Information and contents related to the drugs may be changed either during clinical trials or after the drugs enter into the market. During the clinical trials, which is at the stage of research, it is quite common to change the prescriptions or dosage of the drugs based on the feedbacks. After a drug enters into the market, changes such as replacing the supplier of excipients or optimizing quality control system may also be necessary. Companies may encounter with obstacles on their way of drug research and development or drug optimization if the changing procedure is too complicated or if any kinds of change require approval, regardless of the degree of change, or even regardless of whether it has any impact on the drug safety and efficacy.
The Draft for Comment classifies the changes during clinical trials into ordinary changes and significant changes. Significant changes include changes in clinical study protocols that may affect the safety of the study subjects and changes that will apparently affect drug safety, efficacy, and quality evaluation. The applicants can make ordinary changes directly after analysis and assessment. For significant changes, the relevant applicant should submit an application for change to the CFDA, but the approval approach will be “implied approval if no rejection within the prescribed time limit”, meaning the applicant can implement a significant change if it does not receive any rejections or deficiency notices from the CFDA within the prescribed time limit. Such system can provide the applicants with more autonomy in making changes during clinical trials. Furthermore, the applicants can make ordinary changes during clinical trials in their own decision without any interruption to the then-current clinical trials, which can help the research and development to move forward smoothly.
With respect to post-marketing changes, the Draft for Comment proposes to classify them into three categories according to the degree of impact they could have on drug safety, efficacy and quality control, namely, minor changes, moderate changes and significant changes. Minor changes refer to those that could have slight impact or almost no impact on drug safety, efficacy and quality control, which can be made by the marketing approval holders themselves and filed for recordal with the CFDA in the meantime. Moderate changes refer to those that could have moderate impact on drug safety, efficacy and quality control, for which the marketing approval holders are required to submit a supplementary application, while the approval approach will be “implied approval if no rejection within the prescribed time limit”. Finally, significant changes refer to those that could have apparent impact on drug safety, efficacy and quality control, and the marketing approval holder must obtain approval before their implementation. The Draft for Comment specifies the categories of some changes. For example, changes to the information on the drug package inserts should be managed as significant changes while changes to the name of the marketing approval holder which only adjust the wording should be managed as moderate changes. However, since “slight”, “moderate” and “apparent” are all degree words, the specific categories of other changes will need to be determined according to the actual situation in practice.