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Ronak Savla is scientific affairs manager at Catalent Pharma Solutions.
More work needed to advance drug design and development effectively.
Every design decision made during drug development has the potential to influence patient outcomes. But how do you convince a medicinal chemist or a formulator that their decision today may impact a patient several years later? What tools and information are available for formulators to routinely design patient-centricity into their work? Are there factors beyond dose, dosing frequency, and dosage unit characteristics (size, shape, or color) that a formulator can influence to improve patient friendliness? How do the best companies share knowledge in the development of patient-focused drug products?
With attrition rates that haven’t moved over the past decade and growing pressure from payers and patients, developers are increasingly required to bring drugs to the market that not only have better efficacy and safety but are also designed with patient factors in mind. Scientists involved at any stage of drug development should have a comprehensive understanding of the drug development process and how their design decisions affect downstream development.
Despite increased focus on how dosage form impacts patient adherence, safety and efficacy, pediatric patient requirements can still be overlooked or inadequately addressed. The Catalent Applied Drug Delivery Institute sponsored research with the pediatric pharmacy faculty at the Ernest Mario School of Pharmacy at Rutgers University in New Jersey to evaluate the biggest dosage form and administration challenges in pediatric patients, with the aim to bring these insights for pediatric friendly dosage form development (1).
Many marketed drugs do not have an age appropriate dosage form, which leads to three times higher drug manipulation (e.g., crushing, splitting tablets, mixing the drug with food or water, and extemporaneous compounding from commercial dosage forms) in inpatient pediatric patients, compared to inpatient adult patients. These challenges are also seen in the outpatient as evidenced by a Catalent survey of caregivers (2), which found that many caregivers had no experience with dosage forms such as softgels, sprinkle capsules, or granules.
Challenges in patient acceptance and adherence have seen an increased focus from the industry. These challenges are partly due to the ‘inflated’ physicochemical properties of new molecular entities. The higher LogP and molecular weight lead to poor solubility, low bioavailability, food effects, and patients taking large doses. The implementation of drug delivery technologies has grown to address these molecule challenges, with the aim that it will result in more patient-focused drug products.
In an analysis of drug approvals since 2009, however, the Catalent Applied Drug Delivery Institute found that 65% of the drugs were not outcome-optimized. The definition of “non-optimized” would be those drugs privy to API-wasting formula, mitigable side effects, low bioavailability, food effect, adherence challenges, complex handling, and increased regimen complexity.
Additionally, a survey undertaken by the Institute in November 2018 showed that nearly half the respondents said that they do not have or are notaware of a target product profile (TPP) for the drug they are developing. There is a plethora of literature that investigates drug product characteristics that improve patient acceptance, adherence, and outcomes.
As an industry, we are not doing enough to equip formulators, biopharmaceutical scientists, and medicinal chemists with the tools and training to sift through the data and apply key learnings to their daily jobs. In conclusion, an industry-wide adoption and collaboration is necessary to advance how better treatments for patients are designed and developed.
The aim of the Catalent Applied Drug Delivery Institute is to bring together scientists and leaders through various mechanisms to generate insights and ideas, share experiences and knowledge, and develop new pathways and tools to apply drug delivery technologies to address unmet patient needs and improve outcomes.
1. Catalent Applied Drug Delivery Institute, “Catalent Applied Drug Delivery Institute Partners with Rutgers University to Better Understand the Challenges of Pediatric Drug Formulation and Delivery,” Press Release, July 20, 2017.
2. D. McDonald, et al., “Medication Administration to Children: The Caregiver Perspective,” EuFPI Conference (London, UK Sept. 12–13, 2018).