摘要:

The concomitant use of medicinal products may trigger the development of a fixed combination product with the intention to facilitate for the user and improve compliance. At present, there is a lack of detailed regulatory guidance on the strategies for the non-clinical development of a fixed combination, and companies often seek scientific advice at the European Medicines Agency (EMEA) and its scientific committee, the Committee for Medicinal Products for Human Use (CHMP). Four main scenarios can be identified: combination of well known compounds already approved/used in combination; combination of approved/well known compounds not previously approved in combination; combination of one or more new chemical entity(ies) [NCE] with one or more well known compound(s); and combination of two or more NCEs. The level of knowledge and experience in these scenarios will differ markedly and, therefore, different strategies for the non-clinical development programme are justified.The current paper discusses these different scenarios and addresses specific issues in relation to the need of non-clinical studies to support the development of a fixed combination.

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

At present, there are no really efficacious tools available to counteract cognitive deficits in patients with schizophrenia: even though new atypical antipsychotic drugs represent an advance compared with typical antipsychotic drugs, the results obtained with this class of drugs are actually partial. Acetylcholinesterase inhibitors (AChEIs) that have been proven to be effective on psychiatric symptoms, behavioural abnormalities and cognitive dysfunction of patients with dementia may be effective on cognitive deficit in patients with schizophrenia, and may also improve their psychopathology and behaviour.In the present paper we review the use of AChEIs in the treatment of schizophrenia. Although these AChEIs have different action mechanisms (donepezil only inhibits acetylcholinesterase; rivastigmine also inhibits butyryl-cholinesterase; galantamine also interacts with nicotinic acetylcholine receptors), they have similar clinical effects.We have observed no or mild effects on cognitive deficits and symptoms in double-blind studies, a dramatic effect on a patient’s subjective well-being and ability to cope and subjective judgement of psychiatrists in the case reports and open studies.The question remains as to how we can accurately measure a patient’s capacity to feel, to cope and his/her desire to live with other people − aspects very different from intelligence and cognitive function. Further double-blind placebo studies are required to determine the role of AChEIs in the improvement of quality of life for patients affected by schizophrenia.

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

The risks of biotechnology-derived products and other biologicals are different from the risks of small chemical entities and, thus, their risk management will have special features. For many biological products, the safety is mainly dependent on the starting materials and the manufacturing process. Therefore, their risk management must be focused accordingly. In certain issues, such as immunogenicity of recombinant DNA products, a proper risk management plan can only be built during the pre-licensing studies. Application of special epidemiological methods for investigation of very rare safety signals is crucial for some biologicals, e.g. vaccines. Genetically modified viruses used as vaccines and vectors for gene transfer, as well as xenogeneic cells, carry major public health risks. Therefore, the use of such products is possible only with extensive risk management programmes. Some elements of these programmes may be difficult to enforce because of legal, ethical and practical obstacles.The main special risk of biologicals is the transmission of infectious agents. The mitigation of this risk is complicated by the ever-changing epidemiological situation and the long latency of some infections. The impact of any measure for risk reduction of essential products, such as vaccines and plasma-derived medicinal products, must be considered carefully from the overall benefit/risk point of view. The risk must be reduced to the lowest level that is reasonably achievable without unduly putting the availability of essential products at risk. Adequate expertise and consultations with special experts are important in the risk management of the new advanced therapies in order to ensure the full understanding of the risks and to avoid creating unnecessary barriers for innovation.Due to the sensitive issues linked with biotechnology-derived products and other biologicals, risk communication is of critical importance. From the regulatory point of view, the risk management of biologicals is far from optimal, especially in the EU where legislation lags behind the progress in the field, and where the concerted actions of the national regulatory agencies need improvement. From the industry point of view, the risk management plans for biologicals should be designed in multidisciplinary teams.

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ObjectiveForeign clinical evidence for efficacy and safety of new pharmaceutical drugs was utilised in decisions for marketing approval in Japan without specific regulatory guidelines until a new internationally harmonised guidance for bridging strategy was introduced in 1998. We examined how foreign clinical studies were used in recent marketing approval decisions and also how the new guidelines affected the trends of foreign data acceptance.MethodsNew drug applications (NDAs) approved between 1999 and 2003 with review reports issued by the regulatory authority available on the official website were scrutinised. Focusing on critical clinical trials including dose response studies in phase II and confirmatory studies in phase III, we classified the type of utilisation of foreign clinical data into several groups.ResultsOf the 171 NDAs approved during this period, 55 (32%) contained foreign studies as formally submitted data. Twenty NDAs (12%) were approved based on the bridging strategy. In 24 NDAs (14%) important foreign data were used as references, but not as formally submitted materials. NDAs that were given orphan drug status or priority review status were more likely to be submitted and approved on the basis of foreign clinical data. The number of bridging-based NDAs successfully approved increased from three in 2000 to ten in 2002, although confusion about the application of the new guidelines was observed after the guidelines’ introduction.ConclusionsWhile the traditional method of acceptance of foreign clinical data still persist, the bridging strategy is becoming a common and practical basis for the decision making of marketing approvals of new drugs in Japan.

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1364-9027    

出版商:ADIS    

年代:2004

数据来源: ADIS