Benchmarking biopharmaceutical process development and manufacturing cost contributions to R&D.

This study aims to benchmark and analyze the process development and manufacturing costs across the biopharmaceutical drug development cycle and their contribution to overall research and development (R&D) costs. This was achieved with a biopharmaceutical drug development lifecycle cost model that captured the costs, durations, risks and interdependencies of the clinical, process development and manufacturing activities. The budgets needed for process development and manufacturing at each phase of development to ensure a market success each year were estimated. The impact of different clinical success rate profiles on the process development and manufacturing costs at each stage was investigated, with a particular focus on monoclonal antibodies. To ensure a market success each year with an overall clinical success rate (Phase I to approval) of ~12%, the model predicted that a biopharmaceutical company needs to allocate process development and manufacturing budgets in the order of ~$60 M for pre-clinical to Phase II material preparation and ~$70 M for Phase III to regulatory review material preparation. For lower overall clinical success rates of ~4%, which are more indicative of diseases such as Alzheimer's, these values increase to ~$190 M for early-phase and ~$140 Mfor late-phase material preparation; hence, the costs increase 2.5 fold. The costs for process development and manufacturing per market success were predicted to represent 13-17% of the R&D budget from pre-clinical trials to approval. The results of this quantitative structured cost study can be used to aid decision-making during portfolio management and budget planning procedures in biopharmaceutical development.

[The costs of new drugs compared to current standard treatment]. / Die Preise neuer Arzneimittel im Vergleich zu ihren therapeutischen Alternativen.

BACKGROUND: Until AMNOG came into effect Germany had free pricing of new drugs. Our exemplary work investigates the costs of new drugs that were licensed in the two years prior to AMNOG, and compares them to the costs of standard treatment that has been used in pivotal trials. Also, the important components of pharmaceutical prices will be illustrated. METHOD: We retrospectively analysed the European Public Assessment Reports of proprietary medicinal products that the European Medicinal Agency initially approved in 2009 and 2010 and that were tested against an active control in at least one pivotal trial. RESULTS: If the standard treatment was a generic, the average pharmacy retail price of new drugs was 7.4 times (median 7.1) higher than that of standard treatment. If the standard treatment was an originator drug the average price was 1.4 times (median 1.2) higher than that of the new drug. There was no clear correlation of an increase in costs for new drugs and their "grade of innovation" as rated according to the criteria of Fricke. Our study shows that prices of new drugs must be linked to the evidence of comparative benefit; since German drug pricing is complex, cost saving effects obtained thereby will depend on a range of other rules and decisions.

Drug-mediated toxicity: illuminating the 'bad' in the test tube by means of cellular assays?

Health problems are rising worldwide, be it as a consequence of lifestyle and longevity in increasingly affluent societies or due to a sharp rise in bacterial antibiotic resistance. The pharmaceutical industry is caught between high rates of attrition and the rather slow pace of a historically large regulatory system for pharmacological safety. Meanwhile, the past decade has seen a tremendous evolution of the biological toolbox, most notably of cellular assays, stem-cell differentiation and organ-mimicking systems. These systems were readily adapted for lead-compound identification. However, their use as toxicological test systems is lagging behind, not least because of a lack of regulatory acceptance. This review tries to elucidate the scale of the problem and discusses the applicability of the assays currently available, with particular regard to the use of stem cells.

Toward molecular imaging-driven drug development in oncology.

With current testing strategies, the number of novel targeted anticancer agents will exceed our drug selection capacity. Molecular imaging is a powerful additional tool that can assist us in selecting effective drugs and help patients benefit from targeted agents. Moreover, measurement of the functional effects of such targeted agents could permit dynamic tuning of treatment selection at the earliest time point at which loss of functional effects is observed.

Evidence-based decision on medical technologies in Asia Pacific: experiences from India, Malaysia, Philippines, and Pakistan.

BACKGROUND: This paper discusses national programs implemented in India, Pakistan, Malaysia, and Philippines to generate and apply evidence in making informed policy decisions on the approval, pricing, reimbursement and financing of medicines, diagnostics, and medical devices. APPROVAL: In all countries, the Ministries of Health are generally responsible for approval of health technologies through various agencies like the Central Drugs Standard Control Organisation in India, Bureau of Food and Drugs for medicines and Bureau of Health Devices and Technology for medical devices in the Philippines, the National Pharmaceutical Control Bureau, Health Technology Assessment Unit and Medical Device Bureau in Malaysia, and the Drug Control Organization in Pakistan. Product dossiers are evaluated while taking decisions. PRICING CONTROL: India has a strong price control mechanism through the National Pharmaceutical Pricing Authority. In the Philippines, the Essential Drug Price Monitoring System monitors prices of 37 essential drugs monthly from all drugstore outlets nationwide. In Malaysia and Pakistan registration pricing of new drugs is negotiated/fixed by the government with the vendor. REIMBURSEMENT: A mix of social, voluntary private and community-based health insurance plans are available in India while the Philippine Health Insurance Corporation is responsible for reimbursement of drugs and medical devices in the Philippines. In Malaysia no formal reimbursement system is being practiced, and in Pakistan the government reimburses medical claims of its employees. FINANCING: In both India and the Philippines the bulk of health expenditure is out of pocket while the government pays for 20% and 28% respectively in both countries. The public health care services in Malaysia are heavily subsidized by the government with minimum fee being charged to the public. The government of Pakistan gives free medicines to its citizens at the public health facilities. CONCLUSIONS: In the region under discussion, one of the priority areas that the different regulatory agencies would benefit from is human resource development to facilitate the process of evidence based assessment of health technologies. Higher budgetary allocation and stronger legislation is also needed along with interagency and international coordination and cooperation to harmonize.

Short patent lives jeopardize drug and patient safety.

Exposure of patients to new medications carries potential safety hazards during widespread clinical practice. These are often detected only after a substantial period of use. Thus, there is considerable need for measures reducing drug-related morbidity and mortality, such as adequate, active postmarketing drug-safety surveillance systems with obligatory follow-up studies of suspected safety problems, or even an additional "Phase IV" safety study before marketing. However, drug development processes erode substantially into the useful patent life of a new drug. Therefore, we suggest that the potential benefits of patent life prolongation should be considered, under certain conditions for the sake of patient safety.

Evidence, economics, and emotions: the case for temozolomide.

Temozolomide, given as part of first line therapy in the treatment of grade IV astrocytoma, has been shown to improve survival in the short term. The financial cost of the treatment is considerable in New Zealand. This drug provides a good example in the field of oncology of a modern expensive pharmaceutical being a clear improvement over its cheaper predecessors, but it raises the question of what price should be paid to prolong survival in an incurable illness?

PHARMAC not funding some treatments for rare, life-threatening diseases: bosentan as an example.

Pulmonary arterial hypertension is a devastating and fatal disease for which effective therapies have been developed over the last 10 years. Unfortunately these therapies are expensive. The New Zealand health system which has no discernible strategy to deal with the issue of high-cost treatments has, through its agent, PHARMAC, failed to either clearly state that they recognise the need to fund treatment for this condition or to refuse all effective treatments and defend such a decision in the public arena. Bosentan, an endothelin antagonist, improves symptoms and extends life substantially in this condition, but access has been near impossible as it is expensive. PHARMAC have for the last 18 months refused to fund any effective therapy through the Community Exceptional Circumstances Panel. However, clinicians can approach the patient's DHB to fund treatment and yet the treatment offered and the duration is decided by the Hospital Exceptional Circumstances Panel of PHARMAC. Power without either clinical or fiscal responsibility?

What's happening in PHARMAC--where do all the submissions go? On the trail of gemcitabine.

The process and progress of submissions to PHARMAC for funding of new treatments is unclear. There appears to be a lack of communication or transparency regarding funding applications, decisions, or expected timelines to reach an endpoint. It is difficult to have confidence in a process that lacks such definition. A recent clinician submission for funding of an oncology treatment (gemcitabine) for bladder cancer highlights these issues.