Effective decision-making: progressing compounds through clinical development

Shillingford, Christine A.; Vose, C. W.

doi:10.1016/s1359-6446(01)01945-6

Cited by 29 publications

(11 citation statements)

References 4 publications

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“…An interesting review of the various current philosophies is provided by Shillingford et al [21]. An interesting review of the various current philosophies is provided by Shillingford et al [21].…”

Section: Conclusion: Drug Discovery and Development In Industrymentioning

confidence: 99%

Discover a Drug Substance, Formulate, and Develop It to a Product

deMontigny

Harris

et al. 2015

The Practice of Medicinal Chemistry

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Section: Conclusion: Drug Discovery and Development In Industrymentioning

confidence: 99%

Discover a Drug Substance, Formulate, and Develop It to a Product

deMontigny

Harris

et al. 2015

The Practice of Medicinal Chemistry

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“…Many if not most of these challenging issues and requirements could probably be handled and accepted more easily if it wasn't for the project attrition that keeps haunting virtually all of the pharmaceutical companies [5,6]. The industrial average today is at 90%, meaning that of 10 nominated CDs (NCEs) only 1 will make it through all stages of development (i.a.…”

Section: Preamblementioning

confidence: 99%

“…Whilst the pharma business as a whole is still earning grand sums of money and is seen as being wealthy by the public, the situation faced today has changed quite dramatically and dark clouds are now, at least partly, shadowing the skies. To mention but a few of the "burdens" and challenges that are putting pressure on the companies: cost for development of new drugs keeps on spiraling upwards to unprecedented levels (reference can be made to the "infamous" figure of $802m [1,2] describing the expenditure for taking an NCE (New Chemical Entity) drug through to a registered product which then has to be followed by an equal sum of money or even more to cover the marketing activities), extended approval times for new therapeutics [3], push from health authorities and politicians to reduce the overall cost level for drugs by not approving prime pricing and thus driving down companies profit margins, a fierce competition from generics and parallel import, reluctance to recommend usage of newer and more expensive drugs where similar older generation products are already on the market, continuously increasing demands from regulatory authorities (notably FDA) to provide more and more comprehensive documentation for a given drug often meaning larger and longer clinical trials [4], and, finally, tougher attitudes with regard to granting patent applications and acknowledging their validity from third parties.Many if not most of these challenging issues and requirements could probably be handled and accepted more easily if it wasn't for the project attrition that keeps haunting virtually all of the pharmaceutical companies [5,6]. The industrial average today is at 90%, meaning that of 10 nominated CDs (NCEs) only 1 will make it through all stages of development (i.a.…”

mentioning

confidence: 99%

The Integration of Process R&D in Drug Discovery - Challenges and Opportunities

Federsel¹

2006

CCHTS

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In today's situation where a lot of attention is put on the whereabouts of the pharmaceutical industry, especially focusing on productivity, pricing policies, time lines, and competition, there is an increased need for a critical revision of work practices in the business. The prevailing prioritization of time-to-market is now more and more shifting over to also put quality, risk management, and effectiveness/efficiency in the limelight. Resources in terms of people and money will continue to be constrained and, therefore, best collaborative principles have to be adopted between different parts of the organization. Only by operating this way will we maximize the output. One of the most important key performance indicators in pharma R&D is the number of newly appointed candidate drugs (CDs). However, it is not only a matter of counting numbers but, more so, to nominate compounds with the best properties and likelihood to survive. In that vein the demands on Process R&D have gone up considerably over recent years and there is now a pronounced need to make forecasts on cost of goods for the API (active pharmaceutical ingredient), scalability issues, IP matters, route design etc. On top of this, there is as always an expectation that the supply of material needed to conduct the various studies is timely, fully reliable, and flexible, even if volumes and delivery dates fluctuate widely. To successfully be able to cope with this challenging and sometimes stressful situation a back-integration into earlier parts of Drug Discovery is a must and, hence, connecting to new projects will have to be initiated already during the LO-stage (lead optimization). The consequences of this and its further implications will constitute the core part of the paper.

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“…All in all, as many as 70% of marketed drugs fail to recover the R&D investments (including failures to an average cost of $550m) during their lifetime. 7 The hardships experienced by the pharma business is further underscored by the statistics that of 30,000 active compounds prepared, not more than 8 are approved by the regulatory authorities, equaling the rather scary and barely measurable figure of only 0.027%. 8 A graph displaying this decline in the R&D portfolio during various stages of development is shown in Diagram 1.…”

Section: A Risky Businessmentioning

confidence: 99%

Facing chirality in the 21st century: Approaching the challenges in the pharmaceutical industry

Federsel

2003

Chirality

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How is process R&D organized and operated in today's pharmaceutical industry at the dawn of the 21st century? A way to respond to the challenges with regard to reduced time to market is to build on early involvement and a front-loading approach. This means that activities are initiated during the lead optimization phase starting up to 2 years ahead of candidate drug nomination and a model built on this concept covering the stages through to commercial launch is advocated as the appropriate way forward. However, given the high attrition rate in a pharma R&D pipeline focused risk management needs to be applied and options judiciously evaluated. From a molecular perspective, the chemical targets in many instances present a formidable complexity both with regard to the overall structure but increasingly also when it comes to their stereochemical features. Thus, a novel triazolo pyrimidine compound with six stereogenic centers requiring 28 transformations for its assembly is examined to underscore this, but also the difficulties in designing a feasible route for the relatively simple (S)-azetidinecarboxylic acid are highlighted. Furthermore, the successful development of a unique and highly efficient catalytic asymmetric sulfide oxidation to the corresponding (S)-sulfoxide esomeprazole is discussed, together with the remarkable effect that normal sea sand has on the stereoselectivity of a steroid trans-acetalization.

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Effective decision-making: progressing compounds through clinical development

Cited by 29 publications

References 4 publications

Discover a Drug Substance, Formulate, and Develop It to a Product

Discover a Drug Substance, Formulate, and Develop It to a Product

The Integration of Process R&D in Drug Discovery - Challenges and Opportunities

Facing chirality in the 21st century: Approaching the challenges in the pharmaceutical industry

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