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Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing beta cells in the pancreas. Consequently, T1D patients produce little to no insulin, resulting in absolute insulin deficiency and an inability to regulate blood glucose levels effectively. Insulin replacement is the mainstream treatment for T1D, but it comes with a major drawback—the risk of hypoglycemia unawareness. As such, replenishment of glucose-sensing and insulin-producing beta cells via cell replacement therapy is believed to have great therapeutic value for T1D patients. Human pluripotent stem cells (hPSCs) are considered an attractive source for the derivation of insulin-producing beta-like cells for cell replacement therapy. However, several challenges need to be addressed before hPSC-derived beta-like cells can be used for T1D treatment. In this chapter, we provide a snapshot of the current progress of hPSC therapy with an emphasis on T1D, discuss some of the clinical considerations and technical strategies in the generation of current good manufacturing practice (cGMP)-compliant hPSC-derived beta-like cells and the future outlook for T1D hPSC therapy.

The product authorization from the market can be achieved by following good manufacturing practice (GMP) regulations. It assures the quality of the product by monitoring the materials used in the manufacturing of the product. Reliable products are produced and launched in the market. Quality management of nonclinical safety studies comes under the good laboratory practice (GLP) regulation. The purpose of the regulation is to encourage scientists to arrange and perform their studies in a way that assists the quality and validity of the test data. Novel drug deliveries like nanomedicine have been approved for clinical use if developed as per the GLP and current good manufacturing practice (cGMP) guidelines.

Herbal medicines and remedies are included in the general therapy discipline known as complementary and alternative medicines (CAMs). While global use of these medicines is escalating exponentially, their quality, safety, and efficacy are major concerns due to lack of appropriate regulatory control. Herbal medicines mainly contain plant material consisting of complex constituents where many, if not all, of the active principles are often unknown. The amount of incorporated ingredients can vary greatly due to numerous factors that can result in variation in the quality of raw materials. Quality is highly dependent on the source of plants and related materials, which in turn are dependent on numerous intrinsic (genotype) and extrinsic factors such as taxonomy, selection, and cultivation including environmental conditions and geography. Although, traditional methods do provide anecdotal evidence of preparation of herbal medicines, these methods may not provide details of actual active ingredient(s). Hence, correct identification of species, careful collection, and appropriate storage are essential requirements for the quality control of raw materials to ensure that products containing plant material or extracts are of the requisite quality. Extraction of plant material, isolation, and identification of active ingredients using appropriate validated analytical methods and procedures for QC of products for two specific plants, as examples, are described in this chapter. Unlike allopathic medicines, QC of herbal medicines remains largely unregulated resulting in high variability in specific content and potency between batches and questionable control of impurities and presence of possible toxic contaminants. The application of appropriate extraction procedures and the use of qualified reference standards in conjunction with good manufacturing practice (GMP) to produce high-quality products remains an important objective to ensure appropriate clinical performance of such products.

The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application. This Treg isolation procedure ensured the selection of a pure Treg population that underwent a 300-fold expansion after 36 days of culture, while maintaining a purity of more than 75% CD4+CD25+FOXP3+ cells and a suppressive function of above 80%. Furthermore, we report the successful cryopreservation of the final product, demonstrating the maintenance of phenotype and function. The process outlined in this manuscript has been implemented in the ONE study, a multicenter phase I/IIa clinical trial in which cellular therapy is investigated in renal transplantation.

Tissue engineering ensures the repairing or replacement of diseased organs and tissues for many patients to be promising. Although the field is relatively young, many innovative and exciting research have begun to transfer to the clinic. Translation of tissue-engineered products usually follows similar procedures as regular drug products. Once proof of concept is established for a tissue engineering project, preclinical studies are conducted, followed by process and product development for human use. Once routine processing is established, it gets transferred to a manufacturing team to produce the product in a current good manufacturing practice facility. Subsequently, the product testing is performed by quality control, and quality assurance provides the structure for documentation and oversight to processing, testing, and facility management. The translation into the clinic is guided by FDA regulations. Traditional FDA regulations for drug products are being shifted to be specific to tissue engineering products, and understanding of the latest regulations is essential for a successful translation into the clinic.

Publisher Summary The presence of the four distinct seasons with appropriate temperature and humidity in Japan surrounded by sea fostered the Japanese food eating habit and created a distinctive Japanese food culture. The term “health foods” (HF) is commonly used in Japan to describe what may be called “functional foods” (FF) or “dietary or food supplements” in the USA and other countries. This chapter serves to enhance understanding of HF in relation to various regulatory systems and safety concerns in consumers. The “Foods with Specified Health Uses” (FOSHU) concept is described as it evolved from FF which was first developed and published for the health benefits of foods in our country in 1984. In 1991, the Ministry of Health and Welfare (MHW), now known as the Ministry of Health, Labor and Welfare (MHLW), officially presented the FOSHU system as a basis for making the functional claims of foods (FD). It was in reference to the increase in the occurrence of lifestyle-related diseases (LSRD) that include diabetes mellitus, high blood pressure, cerebro- and cardiovascular diseases and cancer. In 2001, a new regulatory system, “Foods with Health Claims” (FHC) was established and consisted of a new concept of “Foods with Nutrient Function Claims” (FNFC) and innovated FOSHU. In 2005, the MHLW additionally changed the existing FOSHU system. Such change includes the new subsystems of FOSHU: standardized FOSHU, qualified FOSHU and disease risk reduction claims. Lastly, issues directed to the safety and quality of raw materials and HF products are also discussed with the focus on two guidelines that require good manufacturing practice (GMP) and self-investigating systems for safety of raw materials.

Consumers nowadays are faced with food or food ingredients that may derive from distant countries or continents and with a less transparent food supply. Safety concerns must cover the range of different food chains relevant to a certain food product or product group, including all relevant producers, manufacturing sites and food service establishments within a country as well as those importing into the country. Food regulation in the main is aimed at protecting the consumer’s health, increasing economic viability, harmonizing well-being and engendering fair trade on foods within and between nations. Hazard analysis at critical control points, good manufacturing practice and good hygiene practice are major components of the safety management systems in the food supply chain. Principally, ‘a hazard’ is a biological, chemical or physical agent in, or condition of, food that has the potential to cause an adverse health effect. The likelihood of occurrence and severity of the same is important for the assessment of the risk presented by the hazard to the food supply chain. The Government’s regulatory mechanisms in accordance with the World Trade Organization (WTO) agreements (HACCPs, sanitary and phytosanitary (SPS) measures etc.) oversee the analyses of public health problems and their association to the food supply. Under the WTO SPS Agreements and the codes of practices issued by the Codex Alimentarius Commission there now exists a benchmark for international harmonization that guarantees the trade of safe food. It is also becoming clear that non-tariff measures, such as regulatory standards for manufactured and agricultural goods, can have a significant impact on trade.

Quality products are vital to the beverages industry; in contrast, most of the beverage companies do not succeed in ensuring the quality of the products to consumers. Beverage safety can be ensured by the sequence of assessments like the monitoring of raw material quality, production processes, packaging examinations, microbial analysis, and sensory analysis. All these tests include generally the identification of ingredients, pesticides, contamination evidences, and plastic and coloring additives. Analysis of the nutritional values and the quality of ingredients of the products is very important to ensure the safety and quality of the beverages. In the last, sensory investigation by means of color, taste, odor, and textural analysis is efficient for the assessment of the final beverage quality. Quality management system (QMS) including good manufacturing practice. This chapter will mainly deals with the quality issues and control system in beverages.

Summary The discovery of induced pluripotent stem cells (iPSCs) and the concurrent development of protocols for their cell-type-specific differentiation have revolutionized our approach to cell therapy. It has now become critical to address the challenges related to the generation of iPSCs under current good manufacturing practice (cGMP) compliant conditions, including tissue sourcing, manufacturing, testing, and storage. Furthermore, regarding the technical challenges, it is very important to keep the costs of manufacturing and testing reasonable and solve logistic hurdles that permit the global distribution of these products. Here we describe our efforts to develop a process for the manufacturing of iPSC master cell banks (MCBs) under cGMPs and announce the availability of such banks., Highlights • Generation of clinical-grade iPSCs manufactured under a cGMP-compliant process • A robust and reproducible iPSC culture system • A completely defined, serum-free, and feeder-free process • A comprehensive characterization, including gene expression profiles of cGMP iPSCs, Rao, Fellner, and colleagues report the development of a cGMP-compliant process for the manufacturing of iPSC master cell banks and announce the availability of such banks for the development of clinical cell therapy applications. This manuscript highlights the generation of a clinical-grade human iPSC line using a fully cGMP-compliant process starting from tissue sourcing, a robust and reproducible hiPSC generation process, and well established testing.

Continued occurrence of foodborne disease outbreaks; national recalls of human foods due to adulteration or contamination with undeclared allergens; intentional adulteration of food for economic gain with toxic substances, such as melamine; and the growing vulnerability of an increasingly global and complex food supply were factors contributing to the passage of the US Food Safety Modernization Act (FSMA) into law in 2011. Six years later, FSMA is still being implemented due to the enormous scope of the changes that are occurring. A tremendous amount of input from industry, consumers, foreign agencies, and others was carefully weighed in crafting the regulations. Industry training needs have been thoughtfully considered concurrently. By 2016 the seven foundational regulations of FSMA have been finalized. Of these seven regulations, the Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Foods will likely have the largest impact on improving food safety of human foods. This rule, even with its purposeful flexibility, will likely also stimulate the most changes to the way food producers make food and how retail food businesses ensure the quality and safety of their supply chain. The key elements of this regulation, including the Food Safety Plan requirements, are introduced in this chapter. Risk-based, preventative (rather than reactive) approaches to food safety are not new, and this chapter includes a brief history of hazard analysis and critical control point (HACCP) as well as a comparison of HACCP with the preventive controls for human food requirements. Finally, it will be important for retail food businesses to understand and measure their suppliers' compliance with these rules to prepare for new enforcement requirements that will certainly impact their business.

Core-multishell (CMS) nanocarriers (DendroSol) are innovative biocompatible excipients, which can be used to improve the dermal penetration of medicinal drug substances. The basis of CMS nanocarriers is a hyperbranched polyglycerol core surrounded by an amphiphilic shell. By varying chain lengths and charge density, the excipients can be adapted to different drug substances. As excipients within drugs, CMS nanocarriers are required to fulfill regulatory requirements, including 2015/C 95/02—an EU guideline on the formalized risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use. The risk assessment also considers the quality management system, as well as the source and intended use of the excipients. Specifically, CMS nanocarriers are well suited as excipients following a careful risk assessment.

The diversity and range of foods being produced in developing countries that have found and are finding their way into developed country diets and mainstream cuisine is discussed in this chapter. These range from the already well known produce, nuts, fruits and vegetables, cocoa, coffee, coconut, cashew, conch (Strombus giga), pineapple and aubergine (eggplant) to foods such as chow mein, tacos, rotis, jerk, and various curries, to trendier and more exotic foods, including satays, sriracha, and harissa. The increasing prominence of foodborne illness outbreaks, however, has made it necessary that developing country exporters and producers implement systems to become compliant with the traceability, labeling, packaging, residue levels, Good Manufacturing Practice (GMP), Good Agricultural Practice (GAP) and other prerequisite program (PRP) requirements in their food handling facilities. They also have to implement Hazard Analysis Critical Control Points (HACCP)-based food safety systems for their products seeking to enter the retail trade in developed country markets to comply with both market entry requirements, as well as the food safety and quality system (FSQS) requirements demanded by major retailers and buyers. These and other considerations are explored, with an example of the structure of a PRP presented as this chapter introduces the nature and importance of FSQS requirements to the global food trade from developing countries.

Safety considerations that prevent harm to human and animal health and to the environment could often be different at the laboratory scale and at a level required for commercialization. Most large-scale applications rely on the modified organism being no more dangerous than the nonmodified host. In instances where the risk assessment of the host organisms indicates a possibility for causing disease or unforeseen adverse effects, physical, and/or biological containment may offer solutions. This chapter looks at mechanisms that ensure safety in large-scale applications of genetically modified (GM) organisms such as Good Industrial Large-Scale Practices for GM microorganisms, and physical and biological containment appropriate for field release of GM crops. The chapter also discusses Good Manufacturing Practices for the production of medicinal products from biological sources.

This chapter reviews the Food Safety Modernization Act (FSMA) rules and regulations; the first two recalls under the mandatory recall authority provided to the Food and Drug Administration (FDA) under FSMA; and a few early Warning Letters about FSMA violations. The issues in FSMA-related Warning Letters and recalls are tightly linked to food contaminations by specific organisms known to cause human illness. In particular, the current good manufacturing practice violations leading to these contaminated foods are the focus of ongoing enforcement activities. When developing a huge undertaking such as ensuring safe food for US consumers, the metrics for success should be clear: the number of food-borne illnesses should decrease dramatically and immediately as a direct result of the FSMA-related FDA activity.

In this work, an integrated and systematic methodology is presented for the assessment of process performance—e.g., run time and cost—of biopharmaceutical drug product manufacturing. The methodology is represented as an IDEF0 activity model that rigorously defines the interconnections of information and activities with incorporating Good Manufacturing Practice, the quality standard of the pharmaceutical industry. Monte Carlo simulation is used to account for operational uncertainty of the process, and global sensitivity analysis is conducted to identify operations with large impacts on the process performance. The introduction of feasibility indicator permits the integration of industrial know-how in the methodology, and increases its applicability at any level of the shop floor. An industrial case study was conducted on the performance assessment of the cleaning and sterilization processes, where the methodology was applied to identify a set of improvement potentials.

Microwave heat installations are attracting major interest in industry in view of cutting down process times and improving qualities. The number of industrial installations is still small as compared to the wide use of household appliances. There is great interest on the part of the food industry and most global food players are testing microwave applications in their Research and Development Laboratories. However, only a few applications have transferred to the production sites. On the laboratory scale, many applications were developed to a level giving evidence of better process results. Besides the numerous requirements for a reliable and stable design of an industrial microwave, many installations still suffer from little understanding with regard to quality control and requirements of food safety in accordance with Good Manufacturing Practice (GMP) standards. The fact that microwave processes often are not reproducible and that operators do not find the operation of the complex industrial microwave plants easy, adds to this. Due to the fact that there are only a few microwave vendors on the market, global companies fear to use equipment, where second source and intellectual property issues are still fraught with risk. Therefore, the use of microwaves remains a niche technology for the time being. The current chapter explains the requirements of industrial microwave plants and intends to show the potential for unique process results and corresponding economic data, which can be achieved using industrial microwaves. This chapter will help to assess industrial microwave technology with regard to its commercial use.

Parkinson's disease is a complex and progressive neurodegenerative condition that is characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate the striatum. Cell transplantation therapies to rebuild this dopaminergic network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as the source of cells for transplantation. However, reliance on terminations for a Parkinson's therapy presents significant logistical and ethical hurdles. An alternative source of transplantable mDA neurons is urgently needed, and the solution may come from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Protocols to differentiate hESCs/iPSCs toward mDA neurons are now robust and efficient, and upon grafting the cells rescue preclinical animal models of Parkinson's disease. The challenge now is to apply Good Manufacturing Practice (GMP) to the academic discoveries and protocols to produce clinical-grade transplantable mDA cells. Major technical and logistical considerations include (i) source of hESC or iPSC line, (ii) GMP compliance of the differentiation protocol and all reagents, (iii) characterization of the cell product in terms of identity, safety, and efficacy, (iv) characterization of genomic state and stability, and (v) banking of a transplantation-ready cell product. Approaches and solutions to these challenges are reviewed here.

Drug substances and drug products are used for treating various diseases to save the lives of human beings. Drug substances and drug products should be manufactured using clean equipment with appropriate quality and in good environmental condition to avoid contamination of the product and to produce the desired therapeutic effect. Effort should be made to build quality into the product during each stage of the manufacturing process rather than simply testing the product. To regulate the manufacturing process, regulatory agencies along with pharmaceutical industrial organizations developed good manufacturing practice (GMP) guidelines for the preparation/manufacturing of the drug substance and drug products. Various GMP guidelines are followed in respective regions in the world even though the fundamentals of all the guidelines remain the same. The GMP guidelines consist of various processes including quality management, personnel, personal hygiene and qualification, building and facilities, sanitation, documentation and records, material management, production and in-process controls, packaging and labeling of drug substances and drug products, storage and distribution, laboratory controls, validation, rejection and reuse of materials, complaints and recalls, and change control. Clean equipment, cleanrooms, and environmental conditions are critical process parameters to be monitored strictly in the manufacturing process to ensure the highest standard of quality and purity of the product with desired safety and efficacy of the drug product to meet the regulatory requirements.

In many African countries, fermentation processes play significant roles in food security and food ecology of communities. A variety of indigenous fermented condiments are used to flavor dishes and serve as low-cost sources of protein contributing significantly to the dietary intake and economy of rural people. Plant seeds rich in protein and oil are fermented to make seasonings that enhance the flavor of foods including soups and sauces, snack meal, appetizers, and dessert. Often such seeds are inedible in their unfermented state, containing toxic or antinutritional factors. Fermentation results in products with enhanced shelf life, texture, taste, aroma, nutritional value, and safety. Despite enhanced research and scientific interest, production of fermented seasoning agents like other local fermented foods are still based on small-scale kitchen technologies. Often the fermentation processes are uncontrolled, with diverse microbial profiles, resulting in products with unreliable quality and stability. Currently, these African fermented seasonings have not reached global commercial or even trans-border trade status due to poor shelf life, unattractive presentation, and quality variability. This paper reviews the problems hampering the traditional processes, technological improvements, and progress toward standardization for good manufacturing practice, as well as potentials for future exploitation and industrialization of these technologies.

It is ideal for regulatory affairs professionals to have a broad understanding of various regulated products and some of the major differences in their approval/marketing and postmarket processes. The pharmaceutical industry has a very comprehensive regulatory process in place to evaluate drug safety and efficacy which precedes any of the requirements or expectations for dietary supplement products globally. Therefore, despite the considerations that must be taken into account when monitoring the safety of nutraceuticals, the experiences of the pharmaceutical industry provide an excellent framework for adapting established pharmacovigilance methods to nutraceutical vigilance. This topic will use both US and global examples of existing postmarket regulations as a reference point for the pharmacovigilance framework being discussed. The major objectives of this topic are to help the reader/students gain perspective on the current state of global pre- and postmarket safety surveillance regulations for dietary supplements and also understand the practical application of pre- and postmarket safety surveillance strategies from an industry standpoint.

This article describes the 2016 version of the Chinese Food Contact Regulation system of 64 new or revised standards. The major focus is placed on the pre-market approval system and setting the compliance of the food contact material (FCM) industry addressing the aspects: (1) New regulations applicable to the full value chain from raw material (additive or plastic resin) to material and article manufacturers; (2) China food contact horizontal and material specific standards, and (3) the comprehensive compliance requirement scheme including labeling, good manufacturing practice (GMP) and declarations of compliance (DoC) to be issued as respective food contact compliance work.

This case examines the process by which a small beverage manufacturer, Mountain Top Springs Limited (MTSL), in St. Vincent and the Grenadines in the Caribbean was able to successfully implement a modern food safety and quality system. MTSL operates in a developing country environment with limited access to much of the basic technical and scientific support that is required in a modern beverage business. Despite this, MTSL was able to implement and become certified to a HACCP-based good manufacturing practice standard that has significantly transformed the firm and allowed it to access markets in multiple countries. This case examines the basic food safety and quality considerations for a bottled springwater beverage business and how these were addressed in the face of challenges that typically face food safety practitioners in developing countries. Issues of microbiological, chemical and physical hazards, plant layout and design, product and process flows, development and implementation of effective training programs, and analytical regimes are explored. Potential quality and food safety concerns, such as iron bacteria, Pseudomonas aeruginosa, mold, physical contamination, and taint are also discussed.

Pharmaceutical microbiology is a specialist area of microbiology and one concerned with the use of microorganisms in pharmaceutical development and with maintaining contamination control. This chapter introduces the subject and outlines some the typical tests conducted within a pharmaceutical microbiology laboratory (such as microbial limits, sterility, endotoxin, water testing, and environmental monitoring). The chapter further considers the role of the microbiologist in relation to the pharmaceutical processing environment, and the necessary contribution that the microbiologist must make to an organization’s contamination control strategy.

This article details how foods are regulated in the United States and what enforcement actions are available to keep noncompliant products from being offered for consumption. It reviews the basics of US Food and Drug Administration's (FDA) food labeling requirements and provides the mechanisms available for the use of new ingredients and color additives added to foods. It explains the food adulteration standards and major sanitation programs, including good manufacturing practice, hazard analysis and critical control point (HACCP), and preventive controls mandated by the Food Safety Modernization Act (FSMA). Finally, the article describes administrative requirements for food facilities, such as facility registration, prior notice, recordkeeping, and reporting of reportable foods in addition to describing how the FDA works in cooperation with other federal agencies, States, and International Standards Organizations.

Cell therapy is an evolving and exciting field with promising clinical potential. In order to allow commercial use of this therapy, the process has to be scaled up dramatically and automated. Furthermore, to meet current good manufacturing practice (cGMP) standards, in-process controls such as process parameters have to be constantly monitored and analyzed. Cell therapies are a mixture of different kinds of cells with different kinds of culture condition needs ranging from suspension to adherent cells with a wide range of different characterizations; no one platform can fit all types of cells. Nevertheless, to upscale and meet the cGMP requirements cells need to be cultured in a controlled and monitored environment such as a bioreactor. Choosing the correct solution for a specific cell is not an easy task; it has to take into account the batch size, the cells' quality attributes, and the available technologies' advantages, kinetics, and limitations. Downstream processing postculturing needs to be done correctly and defined precisely. This stage is usually the shortest stage but it is the most critical step in the process as any damage or contamination inflected to the cell during this stage will result in failure of the batch. Stress induced to the cells in this critical stage will reflect on the final product; therefore, care and attention to the technologies and processes used should be taken. This chapter summarizes the main bioreactor and downstream platforms used for cell therapy and highlights the main challenges.

Cleaning and disinfection are necessary in order to prevent microorganisms surviving in cleanrooms (and for maintaining a level of hygiene in laboratories). Cleaning is needed to remove soil (such as protein and grease) from a surface, and disinfection if necessary to inactivate or to kill microorganisms. This chapter introduces the types of detergents and disinfectants that are generally available and outlines the criteria that should be considered for their selection. The chapter additionally discusses the aspects of good manufacturing practice (GMP) that need to be addressed and the main steps to be followed when evaluating disinfectants for their efficacy.

This chapter summarizes some of the various Good Manufacturing Practice requirements as stated in the Code of Federal Regulations Part 211. The FDA’s Compliance Program Guidance (CPG) is highlighted and explained as it pertains to active pharmaceutical ingredients and computer controls. Also covered are some key recommendations from the International Committee on Harmonization (ICH) and the American Society for Testing and Materials (ASTM). Reviewing and understanding the regulations and guidance documents of the performance of a process validation program is made much easier. This chapter provides insight into what is expected by the FDA, ICH, and ASTM for a complete and compliant process validation.

This chapter discusses limits and requirements for pesticide residues, contaminants, and additives in citrus and canned products according to national standards; hazard analysis and critical control points for canned citrus processing; good manufacturing practice control during the processing of canned citrus products; and construction of the traceability management system for canned citrus products.

This chapter addresses two key issues that the pharmaceutical microbiologist should be aware of: good manufacturing practice and the role of regulation, especially pertaining to the licensing of new medicines. These two areas underpin the role of the microbiologist within the pharmaceutical sector.

The field of cell-based medicines is moving fast from research and development toward translation into therapeutic treatment options. Correspondingly, the manufacture raises highest demands with respect to sterility and quality of the finished product. On its way from bench-to-bedside, the production process of such advanced therapy medicinal products (ATMPs) must, therefore, finally comply with the principles of Good Manufacturing Practice (GMP). This concept implements quality standards to ensure product consistency and the most possible patient safety.

The ability to elicit robust and long-term transgene expression in vivo together with minimal immunogenicity and little to no toxicity are only a few features that make recombinant adeno-associated virus (rAAV) vectors ideally suited for many gene therapy applications. Successful preclinical studies have encouraged the use of rAAV for therapeutic gene transfer to patients in the clinical setting. Nevertheless, the use of rAAV in clinical trials has underscored the need for production and purification systems capable of generating large amounts of highly pure rAAV particles. To date, generating vector quantities sufficient to meet the expanding clinical demand is still a hurdle when using current production systems. In this chapter, we will provide a description of the current methods to produce clinical grade of rAAV under current good manufacturing practice (cGMP) settings.

Quality control (QC) and quality assurance (QA) are essential to the sustainability of any industrial activity, including citrus production and processing. It is important to assign QC/QA responsibility to a position as high as possible in the corporate management. The hazard analysis critical control point (HACCP) system is applied to ensure safety of the operation. The application of HACCP is enforced in many countries by national and international regulation agencies. In the United States “Juice HACCP” is regulated by the FDA. The main objective of HACCP is to predict and prevent hazards. HACCP does not exclude the use of other systems of quality assurance, such as good manufacturing practice (GMP). Serious outbreaks of Salmonella and Escherichia coli O157:H7, both attributed to citrus juice, underlined the need to consider microbiological quality control as a safety issue. An important function of QC is the prevention of product falsification (authentication of citrus origin). Development of sophisticated fraud detection methods continues to consume considerable time and money.

Dietary supplements are a special type of food product, usually associated with health and well-being. There is increasing consumer interest in them creating a need for precisely controlled production, which can be achieved by good manufacturing practice (GMP). Dietary supplements are produced by both food production companies and pharmaceutical companies. GMP requirements are generally the same for both; however, in the food industry independent control is only recommended, whereas in the pharmaceutical industry it is obligatory. This chapter outlines the main issues related to GMP implementation in the food industry, the legal requirements, implementation stages and the role of management boards. Finally, the benefits and disadvantages of GMP are discussed.

This chapter describes the good manufacturing practice (GMP) for medical devices. It first reviews the history of GMP and essential prerequisites, as well as the main rules to fulfil compliance. The chapter then discusses the major components of a typical GMP quality system, both for the USA and the European Union, with a particular focus on design controls; this chapter focuses on the 21 CFR Part 820 (Quality System Regulation) and ISO 13485, and compares both requirements. GMP is also considered in the frame of the product life span. The chapter then presents the integration of risk management principles into a quality management system.

Banking of cells, especially stem cells, would afford therapeutic cellular products for various clinical applications. Irrespective of cell source or product type, manufacturing and preservation (banking) practice must develop to maintain cell viability, recovery, and potency and to ensure product safety. Comprehension of phases of production (collection, processing, freezing, cryopreservation, shipment, and thaw/infusion) and the adherence to pertinent regulations support effective cell banking process development. This chapter addresses elements and measures to consider to ensure product quality and safety during all phases of production and to support final product stability under long-term cryostorage conditions. It discusses Good Manufacturing Practice principles that apply to therapeutic cell banking, focusing on those that apply to product characterization, and lot release testing as well as those related to the environmental control/monitoring of the cell production facility and cell storage environment.