Data Requirements for Human Drugs Submission

The information presented in this guidance is based on recommendations of the: 

- WHO, as described in the "Guideline on Submission of Documentation for a Multisource (Generic) Finished Pharmaceutical Product (FPP): Quality Part (2010)”;

- ICH, as described in the “M4Q (R1), M4S(R2), and “M4E(R1) (2002)”; and 

- EU, as described in the “Notice to Applicants, Volume 2B: Presentation and content of the dossier (2006)”. 

The data requirements for each application will differ, depending on the drug submission type. However, all the required data should be in accordance with the eCTD structure (i.e. applicants should not modify the overall organization of the eCTD as outlined in this guideline):

a) In case of New Chemical Entity (NCE), Biologicals and Biosimilars ALL the eCTD Modules are required.

b) In case of Generic Products:

In preparing the dossier for generic products, it is acknowledged that certain modules or sections of the eCTD would generally not be applicable and should be marked as such (and not to be deleted).

Please note that for applications of generic drug of a non-SFDA registered reference product should include in addition to the bioequivalence requirements, a comprehensive literature review of the active substance to support the generic product registration. The literature review should be submitted in module 2.5 clinical overview and covers the following aspects:

- The search should be as extensive and relevant as possible

- The rationale for the development of the active substance as well as the generic product. The search should support the efficacy and safety of the active ingredient in each proposed indication.

- Bioequivalence and bioavailability data of the generic product.

- Safety and efficacy of the active substance in each of the proposed indications.

- Methodology of the search used should be stated in detail (database used, keywords used, and filters applied as well as date and time the search was carried on).

- Provide a tabular listing of the identified literature with their citations  and arrange the studies according to the following:

    - Start with the key clinical studies (e.g. confirmatory studies).

    - Well-designed, adequately powered, and preferably multicenter studies.

    - Studies that have registered protocol or registered in clinical trials registries (provide registration status).

    - Evidence from non-randomized controlled trials should be located in a separate section of the table.

    - Post marketing safety studies.

    - If possible, provide study reports for each identified study.

Summarize serious adverse events related to the product (from randomized controlled trials and observational studies as well as periodic safety update reports (PSUR) of the reference product).

- Module 1: Regional Administrative Information

This Module is required to be submitted. It should contain documents specific to SFDA; e.g., application form, proposed labelling, alcohol-content declaration, patents information ... etc. The content and format of this module is further illustrated in this guideline.

- Module 2: Common Technical Document Summaries

The following sections are required to be submitted under Module 2: 

- 2.1 Table of Contents of Module 2-5.

- 2.2 Introduction: 

This section should begin with a general introduction to the pharmaceutical, including its pharmacologic class, mode of action, and proposed clinical use. In general, the introduction should not exceed one page.         

- 2.3 Quality Overall Summary: 

The whole section is required and should reflects the information provided in Module 3. 

- 2.5 Clinical Overview: 

2.5.2 “Overview of Biopharmaceutics”: The summary of the comparative bioequivalence/bioavailability study reports should be provided under this section. In addition, critical analysis of any important issues related to bioavailability that might affect efficacy and/or safety of the to-be-marketed formulation(s) (e.g., dosage form/strength proportionality and influence of food on exposure) should be provided under this section. 

- Module 3: Quality

The whole section is required and the information should be presented according to the structured format described in this guideline.

- Module 4: Non-Clinical Study Reports

Generally not applicable for generic products, however some exceptions may apply.

- Module 5: Clinical Study Reports

It is anticipated that only the following relevant sections of Module 5 will normally be required.

- 5.1 Table of contents for Module 5

- 5.2 Tabular listing of all clinical studies

- 5.3 Clinical study reports

   o 5.3.1 Reports of biopharmaceutical studies

     - 5.3.1.2 Comparative BA & BE Study Reports

The comparative bioavailability/bioequivalence study reports should be presented in Module 5 under section 5.3.1.2 “Comparative BA & BE Study Reports”.

     - 5.3.1.3 In vitro/In vivo Correlation (IV/IVC) study reports:  if available

     - 5.3.1.4 Reports of Bioanalytical and Analytical Methods for Human studies: Bioanalytical or analytical methods for BA/BE or in vitro dissolution studies should ordinarily be provided in the clinical study reports. However, where a method is used in multiple studies, the method and its validation should only be included once in section 5.3.1.4 and referenced in the appropriate individual clinical study reports.

     - 5.3.7 Case Report Forms and Individual Patient Listings: only Case Report Forms (CRFs) for subjects who experienced serious adverse events should be included. All CRFs should be available upon request.

     - 5.4 Literature references

c) Well-Established Use application (WEU):

When an active substance has been used for more than 10 years in a stringent regulatory authority, and its efficacy and safety have been well established, the application for marketing authorization may be based on published scientific literature. 

For medicinal products with a well-established medicinal use, the following shall apply:

- The applicant shall submit Modules 1, 2 and 3 as described in this guideline.

- For Modules 4 and 5, a detailed scientific bibliography shall address non-clinical and clinical characteristics.

The following shall apply in order to demonstrate the well-established medicinal use:

- Factors which have to be taken into account in order to establish a well-established medicinal use of medicinal products are:

o the time over which a substance has been used (must not be less than 10 years),

o quantitative aspects of the use of the substance,

o the degree of scientific interest in the use of the substance (reflected in the published scientific literature) and

o the coherence of scientific assessments.

- The documentation submitted by the applicant should cover all aspects of the safety and/or efficacy assessment and must include or refer to a review of the relevant literature, taking into account pre- and post-marketing studies and published scientific literature concerning experience in the form of epidemiological studies and in particular of comparative epidemiological studies. All documentation, both favourable and unfavourable, must be communicated. It is in particular necessary to clarify that ‘bibliographic reference’ to other sources of evidence (post marketing studies, epidemiological studies, etc.) and not just data related to tests and trials may serve as a valid proof of safety and efficacy of a product if an application explains and justifies the use of these sources of information satisfactorily.

- Particular attention must be paid to any missing information and justification must be given why demonstration of an acceptable level of safety and/or efficacy can be supported although some studies are lacking.

Please note that in the case of generic applications with a well-established use of the active substance, the submission would be considered a generic application and should be made following the generic requirements.

​The following are recommendations for the presentation of the information in the Quality Module for different scenarios that may be encountered:

- For a drug product containing more than one drug substance: one complete “3.2.S” section should be provided for one drug substance, followed by other complete “3.2.S” sections for each drug substance. 

- For a drug substance from multiple manufacturers: one complete “3.2.S” section should be provided for the drug substance from one manufacturer, followed by other complete “3.2.S” sections for each drug substance manufacturer. 

- For a drug product with multiple strengths: one complete “3.2.P” section should be provided with the information for the different strengths provided within the subsections. One complete copy of the dossier should be provided for each strength. 

- For a drug product with multiple container closure systems (e.g. bottles and unit dose blisters): one complete “3.2.P” section should be provided with the information for the different presentations provided within the subsections. 

- For multiple drug products (e.g. tablets and a parenteral product): a separate dossier is required for each drug product. 

- For a drug product supplied with reconstitution diluent(s), the information on the diluent should be provided in a separate part “3.2.P” if the diluent is co-packaged with the drug product. However, if the diluent is not co-packaged with the drug product, the compatibility of the diluent with the drug product should be discussed in 3.2.P.2.6.