In addition to the need for evidence to prove that the drug is effective, the FDA and other drug regulatory agencies around the world also emphasize that the compounds used for patients are safe. The key elements of a successful IND or equivalent application include a sound pharmacokinetic (PK) profile covering absorption, distribution, metabolism and excretion, drug transport activity, and pharmacokinetic-based drug interaction (DDI) potential.
After learning from historical experience and lessons, the current regulatory agency hopes that drug development companies will conduct PK research on candidate compounds at an early stage and eliminate those candidate drugs that fail to meet the threshold during the approval process.
In vitro studies were conducted at an early stage to evaluate the metabolic pathways of drugs. This helps to understand whether clinical drug interaction studies are needed. Many companies consider the results of drug interactions when deciding whether to advance drug development. If a compound is known to be prone to major drug interactions, the company may decide to cancel the compound’s research and development priority.
The FDA emphasizes that prior to the submission of the IND, risk-based methods should be used to examine the potential interactions between drug candidates and drug metabolizing enzymes, their potential as substrates or inhibitors of drug transporters, and their metabolites to drugs. Potential impact on safety and effectiveness. If there are loopholes in the IND scheme or DDI-related problems in the clinic, the sponsor can go back and conduct these studies simultaneously with the clinical trial; however, fully discussing the DDI and ADME parameters before the IND will make the clinical research planning more wise, and Can prevent unexpected results.
Early and comprehensive ADME can increase the chances of success
The poor properties of ADME can destroy the originally promising drug activity.
In the past, more than 40% of drug candidates failed due to poor pharmacokinetic curves, but since 1991, drug development has shifted the exploration of ADME/PK to the early stages of the pipeline, so as to be more effectively screened through in vitro testing in the early stages of development Candidate drugs to avoid the high cost of discovering pharmacokinetic problems in the later stages of the pipeline. Many scientists and professional ADME contract research organizations (CROs) in the pharmaceutical industry have worked hard to effectively conduct in vitro ADME studies at an early stage by improving technology, tools, and processes to verify excellent drug candidates and eliminate those with poor performance. Thus reducing this proportion to <1% before 2008.
Targeting candidate compounds
Understanding the pharmacokinetic characteristics of compounds is of great value. Not only can drug developers discover early whether a candidate drug may fail, but sometimes they can also use this data to make adjustment decisions to optimize their PK before entering the more expensive development phase.
At this stage, choosing institutions that can provide a full set of ADME and PK evaluation services, and even toxicology and efficacy evaluation services, will show its advantages. Because this can fully support all the needs of drugs from early screening to declaration.
Candidate compounds to IND (preclinical drug development)
To some extent, the exact in vitro and in vivo data determines the success or failure of clinical development.
In order to obtain a complete declaration data package, drug developers should refer to the basic in vitro studies recommended by the current guidelines, but should also follow-up studies to further explore inhibition, induction, drug delivery, metabolism, or other areas (if necessary).
If the research has unexpected results (which is often the case for new drugs) and you don’t know how to deal with it, we can mobilize a team of experienced expert consultants to help you understand the tricky data and help you plan your next research and development plan , To meet the requirements of regulatory regulations.
IND to NDA
Sometimes, unexpected situations occur in clinical research, and these situations may be overlooked in the pre-clinical development process. In this case, in vitro and in vivo research can make up for the lack of clinical research to better understand the drug candidate, and sometimes it can be used to explain clinical results.