Sterility Testing Research Articles

Non-Sterile to Sterile Compounding: An Unconventional Response During the COVID-19 Pandemic

The drug supply chain has suffered many interruptions over the past decade. The COVID-19 pandemic exacerbated an already fragile infrastructure for supplying critical medications to hospitals and health-systems. The purpose of this paper is to provide insight to the history, thought-processes, and response to critical medication shortages during the COVID-19 pandemic, with a focus on hydromorphone infusions and the action steps taken to engage in non-sterile to sterile (NSTS) compounding. Over a period of 6 weeks, we compounded 1,613 NSTS hydromorphone infusion bags. All lots were cleared for sterility, particulate, potency, and endotoxin testing by an outside FDA registered laboratory. We did not have any safety reports filed specific to the NSTS compounded hydromorphone infusion bags. Over a period of 15 weeks, 715 infusions were consumed. The drug supply chain suffers frequent interruptions and critical shortages, particularly in times of a natural disaster or a global pandemic. Non-sterile to sterile compounding is often associated with risks of inaccuracies, impurities, and contamination. There are instances in which non-sterile to sterile compounding is appropriate and should be considered in times of drug shortages to support the care of hospitalized patients.

Identification of Iranian BHK-21-C5 Cell Line by Two Steps Polymerase Chain Reaction.

Authentication of animal cell lines in cell banks is one of the most important programs regulated during cell culture and storage. This operation provides a thorough and beneficial document which can be advantageous for the functional use of animal cell lines. Therefore, various procedures are used to prevent misidentified cells, cross-contamination to other cell lines, and mislabeling errors leading to incorrect assessment. These contaminants can result in major financial disadvantages. One of the practical methods in this field is a molecular procedure which can demonstrate more accurate results. In the present study, the BHK-21 (C5) was characterized, and it was tried to determine the identity of BHK-21 (C5) as a continuous cell line by Polymerase chain reaction (PCR) molecular procedure in Iran. The cytochrome c oxidase I (CO1) gene was selected as a prevalent DNA fragment for the authentication of the BHK-21 (C5) cell line, along with six cell lines, including Chinese hamster ovary, Lamb kidney, Razi Bovine Kidney, Medical Research Council cell strain 5, Monkey Green Kidney, and Goat Lymphocyte. After amplification, PCR products were analyzed by agarose gel electrophoresis to ensure their accuracy. The results of characterization were indicated, cell viability was estimated to be about 92%, and a uniform cell culture was obtained. The doubling time and µ ratio equivalent were obtained at 20.5 h and 0.03, respectively. Sterility tests revealed that the cell seed was free of bacterial, mycoplasma, and mycobacterial infections. The results of molecular identification revealed that the identification of this cell line was approved and can be used in studies, diagnosis, production, and quality control of biological products.

Long-term stability of 10 mg/mL dobutamine injectable solutions in 5% dextrose and normal saline solution stored in polypropylene syringes and cyclic-oleofin-copolymer vials

ObjectiveDobutamine is an inotropic agent given to patients with low cardiac output or undergoing cardiac surgery in intensive care units. Routine clinical care protocols recommend a target dilution concentration of...

Preparation and Evaluation of Gliptin Liposomes for Targetting Ocular Region in Neurodegeneration

Background: Neurodegeneration shows the distressing effects of miscommunications between brain cells. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer’s disease and vascular dementia. Gliptins play a role in neurodegeneration due to its neuroprotective effects. Eye is an extension of the brain. Ocular route reduces drug’s adverse effects offering an advantage in minimizing risk by targeted delivery to the brain. Conventional ophthalmic formulations exhibit poor bioavailability. Liposomes serve as promising active carriers of drugs to posterior segment eye disorders due to improvement in intravitreal half-life and targeted sustained drug delivery to the retina. Liposomes act as drug carriers for entrapment of hydrophilic and hydrophobic drugs. Objective: The study aimed to formulate and evaluate sitagliptin liposomal formulation for sustained effect in individuals suffering from neurodegeneration owing to high patient compliance, especially in geriatric patients. Methods: Sitagliptin liposomes were prepared by the ethanol injection method and were evaluated for various physicochemical properties such as visual appearance, particle size distribution, zeta potential, % drug entrapment efficiency, % drug loading capacity and in vitro drug release studies. Results: The optimized formulation (L-3) showed round-shaped distinct particles with good stability. The L-3 shows average diameter (281.9 nm); zeta potential (-11.9 mV); % entrapment efficiency (82.7 ± 0.89%); % drug loading (33.11 ± 0.67%). L-3 followed Korsmeyer- Peppas model with fickian diffusion transport of drug release giving n’ (0.3094), r2 (0.9753), with 83.78 ± 0.97% of sustained drug release. The L-3 passes the sterility test indicating its safe use in ophthalmic purposes. Conclusion: Thus, liposomal drug delivery is a highly effective approach for sustained drug delivery and minimizing the side effects of gliptins for effective therapy in neurodegeneration.

Legal and biological safety of legal reprocessing of medicalhospital materials

Introduction: Procedures using disposable materials in thehealth area began to be performed, for example in cardiaccatheterization, which has a high prevalence of morbidity andmortality. Objective: To justify and reaffirm the reuse of single-use catheters in surgeries, as it is justified by the economicbenefit gained from replacing the purchase of new materialsby reusing them. Materials and methods: A bibliographic anddocumentary narrative review was carried out using LILACSand NCBI as database, with previously defined filters andselection criteria. Resultados: Decontamination, disinfection,conditioning, sterilization, and quality control tests are criticalstages and, therefore, require training. Each of these stages alsohas characteristic risks, which must be minimized. In order toensure the quality of the catheter reuse process, after the cleaningand sterilization process, techniques beyond microscopicand visual evaluation of the device are required. A diversityof techniques is addressed so that the quality of the process isassured. Although legislation and supervision are divergentaround the world, many countries choose to adopt reprocessingwith economic justification in most cases. The reuse ofhospital devices involves several physico-chemical processes,which must be performed with quality and safety. Conclusion:The need for greater rigor in the norms and guidelines thataddress this practice is clear and urgent, as well as the greaterintensity and rigidity of the responsible inspection agencies.The use of luminol as an indicator of organic contaminantsmay generate a false positive result. Therefore, 3M™ Clean-Trace ™ is the best instrument found in the world market toensure that the material that has been reused is free of organicwaste, and thus fit for use in hospitals.

Correction to: Sterility testing using a closed system transfer device in oncology medication compounding: a novel method for testing partially used vials

A correction to this paper has been published: https://doi.org/10.1007/s40267-021-00837-y

Emergency medicine: magnesium sulphate injections and their pharmaceutical quality concerns

ObjectivesWorld Health Organization has recognized magnesium sulphate as the drug of choice for prevention and treatment of fits associated with preeclampsia and eclampsia which are amongst the leading causes of maternal morbidity and mortality. In this study, the pharmaceutical quality of magnesium sulphate injections marketed in Anambra state was assessed. MethodsNinety samples of magnesium sulphate obtained from the 3 senatorial zones in Anambra state were subjected to identification tests, microbiological analysis consisting of Growth promotion test, sterility and endotoxin test. Content analysis using titrimetric method and pH analysis were also carried out on the samples. ResultsTwenty percent (20%) of samples obtained from Onitsha failed identification test as they had no Registration number in Nigeria. All samples subjected to the microbiology tests (sterility and endotoxin test) passed. Twenty percent (20%) and thirty-three percent (33.3%) of samples sourced from Onitsha and Nnewi respectively failed the pH analysis test. All the samples passed microbiological tests and had their Active Pharmaceutical Ingredients (API) within the acceptable limit. ConclusionsThis study reveals that there are still some substandard magnesium sulphate injections in circulation in the locality. The supply chain of these drugs should be monitored to ensure a reduction in the incidences of substandard magnesium sulphate and positive therapeutic outcome which translates to reduced maternal mortality associated with pre-eclampsia and eclampsia in Nigeria.

A compendial automated and rapid sterility testing technology for cell and gene therapy products through regulatory perspective and industrial application

A compendial automated and rapid sterility testing technology for cell and gene therapy products through regulatory perspective and industrial application

First final release test of atmps prior to treatment -validation of a qpcr-based rapid sterility test

First final release test of atmps prior to treatment -validation of a qpcr-based rapid sterility test

Mobilized Peripheral Blood Stem Cells are Pluripotent and Can Be Safely Harvested and Stored for Cartilage Repair

The primary objective of this study was to reproduce and validate the harvest, processing and storage of peripheral blood stem cells for a subsequent cartilage repair trial, evaluating safety, reliability, and potential to produce viable, sterile stem cells. Ten healthy subjects (aged 19-44 years) received 3 consecutive daily doses of filgrastim followed by an apheresis harvest of mononuclear cells on a fourth day. In a clean room, the apheresis product was prepared for cryopreservation and processed into 4 mL aliquots. Sterility and qualification testing were performed pre-processing and post-processing at multiple time points out to 2 years. Eight samples were shipped internationally to validate cell transport potential. One sample from all participants was cultured to test proliferative potential with colony forming unit (CFU) assay. Five samples, from 5 participants were tested for differentiation potential, including chondrogenic, adipogenic, osteogenic, endoderm, and ectoderm assays. Fresh aliquots contained an average of 532.9 ± 166.× 106 total viable cells/4 mL vial and 2.1 ± 1.0× 106 CD34+ cells/4 mL vial. After processing for cryopreservation, the average cell count decreased to 331.3 ± 79.× 106 total viable cells /4 mL vial and 1.5 ± 0.7× 106 CD34+ cells/4 mL vial CD34+ cells. Preprocessing viability averaged 99% and postprocessing 88%. Viability remained constant after cryopreservation at all subsequent time points. All sterility testing was negative. All samples showed proliferative potential, with average CFU count 301.4 ± 63.9. All samples were pluripotent. Peripheral blood stem cells are pluripotent and can be safely harvested/stored with filgrastim, apheresis, clean-room processing, and cryopreservation. These cells can be stored for 2 years and shipped without loss of viability. This method represents an accessible stem cell therapy in development to augment cartilage repair.

Modified pea starch based ocular films of azelastine hydrochloride: Development and characterization

The present study aims at application of modified hydroxypropyl peas starch a novel film forming material for ocular adminstraion of azelastine hydrochloride. Azelastine loaded ocular films based on Lycoat RS 720® were developed by the solvent casting technique. Ocular films were evaluated for thickness, diameter, weight uniformity, drug content, surface pH, folding endurance,dissolution time, tensile strength, in vitro biodegradation, in vitro bioadhesion, sterility testing, stability study, ocular irritancy study, in vitro drug release studies.The rapid dissolution of drug attributed to hydrophilic nature of polymer. Ocular irritancy study demonstrated safety of formulation towards ocular mucosa. In conclusion, Lycoat RS 720®, modified hydroxypropyl pea starch could be suitable carrier for ocular delivery of azelastine hydrochloride.

Development, evaluation and biodistribution of stealth liposomes of 5-fluorouracil for effective treatment of breast cancer

The current research was undertaken to design stealth liposomes of 5-Fluorouracil for reducing its cardiotoxicity and prolong the half-life by developing long-circulating liposomes. The liposomes were prepared by the NH4EDTA gradient method, where EDTA is used as a cardioprotectant. Ascorbyl-6-palmitate was also used which helped for the synergistic effect of 5-Fluorouracil to counteract the cancer cells and provide promising application in the treatment of breast cancer cells. Taguchi design was used for screening of formulation and HSPC phospholipid was selected. The drug-excipient compatibility was checked through FTIR which showed all the excipients were compatible with the drug. The formulation was optimized by using 32 factorial design. The drug to lipid ratio (1:5) and Ascorbyl-6-Palmitate concentration (15 mg) were selected. The vesicle size of the prepared liposomes was found to be 70.12 ± 0.58 nm and uniform distribution was observed. The zeta potential and entrapment efficiency of the stealth liposomes were found −16.28 mV and 92 ± 0.007% respectively. In-vitro drug release study of formulation showed drug release of 63.50 ± 0.94% in 24 hrs. The formulation was sterilized by 0.22 µm Mixed cellulose esters (MCE) membrane filter and passed sterility test. Moreover, a biodistribution study was performed by Fluorescence microscopy and by HPLC method, which showed formulation was circulated for 24 hours. Finally, a cell line study indicated that prepared formulation possess greater anti-tumour activity. The cardiotoxicity study revealed that the stealth liposomes have minimum cardiotoxicity as compare to the plain drug.

Preclinical assessment of transplantable human nasal mucosal epithelial cell sheets.

IntroductionWe previously reported a new cell transplantation therapy for patients with intractable otitis media using autologous nasal mucosal epithelial cell sheets, manufactured using temperature-responsive cell culture inserts. The current study aimed to verify whether the transplantable cell sheets could be manufactured for application in clinical trials, according to standard operational procedures (SOP), in a cell processing facility (CPF).MethodsHuman nasal mucosal epithelial cells from four volunteer donors were aseptically cultured and transplantable cell sheets successfully manufactured, with reproducibility, using temperature-responsive cell culture inserts in the CPF. During the manufacture of cell sheets, the CPF environment was confirmed to be aseptic by sterilization tests. Purity of the cell sheets was confirmed by histological analysis and flow cytometry. Both safety and quality of the human nasal mucosal epithelial cell sheets were validated.ResultsThe cultured and manipulated human nasal mucosal epithelial cells showed no evidence of malignant transformation in vitro. The study confirmed the safety and suitability of the manufactured human nasal mucosal epithelial cell sheets for use in clinical trials.ConclusionsThe results led to the establishment of a coherent system in which transplantation could be achieved smoothly.

Preparation and standardization of Human papillomavirus (HPV) (Genotype 6) Nosode

INTRODUCTION
 
 The Homeopathy nosodes are the preparations sourced from organisms and diseased material such as warts and other cancerous tissues. The nosodes such as Psorinum (1826-30), Tuberculinum (1879), Medorrhinum (1880-85), Syphillinum (1880) and others have been in use in homeopathy practice since early 19th century. In the recent years, certain new nosodes such as HIV nosode, Hepatitis C nosode, Mycobacterium Tuberculosis nosode, Plasmodia Falciparum Nosode, Swine Flu and more have been systematically introduced.
 
 MATERIALS AND METHODS
 
 The scrapping and the tissues from the genital warts clusters were collected carefully and were tested for the evaluation of STD (Sexually Transmitted Diseases) panel and HPV-DNA-PCR for screening high risk type followed by genotype determination. The collected tissue sample was processed as per the procedure defined developing the Nosodes, in the Homeopathy Pharmacopoeia of India. Sterility testing and PCR tests were carried out for safety purpose.
 
 RESULT
 
 Human papillomavirus (HPV Genotype 6) Nosode sourced from the genital wart tissues; detected positive for Human papillomavirus genotype 6 was prepared and standardized for future research and clinical exploration.
 
 DISCUSSION AND CONCLUSION
 
 The HPV (Genotype 6) nosode contained the whole organisms in pure form. The therapeutic potential of HPV (Genotype 6) Nosode may be explored against viral warts affecting the genitals, anus, mouth, and respiratory tract.

Polyhexanide and chlorhexidine loaded chitosan wound dressings

Introduction Wounds may be caused by surgery, trauma, or as a result of diseases such as diabetes. The disruption of the skin/internal tissues and the contact with the external environment may lead to microbial infection. Wound dressings are capable of providing a protective barrier and accelerate the wound healing process [1]. Chitosan is one of the most promising materials for wound dressings, due to its good biocompatibility, low toxicity, haemostatic properties, antibacterial activity and biodegradability [2]. The main goal of this work is to produce chitosan-based hydrogels to be used as efficient and safe drug delivery platforms. Materials and methods Two different chitosan-based materials were produced starting from Bioceramed formulations, AbsorKi (suitable for absorbing exudate from the wound) and HemoKi (enhancing haemostasis). The latter was modified by the addition of genipin, a cross-linking agent. The dressings were individually loaded with two different drugs, polyhexamethylene biguanide (PHMB, also called polyhexanide) and chlorhexidine diacetate (CHX), by soaking in solutions containing each drug (24 h, 5 mL, 36 °C, 180 rpm, 0.5 mg/mL for PHMB and 5 mg/mL for CHX). The physical properties (swelling, tensile strength) of the materials were studied prior and upon sterilisation by high hydrostatic pressure (HHP, 600 MPa, 10 min, 70 °C). Surface morphology was analysed by scanning electron microscopy (SEM). In vitro drug release studies were performed with a Franz diffusion cell system, combined with UV–Vis absorption spectroscopy for drug quantification. The efficiency of HHP was evaluated by sterility tests. Chorioallantoic membrane (HET-CAM) tests were done to study potential irritation of the skin. Results Both dressings present a porous structure and an extremely high swelling capacity (>1700%) before sterilisation. HPP affected the materials in different ways: it increased the swelling capacity of AbsorKi but decreased it for HemoKi. The drug release profiles indicated that the concentrations of PHMB and CHX increased in a sustained way on the first day. HHP increases the amount of drug released, except for AbsorKi with PHMB. Regarding the mechanical properties, sterilisation improved the resistance of both dressings. HET-CAM tests suggest that the produced materials do not lead to irritation. Discussion and conclusions HHP revealed an efficient method to ensure the materials sterilisation making the drug loaded wound dressings potentially efficient devices for the absorption of exudate from the wound bed. The combination of chitosan, a natural antibacterial agent, with the studied disinfectant and antiseptic drugs may lead to promising materials to be used as drug delivery platforms. Further studies in animal models are needed to conclude about the safety and clinical usefulness of the developed dressings.

Evaluation of BACTECTM FX Blood Culture System for Rapid Sterility Testing of Human Medicinal Solutions for Infusion

Human medicinal products for infusion should be tested for sterility at various stages of manufacturing including the final step before marketing. Conventional sterility methods recommended in pharmacopeia need a 14 days incubation period in order to get reliable analytical results. However, rapid alternative methods based on automated detection of microbial growth have the advantage of taking only 5 days for sterility testing of medicinal products which can be very important especially during pandemics and emergency conditions. The aim of the present study is to evaluate the microbial detection potential and capacity of the BACTEC FX system for the rapid sterility testing of Paracerol, a 10 mg/mL paracetamol containing pediatric medicine for infusion, and to specify time required for the detection of a variety of microorganisms. Accordingly, the results showed that there were no significant differences between the BACTEC and conventional membrane filtration methods for detecting contamination. All positive/negative controls and all samples intentionally contaminated with microorganisms were determined correctly by using both methods. BACTEC FX system detected all microorganisms including slow growers significantly faster than the membrane filtration method (p<0.05). This system can be considered as a rapid alternative over conventional sterility methods for the release of human medicinal products for infusion to the markets especially under emergency conditions. However, for each particular products, validation steps should be executed according to European Pharmacopoeia by using a broad range of microorganisms.

Sterility testing using a closed system transfer device in oncology medication compounding: a novel method for testing partially used vials

BackgroundThe National Association of Pharmacy Regulatory Authorities (NAPRA) Model Standards for non-hazardous sterile preparations and the model standards for pharmacy compounding of hazardous sterile preparations, calls for partially used single dose vials to be used or discarded within six hours of first access. This may lead to significant wastage, particularly with less utilized and expensive medications like oncology treatments. If demonstrated that sterility of these partially used vials can be maintained through a compounding procedure, there may be an opportunity to consider their re-uses.ObjectiveThe primary objective is to determine the ability of a compounding procedure, including a closed system transfer device (CSTD), to maintain sterility for partially used vials at two compounding centres at Trillium Health Partners. A secondary objective was to evaluate a novel method for verifying sterility.MethodsA CSTD was incorporated into the standard compounding methods at two hazardous compounding centres. Using growth media to detect any bacterial or fungal contamination that might have occurred during compounding, storage, and repeated access, the vials were tested in various growth conditions.ResultsThere was no growth noted in all compounded samples. The CSTD, when used in our environment with certified personnel, maintained sterility for 14 days, even with repeated access.ConclusionsThis study demonstrates that under our local compounding procedure using CSTD we were able to maintain vial sterility when stored under typical conditions and accessed several times for up to 14 days. This method may be considered to assess a facility’s local compounding procedures and provide valuable information regarding storage and utilization of partial vials, which may result in reduced waste and cost avoidance for the health care system.

Extending the post-thaw viability of cryoprecipitate.

Cryoprecipitate has a short post-thaw expiry time of 6 h. The aim of this study was to assess the stability and function of cryoprecipitate components (FVIII, fibrinogen, vWF, and FXIII) and cryoprecipitate sterility up to 120 h post-thawing when stored at two temperatures (2-6°C and room temperature [20-24°C]). Twenty batches (110 individual units) of time-expired, thawed cryoprecipitate were collected. Units were sampled at the 6-h expiration mark and then stored at 2-6°C or room temperature (RT). They were resampled every 24 h for 120 h. One unit from each batch was sent for sterility testing at 120 h. Samples had FVIII (one stage and chromogenic), fibrinogen, FXIII, vWFag, and vWF:RCo assays performed in batches. Rotational thromboelastometry (ROTEM) was also performed. FVIII levels declined significantly at 120 h post-thawing at both RT and 2-6°C, but still met international standards for FVIII content. Fibrinogen, vWF antigen, and FXIII levels reduced minimally over 120 h and always met international standard requirements when stored at either temperature. ROTEM analysis demonstrated that fibrinogen function was not compromised at 120 h post-thawing under both storage conditions. vWF:RCo levels declined significantly over 120 h at both storage temperatures. No bacterial contamination was detected in 20 units of cryoprecipitate following storage for 120 h post-thawing. These results demonstrate that extension of the storage time of thawed cryoprecipitate to 120 h, stored at either 2-6°C or RT, is feasible while still maintaining required FVIII, fibrinogen, and vWFag levels. Storage at 2-6°C has the advantage of reduced risk of potential bacterial contamination.

Preparation of Coronavirus nosodes sourced from a clinical sample of SARS-Cov-2 positive patient, inactivated strain, and spike glycoprotein

Introduction&#x0D; Nosodes, the homeopathic preparations sourced from biological materials including clinical samples, cultures of organisms, and diseased tissues have been in use against the source-specific infections as well as other diseases. The nosodes have demonstrated some efficacy in managing epidemics, such as influenza, dengue, and leptospirosis. This article presents the need and process of development of nosodes from the SARS-CoV-2 to explore its prophylactic and therapeutic potentials against certain related viral diseases.&#x0D; &#x0D; MATERIALS AND METHODS&#x0D; A clinical sample of SARS-Cov-2 positive patient, based on the cycle threshold (CT) value of the qRT-PCR, heat-inactivated SARS-CoV-2, and spike glycoprotein all were processed for making nosodes as per the method described in Homoeopathy Pharmacopoeia of India. Molecular tests, such as qRT- PCR and sterility tests were performed to establish the live organisms, RNA material, and the absence of contamination.&#x0D; &#x0D; RESULT&#x0D; Three variants of Coronavirus Nosode were developed using a clinical sample, heat-inactivated SARS-CoV-2, and spike glycoprotein. In potencies 3c and above, no detectable SARS-CoV-2 RNA material was found by PCR. The analytical results for nosodes were reported as compliant for sterility testing as per the IP.&#x0D; &#x0D; CONCLUSION&#x0D; Three variants of Coronavirus nosodes were prepared which need to be evaluated further through pre-clinical and clinical studies.

Comparison between centralized and decentralized supply chains of autologous chimeric antigen receptor T-cell therapies: a UK case study based on discrete event simulation

Background aimsDecentralized, or distributed, manufacturing that takes place close to the point of care has been a manufacturing paradigm of heightened interest within the cell therapy domain because of the product's being living cell material as well as the need for a highly monitored and temperature-controlled supply chain that has the potential to benefit from close proximity between manufacturing and application. MethodsTo compare the operational feasibility and cost implications of manufacturing autologous chimeric antigen receptor T (CAR T)-cell products between centralized and decentralized schemes, a discrete event simulation model was built using ExtendSIM 9 for simulating the patient-to-patient supply chain, from the collection of patient cells to the final administration of CAR T therapy in hospitals. Simulations were carried out for hypothetical systems in the UK using three demand levels—low (100 patients per annum), anticipated (200 patients per annum) and high (500 patients per annum)—to assess resource allocation, cost per treatment and system resilience to demand changes and to quantify the risks of mix-ups within the supply chain for the delivery of CAR T treatments. ResultsThe simulation results show that although centralized manufacturing offers better economies of scale, individual facilities in a decentralized system can spread facility costs across a greater number of treatments and better utilize resources at high demand levels (annual demand of 500 patients), allowing for an overall more comparable cost per treatment. In general, raw material and consumable costs have been shown to be one of the greatest cost drivers, and genetic modification-associated costs have been shown to account for over one third of raw material and consumable costs. Turnaround time per treatment for the decentralized scheme is shown to be consistently lower than its centralized counterpart, as there is no need for product freeze-thaw, packaging and transportation, although the time savings is shown to be insignificant in the UK case study because of its rather compact geographical setting with well-established transportation networks. In both schemes, sterility testing lies on the critical path for treatment delivery and is shown to be critical for treatment turnaround time reduction. ConclusionsConsidering both cost and treatment turnaround time, point-of-care manufacturing within the UK does not show great advantages over centralized manufacturing. However, further simulations using this model can be used to understand the feasibility of decentralized manufacturing in a larger geographical setting.