Approved Drug Products with Theurapeutic Equivalence Evaluation - 34th edition

The publication, Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book), identifies drug products approved on the basis of safety and effectiveness by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (the Act). Drugs on the market approved only on the basis of safety (covered by the ongoing Drug Efficacy Study Implementation [DESI] review [e.g., Donnatal® Tablets and Librax® Capsules] or pre-1938 drugs [e.g., Phenobarbital Tablets]) are not included in this publication. The main criterion for the inclusion of any product is that the product is the subject of an application with an effective approval that has not been withdrawn for safety or efficacy reasons. Inclusion of products on the List is independent of any current regulatory action through administrative or judicial means against a drug product. In addition, the List contains therapeutic equivalence evaluations for approved multisource prescription drug products. These evaluations have been prepared to serve as public information and advice to state health agencies, prescribers, and pharmacists to promote public education in the area of drug product selection and to foster containment of health care costs. Therapeutic equivalence evaluations in this publication are not official FDA actions affecting the legal status of products under the Act.

Nanotechnology: balancing benefits and risks to public health and the environment : expert paper

Nanotechnology has been heralded as a "revolution" in science, for two reasons: first, because of its revolutionary view of the way in which chemicals and elements, such as gold and silver, behave, compared to traditional scientific understanding of their properties. Second, the impact of these new discoveries, as applied to commerce, can transform the daily life of consumer products ranging from sun tan lotions and cosmetics, food packaging and paints and coatings for cars, housing and fabrics, medicine and thousands of industrial processes.9 Beneficial consumer use of nanotechnologies, already in the stream of commerce, improves coatings on inks and paints in everything from food packaging to cars. Additionally, "Nanomedicine" offers the promise of diagnosis and treatment at the molecular level in order to detect and treat presymptomatic disease,10 or to rebuild neurons in Alzheimer's and Parkinson's disease. There is a possibility that severe complications such as stroke or heart attack may be avoided by means of prophylactic treatment of people at risk, and bone regeneration may keep many people active who never expected rehabilitation. Miniaturisation of diagnostic equipment can also reduce the amount of sampling materials required for testing and medical surveillance. Miraculous developments, that sound like science fiction to those people who eagerly anticipate these medical products, combined with the emerging commercial impact of nanotechnology applications to consumer products will reshape civil society - permanently. Thus, everyone within the jurisdiction of the Council of Europe is an end-user of nanotechnology, even without realising that nanotechnology has touched daily life.

Appendix: expert paper

Nanotechnology has been heralded as a "revolution" in science, for two reasons: first, because of its revolutionary view of the way in which chemicals and elements, such as gold and silver, behave, compared to traditional scientific understanding of their properties. Second, the impact of these new discoveries, as applied to commerce, can transform the daily life of consumer products ranging from sun tan lotions and cosmetics, food packaging and paints and coatings for cars, housing and fabrics, medicine and thousands of industrial processes.9 Beneficial consumer use of nanotechnologies, already in the stream of commerce, improves coatings on inks and paints in everything from food packaging to cars. Additionally, "Nanomedicine" offers the promise of diagnosis and treatment at the molecular level in order to detect and treat presymptomatic disease,10 or to rebuild neurons in Alzheimer's and Parkinson's disease. There is a possibility that severe complications such as stroke or heart attack may be avoided by means of prophylactic treatment of people at risk, and bone regeneration may keep many people active who never expected rehabilitation. Miniaturisation of diagnostic equipment can also reduce the amount of sampling materials required for testing and medical surveillance. Miraculous developments, that sound like science fiction to those people who eagerly anticipate these medical products, combined with the emerging commercial impact of nanotechnology applications to consumer products will reshape civil society - permanently. Thus, everyone within the jurisdiction of the Council of Europe is an end-user of nanotechnology, even without realising that nanotechnology has touched daily life.

Spéciation chimique des nanoparticules d'argent dans les sols

À cause de leurs propriétés antibactériennes, les nanoparticules d’argent sont couramment utilisées dans un grand nombre de produits tels les tissus, les savons et les produits médicaux. Dans cette industrie en pleine croissance, ces nanoparticules sont produites en grandes quantités et s’accumuleront éventuellement dans l’environnement. Pour comprendre le destin, le transport et la biodisponibilité des nanomatériaux, il est essentiel de comprendre leurs propriétés physicochimiques. Entre autres, il est particulièrement important de quantifier la dissolution des nanoparticules à l’aide de mesures de spéciation chimique. En effet, l’objectif de cette recherche est de déterminer la spéciation chimique des nanoparticules d’argent dans différents sols. Pour y parvenir, différentes concentrations de nanoparticules d’argent ont été incorporées dans un sol et après un certain laps de temps, la forme ionique a été mesurée à l’aide d’une électrode sélective d’argent tandis que l’argent total est mesuré par absorption atomique ou par ICP-MS. L’analyse de la spéciation dans trois sols différents révèle que les caractéristiques des sols influencent grandement la spéciation chimique, plus particulièrement la quantité de matière organique ainsi que le pH du sol. Ainsi, la tendance des résultats semble indiquer que plus un sol est acide, il y aura plus d’ions argent libres tandis que la matière organique adsorbe fortement les ions argent les rendant ainsi moins disponibles en solution. L’observation de la spéciation chimique à long terme indique aussi que les nanoparticules tendent à éventuellement se dissocier et ainsi émettre un plus grand nombre d’ions dans l’environnement. Ces résultats ont des implications importantes dans la détermination des risques environnementaux des nanoparticules métalliques.

Contrafacção/falsificação de medicamentos

A panóplia de medicamentos e produtos de saúde existentes no mercado é enorme, existindo uma escolha alargada para os consumidores. Contudo, por vezes os preços são elevados; o medicamento que o consumidor quer não é legal no país onde se encontra; o consumidor, por vergonha, não se desloca a locais licenciados para comprar o medicamento que quer ou, o país ainda não tem acesso a um determinado medicamento inovador. E por estas razões o consumidor pode obter medicamentos falsificados através da cadeia ilegal de abastecimento, sendo a internet uma via provável de acesso. Contudo não é apenas na cadeia ilegal de abastecimento que se corre o risco de obter produtos falsificados. A cadeia de abastecimento legal tornou-se complexa e o controlo e fiscalização da mesma começou a ser mais difícil de realizar. Esta complexidade e o facto do sistema regulamentar não estar ainda bem implementado, levou ao aparecimento de produtos falsificados na cadeia legal. Para o controlo regulamentar deste problema, ao fim de alguns anos de debate e modificações à proposta existente, foi lançada na União Europeia a Directiva 2011/62/EU que pretende impedir a introdução de medicamentos falsificados na cadeia de abastecimento legal. A nível europeu existem iniciativas e organizações, tais como a International Medical Products Anti-Counterfeiting Taskforce(IMPACT), a Medicrime, Working Group of Enforcement Officers(WGEO), Pharmaceutical Security Institute(PSI), entre outras,cujo objectivo principal é o combate à contrafacção. São organizações e iniciativas com um grau de importância elevado devido ao trabalho que realizam. Para além destas acções as entidades reguladoras dos vários países europeus têm os Single Points of Contact (SPOCs) que permitem a troca de informação e colaboração internacional para que todos tenham acesso à mesma informação e a casos detectados. Em Portugal, o INFARMED I.P. é a Autoridade Nacional do Medicamento e Produtos de saúde e desta autoridade depende a fiscalização e controlo dos diversos intervenientes no ciclo do medicamento. Existe no INFARMED I.P. um departamento designado de Célula 3C que trabalha diariamente para o combate à contrafacção de medicamentos a nível nacional. São pontos essenciais no combate à contrafacção de medicamentos, que a Directiva seja implementada a nível nacional e que os esforços e cooperação entre os vários países perdurem para que haja uma diminuição do risco nos próximos anos.

Contaminação das águas por resíduos de medicamentos: Ênfase ao cloridrato de fluoxetina

The objective of this paper was to review data on residues of medical products in aquatic environments and at wastewater treatment plants. Secondarily the paper presents a discussion about the need for a good management of drugs residues and effluents generated by this sector. Bringing the evidences of environmental possible damages reported by ecotoxicity data on the effects of fluoxetine to Vibrio fischeri and H. azteca, aquatic organisms daily exposed to environmental contaminants. From the results we observed that 0.3 mg.l-1 of fluoxetine hidrochloride induced lethality to H. azteca and 30 mg.l-1 reduced the luminescence of Vibrio fischeri. This assay evidenced higher toxicity when we used the generic product.

Sobre a implantação de boas práticas de distribuição de produtos médicos de acordo com a RDC nº 59 de 27 de junho de 2000 - ANVISA e NBR ISO 9001:2000

Pós-graduação em Ciências Farmacêuticas - FCFAR

Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antimicrobial effectiveness of silver nanoparticles co-stabilized by the bioactive copolymer pluronic F68

Abstract Background Silver nanoparticles (AgNps) have attracted much interest in biomedical engineering, since they have excellent antimicrobial properties. Therefore, AgNps have often been considered for incorporation into medical products for skin pathologies to reduce the risk of contamination. This study aims at evaluating the antimicrobial effectiveness of AgNps stabilized by pluronic™ F68 associated with other polymers such as polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Methods AgNps antimicrobial activity was evaluated using the minimum inhibitory concentration (MIC) method. The action spectrum was evaluated for different polymers associated with pluronic™ F68 against the gram negative bacteria P. aeuroginosa and E. coli and the gram positive bacteria S. Aureus. Results AgNps stabilized with PVP or PVA and co-stabilized with pluronic™ F68 are effective against E. coli and P. aeruginosa microorganisms, with MIC values as low as 0.78% of the concentration of the original AgNps dispersion. The antimicrobial action against S. aureus is poor, with MIC values not lower than 25%. Conclusions AgNps stabilized by different polymeric systems have shown improved antimicrobial activity against gram-negative microorganisms in comparison to unstabilized AgNps. Co-stabilization with the bioactive copolymer pluronic™ F68 has further enhanced the antimicrobial effectiveness against both microorganisms. A poor effectiveness has been found against the gram-positive S. aureus microorganism. Future assays are being delineated targeting possible therapeutic applications.

Tecnologie biomediche per lo studio e la riabilitazione della funzionalita retinica in condizioni fisiopatologiche

L’occhio è l’organo di senso responsabile della visione. Uno strumento ottico il cui principio di funzionamento è paragonabile a quanto avviene in una macchina fotografica. Secondo l’Organizzazione mondiale della sanità (WHO 2010) sulla Terra vivono 285 milioni di persone con handicap visivo grave: 39 milioni sono i ciechi e 246 milioni sono gli ipovedenti. Si evince pertanto la necessità di tecnologie in grado di ripristinare la funzionalità retinica nelle differenti condizioni fisiopatologiche che ne causano la compromissione. In quest’ottica, scopo di questa tesi è stato quello di passare in rassegna le principali tipologie di sistemi tecnologici volti alla diagnosi e alla terapia delle fisiopatologie retiniche. La ricerca di soluzioni bioingegneristiche per il recupero della funzionalità della retina in condizioni fisiopatologiche, coinvolge differenti aree di studio, come la medicina, la biologia, le neuroscienze, l’elettronica, la chimica dei materiali. In particolare, sono stati descritti i principali impianti retinali tra cui l’impianto di tipo epiretinale e subretinale, corticale e del nervo ottico. Tra gli impianti che ad oggi hanno ricevuto la certificazione dell’Unione Europea vi sono il sistema epiretinale Argus II (Second Sight Medical Products) e il dispositivo subretinale Alpha IMS (Retina Implant AG). Lo stato dell’arte delle retine artificiali, basate sulla tecnologia inorganica, trova tuttavia limitazioni legate principalmente a: necessità di un’alimentazione esterna, biocompatibilità a lungo termine, complessità dei processi di fabbricazione, la difficoltà dell’intervento chirurgico, il numero di elettrodi, le dimensioni e la geometria, l’elevata impedenza, la produzione di calore. Approcci bioingegneristici alternativi avanzano nel campo d’indagine della visione artificiale. Fra le prospettive di frontiera, sono attualmente in fase di studio le tecnologie optogenetiche, il cui scopo è la fotoattivazione di neuroni compromessi. Inoltre, vengono annoverate le tecnologie innovative che sfruttano le proprietà meccaniche, optoelettroniche e di biocompatibilità delle molecole di materiali organici polimerici. L’integrazione di funzioni fotoniche nell’elettronica organica offre nuove possibilità al campo dell’optoelettronica, che sfrutta le proprietà ottiche e elettroniche dei semiconduttori organici per la progettazione di dispositivi ed applicazioni optoelettronici nel settore dell’imaging e del rilevamento biomedico. La combinazione di tecnologie di tipo organico ed organico potrebbe aprire in prospettiva la strada alla realizzazione di dispositivi retinici ed impianti di nuova generazione.

Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation?

For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10−6. The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks.

Understanding and improving the manufacturing and changeover process in Saudi Arabian business - a multiple case study approach

The importance of the changeover process in the manufacturing industry is becoming widely recognised. Changeover is a complete process of changing between the manufacture of one product to manufacture of an alternative product until specified production and quality rates are reached. The initiatives to improve changeover exist in industry, as better changeover process typically contribute to improved quality performance. A high-quality and reliable changeover process can be achieved through implementation of continuous or radical improvements. This research examines the changeover process of Saudi Arabian manufacturing firms because Saudi Arabia’s government is focused on the expansion of GDP and increasing the number of export manufacturing firms. Furthermore, it is encouraging foreign manufacturing firms to invest within Saudi Arabia. These initiatives, therefore, require that Saudi manufacturing businesses develop the changeover practice in order to compete in the market and achieve the government’s objectives. Therefore, the aim of this research is to discover the current status of changeover process implementation in Saudi Arabian manufacturing businesses. To achieve this aim, the main objective of this research is to develop a conceptual model to understand and examine the effectiveness of the changeover process within Saudi Arabian manufacturing firms, facilitating identification of those activities that affect the reliability and high-quality of the process. In order to provide a comprehensive understanding of this area, this research first explores the concept of quality management and its relationship to firm performance and the performance of manufacturing changeover. An extensive body of literature was reviewed on the subject of lean manufacturing and changeover practice. A research conceptual model was identified based on this review, and focus was on providing high-quality and reliable manufacturing changeover processes during set-up in a dynamic environment. Exploratory research was conducted in sample Saudi manufacturing firms to understand the features of the changeover process within the manufacturing sector, and as a basis for modifying the proposed conceptual model. Qualitative research was employed in the study with semi-structured interviews, direct observations and documentation in order to understand the real situation such as actual daily practice and current status of changeover process in the field. The research instrument, the Changeover Effectiveness Assessment Tool (CEAT) was developed to evaluate changeover practices. A pilot study was conducted by examining the CEAT, proposed for the main research. Consequently, the conceptual model was modified and CEAT was improved in response to the pilot study findings. Case studies have been conducted within eight Saudi manufacturing businesses. These case studies assessed the implementation of manufacturing changeover practice in the lighting and medical products sectors. These two sectors were selected based on their operation strategy which was batch production as well as the fact that they fulfilled the research sampling strategy. The outcomes of the research improved the conceptual model, ultimately to facilitate the firms’ adoption and rapid implementation of a high-quality and reliability changeover during the set-up process. The main finding of this research is that Quality’s factors were considering the lowest levels comparing to the other factors which are People, Process and Infrastructure. This research contributes to enable Saudi businesses to implement the changeover process by adopting the conceptual model. In addition, the guidelines for facilitating implementation were provided in this thesis. Therefore, this research provides insight to enable the Saudi manufacturing industry to be more responsive to rapidly changing customer demands.

Nanotechnology in food industry II: risk assessment and legislation

Currently, there is increasing use of nanomaterials in the food industry thanks to the many advantages offered and make the products that contain them more competitive in the market. Their physicochemical properties often differ from those of bulk materials, which require specialized risk assessment. This should cover the risks to the health of workers and consumers as well as possible environmental risks. The risk assessment methods must go updating due to more widespread use of nanomaterials, especially now that are making their way down to consumer products. Today there is no specific legislation for nanomaterials, but there are several european dispositions and regulations that include them. This review gives an overview of the risk assessment and the existing current legislation regarding the use of nanotechnology in the food industry.