The acceptance criteria for the structure-related impurities of drug substance shall be established from the perspective of safety in the early stage of clinical trials and the structure-related impurities can be divided into impurities with potential genotoxicity and common impurities. The acceptance criteria for impurities with potential genotoxicity can be found in the ICH M7 guideline. For common impurities, the acceptance criteria shall be supported by the results of related toxicology studies. At the confirmatory stage of clinical trials, the structure-related impurities of drug substance shall be established from the perspective of quality.

1. Yes, the stability test data of finished product is required. See the Guidance on Investigational New Drug Application for details.
2. In accordance with Shu Shou Shi Tzu No. 1000078438 Order, in principle, the stability test data can prove the quality, physical as well as chemical properties of the study drug are all within the acceptable range during the course of the trial. Considering the uniqueness and novelty of the new drug substance and the relevant planning for research & development stages, the stability test of the study drug and the clinical trial can be conducted in parallel, but the results of the stability test must prove the drug stability during the course of the trial. Though the stability test of the study drug and the clinical trial can be conducted in parallel, to support the safety of the study drug during the course of the trial, the stability test data of other batches can be submitted to support the safety of the study drug. In accordance with the Wei Shu Yao Tzu No. 0960305902 Order, if the submitted stability test data collected from the 6-month acceleration and 6-month long-term study indicates the physical and chemical properties of the drug is stable, a temporary effective period of no more than two years is estimated. The hard copies of stability test data and experimental data of the above mentioned study drug shall be kept in the manufacture site and shall be in accordance with the Standards for Medicament Factory Establishments.
3. If the submitted stability test data is collected over a period shorter than 6 months at the time of IND application, the updated data shall be submitted to the Ministry of Health and Welfare in the future and a temporary effective period of no more than two years may be granted after submission of the supplementary data of the 6-month acceleration and 6-month long-term study. For clinical trials with an implementation period shorter than 6 months, the stability data required may be determined on a case-by-case basis; however, the data must cover the period of trial conduction.

Please refer to "Clinical Trial Protocol-Guidance on Technical Documents" announced by the TFDA for details.

The Article 79 of the Medical Care Act protects the right of informed consent of subjects and the contents of ICF should include the following information: Study Objectives and Methods, Possible Side Effects and Risks, Anticipated Study Outcome, Other Possible Treatments and Descriptions, and Acceptance of Withdrawal of Consent by Subjects at any time .

According to the requirement of Article 22 of the Regulations for Good Clinical Practice, the ICF shall include explanations of the 20 items listed.
To ensure the review consistency, the TFDA announced "The Main Review Items for Clinical Trial Protocol" and provides a checklist of the items that need to be included in the ICF. Regarding the format of the Informed Consent Form (ICF), see "Clinical Trial Informed Consent Form (ICF) Template" announced by the TFDA.

In addition, if the clinical trial contains pharmacogenomic studies and genetic test is necessary for the trial, the information of test items or methods shall be explained in the ICF for the main study and specify that participation in the trial is not permitted if specimens are not provided. If the pharmacogenomic study is optional, a separate ICF shall be prepared and the format can be found in The reference for the Informed Consent Form (ICF) related to pharmacogenomic studies can be found in the "Reference Guide for the Informed Consent Form (ICF) of pharmacogenomic Studies" announced by the TFDA.

According to the TFDA Order (Wei-Shu-Yao-Tzu No. 0960305954 Letter), for clinical trials that study drugs with a drug permit license issued by the TFDA for academic purpose, the IRB of the trial institution may manage such trials in accordance with relevant regulations of the Medical Care Act if the drug dose is within the original approved range. Also, clinical trials initiated by the investigators for academic research purpose may be submitted to the Ministry of Health and Welfare for review if the IRB of the trial institution has doubts or believes the safety of the trial in doubt. The study reports of such trials that are conducted for academic research purpose shall not be used as the sole basis for registration of the drug. Please proceed in accordance with related rules in the TFDA Order Wei-Shu-Yao-Tzu No. 0940327777.

If collection of human specimens is involved in the trial, depending on the purpose of collection, the Notice for Collection and Use of Human Specimens for Research (Wei-Shu-Yi-Tzu No. 0950206912) and the Human Biobank Management Act formulated by the Ministry of Health and Welfare shall be referenced for processing. In addition, such collection shall be reviewed by the IRB of the trial institution. If the research institution does not have an IRB, other IRBs may be retained to perform the review.

The medicaments (drugs/medical devices) for a clinical trial can only be imported after the clinical trial is approved by the TFDA. The sponsor shall submit a photocopy of the clinical trial approval letter issued by the TFDA along with the Import Authorization Application Form to the TFDA. For related regulations, please see “Guidance on Investigational New Drug Application”.

If a foreign company plans to conduct a clinical trial in Taiwan, the subsidiary of the company, an agent or a CRO shall be retained for the application. According to the “Guidance on Investigational New Drug Application”, the submission of a clinical trial application shall enclose a photocopy of the drug company license. If the applicant is a CRO, the drug company license of the CRO and the power of attorney signed by the sponsor shall be submitted.

Sponsors may go to the CDE website and apply for consultation service online. They have to provide the background information of the drug (for example, the letters issued by the TFDA for prior BSE applications), relevant international and domestic reference papers or information (e.g. Investigator’s Brochure, etc.) and the clinical trial protocol. CDE may give suggestions based on the draft of study synopsis or study protocol provided by the sponsor.

Following bridging study evaluation, those that received the letter stating the waiver of a bridging study is not granted from the TFDA may refer to the following suggestions and select one for future planning:

1. Submit specific updated and effective relevant information in response to the content of the rejection letter as supplementary information, or make an appeal or re-submission of the application.
2. According to the assessment results and relevant regulations, prepare adequate protocol of the bridging study and submit the protocol to the TFDA for review. 

The complete clinical data package (CCDP) shall be submitted and the bridging data package (BDP) shall be included. The BDP refers to pharmacokinetic/pharmacodynamics studies, dose-efficacy response studies, or efficacy and safety proving clinical trials that were conducted in our citizens or East Asian populations. The complete assessment compares whether there is ethnic difference between CCDP and BDP and determines whether a bridging study may be waived. *During the BSE stage, the CCDP data may be provided in the format of summary report.