Guidelines for clinical trials of locally applied, locally acting products were released by China’s Center for Drug Evaluation (CDE) on May 30, 2022.
This technical guideline is applicable to the development and evaluation of locally applied, locally acting products, including innovative drugs, known active ingredients developed and modified into locally applied, locally acting new drugs, and chemical generic drugs.
Locally applied, locally acting products
These typically include:
external skin preparations, ophthalmic preparations, ear drops, nasal preparations, inhalation preparations for respiratory system, gynecological preparations, preparations that exert local effects on the digestive tract by oral or rectal administration, etc. Compared with systemically administered drugs, locally applied, locally acting products have special characteristics in terms of prescription composition, dosage form characteristics, administration routes, etc.
Drug characteristics of locally applied, locally acting products
- Such products usually require a special dosage form to be retained in the application site (such as cream, gel), or a specific dosage form and device (such as powder aerosol and corresponding device) to reach a specific site and remain in the application site to exert local therapeutic effect.
- In addition to the main active ingredients, this type of drug often requires more excipients to produce the corresponding dosage form, and the selection and change of its prescription and dosage form can directly affect the effectiveness and/or safety of the drug.
The general principles of clinical trial design
(1) Innovative drugs
- In addition to the general concept of innovative drug research and development, the development of locally applied, locally acting products should take into consideration that the drug dose of topical preparations be closely related to the drug concentration and the size of the drug delivery area.
- Although the purpose of applying this class of drugs is to exert the drug effect locally, there may still be safety risks due to drug absorption into the blood. The applicant should preliminarily assess whether there is systemic absorption after topical administration and the potential safety risks brought by systemic absorption in combination with the non-clinical pharmacokinetic characteristics of the investigational drug and the toxicity related to systemic exposure.
(2) Known active ingredients developed and modified into locally applied, locally acting new drugs
This applies to:
- existing systemic drugs already on the market that are developed into locally applied, locally acting products using the same active ingredient:
- such drugs should focus on evaluating the safety and tolerability of topical administration after changing the route of administration, and whether the local absorption and exposure after administration can produce the expected therapeutic effect.
- locally applied, locally acting product that has already been marketed that are developed into locally applied, locally acting products using the same active ingredient:
- comparing the differences between the product under development and the product already on the market. The proposed new product should have significant clinical advantages over the already marketed product.
(3) Generic Drugs
- Select Reference Listed Drugs (RLD) in accordance with the Selection and Determination Procedures for RLD of Chemical Generic Drugs issued by the State Food and Drug Administration.
- The applicant should carry out a step-by-step comparative study based on the characteristics of the drug, and sequentially carry out pharmaceutical, non-clinical and/or necessary clinical comparative studies to support the equivalence evaluation of the generic drug and RLD.
By Yu and Victoria. If you would like to learn more about developing protocols for Clinical Trials of locally applied, locally acting products or our registration services for pharmaceuticals, medical devices, IVDs, cosmetics, health foods, industrial or consumer goods contact Cisema.