There is no questioning the significant benefits prescription drugs can bring to patients’ lives when used appropriately, as per the doctor’s advice. But, that’s not always the case. Prescription medication abuse is a growing challenge affecting the quality of life of millions of people worldwide. This is especially true for drugs capable of affecting the central nervous system (CNS), offering the chemically induced sanctuary of sedation, euphoria and hallucinations.
The health consequences of drug abuse cannot be overlooked. New drug applications (NDA) for formulations that could have an impact on the CNS must come with an abuse liability assessment. This is used to classify drugs into one of five schedules depending on the severity of the abuse potential. Each schedule outlines specific measures to control drug manufacture, distribution and prescription. Scheduling can greatly impact upon the commercial viability of medicines, delaying the development of drugs and their delivery to patients, and placing a significant financial burden on pharmaceutical manufacturers. As a result, the assessment of abuse liability cannot be taken lightly.
Taking an integrated approach to abuse liability assessment
When planning for abuse liability assessment, we recommend that you adopt an integrated, two-tiered approach. First, you should perform a set of tests designed to comprehensively characterize the compound in question and understand its pharmacology. The resulting data should be compared to other relevant molecules, including drugs with known abuse potential, direct market competitors and similar families of therapeutics. Overall, the results generated through this first step can provide an early indication of the drug’s abuse potential. This will reveal whether it is necessary to investigate the drug further through animal and human clinical studies.
Animal behavioral studies, performed in rodents under the latest FDA guidance, are typically undertaken to assess the different aspects of abuse liability. However, it is unlikely that you’ll be able to obtain a full picture of a drug’s potential for abuse through in vivo studies alone. Human abuse liability studies are often required to complete the assessment, in particular when abuse-related adverse effects have been observed in animal behavioral studies.
Key considerations when assessing abuse liability
Because of the length of the scheduling process and its implications on financial return and market access, it is advisable to consider the factors that could impact abuse liability for a particular drug development project ahead of time. By planning for potential abuse liability at the candidate selection stage, you’re most likely to avoid unexpected surprises during early clinical trials.
It’s also important to remember that while insufficient abuse liability evidence could delay a drug-scheduling program, conducting poorly designed studies can have an equally devastating effect. For example, results indicating a high abuse potential can lead to a harsh abuse scheduling, when, in reality, the compound doesn’t cross the blood-brain barrier.
Drug development programs benefit from integrated abuse liability assessment
Taking an integrated approach to drug abuse liability assessment can facilitate effective communication between the individual teams working on a drug development program. That’s an excellent way to reduce the risk that key information will be overlooked and ensure that potential issues will be identified and addressed early in the process. Adopting a collaborative approach also means that experiments can be designed according to what’s best for the program as a whole, and not as disjointed parts of the same process.
An integrated approach adopted in the early stages of development can help streamline the process and ensure new medicines will be available to the patients who need them as quickly and as cost effectively as possible.
To find out more about the key constituent parts and the benefits of an integrated approach to drug abuse liability assessment, read our article in full here.