On March 14, 2022, China’s CDE released the “technical guidelines for clinical trials of new chemical enhanced drugs.”
The CDE has issued a living FAQ inviting industry comments to better align the clinical technical guideline for new modified drugs.
The initial version contains several important aspects that should be analyzed and the time limit for soliciting comments is one month from the date of publication April 14, 2022.
Since the official release of the “technical guidelines for clinical trials of improved new drugs of chemical drugs” in december 2020, the communication and exchange of clinical research and development of improved new drugs has gradually increased, in order to further promote the orderly research and development of improved new drugs in china and better meet the clinical needs of patients, the guiding principles working group has systematically sorted out and discussed the common issues that are more concentrated, forming the “technical guidelines for clinical trials of improved new drugs .
Questions on the Development of New Indications
- The improved new drug developed by our company is expected to improve the efficacy of the drug by optimizing the formulation and process of the marketed drug, adopting the same route of administration, changing the pharmacokinetic and tissue distribution characteristics. Can surrogate endpoints be selected to confirm clinical advantage in a small randomized controlled trial?
- The modified new drug developed by our company intends to develop a new indication by optimizing the formulation and process of the marketed drug, using the same route of administration, changing the pharmacokinetic and tissue distribution characteristics, and whether a controlled study with the modified drug is also required?
Questions on improving safety
- Through literature investigation, our company found that one of the approved chiral molecules had been marketed, and one of its isomers was effective, but there was clear safety issues, removing this isomer, and improving safety, is this modification a modified new drug? What clinical trials are needed?
- Through literature investigation, our company found that one of the approved chiral molecules, although one of its isomers was ineffective and harmless, could make the plasma concentration of the drug more stable after removal. If it was removed, would this modified method be considered a modified new drug? Is it necessary to conduct clinical trials?
- It is reported that the mechanism of adverse reactions of a marketed drug is related to the tissue distribution and pharmacokinetic characteristics of the active ingredient. Our company plans to improve safety by optimizing the pharmacokinetic characteristics of the drug, without changing the route of administration. Is this considered a modified new drug? Is it sufficient to conduct a pharmacokinetic comparison study while observing safety in the study?
Questions on Improving Compliance
- Our modified new drug for chronic diseases requiring long-term use is to change the common drug product marketed for daily administration to a sustained-release formulation with a longer dosing interval without changing the active ingredient and route of administration by optimizing the formulation and process. From the preclinical pharmacokinetic profile, it can support “once every 4 days”. Is this kind of improvement acceptable?
- Our company plans to optimize the route of administration of a marketed drug, such as changing intravenous to subcutaneous formulation to improve patient compliance without changing the indication, is this modification a modified new drug? Is it feasible to compare the primary endpoint of clinical trials as drug exposure and efficacy as a secondary endpoint?
- Our company plans to develop more suitable oral solution for swallowing for special populations (e.g., young children) on the basis of available oral solid dosage forms. Is the rationality of the improved study?
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