• Last updated：2024-08-14
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Technical Dossier Review of Drugs

The Center for Drug Evaluation (hereinafter referred to as the CDE), entrusted by the Taiwan Food and Drug Administration (TFDA), assists in evaluating technical data related to both pre-market and post-approval review.

I.          Pre-market Review

The pre-market evaluation of drugs includes the review of clinical trial protocols, bioavailability/bioequivalence (BA/BE) studies, bridging study evaluations (BSE), and registration of drugs applying for marketing approval. Registration of drug can be categorized into new drug, generic drug, instruction drugs, over-the-counter (OTC) drug , and active pharmaceutical ingredient (API). To ensure the safety of public medication, the CDE also review the Risk Management Plan (RMP) and its assessment report  for drugs with safety concerns (such as known significant risks or potential risks). Additionally, to enhance the quality of APIs used in domestic formulations, the CDE assists the TFDA in the technical evaluation of drug master files (DMF).

(I)        The clinical trial review aims to focus on ensuring that participants engage in well-designed clinical trials using quality-controlled drugs, with adequate safety monitoring and protective measures throughout the trial to safeguard participants' rights.

(II)       The evaluation of BA/BE study protocol and report considers:

1.    The purpose of the BA/BE study and the appropriateness of the reference product selection.

2.    Basic chemical, manufacturing, and control data comparing the test drug and the reference drug.

3.    Reasonableness of the study design

4.    Statistical analysis methods

The study report also includes

1.    Validation of analytical methods for sample content

2.    Study sample analysis

3.    Statistical results of the study.

(III)       Bridging study evaluation involves evaluating the pharmacokinetic/pharmacodynamic or efficacy and safety data of the drug, comparing data from East Asian populations (e.g., Taiwan) with non-East Asian populations to assess whether foreign clinical trial data can be extrapolated to the domestic population, and facilitating the rational evaluation of dosage and administration for domestic patients.

(IV)       The focus of new drug application technical data evaluation is on ensuring:

1.    Chemical, manufacturing, and control data demonstrate good quality control of the API and formulation, with consistent quality across different batches.

2.    Animal pharmacology and toxicology data that support the drug's mechanism of action, enabling a comprehensive assessment of potential toxic reactions.

3.    The basic characteristics of the drug are elucidated by pharmacokinetic/pharmacodynamic data from animals and humans. Drug interaction data and pharmacokinetic information of special population facilitate the evaluation of rational for dosage adjustment of special populations and in combination with other drugs.

4.    Credible efficacy and acceptable safety for the populations with the claimed indications can be demonstrated by clinical trial results, which substantiate the rationality of the claimed dosage and administration.

(V)       The focus of generic drug application technical dossier evaluation is on ensuring:

1.    Chemical, manufacturing, and control data can demonstrate comparable quality between the generic and reference drugs; the quality of its API and formulation is well controlled, and there's consistent quality across different batches.

2.    Pharmacokinetic technical data, such as bioequivalence studies, can demonstrate bioequivalence between the generic and reference drugs, thereby corroborating similar efficacy and safety. Alternatively, in vitro comparison data (dissolution profile comparison or other methods) can confirm bioequivalence under specific circumstances.

(VI)       For drug that category in the Guidelines on the Review of Instruction Drugs , the primary objective is to guarantee consistent quality across various batches, as the main ingredients have been confirmed to be safe and effective. This is achieved through the use of chemical, manufacturing, and control data.

(VII)       The primary focuses of the risk management plan review are the following: the extent to which patients and healthcare providers are adequately informed about potential drug risks, the appropriateness of risk prevention and mitigation measures, the execution method of the risk management plan, and the methods of performance evaluation. On the other hand, the focus of the risk management plan assessment report is on evaluating execution performance, compliance with the risk management plan, and the effectiveness of drug safety monitoring.

(VIII)      The focus of API registration/ Drug master file technical dossier evaluation is on the identification, content, purity, and safety-related quality characteristics of the API to support the quality, safety, and efficacy of the drug.

II.       Post-approval change

After a drug 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 parts that 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 dosage and administration, the review focuses on whether the clinical trial data is sufficient to support the intended changes. For changes in the manufacturing process, manufacturing site, or excipients, the review focuses on whether the drug product remains consistent in quality, demonstrates bioequivalence, or has a similar in-vitro dissolution profile 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 instruction drugs is mainly about indications, dosage and administration,  and package inserts.

III.  Description of the Review Process

Upon submission of an application at the TFDA's Division of Medicinal Products, the project manager (PM) is responsible for administrative tasks and project management, initiating the formation of a review team. The team members, depending on the case type, can include experts in chemical manufacturing control, pharmacology and toxicology, pharmacokinetics and pharmacodynamics, statistics, and clinical. If necessary, the project manager (PM) will convene review meetings based on standard operating procedures. In order to consummate the review report and conclusions, the team leader will preside over these meetings to deliberate on the technical dossier of the case. After the review team completes the review report, it may be submitted for discussion to the TFDA's Drug Advisory Committee/Regenerative Medicine Advisory Committee/Rare Diseases and Drugs Review Committee, if necessary. The project manager (PM) 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 the TFDA’s final decision..