Clinical trials (CTs) are research studies that evaluate the clinical, pharmacological, and/or pharmacodynamic effects of an investigational product and are intended to identify Adverse Drug Reactions (ADRs) in humans to determine its safety and efficacy. They are part of the Saudi Food and Drug Authority (SFDA) drug registration requirements for new drugs and biotechnology products. This article will explain the SFDA clinical trials requirements, their application, and other related regulations in Saudi Arabia.

Clinical Trials Phases

There are 4 phases of clinical trials:

Phase I studies typically test new drugs for the first time in a small group of healthy human participants/volunteers to determine a safe dosage range and identify potential side effects.
Phase II studies test treatments that were proven safe in Phase I, in a larger number of human participants, including patients, to verify the investigational drug’s safety and efficacy and to monitor for any adverse effects.
Phase III studies are conducted on larger populations in various regions and countries and are often the final step before a new treatment is approved.
Phase IV studies are conducted after country approval and require further testing in a broader population over a longer timeframe.

Stakeholders Involved

Stakeholder	Role
Sponsor	Individual, company, institute, establishment or organization which takes the responsibilities of starting, managing and financing the clinical trial.
CRO	It is the individual or institution who/which the trial sponsor contract with to perform some or all of the trial’s responsibilities.
CRA	A Clinical Research Associate monitors clinical trials to ensure they are conducted in compliance with the study protocol, Good Clinical Practice (GCP), regulatory requirements and sponsor standards while safeguarding participant safety and data integrity.
Investigator	A clinical trial investigator is a qualified physician or researcher responsible for conducting the study at the site, ensuring participant safety, protocol compliance and the accuracy and integrity of study data.
IRB/IEC	An independent body that reviews clinical trials to ensure participants’ rights, safety, and well-being are protected and that the trial complies with Good Clinical Practice (GCP). Also reviews amendments and safety updates.

Clinical Trial Application (CTAp) Requirements

Sponsors without a legal entity in Saudi Arabia must apply through an SFDA-licensed Saudi Clinical Research Organization (CRO). On the other hand, sponsors with a Saudi legal entity can apply directly or through a CRO.

The SFDA also specified who should apply according to the CT sponsorship. If the Clinical trial is sponsored by:

The Governmental Sectors: The applicant will be the research center, hospital, CRO, or Principal Investigator (PI) authorized by the sponsor.
Private Sector: The sponsor institution or the CRO.
Unsponsored clinical trial: The applicant will be the principal investigator or the CRO.

To initiate the Clinical Trial Application (CTAp) in Saudi Arabia, sponsors or licensed CROs should create an account on the Saudi Clinical Trials Registry (SCTR) to comply with the SFDA clinical trials regulations.

SFDA should be notified if the applicant has used Artificial Intelligence (AI) in the submitted clinical documents.

The continued supply of an investigational product to participants in an SFDA-approved clinical trial is mandatory and is referred to as the post-clinical trial drug access program (PTAP), which is distinct from the Special Access Program (SAP). The requirements for PTAP by SFDA must be submitted within 60 days prior to closure of the original clinical trial.

Bioequivalence studies must be conducted in centers licensed by the SFDA, the local authority, or the Gulf Health Council (GHC).

An import license is required for clinical trial drugs and materials, which may be released during study preparation, while investigational products require full study approval before release.

The Reliance Pathway allows applicants to use a prior RRA approval to expedite SFDA review, subject to SFDA validation of the submitted approval documents.

Amendments

Submitted when changes to the approved trial could impact participant safety, study integrity, or regulatory compliance.

Example: Protocol revisions, Investigator or site changes, Safety-related modifications such as new risk mitigation measures.

SFDA classifies amendments as either substantial or non-substantial.

Substantial Amendment

A change to the clinical trial protocol or supporting documents that may affect participant safety, study validity, or the safety, efficacy, or quality of the investigational product.

Non-substantial Anendment

A change to the protocol or trial-related documents that does not affect participant safety, the scientific validity of the study, or the safety, quality, or efficacy of the investigational product.

Clinical Trials Fees

The applicant must pay fees for the SFDA clinical trial evaluation. Refer to the SFDA fees post for the amount details.

Trials excluded from paying the fees are:

Clinical trials that the Governmental Sectors sponsor.
Unsponsored CT submitted by researchers.
Phase IV studies.

Current approved list of Referenced Regulatory Authority (RRA)

United States Food and Drug Administration -US FDA.
European Medicines Agency- EMA.
United Kingdom’s Medicines and Healthcare products Regulatory Agency- MHRA
Swiss Agency for Therapeutic Products (Swissmedic)

CRO Requirements

Organizational Structure

The CRO organizational structure should include departments or individuals responsible for ensuring the conduct of high-quality, compliant, credible, and accurate clinical trials. The structure should also reflect the services provided to perform one or more clinical trial-related activities; accordingly, it should be updated every five years or as per institutional policy.

Monitoring of the Clinical Trials

Delegation

Sponsors delegate CROs to perform clinical trial monitoring responsibilities. CROs must operate under a written agreement with sponsors that defines all required responsibilities, including those of the Saudi pharmacovigilance system.

Monitoring Methods and Plan

It includes on-site and centralized monitoring, as well as factors to consider when choosing the best approach for a specific Clinical Trial Application (CTAp).

A monitoring plan is an essential part of each SFDA clinical trial. It describes the monitoring methods, responsibilities, and requirements for the CT and should include a brief description of the study, its objectives, and the critical data and procedures.

On-site monitoring is an in-person assessment by the sponsor or CRO personnel at the clinical trial’s site. Factors affecting the extent of the monitoring plan and that may necessitate on-site monitoring are:

Complex Study Design (e.g., adaptive, stratified, or complex dose-titration designs).
Study Endpoints (interpretative or subjective).
Study Population (seriously ill or vulnerable).
Geography
Experience of the Principal Investigator (PI) and sponsor.
The Electronic Data Capture (EDC).
Safety of the investigational product
Stage of the study (initiation and during the early stages of a trial).
Quantity of data

Trial Master File (TMF)

The sponsor is ultimately responsible for the trial activities and oversight. Therefore, the sponsor should grant the Saudi-licensed CRO access to the TMF and specify which parts of the TMF it can access to fulfill its responsibilities. The sponsor or the CRO should implement risk-based Quality Checks (QC) or review processes to ensure that the TMF is up to date and includes all essential documents.

Clinical Research Associate (CRA) Employees

The sponsor and the licensed CRO should select qualified monitors based on education, training, and experience. The SFDA recommended that CRA employees should be:

A citizen or legal resident of Saudi Arabia authorized to work for local companies and organizations.
The sponsor or licensed CRO should submit documents to prove CRA education, training, and experience qualifications in accordance with SFDA requirements.

Clinical Trials Agreement

The sponsors or CRO should submit the clinical trial agreement to the SFDA in bilingual (Arabic and English) and should be reviewed by the legal department, consultation legal office, or a licensed attorney.

Documents & Data Retention

The applicant must retain the essential document(s) and data generated during the clinical trial in Saudi Arabia for at least 15 years after completion or discontinuation of the trial, or for at least 2 years after registering the Investigational Medicinal Product (IMP) with SFDA.

Clinical trials safety reporting:

In the case of any Suspected Unexpected Serious Adverse Reactions (SUSAR), an applicant must report to the SFDA through the National Pharmacovigilance Center by email within 15 days, with a follow-up report in XML format.

If the SUSAR is life-threatening, it must be reported within 7 days, per the International Conference for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline, accompanied by a detailed follow-up report within the next 8 days.