; Drug Discovery; Drug Packaging; Global Health; Health Knowledge, Attitudes, Practice; Humans; Patient Safety; Public Opinion; Risk Assessment; Risk Factors
PubMed: 34580837
DOI: 10.1007/s40290-021-00402-y -
Journal of Pharmaceutical Sciences May 2021Advanced therapy medicinal products (ATMPs), such as somatic cell-therapy medicinal products or tissue-engineered products for human use, offer new and potentially... (Review)
Review
Advanced therapy medicinal products (ATMPs), such as somatic cell-therapy medicinal products or tissue-engineered products for human use, offer new and potentially curative opportunities to treat yet untreatable diseases or disorders. For cell-therapy medicinal products (CBMPs), multiple stability and quality challenges exist and relate to the cellular composition and unstable nature of these parenteral preparations. It is the aim of this review to discuss open questions and problems associated with the development, manufacturing and testing of CBMPs from a pharmaceutical drug product perspective. This includes safety, storage and handling, particulates, the choice of container closure systems and integrity. Analytical methods commonly used to evaluate the quality of the final CBMP to ensure patient's safety will be discussed. Particulate contamination in final products deserve special attention since CBMPs cannot be sterile filtered. Visible and sub-visible particles may represent environmental contaminations or may form during storage. They may be introduced from processing materials such as single use product contact materials, ancillary materials, or any components such as primary packaging used for the final product. Currently available analytical methods for detecting particulates may not be easily applicable to CBMPs due to their inherent particulate nature and appearance.
Topics: Drug Contamination; Drug Packaging; Humans; Pharmaceutical Preparations
PubMed: 33307042
DOI: 10.1016/j.xphs.2020.11.040