Comparison of new Brazilian legislation for the approval of advanced therapy medicinal products with existing systems in the USA,European Union and Japan

Background aimsAdvanced therapy medicinal products (ATMPs) are a class of biological products for human use that are based on genes, cells and tissues. The first ATMP received marketing authorization in Europe in 2009, whereas Brazil granted the first authorization in 2020. The objective of this study was to compare the regulatory models adopted by Brazil, the USA, Japan and the European Union, which comprise the member countries of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, with regard to the marketing authorization of ATMPs.MethodsThe authors performed a review of the scientific literature and official documents of the regulatory agencies in the aforementioned countries.ResultsThe legislation and regulatory guidelines adopted by the regulatory agencies exhibit similarities and differences. It was not possible to assess whether these differences can be translated into divergent final recommendations by regulatory authorities upon a request for marketing authorization.ConclusionsIn the future, it will be appropriate to start a progressive process of harmonization between these agencies in terms of terminology, legal recommendations and characterization requirements. This is particularly important for emerging countries such as Brazil. In this sense, some measures can be taken to achieve alignment between regulators.     

Use of out-of-field contact shielding on patients in medical imaging: A review of current guidelines,recommendations and legislative documents

The use of patient contact-shielding has become a topic of intensive scientific debate. While it has been common practice during the last decades, some studies have questioned the efficiency of using such shielding while others have highlighted the inconsistencies in its application. The objective of this work is to review current recommendations and legislative documents on the use of out-of-field shielding in X-ray imaging, including those from national authorities and from international and national organisations and professional bodies.The review, performed within the framework of the activities of EURADOS Working Group 12, covers available recommendations on use of contact shielding in adult, pregnant and paediatric patients in general radiography, fluoroscopy, computed tomography, mammography and dental radiology. It includes a comprehensive search of 83 documents from 32 countries and 6 international organisations over the last 39 years. In general, using shielding is recommended only under two conditions: if it does not compromise the diagnostic task and the performance of the procedure and/or if it reassures the patient and comforters that they are appropriately protected against potentially harmful effects of radiation. There are very few specific regulatory requirements to use shielding in a particular imaging modality, although they may consider use of shielding either as part of good radiological practice or as requirements for availability of protective or ancillary tools, without further specification of their use. There is a wide variety of positions among documents that recommend out-of-field shielding, those that do not recommend it and those that are not specific. Therefore, evidence-based consensus is still needed to ensure best and consistent practice.     

Les inhibiteurs spécifiques de la recapture de la sérotonine dans la dépression de l’enfant et de l’adolescent: revue des controverses récentes

European and US drug regulatory authorities have recently warned against the use of selective serotonin reuptake inhibitors (SSRIs) in childhood and adolescent depression. Through an extensive literature review on the use of SSRIs to treat depression in children and adolescents — including psychiatric clinical trials, pharmacology, and drug safety data — we will: i) describe the main arguments justifying various regulatory decisions; ii) present published data and subsequent meta-analyses; iii) discuss how to integrate the recommendations into daily clinical practice, freeing professionals from a Manichean approach. We reach the limits of evidence-based medicine, which provide the basis of the scientific work of the regulatory authorities.     

Tracheal bioengineering: the next steps. Proceeds of an International Society of Cell Therapy Pulmonary Cellular Therapy Signature Series Workshop,Paris, France,April 22, 2014

There has been significant and exciting recent progress in the development of bioengineering approaches for generating tracheal tissue that can be used for congenital and acquired tracheal diseases. This includes a growing clinical experience in both pediatric and adult patients with life-threatening tracheal diseases. However, not all of these attempts have been successful, and there is ongoing discussion and debate about the optimal approaches to be used. These include considerations of optimal materials, particularly use of synthetic versus biologic scaffolds, appropriate cellularization of the scaffolds, optimal surgical approaches and optimal measure of both clinical and biologic outcomes. To address these issues, the International Society of Cell Therapy convened a first-ever meeting of the leading clinicians and tracheal biologists, along with experts in regulatory and ethical affairs, to discuss and debate the issues. A series of recommendations are presented for how to best move the field ahead.     

Épico project. Development of educational recommendations using the DELPHI technique on invasive candidiasis in non-neutropenic critically ill adult patients

BackgroundAlthough there has been an improved management of invasive candidiasis in the last decade, controversial issues still remain, especially in the diagnostic and therapeutic approaches.AimsWe sought to identify the core clinical knowledge and to achieve high level agreement recommendations required to care for critically ill adult patients with invasive candidiasis.MethodsA prospective Spanish survey reaching consensus by the DELPHI technique was made. It was anonymously conducted by electronic mail in a first term to 25 national multidisciplinary experts in invasive fungal infections from five national scientific societies, including intensivists, anesthesiologists, microbiologists, pharmacologists and infectious diseases specialists, who answered to 47 questions prepared by a coordination group after a strict review of the literature in the last five years. The educational objectives spanned five categories, including epidemiology, diagnostic tools, prediction rules, and treatment and de-escalation approaches. The level of agreement achieved among the panel experts in each item should exceed 75% to be selected. In a second term, after extracting recommendations from the selected items, a face to face meeting was performed where more than 80 specialists in a second round were invited to validate the preselected recommendations.ResultsIn the first term, 20 recommendations were preselected (Epidemiology 4, Scores 3, Diagnostic tools 4, Treatment 6 and De-escalation approaches 3). After the second round, the following 12 were validated: (1) Epidemiology (2 recommendations): think about candidiasis in your Intensive Care Unit (ICU) and do not forget that non-Candida albicans–Candida species also exist. (2) Diagnostic tools (4 recommendations): blood cultures should be performed under suspicion every 2–3 days and, if positive, every 3 days until obtaining the first negative result. Obtain sterile fluid and tissue, if possible (direct examination of the sample is important). Use non-culture based methods as microbiological tools, whenever possible. Determination of antifungal susceptibility is mandatory. (3) Scores (1 recommendation): as screening tool, use the Candida Score and determine multicolonization in high risk patients. (4) Treatment (4 recommendations): start early. Choose echinocandins. Withdraw any central venous catheter. Fundoscopy is needed. (5) De-escalation (1 recommendation): only applied when knowing susceptibility determinations and after 3 days of clinical stability. The higher rate of agreement was achieved in the optimization of microbiological tools and the withdrawal of the catheter, whereas the lower rate corresponded to de-escalation therapy and the use of scores.ConclusionsThe management of invasive candidiasis in ICU patients requires the application of a broad range of knowledge and skills that we summarize in our recommendations. These recommendations may help to identify the potential patients, standardize their global management and improve their outcomes, based on the DELPHI methodology.This article is also published in Spanish in this issue. It can be found in 10.1016/j.riam.2013.05.005     

Personal protective equipment for registration purposes of pesticides

Regulatory authorities in North America, Europe and Australia use different approaches for the estimation of exposure reduction effectiveness of personal protective equipment (PPE) in registration processes of agrochemical pesticides. TNO has investigated current views and facts for the use of default values and set up a discussion paper which can be used as a starting point to achieve an internationally harmonised set of PPE protection factors for regulatory use. For inhalation exposure Loading it is proposed to use the assigned protection factors (APF) as deduced by BSI (British Standard Institution) and ANSI (American National Standards Institution). Since these values are somewhat variance and since in agricultural settings efficient control and proper training and education with respect to inhalation protection devices is generally absent, it is good to err on the safe side and to use the Lowest of both values, if available. For dermal exposure Loading differentiations are made for operators and re-entry workers and further for hand and body protection. Next to this the restrictions and framework for the use of the proposed defaults are very relevant. Oral exposure loading is only considered in special cases where dermal exposure may be relatively high and the hand-mouth shunt may lead to appreciable oral exposure loading. The presented defaults for PPE have been discussed with experts of regulatory authorities and industry, but a formal discussion still has to take place. This needs to be done on EU level between Member States. The current proposal is based on state-of-the-art knowledge and policy considerations, but further research is needed to better underpin the proposed values and/or to adapt them.     

Pharma-Planta: road testing the developing regulatory guidelines for plant-made pharmaceuticals

Significant advances over the last few years have seen plant-made pharmaceuticals (PMPs) move from the exploratory research phase towards clinical trials, with the first commercial products for human use expected to reach the market by 2009. Europe has yet to witness the commercial application of PMP technology, although at least one product has begun phase II clinical trials with others following close behind. These emerging products are set to challenge the complex and overlapping regulations that currently govern GM plants and ‘conventional’ pharmaceutical production. The areas of responsibility are being mapped out between the different EU regulatory agencies, with specific guidelines currently being drawn up for the regulation of PMPs. This article discusses issues surrounding the development of robust risk-assessment and risk-management practices based on health and environmental impact, while working with EU regulatory authorities to ensure appropriate regulatory oversight.     

EPICO 2.0 project. Development of educational therapeutic recommendations using the DELPHI technique on invasive candidiasis in critically ill adult patients in special situations

BackgroundAlthough there has been an improved management of invasive candidiasis in the last decade, still controversial issues remain, especially in different therapeutic critical care scenarios.AimsWe sought to identify the core clinical knowledge and to achieve high agreement recommendations required to care for critically ill adult patients with invasive candidiasis for antifungal treatment in special situations and different scenarios.MethodsSecond prospective Spanish survey reaching consensus by the DELPHI technique, conducted anonymously by electronic e-mail in the first phase to 23 national multidisciplinary experts in invasive fungal infections from five national scientific societies including intensivists, anesthesiologists, microbiologists, pharmacologists and infectious disease specialists, answering 30 questions prepared by a coordination group after a strict review of literature in the last five years. The educational objectives spanned four categories, including peritoneal candidiasis, immunocompromised patients, special situations, and organ failures. The agreement among panelists in each item should be higher than 75% to be selected. In a second phase, after extracting recommendations from the selected items, a meeting was held with more than 60 specialists in a second round invited to validate the preselected recommendations.Measurements and main resultsIn the first phase, 15 recommendations were preselected (peritoneal candidiasis (3), immunocompromised patients (6), special situations (3), and organ failures (3)). After the second round the following 13 were validated: Peritoneal candidiasis (3): Source control and early adequate antifungal treatment is mandatory; empirical antifungal treatment is recommended in secondary nosocomial peritonitis with Candida spp. colonization risk factors and in tertiary peritonitis. Immunocompromised patients (5): consider hepatotoxicity and interactions before starting antifungal treatment with azoles in transplanted patients; treat candidemia in neutropenic adult patients with antifungal drugs at least 14 days after the first blood culture negative and until normalization of neutrophils is achieved. Caspofungin, if needed, is the echinocandin with most scientific evidence to treat candidemia in neutropenic adult patients; caspofungin is also the first choice drug to treat febrile candidemia; in neutropenic patients with candidemia remove catheter. Special situations (2): in moderate hepatocellular failure, patients with invasive candidiasis use echinocandins (preferably low doses of anidulafungin and caspofungin) and try to avoid azoles; in case of possible interactions review all the drugs involved and preferably use anidulafungin. Organ failures (3): echinocandins are the safest antifungal drugs; reconsider the use of azoles in patients under renal replacement therapy; all of the echinocandins to treat patients under continuous renal replacement therapy are accepted and do not require dosage adjustment.ConclusionsTreatment of invasive candidiasis in ICU patients requires a broad range of knowledge and skills as summarized in our recommendations. These recommendations may help to optimize the therapeutic management of these patients in special situations and different scenarios and improve their outcome based on the DELPHI methodology.     

Chinese plasma-derived products supply under the lot release management system in 2007–2011

In 2007, the Chinese State Food and Drug Administration (SFDA) implemented a management system for lot release of all plasma-derived products. Since then, there have been only a few systematic studies of the blood supply, which is a concern when considering the small amount of plasma collected per capita (approximately 3 L/1000 people). As a result, there may be a threat to the safety of the available blood supply. In this study, we examined the characteristics of the supply of Chinese plasma-derived products. We investigated the reports of lot-released biological products derived from all 8 national or regional regulatory authorities in China from 2007 to 2011. The market supply characteristics of Chinese plasma-derived products were analyzed by reviewing the changes in supply varieties, the batches of lot-released plasma-derived products and the actual supply. As a result, the national regulatory authorities can more accurately develop a specific understanding of the production and quality management information provided by Chinese plasma product manufacturers. The implementation of the lot release system further ensures the clinical validity of the plasma-derived products in China and improves the safety of using plasma-derived products. This work provides an assessment of the future Chinese market supply of plasma-derived products and can function as a theoretical basis for the establishment of hemovigilance.     

Radiopharmaceutiques et réglementations

The radiopharmaceuticals are products that combine two very stringent regulatory requirements from two different authorities: as medicine from a pharmaceutical point of view (Afssaps) and as radioactive source with specific authorization (ASN). This article discusses the different regulatory constraints imposed by these authorities but suggests also that legislation is supposed to be modified in the coming years in collaboration with nuclear physicians and their Society (SFMN).     

WHO informal consultation on the application of molecular methods to assure the quality, safety and efficacy of vaccines, Geneva, Switzerland, 7-8 April 2005.

In April 2005, the World Health Organization convened an informal consultation on molecular methods to assure the quality, safety and efficacy of vaccines. The consultation was attended by experts from national regulatory authorities, vaccine industry and academia. Crosscutting issues on the application of molecular methods for a number of vaccines that are currently in use or under development were presented, and specific methods for further collaborative studies were discussed and identified. The main points of recommendation from meeting participants were fourfold: (i) that molecular methods should be encouraged; (ii) that collaborative studies are needed for many methods/applications; (iii) that basic science should be promoted; and (iv) that investment for training, equipment and facilities should be encouraged.     

WHO informal consultation on regulatory evaluation of therapeutic biological medicinal products held at WHO Headquarters, Geneva, 19-20 April 2007.

This report reflects the discussion and conclusions of an informal consultation held on 19-20 April 2007 at the World Health Organization concerning the regulatory evaluation of therapeutic biological medicinal products. The objectives of this meeting were to discuss the current status of so-called "similar" biological medicinal products (biosimilars) and to review regulatory pathways and challenges in evaluating the quality, safety and efficacy of these products. Biosimilars are products that are subject to licensing with a reduced data package due to a proven 'similarity' to the licensed reference product. The meeting was attended by experts in biotherapeutics from regulatory agencies, industry and academia representing 16 countries worldwide. Dr. Elwyn Griffiths (Canada) acted as Chairman and Dr. James Robertson (UK) was the Rapporteur. The meeting strongly focused on the usage of biosimilars and the current regulatory situation in many different countries. The application of International Nonproprietary Names (INN) to biosimilars, their potential immunogenicity, and WHO international standards and reference materials were also discussed, alongside presentations from the innovator and generic manufacturing industries. The consultation recognized the importance of the terminology as well as a definition of biosimilars for future considerations of these products. However, achieving a global consensus on the terminology for these new challenging products was not attempted at the Consultation, and it was decided that a future WHO working group should act on this issue as a next step. For purposes of this meeting report only, the term 'biosimilars' is temporarily used to refer to this category of products. It became clear that biotherapeutics authorized on the basis of a reduced data package are available and being used in some countries, with more appearing on the market. The existence of divergent approaches to the regulatory oversight of biosimilars in different countries revealed a need for defining regulatory expectations for these products at the global level. While many countries are following the guideline developed within the EU for quality aspects, discrepancies remain regarding the non-clinical and clinical studies of these products. The Consultation recommended that the WHO should develop a guideline in this area in order to provide a framework for the development of regulatory pathways for these products worldwide. For this purpose, agreement on the scope, definition and terminology of these products was deemed necessary. The interchangeability and substitution of products were also flagged as areas in need of harmonization. A WHO working group should be established to develop a guideline that would promote global consensus on the regulation of biosimilars, assist in their registration and enhance the availability of safe and effective biosimilar products worldwide.     

Role of regulatory agencies

In this paper the authors discuss the role of regulation in assuring blood safety. After an overview of the subject by a leading expert, examples are provided of regulatory systems for blood transfusion services in several countries and regions. Additionally, the perspective of WHO is given on the essential role of national regulatory authorities in assuring the quality of national blood programmes.Collectively, the sections of this paper afford an opportunity for readers to make comparisons among different regulatory frameworks and to "benchmark" among the existing systems. Despite many differences in approach, a clear pattern emerges of worldwide efforts to strengthen blood regulatory systems.     

WHO/KFDA joint workshop on implementing WHO guidelines on evaluating similar biotherapeutic products, Seoul, Republic of Korea 24-26 August, 2010

In August 2010, the World Health Organization and the Korea Food & Drug Administration jointly organized the first implementation workshop of WHO guidelines on evaluating similar biotherapeutic products (SBPs) at the global level. The objective of the Workshop was to facilitate implementation of the newly adopted WHO Guidelines into the practice of national regulatory authorities (NRAs). WHO Guidelines were recognized by the workshop participants as a tool for harmonizing regulatory requirements worldwide. By reviewing and practicing several case studies, better understanding and consensus on the principles of clinical trial designs were reached. However, variations in terms of the national requirements for quality, safety and efficacy of these products revealed diversity in the regulatory expectations in different countries and regions. In addition, lack of terminology for the products developed as copy products (so called "me too" products) with a partial comparability to an RBP, led to a great diversity in evaluating as well as naming these products. The workshop participants proposed the following actions: a) NRAs should make efforts to build their capacities for regulation of SBPs; b) WHO should revise WHO Guidelines for assuring the quality of products prepared by recombinant DNA technology (WHO TRS 814) and continue monitoring progress with the implementation of the Guidelines on evaluating SBPs. Publication of the outcome of the Workshop was recognized as another action that WHO should coordinate.     

Development and regulation of stem cell‐based therapies in China

BackgroundClinical researches of stem cell‐based therapies are highly active in China, while it was arduous to determine the most effective way of clinical translation of those advanced therapies.MethodsThis article briefly introduced the regulatory framework development, the progress in stem cell clinical researches and clinical trials of commercially developed stem cell‐based products, as well as the clinical review concerns of stem cell‐based products in China.Main findingsThe current regulatory framework of stem cell clinical researches in China was launched in 2015, when regulatory authorities issued “Administrative Measures on Stem Cell Clinical Research” (AMSCCR) detailing the rules of stem cell clinical research. Thereafter, the rapidly growing stem cell clinical researches were rigorously managed and clinical use of stem cell therapy was halted. Meanwhile, commercially developed stem cell‐based products are supervised by Drug Administration Law (DAL).ConclusionThe regulatory framework of stem cell‐based therapy in China has progressed in the last few decades, which is currently regulated according to AMSCCR and DAL. Well‐designed and patient‐focused clinical trial is required for commercially developed stem cell‐based products, and definite clinical benefit evidence is crucial to obtain marketing authorization.

This article briefly introduced the regulatory framework development of stem cell‐based therapy, progress in stem cell‐based clinical studies and clinical review concerns in China.     

Assessment of Needs for Plasma for Fractionation in Europe

In the early 1990s, a series of outbreaks of hepatitis C (HCV) infections clustering among recipients of certain lots of plasma-derived medicinal products (PDMP) alarmed regulatory authorities, manufacturers and the public alike. Also, a few episodes of Hepatitis A (HAV) infections occurred in haemophiliacs receiving solvent-detergent-treated factor VIII concentrates. Thus, several measures were brought into effect to reestablish the safety of the incriminated products and to further increase the margin of safety of PDMP in general. Therefore, intramuscular immunoglobulins had to be free of HCV RNA as shown by nucleic acid amplification technology (NAT) in the final products. Furthermore, the manufacturing process of PDMP had to be validated for both viral inactivation and elimination. Finally, HCV-NAT was to be standardised and implemented as a validated test of plasma pool samples.In 1994, a joint meeting of EPFA, EAPPI and Regulatory Authorities was held in Brussels to outline the state of the art and to delineate the actions to be taken. Five years later, in 1999, the incidence rates of HIV, HBV and HCV in unpaid blood donors have been minimized, especially in European countries. With probabilities for window period donations as low as 0.6 in 1 million for both HIV and HCV and 2.1 in 1 million for HBV in Switzerland, labile blood products have reached extreme, but not absolute safety. The introduction of HCV-NAT roughly doubles this safety resulting in a 1 in 3 million probability of a window donation.Concomittantly, extensive viral validation studies document effective inactivation and removal of viruses in PDMP. The demonstrated margins of safety, expressed as logarithmical reduction factors (LRF), range from 4 to over 20 log(10), depending on product, virus, and inactivation procedure used. Further progress to even safer PDMP shall be acomplished by consolidating the GMP processes, abandoning of obsolete requirements and harmonising national regulations within Europe. Before introducing new measures for additional agents such as HAV or Parvovirus B 19, gains and risks and even potential new threats have to be carefully assessed. Alternative efforts for the safeguard of patients, e.g. vaccination for HAV, need to be balanced against the risks of changing established and validated manufacturing procedures of PDMP with long-lasting safety records.     

Quality control of biotechnology-derived vaccines: technical and regulatory considerations

Vaccines for human use have been produced for decades using classical manufacturing methods including culture of viruses and bacteria followed by various concentration-, inactivation-, detoxification-, conjugation production processes. Availability of techniques for molecular biology and for the complete chemical synthesis of genes provides prospects of genetic engineering of microorganisms so as to generate novel biotechnological/biological-derived vaccines. The potential large-scale availability of biotechnology-derived vaccines makes feasible their evaluation in the prevention and/or treatment of various infectious, chronic, degenerative and cancer human diseases. There are potential safety concerns that arise from the novel manufacturing processes and from the complex structural and biological characteristics of the products. These products have distinguishing characteristics to which consideration should be given in a well-defined quality control testing programme. The evaluation of their quality, safety, efficacy and stability necessitate complex analytical methods and appropriate physicochemical, biochemical and immunochemical methods for the analysis of the molecular entity. A flexible approach to the control of these novel products is being developed by regulatory authorities so that recommendations can be modified in the light of experience of research and development in vaccinology, production and use of biotechnology products and with the further development of new technologies.     

Regulatory issues concerning the safety, efficacy and quality of herbal remedies

Herbal remedies and alternative medicines are used throughout the world, and in the past herbs were often the original sources of most drugs. Today we are witnessing an increase in herbal remedy use throughout the Western world raising the question as to how safe are these preparations for the unborn fetus? Many women use herbal products during pregnancy. The dilemma facing most regulatory authorities is that the public considers these products as either traditional medicines or natural food supplements. The user sees no reason for regulation. Most countries have laws concerning foods, drugs, and cosmetics, the details of which seldom clearly define to what section of the law and regulations alternative remedies belong. In most countries alternative remedies are regulated as foods, provided that no medicinal claim is made on the label. The global regulatory sector, however, is changing rapidly. The Therapeutic Goods Administration (TGA) in Australia created a Complimentary Medicines Evaluation Committee in late 1997 to address this issue, and Canada has created a new Natural Health Products Directorate in the realigned Therapeutic Products and Foods Branch in 2000. In parallel, the European Agency for the Evaluation of Medicinal Products has drafted test procedures and acceptance criteria for herbal drug preparations and herbal medicinal products. In the US, the Food and Drug Administration classifies these natural products as dietary supplements. Manufacturers must label a dietary supplement thus: “this statement has not been evaluated by the FDA [, and] this product is not intended to diagnose, treat, cure or prevent any disease.” Whether these products are foods or drugs is undecided. To add complexity to this issue, most of the potential deleterious effects of natural products on the unborn may be related to hormonal effects (e.g., phytoestrogens) and nutriceutical drug interactions (e.g., St. John's Wort and antidepressants), rather than direct embryotoxicity per se. We suggest that ensuring quality of herbal products should receive immediate attention by regulatory authorities, before embarking on the more arduous tasks of safety and efficacy. Birth Defects Res B 68:505–510, 2003. © 2003 Wiley‐Liss, Inc.     

Lactic acid bacteria in a changing legislative environment

The benefits of using lactic acid bacteria in the food chain, both through direct consumption and production of ingredients, are increasingly recognised by the food industry and consumers alike. The regulatory environment surrounding these products is diverse, covering foods and food ingredients, processing aids, feed additives and dietary supplements. On a global basis, there are different approaches taken by the various regulatory authorities. While in Europe, the national legislation is gradually being harmonised, predominantly through the Novel Foods Regulation, there is still a wide disparity between the stringency of regulation of microbial products fed to animals and the comparatively relaxed approach to non-novel microbial products intended for human consumption. In the United States, the onus is on self-regulation of the manufacturer, with the Generally Recognised As Safe (GRAS) and Dietary Supplement Health Education Act (DSHEA) notification schemes encouraging industry to be more open about the ingredients they market. In Japan, the Foods for Special Health Use system continues to gain recognition as more products are approved, and is a potential model for other countries in regulating functional foods. Despite the different approaches to regulating these products, safety of microorganisms such as lactic acid bacteria in the food chain is paramount in all countries. This paper discusses the regulatory requirements of microbial products, predominantly lactic acid bacteria within the global markets, focusing mainly on the developments in Europe.     

Cell and tissue therapy regulation: worldwide status and harmonization

Rapid developments in scientific and technological aspects in stem cell biology and tissue engineering have led to the increased use of human cells and tissues for the treatment of various diseases and injuries. The regulatory environment for CTT products is rapidly evolving and drug regulatory agencies are working towards establishment of a risk-based system with some common features. Various drug regulatory agencies in many countries/regions have implemented regulatory controls in the last few years. This article will highlight some of works done till date to regulate CTT products in Australia, Canada, Europe, Japan, Korea, Singapore and United States of America.