Company insight
Precision micro-dosing for clinical development
Rebecca Coutts PhD, general manager at PCI Pharma Services, centre of excellence for the development and manufacturing of highly potent products, discusses Xcelodose, a precision micro-dosing technology delivering drugs directly into capsules and vials for early stage clinical development.
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s demand to reduce drug development times, waste and costs increase, technological advances in the form of micro-dosing solutions provide a real alternative to the traditional formulation development pathway. As medicines increase in specificity, the value of the medicines themselves is also increasing, further driving the requirement for faster and more cost-efficient solutions. The traditional product development route of a formulated solid oral drug for phase-I clinical trials involves a range of complex activities. These include the initial compatibility studies, analytical method development, prototype development, short-term stability, process/formulation refinement, phase-I method validation, and, finally, clinical manufacture and release testing. This process can often take in excess of nine months to complete and incur significant costs for product development alone, not taking into account delivery of the trial itself. The ability of pharmaceutical companies to remain commercially competitive depends on transforming new chemical entities (NCEs) into clinical products and on to commercial launch.
development, minimising the use of often costly API, and the associated formulation and analytical development required to support an investigation new drug (IND) application or investigational medicinal product dossier (IMPD).
Progressing this concept of filling neat API directly into capsules or vials and taking advantage of technological solutions leads one to the concept of using an automated micro-dosing technology. Such a solution eliminates the need for initial formulation screening and associated stability testing, enabling a company to achieve faster times to first- in-human studies and importantly inform the key go/no-go decision point of phase- I clinical studies for the development of new molecules.
Put into context, using the micro-dosing pathway, the timescale to early phase clinical manufacture could be reduced by as much as 50% to between four and six months, and lead to an overall cost reduction of around 70%, depending on the cost of API.
An additional market factor that requires consideration would be that as the biological activity and the specificity of the API
“PCI utilises the Xcelodose micro-dosing technology and applies its centre of excellence philosophy of using a fully contained engineering solution by utilising Xceloprotect isolators.”
The API approach
Filling an active pharmaceutical ingredient (API) directly into a capsule or vial is potentially the fastest option for entering early phase clinical trials. This approach offers a reduction in time and financial investment at the earlier stages of drug
Clinical Trials Insight /
www.worldpharmaceuticals.net
increases, we see dosage strengths decreasing, making APIs more potent in terms of occupational handling for drug product manufacture. In this instance, the more traditional open processing methods, such as hand-filling or semi-automatic filling techniques, are not suitable and, in any case,
such processes may lead to time-consuming inconsistencies and additional costs.
Trend towards potency The trend for more potent compounds is set to continue with focus on therapy areas, such as oncology, immunology, antivirals and opioid-based analgesics. This, coupled with the distinct lack of toxicity data available at the earlier stages of development, requires an increased focus on operator safety, with best practice being the use of contained processing as opposed to the more traditional personal protective equipment (PPE). To address this, PCI utilises the Xcelodose micro-dosing technology and applies its centre of excellence philosophy of using a fully contained engineering solution by utilising Xceloprotect isolators. The high levels of containment afforded by this equipment ensures an occupational exposure limit (OEL) as low as <0.1µg/m3 over an eight-hour time-weighted average, meeting the intended regulations for Safebridge 3 and 4 applications. So, in summary, as the industry continues to focus on products being developed to treat more specialist and rarer disease areas, the trend towards the development of more potent, expensive molecules is set to continue. This in turn increases the pressure on the need to identify alternative and innovative technology driven solutions able to deliver greater cost and time efficiencies. One such option favoured by PCI is that of Xcelodose micro-dosing technology and ensuring the highest standards of safety are met using full engineering containment, where the molecule is classified as being highly potent. ●
www.pci.com 23
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