scholarly journals Investigating Alternative Container Formats for Lyophilization of Biological Materials Using Diphtheria Antitoxin Monoclonal Antibody as a Model Molecule

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1948
Author(s):  
Kiran P. Malik ◽  
Chinwe Duru ◽  
Paul Stickings ◽  
Esther Veronika Wenzel ◽  
Michael Hust ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Biological Materials ◽  
International Standards ◽  
Size Exclusion ◽  
Long Term Storage ◽  
Model Molecule ◽  
Freeze Dried ◽  
Diphtheria Antitoxin ◽  
The Stability ◽  
And Control

When preparing biological reference materials, the stability of the lyophilized product is critical for long-term storage, particularly in order to meet WHO International Standards, which are not assigned expiry dates but are expected to be in use for several decades. Glass ampoules are typically used by the National Institute for Biological Standards and Control (NIBSC) [PM1] for the lyophilization of biological materials. More recently, a clear need has arisen for the filling of smaller volumes, for which ampoules may not be optimal. We investigated the use of plastic microtubes as an alternative container for small volume fills. In this study, a recombinant diphtheria antitoxin monoclonal antibody (DATMAB) was used as a model molecule to investigate the suitability of plastic microtubes for filling small volumes. The stability and quality of the dried material was assessed after an accelerated degradation study using a toxin neutralization test and size exclusion HPLC. While microtubes have shown some promise in the past for use in the lyophilization of some biological materials, issues with stability may arise when more labile materials are freeze-dried. We demonstrate here that the microtube format is unsuitable for ensuring the stability of this monoclonal antibody.

scholarly journals Review on Basic Components of E-Kart

2022 ◽  
Vol 10 (1) ◽  
pp. 342-345
Author(s):  
Prof. Mayur Shelke
Keyword(s):  
Energy Flow ◽  
Lithium Ion ◽  
International Standards ◽  
Brushless Dc Motor ◽  
Frame Design ◽  
Brushless Dc ◽  
Hazardous Gases ◽  
The Stability ◽  
And Control ◽  
Motor Controls

Abstract: This review paper presents the design and development of an E-kart. The moto behind making this Electric-kart is to lower the number of pollutants and hazardous gases such as carbon monoxide, hydrocarbons, nitrogen oxide, etc. These types of gases are produced in an immense amount from vehicles. Therefore, we decided to make a vehicle that works efficiently on an electric motor and controller. We have used BLDC (brushless dc motor) motor which is powered by direct current and voltage. Motor control the motor controls the energy flow to the motor processes like throttle, brake, and control switches are connected to controller commands from these inputs i.e. Throttle, brake, etc., and control very precisely torque, speed, direction on and horsepower of the vehicle. The battery we used is a rechargeable lithium-ion battery. The main focus during the frame design was the stability of the E-kart and the safety of the driver. We also surveyed the market on chassis material, motor, brake, controller, and transmission system for cost and availability. International standards were followed during the whole project.

scholarly journals Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Brittany K. Chavez ◽  
Cyrus D. Agarabi ◽  
Erik K. Read ◽  
Michael T. Boyne II ◽  
Mansoor A. Khan ◽  
...  
Keyword(s):  
High Performance ◽  
Storage Conditions ◽  
Size Exclusion ◽  
Worst Case ◽  
Long Term Storage ◽  
Improved Stability ◽  
Bioreactor System ◽  
The Stability ◽  
Storage Buffer

Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 24full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Thus, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.

The Stability and Shelf-Life of Liposome Encapsulated Hemoglobin: A Potential Blood Substitute

1987 ◽  
Vol 110 ◽  
Author(s):  
Alans Rudolph ◽  
Lewis P. Stratton ◽  
Wayne K. Knoll ◽  
Sandra Bayne ◽  
Frances Ligler
Keyword(s):  
Shelf Life ◽  
Blood Substitute ◽  
Oxidative Process ◽  
Long Term Storage ◽  
Freeze Dried ◽  
Great Progress ◽  
The Stability ◽  
Long Term Preservation ◽  
Term Storage

AbstractFor any viable blood substitute, questions of long-term storage and shelf-life must be addressed. Recently, we have made great progress in improving the stability of the blood substitute, liposome encapsulated hemoglobin (LEH). We have concentrated our efforts on protecting LEH in solution and in the long-term preservation of LEH by lyophilization. In particular, we have been able to retard and in some cases, reverse the oxidative process of metHb formation in solution by the addition of antioxidants such as NADH and glutathione. We have been able to regenerate Hb preparations with 60% metHb by the addition of 10 mM NADH and glutathione. In these preparations addition of these antioxidants results in a decrease of metHb levels from 62% to 15% over the course of 12.5 days at 4°C. We have also explored the use of protective solutes such as the disaccharide trehalose in the preservation of LEH in the freeze-dried state. Addition of increasing amounts of trehalose and other disaccharides results in the inhibition of lyophilization-induced fusion events and in the retention of hemoglobin within the unilamellar liposomal vesicles following rehydration.

Factor VIII International Units and Reference Materials

1974 ◽  
Vol 31 (01) ◽  
pp. 003-011 ◽  
Author(s):  
Derek R Bangham ◽  
Milica Brozović
Keyword(s):  
Factor Viii ◽  
International Standards ◽  
National Standards ◽  
National Standard ◽  
Clotting Factors ◽  
Working Standard ◽  
Long Term Storage ◽  
Freeze Dried ◽  
Term Storage

SummaryThe establishment of the International Standard for factor VIII has introduced a common yardstick, the international unit, which all countries can apply. This standard is a concentrate of intermediate purity, shown to be very stable on long term storage. As with all international standards it is available in limited quantities and is primarily used for the calibration of national standards used to monitor patients and in the control of therapeutic preparations.Since 1969 in Great Britain such a national standard has been made from freeze-dried pooled plasma. This has been available in larger quantities and has been introduced into routine use in coagulation laboratories. As factor VIII in freeze-dried plasma has limited stability even when stored at —20° C, successive new batches are prepared every two years or so. The availability of a common working standard with factor VIII content specified in international units makes it possible to define diagnostic and therapeutic criteria with more precision than hitherto. This system can be applied in other countries and to other clotting factors for which an international yardstick is needed.

Impact of different cryoprotectants on the survival of freeze-dried Lactobacillus rhamnosus and Lactobacillus casei/paracasei during long-term storage

2015 ◽  
Vol 6 (3) ◽  
pp. 381-386 ◽  
Author(s):  
A. Jofré ◽  
T. Aymerich ◽  
M. Garriga
Keyword(s):  
Shelf Life ◽  
Lactobacillus Casei ◽  
Freeze Drying ◽  
Lactobacillus Rhamnosus ◽  
Skim Milk ◽  
Storage Period ◽  
Starter Cultures ◽  
Long Term Storage ◽  
Freeze Dried ◽  
The Stability

The production of long shelf-life highly concentrated dried probiotic/starter cultures is of paramount importance for the food industry. The aim of the present study was to evaluate the protective effect of glucose, lactose, trehalose, and skim milk applied alone or combined upon the survival of potentially probiotic Lactobacillus rhamnosus CTC1679, Lactobacillus casei/paracasei CTC1677 and L. casei/paracasei CTC1678 during freeze-drying and after 39 weeks of storage at 4 and 22 °C. Immediately after freeze-drying, the percentage of survivors was very high (≥94%) and only slight differences were observed among strains and cryoprotectants. In contrast, during storage, survival in the dried state depended on the cryoprotectant, temperature and strain. For all the protectants assayed, the stability of the cultures was remarkably higher when stored under refrigeration (4 °C). Under these conditions, skim milk alone or supplemented with trehalose or lactose showed the best performance (reductions ≤0.9 log units after 39 weeks of storage). The lowest survival was observed during non-refrigerated storage and with glucose and glucose plus milk; no viable cells left at the end of the storage period. Thus, freeze-drying in the presence of appropriate cryoprotectants allows the production of long shelf-life highly concentrated dried cultures ready for incorporation in high numbers into food products as starter/potential probiotic cultures.

scholarly journals Clinical validation of optimised RT-LAMP for the diagnosis of SARS-CoV-2 infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Boon Lim ◽  
Jeremy Ratcliff ◽  
Dorota A. Nawrot ◽  
Yejiong Yu ◽  
Harshmeena R. Sanghani ◽  
...  
Keyword(s):  
Colorimetric Detection ◽  
Free Water ◽  
Lamp Assay ◽  
Cross Reactivity ◽  
Single Step ◽  
Long Term Storage ◽  
Freeze Dried ◽  
Human Coronaviruses ◽  
The Stability ◽  
The Uk

AbstractWe have optimised a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of SARS-CoV-2 from extracted RNA for clinical application. We improved the stability and reliability of the RT-LAMP assay by the addition of a temperature-dependent switch oligonucleotide to reduce self- or off-target amplification. We then developed freeze-dried master mix for single step RT-LAMP reaction, simplifying the operation for end users and improving long-term storage and transportation. The assay can detect as low as 13 copies of SARS-CoV2 RNA per reaction (25-μL). Cross reactivity with other human coronaviruses was not observed. We have applied the new RT-LAMP assay for testing clinical extracted RNA samples extracted from swabs of 72 patients in the UK and 126 samples from Greece and demonstrated the overall sensitivity of 90.2% (95% CI 83.8–94.7%) and specificity of 92.4% (95% CI 83.2–97.5%). Among 115 positive samples which Ct values were less than 34, the RT-LAMP assay was able to detect 110 of them with 95.6% sensitivity. The specificity was 100% when RNA elution used RNase-free water. The outcome of RT-LAMP can be reported by both colorimetric detection and quantifiable fluorescent reading. Objective measures with a digitized reading data flow would allow for the sharing of results for local or national surveillance.

The Stability of the WHO Reference Thromboplastin NIBS & C 67/40

1979 ◽  
Vol 42 (04) ◽  
pp. 1135-1140 ◽  
Author(s):  
G I C Ingram
Keyword(s):  
Human Brain ◽  
Collaborative Study ◽  
Calibration Constant ◽  
Long Term Stability ◽  
Freeze Dried ◽  
Show Evidence ◽  
Human Material ◽  
Reference Preparation ◽  
The Stability

SummaryThe International Reference Preparation of human brain thromboplastin coded 67/40 has been thought to show evidence of instability. The evidence is discussed and is not thought to be strong; but it is suggested that it would be wise to replace 67/40 with a new preparation of human brain, both for this reason and because 67/40 is in a form (like Thrombotest) in which few workers seem to use human brain. A �plain� preparation would be more appropriate; and a freeze-dried sample of BCT is recommended as the successor preparation. The opportunity should be taken also to replace the corresponding ox and rabbit preparations. In the collaborative study which would be required it would then be desirable to test in parallel the three old and the three new preparations. The relative sensitivities of the old preparations could be compared with those found in earlier studies to obtain further evidence on the stability of 67/40; if stability were confirmed, the new preparations should be calibrated against it, but if not, the new human material should receive a calibration constant of 1.0 and the new ox and rabbit materials calibrated against that.The types of evidence available for monitoring the long-term stability of a thromboplastin are discussed.

Prothrombin Time Standardization: Report of the Expert Panel on Oral Anticoagulant Control

1979 ◽  
Vol 42 (04) ◽  
pp. 1073-1114 ◽  
Keyword(s):  
Prothrombin Time ◽  
Expert Panel ◽  
The Other ◽  
Rabbit Brain ◽  
Calibration Constant ◽  
Freeze Dried ◽  
The Mean ◽  
Point Of Intersection ◽  
And Control ◽  
Standardization Report

SummaryIn collaborative experiments in 199 laboratories, nine commercial thromboplastins, four thromboplastins held by the National Institute for Biological Standards and Control (NIBS & C), London and the British Comparative Thromboplastin were tested on fresh normal and coumarin plasmas, and on three series of freeze-dried plasmas. One of these was made from coumarin plasmas and the other two were prepared from normal plasmas; in each series, one plasma was normal and the other two represented different degrees of coumarin defect.Each thromboplastin was calibrated against NIBS&C rabbit brain 70/178, from the slope of the line joining the origin to the point of intersection of the mean ratios of coumarin/normal prothrombin times when the ratios obtained with the two thromboplastins on the same fresh plasmas were plotted against each other. From previous evidence, the slopes were calculated which would have been obtained against the NIBS&C “research standard” thromboplastin 67/40, and termed the “calibration constant” of each thromboplastin. Values obtained from the freeze-dried coumarin plasmas gave generally similar results to those from fresh plasmas for all thromboplastins, whereas values from the artificial plasmas agreed with those from fresh plasmas only when similar thromboplastins were being compared.Taking into account the slopes of the calibration lines and the variation between laboratories, precision in obtaining a patient’s prothrombin time was similar for all thromboplastins.

Evaluation of the Efficiency of Protein A Affinity Chromatography to Purify a Monoclonal Antibody for Cancer Treatment and its Purity Analysis

2020 ◽  
Vol 7 (2) ◽  
pp. 121-133
Author(s):  
Ayesha Akhtar ◽  
Shivakumar Arumugam ◽  
Shoaib Alam
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Affinity Chromatography ◽  
Protein A ◽  
Exchange Chromatography ◽  
Size Exclusion ◽  
High Yield ◽  
Staphylococcal Protein A ◽  
Purification Step ◽  
Purity Analysis

Background:: Protein A affinity chromatography is often employed as the most crucial purification step for monoclonal antibodies to achieve high yield with purity and throughput requirements. Introduction:: Protein A, also known as Staphylococcal protein A (SPA) is found in the cell wall of the bacteria staphylococcus aureus. It is one of the first discovered immunoglobulin binding molecules and has been extensively studied since the past few decades. The efficiency of Protein A affinity chromatography to purify a recombinant monoclonal antibody in a cell culture sample has been evaluated, which removes 99.0% of feed stream impurities. Materials and Method:: We have systematically evaluated the purification performance by using a battery of analytical methods SDS-PAGE (non-reduced and reduced sample), Cation Exchange Chromatography (CEX), Size-exclusion chromatography (SEC), and Reversed phased-Reduced Chromatography for a CHO-derived monoclonal antibody. Results and Discussion:: The analytical test was conducted to determine the impurity parameter, Host Cell Contaminating Proteins (HCP). It was evaluated to be 0.015ng/ml after the purification step; while initially, it was found to be 24.431ng/ml. Conclusion:: The tests showed a distinct decrease in the level of different impurities after the chromatography step. It can be concluded that Protein A chromatography is an efficient step in the purification of monoclonal antibodies.

scholarly journals Data-Driven Stability Assessment of Multilayer Long Short-Term Memory Networks

2021 ◽  
Vol 11 (4) ◽  
pp. 1829
Author(s):  
Davide Grande ◽  
Catherine A. Harris ◽  
Giles Thomas ◽  
Enrico Anderlini
Keyword(s):  
Neural Network ◽  
Network Architecture ◽  
Short Term Memory ◽  
Moving Average ◽  
Machine Learning Algorithms ◽  
Physical Models ◽  
Data Driven ◽  
The Stability ◽  
And Control ◽  
Nonlinear Autoregressive

Recurrent Neural Networks (RNNs) are increasingly being used for model identification, forecasting and control. When identifying physical models with unknown mathematical knowledge of the system, Nonlinear AutoRegressive models with eXogenous inputs (NARX) or Nonlinear AutoRegressive Moving-Average models with eXogenous inputs (NARMAX) methods are typically used. In the context of data-driven control, machine learning algorithms are proven to have comparable performances to advanced control techniques, but lack the properties of the traditional stability theory. This paper illustrates a method to prove a posteriori the stability of a generic neural network, showing its application to the state-of-the-art RNN architecture. The presented method relies on identifying the poles associated with the network designed starting from the input/output data. Providing a framework to guarantee the stability of any neural network architecture combined with the generalisability properties and applicability to different fields can significantly broaden their use in dynamic systems modelling and control.

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