Principles Of Good Manufacturing Practice Research Articles

Fully automated radiolabeling of [68Ga]Ga-EMP100 targeting c-MET for PET-CT clinical imaging

Backgroundc-MET is a transmembrane receptor involved in many biological processes and contributes to cell proliferation and migration during cancer invasion process. Its expression is measured by immunehistochemistry on tissue biopsy in clinic, although this technique has its limitations. PET-CT could allow in vivo mapping of lesions expressing c-MET, providing whole-body detection. A number of radiopharmaceuticals are under development for this purpose but are not yet in routine clinical use. EMP100 is a cyclic oligopeptide bound to a DOTA chelator, with nanomolar affinity for c-MET. The aim of this project was to develop an automated method for radiolabelling the radiopharmaceutical [68Ga]Ga-EMP100.ResultsThe main results showed an optimal pH range between 3.25 and 3.75 for the complexation reaction and a stabilisation of the temperature at 90 °C, resulting in an almost complete incorporation of gallium-68 after 10 min of heating. In these experiments, 90 µg of EMP-100 peptide were initially used and then lower amounts (30, 50, 75 µg) were explored to determine the minimum required for sufficient synthesis yield. Radiolysis impurities were identified by radio-HPLC and ascorbic acid and ethanol were used to improve the purity of the compound. Three batches of [68Ga]Ga-EMP100 were then prepared according to the optimised parameters and all met the established specifications. Finally, the stability of [68Ga]Ga-EMP100 was assessed at room temperature over 3 h with satisfactory results in terms of appearance, pH, radiochemical purity and sterility.ConclusionsFor the automated synthesis of [68Ga]Ga-EMP100, the parameters of pH, temperature, precursor peptide content and the use of adjuvants for impurity management were efficiently optimised, resulting in the production of three compliant and stable batches according to the principles of good manufacturing practice. [68Ga]Ga-EMP100 was successfully synthesised and is now available for clinical development in PET-CT imaging.

The Importance of Good Manufacturing Practices (GMP) in the Healthcare Industry

In the healthcare industry, maintaining high-quality standards is crucial to ensure the safety and efficacy of medical products. Good Manufacturing Practices (GMP) provide a set of guidelines and regulations that help ensure the consistent production, control, and quality assurance of pharmaceuticals, medical devices, and other healthcare products. This paper explores the significance of GMP in the healthcare industry, highlighting its background, objectives, role in safeguarding patient health and maintaining public trust. It examines the key principles of GMP, its regulatory framework, and its impact on various aspects of the healthcare sector, including drug manufacturing, quality control, product safety, and regulatory compliance. Furthermore, the paper discusses the challenges and future perspectives of GMP implementation, emphasizing the need for ongoing advancements to meet the evolving demands of the industry. To summarize, adherence to GMP standards is crucial for the healthcare industry to produce high-quality, safe, and effective healthcare products. GMP compliance promotes patient safety, regulatory compliance, and innovation in the pharmaceutical industry.

The Use of Amplified ATP Bioluminescence for Rapid Sterility Testing of Drug Product Formulations.

The use of amplified adenosine trisphosphate (ATP) bioluminescence has been established within AstraZeneca as a technique for assessing the sterility of drug product formulations. A platform validation was generated that challenged the technology with a range of organisms and inoculum levels, and the approach to onboarding additional drug products has been designed to maximize the understanding of the drug product behavior when samples may be limited during the development phases of the life cycle of a drug product. Many activities to support sterility assurance take place during product development. However, sterile material manufactured under Good Manufacturing Practice (GMP) conditions may not always be available, for example, during studies to understand the bacterial retention of sterilizing grade filters. In cases of bactericidal products, the use of surrogates may be justified if they are suitably representative of the final drug product formulation. It may not be possible to secure GMP facility access to prepare such surrogate formulations; in those cases, the principles of GMP may be applied in a controlled laboratory setting. The rapid sterility test was used to provide the sterility assurance of the prepared surrogate material. In this case study, the application of amplified ATP bioluminescence sterility testing enabled a fast response to ensure mitigations could be executed in a timely manner. This meant that overarching project plans could be met. The case study also provides information on the rapid identification technique used to identify the slow growing and difficult to recover organism, which allowed faster indication of a nonsterile material. The example also highlights some of the aspects of the challenges of culturing microorganisms and the value of modern techniques in their ability to indicate a quality drift. Dermacoccus nishinomiyaensis was isolated from the test article, and throughout the investigation, it was not possible to culture this organism on standard tryptic soya agar.

GMP-Compliant Mesenchymal Stem Cell-Derived Exosomes for Cell-Free Therapy in Cancer.

Cancer is categorized as one of the life-threatening disease in the world, which has recently been associated with a significant increase in the incidence and prevalence rate. Hence, the discovery of effective approaches for prevention, early diagnosis, and effective treatment for cancer has been prioritized by oncology researchers. In recent decades, mesenchymal stem cells show great potential to advance the field of regenerative medicine and oncology research due to representing prominent characteristics. Recently, studies indicate that mesenchymal stem cells can play an important role by secreting extracellular vesicles like exosomes in modulating the biological functions of target cells through paracrine regulation. Indeed, the exosomes derived from mesenchymal stem cells can represent the same therapeutic potential as parent cells with fewer side effects. Therefore, it can be demonstrated that exosomes can be a suitable drug delivery candidate in regenerative medicine and targeted therapy. It is also noteworthy that as the use of exosome therapy becomes more common in clinical studies, the importance of improving basic criteria such as safety, efficiency, and quality of stem cell products will also be highlighted. Based on this concept, the good manufacturing practice principles were put forward to examine the standard of cell products from different qualitative and quantitative aspects to progress the cell therapy. In other words, the principles of good manufacturing practice should be observed not only in the extraction and isolation of stem cells but also in the extraction of products related to stem cells such as exosomes in the field of treatment.

National Blood Foundation 2021 Research and Development summit: Discovery, innovation, and challenges in advancing blood and biotherapies.

National Blood Foundation 2021 Research and Development summit: Discovery, innovation, and challenges in advancing blood and biotherapies.

Designing Food Safety Management and Halal Assurance Systems in Mozzarella Cheese Production for Small-Medium Food Industry

All food businesses are required by law to implement and maintain food safety management systems based on the Codex Hazard Analysis Critical Control Points (HACCP) principles. However, more than half of small and medium-sized enterprises (SMEs) in Indonesia are having difficulty complying with these regulations. This research designed a food system by identifying the application of Good Manufacturing Practices (GMP) and the HACCP to Dairy Farm SMEs based on the survey, in-depth interviews, and document standard review. The food safety system was implemented using HACCP, and six Critical Control Point (CCP) processes were identified, including milking (raw material), storage, pasteurization, curd filtering, and cheese packaging. The halal assurance system is implemented at Dairy Farm SMEs by identifying and improving the company's business processes and the mozzarella cheese production process. In addition, a Standard Operating Procedure (SOP) was developed, including a food safety system and a halal assurance system. It can be used as a reference in designing a food safety system by identifying and applying the principles of GMP and HACCP that pay attention to critical points in the mozzarella cheese production process. The results of the research can be used wisely by Dairy Farm SMEs to assist in obtaining recommendations from the Food and Drug Supervisory Agency (BPOM) and halal certification, specifically the existence of SOPs, forms for each production process, improvements to each production process, and improvements to company business processes.

Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells

IntroductionMesenchymal stromal cells (MSCs) have opened a new window to treat inflammatory and non-inflammatory diseases. Nonetheless, their clinical applications require rigorous control and monitoring procedures to ensure full compliance with the principles of good manufacturing practice (GMP). Various evaluations should be passed in conjunction with the development of these newly emerging therapeutic products from bench-to-bedside. These evaluations include in vitro characterization, preclinical studies, and clinical trials to ensure product safety and efficacy. Therefore, a robust and well-designed preclinical study is critical to confirm product safety. This study aims to determine the probable toxicity effects of local and systemic injections of cryopreserved human bone marrow-derived clonal MSCs (BM-cMSCs) during subacute and subchronic periods of time.MethodsBM-cMSCs were characterized according to the International Society for Cell and Gene Therapy (ISCT) criteria for MSCs. Both safety and toxicity of the BM-cMSCs population produced under GMP-compatible conditions were assessed in both sexes of Sprague Dawley (SD) rats via systemic intravenous (IV) administration and local injection in intervertebral disc (IVD). Behavioral changes, clinical signs of toxicity, and changes in body weight, water and food consumption were the important variables for product toxicity testing over 14 consecutive days during the subacute period and 90 consecutive days during the subchronic period. At the end of the assessment periods, the rats were killed for histopathology analysis of the target tissues. The BM-cMSCs potential for tumorigenicity was checked in nude mice.ResultsSingle IV and IVD injections of BM-cMSCs did not cause significant signs of clinical toxicity, or changes in laboratory and histopathology data during the subacute (14 day) and subchronic (90 day) periods. Ex vivo-expanded and cryopreserved BM-cMSCs did not induce tumor formation in nude mice.ConclusionThe results suggest that local and systemic administrations of xenogeneic BM-cMSCs in both sexes of SD rats do not cause toxicity during the subacute and subchronic periods of time. Also, BM-cMSCs were non-tumorigenic in nude mice.

Halal Assessment Model Design in Bakery Industry

Bakery product is a product with huge business opportunities in the domestic and international halal food market. Bakery companies are demanded to keep the trust of the consumers to the bakery product. The design of the halal assessment model is required to determine the critical point in the bakery-making business process. This assessment tool is intended to understand, know, and determine the critical point of the bakery production process from the halalness degree and is reviewed from all aspects such as the materials’ content, as well as the material acquisition and processing method based on 18 criteria of GMP principles (Good Manufacturing Practices). The halal assessment model designed in this research used QFD (Quality Function Deployment) approach which was integrated into the company’s business process and the halal critical bakery was grouped based on SCOR (Supply Chain Operations Reference) model. Matrix 1 integrated GMP (Good Manufacturing Practices) and business process (BP), matrix 2 integrated GMP (Good Manufacturing Practices), and halal critical bakery (HCB). The results of the design model implementation based on the standards set by the Halal Auditor of LPPOM MUI found that the standard matrix component 1 was met by the company by 47%, while the matrix component 2 was only able to meet the Auditor standards by 34% and the matrix component 3 standards were able to fulfilled by the company by 75%. The fulfillment value of each matrix is influenced by the negative gap that occurs, the negative gap occurs because of the standard criteria in the technical matrix that are not met. The result of this halal assessment model design is expected to help the company in evaluating and controlling critical points found in the business processes.

Comparison Review of Two Regulatory Agencies Regulation: Therapeutic Goods Administration (TGA) and the European Medicine Agency (EMA) in Relation to Good Manufacturing Practice (GMP) Guideline

There are some regulatory bodies in the world that impacting the pharmaceutical industry to operate and perform Good Manufacturing Practice (GMP) principles. These regulatory bodies exist to ensure that the pharmaceutical product and other human supporting products have a high standard of quality, safety, and efficacy from product registration to product distribution to the patient. This article reviews some aspects which is regulated by two of regulatory entities including Therapeutic Goods Administration (TGA) and European Medicines Agency (EMA) in relation with Good Manufacturing Practice (GMP) principles. The GMP principles which is structured by these regulatory agencies may be originally created by the agencies or influenced by other regulatory body concepts. The guidance can be a primary source or second reference for the pharmaceutical industry in impacting countries depending on the guideline’s legal status. It is noticeable that both regulatory bodies have some similar concepts to support GMP implementation and some differentt practices which may be considered by the pharmaceutical industry when it is aimed to market their product in the regulated countries.

Principles of Good Manufacturing Practices and Good Hygienic Practice in Food Processing

The paper emphasizes the importance and considers the most important requirements of the Prerequisite Programs (PRPs), so-called Good Manufacturing Practices (GMP) and Good Hygienic Practice (GHPs). Their proper implementation, consistent application and continuous improvement are the basis to fulfilled the requirements of modern food safety management systems (FSMS).

GMP-Compliant Production of Human Placenta-Derived Mesenchymal Stem Cells.

Mesenchymal stem cells are one of the most attractive sources for stem cell research and therapy. Their safety and efficacy have been demonstrated in many clinical trials. Because of their low immunogenicity and immunomodulatory properties, allogenic MSCs have been transplanted in different clinical studies. MSCs could be in different adult- and fetal-derived tissues including pregnancy products. Placenta-derived mesenchymal stem cells (PLMSCs) that can be harvested without using any invasive procedures from a discarding tissue are one of the important types of mesenchymal stem cells for therapeutic applications. Stem cell manufacturing for therapeutic applications should be in compliance with the basic principles of good manufacturing practice (GMP). Herein, the current chapter is to describe GMP-compliant production of human PLMSCs, which are suitable for clinical applications.

Analysis of the Production Routine of Iodine123 at IEN and an Adaptation Proposal for a New Radiopharmaceuticals Production Facility

The Brazilian Nuclear Energy Commission (CNEN) is the main manufacturer of radiopharmaceuticals in Brazil. The Nuclear Engineering Institute (IEN), located at Rio de Janeiro, is one of its main research and production centers, supplying public and private hospitals in the country. This radiopharmaceutical production is used in diagnostic and therapy procedures and allows one and a half million nuclear medicine procedures annually. However, IEN facilities were designed in the 60's and today its structure is inadequate in relation to the good manufacturing practices established by sanitary regulator (ANVISA) for the production of radiopharmaceuticals, leading to the need for a new project. In order to adapt and increase production in the country, a new plant will be built and integrated to the existing facilities with a new 30 MeV Cyclotron. Thus, it is proposed an analysis of the productive capacity of this plant in accordance with the principles of good manufacturing practices in order to define daily production and propose an optimized routine. As a result, the IEN / CNEN will in the future have a well-defined and standardized production process, with the flexibility to produce several radioisotopes required in nuclear medicine, obtaining a greater efficiency in its operation.

Microbiological evaluation in street food outside the Universidad del Atlántico North Campus

Background: The street foods are distributed in all the countries of the world, representing a part of the culture and gastronomy of each country, they are ready for consumption and easily acquired. They are exposed to unfavorable conditions that lead to rapid deterioration and increased microbial load. The study consisted of microbiologically evaluating a street food outside the Universidad del Atlántico North Campus.Methods: A survey was applied to know the most consumed food in the university community. In addition, it structured a randomized 3x2 factorial arrangement, where two sampling points will analyze design: Black and Fritos Fritos Juanca, of which 3 samples of the same food were extracted for evaluation of their quality and microbiological safety. Results: Counting microorganisms yielded 16.67% of the samples contaminated by fecal coliforms with 25 CFU / g, total coliform count was present in 50% of the samples with 27.5 and 75.0 results between CFU/ g, whereas 100% of the samples had presence of aerobic mesophiles, and in the total of these there was no presence of sulfite-reducing spores and Staphylococcus aureus.Conclusion: Therefore, all quality control measures must be taken to reduce the growth of microorganisms and prevent food contamination through hygiene techniques, training in health education, basic principles of Good Manufacturing Practices and hygienic practices in food handling.

Extemporaneous Compounding: Cautions, Controversies and Convenience

Pharmacists are only knowledgeable and skilled healthcare professionals dedicated to compounding and preparing medications to meet the unique needs of patients. The safe and effective extemporaneous compounding of prescription products for patients require in special care is fundamental to the pharmacy profession. But there are much to do for secundum artem. It is not at all economical for a pharmaceutical company to marketize a product in 10 different probable doses or in 5 different dosage forms to meet the needs of the entire range of individuals receiving therapy. Although development is a continuous process, companies are customizing features to meet the majority of patient needs, but the very nature of the process cannot meet all patient needs. The risk-benefit ratio of using traditionally compounded medicines is favorable for patients who require specialized medications that are not commercially available, as they would otherwise not have access to suitable treatment. However, if an FDA-approved drug is commercially available, the use of an unapproved compounded drug confers additional risk with no commensurate benefit. Published reports of independent testing by the FDA, state agencies, and others consistently show that compounded drugs fail to meet specifications at a considerably higher rate than FDA-approved drugs. Compounded sterile preparations pose the additional risk of microbial contamination to patients. In the last 11 years, three separate meningitis outbreaks have been traced to purportedly ‘sterile’ steroid injections contaminated with fungus or bacteria, which were made by compounding pharmacies. The 2012 outbreak has resulted in intense scrutiny of pharmacy compounding practices and increased recognition of the need to ensure that compounding is limited to appropriate circumstances. Purpose of The Study: The article aims to physico-chemical and economic considerations before compounding; factors and quality control issues; compounding support, training, chemical supplies, types of compounding (specially in hospital and ambulatory care compounding). It should aid to practice the extemporaneous preparation of basic and advanced formulations including pharmacopoeial and non-pharmacopoeial formulations encountered in pharmacy practice, together with requisite documentation, labeling, packaging and counseling requirements. Along with this, they have to study the analysis of formulations and their components and relate these to the clinical performance of medicines. This will help them to investigate, evaluate and report the physical characteristics of formulations including release kinetics and relate these to quality control and preformulation requirements; relate the application of quality control, quality assurance and the principles of good manufacturing practice to regulation of medicine production in home and abroad. Outline: Background; Introduction; Compounding Factors; Types of Compounding; Identifying Errors and Cause

Establishing the Production of Male Schistosoma mansoni Cercariae for a Controlled Human Infection Model.

To accelerate the development of novel vaccines for schistosomiasis, we set out to develop a human model for Schistosoma mansoni infection in healthy volunteers. During natural infections, female schistosomes produce eggs that give rise to morbidity. Therefore, we produced single-sex, male Schistosoma mansoni cercariae for human infection without egg production and associated pathology. Cercariae were produced in their intermediate snail hosts in accordance with the principles of good manufacturing practice (GMP). The application of GMP principles to an unconventional production process is a showcase for the controlled production of complex live challenge material in the European Union or under Food and Drug Administration guidance.

Bacterial water quality and risk evaluation of bottled drinking water in China

In this paper, bacterial water quality of bottled water in China was reviewed. National spot-check results revealed that 17.5% of samples were contaminated, 79.3% of which were due to exceeding microbial level. The annual infectious risk of people drinking bottled water everyday exceeded 1:10000 for all ages. Assuming acceptable risk is 10−4 per year, it would be considered safe if annual exposure times are less than 78 days. Strict adherence to principles of good manufacturing practices is essential through process control and personal hygiene should be maintained at the processing facility, to reduce the infection risks. Enforcement of the existing regulations and laws is also necessary to achieve this goal. Further research is needed on relationships between common bacteria and pathogens in drinking water, in order to better understand the ecology of microorganisms, and to perform a better health risk analysis for pathogens in bottled water.

Cell therapy must be regulated as medicine.

Cell therapy must be regulated as medicine.

Quality in blood components – it all starts with the donation

Blood transfusion is not risk free, so should only be prescribed when it is in the patient's best interest to do so. Blood establishments have a recognized obligation to promote optimal use of blood and blood components while minimizing risk to the health of the recipient. Processes are therefore focused on producing quality components that are efficacious and safe. In manufacturing processes, the quality of final products is heavily dependent on the quality and reliability of the starting materials, and therefore, control of these materials to reduce variation is a critical quality assurance activity. The starting material or primary product for the manufacture of blood components is the blood donation. If the quality of that donation is not assured, the efficacy and safety of the blood components manufactured from it will be potentially compromised no matter how good the rest of the manufacturing process may be. The challenge, however, is that blood is a biological material and collection is subject to a number of variations: Donations are collected from donors of various ages with different demographics, health profiles and behaviours. The donations have different characteristics, for example volume of donation, numbers of platelets, levels of immunoglobulin, blood group antibodies. The collection process depends largely on manual procedures with the exception of apheresis collections. Donations may be collected, stored and transported under varying environmental conditions. Because of these variations, controlling the quality and consistency of the primary blood donation can be more challenging than controlling starting material for an industry such as pharmaceutical manufacture. In recent years, there have been a number of developments aimed at improving the quality of the blood donation. These have largely focused on controlling and reducing variations in the process steps that are most likely to have an impact on quality or safety. These are called critical control points, and for the donation process, it includes the following: Selection of blood donors, Collection of the donation, Handling and storage of the donation, Transport of the donation to the processing centre. A number of the developments are new technologies that automate the critical control points as far as possible, such as decision support systems to improve the consistency of interpretation of donor selection guidelines, vein viewer systems that improve the venepuncture process and transport containers that can control temperatures. There have also been developments of internationally accepted component standards and principles of good manufacturing practices that provide the framework for quality in blood establishments and have been able to drive significant improvements in processes and component quality. In combination, these recent developments can provide a high degree of assurance that the starting point for the manufacture of safe and efficacious blood components will be a quality donation.

ASSESSMENT OF GMP COMPLIANCE IN WATER TREATMENT SYSTEMS OF PHARMACEUTICAL INDUSTRIES IN ETHIOPIA

Water is widely used as a raw material, ingredient, and solvent in the processing, formulation, and manufacture of pharmaceutical products, and assessing its quality is of paramount importance. To the best of the authors’ knowledge, there hasn’t been any baseline assessment made with regard to the implementation status of Good Manufacturing Practices (GMP) principles in water treatment systems of pharmaceutical industries in Ethiopia. Hence, to assess the level of compliance to GMP in water treatment systems of pharmaceutical industries in Ethiopia, a national survey was conducted in all pharmaceutical industries of the country. Data were collected by employing quantitative and qualitative methods. Self-administered questionnaires were distributed to nine pharmaceutical industries and the response rate was 8 (88.5%). According to the results, none of the industries had an influent and effluent total organic carbon monitoring system. Among the available storage tanks for purified water and water for injection, 7 (87.5%) of them were of a sanitary material. However, in 4 (50%) industries pipes were not made of sanitary material, purified water was not kept circulating at 70-80 o C and there were dead legs in the water lines. The validation results were investigated and corrective action was taken only in 1 (12.5%) of the industries. The compliance of the water treatment systems of most of the industries to WHO GMP principles was found to be below the standard in many aspects. Therefore, it is recommended that the industries should exert maximum efforts to comply with GMP principles.

Strengthening Radiopharmacy Practice in IAEA Member States

Radiopharmaceuticals are essential components of nuclear medicine procedures. Without radiopharmaceuticals nuclear medicine procedures cannot be performed. Therefore it could be said that 'No radiopharmaceutical-no nuclear medicine.' A good radiopharmacy practice supports nuclear medicine activities by producing radiopharmaceuticals that are safe and are of the required quality in a consistent way. As with any medicinal product, radiopharmaceuticals are required to be produced under carefully controlled conditions and are tested for their quality, prior to the administration to patients, using validated standard operating procedures. These procedures are based on the principles of Good Manufacturing Practice (GMP). The GMP principles are based on scientific knowledge and applicable regulatory requirements and guidance related to radiopharmaceutical productions and use. The International Atomic Energy Agency (IAEA) is committed to promote, in the Member States (MS), a rational and practical approach for the implementation of GMP for compounding or manufacturing of diagnostic or therapeutic radiopharmaceuticals. To pursue this goal the IAEA has developed various mechanisms and collaborations with individual experts in the field and with relevant national and international institutions or organizations. IAEA's activities in promoting radiopharmaceutical science include commissioning expert advice in the form of publications on radiopharmaceutical production, quality control and usage, producing technical guidance on production and regulatory aspects related to new radiopharmaceuticals, creating guidance documentation for self or internal audits of radiopharmaceutical production facilities, producing guidance on implementation of Quality Management System and GMP in radiopharmacy, assisting in creation of specific radiopharmaceutical monographs for the International Pharmacopoeia, and developing radiopharmacy-related human resource capabilities in MS through individual and regional training courses and education programs. IAEA strongly supports development of clinical nuclear medicine services by assisting MS in setting up reliable Radiopharmaceutical production facilities for single photon emission computed tomography, positron emission tomography, and for therapeutic applications.