Regulation and Requirements for Conducting Clinical Trials on Drug

Authority: The Saudi Food and Drug Authority.

Clinical Trials: Each research (study) that concerns collecting and analyzing information related to volunteers and patients to reach general knowledge that could be applied to other patients according to the mechanism of diseases occurrence, diagnosis, its spread, or treatment.

Sponsor: An individual, company, institute, establishment or organization that takes the responsibilities of starting, managing and financing the clinical trial.

CRO: An individual or institution with whom trial sponsor contracts with to perform some or all of the trial's responsibilities.

Saudi Clinical Trials Registry (SCTR): An electronic system with an electronic database that includes an official records of all drugs clinical studies in Saudi Arabia to ensure that all received information are accurate and completed along with publishing the minimum amount of information about the clinical trials, which is globally agreed, so it can be viewed by the public.

Institutional Review Board (IRB): An independent research licensing committee that is formed in accordance with the living creature's ethics law and its implementing regulation.

Good Clinical Practices (GCP): An international guideline to control the design, conduct, monitor and review of clinical trial to ensure the quality and accuracy of the trials, in addition to protecting the safety, rights and confidentiality of the participants data.

Clinical trial site: Any institution that is licensed to provide health care services and/or conducting the clinical trials.

Phase IV studies: The studies that are conducted on pharmaceutical products that are registered with Saudi Food & Drug Authority in order to collect more information about the product's safety and efficacy. 

Phase I studies: The clinical studies that are conducted on human for the first time to test the safety of the product. Usually, the trials in this phase are conducted on healthy participants.

Phase II-III studies: Clinical studies that conducted on the patients to test product's safety and efficacy.

Bioequivalence studies: Studies which are conducted to determine any statistical differences in the bioavailability levels between two pharmaceutical products.

Non-Substantial Amendment: An adjustment to the protocol, regarding how to manage the study or any other supported documents in a way that doesn't affect the participant or the scientific value of the study, or the safety, quality and efficacy of the tested product.

Substantial Amendment: An adjustment to the protocol, regarding how to manage the study or any other supported documents that could affect the participant or the scientific value of the study, or the safety, quality and efficacy of the tested product.

Suspected Unexpected Serious Adverse Reaction:  A serious adverse reaction (side effect) that is suspected to be related to research drug, and its nature or seriousness is not aligned with the information mentioned in the investigator brochure.

The applicant: The researcher, study sponsor or the contract research organization (CRO). ​​

1. According to the Saudi Food and Drug Authority law issued on 25/1/1428 H by Royal decree (M/6),  along with its implemented regulation issued by the authority’s (SFDA’s)  board of directors decision number (7-7-1428) dated 25/7/1429 H, and the authority’s memo number (3476) dated 13/2/1431 H, all clinical studies should be registered at the SFDA through the Saudi Clinical Trial Registry system (SCTR), It is important to note that the registration of a clinical trial (registering the trial in the system) does not mean the approval of the trial. For more information about the registration process, you can check the registration guidelines through this link: https://sctr.sfda.gov.sa/Guidance.aspx    

2. The following regulations, memos and guidelines must be followed: 

 Guideline for Good Clinical Practice.

 The Law of ethics of research on living creatures and its implemented regulation, which was issued on 14/9/1431 H by Royal decree number (M/59).

 The memo number (15421) and (15482) dated on 13/5/1434 H in regard to the registration of local institutional review boards (IRBs). 

3. The applicant must be located or have a legal representative inside the Kingdom of Saudi Arabia.

4. If the study sponsor does not have an official presence or a legal representative inside the Kingdom of Saudi Arabia, the contract research organization (CRO) or the principal investigator should be authorized by the study sponsor, the authorization must include all responsibilities related to the trial and all legal procedures.

5. Applicants who can submit an application:

 Clinical trial sponsored by Governmental Sectors: The applicant will be the research center, hospital, CRO or principal investigator who is authorized by the sponsor.

 Clinical trial sponsored by Private Sector:  The sponsor institution or the CRO.

 Unsponsored clinical trial: The applicant will be the principal investigator or the CRO.

6. According to the memo number (9699) which, issued on 23/4/1432H, the applicant must pay a fee 15,000 Saudi Riyals for evaluating the clinical trial file. Clinical trials sponsored by Governmental Sectors, unsponsored trials by researchers and Phase IV studies will be exempt from this fee.

7. Phase IV studies:

A. The applicant can start the clinical trial after obtaining local IRB approval. They should notify the SFDA by registering the trial at the SCTR and sending the requirements listed in Table 1 to the Clinical Trials Department (ct.drug@sfda.gov.sa) within 20 working days after obtaining local IRB approval. The authority reserves the right to suspend the trial if it is not classified as a phase IV study.

B. When changing or adding a clinical trial site, the applicant should notify the SFDA by sending the IRB approval and the researcher obligation form (Form 4) to the email ct.drug@sfda.gov.sa.

C. It is mandatory to obtain SFDA approval before conducting clinical trials on registered drugs that are not phase IV trials and are considered as early phase trials, such as trials for:

 New indication or off-label use

 Change of dosage regimen or route of administration. 

 Change in dosage form.

D. For non-interventional phase IV trials, which aim to gather information about the safety of registered products, the applicant should adhere to the Good Pharmacovigilance Guidelines (GVP).

​8. Early phases trials (phase I,II,III):

A. It is mandatory to obtain SFDA approval before conducting clinical trials, in accordance with the requirements in Table 1. The clinical trial will not be registered if it has started without the authority’s approval.

B. The applicant must annually submit a progress report on the ongoing trials by completing the Progress Report (Form No. 1) and submit it to the clinical trials department through the email ct.drug@sfda.gov.sa . The report must be submitted after obtaining the approval by one year.  However, in case the trial duration is less than one year, the applicant must submit the progress report after half the study duration has passed. In addition, the delegation log for each trial site and proof of adequate training in GCP for all research team members must be submitted.

C. Clinical trials amendments:

 In case of non-substantial amendments, the SFDA should be notified via the annual progress report.

 In case of substantial amendments, it is mandatory to obtain SFDA approval before implementing any amendments, in accordance with the requirements in Table 2.

 The applicant can apply (Implement) amendment immediately if the participants are exposed to hazardous condition or harm during the trial, and inform the authority immediately by sending an email to ct.drug@sfda.gov.sa .

 The applicant must adhere to the requirements in Table 2 If the amendment includes changing the principal investigator, the addition of or the closure of a clinical trial site.

D. Phase I trials:

The Phase I trials must be conducted in an accredited Phase I unit by the SFDA. In addition, the applicant must adhere to the (Guideline on strategies to identify and mitigate risks for first-inhuman and early clinical trials with investigational medicinal products).

​9. Bioequivalence Studies:

A. Having the authority’s approval is essential before conducting the bioequivalence studies, in accordance with the requirements in Table 1.

B. The bioequivalence studies must be conducted in centers that are licensed by the SFDA or the authority or the Gulf Health Council.

10. Importing Drugs/Study Materials Related to Clinical Trials:

According to the import and export procedures guideline which is published in the SFDA’s website, it is mandatory to obtain an importation license for drugs or study materials that are related to clinical trials from the drug’s importing license department at the Operation sector.

​11. Exporting Clinical Trial Bio-samples:

A. The applicant must adhere to the regulations of the Research Ethics Code on Living Creatures, issued by Royal decree no. M/59 on 14/9/1431 H, which regulates bio-sample exportation.

B. The applicant must provide the SFDA with a copy of the local IRB exportation permission.

​12. Reporting Clinical Trials Adverse Drug Reactions:

A. It is mandatory to inform the SFDA immediately about any suspected unexpected serious adverse reactions (SUSAR) for local cases and global cases for trials ongoing in Saudi Arabia on “Form No. 2” as soon as possible, no later than 15 days after the event, followed by the follow-up report as soon as possible. If the SUSAR is fatal or life threatening, the SFDA must be informed as soon as possible, no later than seven days in accordance with the ICH-E2A guideline, with a follow-up report succeeding it within eight days.

B. It is mandatory to inform the SFDA of any SUSAR that occurs internationally for an investigational drug involved in ongoing clinical trials in Saudi Arabia as soon as possible by adopting the same procedures mentioned above.

C. SUSARs should be reported through the National Pharmacovigilance Center via email (ICSR.DRUG@sfda.gov.sa). It is necessary to provide the SCTR number and the e-mail subject must be “SUSAR Case.” 

D. The applicant must send SUSARs in (XML) format in addition to completing the (CIOMS) Form. It is adequate to send the report to the attached Form 2 if it is received from the researcher. 

E. The applicant must annually send a development safety update report (DSUR) to the authority with the SCTR number.

​13. Completion, Termination, or Suspension of Clinical Trials:

A. The SFDA has the right to temporarily suspend the clinical trial in order to protect human subjects in case of the following:

 Non-compliance with Good Clinical Practice.

 Safety concerns affecting participants.

 Non-compliance with SFDA regulations and requirements.

While the clinical trial is temporarily suspended, the SFDA will launch an investigation. Once the investigation is complete, the SFDA will decide on one of the following:

1. Lift the suspension. 

2. Terminate the study.

B. The applicant must inform the SFDA within 60 days with proof of IRB approval regarding completing, terminating or suspending the clinical trials. In addition, it is mandatory to submit the final clinical trial report within one year of the end of the trial in accordance with ICH-E3 guidelines.

​14. The Qualifications of the Clinical Trial Research Team. 

To ensure the safety of clinical trial subjects, all members of the research team must provide proof of adequate training in GCP. It is mandatory that the latest training be completed no longer than three years ago.

​15. Study Monitoring:

The applicant must provide SFDA with a clinical trial monitoring plan that complies with the Good Clinical Practices (GCP) guideline. Moreover, a curriculum vitae and a GCP certificate must be provided for the monitor of the study. 

16. The period (timeline) needed to respond to the applicant requests after completing all the required documents is:

 10 working days for phase IV trials.

 15 working days for bioequivalence studies.

 30 working days for phase III trials.

 40 working days for phase II trials.

 60 working days for phase I trials and the biological products studies (Vaccines, gene therapy, stem cells and biosimilars).

The applicant will be notified if there are any missing documents, deficiencies or comments related to the trial file and the timelines stated above will paused. The time taken to respond to the SFDA will not be considered within the specified timeline. However, the requirements should be provided within 90 days otherwise the application will be rejected if the applicant fails to provide these requirements during this period, and a new application should be submitted.

​17. Clinical Trials in Special cases

a. The SFDA has the right to take the appropriate measures regarding regulatory requirements and applications review priority in the following cases:

- Pandemics, epidemics and national emergencies declared by the Ministry of Health and the Public Health Authority.

- Trials on drugs submitted for registration purposes with no alternative treatment in Saudi Arabia.

- Trials on drugs related to national initiatives from the SFDA and related bodies.

b. Special cases requests are processed according to the following criteria:

- Applications will be given priority in submissions.  

- Priority review.

- Priority regulatory consultation meetings.

- Pandemics, epidemics and national emergencies declared by the Ministry of Health and the Public Health Authority: Parallel submission is acceptable without requirements no. (2-8-9-10-11-15-16-17-18-19-20) in Table 1 during initial submission, with commitment to completing the remaining requirements during the application review period.

​18. The applicant must submit the trial documents electronically via SFDA cloud service organized in folders in accordance with Table 1 in the same day of the booked appointment via the electronic system. Moreover, the applicant can request the SFDA cloud link via email (ct.drug@sfda.gov.sa) in case a link was not received. Furthermore, it must be ensured that its contents can be copied, searched and are not in image format.​