Regulatory Framework for Regenerative Medicines

Regenerative medicines encompasse therapeutic approaches intended to restore, replace, repair, or regenerate human cells, tissues, organs, or physiological functions. These approaches may involve cell- and tissue-based therapies, tissue engineering, genetic modification, or combinations of these technologies.

Cell-based therapies represent a major area of regenerative medicines and may comprise autologous or allogeneic cells including stem cells, progenitor cells, and other specialized cell populations. Depending on their characteristics, degree of manipulation, and intended use, cell-based products may be developed to repair, regenerate, or replace human cells or tissues, or to restore or modify physiological functions.

Tissue-engineered products contain or consist of engineered cells or tissues intended to regenerate, repair, or replace human tissue. Such products may also incorporate biomaterials, scaffolds, or other components. Where a medical device forms an integral part of an advanced therapy medicinal product, the product may be classified as a combined advanced therapy medicinal product in accordance with the applicable SFDA guideline on Classification of Advanced Therapy Medicinal Products.

Gene-based technologies have also become increasingly integrated with regenerative medicine. Genetic modification may be performed ex vivo, including through the genetic modification of cells before administration, or in vivo, through the delivery of genetic material directly to the patient. While certain gene therapies have a direct regenerative or restorative purpose, others are intended to achieve different therapeutic effects, such as modifying immune-cell function or targeting malignant cells. Nevertheless, gene therapies share important scientific and regulatory considerations with regenerative medicines. Accordingly, this framework includes gene therapy medicinal products irrespective of whether their primary therapeutic effect is regenerative, to provide a comprehensive and coherent regulatory pathway for these technologies.

Other emerging technologies seek to promote endogenous repair or regeneration by influencing the biological environment of damaged tissues, and may involve biologically active molecules or other cell-derived preparations; such technologies may be considered under this framework. The regulatory classification of such products depends on their composition, biological characteristics, intended use, and mode of action.

Accordingly, the Saudi Food and Drug Authority (SFDA) establishes this framework to provide a clear, predictable, science- and risk-based regulatory pathway for regenerative medicinal products intended for human use. The framework sets out the approach to their classification, registration, and regulatory oversight, applying requirements proportionate to product characteristics and associated risks while ensuring appropriate standards of quality, safety, and efficacy.​

This framework applies to regenerative medicinal products intended for human use throughout their product lifecycle, including marketing authorization and post-authorization regulatory oversight, as follows:

• Advanced Therapy Medicinal Products (ATMPs).

• Allogeneic Products for Homologous Use (APHU) that are not substantially manipulated.

The applicable regulatory requirements and level of oversight are determined using a risk-based approach, taking into account factors including the origin of cells or tissues, degree of manipulation, intended clinical use, mode of action, and product characteristics. Products classified as ATMPs or APHU shall follow the respective regulatory pathways and requirements described in this framework.

The following are outside the scope of this framework:

• Non-viable human cells and tissues, including, but not limited to, bone, ligament, skin, dura mater, heart valves, and cornea, where regulated under other applicable frameworks.

• Autologous, non-substantially manipulated cells or cell-derived products intended for homologous use that constitute clinical practice and are not regulated by the SFDA as medicinal products.

• Products intended solely for cosmetic use.

• Xenogeneic cell- or tissue-based products intended to restore, replace, repair, or regenerate human tissues or physiological functions. ​

• Autologous

Refers to cells, tissues, or other human biological materials that are collected from and administered to the same individual.

• Allogeneic

Refers to cells, tissues, or other human biological materials that are collected from one individual and administered to another individual.

• Non-Substantial Manipulation (NSM)

According to SFDA’s guideline on Classification of Advanced Therapy Medicinal Products, the term non-substantial or minimal manipulation is defined as processing that does not alter the original relevant characteristics of  the structural tissue relating to the tissue’s utility for reconstruction, repair, or replacement, or, in the case of cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells or tissues. This includes, but is not limited to: centrifugation, density gradient separation, cryopreservation, thawing, washing, and dilution. Processes such as cell expansion, activation (e.g., with cytokines beyond supplemental amounts), encapsulation, or genetic modification constitute substantial manipulation.

• Substantial Manipulation (SM)

A cell-based product in which processing of cells or tissues alters their relevant biological characteristics or characteristics relevant to the tissue utility, including processes such as cell expansion, activation (e.g., with cytokines beyond supplemental amounts), encapsulation, or genetic modification.

• Homologous Use

As for the intended clinical application and for the purpose of this framework, homologous use refers to a cell-based product that performs “same essential function”, following removal from its original environment in the human body, the cells are intended to perform and maintain their original function(s) when administered into the same or a comparable anatomical or histological environment.

• Non- Homologous Use

A cell-based product shall be considered to have non-homologous use when, following removal from its original environment in the human body, the cells are not intended to perform and maintain their original function(s), or are admin​istered into an anatomical or histological environment that is neither the same as nor comparable to their original environment.

The level of regulatory oversight is determined through a risk-based approach that considers multiple factors associated with regenerative medicinal product. These factors include the source of cells or tissues (e.g., autologous or allogeneic), the degree of processing and manufacturing involved (including whether the product undergoes SM or NSM), and the intended clinical application (including homologous or non-homologous use). Collectively, these considerations form the basis for product classification and the corresponding regulatory requirements under this framework, as set out below:

Table 1: Classification of regenerative medicines based on source, processing level, and intended use.

The SFDA offers classification service for borderline products through Product Classification System. Applicants can find more information on (link).

In addition, the applicants may seek scientific advice and guidance from the SFDA regarding classification and other related scientific aspects of the product (link).

Note: Administration devices may be co-packaged with the cell therapy product. Such devices shall be subject to applicable regulatory requirements and may undergo separate evaluation pathways and timelines, based on their assigned classification.​

Products classified as ATMPs (Table 1) are governed by the Regulations  of the Law of Pharmaceutical  and Herbal Establishments  and Products (link) and applicable SFDA regulatory framework for drug approval (link). Accordingly, ATMPs shall comply with all relevant SFDA requirements.​

Following the granting of marketing authorization, ATMPs remain subject to ongoing regulatory oversight throughout their lifecycle. Any proposed change to the approved quality, safety, efficacy, labeling, or other relevant aspects of the product must be submitted to SFDA in accordance with the Guideline for Variation Requirements (link).

5.3. Data Requirments for Advanced Therapy Medicinal Products​

ATMPs are governed by the Regulations  of the Law of Pharmaceutical  and Herbal Establishments  and Products (link) under the Regulatory Framework for Drug Approval (link), which establishes the overarching requirements for marketing authorization of medicinal products in Saudi Arabia. As biological products of inherent complexity, ATMPs are associated with a higher level of risk and scientific uncertainty than conventional medicines, owing to factors such as their biological origin, complex manufacturing processes, and novel mechanisms of action. Accordingly, the data requirements for human medicines (link) should be met at the time of submission, supported by additional data specific to the nature of the product, to ensure a comprehensive evaluation of its quality, safety, and efficacy.

​These products are classified as APHU and are governed by the applicable SFDA regulatory framework for drugs approval (link). In general, the data requirements for human medicines (link) should be considered for data submission. However, given the low-to-moderate risk level associated with APHU, it is expected that not all sections of the Electronic Common Technical Document (eCTD) are applicable or required. At a minimum, the applicant should provide the essential requirements in section 5.3. 

6.1. Registration Pathways for Allogenic Products for Homologous Use (APHU)

Upon submission of newBiological Marketing Authorization Application in Saudi Drug Registration system (SDR), the applicant should indicate the class of product as “Allogeneic Products for Homologous Use" in the cover letter provided in Module 1 (Section ‎11).

APHUs are subject to either a regular or a priority review pathway by the SFDA. A regular review involves a comprehensive evaluation of the submitted data and supporting documentation to ensure that the product's benefits outweigh its risks and that it is suitable for marketing authorization in the Kingdom of Saudi Arabia. While priority review is intended to expedite the assessment of products that address serious or life-threatening conditions, fulfill unmet medical needs, or improve product availability (link).

In Table 3, an overview of the SFDA regulatory pathways, designations, tools, and incentives for APHUs.

6.2. Variation of Marketing Authorization for Allogenic Products for Homologous Use (APHU)

The principles outlined in the Guidelines for Variation Requirements  are applicable to APHU throughout its lifecycle. Following the granting of marketing authorization, any proposed changes to the approved quality, safety, efficacy, labeling, or other relevant aspects should be submitted and managed in accordance with the applicable SFDA variation requirements to ensure the continued quality, safety, and efficacy of the product.

6.3. Data Requirments for Allogenic Products for Homologous Use

The data requirements should generally follow the eCTD format, as outlined below:

6.3.1 Administrative Information and Prescribing Information 

Administrative information, such as the cover letter, application form, product information, relevant certificates, supporting documents, pricing information, information on relevant experts, required statements/declarations, and any other relevant additional data or supporting information, should be submitted as applicable.

As for pharmacovigilance, kindly refer to the following:

6.3.1.1 Risk Management Plan

The aim of a Risk Management Plan (RMP) is to document the risk management system considered necessary to identify, characterize and minimize the important risks. The RMP should be submitted with the application for product registration.  Saudi-Specific Annex (SSA) should be submitted whenever a European Union RMP (or alternative RMP where no current European Union RMP exists).  

6.3.1.1.1 Risk Minimization Measures

High-priority risks should be mitigated. Part V of the RMP should provide details of the risk minimization measures which will be taken to reduce the risks associated with respective safety concerns. The following information should be provided:

• Routine risk minimization activities, including details of whether only inclusion in the Summary of Product Characteristics (SPC) and Patient Information Leaflet (PIL) is foreseen, or any other routine risk minimization activities are proposed.

• Additional risk minimization activities (if any), including individual objectives and justification of why needed, and how their effectiveness will be measured.

6.3.1.1.2 RMP Content 

The RMP is a detailed description of the risk management system for the medicinal product.  An outline of RMP content is listed below:

a) Product(s) overview

b) Safety specification 

c) Pharmacovigilance plan (including post-authorization safety studies)

d) Plans for post-authorization efficacy studies Risk minimization measures (including evaluation of the effectiveness of risk minimization activities)

e) Summary of the RMP

f) Annexes

6.3.1.1.3 RMP Assessment Timetable

Timetable for submission of assessments of the RMP by the applicant.

6.3.1.1.4 RMP Materials 

A comprehensive list of all additional risk minimization measures (aRMMs) materials required for the RMP (e.g., enrollment forms, educational materials, counseling tools, monitoring forms, and patient-provider agreements).

The actual RMP materials should be provided as an appendix to the RMP submitted to SFDA.

6.3.1.1.5 RMP Supporting Documents

Expands on information in the RMP document, and provide additional information about the RMP, such as the rationale for and supporting information about the design, implementation, and assessment of the RMP (e.g., why a RMP is necessary, how the RMP would ensure that the benefits of the therapeutic product outweigh the risks, implementation processes, compliance and enforcement policies and procedures, definitions, knowledge assessment analysis approach, and the RMP assessment plan). Special pharmacovigilance requirements (e.g., registry, Post-Authorization Safety Study, etc.) including long term follow-up of patients might be requested on a case-by-case analysis.

6.3.1.2 Traceability Requirements

The objectives of Post Marketing Surveillance Activities are to identify significant and serious Adverse Events (AEs) while establishing causal relationships between medications and these adverse effects. To accomplish this goal, robust data collection and investigation tools have been developed to ensure that the information concerning the association between drugs and Adverse Events (AE)s are both comprehensive and reliable. The information outlined below shall be used along with SFDA guideline on Good Pharmacovigilance Practices (GVP).  

6.3.1.3 Saudi Vigilance Reporting System (تيقظ)

A key element in developing an effective national spontaneous drug safety program is the establishment of an electronic system for collecting Adverse Drug Events (ADEs), events related to vaccines following immunization, and reports of lack of efficacy for drugs. Initiated in 2018, the current system, known as ‘تيقظ’, aims to streamline the reporting process and maintain data integrity. It enables the public, healthcare professionals (HCPs), and pharmaceutical companies to report adverse drug events, medication errors, and defects in product quality.

To ensure the system's success, SFDA strongly encourages all medical field members to participate and report through https://ade.sfda.gov.sa/ or via other channels outlined in the patient information leaflet (PIL) included with marketed medications. Additional details can also be accessed through the Saudi Drug Information System (SDI) at https://sdi.sfda.gov.sa/. For guidance on using the electronic reporting system ‘تيقظ’.

6.3.1.3.1 Serious Adverse Event 

To avoid confusion or misunderstanding regarding the terms “serious” and “severe,” the following clarification is provided:

• Severe is used to describe the intensity (or severity) of a specific reaction (e.g., mild, moderate, or severe). However, the reaction itself may be of relatively minor medical significance (such as a severe headache).

• Seriousness (not severity) is based on the patient’s outcome or the action required. This distinction serves as a guide for defining regulatory reporting obligations.

6.3.1.3.2 Seriousness Criteria

A serious adverse event or serious adverse reaction is any untoward medical occurrence that may cause at any dose one of the following outcomes: 

• Death

• Life-threatening

• Require or prolong hospitalization

• Cause disability

• Cause congenital anomaly/birth defect

• Requires intervention to prevent permanent injury

Table 4: Time frames for reporting serious and non-serious adverse events, including cases of lack of drug efficacy.

6.3.1.3.3 How to Identify Adverse Drug Reactions

The expectedness of a report is assessed according to the Summary of Product Characteristics (SPC).

Expectedness:

• Expectedness refers to a reaction whose nature, severity, specificity, and outcome are clearly stated within the SPC.

• Unexpected Reaction is defined as one whose nature, severity, or outcome is inconsistent with the SPC. This includes class-related reactions mentioned in the SPC but not specifically described as occurring with the product in question.

6.3.1.3.4 Assessment of Report Relatedness

The relatedness of a report is evaluated to determine the relationship between events and the products used. The following terms are utilized:

• Un-assessable: The report suggests an adverse reaction but cannot be evaluated due to insufficient or contradictory information.

• Conditional: Additional data is required for proper assessment, or further investigation is ongoing.

• Unlikely: The event has a time relation to drug intake that makes a relationship improbable, with plausible explanations from diseases or other medications.

• Possible: There is a reasonable time relationship to drug intake; however, the event may also be explained by underlying conditions or other drugs, and information on withdrawal may be unclear.

• Probable: The event has a reasonable time relationship to drug intake, is unlikely to be attributed to other factors, and shows a clinically reasonable response to withdrawal.

• Certain: The event has a plausible time relationship to drug intake, cannot be explained by other factors, and the response to withdrawal is pharmacologically or pathologically plausible, indicating a definitive medical disorder.

For registered and marketed products, the unexpected reactions will be handled as safety signals. If the safety signal has been validated and confirmed then the product information will be updated to reflect the new risk. Additional regulatory actions might be considered based on case-by-case analysis.

6.3.1.3.5 Reporting Adverse Evenets 

• It helps in detecting rare adverse drug events.

• Detection of safety in special populations (e.g., pregnant women)

• Determining long term safety of the products in the market.

• Assessment of drug safety in real-world circumstances (e.g., patients with polypharmacy or patients with co-morbidities)

6.3.1.3.6 Traceability of Adverse Drug Reactions 

Marketing Authoirization Holders (MAH) shall establish mechanisms enabling the traceability and follow-up of adverse reaction reports while complying with the data protection legislation. 

Pharmacovigilance data and documents relating to APHU products shall be retained as long as the product is authorized and for at least 10 years after the marketing authorization has ceased to exist. However, the documents shall be retained for a longer period where SFDA law so requires. 

Periodic Benefit Risk Evaluation Report / Periodic Safety Update Report (PBRER/PSUR) 

MAHs shall submit PBRER/PSUR every two months for the first 6 months post-launch. Then the frequency of PBRER/PSUR submission will follow the timeline outlined in the SFDA guideline GVP.

6.3.2 Common Technical Document Summaries

Applicable Module 2 data should be submitted under the relevant sections of the module, as appropriate.

6.3.3 Quality

Chemistry, Manufacturing and Controls (CMC) information should be submitted in accordance with the applicable sections of Module 3 – Quality, taking into consideration the following recommendations and guidance documents, as applicable:

6.3.3.1 Manufacturing/Preparation Process

a) Process description with scientific justification of NSM, specifically addressing how the processes listed below do not alter the relevant biological characteristics of the APHU product:

• In- process controls and acceptance criteria. Description of controls including but not limited to: Recovery Efficiency (Ex. Percentage of cell recovery post processing):

- Cleaning/rinsing procedures.

- Cutting/shaping (tolerances).

- Packaging and integrity.

• Material controls and supplier qualifications:

- Critical reagents and solutions (e.g., saline, cryoprotectants) including Certificates of Analysis.

- If antibiotics are used: Provide justification for use, quantitative analysis of residual levels in the final product, and a risk assessment.

- Procedures to remove residues as applicable. 

• Lot history (batch records) to demonstrate process consistency. 

• Environmental controls including measures for prevention of contamination and cross contamination (e.g., International Organization for Standardization (ISO) Cleanroom classification wherever applicable). 

• Deviations and Corrective Action and Preventive Action (CAPA) handling.

• If the applicant wishes to supply the product from multiple sites, demonstration for equivalence must be provided. 

b) Homologous use (should be included in the label). 

Use of Penicillin/Streptomycin antibiotics is generally discouraged. Nonetheless, clinical risks of other antibiotics should be considered. It is also important to note that testing of residual antibiotics is a release requirement. In case of use of antibiotics, the patient should be evaluated for sensitivity to the antibiotic used in the manufacturing of the cell therapy product, which should be clearly stated on the label, after careful evaluation of patient history and obtaining patient consent.

c) Description of any additives/excipients and why they are permitted including dose and intended use, for novel excipients, full characterization should be provided.

6.3.3.2 Eligibility

• Donor starting materials testing results (communicable diseases).

• Laboratory certifications.

• Donor eligibility determination (Eligible/Ineligible Determination).

6.3.3.3 Product Characterization 

Defined product description including:

• Tissue/ Cell Source (this can be confirmed using histological tests, cell type presence by cell count).

• Human tissue/cells used (e.g., amniotic membrane, adipose tissue, bone).

• Anatomical origin.

• Living vs deceased donor.

6.3.3.4 Product Specifications 

1. Final product form:

• Suspension/graft/particulates.

• Fresh/cryopreserved.

• Defined Ranges of dimensions (Length, Width, Thickness) or volume.

2. Physical characteristics:

• Color, texture, size range (with acceptance criteria for release).

3. Relevant Biological characteristics:

• Cell Viability (with acceptance criteria specific to each product).

• Cell Count/Total Dose or specific phenotypic markers.

4. Purity and safety attributes (e.g., sterility, endotoxin, mycoplasma where applicable).

6.3.3.5 Product Stability

Shelf life and storage conditions with rationale (supported by scientific justification or stability studies):

• Statement of storage conditions (e.g., -20°C, 2-8°C).

• Shelf life (e.g., 24 hours, 6 months) with rationale supported by stability studies or published literature/scientific justification.

• In-use stability shelf life and storage conditions.

• Stability of manufacyuring intermediates, if any.

6.3.3.6 Traceability and Tracking 

• Chain of Identity (CoI) System linking donor → product → recipient (uniform label) (two-way traceability).

• Chain of custody (CoC): to ensure unbroken sequence of possessions from donor to recipient specifying country of origin and facility location.

• Shipping traceability: Continuous real-time temperature data logger records with defined acceptance ranges for shipping temperature and procedures for handling excursions.

• Record management and written procedures applicable for batch recall.

6.3.3.7 Donor Material Qualification Determination

The recommendations herein are intended to provide detailed guidance and do not replace or supersede any existing SFDA laws or regulations. In the event of any conflict between this document and the overarching SFDA Medical Devices, Biologics, or other applicable regulations, the official regulations shall prevail. Applicants are responsible for ensuring full compliance with all current SFDA requirements.

These following requirements outline the core principles and requirements for determining the eligibility of donors of cells and tissues used in the manufacture of NSM APHU. The primary goal is to prevent the transmission of infectious diseases and to ensure the safety, quality, and efficacy of the final therapeutic product.

These requirements apply to all allogeneic (donor-derived) NSM products. For autologous (patient-derived) donations, the donor eligibility determination is not required; however, rigorous testing for relevant communicable diseases and agents is mandatory to ensure the safety of handling personnel and to prevent cross-contamination.

6.3.3.8 General Principles Donor 

The responsibility for determining donor eligibility rests with the establishment (e.g., tissue bank, processing facility) that performs the donor screening and testing, and this must be documented prior to clinical use.

6.3.3.9 Donor Eligibility 

Donor eligibility must be determined based on:

• A review of relevant medical records.

• The results of donor screening through a Donor Risk Assessment

• Interview (DRAI) according to the local relevant authority guidelines and regulations 

• The results of required laboratory testing

All procedures for donor screening, testing, and eligibility determination must be described in approved Standard Operating Procedures (SOPs).

Donor Screening and Risk Assessment

A qualified healthcare professional must conduct a comprehensive DRAI with the living donor or a knowledgeable person for a deceased donor. The DRAI must be designed to identify behaviors and exposures that increase the risk of transmission of Relevant Communicable Diseases and Agents (RCDAs).

6.3.3.10 Screening 

The screening must assess risks for, but not limited to, the following:

• Human Immunodeficiency Virus (HIV), Types 1 and 2

• Hepatitis B Virus (HBV)

• Hepatitis C Virus (HCV)

• Human T-Lymphotropic Virus (HTLV), Types I and II

• Treponema pallidum (Syphilis)

• West Nile Virus (WNV) 

• Trypanosoma cruzi (Chagas disease)

• Emerging respiratory pathogens as per SFDA advisories

• Risk of variant Creutzfeldt-Jakob Disease (vCJD) based on geographic residence, surgical history and other risk factors

6.3.3.11 Laboratory Testing 

Donor testing must be performed on a blood specimen collected at the time of donation from a living donor, or from a specimen collected post-mortem from a deceased donor.

Testing must be performed using licensed or approved test kits recognized by SFDA, and in a laboratory that operates under a quality system equivalent to SFDA requirements for medical laboratories.

The following tests must be performed for all allogeneic donors:

• HIV-1 and HIV-2: Nucleic Acid Test (NAT) and/or serological test for HIV p24 antigen and HIV-1 and HIV-2 antibodies.

• HBV: NAT for HBV DNA and serological test for HBsAg and anti-HBc.

• HCV: NAT for HCV RNA and/or serological test for anti-HCV.

• HTLV-I and HTLV-II: Serological test for antibodies.

• Treponema pallidum: A validated serological test (e.g., RPR/VDRL with confirmatory test).

• For deceased donors in endemic areas or with relevant risk, testing for WNV (by NAT) and Trypanosoma cruzi (by serological test) is required.

A donor must be determined ineligible if laboratory tests are reactive, positive, or repeatedly reactive for any of the required tests.  

6.3.3.12 Eligibility Determination and Record Keeping 

A final determination of donor eligibility must be made by a designated, trained individual who has reviewed all screening and testing records, in accordance with the relevant local authority guidelines and regulations. 

The determination and the justification must be clearly documented and maintained for a minimum period as defined by SFDA record-keeping regulations stated in the Guide to Good Manufacturing Practice for Medicinal Products (link​) (e.g., a minimum of 30 years after the expiry of the product, or as per the latest SFDA guidance).

All records, including the DRAI, laboratory test results, and the final determination report, must be traceable to the specific donation and the resulting APHU.

6.3.4 Facility and Related Documentation

6.3.4.1 Manufacturers 

Manufacturing facility details including relevant certificates and documents such as GMP Certificate and license from local authority, Site Master File (SMF), and certificate of analysis for starting materials / finished product as applicable. Data requirements include submission of information on container closure Systems.

6.4 Nonclinical Study Reports 

In Module 4, preclinical data submission is not mandated for APHU applications; however, the SFDA may request such data on a case-by-case basis where deemed necessary.

6.5 Clinical Study Reports

In Module 5, a clinical development program must be submitted to support the safety and efficacy of the product for the intended therapeutic indication/s and target population/s. For novel treatments, additional robust clinical data may be required to establish proof of concept

- SFDA Guideline on Classification of Advanced Therapy Medicinal Products.

- Guidance on Submission of Chemistry, Manufacturing, and Control (CMC) Information for Cell-based Clinical Trial Applications.

- Guidance on Submission of Chemistry, Manufacturing, and Control (CMC) Information for Gene Therapy Clinical Trial Applications.

- General Considerations for CAR-T Cell Products annex.

- Annex 2A for Guide to Good Manufacturing Practice for Medicinal Products (Manufacture of Adnaced Therapy Medicinal Products for Human Use).

- Requirements for Importation of Minimally Manipulated Biological Products Intended for Human Application.

- Guideline on Good Pharmacovigilance Practices (GVP).

- Guideline on Good Pharmacovigilence Practices for ATMPs.

- General Considerations for Preclinical Studies Submissions.

- Clinical Considerations for Efficacy and Safety Assessment.​​

Abbreviation   .....................................     Definition

ADEs ........................................................ Adverse Drug Events

AEs  ........................................................ Adverse Events

anti-HBc  ................................................ Antibody to Hepatitis B Core Antigen

APHU  ........................................................ Allogeneic Products for Homologous Use

ATMP  ........................................................ Advanced Therapy Medicinal Product

BMP  ........................................................ Breakthrough Medicine Program 

CMC  ........................................................ Chemistry, Manufacturing and Controls 

CoC  ........................................................ Chain of Custody

CoI  ........................................................ Chain of Identity

CTD  ........................................................ Common Technical Document

DNA  ........................................................ Deoxyribonucleic Acid

DRAI  ........................................................ Donor Risk Assessment Interview

FMEA  ........................................................ Failure Mode and Effects Analysis

GMP  ........................................................ Good Manufacturing Practices 

 GVP  ........................................................ Good Pharmacovigilance Practices

HBsAg  ........................................................ Hepatitis B Surface Antigen

HBV  ........................................................ Hepatitis B Virus

HCPs  ........................................................ Healthcare Professionals

HCV  ........................................................ Hepatitis C Virus

HIV  ........................................................ Human Immunodeficiency Virus

HTLV-I / HTLV-II  ................................... Human T-Lymphotropic Virus Type I / Type II

ICUs  ........................................................ Intensive Care Units

ISO  ........................................................ International Organization for Standardization

MAH  ........................................................ Marketing Authorization Holders

MSCs  ........................................................ Mesenchymal Stem Cells

NAT  ........................................................ Nucleic Acid Test

NSM  ........................................................ Non-Substantial Manipulation

p24 antigen  ........................................... HIV p24 Capsid Protein Antigen

PBRER  ..................................................... Periodic Benefit-Risk Evaluation Report

PIL  ........................................................ Patient Information Leaflet

PRP  ........................................................ Plasma Reagin Pattern

PSUR  ........................................................ Periodic Safety Update Report

RCDAs  ........................................................ Relevant Communicable Diseases and Agents

RNA  ........................................................ Ribonucleic Acid

RMP  ........................................................ Risk Management Plan

SDI  ........................................................ Saudi Drug Information System

SFDA  ........................................................ Saudi Food and Drug Authority

SM  ........................................................ Substantial Manipulation

SMF  ........................................................ Site Master File

SOPs  ........................................................ Standard Operating Procedures

SPC  ........................................................ Summary of Product Characteristics

SSA  ........................................................ Saudi Specific Annex 

VDRL  ........................................................ Venereal Disease Research Laboratory Test

WNV  ........................................................ ​West Nile Virus

Allogenic Therapies
Therapies that use cells obtained from a donor and administered to a different recipient. These therapies offer advantages such as scalability, standardized manufacturing, and immediate product availability, although they may require immune compatibility assessment and immunosuppressive management.

Autologous Therapies
Therapies that utilize cells derived from and re-administered to the same individual. This approach minimizes the risk of immune rejection and improves long-term tolerability and safety.

Bioengineered Support Systems
Engineered systems designed to replicate specific physiological functions, such as artificial liver or pancreatic systems.

Biomaterial-Based Therapies
Therapies that combine cells, scaffolds, and biologically active molecules to restore tissue structure and function. Their regulatory classification depends on the mechanism of action and overall product design.

Cell-Based Gene Therapies
Therapies that combine cellular engineering and genetic modification technologies to restore or enhance specific biological functions. Examples include viral vector-mediated gene therapies, CRISPR-Cas9 gene editing, and RNA-based therapeutics for inherited, malignant, degenerative, and immune-mediated diseases.

Cell-Based Regenerative Medicine
A branch of regenerative medicine involving cell-based therapies such as stem cell or progenitor cell administration, as well as immunomodulatory therapies in which biologically active molecules or cell-derived secretions promote tissue repair and regeneration.

Cord Blood–Derived Stem Cells
Stem cells obtained from umbilical cord blood that are considered promising for regenerative applications due to their accessibility, proliferative capacity, and relatively low immunogenicity. They are being investigated for metabolic, cardiovascular, and neurological disorders.

Human Pluripotent Stem Cells (hPSCs)
Human-derived pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, characterized by unlimited self-renewal capacity and the ability to differentiate into cell types from all three germ layers.

Immunomodulatory Regenerative Therapies
Therapies that utilize biologically active molecules, extracellular vesicles, cytokines, or cell-derived secretomes to stimulate endogenous repair pathways and regulate inflammatory responses. These approaches aim to create a pro-regenerative environment that enhances tissue healing while reducing fibrosis and chronic inflammation.

Mesenchymal Stem/Stromal Cells (MSCs)
Multipotent progenitor cells with limited in vitro self-renewal capacity and the ability to differentiate into mesenchymal lineages such as osteoblasts, chondrocytes, and adipocytes. MSCs also possess immunomodulatory and anti-inflammatory properties.

Stem Cell–Based Therapy
A major area of regenerative medicine involving the use of pluripotent and multipotent stem cell populations for tissue repair and regeneration.

Tissue Engineering
A regenerative medicine approach involving the transplantation of laboratory-grown tissues or organs. It is commonly associated with the repair or replacement of structural tissues such as bone, cartilage, blood vessels, skin, and bladder, where restoration of both biological and mechanical function is essential.​

1. Introduction

This Annex is intended to streamline and accelerate the registration of Advanced Therapy Medicinal Products (ATMPs) under the Regulatory Framework for Regenerative Medicines through a flexible, science- and risk-based approach to Chemistry, Manufacturing, and Controls (CMC) data requirements. It defines the procedures for requesting exemptions from CMC requirements in cases where such exemptions are scientifically justified and product quality can be adequately assured at the time of approval. This approach supports the efficient submission of Module 3 (Quality) of the Common Technical Document (CTD) while ensuring that sufficient evidence is provided to demonstrate product quality.

2. Scope

​This exemption applies only to ATMPs that have been granted Breakthrough Medicine Designation (link) or Orphan Drug Designation (link).

3. Procedure for Requesting CMC Exemptions

Step 1: Submission of Request

Following the granting of designation, the applicant may submit request for exemption from certain CMC requirements to Designation.Drug@sfda.gov.sa, using the subject line "CMC Exemption Requests for ATMP".

The request shall include:

a) A copy of the designation Letter.

b) A complete ATMP Submission Plan Form, including the required information (justification and supported data) for each requested CMC exemption (link).

​This form shall be used by the applicant to request exemption for Chemistry, Manufacturing, and Controls (CMC) requirements, prior to the official submission of marketing authorization application of ATMP to the SFDA.

1. Product Information:

2. Check List for CMC Data (Module 3):

Notes:

• Where CMC data are partially available, unavailable, or proposed for waiver, the applicant shall provide a scientific justification with supportive data and expected submission date (when applicable) to facilitate SFDA assessment of the proposed CMC package.

• For each requested exemption, the required information shall be clearly identified and referenced to the relevant CTD Module 3 section.

Table​

سعادة نائب الرئيس التنفيذي لقطاع الدواء                                                  سلمه الله

الهيئة العامة للغذاء والدواء

السلام عليكم ورحمة الله وبركاته،،،

نتقدم إلى سعادتكم بطلب الحصول على تسجيل المستحضر الموضحة بياناته أدناه، علما بأنه تم إرفاق جميع البيانات والدراسات المطلوبة مع هذا الخطاب:

* Must be filled if deputation letter has been given to a consultant office to submit this product file

          وتقبلوا سعادتكم خالص التحية والتقدير

                                                                    مدير شركة ........................                                                          

                                                                                                                                                                                             الاسم:

                                                                                                                                                                                             التوقيع:

                                                                                                                                                                                              التاريخ:

                                                                                                                                                                                                                                 ختم الشركة​