scholarly journals Design of CGMP Production of18F- and68Ga-Radiopharmaceuticals

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yen-Ting Chi ◽  
Pei-Chun Chu ◽  
Hao-Yu Chao ◽  
Wei-Chen Shieh ◽  
Chuck C. Chen
Keyword(s):  
Radiochemical Purity ◽  
Drug Product ◽  
Radiochemical Yield ◽  
Active Pharmaceutical Ingredient ◽  
Automated System ◽  
Acceptance Criteria ◽  
Yield And Purity ◽  
Pet Radiopharmaceuticals ◽  
Hplc Analyses

Objective.Radiopharmaceutical production process must adhere to current good manufacturing process (CGMP) compliance to ensure the quality of precursor, prodrug (active pharmaceutical ingredient, API), and the final drug product that meet acceptance criteria. We aimed to develop an automated system for production of CGMP grade of PET radiopharmaceuticals.Methods.The hardware and software of the automated synthesizer that fit in the hot cell under cGMP requirement were developed. Examples of production yield and purity for68Ga-DOTATATE and18F-FDG at CGMP facility were optimized. Analytical assays and acceptance criteria for cGMP grade of68Ga-DOTATATE and18F-FDG were established.Results.CGMP facility for the production of PET radiopharmaceuticals has been established. Radio-TLC and HPLC analyses of68Ga-DOTATATE and18F-FDG showed that the radiochemical purity was 92% and 96%, respectively. The products were sterile and pyrogenic-free.Conclusion.CGMP compliance of radiopharmaceuticals has been reviewed.68Ga-DOTATATE and18F-FDG were synthesized with high radiochemical yield under CGMP process.

Fully-Automated Synthesis of 177Lu Labelled FAPI Derivatives On The Module Modular Lab-Eazy

2021 ◽  
Author(s):  
Kurtulus Eryilmaz ◽  
Benan KILBAS
Keyword(s):  
Quality Control ◽  
Chromatographic Analysis ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Automated System ◽  
Automated Synthesis ◽  
Modular Approach ◽  
Stability Studies ◽  
European Pharmacopoeia ◽  
First Time

Abstract Backround: To the best of our knowledge, manually production of [177Lu]Lu-FAPI radiopharmaceutical derivatives has been only described in literature. In this work, a fully-automated [177Lu]Lu-FAPI synthesis has been well designed for the first time using commercially available synthesis module. In addition to the development of an automated system with disposable cassette, quality control (QC) and stability studies were comprehensively employed. Results A fully automated synthesis of [177Lu]Lu-FAPI derivatives was achieved on the Modular Lab Eazy (ML Eazy) with high radiochemical yield (85–90%). Chromatographic analysis indicated the formation of radiosynthesis with an absolute radiochemical purity (99%). Stability experiments clarified the durability of the products within 4 days. All obtained specifications are consistent to European Pharmacopoeia. Conclusion A fully automated synthesis of [177Lu]Lu-FAPI radiopharmaceuticals were accomplished regarding quality control standards and quality assurance by using commercially available a modular approach namely ML Eazy with disposable customized cassette and template.

scholarly journals Fully-automated synthesis of 177Lu labelled FAPI derivatives on the module modular lab-Eazy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kurtulus Eryilmaz ◽  
Benan Kilbas
Keyword(s):  
Quality Control ◽  
Chromatographic Analysis ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Automated System ◽  
Automated Synthesis ◽  
Modular Approach ◽  
Stability Studies ◽  
European Pharmacopoeia ◽  
First Time

Abstract Background To the best of our knowledge, manually production of [177Lu]Lu-FAPI radiopharmaceutical derivatives has been only described in literature. In this work, a fully-automated [177Lu]Lu-FAPI synthesis has been well designed for the first time using commercially available synthesis module. In addition to the development of an automated system with disposable cassette, quality control (QC) and stability studies were comprehensively presented. Results A fully automated synthesis of [177Lu]Lu-FAPI derivatives was achieved on the Modular Lab Eazy (ML Eazy) with high radiochemical yield ([177Lu]Lu-FAPI-04; 88% ± 3, [177Lu]Lu-FAPI-46; 86% ± 3). Chromatographic analysis indicated the formation of radiosynthesis with an absolute radiochemical purity (99%). Stability experiments clarified the durability of the products within 4 days. All obtained specifications are consistent to European Pharmacopoeia. Conclusion A fully automated synthesis of [177Lu]Lu-FAPI radiopharmaceuticals was accomplished regarding quality control standards and quality assurance by using commercially available a modular approach namely ML Eazy with disposable customized cassette and template. Graphical abstract

Regulatory requirements and comparison in approval of new and generic drugs in United States of America and Japan:-Implication for Future strategies

2020 ◽  
Vol 07 ◽  
Author(s):  
Paramjeet Malik ◽  
Neelam Pawar ◽  
Kavita Bahmani
Keyword(s):  
Generic Drugs ◽  
Drug Product ◽  
Drug Approval ◽  
Approval Process ◽  
Regulatory Requirements ◽  
Team Members ◽  
Regulatory Authorities ◽  
Effective Manner ◽  
Review Team

: Safety, efficacy and quality of a therapeutic product is the major concern for the pharmaceutical companies. FDA and PMDA are the main regulatory authorities in USA & JAPAN respectively that ensures the maintenance of these required parameters by forming standard guidelines and process for drug approval. These regulatory authorities’ reviews each step of a pharmaceutical drug product from its discovery phase to marketed product. Dossier plays an important role during the approval process of a drug product, as it allows both applicant and review team members to evaluate the data in an effective manner. A dossier consists of five modules containing informative data of various stages of a drug product but in a brief pattern with folders and subfolders. In the present paper, the authors focus on in-depth review of approval process for new and generic drugs in USA and Japan.

scholarly journals [18F]F-PSMA-1007 Radiolabelling without an On-Site Cyclotron: A Quality Issue

2021 ◽  
Vol 14 (7) ◽  
pp. 599
Author(s):  
Valentina Di Iorio ◽  
Stefano Boschi ◽  
Anna Sarnelli ◽  
Cristina Cuni ◽  
David Bianchini ◽  
...  
Keyword(s):  
Quality Assurance ◽  
Radiochemical Purity ◽  
Competent Authority ◽  
Radiochemical Yield ◽  
Synthesis Process ◽  
Control Parameters ◽  
Quality Issue ◽  
Assurance System ◽  
Quality Control Parameters ◽  
Specific Membrane

Radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA) has become the gold standard for PET imaging of prostate cancer. [68Ga]Ga-PSMA-11 has been the forerunner but a [18F]F-PSMA ligand has been developed because of the intrinsic advantages of Fluorine-18. Fluorine-18 labelled compounds are usually prepared in centers with an on-site cyclotron. Since our center has not an on-site cyclotron, we decided to verify the feasibility of producing the experimental 18F-labelled radiopharmaceutical [18F]F-PSMA-1007 with [18F]F- from different external suppliers. A quality agreement has been signed with two different suppliers, and a well-established and correctly implemented quality assurance protocol has been followed. The [18F]F- was produced with cyclotrons, on Nb target, but with different beam energy and current. Extensive validation of the [18F]F-PSMA-1007 synthesis process has been performed. The aim of this paper was the description of all the quality documentation which allowed the submission and approval of the Investigational Medicinal Product Dossier (IMPD) to the Competent Authority, addressing the quality problems due to different external suppliers. The result indicates that no significant differences have been found between the [18F]F- from the two suppliers in terms of radionuclidic and radiochemical purity and [18F]F- impacted neither the radiochemical yield of the labelling reaction nor the quality control parameters of the IMP [18F]F-PSMA-1007. These results prove how a correct quality assurance system can overcome some Regulatory Authorities issue that may represent an obstacle to the clinical use of F-18-labelled radiopharmaceuticals without an on-site cyclotron

scholarly journals Novel late-stage radiosynthesis of 5-[18F]-trifluoromethyl-1,2,4-oxadiazole (TFMO) containing molecules for PET imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nashaat Turkman ◽  
Daxing Liu ◽  
Isabella Pirola
Keyword(s):  
Late Stage ◽  
Histone Deacetylases ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Single Step ◽  
The Novel ◽  
Molar Activity ◽  
The Central Nervous System ◽  
Class Iia Hdacs ◽  
18F Fluoride

AbstractSmall molecules that contain the (TFMO) moiety were reported to specifically inhibit the class-IIa histone deacetylases (HDACs), an important target in cancer and the disorders of the central nervous system (CNS). However, radiolabeling methods to incorporate the [18F]fluoride into the TFMO moiety are lacking. Herein, we report a novel late-stage incorporation of [18F]fluoride into the TFMO moiety in a single radiochemical step. In this approach the bromodifluoromethyl-1,2,4-oxadiazole was converted into [18F]TFMO via no-carrier-added bromine-[18F]fluoride exchange in a single step, thus producing the PET tracers with acceptable radiochemical yield (3–5%), high radiochemical purity (> 98%) and moderate molar activity of 0.33–0.49 GBq/umol (8.9–13.4 mCi/umol). We validated the utility of the novel radiochemical design by the radiosynthesis of [18F]TMP195, which is a known TFMO containing potent inhibitor of class-IIa HDACs.

scholarly journals Quality Assessment of Some Essential Children’s Medicines Sold in Licensed Outlets in Ashanti Region, Ghana

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Grace Frimpong ◽  
Kwabena Ofori-Kwakye ◽  
Noble Kuntworbe ◽  
Kwame Ohene Buabeng ◽  
Yaa Asantewaa Osei ◽  
...  
Keyword(s):  
Quality Evaluation ◽  
Active Pharmaceutical Ingredient ◽  
Poor Quality ◽  
Surveillance Systems ◽  
Ashanti Region ◽  
The United Kingdom ◽  
The Poor ◽  
Medicine Outlets ◽  
Children’S Medicines

The quality of 68 samples of 15 different essential children’s medicines sold in licensed medicine outlets in the Ashanti Region, Ghana, was evaluated. Thirty-two (47.1%) of the medicines were imported, mainly from India (65.6%) and the United Kingdom (28.1%), while 36 (52.9%) were locally manufactured. The quality of the medicines was assessed using content of active pharmaceutical ingredient (API), pH, and microbial limit tests, and the results were compared with pharmacopoeial standards. Twenty-six (38.2%) of the samples studied passed the official content of API test while 42 (61.8%) failed. Forty-nine (72.1%) of the samples were compliant with official specifications for pH while 19 (27.9%) were noncompliant. Sixty-six (97.1%) samples passed the microbial load and content test while 2 (2.9%) failed. Eighteen (26.5%) samples passed all the three quality evaluation tests, while one (1.5%) sample (CFX1) failed all the tests. All the amoxicillin suspensions tested passed the three evaluation tests. All the ciprofloxacin, cotrimoxazole, flucloxacillin, artemether-lumefantrine, multivitamin, and folic acid samples failed the content of API test and are substandard. The overall API failure rate for imported products (59.4%) was comparable to locally manufactured (63.9%) samples. The results highlight the poor quality of the children’s medicines studied and underscore the need for regular pharmacovigilance and surveillance systems to fight this menace.

The structure and application of an automated system for monitoring passenger traffic

2021 ◽  
Vol 14 (3) ◽  
pp. 4-11
Author(s):  
Evgeniy Anikeev
Keyword(s):  
Data Collection ◽  
General Structure ◽  
Automated System ◽  
Passenger Transport ◽  
Service Levels ◽  
Passenger Traffic ◽  
Advantages And Disadvantages ◽  
Transport Services ◽  
Transport Control

Various methods of collecting data on passenger traffic, their advantages and disadvantages are considered. It is shown that in order to improve the quality of transport services, it is necessary to regularly collect and refine data on passenger traffic. The goals and methods of obtaining information about passenger traffic in the system of municipal passenger transport are indicated. All currently existing methods are divided into three categories: data collection using technical means, data collection with the help of censors and volunteers, and interpretation of fare payments. All the methods presented in the article were compared in terms of labor intensity, costs and accuracy of the results obtained. The advantages and disadvantages of each method are considered. The general structure of an automated system for collecting data on passenger traffic is presented. The necessity of creating a centralized system for collecting and processing data associated with all passenger transport control systems has been substantiated. The tasks solved by this system at all levels of transport services for passengers are shown. Each of the tasks is assigned to one of three service levels: pre-transport, transport and post-transport. It is shown that only solving problems at all levels can ensure high-quality operation of the municipal passenger transport system.

scholarly journals Development and evaluation of an automated system for testing current meters

2016 ◽  
Vol 20 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Ezequiel Saretta ◽  
Antonio P. de Camargo ◽  
Tarlei A. Botrel ◽  
Marinaldo F. Pinto ◽  
Geancarlo T. Katsurayama ◽  
...  
Keyword(s):  
User Interface ◽  
Data Acquisition ◽  
Flow Velocity ◽  
Reference Value ◽  
Vertical Axis ◽  
Automated System ◽  
Step Motor ◽  
Simple Task ◽  
Rivers And Streams

ABSTRACT Current meters are equipment widely used for estimating flow velocity in rivers and streams. Periodic calibrations of current meters are important to ensure the quality of measurements, but the required testing facilities are complex and only available in a few institutions. However, advances in electronics and automation may contribute to developing simple and reliable calibration systems. Thus, this study aimed to develop an automated system for testing current meters, which consisted of a trapezoidal channel, a step motor, a tow car and a management system, composed of a supervisory application and microprocessed modules to control the motor and the data acquisition. Evaluations of the displacement velocity showed that it matched the reference value up to 1.85 m s-1 for a vertical-axis current meter and 2.3 m s-1 for a horizontal-axis one. The developed system showed reliability during tests, for both current meter movement and data acquisition. The management of the system based on the developed modules and the supervisory application improved its user interface, turning all the procedure into a simple task.

scholarly journals Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

2020 ◽  
Author(s):  
Richard Edwards ◽  
Hannah Greenwood ◽  
Timothy Witney
Keyword(s):  
Large Scale ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Reaction Conditions ◽  
Positron Emission ◽  
Optimized Protocol ◽  
Cancer Types ◽  
Automated Procedures ◽  
Phosphate Buffered Saline ◽  
High Radioactivity

<p><i>Purpose</i>: (S)-4-(3-<sup>18</sup>F-Fluoropropyl)-ʟ-Glutamic Acid ([<sup>18</sup>F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x<sub>C</sub><sup>-</sup>, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [<sup>18</sup>F]FSPG production are required. Here, we report a cassette-based method to produce [<sup>18</sup>F]FSPG at high radioactivity concentrations from low amounts of starting activity.</p><p><i>Procedures</i>: An automated synthesis and purification of [<sup>18</sup>F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [<sup>18</sup>F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [<sup>18</sup>F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [<sup>18</sup>F]FSPG in phosphate-buffered saline. Subsequently, the [<sup>18</sup>F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.</p><p><i>Results</i>: The optimized protocol produced [<sup>18</sup>F]FSPG in 38.4 ± 2.6% RCY and 96% radiochemical purity. Small alterations, including the implementation of a reverse elution and an altered hypercarb cartridge, lead to significant improvements in radiotracer concentration from <10 MBq/mL to >100 MBq/mL. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [<sup>18</sup>F]fluoride.</p><p><i>Conclusions: </i>We have developed a robust and facile method for [<sup>18</sup>F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [<sup>18</sup>F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of cassettes for an ‘out the box’ synthesis on a synthesis module routinely used for clinical production make the method amenable to rapid and widespread clinical translation.</p>

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