Technical Dossier Evaluation on Drugs
Introduction
Technical Dossier Review of Drugs
The Center for Drug Evaluation (CDE) is commissioned by the Ministry of Health and Welfare (MOHW) and the Taiwan Food and Drug Administration (TFDA) to assist in pre- and post-market technical dossier review of medicinal products.
  • Pre-market Evaluation

    The primary purpose of pre-market review is to evaluate whether the technical dossier submitted by an applicant is sufficient to justify the safety, efficacy and quality of a drug. The pre-market review includes the clinical 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 Application (OTC). Furthermore, with a view to increasing the quality control of active pharmaceutical ingredients (APIs) used in drug products, the 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 Bridging Study Evaluation is to evaluate whether foreign clinical trial data can be extrapolated to the corresponding population in Taiwan so as to justify the administration and dosage of a drug prescribed to 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 Asian and non-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 APIs and drug products, as well as to exhibit stable quality consistency among different batches. (2) To assess whether the animal pharmacological and toxicological data is 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 study 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 generic product application 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 product 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 reference product in order to justify that the generic drug has equivalent efficacy and safety to its reference product.
    Since the efficacy and safety of the active ingredients of OCT drugs (such as: antitussives and expectorants, insect repellents, ophthalmic preparations, anti-nausea agents, general dermatological agents for external use, anti-allergic agents, general cold relief, gastrointestinal agents, laxatives, and antipyretic analgesics) have already been proved and established, the technical dossier review of an OTC drug 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 Drug Master File (DMF) focuses on the manufacturing process control, as well as the APIs’ quality properties, especially about identification, content purity and safety related characteristics are able to justify the quality, safety and efficacy of a drug.

  • 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, direct 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 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. The review of post-approval changes of non-prescription drugs is mainly about the changes in indications, administration and dosage, packaging types, drug category and the contents of package inserts.

  • A Description of the Review Process

    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 medicine. 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.