Pharmaceutical Inspection Cooperation Scheme Research Articles

Pharmaceutical Inspection Co-operation Scheme: An Overview.

To address the challenges posed by the globalization of regulatory agencies, it is essential to harmonize regulatory requirements, assess Good Manufacturing Practice (GMP) compliance, license production facilities, manage product recalls, and improve information exchange. The Pharmaceutical Inspection Co-operation Scheme (PIC/S) provides a robust framework for tackling these global issues. Through the PIC/S GMP Forum, PIC/S facilitates informal interactions among non-member authorities, professionals, and various organizations with the Committee, fostering networking and collaboration. Furthermore, PIC/S has developed a comprehensive guide on GMP requirements for inspectorates and organizations, ensuring consistent standards across borders. The scheme collaborates with other organizations to enhance and complement collective efforts. With 56 countries involved in PIC/S, whether as members or through the Accession and Pre-Accession Process, the exchange of inspection reports among authorities verifies compliance with PIC/S standards, leading to fewer and more targeted inspections and reducing redundancy. This study's purpose is to establish uniform GMP standards by providing extensive training for inspectors and promoting collaboration and networking among regional and international bodies, regulatory authorities, and other relevant organizations. This approach seeks to build trust in inspections, optimize resource use, and foster a more efficient regulatory environment. Through these efforts, PIC/S continues to play a pivotal role in advancing global pharmaceutical regulatory practices.

A global comparative analysis of guidelines for herbal medicines Pharmacopoeia and Good Manufacturing Practice, with a case study of Panax ginseng C.A Meyer

IntroductionThe use of herbal medicines is widespread, and ensuring their quality control, as guaranteed by pharmacopoeia and Good Manufacturing Practice (GMP) guidelines, has garnered significant attention. Discrepancies in quality standards across different regulatory agencies challenge the global marketing of herbal medicines and hinder public access to these products. Therefore, this research aims to compare pharmacopeia on Panax ginseng C.A. Meyer (P. ginseng) and GMP guidelines for herbal medicines to provide an evidence-based understanding of quality control standards. MethodsDefinitions of herbal medicines across regulatory authorities, including the World Health Organization (WHO), Pharmaceutical Inspection Co-operation Scheme (PIC/S), European Union (EU), China, Japan, South Korea, and Vietnam, were collected. Additionally, pharmacopeial standards on Panax ginseng case study were analysed, focusing on aspects such as origin, identification, testing methods, extractives, assay, purity, and drug information. The study also compared GMP requirements for herbal medicines, which included personnel, premises and equipment, documentation, production, quality control, contract manufacturing and analysis, complaints and product recall, and self-inspection. ResultsDefinitions of herbal medicines are similar among the WHO, PIC/S, and the EU, while distinct definitions based on scientific evidence and traditional practices were presented in China, Japan, South Korea, and Vietnam. Pharmacopeia standards varied across regulatory agencies, as evidenced by the P. ginseng case study. However, testing methods closely resembled each other between China and Vietnam, as well as between Japan and South Korea. Among pharmacopoeias, the WHO monographs offered the most comprehensive drug information on P. ginseng. In contrast, the European Pharmacopoeia lists such details separately in a P. ginseng assessment report. Regarding GMP requirements, although examined components varied among regulatory agencies, significant resemblances exist between the GMP guidelines of PIC/S, the EU, and South Korea, and between those of the WHO and Vietnam. ConclusionsDisparities in quality standards across jurisdictions highlight the necessity for international collaboration to achieve harmonization. Harmonizing these standards aims to promote the global availability of standardized herbal medicinal products, benefiting public health.

Comparative analysis of rule elements for transportation of cell therapy products among regulations and standards.

Aim: This study aimed to identify the elements involved in the transportation of cell therapy products by conducting a comparative analysis of four related international standards for temperature-controlled delivery and good distribution practice (GDP). Methods: An analytical framework was constructed to cover the entire transportation process. The descriptions of each element in the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) GDP, International Organization for Standardization (ISO) 21973, Foundation for the Accreditation of Cellular Therapy Common Standards for Cellular Therapies and ISO 23412 were compared. Results: The study identified some elements that were present in the PIC/S GDP and other standards but were absent in ISO 21973, and vice versa. These elements are crucial in view of the increasing opportunities to transport allogeneic cells in the future. Conclusion: The study identified the necessary elements that should be included in the development of transport regulations for cell therapy products.

Difusão de política na prática: o caso da regulação brasileira de medicamentos

Abstract The present study seeks to contribute to a better understanding of policy diffusion processes, more specifically, of the diffusion process from a transnational arena that influenced the regulation of Good Manufacturing Practices (GMP) for medicinal products in Brazil in a context surrounded by international authorities. By conducting qualitative research, we analyzed the process of adhesion of the Brazilian Health Regulatory Agency (Anvisa) to the Pharmaceutical Inspection Co-operation Scheme (PIC/S), initiated in 2010 and achieved in 2021. A process influenced by two constellations of diffusion was identified, motivated by the national agency’s interests in maintaining its relevance and by actors that make up the National Sanitary Surveillance System, in which the PIC/S model of regulatory equivalence and convergence proved to be fundamental for the adaptation of the international reference to the national level, keeping the national system functioning. Such a policy diffusion process became even more relevant in the past years due to the expansion of regulatory convergence and potentially making the various health authorities’ GMP assessment of medicinal products more efficient.

The Utility of Remote Inspections During the COVID-19 Health Emergency and in the Postpandemic Setting

PurposeThe COVID-19 pandemic has affected the management and operation of regulatory agencies and the pharmaceutical industry around the world. It has prompted regulatory authorities to consider new ways of working and introduced, among others, remote inspections to validate the integrity of the regulatory data submitted by companies, to evaluate the quality of production and manufacturing sites, and to ensure the conformity with Good Regulatory Practices with the overall goal of guaranteeing patient safety during the crisis.MethodThis article summarizes and discusses remote inspection guidelines and other related information made available by the Therapeutic Goods Administration (Australia), the European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency (Japan), the Medicines and Healthcare Products Regulatory Agency (United Kingdom), and the US Food and Drug Administration (FDA). We also analyze the effect of the pandemic on inspections conducted by the inspectorates of the EMA and the FDA.FindingsThe regulatory authorities that we studied all recognized the importance of implementing regulatory policies on remote inspections in response to the COVID-19 pandemic. The remote inspection guidelines from the 5 selected regulatory authorities aimed at mitigating the impact of the pandemic but, while providing valuable advice to the pharmaceutical companies and being similar in intent, were not always aligned in terms of approach and solutions.ImplicationsOn-site inspections are likely to continue to be the norm and the preferred standard for the foreseeable future. However, health authorities will need to further adopt a risk-based inspection approach and stimulate the increased uptake of inspection reliance as proposed by the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme not to overwhelm the pharmaceutical companies with repeat and redundant inspections. Remote inspections have proven to be a new inspection tool, but health authorities should align on their approach to remote inspections in terms of methods applied and documentation requested.

Explicit Microsoft Excel Methods For Computerized System Validation

To combat CSV non-compliance, established here are cost and time effective explicit methods to verify and validate Microsoft Excel Workbooks designed to meet standards set by Australian regulatory bodies: The Therapeutic Goods Administration (TGA) and Pharmaceutical Inspection Co-operation Scheme (PIC/S).

Regulatory advances and prospects of variation filing for the registered parenteral products in USA and Europe

Drug Regulatory Affairs (DRA) is a vital unit in a pharmaceutical company. It is concern about the healthcare product lifecycle, it provide strategic, tactical and operational direction and support for working within regulations to expedite the development and delivery of safety and efficacy in pharmaceuticals, veterinary medicines, medical devices, cosmetics and complementary medicines, healthcare products to individuals around the world. Regulatory affairs (RA) professionals are employed in pharmaceutical industry, government, academic research and clinical institutions. As India is growing very rapidly in pharmaceutical sector, there is a need of regulatory affairs professionals to cater the current needs of industries for the global competition. Regulatory affairs professionals are the link between pharmaceutical industries and worldwide regulatory agencies. A regulatory affair is a somewhat new profession which has developed from the desire of governments to defend public health. Substantial documentation and data are required in these types of submissions, resulting in large, complex applications. Today 35 member countries along with 11 candidate countries and 4 international agencies have joined together to create the Pharmaceutical Inspection Cooperation Scheme (PIC/S) to promote a globally accepted GMP. Current constrain of Regulatory Affairs reveals diverse countries need to follow different regulatory requirements for marketing authorization Application (MAA) approval of new drugs. In this present exertion, study expresses the drug approval process and regulatory requirements according to US Food and Drug Administration (UDFDA), European Medical Agency (EMA) and Central Drug Standard Control Organization (CDSCO).

Pharmaceutical good manufacturing practice: Leuplin® production in Japan identifies major international shortcomings.

In Japan, the production of Leuplin®, a key drug for the treatment of prostate cancer and breast cancer, was temporarily suspended in 2020 by the manufacturer. The incident illustrated several significant failings, namely the lack of uniformity in international GMP (Good Manufacturing Practice) regulations, the lack of mechanisms to resolve disputes between PIC/S (Pharmaceutical Inspection Co-operation Scheme) member countries, and the importance of maintaining a stable supply of safe GMP-compliant essential medicines.

Regulatory aspects of GMP in accordance with pharmaceutical inspection co-operation scheme

The PIC/S strives to harmonize inspection procedures all over the world by establishing specific GMP guidelines and supplying inspectors with training opportunities. This is additionally proposed to advance co-operation and systems administration between capable specialists, local and foreign associations, in this manner becoming common confidence. At present, harmonization efforts need to be improved in setting regulatory standards, monitoring and assessing GMP compliance, licensing production sites, retrieving faulty lots, and increasing the sharing of information due to expanded regulatory authorities for globalization. PIC/S provides an appealing and sustainable platform to give a response to globalization’s challenges. PIC/S actively facilitates networking by organizing a PIC/S GMP Forum," which enables non-member, technical and other organizations to meet informally with the PIC/S committee. Co-Operation Scheme for the Pharmaceutical Inspection is available to any systems administration having a practically identical GMP investigation framework. Co-Operation Scheme for the Pharmaceutical Inspection has built an integrated manual on GMP necessities for inspectorates and also for the industries. The primary harmonization device has been the Co-Operation Scheme for the Pharmaceutical Inspection GMP Guide. The last was initially gotten from the WHO Guide to GMP and further created so as to consent to exacting assembling and wellbeing pre-requisites in the Co-Operation Scheme for the Pharmaceutical Inspection nations, to cover new zones (for example, biological and radio-pharmaceuticals) and to adjust to logical and mechanical innovation.

Evaluation of New Risk-based Regulatory Approach to Classification of GMP Deficiencies (Review)

Introduction . This paper is devoted to analysis of a new risk-based regulatory approach to the classification of deficiencies found by inspections of medicines manufacturers, which is undoubtedly relevant. Text . The article describes the new definitions for the deficiencies found in the medicinal products manufacturing, the proposed gradation of non-conformances distinguishes from the one that is currently used. The proposed innovation in regulatory activity is that a critical deficiency can consist of several related nonconformities, none of which can be critical on their own, but which together can constitute a critical nonconformity or system failure. The proposed approach to the classification of deficiencies, which is based on a risk assessment for the patient, is described. The main stages of the risk-based algorithm are characterized: a detailed assessment of the deficiency for its preliminary classification; assessment of risk increase or decrease factors, regardless of the initial classification; making a decision on the final classification, taking into account the factors of increasing, reducing risk or their absence. Block diagrams and illustrative examples are described, on the basis of which preliminary assignment of a revealed deficiency of one or another level of criticality is carried out. The factors of increasing or decreasing risk are considered. These factors are extrapolated to the category of deficiency and they can both increase the preliminary assigned category or decrease it, and can leave the preliminary classification unchanged. Conclusion . A new risk-oriented regulatory approach to the classification of non-conformances with the requirements of Good Manufacturing Practice, proposed by the Pharmaceutical Inspection Co-operation Scheme PIC / S, is described. An analysis of this approach and its characterization are made. The new approach is based on the systematic and methodological application of risk management tools, aimed at justifiably assigning a certain criticality category to a revealed deficiency. The implementation of the new approach allows to increase the objectivity and transparency of inspection procedures. Further detailed study and possible step-by-step implementation of this new approach is very important for regulators so for medicines manufacturers.

Clinical Therapeutics in Hong Kong

Hong Kong is a compact territory in Southern China that enjoys a high degree of autonomy. Despite its dense population and uneven wealth distribution, infant mortality is low and life expectancy is long. The health service is more hospital and clinic based than community based. This seems cost-effective while professional standards are high and rigorously maintained. Drug registration follows American and European requirements. Hong Kong is a part of the Pharmaceutical Inspection Cooperation Scheme, which brings a high standard of drug regulation. Hong Kong is a good choice for clinical trials because the subjects are Chinese and protocols in English do not need to be translated. There are also 2 well-established clinical trials centers in university hospitals that also run Phase I and clinical pharmacology studies.

Global perspectives on ensuring the safety ofpharmaceutical products in the distribution process .

The distribution of counterfeit or falsified drugs is increasing worldwide. This can contribute to the high burden of disease and cost to society and is of global concern with the worldwide circulation of pharmaceuticals. The preparation and implementation of good distribution practice should be one of the most important aspects of ensuring safe drug circulation and administration. This research aimed to compare and analyze good distribution practice guidelines from advanced countries and international organizations, and to evaluate the status of the current good distribution practice guidelines in the world. Advanced pharmaceutical countries and international organizations, such as the World Health Organization, European Union, Pharmaceutical Inspection Co-operation Scheme, United States of America, Canada, and Australia, which have stable good distribution practice guidelines and public confidence, were included in the analysis. The World Health Organization and European Union guidelines are models for standardized good distribution practice for nations worldwide. The United States of America has a combination of four different series of distribution practices which have a unique structure and detailed content compared to those of other countries. The Canadian guidelines focus on temperature control during storage and transportation. The Australian guidelines apply to both classes of medicinal products and medical devices and need separate standardization. Transparent information about the Internet chain, international cooperation regarding counterfeiting, a high-standard qualification of sellers and customers, and technology to track and trace the whole life cycle of drugs should be the main focus of future good distribution practice guidelines worldwide. .

Import Testing: An Outdated Practice? Opportunities for Improved Access to Safe and Efficient Medicines.

Import testing of medicines is performed in the middle of the legitimate supply chain when a product enters a country. Risks, however, are identified in the illegitimate supply chain and in the trade within a country. Hence, import testing does not add any significant value to the quality and safety of drugs nor reduces risks, provided the manufacturers apply good practices, for example, Good Manufacturing Practices (GMPs) and Good Distribution Practices (GDPs). The consideration to implement additional regulations does not correlate with the increasing convergence between National Regulatory Authorities (NRAs) and international harmonization, for example, Pharmaceutical Inspection Co-Operation Scheme (PIC/S) and International Council for Harmonisation (ICH). This publication reflects the historical application of import testing and today's practice, concerns, and misconceptions of this redundant procedure. It explains why postmarketing surveillance testing is better suited to control the quality of medicines, addressing highly relevant concerns: counterfeits and supply interruptions.

Practical implementation of the PIC/S principles in Ukraine after its accepting international requirements for quality control of medicinal products

Pharmaceutical Inspection Cooperation Scheme (PIC/S) is an international instrument of interaction between countries and regulatory authorities in the sphere of quality control of medicines (by national pharmaceutical inspectorates), which together provide an active and constructive cooperation in the field of good manufacturing practices (GMP), inspection and licensing. Aim. To develop a strategy, tactics and sequence of applying adaptation mechanisms to the pharmaceutical industry legislation of Ukraine according to EU and the PIC/S requirements. Results. In 2010, within Ukraine joining to the PIC/S the starting audit of researches on adaptation of medicinal products quality standards to the international requirements was carried out. In the period from March 22 to 26, 2010 the PIC/S audit team performed the final audit in order to check the readiness of Ukraine to join the PIC/S. On November 8,2010 a decision on Ukraine’s membership was made in Kuala Lumpur (Malaysia). Since January1, 2011 Ukraine has become the PIC/S member within the system of medicinal products circulation and quality control in accordance with GMP/GDP and EU Directive 2001/83/EC. During the period of Ukraine’s accession to the PIC/S system, accordingly, this Directive was improved. At the VIII National pharmaceutical Congress (Kharkiv, September 14-16, 2016) 26 additions to the decision of Congress were proposed, including questions related to the PIC/S and other legislative initiatives. Conclusions. Legislative documents of the system of medicines quality control and circulation inspection are the international requirements of the PIC/S. The principles, measures and requirements were developed, discussed and accepted that contributed to the accession of Ukraine to the PIC/S system in 2011.

A practical and pyrogen-free preparation of 11C-L-methionine in a good manufacturing practice-compliant approach

Aims: 11C-L-methionine, an amino acid tracer used to delineate certain tumor tissues, has proven to be a prevailing nonfluorodeoxyglucose positron emission tomography (PET) radiopharmaceutical. We intended to prepare 11C-L-methionine by following modified synthetic strategies at a rebuilt working area to meet the PET drug current good manufacturing practice (cGMP) and Pharmaceutical Inspection Co-operation Scheme (PIC/S) regulations. Furthermore, we overcame the problem of pyrogen cross-contamination using a cleaner and more efficient program. Material and Methods: The task of upgrading air filtration equipment was integrated with the set of Web-Based Building Automation system (WebCTRL®). 11C-L-methionine synthesis was carried out in accordance with redesigned methods to meet the requirements of PET drug cGMP. The product quality was tested by a series of quality control tests and was found to be satisfactory. Depyrogenation was carried out by three different methods with different flow rates and flushing durations. The results were examined through limulus amebocyte lysate clotting test. Results: The level of air cleanliness in each section meets the PIC/S GMP standards after the reconstructions. Moreover, after delicate modifications, the radiochemical yield of 11C-L-methionine was 36.20% ± 3.59% (based on 11C-CH3I, n = 7), which is about 10% higher than the average former yield. Besides, the used depyrogenation methods could wipe the bioburden off within 8 h. Conclusions: The modifications done not only offer a good production environment but also protect the products from contamination. The modified approaches in both 11C-L-methionine production and depyrogenation resulted in prominent progress in stability and efficiency as well.

Development of the risk-based, phased-in approach for the international harmonization of the regulation of container closure systems for drugs in Taiwan

The main concern for container closure systems of drugs is to ensure suitability for the intended use which is associated with issues regarding protection, compatibility, safety, and performance. Among various concerns, leachables may pose a safety hazard to patients, while risks might vary depending on the dosage form and the administration route. Stringent regulatory authorities such as the European Medicines Agency and the United States Food and Drug Administration have established risk-based regulatory requirements and published corresponding guidelines to facilitate implementation. Taiwan, a member of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, makes every effort to harmonize with international regulations and to strengthen protection of public health through regulatory controls. The aim of the present study was to investigate the regulatory framework and policies set by stringent regulatory authorities. The strategy proposed for the development of an eventual guideline was sent to the Taiwan Food and Drug Administration for decision. A risk-based, phased-in approach which was extensively discussed in the expert committee was proposed. The approach proposed herein could also serve as a starting point which is worth considered by other countries in which international harmonization is in process.

The evolution and challenges for the international harmonization of the regulation of pharmaceutical excipients in Taiwan

Excipients, once considered an inert component, have been shown to greatly influence the characteristics of the drug product, such as quality and safety. Functionality-related characteristics of excipients could affect the performance of the drug product. Moreover, the impact of globalization has complicated the issue and made the supervision of supply chain highly important. Taiwan, a member of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, makes efforts to harmonize with international regulations and to strengthen the protection of patients through regulatory controls. In order to improve the harmonization and the transparency of regulatory requirements, the aim of the present study was to investigate the regulatory framework and considerations of stringent regulatory authorities and to propose the draft regulatory requirements to the Taiwan Food and Drug Administration for jurisdiction. The proposal which was extensively discussed in the expert committee includes the regulatory considerations to ensure the safety and quality of the excipients and may serve as a platform to facilitate the communication with industries about the current thinking on related issues. Moreover, through the review of the recent guidelines published by the stringent regulatory authorities, the trend of the regulatory considerations was revealed and discussed.

Lessons Learned from Compounding Tragedies

Several months have passed since news broke of a horrific compounding tragedy at the New England Compounding Center (NECC) in Framingham, Massachusetts. An outbreak of fungal meningitis in fall 2012 was traced to contaminated methylprednisolone acetate prepared by the NECC. According to the US Centers for Disease Control and Prevention (CDC), as of May 11, 2013, 55 deaths and a total case count of 741 had been attributed to the contamination, and the numbers continue to rise. Patients who received medications from this pharmacy have also experienced paraspinal, spinal, and peripheral joint infections. The Institute for Safe Medication Practices (ISMP) has compiled a list of selected compounding misadventures since the 1990s. For legal reasons, many compounding misadventures never become public, but the US Food and Drug Administration (FDA) has been actively inspecting compounding pharmacies with a history or suspicion of large-scale compounding or quality concerns. Compounding problems are not isolated to the United States. Recently, more than 1200 cancer patients in Ontario and New Brunswick received chemotherapy solutions with concentrations below labelled specifications. It appears that jurisdictional issues regarding proper oversight of this operation and others were similar to the problems identified in relation to the NECC event. It is time to face our naivete and our occasional arrogance about safe compounding practices. We must learn from these events and take measures to ensure that we are doing everything possible to protect patients and reduce the risk of improperly compounded sterile preparations. On a personal level, I have been profoundly affected by the NECC event, and I continue to be perplexed by the actions of some of my colleagues who somehow still believe that the principles of contamination control and robust quality systems don’t apply to them. As a pharmacist and a potential future patient, I ask, “What are you doing for your present-day and future patients in light of these recent issues?” Whether you agree or disagree with United States Pharmacopeia (USP) Chapter and other USP chapters critical to compounding or the Pharmaceutical Inspection Cooperation Scheme’s compounding guide, the message couldn’t be clearer. Business as usual is no longer acceptable. We must embrace standards and guidelines that incorporate evidencebased science and best practices that have been vetted through public comment and review cycles. More specifically, it is time to perform risk assessments of the compounding methods used in our own pharmacies, so that inherent risks can be identified and mitigated through detailed policies and procedures, robust training programs and quality systems. Pharmacy staff members must know not only what is expected of them as they prepare sterile dosage forms, but also why they are expected to do these things. We must move away from the pure apprenticeship model of training and instead deploy methods and procedures that establish a solid foundation for quality work practices that will prevent compounding errors. Pharmacy practitioners are increasingly challenged to prepare compounded sterile dosage forms that are not commercially available, at times using nonsterile active pharmaceutical ingredients. Handling and transforming these components into appropriate sterile dosage forms may require greater experience and expertise than a particular pharmacy possesses. In such cases, we must take these limitations into account and recognize the risks they pose to our patients. In particular, only robust and validated procedures should be used. We have the responsibility to ensure that any compounded preparation is what it is expected to be and, to the degree possible, to ensure and measure its sterility. Conversely, if we don’t have the requisite expertise, we should not undertake these activities. Historically, pharmacists compounded medications in a “just in time” manner. However, current distribution models require that more compounded sterile preparations be stored at room temperature, prompting the desire for longer beyond-use dating. The sterility tests described in USP Chapter

How Risky Are Pinholes in Gloves? A Rational Appeal for the Integrity of Gloves for Isolators

Isolators provide a high degree of protection for the product and/or the environment and operators in pharmaceutical production, as well as for analytical and sterility testing. Gloves allow for performing testing and for easy access to the process. Due to their nature-thin plastic, highly flexible-and their risk of puncture or rupture, they are regarded as one of the main potential sources of contamination. Glove integrity testing is therefore a main issue and has been addressed by many regulations such as those imposed by the USP, U.S. Food and Drug Administration, and Pharmaceutical Inspection Convention. This paper presents a short overview of different glove integrity test procedures and their ability to detect leaking gloves. Additionally, extensive microbiological tests have been performed to give more evidence and cross-correlation to physical testing. Most of the physical tests have limitations either in detecting pinholes and/or they are difficult to implement for routine testing. Microbiological tests are only applicable for evaluation and validation purposes, but not for routine testing, because they are time-consuming and do not allow immediate action. Routine visual verification of gloves by trained personnel turns out to be a very reliable technique. Additional microbiological tests supported by microbiological environmental monitoring helped to develop a new concept presented here on how to handle gloves with pinholes. It is proposed not to automatically consider a pinhole in a glove as a breach in isolator integrity, but to consider any action in view of controlling and monitoring the effective bioload on the outside of the gloves. With the combination of semi-automatic physical testing with independent protocol, visual inspection, and control of bioload through microbiological environmental monitoring potential contamination, risks can be minimized and maximum safety maintained. Isolators are enclosure designs to protect critical handling and process steps in pharmaceutical environments. They provide a high degree of protection for product and/or environment and operators against particles, potentially hazardous active principles, and microbial load. Gloves mounted on windows and doors of the isolator allow for manipulation, performing testing, and access to the process. Due to their nature and their use with risk of puncture or rupture, they are regarded as a potential source for contamination. Glove integrity testing has therefor been addressed by regulations such as those imposed by the USP and the Food and Drug Administration. This paper presents a short overview of various glove integrity test procedures and their ability to detect leaking gloves. Most of the tests have limitations either in detecting pinholes and/or they are difficult to implement for routine testing. Routine visual verification of gloves by trained personnel turns out to be a very reliable technique. Additional microbiological tests led to a new concept presented here on how to handle gloves with pinholes and how to take action. With this approach, risks can be minimized and maximum safety maintained by controlling and monitoring the effective bioload on the outside of the gloves.

GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP “Fluorodopa F 18 Injection”

Lately, 6-[(18)F]fluoro-L: -DOPA (FDOPA) has found increase in its clinical demand for whole-body positron emission tomography (PET) scans, and two key issues in fulfilling this demand are the difficulties in producing FDOPA under the recently imposed PET drug good manufacturing practice (GMP) regulations and in providing it in the quality meeting the terms of major compendia. This paper describes the approaches for the GMP production of FDOPA and for the product testing to meet the standard of United States Pharmacopeia (USP) "Fluorodopa F 18 Injection." FDOPA was produced by the carrier-added electrophilic aromatic substitution reaction in the facility complying Pharmaceutical Inspection Cooperation Scheme clean room standard. The special aseptic handling technique was applied to minimize the bioburden. The product quality control followed all testing items and procedures, including three different settings of HPLC. The process yielded FDOPA average 2.60±0.26GBq (N=22) in every batch. All qualities of the product were within the specifications described in the USP "Fluorodopa F 18 Injection." The entire production was audited by the government authority and certified to comply with the latest PET drug GMP regulation. Our efforts in producing FDOPA following all aspects of GMP requirements have resulted in a product with the USP quality and certified as GMP complied. The routine production yields enough doses for three to four whole-body scans in each batch. The issues discussed in the report provide good reference for producers planning in routine production for PET drugs that are not commonly produced or with complicated compendial quality control tests.