Advanced therapy medicinal products in Saudi Arabia: Regulation and development

Abstract

Advanced therapeutic medicinal products (ATMPs) such as gene, somatic cell, and tissue-engineered therapies have transformed modern healthcare by treating previously unmanageable genetic, oncologic, and degenerative diseases. Although regulatory and developmental frameworks for ATMPs are established in the United States, Europe, and China, limited data exist on their implementation in emerging markets such as Saudi Arabia. This review provides the first comprehensive analysis of ATMP regulation and development in Saudi Arabia while offering novel insights into the nation's evolving clinical trial landscape, regulatory infrastructure, and biomanufacturing capabilities. We conducted a narrative review of the Saudi Food and Drug Authority (SFDA) guidelines, peer-reviewed literature, and clinical trial registrations from 2010 to 2025. As of 2025, the SFDA has approved eight ATMPs, including chimeric antigen receptor T-cell therapy (CAR-T) therapies, adeno-associated virus (AAV) based vectors, and clustered regularly interspaced short palindromic repeats (CRISPR) based therapies, reflecting growing regulatory maturity and international alignment. Clinical trial activity continues to expand, with a concentration in oncology, hematology, and rare genetic diseases. National research institutions such as the King Faisal Specialist Hospital and Research Centre (KFSHRC) and King Abdullah International Medical Research Center (KAIMARC) have pioneered advances in CAR-T manufacturing, while biobanking initiatives are driving translational research. Despite ongoing challenges in workforce capacity, good manufacturing practice (GMP) infrastructure, and reimbursement mechanisms, Saudi Arabia is positioned to become a regional leader in advanced therapies through continued regulatory innovation, local manufacturing, and international collaboration.

Abbreviations

ATMPs

Advanced Therapy Medicinal Products

SFDA

Saudi Food and Drug Authority

KFSHRC

King Faisal Specialist Hospital and Research Centre

KAIMRC

King Abdullah International Medical Research Center

CAR-T

Chimeric Antigen Receptor T Cell

1. Introduction

Advanced therapeutic medicinal products (ATMPs) are a distinct class of advanced biopharmaceutical products including gene therapy, somatic cell therapy, and tissue-engineered products [1,2]. Unlike conventional small-molecule or protein-based drugs that manage symptoms, ATMPs act at the cellular and molecular levels to repair, replace, or modify dysfunctional genes, cells, or tissues, thereby treating the cause of disease [3,4]. Their therapeutic potential can lead to robust and curative outcomes in conditions previously considered untreatable, such as inherited genetic disorders, hematologic malignancies, and degenerative diseases [5,6]. Therefore, ATMPs have transformed personalized and regenerative medicine by shifting the therapeutic standards from symptom management to disease modification and tissue restoration [6].

The approval of ATMPs follows a stringent multistage process that guarantees product quality, safety, and efficacy prior to marketing. Generally, developers are required to provide regulatory bodies with thorough information on their risk management plans, chemistry manufacturing and controls (CMC), as well as non-clinical and clinical studies. These submissions are subject to scientific evaluation and inspection in line with good manufacturing practice (GMP) guidelines and benefit–risk assessments to verify the therapeutic value prior to patient use [3,7].

Internationally, the approval of ATMPs has transformed the modern medicine landscape and signaled a major shift in the treatment of complex diseases. This has resulted in the regulatory approval of approximately 50–60 ATMPs worldwide [8]. Below is an overview of all cumulative approvals demonstrating the global reach of advanced therapies beyond traditional Western markets. The U.S. Food and Drug Administration (FDA) has approved 46 products [9], and the European Medicines Agency (EMA) has authorized more than 27 ATMPs by mid-2025 [10], which indicates an acceleration in recent years. Moreover, the Saudi Food and Drug Authority (SFDA) has strategically approved eight products between 2020 and 2025 [11]. These approvals span three main categories: gene therapy, medicinal products, and tissue engineering products. Gene therapy medicinal products include breakthrough treatments such as Luxturna for inherited blindness, Zolgensma for spinal muscular atrophy, and Casgevy as the first CRISPR-based therapy approved across multiple authorities. Medicinal products featuring transformative CAR-T gene therapies, such as Kymriah, Yescarta, and Carvykti, have achieved multiregional approval. Saudi Arabia's implementation of a breakthrough medicine program has facilitated rapid access to innovative therapies, as exemplified by Casgevy's approval within one year of global authorization [12,13].

Globally, regulatory agencies have developed specialized frameworks to address the unique scientific and clinical challenges posed by ATMPs. The EMA established the Committee for Advanced Therapies (CAT) to oversee ATMP evaluation, coupled with initiatives such as the Priority Medicines (PRIME) scheme to accelerate access to innovative therapies [14]. In the United States, the FDA regulates ATMPs through the Center for Biologics Evaluation and Research (CBER), which provides expedited pathways such as the Regenerative Medicine Advanced Therapy (RMAT) designation [3,15]. In China, the National Medical Products Administration (NMPA) has implemented significant regulatory reforms, including dedicated guidelines for ATMP development and multiple expedited review programs [16]. Similarly, Japan's Pharmaceuticals and Medical Devices Agency (PMDA) has pioneered a conditional, time-limited approval system to enable earlier access to regenerative therapies while maintaining post-market oversight [17].

Driven by the National Vision 2030 initiative, which emphasizes growth of the biotechnology sector and advancement of healthcare innovation, Saudi Arabia has made crucial strides toward establishing a comprehensive regulatory framework for ATMPs [18]. This is consistent with its broader goals of achieving pharmaceutical self-sufficiency, encouraging local manufacturing, and facilitating international collaboration. However, the regulation and development of ATMPs in Saudi Arabia present unique challenges and opportunities that differ from those encountered in more mature markets, including a shortage of skilled professionals in bioprocessing and clinical research, as well as limited GMP-compliant facilities for large-scale production. Furthermore, the complexity and high cost of ATMP manufacturing further delay local capacity building. In addition, Saudi Arabia's capacity for large-scale production remains constrained by the high cost of establishing and maintaining GMP-compliant facilities, as well as reliance on imported technologies [3,18]. Addressing these barriers will require coordinated investment in workforce development, GMP infrastructure, and cross-sector collaboration to strengthen the Kingdom's ATMP ecosystem.

This review aims to provide a comprehensive overview of the regulatory landscape governing ATMPs in Saudi Arabia and to highlight the current state of their development in the country. It also examines the opportunities and challenges associated with advancing ATMPs and proposes strategic considerations for fostering a robust, innovation-driven environment for these transformative therapies.

2. Regulatory framework and process

2.1. SFDA regulatory guidelines

The SFDA's regulatory framework for ATMP comprises guidance documents covering submissions, classification criteria, CMC requirements, and GMP standards. Table 1 summarizes the key SFDA documents clarifying ATMP regulation. These documents are intended to standardize the evaluation processes and provide regulatory clarity for stakeholders. The framework aligns with FDA and EMA guidelines, thereby reflecting an adaptation of established international regulatory approaches. The degree of harmonization between the SFDA guidelines and international standards varies across different aspects of ATMP regulation. While the technical requirements align substantially with the FDA and EMA frameworks, implementation practices and enforcement mechanisms may differ. This regulatory approach aims to facilitate market access to international products while maintaining national regulatory rules [19,20]. This approach led to achieving WHO Maturity Level 4 for regulatory capacity, which represents the highest level of recognition among national regulatory authorities [27,28]. This achievement demonstrates the regulatory infrastructure's ability to evaluate complex therapeutic products and maintain international regulatory oversight standards.

Table 1.

Key SFDA documents supporting ATMP regulation.

Subject	Document	Summary	Key points
General	SFDA Guideline on Classification of Advanced Therapy Medicinal Products [19].	Describes definitions and classification criteria for ATMPs, including gene therapy, somatic cell therapy, and tissue-engineered products.	Supports stakeholders such as pharma companies and manufacturers in determining if their product qualifies as an ATMP and which regulatory path applies.
	Guidance for submission [20].	Provide guidance on procedures for submitting a new Marketing authorization (MA) •Variations of MA •Renewal of MA •eCTD Baseline Submission. •Migration dossiers to SFDA, including registration platform use and document formats.	Clarifies regulatory submission expectations and facilitates early communication with SFDA.
CMC	Guidance on Submission of CMC Information for Human Gene Therapy Clinical Trial Applications	Details CMC requirements for gene therapy products, including vector design, manufacturing, and control. For evaluating the Chemistry Manufacturing and Control (CMC) Information sections of Investigational New Drug Applications (INDs) that are submitted to the Saudi Food and Drug Authority, this guideline covers the particular documentation requirements. The following guidelines serve as the basis for the standards outlined in this guideline: •The FDA's Human Gene Therapy INDs Content and Review of CMC Information [21]. •The EMA Guideline on the standards for high-quality documentation pertaining to clinical studies of biological investigational medicinal products [22]. This document's aim is to address the quality needs of an investigational medication for a specific clinical trial; it does not offer advice on a company's broader approach to medication development.	Supports structured documentation for gene therapy IND submitted to the SFDA
	Guidance on Submission of CMC Information for Cell-based Clinical Trial Applications [23].	This guideline covers the documentation needs for assessing the CMC information sections of INDs that are submitted to the Saudi Food and Drug Authority.	Clarifies CMC documentation for cell therapy IND
	Draft Annex for CAR T CELL (from https://istitlaa.ncc.gov.sa/) [24].	Provides technical guidance specific to CAR T-cell therapy, covering vector engineering, transduction, and potency.	Supports product-specific controls for genetically modified T cells and in-process controls.
GMP	Updated Annex A2 – Manufacture of ATMPs (GMP Guide) [25].	Supplements GMP guidance to address ATMP-specific manufacturing processes, including gene and cell therapy.	Clarifies cleanroom requirements, aseptic processing, and traceability across the ATMP lifecycle
Clinical	Expedited Program for Rare Disease/Breakthrough Program (e.g., Casgevy) [26].	Establishes a fast-track regulatory pathway for new drugs targeting serious or life-threatening conditions, such as ATMPs.	Enables accelerated review timelines for innovative therapies with high unmet medical need.
SFDA Advice	SFDA Scientific and Regulatory Advice	Overview of the procedure for obtaining SFDA scientific and regulatory advice	Provide guidance to applicants in preparing regulatory requests.

2.2. Classification of ATMP

ATMPs include genetically engineered molecules and modified cellular products designed for therapeutic applications. These products use recombinant DNA technology and cellular modifications to achieve therapeutic, prophylactic, or diagnostic outcomes. The SFDA has established a comprehensive classification system for ATMPs in accordance with its ATMP classification guidelines [19]. This system categorizes ATMPs into three primary categories with defined regulatory criteria and evaluation processes, as illustrated in the classification decision tree (Fig. 1, Fig. 2). Gene Therapy Medicinal Products (GTMPs) are biological medicinal products containing recombinant nucleic acid sequences intended to modify or regulate gene expression for therapeutic purposes [29,30]. Cell-Based Medicinal Products (CBMPs) encompass therapies involving cells or tissues that have been substantially manipulated or are intended for functions different from their original biological role in the donor [30]. CBMPs exert therapeutic effects through pharmacological, immunological, or metabolic mechanisms and include two subcategories: somatic Cell Therapy Medicinal Products (sCTMPs) and tissue-engineered products (TEPs). Combined ATMPs are products that incorporate medical devices or active implantable medical devices as integral components, in which cellular or tissue components contain viable cells or nonviable elements that provide the primary therapeutic action. For these classified products, the SFDA provides guidance that covers the CMC information requirements for both gene therapy and cell-based clinical trial applications, as listed in Table 1 [25]. These guidelines address the controls for starting materials, traceability requirements, manufacturing processes, analytical testing protocols, stability studies, analytical comparability assessments, and consistency standards across multiple manufacturing sites for substances and drugs. For combined ATMP products, the SFDA Medical Device Department provides additional regulatory guidance through the MDS-REQ1 and MDS-G008 documents, which address integrated device components and their regulatory requirements [31].

Fig. 1.

Workflow for the classification of advanced therapy medicinal products (ATMPs) and gene therapy medicinal products (GTMPs) under the SFDA framework

This flowchart illustrates the decision-making process used by the Saudi Food and Drug Authority (SFDA) to determine whether a product qualifies as an ATMP. The classification is based on product composition, mechanism of action, and degree of manipulation. GTMPs are defined as biological medicinal products containing recombinant nucleic acid sequences intended to modify or regulate gene expression for therapeutic purposes. Abbreviations: ATMP, advanced therapy medicinal product; GTMP, gene therapy medicinal product.

Fig. 2.

Evaluation pathway for Cell-Based Medicinal Products (CBMPs), including Somatic Cell Therapy Medicinal Products (sCTMPs) and Tissue-Engineered Products (TEPs), within the SFDA regulatory framework

This diagram presents the assessment pathway used by the Saudi Food and Drug Authority (SFDA) to determine the classification and quality-control requirements for CBMPs. The pathway includes the evaluation of donor eligibility, degree of manipulation, intended function, and therapeutic mechanism (pharmacological, immunological, or metabolic). It indicates the sub-categorization into somatic cell therapies and tissue-engineered products, with reference to Chemistry Manufacturing and Control (CMC) data required at each stage. Abbreviations: CBMP, cell-based medicinal product; sCTMP, somatic cell therapy medicinal product; TEP, tissue-engineered product; SFDA, saudi food and drug authority; CMC, chemistry manufacturing and controls.

2.3. ATMP review processes and regulatory pathways

The SFDA has established structured review procedures for ATMP applications that incorporate both standard and expedited regulatory pathways. The evaluation process follows a sequential framework that begins with pre-submission consultations and proceeds through electronic dossier submission, technical and business validation, scientific assessment (including dossier review, facility inspection, and product testing when applicable), pricing evaluation, and final licensing decisions by the Registration Committee [32,33].

To foster innovation and regulatory efficiency, the SFDA provides early engagement opportunities for product developers during the classification and pre-submission phases. Several regulatory pathways are available to facilitate timely access to critical therapies. These include the standard pathway for full scientific assessments of innovative or complex products, the abridged pathway for products previously approved by at least one reference authority (e.g., FDA or EMA), and the verification pathway for products approved by multiple reference agencies with harmonized labeling and manufacturing information.

Expedited mechanisms include the Priority Review Pathway, which applies to medicines addressing serious or life-threatening conditions or fulfilling unmet medical needs. This designation must be requested prior to submission and is typically assessed within 15 working days. Products granted Priority Review benefit from approximately a 40% reduction in evaluation timelines, with review durations for biologics shortened from 405 to 243 working days. Eligibility also extends to the first biosimilar of an innovative product approved in Saudi Arabia [33,34]. Although the abridged and verification pathways were originally developed for biologics, they were previously applied to certain ATMPs prior to the issuance of the updated ATMP classification guidance in 2023, which now defines dedicated regulatory routes for advanced therapies [33].

In parallel, the SFDA conducts inspections of manufacturing facilities to ensure compliance with good manufacturing practice (GMP) requirements [25]. Comprehensive GMP guidelines have been issued, including Annex A2: Manufacturing of ATMPs for Human Use. This annex establishes tailored regulatory and quality requirements applicable to both investigational and market-authorized ATMPs, including products manufactured in hospital settings and under compassionate use programs. It addresses critical aspects such as aseptic processing, product characterization, and risk-based quality management. An overview of the regulatory review workflow is presented in Fig. 3. Following market authorization, ATMPs are subject to post-marketing surveillance to ensure their continued safety, quality, and clinical performance.

Fig. 3.

Regulatory review workflow for advanced therapy medicinal products (ATMPs) at the Saudi food and drug authority (SFDA)

This figure illustrates major steps, from classification to product licensing. The process includes consultations and pre-submission meetings, followed by classification and online submission for registration. Applications undergo technical and business validation by a Registration Committee before proceeding to scientific assessment, pricing, and final product licensing. This figure summarizes sequential steps of the ATMP evaluation process at SFDA, while encompassing pre-submission consultation, dossier submission through the online platform, technical and business validation, scientific assessment (including inspection and testing when applicable), and final licensing by the Registration Committee. The post-authorization phase covers pharmacovigilance, periodic safety updates, and Good Manufacturing Practice (GMP) inspections. Abbreviations: ATMP, advanced therapy medicinal product; SFDA, saudi food and drug authority; GMP, good manufacturing practice.

2.4. The post-marketing surveillance program

Post-marketing surveillance (PMS) is a structured, coordinated, and continuous process for monitoring pharmaceutical products throughout their lifecycle to ensure that quality-compliant products remain available to the public. From a quality management perspective, PMS constitutes a core responsibility of the quality department following market authorization and is distinct from pre-market regulatory review activities. Post-approval quality oversight includes trend analysis of critical quality attributes, monitoring batch-to-batch consistency, managing quality-related signals, overseeing post-approval changes, and ensuring continued compliance with approved manufacturing specifications [33].

For ATMPs, PMS is particularly critical due to their inherent biological complexity, manufacturing variability, and potential long-term clinical effects. Real-world data on product quality and therapeutic performance provide essential input for ongoing benefit–risk assessment. Continuous monitoring enables the identification of emerging trends, supports demonstration of long-term product robustness, and informs risk-based regulatory decision-making across the ATMP lifecycle. Effective tracking mechanisms facilitate systematic collection of post-marketing quality data, integration into lifecycle management systems, and implementation of continuous improvement measures to support long-term regulatory compliance [35].

This role aligns with international quality governance frameworks and regulatory expectations, including those of the EMA, the WHO, and the International Council for Harmonization, which recognize PMS as an integral component of post-authorization quality systems rather than an extension of pre-licensing regulatory scrutiny [36,37].

2.5. SFDA's initiatives to support ATMPs access and development

The SFDA has established several initiatives to support innovative drug development and accelerate access to promising therapies. The breakthrough medicines program facilitates and accelerates the development, review, and approval of new drugs to address serious and life-threatening conditions. This allows for early interaction with drug developers to optimize development strategies and streamline regulatory assessments [26]. An application for breakthrough designation may be submitted at the end of the Phase 2 clinical trials or later. The Advisory Committee for Advanced Therapy provides expert guidance on the evaluation and oversight of advanced therapeutic products [38]. This committee is composed of scientific experts who contribute to evidence-based regulatory decision-making on complex issues [38]. Lastly, the pre-submission meetings and consultations are intended to clarify regulatory pathways and provide guidance on development programs prior to formal submission.

2.6. International collaboration and harmonization

The SFDA actively participates in international collaborations to promote regulatory convergence and harmonization. It also contributes to the International Conference on Harmonization (ICH) Cell and Gene Therapy Discussion Group by supporting global efforts to align standards and best practices for ATMP regulation [[39], [40], [41]]. Moreover, the SFDA participates in the International Pharmaceutical Regulators Program (IPRP) Cell and Gene Therapy Working Groups to facilitate knowledge sharing and regulatory alignment with international partners [42]. Additionally, the SFDA contributes to the International Coalition of Medicines Regulatory Authorities (ICMRA) Innovation Group, particularly in areas such as point-of-care manufacturing, to promote innovation while maintaining safety and compliance [43].

3. Market landscape and development status

3.1. Product approvals and market authorization

Several ATMP products have received regulatory approval from the SFDA, thereby demonstrating the capacity of this framework for evaluating advanced therapeutic modalities. An AAV5-based gene therapy for hemophilia B, Hemgenix (etranacogene dezaparvovec), obtained regulatory approval in early 2022 through the SFDA after gaining marketing authorization through the FDA and EMA [44,45]. Over the same time frame, in 2024, the SFDA approved the first CRISPR-based therapy for the treatment of sickle cell disease and β-thalassemia, Casgevy (exagamglogene autotemcel) [46]. This approval represents authorization for gene-editing technology within the Saudi regulatory framework. Under early access and compassionate-use programs conducted through accredited centers, including the King Faisal Specialist Hospital and Research Center (KFSHRC) and in coordination with the SFDA, the use of CAR-T cell therapies —classified by the SFDA as gene therapies—has been authorized [47]. These include tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), which are available through controlled access programs [11]. These regulatory developments reflect Saudi Arabia's ongoing efforts to expand innovation while preserving patient safety. The SFDA also provides multilateral strategic support for intramural medical needs by establishing Saudi Arabia as a regional regulatory agency for modern biopharmaceuticals.

Saudi Arabia has achieved significant milestones in ATMP approval, thus demonstrating the maturity and effectiveness of its regulatory framework. Product approvals have generally followed regulatory authorization from the FDA and EMA, thereby demonstrating strong alignment with established international evaluation criteria. Table 2 summarizes the ATMPs approved by the SFDA, which highlights the agency's growing regulatory maturity and alignment with global standards in the field of advanced therapies. It also reflects the SFDA's evolving regulatory infrastructure and capacity to evaluate complex gene-based products, including CAR-T, AAV-based vectors, and CRISPR-edited therapies.

Table 2.

ATMPs approved by the Saudi food and drug authority (SFDA) compared with the FDA and EMA.

Name	Registration Pathway & Designation at SFDA	SFDA Approval Date	FDA Approval	EMA Approval	Type	Indication
KYMRIAH	Abridgeda	2020	2017	2018	Gene Therapy (CAR-T)	CD19-directed genetically modified autologous T-cell therapy for relapsed/refractory pediatric and young adult ALL, diffuse large B-cell lymphoma, and follicular lymphoma.
LUXTURNA	Verificationa	2020	2016	2018	Gene Therapy (AAV-based)	Confirmed biallelic RPE65 mutation-associated retinal dystrophy.
ZOLGENSMA	Priority	2022	2017	2018	Gene Therapy (AAV-based)	Pediatric ($ < $2 years) spinal muscular atrophy (SMA) with bi-allelic SMN1 mutations.
CARVYKTI	Priority	2023	2022	2022	Gene Therapy (CAR-T)	Adults with relapsed/refractory multiple myeloma after ≥1 prior line of therapy (PI, IMID), and refractory to lenalidomide.
YESCARTA	Priority	2023	2017	2018	Gene Therapy (CAR-T)	Treatment of adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or relapses within 12 months, and relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Also approved for relapsed or refractory follicular lymphoma (FL) under accelerated approval. Not indicated for primary CNS lymphoma.
CASGEVY	Breakthrough	2024	2023	2024	Gene Therapy (CRISPR/Cas9-based)	Autologous gene-edited cell therapy for sickle cell disease (SCD) with VOCs and transfusion-dependent β-thalassemia (TDT).
TECARTUS	Priority	2025	2020	2020	Gene Therapy (CAR-T)	CD19-directed autologous CAR T-cell therapy for relapsed/refractory mantle cell lymphoma (MCL) and B-cell precursor acute lymphoblastic leukemia (ALL).
HEMGENIX	Priority	2025	2022	2023	Gene Therapy (AAV-based)	Adeno-associated virus vector gene therapy for adults with Hemophilia B.

^aAbridged and verification pathways were previously reported for selected ATMP approvals; however, under current SFDA guidance, ATMPs are excluded from these reliance-based pathways.

3.2. Therapeutic focus areas and regional disease priorities

ATMP development in Saudi Arabia strategically aligns with global therapeutic priorities and regional disease prevalence patterns, as assessed through coordinated efforts among the Saudi Ministry of Health (MoH), the SFDA, and the Saudi Health Council. These entities evaluate national health needs based on disease burden data, epidemiological surveillance, and strategic frameworks such as Vision 2030's Healthcare Transformation Program, while ensuring that regulatory and research initiatives target high-priority conditions, such as cancer, rare genetic disorders, and hematological diseases [18,48]. The focus on oncology applications, particularly for hematologic malignancies, reflects global ATMP trends and addresses significant unmet medical needs [14,49]. The high prevalence of genetic conditions like β-thalassemia and sickle cell disease in the regional population has led to genetic disorders becoming a focal area driving the development of gene therapies and gene-editing approaches [50,51]. Furthermore, regenerative medicine, which encompasses applications in tissue repair, organ regeneration, and the treatment of degenerative diseases, represents an emerging area of focus, with particular attention to conditions affecting the aging population and trauma-related injuries.

3.3. Infrastructure and capabilities

Since 2019, Saudi Arabia has invested significantly in infrastructure for the clinical trials of ATMPs [48]. These developments align with Vision 2030's larger objective of making the Kingdom a regional leader in the field of medical innovation and biotechnology [18,52]. The number of registered clinical trials has increased annually [53]. Between 2020 and 2025, Saudi Arabia has experienced steady growth in early-phase clinical trials involving biologics and ATMPs, thereby reflecting the nation's expanding research capacity. Moreover, the number of biologic trials increased from 21 to 23, peaking at 26 in 2024. Meanwhile, the number of ATMP trials increased from four to six, indicating accelerated progress in advanced therapy research after 2023.

4. Statistics and examples of clinical trials and commercial ATMPs

4.1. Clinical trial applications and registration process at the SFDA (2010–June 2025)

The Clinical Trials Administration was established by royal decree (M/6) issued in 2007 and SFDA regulations (7-7-1428) issued in 2010, which require all clinical trials conducted in Saudi Arabia to be registered in the Saudi Clinical Trial Registry (SCTR) at the SFDA [54]. The SFDA launched several pathways and designations to support innovative drug development for clinical trial registration and marketing authorization. Drug marketing authorization pathways and designations are presented in Table 3. In contrast, clinical trial registration follows a unified registration pathway with different regulatory timeframes based on the stage of the clinical trial and the type of investigational product, as illustrated in Fig. 4a.

Table 3.

SFDA marketing authorization pathways and regulatory designations relevant to ATMPs.

Regulatory pathway and designation	Purpose	Main application	Regulatory relevance to ATMPs
Standard pathway	Full scientific assessment of quality, safety, and efficacy before granting marketing authorization [33].	Novel products or products requiring complete regulatory review [33].	Relevant for complex ATMPs requiring full CMC, nonclinical, clinical, and risk–benefit evaluation [19,33].
Abridged pathwaya	Reliance-based registration pathway for products previously approved by recognized regulatory authorities, particularly the EMA or FDA [32].	Products with prior approval by reference regulatory authorities and meeting SFDA reliance criteria [32].	Included as a general SFDA marketing authorization route; however, ATMPs are excluded from the abridged pathway under current SFDA guidance [32].
Verification pathwaya	Verification-based pathway for products approved and marketed by both the EMA and FDA [32].	Products with established approvals and harmonized documentation meeting SFDA verification criteria [32].	Included as a general SFDA marketing authorization route; however, ATMPs are excluded from the verification pathway under current SFDA guidance [32].
Priority review	Accelerated review for products addressing unmet medical needs or public health priorities [34].	Innovative, life-saving, or high-impact therapies where faster review may be justified [34].	Potentially relevant for ATMPs targeting serious, life-threatening, or high-burden diseases where timely access is needed [34].
Breakthrough medicine designation	Facilitated regulatory designation intended to expedite access to innovative and effective treatments for serious diseases where existing therapies may be inadequate [12].	Medicines with clinical evidence suggesting promising efficacy and safety, significant therapeutic advantage, serious or life-threatening target condition, and positive benefit–risk balance [12].	Highly relevant for innovative ATMPs, especially gene and cell therapies addressing serious, life-threatening, or rare diseases [12].
Orphan drug designation	Regulatory facilitation for products intended to treat rare diseases affecting fewer than 5 in 10,000 individuals in Saudi Arabia [55].	Rare disease therapies, including products for serious, chronic, life-threatening, or seriously debilitating conditions [55].	Important for ATMPs such as gene therapies for inherited disorders, ultra-rare diseases, and other rare conditions [55].

^aVerification and abridged pathways are presented as general SFDA marketing authorization routes. However, ATMPs are excluded from these reliance-based pathways under the current SFDA guidance governing registration through the verification and abridged pathways [32].

Fig. 4.

Clinical trial applications and growth dynamics in Saudi Arabia A. The Saudi Food and Drug Authority (SFDA) established regulatory timeframe for different types of clinical trials and requires that all clinical trials be registered in the SCTR. B. Comparative trend of ATMP, biologic, and chemical investigational product applications (2017–2025), showing increased numbers in 2020 due to the COVID-19 pandemic and rising trends in biologic and ATMP submissions between 2021 and 2024. C. Growth rate of clinical trials from 2018 to 2025, showing the initial yearly fluctuation (−93% in 2018; +190% in 2019), followed by sustained positive growth through 2024. The apparent negative growth in 2025 reflects incomplete data resulting from the cut-off date occurring mid-year.

4.2. Growth rate of clinical trials

Based on internal SFDA data from 2010 to 2025, 436 early-phase clinical trials (phases I–III) and 269 Phase IV trials have been registered. The cut-off date for this study was June 2025. The number of clinical trial applications peaked in 2020 during the COVID-19 pandemic, with 33 applications for chemical products and 21 for biological investigational products (Fig. 4a and b) [56]. Moreover, a significant increase in the number of clinical trial applications was observed from 2021 to 2025, in contrast to the period before 2020, as shown in Fig. 4c. The number of biological and chemical investigational products increased over time, with year-to year fluctuations. In 2024, the number of biologic investigational products increased sharply to 26, including six ATMP applications. By comparison, the highest number of chemical product applications (33) was recorded in 2020 (Fig. 4b).

Sophisticated and innovative applications for investigational compounds and/or new clinical trials were submitted to the SFDA. Unique applications of biological products were classified as “not ATMPs” such as the ChAdOx1 MERS vaccine and plasma DNA vaccines. These products are not considered ATMPs based on their mechanism of action and classification to prevent infectious diseases (Fig. 4a and b). In contrast, for chemical products, ALN-TTRSC02 (Vutrisiran) presented challenges from both manufacturing and classification perspectives. Certain clinical trial designs, such as the platform design used in the REMAP-CAP trials, posed regulatory challenges owing to the limited availability of regulatory guidance in 2020. This design is primarily used for oncology trials [57], whereas the submitted applications were for COVID-19 trials.

Growth in clinical trials varied from 2018 to 2025. The largest percentage increase occurred in 2019 (190%), which subsequently decreased until 2022. From 2022 to 2024, the growth rate increased slightly each year. The latest data expects the curve to decline again in 2025 (−31%); however, this value is not representative because the study cut-off date was June 2025. The cumulative value of clinical trial applications, with 147 applications from 2010 to 2017, is considered a primary limitation. Furthermore, there was a significant decline in the growth rate was observed in 2018 (−93.2%). (Fig. 4a and b).

4.3. Investigational ATMPs (data curated from SFDA internal database)

ATMP clinical trial applications began in 2011 and continued through June 2025, totaling 20 applications. The SFDA approved the first Phase I investigational medicinal product classified as an ATMP, recombinant adeno-associated virus (rAAV2-VMD2-hMERTK). This product was designed to treat patients with retinal diseases caused by mutations in MERTK. Subsequently, a gap emerged in ATMP clinical trial applications between 2011 and 2020, with a steady stream of submissions for biological investigational products. COVID-19 treatments and vaccines have been considered catalysts to replenish ATMP applications at the SFDA. ATMP applications include both gene and cell therapies (Table 4), ranging from Phases I to III, with the highest number of applications in Phase II. The SFDA played a major role in evaluating and approving clinical trials, which led to local and international marketing authorizations for products, such as Casgevy, Zolgensma, Carvkti, and Hemgenix (Table 2, Table 3). Currently, 10 ATMP applications are ongoing, 7 are under review, and 1 fall into the Completed, Canceled, or Terminated categories (Table 4). However, the applications under review have been pending since 2020 owing to challenges associated with ATMPs, including inconsistencies in analytical and manufacturing quality criteria between batches for one participant and/or between participants. The most common therapeutic areas for ATMPs are Oncology and Hematology, followed by Endocrinology and Metabolism, Ophthalmology, and Immunology. Data on clinical trial activity and ATMP approval were obtained from the unpublished internal records of the Saudi Food and Drug Authority.

Table 4.

Summary of ATMP clinical trials in Saudi Arabia (2011–2025).

No.	SCTR no.	Year	Investigational product	Therapeutic area and Disease	Clinical Trials Stages	Status of clinical trials
1.	Not found	2011	rAAV2-VMD2-hMERTK Recombinant Adeno-Associated Virus	Ophthalmology _retinitis pigmentosa due to MERTK mutation	phase I	Completed
2.	19122603	2020	CD19-CART	Oncology_ relapsed/refractory CD19 Positive Acute Lymphoblastic Leukemia (ALL)	Phase I	Ongoing
3.	20010802	2020	Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)	Hematology _Sickle Cell Disease	Phase III	Ongoing
4.	20020403	2020	CD19-CART	Oncology_ relapsed/refractory CD19 Positive Non-Hodgkin's Lymphoma (NHL)	Phase I/II	Under review
5.	20082402	2020	CD19-CART	Oncology_ CD19 Positive Relapsed and Refractory Acute Lymphoblastic Leukemia or Lymphoma	Phase I	Cancelled
6.	21111402	2021	Ciltacabtagene Autoleucel (Carvkti)	Oncology Multiple Myeloma (CARTITUDE-2)	Phase II	Ongoing
7.	21121402	2022	PHE885 (CAR-T Cell)	Oncology relapsed and refractory multiple myeloma	Phase II	Terminated
8.	23110904	2023	Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) (Casgevy)	Hematology_ Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease	Phase III	Ongoing
9.	23122002	2024	Etranacogene Dezaparvovec (HEMGENIX)	Hematology (General)_ Severe or Moderately Severe Hemophilia B	Phase III b	Ongoing
10.	24011602	2024	OAV101 (formerly AVXS101) (Zolgensma)	Other_ Spinal Muscular Atrophy	Phase III	Ongoing
11.	24070702	2024	mRNA-3927	Endocrinology and metabolism_ Propionic Acidemia	Phase I/II	Ongoing
12.	24111402	2024	Allogeneic Mesenchymal Stem Cells	Ophthalmology_ corneal epithelial defects	Phase II	Under review
13.	24112102	2024	UF-KURE19 cells	Hematology (Oncology) _ Relapsed or refractory B cell Non- Hodgkin lymphomas	Phase II	Under review
14.	24112502	2024	HGI-001-C01(LentiHBBT87Q)	Hematology_β-Thalassemia and Severe Sickle Cell Anemia	Phase II	Under review
15.	24120802	2025	Rapcabtagene Autoleucel (YTB323)	Immunology_ severe active Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA)	Phase II	Ongoing
16.	25020303	2025	Rapcabtagene Autoleucel (YTB323)	Rheumatology_ severe refractory idiopathic inflammatory myopathies	Phase II	Under review
17.	25030302	2025	VX 880	Endocrinology and metabolism__Type 1 Diabetes Mellitus with Impaired Hypoglycemic Awareness and Severe Hypoglycemia	Phase III	Ongoing
18.	25030303	2025	VX 880	Endocrinology and metabolism_ Type 1 Diabetes With a Kidney Transplant	Phase III	Ongoing
19.	25020902	2025	Rapcabtagene autoleucel (YTB323)	Immunology Systemic lupus erythematosus (SLE), with active, refractory lupus nephritis (LN)	Phase II b	Under review
20.	25051403	2025	mRNA-3705	Endocrinology and metabolism_ Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency	Phase II	Under review

5. Research infrastructure and capacity

Saudi Arabia's advancement in ATMPs is bolstered by a robust network of institutions that integrate clinical excellence with research infrastructure. At the forefront is the KFSHRC, which contributes to over 50% of the open clinical trials in Saudi Arabia, with >700 active research proposals by the end of 2024 [58]. KFSHRC is a frontrunner in CAR-T cell therapy, having treated over 200 patients and established the region's first on-site manufacturing facility using the CliniMACS Prodigy system, which significantly reduces treatment delivery time and cost [59,60]. The center also spearheads first-in-human trials for gene therapy in hemophilia and inherited retinal diseases and maintains one of the world's largest registries for bone marrow failure syndromes [58,59].

The KAIMRC plays a pivotal role in housing Saudi Arabia's sole Phase I-accredited clinical trial unit and overseeing GMP factories, FACT-certified cord blood banks, Saudi iPSC banks, and Saudi biobanks [61,62]. These resources are crucial for translational research, particularly for diseases such as β-thalassemia and sickle cell disease that are highly prevalent in the region. Moreover, the Saudi National Institute of Health (SNIH) was established in 2022 to centralize and expedite clinical research coordination, funding, regulatory assistance, and infrastructure for Phase I trials, including fast-track approvals for gene and cell therapy studies [63,64].

Academic institutions such as King Saud University, King Abdulaziz University, and KAUST are integral to this ecosystem, training researchers and fostering biotech startups through innovation parks and bioengineering programs [48]. Their collaboration with clinical centers is vital for developing a national talent pool and promoting the translation of ATMPs from bench to bedside. Ongoing national investment in an integrated clinical research infrastructure, including GMP-grade biobanking and production facilities as well as multi-omics platforms, is positioning Saudi Arabia towards self-sufficiency in ATMPs and early-phase human clinical trials [61,65].

6. Industry engagement and strategic partnerships

Saudi Arabia's strong interest and funding capabilities make it attractive to international pharmaceutical companies, bolstered by domestic biotech startups. Strategic alliances, technology transfer, and local manufacturing efforts have accelerated ATMP development and access. Collaborative frameworks involving national regulators, academic medical centers, and global technology holders have facilitated the introduction of CAR-T cell therapies and other gene- and cell-based treatments, thereby contributing to the gradual establishment of local manufacturing and quality-control capabilities [[66], [67], [68]]. This has introduced advanced gene and cellular therapies to stimulate local production capacity. Concurrently, memoranda of understanding with international stakeholders have emphasized infrastructure development, workforce training, and knowledge transfer, while aiming to achieve a 75% locally-sourced biotechnology workforce within 10 years [68]. Following the regulatory authorization of gene-editing therapies, additional cooperative efforts have focused on domestic manufacturing, translational research, and the expansion of genome-editing expertise within the Kingdom [46].

Domestic innovation has also advanced through the emergence of local biotechnology start-ups developing novel gene-delivery and therapeutic platforms targeting high-prevalence genetic diseases, such as sickle cell disease. These initiatives, often conducted in collaboration with national research institutions and universities, have progressed toward early clinical evaluation with long-term commercialization goals. These local collaborations resulted in the launch of a pilot clinical study aimed at commercializing the therapy by 2030 while potentially benefiting approximately 42,000 patients [69]. The company also participates in international incubators, such as Charles River Laboratories, to gain global expertise. Furthermore, the Public Investment Fund (PIF) has supported the creation of integrated biopharmaceutical holding structures to strengthen manufacturing capacity, thereby enabling contract development and manufacturing organization (CDMO) deals with in-house ATMP production [65]. Collectively, these efforts reflect a coordinated national strategy to reduce reliance on external treatment pathways, build sustainable manufacturing autonomy, and position Saudi Arabia as a regional hub for ATMPs.

7. Challenges and future directions

Despite significant progress in the development and regulation of ATMPs, Saudi Arabia faces several key challenges. A primary obstacle is the shortage of a skilled workforce with critical expertise in areas such as bioprocessing, regulatory affairs, and the clinical application of ATMPs. Although academic biotechnology programs are expanding, a gap in human resources persists, which impedes regulatory reviews and domestic product development [19,70].

Manufacturing and logistics complexities are also major hurdles. ATMPs, particularly personalized therapies such as CAR-T cells, are expensive and require GMP-compliant production processes that are difficult to scale. This is compounded by the high cost of technology acquisition and transfer, as well as a shortage of certified GMP-compliant manufacturing facilities. While institutions such as the KFSHRC have initiated this capability, establishing large-scale, standardized domestic production remains a future goal [19,68]. These manufacturing challenges create regulatory complexities related to CMC, including lot-to-lot comparability and quality control, which are further complicated by the small, highly variable batches typical of ATMPs.

Clinically, ATMP trials in Saudi Arabia have encountered challenges including limited resources, inadequate infrastructure, time constraints, and insufficient funding [19,56]. The gaps in research methodology, data management, and Good Clinical Practice (GCP) competencies necessitate comprehensive training and capacity-building initiatives [70]. Furthermore, sustainable reimbursement policies and health economic models for these high-cost single-intervention treatments are not yet well defined, although performance-based models are under discussion.

To address these issues, future efforts should focus on strategic investments in workforce training, digital infrastructure, and certified ATMP production centers [70]. Constructing integrated networks that foster collaboration among academic institutions, regulatory authorities, and industry is essential to harmonize standards and accelerate the bench-to-bedside translation of innovative therapies [64]. The SFDA remains committed to this path, with the aim of formalizing regulatory pathways for technology transfer and developing innovative, safety-focused oversight mechanisms tailored for ATMPs [71].

8. Conclusion

Saudi Arabia is currently at a pivotal stage in the development of its biopharmaceutical sector, with ATMPs becoming fundamental for healthcare transformation. It continues to lay foundational perspectives on regulations through insightful approaches to SFDA guidelines, classifications, and global GMP adjuncts. Vision 2030 has significantly increased investments across the value chain including, but not limited to, clinical trials and institutional linkages extending beyond genomic initiatives focused primarily on economics and localizing manufacturing. Ongoing issues and concerns regarding the implementation of regulations, logistics, technical capacity, clinical trial capacity, and basic infrastructure remain to be addressed. An enduring commitment to research funding, regulated innovations, and due diligence in human capital planning is vital for addressing these challenges. With unified leadership and sustained financial investment, Saudi Arabia is poised to establish itself as a regional leader in advanced therapies and a major player on the global stage of innovation in regenerative medicine and personalized healthcare.

Disclaimer statement

The views and opinions expressed in this paper are those of the authors and do not necessarily reflect the official policy of the Saudi Food and Drug Authority (SFDA) or its stakeholders. The authors are solely responsible for the accuracy and validity of the data and the conclusions presented in this study.

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Data availability

Data supporting this study are available from the corresponding author upon reasonable request.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work the authors used OpenAI ChatGPT to assist with text refinement, grammar correction, and manuscript formatting. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.

Declaration of competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.