High-quality clinical evidence is essential to secure a Marketing Authorization Application (MAA) in Saudi Arabia. To obtain marketing authorization for new medicines, benefit-risk clinical trials must be established and sponsored by the applicants. In certain situations where these sponsored trials are not available, the Saudi Food and Drug Authority (SFDA) may accept Literature-Based Submissions (LBS). Note that the exact SFDA drug registration requirements apply to such applications.
This article presents the rules for LBS based on existing clinical research, including bioequivalence studies, clinical trials, and systematic reviews. This, in turn, makes evaluation easier and saves time.
Table of contents
Examples of Literature-Based Submission
In the following situations, the SFDA allows LBS:
| Product Category | How is it defined? |
|---|---|
| Generic Drugs | A Generic Drug contains the same active ingredient as a reference product. If the reference product is not registered with the SFDA, the applicant must rely on published clinical research (e.g., bioequivalence studies) to support the submission. |
| Known Active Substances | A Known Active Substance is an active pharmaceutical ingredient already authorized in Saudi Arabia and being applied for in a different form, strength, route of administration, or indication. KAS products mostly fall under the variations in the SFDA system. |
Application Submission Process
Pre-Submission Meeting
The SFDA) advises the applicant to arrange a meeting with the authority prior to three months of submission of an application to discuss:
- The rationale behind the application, including the objective and anticipated benefits.
- Product type (new, generic, or Known Active Substance).
- Clinical data requirements.
- Literature search methodology
LBS Requirements for Published Clinical Research Data
All data submissions must follow the eCTD (electronic Common Technical Document) framework. The clinical research data needed for each application depends on the type of product:
For Generic Products
- For an SFDA-registered Reference Product: Must follow the SFDA bioequivalence guideline.
- For a non-SFDA-registered Reference Product, submit literature-based evidence in accordance with the product’s worldwide registration status, using the electronic Common Technical Document (eCTD) format. Key sections include:
| Requirements as per eCTD format | Registered with SRA | Not Registered with SRA |
|---|---|---|
| Module 1 | Clinical expert info | Clinical expert info |
| Module 2 | ||
| • Product development rationale | ✓ | ✓ (with current market registration status) |
| • Biopharmaceutics | ✓ | ✓ |
| • Clinical pharmacology | ✓ | ✓ |
| • Efficacy & safety | • Literature review • Insufficient evidence: Meta-analysis of clinical data | • Systematic literature review • Insufficient evidence: meta-analysis of clinical data. |
| • Orphan Drugs | Exempted | Exempted |
| • Literature search methodology including keywords, databases, filters, date and time | ✓ | ✓ |
| • Tabular listing of studies | ✓ | ✓ |
| • Serious Adverse Events (ADEs) & Periodic Safety Update Reports (PSURs) of reference product | ✓ | (including post-marketing safety data) |
| • Benefit-risk evaluation | ✓ | ✓ |
| • Full-text references (PDFs) | ✓ | ✓ |
For Known Active Substance Product
- It applies when the drug product containing the active ingredient is already marketed in Saudi Arabia in a new dosage form, strength, route, or indication, often classified by the SFDA as a variation.
- The SFDA assesses each case individually. Ensuring all submissions meet the required standards and guidelines facilitates a smooth review process.
- The authority may accept literature-based evidence or request additional clinical data, for instance, company-sponsored trials in case LBS is not sufficient.
- Applicants shall submit a summary report of published clinical research, including:
- Literature search methodology
- Clinical development program (if any)
- Study details (tabular listing, results)
- List of relevant literature and reference materials.
Steps to Literature Search Strategy
A scientifically valid literature search strategy is considered the key determinant of success.
- Step 1: Formulate a question using the PICO (Patients, Populations or Problems, Intervention, Comparison, Outcome) structure.
- Step 2: Search: Use standardized search terms MeSH using ANDOR/ Boolean operators in PubMed, i.e., literature from MEDLINE, to make results comprehensive and precise.
- Step 3: Relevance screening: Apply inclusion criteria. Document the abstract/full-text review process.
- Step 4: Assess Study Quality: Apply a structured quality assessment using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the strength and reliability of the selected studies.
- Step 5: Data Extraction and Analysis: Using a structured extraction template, conduct a double review, assess the risk of bias using appropriate tools (e.g., the Cochrane Risk of Bias Tool 2 for randomized controlled trials and the ROBINS-I tool for non-randomized studies) , and perform a meta-analysis if applicable.
- Step 6: Report Findings: The data are summarized under clear headings: intro, methods, results, discussion, and conclusions. There is also a table of key studies and a complete reference list.
Registration Support
PharmaKnowl Consulting delivers expert regulatory guidance aligned with the SFDA’s expectations for literature-based submissions. We support your submission eligibility, document organization in accordance with eCTD standards, and overall compliance.
You may contact us to help you navigate your journey toward success.
About the Author
Contributed by the PharmaKnowl regulatory affairs team, based in Riyadh. Written and reviewed by our SFDA-experienced consultants.
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