1. The primary purpose of pre-market review is to evaluate whether the submitted technical dossier is sufficient to justify approval in respect of safety, efficacy and quality of a drug. The pre-market review includes the clinical trial protocol review, the bridging study evaluation and the application for drug marketing approval. Applications for marketing approval include the following types: New Drug Application (NDA), Abbreviated New Drug Application (ANDA) for generic drugs and Over-the-Counter (OTC) Application. To ensure safe use of drugs, Risk Management Plan (RMP) is requested for known or potential serious risks at pre-market evaluation. CDE will evaluate the RMP and further follow the corresponding assessment reports. Furthermore, with a view to increase the quality control of drug substances, CDE also supports the TFDA in reviewing the technical dossier of Drug Master File (DMF).
   
   • The Clinical Protocol Review primarily focuses on ensuring that a clinical trial is well designed and experimental drug is of good quality control. Adequate safety monitoring and protective measures are in place to protect the trial subjects’ rights and interests.
   • The review of bioavailability/ bioequivalence (BA/BE) study protocol and report is focused on the following: (1) The reference product should appropriately chose for its study purpose, (2) The CMC documents of the investigational products, (3) Study is well design (study population, dosing regimen, sampling time, administration dose…etc.), (4) Statistical method. In addition, (1) Bioanalytical method validation report, (2) Study sample analysis, and (3) The statistical result are also the main focus of reviewing BA/BE study report
   • The Bridging Study Evaluation is to evaluate whether foreign clinical trial data can be extrapolated to the corresponding population in Taiwan (or east-Asian), then making a justification of the administration and dosage of a drug prescribed for the people in Taiwan. This assessment is carried out through evaluating pharmacokinetics (PK)/ pharmacodynamics (PD) data and data of efficacy and safety in the context of a comparison between east Asian and non-east Asian ethnic groups.
   • The technical dossier review for a New Drug Application (NDA) focuses on the followings: (1) To assess whether the chemistry, manufacturing and controls (CMC) data is sufficient to demonstrate adequate control over the quality of drug substances and drug products, as well as to exhibit stable quality consistency among different batches. (2) To assess whether the animal pharmacological and toxicological data are sufficient to justify the action mechanism of a drug and to fully evaluate potential toxic reactions. (3) To understand the fundamental pharmacokinetics (PK)/ pharmacodynamics (PD) properties of a drug based on the studies of PK/PD data on animals and humans, and to justify the adjustment of the administration and dosage of a drug for the use in special populations or in concomitant with other drugs through analyzing the PK data on this particular group and the data of drug interaction.(4) To assess whether the human clinical trial results are able to demonstrate that a drug is acceptably safe and credibly effective for the claimed indications and to justify the claimed administration and dosage of the drug.
   • The technical dossier review for Abbreviated New Drug Application (ANDA) focuses on the followings: (1) To assess whether the chemistry, manufacturing and controls (CMC) data is able to demonstrate that a generic drug and its reference listed drug (RLD)are identical in quality, as well as to exhibit good quality control over drug substances and drug products and to exhibit stable quality consistency between different batches; (2) To assess whether the data of bioequivalence (BE) study is able to demonstrate the bioequivalence between a generic drug and its RLD in order to justify that the generic drug has equivalent efficacy and safety to its RLD. For certain circumstances, in vitro comparison studies (like dissolution profile comparison or other type of in vitro study) might be used to support bioequivalence.
   • Since the efficacy and safety of the drug substances of OTC drugs in line with “Guidelines on the Review of Instruction Drugs” have already been proved and established, the technical dossier review of an OTC application focuses on whether the chemistry, manufacturing and controls (CMC) data is able to demonstrate adequate quality control over the drug products and to exhibit stable quality consistency between different batches.The technical dossier review of a Risk Management Plan (RMP) focuses on whether the patients and health care providers are fully informed about the drug’s potential risks, the appropriateness of the risk prevention and minimization measures, the implementation of RMP and assessment tools of RMP. The review of RMP assessment report focuses on the evaluation of RMP effectiveness, compliance and drug safety surveillance.
   • The technical dossier review of a Drug Master File (DMF) focuses on quality issues associated with the identity, assay, purity and safety of the drug substances in order to support the quality claims of the drug product on quality, safety and efficacy.

After a drug product is approved for marketing, any variations of the approved items are subject to the application for post-approval changes. The CDE assists the TFDA in performing the technical dossier review on applications of post-approval changes of package insert, indication, administration and dosage, drug category, manufacturing site, dosage form, specification and analytical method, excipients, primary packaging materials, etc., for those technical part may be involved. The focus of the review of post-approval changes depends on the contents of the applications. Generally speaking, for changes in indications or administration and dosage, the review focuses on whether the clinical trial data is sufficient to support the intended changes. For changes in manufacturing process, manufacturing site or excipients, the review focuses on whether the drug product remains consistent in quality, demonstrates bioequivalence, or has similar in-vitro dissolution curves before and after the changes. For changes in specification and analytical methods, the review emphasizes on whether the basis supporting such changes is justifiable and whether such changes can still ensure the quality control of the drug product. The review of post-approval changes of OTC is mainly about indications, administration and dosage, packaging types, drug category and the contents of package inserts.

Applications should be filed via the contact window of the Division of Medicinal Products of the TFDA. Upon the CDE’s receipt of an application, an administrative reviewer will be appointed to take charge of the administration and the management of this case. A review team will be formed for each case. Depending on the type of the application, a review team may consist of experts in chemistry, manufacturing and controls (CMC), pharmacology/ toxicology, pharmacokinetics (PK)/ pharmacodynamics (PD), statistics, and clinical. The administrative reviewer shall follow the SOP to convene review team meetings. The team leader will conduct the meeting to discuss the technical dossiers and draw conclusions to complete the review report. If deemed necessary, the review report may be submitted to the Drug Advisory Committee for discussion. The administrative reviewer in charge of the case will put together the CDE final review report and the Drug Advisory Committee’s recommendations, and submit the results for government officials’ approval and instructions.