KSA 2024 Regulatory Updates: Key Medical Device & Pharma Developments
Healthcare & Life Sciences Focus
Christina SochackiSenior Counsel,Corporate Commercial
The regulatory landscape in Saudi Arabia continued to evolve in 2024. Staying on-top of the updates and new regulations, circulars, and guidance from the Saudi Food & Drug Authority (‘SFDA’) is no longer a passive exercise; things are changing too quickly. Set out below, we summarise the key new or updated pieces of legislation issued in 2024 that are pertinent to pharmaceuticals, biologics, medical devices and other medical products in the KSA.
The last version, version 5.2, was updated in 2022 and added the criteria for both first generics and biosimilars qualifying for priority review designation. The priority review process for the first generic drug was intended for the product considered the first generic to the innovative product that is already registered in SFDA. However, this new Version 5.3 removed the criteria for the first generic qualifying for priority review designation. The drug types that may request priority review designation are:
New drug
Biosimilar
Biologic
Conditional approval is issued when technical requirements that must be provided in the dossier are not met or completed and the benefits of the product outweigh its potential risks, as determined by SFDA. SFDA has adopted this accelerated pathway to facilitate timely access of promising new therapies while ensuring the scientific rigor of the assessment of their quality, safety, and efficacy.
However, conditionally approved medicinal products are exclusively for government health sector supply. The conditional approval is effective for two years, as this approval is not intended to remain conditional indefinitely. Up to two extensions, each of 2 years are available, resulting in a possible maximum conditional approval period of 6 years.
This new guidance document sets out the eligibility requirements, obligations, rules on the granting of such a ‘Conditional Approval’ for new human medicines, including biologics. Specifically, this document applies to new medicinal products (including biologics) for human use that belong to one of the following categories:
Medicinal products that aim at the treatment, the prevention or the medical diagnosis of seriously debilitating diseases or life-threatening diseases; or
Medicinal products to be used in emergency situations, such as in the situation of a pandemic; in response to public health threats duly recognized either by the World Health Organization or by the Ministry of Health of Saudi Arabia.
Amongst other additions and modifications, the SFDA added requirements that in Module 1:
a declaration letter is submitted on the patent status of the product; and
a Marketing Authorization holder section, which should contain an “Authorization Letter” on a “Finished Product Manufacturer” letterhead appointing the “Marketing Authorization Holder” (which is a company that owns the right to market the product in the Kingdom and is fully responsible for its quality, effectiveness, safety and post-marketing surveillance after it is marketed as well as related procedures from the sale, withdrawal or discard.).
Every submission to the SFDA is required to include certain preclinical data to support the safety and efficacy of the pharmaceutical product. The required preclinical data depends on the type of submission. This guidance provides recommendations on the minimum preclinical data requirements for human medicinal and biological products. It applies to data supporting clinical trials applications and marketing authorization / variation applications (including impurity qualification) of chemical and biological pharmaceutical substances and products.
This document is composed of two parts:
Part A of the document is intended as a guidance tool for applicants to ensure that the minimum required preclinical data to establish the product’s safety and efficacy are included in the applicant’s submission; and
Part B of the document is a writing guide, which provides guidance to applicants in regard to the format and content of the non-clinical data submitted to the SFDA.
The SFDA reserves the right to request information or material not specifically described in this guide in order to assess the safety, efficacy, or quality of a therapeutic product. The guide is to be read in conjunction with other applicable SFDA documents, as well as the International Council for Harmonization (ICH) guidelines that are implemented by SFDA.
The information discussed in this new guidance does not apply to veterinary and herbal product submissions.
Some of the main changes in the new version are summarised, below.
Adds a new section on “regulation of raw materials”;
Raw materials regulation in SFDA depends on several criteria, such as the statutory definitions, the manufacture intended purpose, and the current SFDA’s regulations and standards.
SFDA has published a guidance to provide manufactures and stakeholders with information regarding the regulatory path of these materials.
Updates the classification and regulatory path of food supplements;SFDA has updated the regulation of food supplements and issued a circular to clarify the classification criteria. Food supplements will be classified as “Pharmaceutical Product” if meets any of the following criteria:
Contains medicinal herb(s) or herbs with medical intended purpose: Herbal Product;
Concertation(s) is/are above the daily allowed limit stated in technical standards SFDA.FD 55: Human Pharmaceutical Product;
Intended to treat, prevent and/or diagnose a human disease: Human Pharmaceutical Product;
Contains active medicinal/ pharmaceutical ingredient:Human Pharmaceutical Product;
Not intended for ingestion such as topicals, inhalers, suppositories. Etc:Human Pharmaceutical Product;
Concertation(s) is/are within the daily allowed limit stated in technical standards SFDA.FD 55 and intended to treat, prevent and/or diagnose a human disease:Health Product;
Products contain: fatty acids, amino acids, enzymes, prebiotics and probiotics, collagen, dietary fibers, and intended to treat, prevent and/or diagnose a human disease: Health Product.
See also, Circular 1337 Updating classification criteria for food supplement.
Food supplements must comply with technical standards SFDA.FD 55 Food Supplements.
Updates to the customer-made medical devices section;
Products for clearance section added, detailing that some products do not need a marketing authorization/ registration application; however, a clearance approval must be obtained in order to permit the entry of the product into Saudi Arabia. Products in this category may include but are not limited to:
Unregistered Drug or Products;
Unregistered Veterinary Products;
Samples;
Raw Medical Plants;
Animal grooming;
Proficiency Test samples for food products;
Medical Devices (see SFDA MDS-REQ 5, Clearance for Requirements of Medical Devices); and
Food (see SFDA Food Clearance Conditions and Requirements).
Innovative medical devices receive priority review if they demonstrate significant advantages over existing alternatives.
SFDA guidance MDS-G009 defines and clarifies the requirements of manufacturers of point of care (‘POC’) medical devices. In-house in vitro diagnostic (‘IH-IVD’) medical devices are a subset of POC medical devices. This guidance outlines the development and post market activities for IH-IVD medical devices.
IH-IVDs may have been designed in-house, could use components that have been brought together and given a medical intended purpose, or could be a commercial kit where the lab has changed the intended purpose that includes changing sample type or population.
The quality management system (‘QMS’) section of the guide describes the general requirements for in-house assays in KSA and creation of performance data and documents required. This documentation may be required to be submitted to SFDA on request and should therefore be available.
The design and development should align with the core requirements, detailed in the guide, that should be defined and documented in the quality system in order to generate data and records that provide objective evidence of the design process.
Further, the tests need to be designed to meet the needs of patients, clinicians and should be state of the art – they need to produce clinically relevant information to support medical practice. The Essential Principles (set out in MDS-REQ1, Requirements for Medical Devices Marketing Authorization) should be considered throughout the design of the test according to the QMS and the data generated must support the intended use of the test as described in labelling and on Medical Device Application Form MDS – G009 Annex 1. There are many elements to consider when describing the intended use; Table 1 includes a non-exhaustive list of considerations.
Other topics covered by the guide are risk, performance, manufacture/production, labelling, packaging and transport of the IH-IVD within the laboratory, and post-market surveillance.
The purpose of this document is to assist the manufacturers and authorized representatives of surgical sutures with/without needles, used for general soft tissue approximation and wound closure/ support, to comply with the SFDA Requirements for Medical Devices Marketing Authorization (MDS-REQ 1). This document does not add any requirements related to compliance with the essential principles of safety and performance, which are specified in MDS-REQ 1; rather, it just indicates some information and guidance of surgical sutures related characteristics.
The guidance applies to biotechnology-based medical device manufacturers. The guidance aims to: clarify regulatory and technical requirements to be taken into consideration during the design and manufacturing stages of biotechnology-based medical devices and its products; clarifying lists of relevant standards and guidelines; as well as provide important contact information and links.
A variety of new key definitions were added, as well as: a new section on data processing systems, for when computerized systems are used; a new section regarding the control of equipment and materials; requirements for the release of blood and blood components and standard operating procedures; new sections on donor eligibility, collection of blood and blood components, and testing for infectious markers; amongst other updated and additions.
Each blood establishment must develop and maintain a “Quality System” that is based on the principles of “Good Manufacturing Practices” (‘GMP”). For blood and blood components imported from countries outside Saudi Arabia and intended for use or distribution in Saudi Arabia, there must be a “Quality Management System” for blood establishments in the stages preceding importation equivalent to the “Quality Management System” established in Saudi Arabia.
The SFDA issued a new guidance document on the approach to dealing with patents when registering generic drugs with the SFDA.
Back in 2022, the SFDA issued for public consultation a draft "procedure to deal with patent when registering generic products in the SFDA". SFDA's goal is to raise the level of transparency in the procedures of the SFDA, promote trust int he procedures for dealing with patents related to pharmaceutical products, and facilitate the procedures for registering generic pharmaceuticals.
Now, in cooperation with the Saudi Authority for Intellectual Property (‘SAIP’), the new guidance provides requirements for 1) generic companies wishing to register their products with the SFDA, and 2) innovator companies who claim that the generic company has violated their patents.
Requirements for Generic Companies When Seeking to Register Products Covered by an Innovator Patent
when the generic company applies for registration of its product in SFDA, if there is a patent in the innovator product file in SFDA, then SFDA will request a Freedom to Operate ("FTO") letter from the generic company (in the form specified by the SFDA, which includes a declaration from the generics company);
Generic companies must assign an intellectual property agent licensed by SAIP to conduct such studies;
In addition, the generic company must submit a declaration that its generic product does not infringe a patent of any product (SFDA provide a specific form for this);
Based on the FTO letter, SFDA will register the generic product; and
If an FTO letter is not produced, registration of the generic will be rejected.
Of particular interest is that the generic company has the right to apply for the registration of a generic product of an innovative product, without submitting FTO letter, if the application is made within six months before the expiry of the patent, taking into consideration that the marketing of the generic product will not be allowed before patent expiration.
In terms of the innovator companies, they must submit a copy of the patent document issued by SAIP in the registration file for products submitted to SFDA.
If the patent document of the innovated product has not been issued at the time of submitting the registration file, the innovator company must submit such document to SFDA within (30) days from its date of issue. If the innovator company seeks to claim that the generic product infringes the patent of its product, the company may process their claims in the Commercial Court. If a final judgment is issued by the court in favor of the innovator company, then SFDA will comply with that judgment.
SFDA issued a new guidance document, entitled Economic Evaluation Studies Guidelines, Version 1 of July 2024 (‘EES Guidance’). It aims to help manufacturers, marketing authorization holders, and agents by describing a standard method for performing, submitting, or publishing an Economic Evaluation Study (‘EES’).
This guidance will have a phased implementation as follows:
July-December 2024, voluntary for General Requirements and For Economic Evaluation Requirements;
January - June 2025, mandatory for General Requirements and voluntary for Economic Evaluation Requirements; and
July 2025, mandatory for both General and Economic Evaluation Requirements.
SFDA uses EES' to determine the added value deserved over the current standard of practice utilized in Saudi Arabia’s healthcare system. During SFDA’s pricing of pharmaceutical products, SFDA may consider economic studies; innovative and biological product pricing should take into account “clinical comparative studies and pharmacoeconomic studies with registered therapeutic alternatives” (Article 3 of the Pharmaceutical Pricing Rules).
This new EES Guidance applies to all human pharmaceutical products undergoing pricing procedures including, registration, price re-evaluation, and renewal in SFDA.
General requirements include:
Epidemiological Data: Information on the disease, its prevalence, incidence, targeted population, no. of patients both globally and in Saudi Arabia;
Market Share: The proportion of the pharmaceutical product sales in volume and value compared to the total number of alternatives used in treating the same condition. Information on the current market share of the product in Saudi Arabia are required to be documented in the submission file to the SFDA. In case of a new product, the estimates of the market share for the upcoming five years are required to be documented;
Drug Marketing Plan: Drug marketing plan refers to the targeted segment of healthcare in Saudi Arabia that the product is mainly distributed in. Information on the targeted segment should be presented in the submission file to the SFDA; and
Access Agreements: Access agreements are defined as arrangements with companies at time of submission to address points supporting the access of medicine, such as: 1. Entry agreements; 2. Localization; 3. Incentives granted; 4. Breakthrough designation; 5. Patient Support Program (PSP); or 6. any other initiatives to support the access of medicine.
In addition, a summary conclusion from the following Health Technology Assessment (HTA) agencies are required to be presented, such as: The National Institute for Health and Care Excellence (NICE); Institute for Clinical and Economic Review (ICER); Canadian Agency for Drugs and Technologies in Health (CADTH); Haute Autorité de santé (HAS); Pharmaceutical Benefits Advisory Committee (PBAC) …etc.
The SFDA EES Guidance provides information on the most suitable EES based on the product type (such as new chemical, biologic, general chemical, biosimilar), including full economic evaluation (such as cost effectiveness analysis, cost minimization analysis, and cost utility analysis) and partial economic evaluation (such as budget impact analysis).
For generic chemical products, it’s optional to submit an EES.
The relevant forms are attached in the EES Guidance's appendix, which should be submitted to the SFDA as part of the eCTD section 1.8.2 (Other documents related). The applicant must provide justifications for not submitting any required data.
SFDA issued an amended guideline on "Regulatory Framework for Drug Approvals", version 6.4, of June 2024 (‘Drug Approval Guideline’). The updates focus on granting SFDA more discretion in cancelling application requests and and adds a section regarding the process for designating a medicine as a breakthrough medicine.
Guideline OverviewIn general, the SFDA has developed this administrative document to provide assistance for stakeholders on how to submit applications for various types of drug products and the procedure to approve the applications. Besides the Market Authorization Application (‘MAA’) of various types of drug products, it also describes variations applications and renewal of the MAA. Time-frames for processing applications through to marketing the product in Saudi Arabia are also included in this document.
This framework applicable to all types of drug product submitted for registration, variation or renewal.
New Marketing Authorization ApplicationAmendments in this section focus on the parameters surrounding SFDA's ability to cancel an application request, lowering the threshold and providing SFDA more discretion in cancelling an application.
SFDA has clarified that an MAA request may also be rejected "if the applicant provided unsatisfied requirements or did not include the required documents or justification for the absence of a document according to SFDA guidelines." Previously it was stated that the application would be rejected for "Failure to provide acceptable clarifications after the third wave.", but this has been removed. It remains that it may be cancelled in the case that there is no response from the applicant within 30 working days.
Previously, "The applicant will have a total of four (4) waves for Evaluation / inspection and Pricing" and "The registration request will be rejected in . . . Failure to provide acceptable clarifications after the 4th wave."
Now, the updated version gives SFDA an lower threshold to cancel the application, stating "The applicant will have a maximum of four (4) waves for Assessment and pricing, and the SFDA has the right to take a decision at any time during the assessment step, regardless of the wave number." Allowing the SFDA to cancel the registration request "If the applicant provided unsatisfied requirements or did not include the required documents or justification for the absence of a document according to SFDA guidelines."
Breakthrough Medicine Designation:This new section incorporates the updated (v1.1 of the April 2024) Breakthrough Medicine Program guidance document. The Breakthrough Medicine Program is intended to expedite the development and review of new drugs that can treat serious or life-threatening conditions where there is a lack of effective treatment options. The goal is to ensure that promising drugs are made available as soon as possible, provided that their benefits outweigh their risks. (See my subsequent post on the Breakthrough Medicine Program guideline).
Variation of Marketing Authorization:Similar to the MAA application section, SFDA has expanded its authority to cancel a variation application, granting itself more discretion.
Previously, an application would be cancelled for "Failure to provide acceptable clarifications after the second wave". Now, "If the applicant chose the wrong variation type according to the Guidelines for Variation Requirements, provided unsatisfied requirements, or did not include the required documents or justification for the absence of a document according to relevant SFDA guidelines." It remains that SFDA may cancel the variation request if no response is received from the applicant within 30 working days.
Similarly, it was added that while the applicant will have a maximum of three (3) waves for Assessment, and pricing, "the SFDA has the right to take a decision at any time during the assessment step, regardless of the wave number", and cancel the application.
Finally, reference to the applicants right to appeal within 60 calendar days of the SFDA’s final decision, was removed, however, it is expected that the right to appeal a decision, submitting an Objection Request, is still available to applicants under the latest version of the SFDA's appeal policy on the eSDR website.
Objection RequestsAs per the eSDR website, the types of objections that can be made are:
If the product registration request is accepted, the system allows the company representative to raise objection to the price and the expiry duration;
If the request for "Variation" is accepted, the system allows the representative of the company to raise objection to the price only;
If the product registration request is rejected, the system allows the company representative to raise objection to the rejection decisions;
If a price adjustment request is rejected, the system allows the company representative to raise objection to the rejection decisions;
If a request for modification of non-price data is rejected, the representative of the company is not allowed to request an objection, and requests variation again;
If a request for a price adjustment and other data is rejected in the same order, the representative of the company can only raise objection to the decision of rejecting the price and submit a request for an adjustment to the rest of the data;
If a request for cancellation is rejected, the representative of the company can submit objection to the rejection decision;
If a renewal request is rejected, the representative of the company can raise objection to the rejection decision; and
If the renewal request is accepted, the company representative is not allowed to object any rejected request prior to the renewal date.
Renewal of Marketing AuthorizationAs with the other sections, the SFDA removed "failure to provide acceptable clarifications after the first wave" and instead, SFDA may now cancel a renewal request for "failure to provide acceptable clarifications."
It remains that the applicant has the right to appeal a pricing decision within 60 calendar days of the SFDA’s final decision (for more information refer to the SFDA Policy of Appeal to Drug Sector Decisions).
SFDA issued a new version of its Requirements for Clinical Trials of Medical Devices, MDS REQ 2, V.5 (‘Guidance’). The purpose of this document is to specify and clarify the requirements for conducting clinical trials of medical devices within KSA.
In general, the Guidance was updated to bring it in line with the Medical Devices Law (Royal Decree No. (M/54) dated 6/7/1442 AH) & its Implementing Regulations, update references to new regulatory pathways (including for clinical trials involving innovative medical devices), and clarify specifics of the required documents.
Specific Updates HighlightedThe "Procedures" section adds details concerning the requirements to and process for notifying The National Center for Medical Devices Reporting regarding any serious adverse events within the specified time period indicated in the Guidance. New processes and timeframes were added for suspension of clinical trials.
The Guidance also provides additional clarity regarding the "Required Documents", including the requirements now for version-controlled documents. There is also the addition of a Case Report Form:
"A version-controlled paper or electronic CRF to collect data from trial subjects and capture all the information required by the protocol. The CRFs shall include information on the condition of each subjects upon entering, and during the course of the clinical trial, exposure to the investigational device and any other therapies. The CRF shall specify the version number and date of the document as approved by the local EC/IRB."
In line with other updates we have seen over recent years, SFDA is swiftly acting to incorporate new legislation, innovations, and stakeholder feedback into its regulatory processes. We expect such updates to continue to occur throughout a swath of legislation, as the Kingdom continues is transformation program.
SFDA updated its dedicated pathway for "Innovative Medical Devices", with the goal of accelerating the regulatory procedures and facilitate patients’ and healthcare practitioners’ access to novel technologies with significant benefits over available products, all while ensuring safety and effectiveness.
An Innovative Medical Device is defined as a medical device with an innovative idea in technology, use or performance, and which has not previously placed on the market, locally or internationally.
The new SFDA guidance applies to innovators, developers, manufacturers, and authorized representatives wishing to obtain Medical Devices Marketing Authorization for Innovative Medical Devices.
Two PathwaysThis new pathway will continue to require providing evidence that the medical device meets the Essential Principles for Safety and Performance (‘EPSP’). The pathway is comprised of two stages:
Pre-Submission Assessment: where continuous feedback and guidance is provided by SFDA, based on SFDA expectations and regulatory requirements, during medical device’s technical file preparation and prior to applying for marketing authorization; and
Priority Assessment for Marketing Authorization: the innovative medical device's MDMA application in given priority review, and is to be reviewed in front of the MDMA applications queue. Such priority does not mean that MDMA technical file assessment will be shortened or reduced in any way; it just means that the assessment, that will continue to be comprehensive due to the novelty of the technology, will commence sooner after receipt of the technical file.
EligibilityA medical device may be designated as an Innovative Medical Device if it meets the following conditions:
The medical device is designed with innovative features in the technology, indications for use, or performance attributes that have no equivalence in the local/global market;
The medical device provides a considerable clinical/medical advantage over existing alternative treatments;
Any other criteria to be determined by the SFDA and published through the website.
Applicants must justify how the medical device meets these criteria; SFDA may request additional information from applicants if needed to make a final determination.
Conditional marketing authorization may be granted to some Innovative Medical Devices that comply with valid clinical evidence. Conditional marketing authorization would allow the applicant to market the Innovative Medical Device but the devices would be subject to SFDA post-market requirements (such as limitations on distribution), and post-market surveillance studies. Full marketing authorization could be obtained if the application fulfils all SFDA MDMA requirements.
The SFDA’s initiative aims to support investment and industry in the field of medical device and supply software. SFDA expects that the new guidance will pave the way for innovators, research centers, and investors to introduce modern technologies in the Kingdom of Saudi Arabia, as well as to contribute to the advancement of digital diagnosis and treatment mechanisms.
For further information,please contact healthcare@tamimi.com.
Published in January 2025
