Comprehensive Temperature Excursion Management Program for the Commercial Distribution of Biopharmaceutical Drug Products

Desai, Kashappa Goud H.; Colandene, James D.; Adams, Monica

doi:10.1016/j.xphs.2020.04.006

Cited by 7 publications

(6 citation statements)

References 24 publications

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“…During all the experimental flights, the MKT of the cargo was found to be within the required specification (2 • C to 8 • C, Figure 12), based on calibrated sensor data [52]. For trial 1 (Thorney Island fixed-wing), temperatures were not affected by flights.…”

Section: Temperature Analysis (Trials 1 2 3)mentioning

confidence: 77%

Quantifying the Effects of Vibration on Medicines in Transit Caused by Fixed-Wing and Multi-Copter Drones

Oakey

Waters

Zhu

et al. 2021

Drones

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The concept of transporting medical products by drone is gaining a lot of interest amongst the medical and logistics communities. Such innovation has generated several questions, a key one being the potential effects of flight on the stability of medical products. The aims of this study were to quantify the vibration present within drone flight, study its effect on the quality of the medical insulin through live flight trials, and compare the effects of vibration from drone flight with traditional road transport. Three trials took place in which insulin ampoules and mock blood stocks were transported to site and flown using industry standard packaging by a fixed-wing or a multi-copter drone. Triaxial vibration measurements were acquired, both in-flight and during road transit, from which overall levels and frequency spectra were derived. British Pharmacopeia quality tests were undertaken in which the UV spectra of the flown insulin samples were compared to controls of known turbidity. In-flight vibration levels in both the drone types exceeded road induced levels by up to a factor of three, and predominant vibration occurred at significantly higher frequencies. Flown samples gave clear insulin solutions that met the British Pharmacopoeia specification, and no aggregation of insulin was detected.

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Section: Temperature Analysis (Trials 1 2 3)mentioning

confidence: 77%

Quantifying the Effects of Vibration on Medicines in Transit Caused by Fixed-Wing and Multi-Copter Drones

Oakey

Waters

Zhu

et al. 2021

Drones

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“…The kinetic model, however, can also be applied under non-stable temperatures, by solving the differential equations numerically given the temperature profile over time after the values of the kinetic parameters have been estimated. This is important for vaccines, especially for thermosensitive ones recently developed against COVID-19, as there is no guarantee that, during transport, for example, the temperature will remain constant and, at the point of care where the vaccine is administered, the conditions may not be as tightly controlled as in the labs of the manufacturer [ 12 , 13 , 14 ].…”

Section: Resultsmentioning

confidence: 99%

Use of Stability Modeling to Support Accelerated Vaccine Development and Supply

Campa¹,

Pronce

Paludi³

et al. 2021

Vaccines

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Stability assessment of pharmaceuticals in specific storage and shipment conditions is a key requirement to ensure that safe and efficacious products are administered to patients. This is particularly relevant for vaccines, with numerous vaccines strictly requiring cold storage to remain stable. When stability evaluation is exclusively based on real-time data, it may represent a bottleneck for rapid and effective vaccine access. Stability modeling for vaccines represents a key resource to predict stability based on accelerated stability studies; nevertheless, this approach is not fully exploited for these kinds of products. This is likely because of the complexity and diversity of vaccines, as well as the limited availability of dedicated guidelines or illustrative case studies. This article reports a cross-company perspective on stability modeling for vaccines. Several examples, based on the direct experience of the contributors, demonstrate that modeling approaches can be highly valuable to predict vaccines’ shelf life and behavior during shipment or manipulation. It is demonstrated that modeling methodologies need to be tailored to the nature of the vaccine, the available prior knowledge, and the monitored attributes. Considering that the well-established strategies reported in ICH or WHO guidelines are not always broadly applicable to vaccines, this article represents an important source of information for vaccine researchers and manufacturers, setting the grounds for further discussion within the vaccine industry and with regulators.

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“…For example, changes in the pH and salt concentration during the chromatography, viral inactivation, and buffer exchange steps may destabilize the protein structure and/or cause chemical modifications to the protein. , Furthermore, interactions with a range of matrices and surfaces, such as filters, columns, and membranes, as well as physical stress and shear forces caused by sparging, pumping, mixing, and shaking, may lead to loss of the native protein structure and potentially protein function. , During bioprocessing, aggregate levels may reach up to 30% at the cell culture stage and may be as high as 25% when eluting from the Protein A column due to the low pH conditions . In addition to the upstream and downstream processing steps, packaging, transportation, storage, and administration steps following production can also negatively impact protein stability, for example due to temperature variations, where the mAb is exposed to temperatures outside the acceptable range, unintentional freeze–thaw cycles, interfacial stresses, and exposure to light. ,,− …”

Section: Introductionmentioning

confidence: 99%

“… 9 In addition to the upstream and downstream processing steps, packaging, transportation, storage, and administration steps following production can also negatively impact protein stability, for example due to temperature variations, where the mAb is exposed to temperatures outside the acceptable range, unintentional freeze–thaw cycles, interfacial stresses, and exposure to light. 5 , 7 , 10 − 13 …”

Section: Introductionmentioning

confidence: 99%

Study of Monoclonal Antibody Aggregation at the Air–Liquid Interface under Flow by ATR-FTIR Spectroscopic Imaging

van Haaren,

Byrne,

Kazarian

2024

Langmuir

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Throughout bioprocessing, transportation, and storage, therapeutic monoclonal antibodies (mAbs) experience stress conditions that may cause protein unfolding and/or chemical modifications. Such structural changes may lead to the formation of aggregates, which reduce mAb potency and may cause harmful immunogenic responses in patients. Therefore, aggregates need to be detected and removed or ideally prevented from forming. Air–liquid interfaces, which arise during various stages of bioprocessing, are one of the stress factors causing mAb aggregation. In this study, the behavior of an immunoglobulin G (IgG) at the air–liquid interface was investigated under flow using macro attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic imaging. This chemically specific imaging technique allows observation of adsorption of IgG to the air–liquid interface and detection of associated secondary structural changes. Chemical images revealed that IgG rapidly accumulated around an injected air bubble under flow at 45 °C; however, no such increase was observed at 25 °C. Analysis of the second derivative spectra of IgG at the air–liquid interface revealed changes in the protein secondary structure associated with increased intermolecular β-sheet content, indicative of aggregated IgG. The addition of 0.01% w/v polysorbate 80 (PS80) reduced the amount of IgG at the air–liquid interface in a static setup at 30 °C; however, this protective effect was lost at 45 °C. These results suggest that the presence of air–liquid interfaces under flow may be detrimental to mAb stability at elevated temperatures and demonstrate the power of ATR-FTIR spectroscopic imaging for studying the structural integrity of mAbs under bioprocessing conditions.

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Comprehensive Temperature Excursion Management Program for the Commercial Distribution of Biopharmaceutical Drug Products

Cited by 7 publications

References 24 publications

Quantifying the Effects of Vibration on Medicines in Transit Caused by Fixed-Wing and Multi-Copter Drones

Quantifying the Effects of Vibration on Medicines in Transit Caused by Fixed-Wing and Multi-Copter Drones

Use of Stability Modeling to Support Accelerated Vaccine Development and Supply

Study of Monoclonal Antibody Aggregation at the Air–Liquid Interface under Flow by ATR-FTIR Spectroscopic Imaging

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