Healthcare & Life Sciences Focus
Christina SochackiSenior Counsel, Head of Healthcare & Life Sciences - Saudi Arabia
Abdulmohsen AlSalehTrainee Lawyer,Corporate Commercial
As anticipated, the increase in regulatory activity over the last few years across the Middle East has not slowed down. With a vast array of significant healthcare transformation announcements coming out of the Kingdom of Saudi Arabia ("KSA" or “Saudi” or “Kingdom”) this year, we expect the next few years to bring further significant announcements and regulatory changes as the Kingdom’s Vision 2030 programme is well underway.
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 pertinent to pharmaceuticals, biologics, medical devices and other medical products in the KSA issued in 2022, through November.
SFDA Product Classification Guidance V.6.1 – new versionA new version of the SFDA Products Classification Guidance was issued in October to update a variety of sections.
Of particular interest is the clarification that chemicals labelled as for research use only and imported for educational and research institutions are not regulated by SFDA; these chemicals must obtain an importation license from Ministry of Education. Devices for educational and training purposes are not regulated as medical devices under the SFDA, for example: mock-ups and patient simulators.
Further, a new section was added for Veterinary Herbal Medicinal Products, to coincide with the earlier published new Data Requirement for Veterinary Herbal Medicinal Products.
Mechanism for Applying the Pricing of Pharmaceutical Products – new documentFollowing the issuance of new pricing rules for pharmaceutical products in 2021 (the Pricing Rules for Pharmaceutical Products), this new guidance details the process to apply new pricing to pharmaceuticals that are already in the market, including the requirement to apply over the old price a non-removable sticker showing the new price. The guidance aims to achieve the following:
Limiting the delay of members of the supply chain in relation to updating the pricing on new packages of registered pharmaceutical products;
Limiting pharmaceutical products that have old pricing from being shown at pharmacies and points of sale; and
Ensuring pharmaceutical products have a fair pricing which is accessible to patients.
This guidance should be read in conjunction with the Policy of Appeal to Drug Sector Decisions, Pricing Rules for Pharmaceutical Products, and the SFDA Circular on the Cancellation of the Requirement of Price Marking.
The Policy of Appeal to Drug SectorDecisions v1.2 – new versionThis new guidance document sets out the process of appealing a decision issued by the Drug Sector of the SFDA, and sets out the procedures of submitting a price revaluation request for the pharmaceutical products.
The scope of this guidance is limited to the permanent cessation of marketing of medical products, pricing decision appeal, and re-evaluation of a rejection decision of registration in relation to pharmaceuticals, herbals, and veterinary products.
Guidelines for Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products v3.4– new versionThis new version mainly removes text. For the selection of batches, where there are existing active substances that are known to be stable, it is no longer sufficient to provide data from two primary batches. Data from stability studies on at least three primary batches of the API should normally be provided.
Further, in relation to storage condition for existing substances that are known to be stable, it is no longer sufficient to provide data covering a minimum of six months. The long-term testing should normally take place over a minimum of 12 months for the number of batches specified in the section concerning the selection of batches, at the time of submission, and should be continued for a period of time sufficient to cover the proposed re-test period or shelf-life.
Finally, for the selection of batches, in the case of conventional dosage forms with APIs that are known to be stable, it is no longer sufficient to provide data from two primary batches. Data from stability studies should be provided on at least three primary batches of the finished pharmaceutical product.
Further, the new version provides updated recommendations for labelling statements.
Stability Testing of New Veterinary Drug Substances “Active Pharmaceutical Ingredients (APIs)” and Medicinal Products “Finished Pharmaceutical Products (FPPs)”– new documentThis new guideline is adapted from a revised version of the European Medicine agency’s GL3 VICH. The guideline addresses the information to be submitted in registration applications for new veterinary drug substances and associated medicinal products. This guidance does not currently seek to cover the information to be submitted for abbreviated or abridged applications, variations, or clinical trial applications.
Guide to Good Manufacturing Practice for Medicinal Products v4.1 – new versionGood Manufacturing Practice ("GMP") is part of quality management, which ensures that products are consistently produced and controlled to applicable quality standards. The SFDA’s update to its guide to GMP for medicinal products.
Updated Annexure 2, by adding a section (Annex 2B) in relation to manufactures of biological medicinal substances and products for human use. Biological medicinal substances and products can be defined largely by reference to their method of manufacture; the annex provides guidance on the full range of medicinal substances and products defined as biological.
Part A of the Annex contains supplementary guidance on the manufacture of biological medicinal substances and products – from control over seed lots and cell banks or starting material through to finishing activities and testing. Part B contains further guidance on selected types of biological medicinal substances and products.
The inclusion of some early steps of manufacture within the scope of the Annex does not imply that those steps will be routinely subject to inspection by the authorities. While antibiotics are not defined or included as biological products, where biological stages of manufacture occur, guidance in this Annex may be used.
In certain cases, other legislation may be applicable to the starting materials for biologicals.Data Requirements for Human Drugs Submission, Content of Dossier, v 3 – new versionA section was added to address generic products and the modules or section of the eCTD that would generally not be applicable. Further, a variety of additions were made to address addition information required to be submitted.
Guidance for Submission v5 – new versionThis guidance assists applicants and the industry in the preparation and submission of product applications for new marketing authorizations as well as renewals and variations to existing products to the SFDA. The guidance provides an outline of how the regulatory framework will be managed with respect to product applications by the SFDA. A variety of new document requirements and updates have been made.
Data Requirements for the Renewal of Marketing Authorisation for Human Medicinal Products v2.0 – new versionModule 1 and Module 3 have been updated in this new version, deleting from the modules certain sections.
This guideline considers issues associated with the processing of renewals with the aim of giving procedural guidance to marketing authorization holders ("MAHs") and applies to all types of human medicinal product registration pathways that are described in the Regulatory Framework for Drugs Approval.
The Registration Rules of Pharmaceutical, Herbal and Health Product Manufacturersand their Products Guideline v3 – new versionArticle 20/4 of the Implementing Regulations of the Law of Pharmaceutical and Herbal Establishments and Products, requires the registration committees to conduct certain updated tasks; this new version incorporates such updates and sets the regulatory frameworks for registering pharmaceutical, herbal, and health product manufacturers and their products.
Data Requirement for Veterinary Herbal Medicinal Products – new documentThis new document introduces to the SFDA regulation of herbal products for veterinary use, which has also now been added to the most recent version of SFDA’s Product Classification Guidance.
This guideline is mainly adapted from a revised version of both the EMA guideline on quality of herbal medicinal products/traditional herbal medicinal products and the SFDA Data Requirements for Veterinary Medicinal Products. It is intended to assist applicants in the preparation of Veterinary Herbal Medicinal Products ("VHMP") submissions to the SFDA. The data requirements for VHMP for each application will differ, based on the type of product VHMP, such as traditional medicines, vitamins, and minerals.
Products containing chemically defined isolated constituents or a mixture thereof are not herbal medicinal products. A VHMP is considered to be any plant or herb manufactured in a pharmaceutical dosage form and presented for the purpose of preventing or treating a disease in an animal. However, preparations consisting of dried or crushed herb(s) that form a minor component of a product intended for oral administration to healthy animals, as part of the animal’s diet, are not regarded as VHMP, provided that:
No indication for use of the product as an herbal veterinary medicine is made; and
None of the herbal substance(s) has pharmacological action on physiological function at the dose administered to the target animal, or the quantity of herb(s) is representative of that which might reasonably be expected to be ingested by an animal grazing on native pasture
The guideline should also be read in conjunction with Annex 7 “Manufacture of Herbal Medicinal Products” of the SFDA Good Manufacturing Practice for Medicinal Products. Contract Research Organization Guideline – new document
This new guideline is intended to be read in conjunction with guidelines previously published by the SFDA on clinical trials. It is implemented following public consultation earlier this year.
The guideline outlines the process to submit a Clinical Trials application. The process differs if such an application is made by a sponsor with a legal entity in Saudi Arabia, or by a sponsor without a legal entity in Saudi Arabia. The guideline also includes recommendations on organizational structure and service requirements for licensed CROs conducting clinical trials in Saudi Arabia. The SFDA encourages and recommends that licensed CROs include departments or individuals that ensure clinical trials are conducted in accordance with relevant regulations.
The guideline provides recommendations for the monitoring of clinical trials, which must be adhered to by licensed CROs and sponsors. These include, but are not limited to, recommendations for monitoring methods, monitoring plans, and the delegation of monitoring responsibilities to a licensed CRO. The SFDA also recommends that Clinical Research Associate (‘CRA’) employees working on clinical trials in Saudi Arabia should be citizens or permanent legal residents of Saudi Arabia, and should be authorized to work in Saudi Arabia, in accordance to local regulations.
The guideline highlights contractual obligations to be observed by Parties engaged in clinical trial activities in Saudi Arabia. All clinical trial and associated agreements must be submitted to the SFDA, in both Arabic and English. The terms and conditions governing these agreements must be in compliance with the Saudi Arabian laws and regulations. The SFDA issued version 4, consisting of 375 pages, in line with the European Commission Volume 4 of ‘The rules governing medicinal products in the European Union’ laid down in Commission Directives 91/356/EEC, as amended by Directive 2003/94/EC, and 91/412/EEC respectively.
It is mandatory to obtain SFDA approval before conducting clinical trials or bioequivalence studies, in accordance with the requirements in Table 1 of this regulation.
Regulations and Requirements for Conducting Clinical Trials on Drugs v2.3 – new versionIt is mandatory to obtain SFDA approval before conducting clinical trials or bioequivalence studies, in accordance with the requirements in Table 1 of this regulation. The clinical trial will not be registered if it was started without the authority’s approval. Phase 1 trials must be conducted in an SFDA accredited phase 1 unit. On the other hand, The bioequivalence studies must be conducted in centres that are licensed by SFDA or the Gulf Health Council.
Added in this version is a clarification that in case the trial duration is less than one year, the applicant must submit the progress report every three months. Further detailed in this new version are the cases in which the SFDA has the right to temporarily suspend the clinical trial in order to protect human, investigate the same, and then decide whether to lift the suspension or terminate the study.
Finally, further clarity is provided regard when the SFDA can provide review priority and amend/lift certain regulatory requirements, including during pandemics, national emergencies, and where there is no alternative treatment in Saudi Arabia in respect of the trial drugs submitted for registration purposes.
Guidance on Good Pharmacovigilance Practices (GVP) v 3 – new versionA variety of clarifications have been provided in this new version, including in relation to the qualifications of the qualified person responsible for pharmacovigilance in KSA, delegation of pharmacovigilance tasks to third parties, new requirements for pharmacovigilance consultation service agencies, and a variety of other clarifications, additions, and deletions.
Guidance on Publication of Public Assessment Reports for Medicinal Products for Human Use (Saudi-PAR) – new documentThe SFDA publishes on its website information relating to the evaluation of applications via public assessment reports, 'Saudi Public Assessment Report (‘Saudi-PAR’) for medicinal products for human use within 90-120 working days of authorisation. This guidance for the marketing authorization applicants is intended to provide the rationale, approach, and procedure for publishing the Saudi-PAR with clarification of SFDA's policies for developing Saudi-PAR from the Original Assessment Reports, which were generated during the quality, safety and efficacy evaluation for the medicinal products submitted to SFDA. This guidance contains the clarification of the commercially confidential data and personal data that will be deleted from the report in accordance with the Saudi system and relevant international agreements.
Conditional Approval for Medicinal Productsfor Human Use – new documentIn order to meet unmet medical needs of patients and in the interests of public health, it may be necessary to grant marketing authorizations on the basis of less complete data than is normally the case and subject to specific obligations, hereinafter ‘conditional approval’. In line with Chapter 3, Article 17 of the Registration Rules of Pharmaceutical, Herbal, and Health Product Manufacturers and their Products Guideline, SFDA has adopted this accelerated pathway to facilitate timely access of promising new therapies however, conditionally approved medicinal products are exclusively for hospital supply under certain distribution conditions.
Guidance for Graphic Design of Medication Packaging v 3.1 – new versionAdditional guidance has been provided regarding the method of reporting medication errors, differentiating between similar product names, and a guide to labelling and packaging of ophthalmic preparations and paralyzing agents.
Licensing Requirements for Medical Devices and Equipment Installations (MDS-REQ 9) – new document.
This new SFDA guidance sets out the requirements for the licensing of medical device and equipment installations. As such, this new guidance replaces a wide range of documents related to the procedural rules and guidelines for the licensing of the above-mentioned activities.
The scope of this guidance covers medical device and equipment installations, including manufacturers/factories, authorised representatives, importers, suppliers, optics, warehouses, clinical trial inspections, conformity inspections, laboratories, quality inspection of radiology facilities at health institutions, medical maintenance, and technical consultations. Installations conducting retail activities as their main form of business are excluded from the application of this guidance.
Guidance on Innovative Medical Devices v 2 (MDS-G00 2) – new versionIn March, version 2 of the Guidance on Innovative Medical Devices was issued to update it from MDS-G43 to MDS-G002.
In accordance with article 9 of the KSA Medical Device Law of 1442H, permitting the SFDA to exempt innovative medical devices from some of the requirements and procedures to obtain a marketing authorisation, the SFDA developed a pathway for “Innovative Medical Devices” to allow patients access to novel technologies is a timely manner.
This guidance defines the designation criteria for Innovative Medical Devices, outlines the requirements for applying through the Innovative Medical Devices Pathway, and explains the submission process.
A 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; or
Any other criteria to be determined by the authority and published through the website.
Applicants must justify to the SFDA how the medical device meets these criteria and the SFDA may request additional information from applicants if needed to make a final determination.
Requirements of Importation and Re-Exportation for Radioactive Materials Usedin Medical Applications (MDS-REQ 6)– new documentThis new document replaces MDS-G24 v2, dated 01/01/2021, and reflects the new Medical Devices Law (issued by Royal Decree No. (M/54) dated 06/07/1442 H and its executive regulations, Board Resolution No. (3-29-1443) dated 2/19/1443 H). Thus, general amendments have been made to align the guidance with the new law, including updating the required documents section.
Requirements for Unique Device Identification (UDI) for Medical Devices v 4 (MDS-REQ 7)– new versionThis new version is updated reflect the new Medical Devices Law. Under the prior version, there were provisional accredited issuing agencies; the accepted issuing agencies for UDI are GS1, HIBCC and ICCBBA.
On the other hand, references to UDI in healthcare delivery have been removed. Under version 3, health systems were required to take steps necessary to facilitate and leverage the implementation of UDI throughout KSA by putting systems and processes in place to capture and use UDI in real-time, including the documentation of the use or implementation of a device’s UDI within patient’s electronic health records, the inclusion of UDI in inventory management and billing systems, the use of UDI in the communication of device safety concerns, and leveraging UDI for the easily accessible clinician and patient information. Medical devices imported before compliance date can be distributed for 1 years after the compliance date. The enforcement plan will be in phases based on device risk classes and according to SFDA announcement on the website here.
Requirements for Shipments Clearance Medical Devices at Ports of Entries v 5 (MDS-REQ 5) – new versionThe SFDA updated this new version from MDS-G21 to MDS-REQ5. It sets out the necessary steps to obtain SFDA approval to release imported or exported medical devices at port of entries in KSA. One of the key changes is that the requirements not only apply to imported medical devices, but also exported medical devices.
The updated MDS-REQ5 has clarified the requirements for “storage and transportation of the product”, and “product shelf life” of medical devices, as it now sets out the necessary procedures with which importers need to comply. Furthermore, Annexure 2 has been added to the updated version, which contains a list of all the other SFDA requirements that may be applicable depending on the nature of the medical device in question.
Requirements for Safe Use of Medical Devices Inside Healthcare Facilities (MDS-REQ 3)– new documentThis new guidance replaces the following documents:
Guidance for Healthcare Providers for Storage and Transportation of Medical Devices (MDSG17); and
Requirements for Quality, Safety and Effectiveness of Medical Devices at Healthcare Facilities.
The guidance sets out the requirements for safe use of medical devices and radioactive medical materials inside healthcare facilities in order to ensure safety, efficiency and quality of them, and reduce potential risks corresponding to use and handle them inside healthcare facilities.We do not expect legislation developments to slow down anytime soon. Stay tuned for more updates.
For further information, please contact healthcare@tamimi.com.
Published in January 2023
