Dobra proizvođačka praksa: uloga domaćih proizvođača i nadležnih tijela

In every country, a manufacturer of medicinal products for either human or veterinary use is required to operate in compliance with local legislation effect that they are committed to abide by the same standards. The candidate countries transpose the acquis into their national legislation, including the good manufacturing practice (GMP). Consequently, the local manufacturer is required to strictly comply with GMP and the manufacturing licence, including for medicinal products exclusively intended for export. A vital role is also played by national regulatory authorities, in Croatia by the Agency for Medicinal Products and Medical Devices which issues the manufacturing licence, GMP certifi cate, and the Certifi cate of a Pharmaceutical Product (CPP) and conducts laboratory control of products. GMP inspection is carried out by the Pharmaceutical Inspectorate with the Ministry of Health and Social Welfare. Both authorities are responsible only for human medicines. There are legislative issues not yet harmonised with the acquis, but as a country aspiring for the EU membership, Croatia is expected to demonstrate that its industry and competent authorities are able to conform to current requirements and thus fully adhere to the integrated European regulatory network. Hence the importance of strengthening the institutional capacity of the competent authorities, as insuffi cient resources may have a direct bearing on patients by limiting their access to affordable treatment.U svakoj zemlji proizvođač lijekova za humanu ili za veterinarsku uporabu obavezan je poslovati sukladno lokalnom zakonodavstvu, koje je u EU usklađeno za sve članice koje moraju poštivati jednake standarde. Zemlje kandidati za članstvo ugrađuju europsko zakonodavstvo u nacionalno i na taj način implementiraju dobru proizvođačku praksu (GMP). Sukladno tomu, proizvođač lijeka obvezan je osigurati da se svi proizvodni postupci za lijekove izvode u skladu s dobrom proizvođačkom praksom i proizvodnom dozvolom uključujući i lijekove koji su namijenjeni samo za izvoz. Ovdje je nezaobilazna i uloga nacionalnih regulatornih tijela posebno Agencije za lijekove i medicinske proizvode koja izdaje proizvodnu dozvolu, GMP certifi kate i certifi kate o farmaceutskom proizvodu - lijeku (CPP) te provodi laboratorijsku kontrolu proizvoda. GMP inspekciju provodi farmaceutski inspektorat koji je u sastavu Ministarstva zdravstva i socijalne skrbi. Oba su tijela nadležna samo za lijekove za humanu uporabu. Postoje još neka neusklađena pitanja što se tiče prihvaćanja Pravne stečevine na ovome polju, ali kako je Hrvatska zemlja kandidat za punopravno članstvo u EU, očekuje se da će moći demonstrirati da njezina industrija i nadležna tijela poštuju važeće zahtjeve EU i tako potpuno pristupaju europskoj regulatornoj mreži. Stoga je važno jačati institucionalni kapacitet nadležnih tijela, jer nedostatni potencijali mogu izravno utjecati na pacijente ograničavajući im pristup dostupnim terapijama

'Rumours' and clinical trials: a retrospective examination of a paediatric malnutrition study in Zambia, southern Africa

BACKGROUND: Many public health researchers conducting studies in resource-constrained settings have experienced negative 'rumours' about their work; in some cases they have been reported to create serious challenges and derail studies. However, what may appear superficially as 'gossip' or 'rumours' can also be regarded and understood as metaphors which represent local concerns. For researchers unaccustomed to having concerns expressed from participants in this manner, possible reactions can be to be unduly perturbed or conversely dismissive.This paper represents a retrospective examination of a malnutrition study conducted by an international team of researchers in Zambia, Southern Africa. The fears of mothers whose children were involved in the study and some of the concerns which were expressed as rumours are also presented. This paper argues that there is an underlying logic to these anxieties and to dismiss them simply as 'rumours' or 'gossip' would be to overlook the historic and socio-economic factors which have contributed to their production. METHODS: Qualitative interviews were conducted with the mothers whose children were involved in the study and with the research nurses. Twenty five face-to-face interviews and 2 focus group discussions (FGDs) were conducted with mothers. In addition, face-to-face interviews were conducted with research nurses participating in the trial. RESULTS: A prominent anxiety expressed as rumours by the mothers whose children were involved in the study was that recruitment into the trial was an indicator that the child was HIV-infected. Other anxieties included that the trial was a disguise for witchcraft or Satanism and that the children's body parts would be removed and sold. In addition, the liquid, milk-based food given to the children to improve their nutrition was suspected of being insufficiently nutritious, thus worsening their condition.The form which these anxieties took, such as rumours related to the stealing of body parts and other anxieties about a stigmatised condition, provide an insight into the historical, socio-economic and cultural influences in such settings. CONCLUSIONS: Employing strategies to understand local concerns should accompany research aims to achieve optimal success. The concerns raised by the participants we interviewed are not unique to this study. They are produced in countries where the historic, socio-economic and cultural settings communicate anxieties in this format. By examining this study we have shown that by contextualizing these 'rumours', the concerns they express can be constructively addressed and in turn result in the successful conduct of research aims

Standardising Clinical Caremaps: Model, Method and Graphical Notation for Caremap Specification

Standardising care can improve patient safety and outcomes, and reduce the cost of providing healthcare services. Caremaps were developed to standardise care, but contemporary caremaps are not standardised. Confusion persists in terms of terminology, structure, content and development process. Unlike existing methods in the literature, the approach, model and notation presented in this chapter pays special attention to incorporation of clinical decision points as first-class citizens within the modelling process. The resulting caremap with decision points is evaluated through creation of a caremap for women with gestational diabetes mellitus. The proposed method was found to be an effective way for comprehensively specifying all features of caremaps in a standardised way that can be easily understood by clinicians. This chapter contributes a new standardised method, model and notation for caremap content, structure and development

The Protein Partners of GTP Cyclohydrolase I in Rat Organs

GTP cyclohydrolase I (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin biosynthesis and has been shown to be a promising therapeutic target in ischemic heart disease, hypertension, atherosclerosis and diabetes. The endogenous GCH1-interacting partners have not been identified. Here, we determined endogenous GCH1-interacting proteins in rat.A pulldown and proteomics approach were used to identify GCH1 interacting proteins in rat liver, brain, heart and kidney. We demonstrated that GCH1 interacts with at least 17 proteins including GTP cyclohydrolase I feedback regulatory protein (GFRP) in rat liver by affinity purification followed by proteomics and validated six protein partners in liver, brain, heart and kidney by immunoblotting. GCH1 interacts with GFRP and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I (EIF3I) in all organs tested. Furthermore, GCH1 associates with mitochondrial proteins and GCH1 itself locates in mitochondria.GCH1 interacts with proteins in an organ dependant manner and EIF3I might be a general regulator of GCH1. Our finding indicates GCH1 might have broader functions beyond tetrahydrobiopterin biosynthesis

An Introduction to Sphingolipid Metabolism and Analysis by New Technologies

Sphingolipids (SP) are a complex class of molecules found in essentially all eukaryotes and some prokaryotes and viruses where they influence membrane structure, intracellular signaling, and interactions with the extracellular environment. Because of the combinatorial nature of their biosynthesis, there are thousands of SP subspecies varying in the lipid backbones and complex phospho- and glycoheadgroups. Therefore, comprehensive or “sphingolipidomic” analyses (structure-specific, quantitative analyses of all SP, or at least all members of a critical subset) are needed to know which and how much of these subspecies are present in a system as a step toward understanding their functions. Mass spectrometry and related novel techniques are able to quantify a small fraction, but nonetheless a substantial number, of SP and are beginning to provide information about their localization. This review summarizes the basic metabolism of SP and state-of-art mass spectrometric techniques that are producing insights into SP structure, metabolism, functions, and some of the dysfunctions of relevance to neuromedicine