English — official EDA PDF (current v02/2025 file on the guidelines index)

1. Introduction

This Guideline concerns the regulatory procedures for registering locally manufactured medical devices for factories holding ISO 13485:2016 certificate without CE certificate. This decision shall be implemented in accordance with the following : Registration of a medical device that was registered before during the validity of the CE certificate and the registration license is still valid Manufacturer submits a petition, after which the manufacturer will be granted a non-renewable 6-month period for production from the date of accepting the petition before submitting the registration file, provided that the factory applies GMP in accordance with the procedures of Central Administration for inspection of pharmaceutical institutions . Production is permitted for a period of one year from the date of submitting the registration file, provided that the factory applies GMP in accordance with the procedures of Central Central Administration for inspection of pharmaceutical institutions If the requirements of re-registration file are not met upon the expiration of this period, production of the device and raw materials importation shall be ceased. Registration of a sterile/non-sterile medical device that was registered before during the validity of the CE certificate and whose registration license has expired Production will be permitted for a period of one year from the date of submitting the registration file, provided that the factory applies Good Manufacturing Practices (GMP) in accordance with the procedures of Central Administration for inspection of pharmaceutical institutions If the requirements of the re-registration file are not met at the end of this period, production of the device and raw materials importation shall be ceased. Registration of a non- sterile Class IIa, IIb and III medical device not registered before Trading will not be permitted until the completion of the registration procedures. -Factories are granted a period of one year to reconcile their situations from the issuance date ofthis guidelines to complete the registration procedures. -During the granted period, trading is the responsibility of the manufacturer, as the followed procedures before the issuance of the guidelines. -Medical devices that do not have an initial acceptance number will not be permitted to be traded after One year from the issuance of this guidelines. Registration of a sterile medical device not registered before Trading will not be permitted until the completion of the registration procedures. Version number/year:02/2025

2. Definitions

1. Medical device: Any device, instrument, medium, machine, or application, including what is being implanted, or any laboratory reagent used in the laboratory, or electronic program, or substance or any other similar or related manufactured by the manufacturing company for the purpose of human use, whether used alone or in combination for one or more of the following medical purposes: ➢ Diagnosis, prevention, monitoring, treatment, alleviation of disease. ➢ Diagnosis, monitor, treatment, alleviation, compensation for an injury. ➢ Investigation, replacement, modification, or support of the anatomy or of a physiological process. ➢ Supporting or sustaining life. ➢ Control of conception. ➢ Disinfection of medical devices. ➢ Providing information by means of in vitro examination of specimens derived or taken from the human body. Provided that it does not achieve its primary intended action by pharmacological, immunological, or metabolic means, in or on the human body, but which may be assisted in its intended function by such means. 2. Locally manufactured medical devices: The medical devices that are manufactured in factories inside the Arab Republic of Egypt. 3. non-sterile medical device: A medical device that is manufactured without being sterilized and is used as it is without sterilization or requires sterilization by the user before the use. 4. Factory: A local factory for medical devices. 5. Registration License: The EDA approval of the production, sale and promotion of a device inside the Arab Republic of Egypt after reviewing the device support guides. 6. Registration applicant: A local manufacturer, a scientific office for a local manufacturer. 7. Registration applicant representative: The authorized representative of the registration applicant to follow up all the works within the registration department. 8. Validation: A documentation process to verify that a process, procedure or activity will always lead to the expected results, and often includes qualification of systems and equipment, which is a requirement of GMP. 9. Step over benches: They are used in change rooms to form part of the change procedures, allowing personnel to change their clothing and footwear safely inside the cleanroom to minimize the risk of cross contamination

3. Related guidelines

• Regulatory Guideline for registration of Imported and Locally Manufactured Medical Devices with International Quality Certificates • Regulatory Guideline for Labelling Requirements for Medical Devices, Medical and Laboratory Equipment and in vitro Diagnostics, Components and Production Inputs • Guideline for Using International Barcodes for All Medical Devices (UDI) Version number/year:02/2025

4. Classification of medical devices (EU-MDD Annex IX)

a) Class I – Is (sterile) – I m (measurable), I (non-sterile) b) Class II a c) Class II b d) Class III - These requirements apply to medical devices' factories classified as class Is, IIa, IIb, and III. - These requirements are not applied to medical devices' factories classified as I non-sterile, except for devices in pharmaceutical dosage form.

5. Technical requirements for medical devices factories

5.1 General conditions for a manufacturing site

1. Factory must have obtained the necessary approvals from the competent authorities (Industrial Development Authority, Investment Authority, or General Authority for Suez Canal Economic Zone). 2. Factory must have its own independent entrances and exits. 3. Factory name must be shown in a visible signboard. 4. Height between the factory floor and the lower surface of the ceiling should not be less than 2.60 m. 5. Facility floor must be at the same level as the neighbouring land or higher, except when adequate precautions are taken to prevent water leakage into the factory, including creating a drainage network at an appropriate distance in order not to be a source of pollution. In all cases, manufacturing or storage steps must not be in a basement, with the exception of network services and utilities. 6. Manufacturing site must conform to the engineering drawings submitted to EDA. No modification may be made to the site before submitting a request for the required modification and conducting an actual inspection of the factory to ensure that health and technical requirements are met. 7. There must be a generator connected to the factory electrical circuit (for emergencies only). Recommendation: The committee recommends the presence of an uninterrupted power supply (UPS) device for operations or steps that require an uninterrupted power supply. The committee also recommends submitting the following recommendations to the Industrial Development Authority (IDA): 1) The presence of a ground connection grid 2) When allocating land for the establishment of a medical devices factory, it should be taken into account that it is far from sources of infection and pollution and that it is in an environmentally appropriate area. 3) Spaces should be suitable for the number of workers. Version number/year:02/2025

5.2 Technical requirements of factory

1. Separate bathrooms from changing rooms, with bathrooms being located before the gowning area; 2. Put a shoe rack (open stand) for street shoes and another for bathrooms; 3. Provide a ventilation source in bathrooms; 4. Place air curtains and insect zappers at all factory entrances (directly overlooking the street); 5. Regarding the primary gowning area, where street clothes are replaced with factory clothes and they are not unclassified, the following must be observed: 1) Separate street shoes from shoes worn inside the factory, 2) Separate workers’, outer clothes from factory clothes, (de-gowning from gowning) 3) Have a ventilation source, 4) Provide lockers and a step-over bench (made of painted metal or stainless steel), 5) Designate a gowning area for women and another one for men, 6) Assign lockers for street clothes and others for factory clothes, 7) Do not put hand-washing basins near production areas, and a disinfectant for hand-washing, should be available 8) Have stout and smooth walls and floors with no visible joints, 9) Provide well, indirect ventilation (no fans), and good covered lighting, 10) Place stainless wire mesh nets over any ventilation openings. 5.2.1 Warehouses are divided into the following areas: “According to the nature of the final product and production components” - Receiving area - Raw material storage area - Packaging materials storage area - Sampling area (classified as the same class as the production area if powders are used as raw materials) or an “inspection area” with controlled environmental conditions - Weighing area (classified as Class D/ISO 8 in the case of using powers as raw materials) - Rejection area, which must be tightly closed and secured - Final product storage area - Storage area for any raw materials or products that require special storage conditions. Version number/year:02/2025 Requirements for warehouses: - Have a place covered with a canopy to ensure that the products or raw materials are not exposed to sunlight or any weather changes during loading to and from the warehouses; - Have a receiving area that: • Have a main door with an “Interlocked” door system, • Is equipped with an air curtain and insect zappers, • Is ventilated like the whole warehouse. - Well-ventilated; - Temperature and humidity levels must be appropriate to the product nature, - Monitor temperature and humidity through the factory’s data loggers and thermal mapping, - Floors must be strong,), for example but not limited to helicopter floors - There should be rodent control system, In case there is an emergency door, it must conform to the specifications of emergency doors in accordance with the requirements of the Civil Defence Agency, with the presence of an audible and flexible alarm system, - There should be a fire extinguishing system and an alarm system in accordance with the requirements of the Civil Defence Agency, - All warehouse doors must be tightly closed to prevent the entry of dust or insects, - Have a wire mesh nets over any ventilation openings, with opaque glass to prevent direct sunlight, - Sufficient lighting, - No direct source of water in the storage area, - Do not store directly on the floor non-flammable pallets or stands should be available. Storage should be 60 cm below the ceiling and 20 cm away from walls. * All the above-mentioned requirements must be met in case of there is an independent warehouse for final products 5.2.2 Water treatment station: “A water treatment station may only be set up in case a production line is licensed and needs treated water in its production” Water treatment station consists of: a. City water tank made of stainless-steel grade 316 L, or polyethylene or polypropylene, b. A sand filter, c. Carbon filter (activated granular carbon), at least one filter, d. Two duplex softeners, Version number/year:02/2025 e. A storage tank for soft water, f. Reverse osmosis or ion exchange resin or electro dialysis (for water purification), g. UV lamp, h. A 0.2-micron bacterial filter, I. A stainless steel tank for storing purified water, provided that storage conditions are either above o C or below 25 o C. The following requirements must be observed at water treatment station: • Water specification must be suitable for the nature of the medical device needed to be licensed; • All rustable metals (iron, aluminium and copper) must be excluded; • There should be a spray ball or vent filter in the purified water storage tank; • Dead legs (ends) must be avoided in order not to be a source of pollution; • There should be continuous water circulation (no stagnancy); • Daily monitor water at multiple sampling points; • All water storage tanks must be identified and water direction must be labelled • In case of water is supplied an external body, the agreement with the supplier and water analysis certificate must be submitted. 5.2.3 Laboratories are divided according to the final product nature to: A. Physiochemical laboratory - Laboratory must be in a separate room, with its area being appropriate for the number of workers and the type and size of activity; - Make sure that a suitable place is available to store chemicals in accordance with the storage requirements written on the containers; - Ensure safety measures inside laboratory; - Laboratory must be equipped with the necessary equipment in accordance with the requirements, provided that all devices are calibrated. * In case of physicochemical examination of the product is carried out through manufacturing steps, the presence of a separate place for the laboratory may be overlooked and be considered part of the controlled area. *Outsourcing is allowed. B. Microbiological laboratory - It should be in the controlled area; - It should have a separate entry, divided from inside into physically distanced areas to prevent cross contamination according to the following laboratory activities: Version number/year:02/2025 1. Washing area, 2. Preparation area, 3. Incubators area, at least 2, 4. An autoclave for sterilization, 5. An autoclave for destruction, 6. A laminar air flow (LAF) unit with the following specifications: → Surrounding area shall be classified as the same as the production room, provided that the area shall not be less than Class D/ISO 8, → Preceded by an airlock for changing clothes classified D/ISO 8, → Floor shall be covered with a smooth material with technical specifications not less than that of epoxy without joints, and the junction point of walls and floors shall be curved, → Classification is not required for non-sterile devices, → There must be a dynamic pass box in the LAF room. - All devices must be calibrated, - There should be differential pressure meters, - There should be temperature and humidity measuring devices, - In the case of producing sterile pharmaceutical dosage forms, for example eye drops, the laboratory must meet the same conditions required for sterile pharmaceutical laboratories.

5.3 Sterilization

* Note: Regarding non-sterile medical devices (i.e., ready to be sterilized), the manufacturer’s valid and approved method of sterilization shall be included inside the packages. Outsourcing is permitted to carry out the sterilization process. The external manufacturer is required to be subject to inspection by EDA’s Pharmaceutical Inspection Department, or that the manufacturer submits a pledge of their readiness to enable the department to enter the factory that performs sterilization at any time. * In case of use of sterilization methods other than the following, each case will be studied individually. A. In case of sterilization by gamma radiation - The Medical Devices Factories Inspection Department verifies the existence of a contract between the factory and the Egyptian Atomic Energy Authority (EAEA). B. In case of sterilization by steam - An approved calibration certificate shall be available, - Medical Devices Factories Inspection Department follows up the validation, - If using a water station, the requirements for a water station must be followed, - In the absence of a water station in the factory, a softener device is used at the water inlet of the autoclave for sterilization. Version number/year:02/2025 C. In case of sterilization by ethylene oxide/nitrogen dioxide - An acceptance certificate from the device’s manufacturer shall be available, including the acceptance test, operation qualification, OQ, and IQ (installation qualification), - Conduct sterilization in a separate place, - Provide a safe place to store gas cylinders (separate empty tubes from full ones), - Use suitable pallets in accordance with the device operating manual released by the manufacturer. The aeration room should: a. Be proportional in area to the size of the sterilization device, b. Have temperature and humidity measurement meters, c. Have a source of heating (heater) in case of need, d. Well ventilated. Regarding production areas, the following should be observed in accordance with the product nature: - For sterile medical devices: Production and packaging take place inside the clean room; - For non-sterile medical devices and ready for sterilization before use: Production inside a classified area is not required, and packaging takes place inside the clean room; - Medical devices produced and used non-sterile: Production and packaging are not required to take place in a classified area (unless the manufacturing specification states so); - In case any of the manufacturing stages or production components requires special conditions, these conditions must be taken into account.

5.4 Controlled room

It is the area in which the unpackaged and unsterilized product is prepared, and the following conditions should be observed: - The controlled room should be separate (not used as a corridor); - Designate a place for changing clothes before entering the controlled room; - Designate a place for cleaning and removing the outer package of raw materials before being taken to the controlled room, and the place should contain a ventilation source and an exhaust fan; - It should be well ventilated, with temperature not exceeding 30°C, and fans are not allowed; - Put a temperature and humidity meters inside the controlled room, with temperature not exceeding 30°C and humidity 65%; - Floors must be strong, smooth and clean – that is to be, for example, tiles or epoxy; Version number/year:02/2025 - Designate a place to store the Molds attached to the controlled room when needed; - Make sure when taking the product ((i.e., a classified airlock or a dynamic pass box)) out of the controlled room that it enters the clean room safely (place it inside a double bag) for example (through a classified airlock or a dynamic pass box) or be stored in intermediate store that conforms to the requirements for sound storage.

5.5 Clean room

- Should be preceded by a secondary gowning room and a de-gowning room, and then pass by a step- over bench to wear the clean room gowning; - Doors should be interlocked; - Secondary gowning room should be Class D/ISO 8; - Pressure should be cascading by having pressure differential meters. The pressure differential between adjacent cleanrooms or clean zones of different cleanliness level should lie typically in the range of 5 Pa to 20 Pa, to allow doors to be opened and to avoid unintended cross-flows due to turbulence i.e.: - Between rooms of different grades should have pressure differential of approximately 10-15Pa; - Doors open in the cleaner direction that has more pressure; - Floors must be strong and smooth, such as epoxy or vinyl; - Walls must be smooth and the connection between walls and floors must be curved; - Temperature should not exceed 22°C and humidity 65%; - In case of printing on the product, the printing must take place within the clean room; in case of using inks, the area where the inks are used must be physically separated; - In case of printing outside the clean room, justification shall be provided; - Raw materials enter through the aerated pass box or classified airlock; - Install pressure differential meters at all doors and pass boxes of the clean room; - Supply grills should be in the ceiling and the return grills in the side walls 50 cm above the floor; - Height between the floor and the ceiling should not be less than 2.60 m; - Air change rate ranges between 15-20 per hour.

5.6 Air handling unit (HVAC system)

It should not be applied to products not manufactured or packaged in a clean room - There should be an air handling unit including a prefilter, a bag filter, and an HEPA (high-efficiency particulate air) filter; - There should be a pressure differential meter for the prefilter and bag filter, and another one before and after the HEPA filter; - The air handling unit should be placed in the technical room or be covered with a canopy. The floor should be tiled and the area around is clean. Scope of application o These requirements have been set for the factories that will be established and licensed for the first time. o For factories that had been licensed before the requirements were issued, they are given a period of six months to reconcile their situation, which can be extended for another six months if the factory submits a request to extend the period . o In case of the factory does not implement any of the previous requirements due to the nature of manufacturing the medical devices, the factory must submit studies supported by justification and reference that will be presented to the Supreme Inspection Committee for evaluation . o Manufacturers of medical dosage-form devices are subject to GMP for pharmaceutical preparations in accordance with WHO. Version number/year:02/2025

6. Registration of locally manufactured devices without international certificates

without international quality certificate: Pre-registration procedures: 1. The factory shall obtain a technical operation license (data certificate) from the General Administration of Licensing in the Central Administration for licensing of pharmaceutical institutions. After the issuance of the aforementioned certificate, manufacturer shall head to the Medical Devices Inspection Department in the Central Administration for licensing of pharmaceutical institutions the following: ➢ Ensure that the factory is applying the technical requirements of the manufacturing site within 20 working days, ➢ Manufacturer is informed of the required corrective measures, ➢ Manufacturer completes the technical requirements for the manufacturing site within a maximum of 120 working days, ➢ If the 120 working days have expired and the manufacturer has not completed the corrective measures, the manufacturer has the right to apply for an additional grace period of another 40 working days, after which an inspection report will be issued stating that the factory applies the GMP regarding the procedures of the Central Administration for inspection of pharmaceutical institutions 2. Production of pilot batch is permitted, provided that this batch is never traded in the local market, and the registration procedures and studies required for it are completed. 3. Manufacturer applies online to register a medical device without international quality certificates on the electronic platform at: http://medevice.edaegypt.gov.eg 4. Medical Devices Inspection Department withdraws samples from the pilot batch for analysis in the EDA’s laboratories or any other body approved by EDA and chosen by the competent department. The registration applicant is obligated to submit the analysis file to EDA containing the documents and attachments required for the analysis file. Version number/year:02/2025 Version number/year:02/2025 6.1 Procedures for receiving registration file 1. The Reception pharmacist will meet with the registration applicant to add the name of the medical device to the payment receipt of the fees and services. The medical device registration application fees are collected for the fees category mentioned in the executive regulations of the EDA establishment law issued by Prime Minister’s Resolution No. 777 of 2020 and for the services in accordance with EDA chairman's decision in this regard. 2. Company applies online at the following link: http://medevice.edaegypt.gov.eg 3. Company will receive a reply through the platform within 10 working days from the date of submitting the request. ➢ If the application is accepted: The request will be directed to the reviewing pharmacist who studies the request and sends the requirements to the company to complete the procedures within 20 working days, ➢ If the application is suspended until completion: The application is suspended if any of the documents are not completed according to the announced checklist for a maximum period of 90 working days, after which the application will be rejected. If the documents are complete after the aforementioned period, the fees of the service must be paid in full. When the company fulfils the required documents within 90 working days, the application may be completed on the platform using the same application number submitted previously. ➢ If the application is rejected: the application will be rejected in case the medical device data in application doesn’t match with that mentioned in payment receipt or the application is not relevant to the administration to which the application is directed. 6.2 Procedures for evaluating medical device registration file - The file shall be reviewed and the needed requirements shall be identified on the platform within 20 working days from the date of acceptance of the file; - Medical device vigilance procedures are followed as detailed in Clause 6.4; - Medical device shall be to presented to the specialized scientific committee to be evaluated; - Specialized scientific committee for stability studies & Biocompatibility evaluation procedures shall be followed to evaluate the safety mentioned in Clause 6 of the Regulatory Guidelines for the Procedures for Registering Imported and Local manufactured Medical Devices with International Quality Certificates. Version number/year:02/2025 6.3 Procedures for completing the medical device registration file - Completions of the registration file are submitted on the platform and a receipt for payment of the completion fees is attached; - Completions submitted by the manufacturer shall be reviewed within 10 working days; - If a calendar year has elapsed from the date of acceptance of the registration file and the factory has not completed the file, the registration application shall be considered cancelled; In case of non-sterile medical devices: The applying company shall be given a period of 6 months from the date of submitting the registration file for trading after the initial evaluation of the file. 6.4 Medical devices vigilance procedures 6.4.1 Medical devices vigilance requirements ** A Class I and Class IIa medical device submitted for re-registration and no regulatory procedures have been taken. Factories must submit the commitment (attached) to the General Administration for registration, and a transfer letter will be issued for them to follow with the vigilance Administration. ** A Class I and Class IIa medical device submitted for re-registration and regulatory procedures have been taken over the three years that had preceded the application date. • Factories shall go to the vigilance Administration pursuant to a transfer letter from the General Administration for Registration to submit the documents required to evaluate the safety within the re- registration/variables framework, which does not include a summary of marketing history (SMH). • Submit the required commitment (attached), to be sent to the Medical Devices Registration Department. ** Class IIb and III medical device submitted for re-registration • Factories are instructed to go to the Medical Devices Safety Department according to a transfer letter from the General Administration for Registration to submit the documents required for safety evaluation within the re-registration/variation framework, which includes SMH. • Submit the required commitment (attached), to be sent to the Medical Devices Registration Department. 6.4.2 vigilance requirements for companies (not linked to registration) 1-In case of a request for registration/re-registration, the local manufacturer is obligated to submit a commitment of the presence of a medical devices vigilance system and the follow-up of all its activities and requirements in accordance with the guidelines for the medical devices vigilance system with the Medical Devices Safety Department at the (Egyptian Pharmaceutical Vigilance Center) 2-The local manufacturer is obligated to report any recall, FSN (field safety notice) or FSCA (field safety corrective action) procedures that take place globally or any incidents that are monitored in the Arab Republic of Egypt to the Medical Devices Safety Department at the Egyptian Pharmaceutical Version number/year:02/2025 Vigilance Centre, according to the time periods specified in the guidelines for the medical devices vigilance system. 3-Companies are obligated to appoint a vigilance officer or add his duties to a supervisory affairs officer and submit his nomination letter to the Medical Devices Safety Department. 4-Companies are obligated to pay for the services when submitting their files to the Medical Devices Safety Department. Companies comply with all applicable regulatory rules and guidelines and their amendments regarding safety requirements (if any). 6.5 Issuance of registration license A registration license for the local medical devices without quality certificates shall be issued and is valid for a period of five years from the date of issuance of the registration license. Factories are obligated to analyse the first three batches produced after the issuance of the registration license, provided that the batch will not be released until the conformity result of the analysis is issued. 6.6 Re-registration procedures - Medical devices are re-registered every five years based on an application submitted to the Central administration of Medical Devices during the first three months of the last year of the valid registration license. - Applicant is obligated to submit the re-registration file according to the list of required documents. - Fees for services are collected in accordance with a decision of EDA chairman in this regard. - The re-registration procedures shall be presented to the specialized scientific committee to assess the medical device. Specialized scientific committee for stability studies & Biocompatibility evaluation ➢ Medical device re-registration shall not be submitted to the Specialized scientific committee for stability studies & Biocompatibility evaluation if no modification has occurred in the raw materials of the package and if a Real Time Stability Study is submitted for the first time of registration or during the registration license validity. ➢ If the Real Time Stability Study is not submitted upon first registration or within the period of registration license validity., device will be assessed upon re-registration. ➢ In case of a change in the raw materials, the biocompatibility study is re-assessed by Specialized scientific committee for stability studies & Biocompatibility evaluation. ➢ If the sterilization method is changed, the following shall be re-assessed by the specialized scientific committee for stability studies & Biocompatibility evaluation: - New stability study including sterilization validation only and re-evaluation of biological risk assessment. ➢ In case of a change in the packaging dimension or packaging material, the following shall be re-assessed by Specialized scientific committee for stability studies & Biocompatibility evaluation Version number/year:02/2025 - New stability study including packaging validation only and re-evaluation of biological risk assessment. ➢ If the shelf life and/or storage conditions are changed, the following shall be re-assessed by specialized scientific committee for stability studies & Biocompatibility evaluation: - New stability study and re-evaluation of biological risk assessment. - Applicant is obligated to complete the re-registration procedures within the last year of the registration license production and trading is permitted during this year. If the requirements of the final file are not met at the end of this period, the production or importation of raw materials shall be ceased, and the application shall be considered cancelled.

7. General requirements

Manufacturer should: - Obtain ISO 13485:2016 Certificate; - Print all data and registration number on the package according to the Regulatory Guideline for Labelling Requirements for Medical Devices, Medical and Laboratory Equipment and in Vitro Diagnostics, Components and Production Inputs . - Import raw materials used in the medical device after obtaining approval from the Central administration of Medical Devices or submitting evidence of purchasing it locally. If the factory is located in a free zone, manufacturer should: - Provide evidence of importing raw materials used in the medical device or purchasing them locally; - Make no change to the medical devices except after obtaining the approval of the Central administration of Medical Devices according to the applicable procedures in accordance with the type of change, otherwise the registration license will be cancelled; - Make no change to the critical component’s suppliers of raw materials except after obtaining the approval from the Central administration of Medical Devices to re-evaluate the device supplier, otherwise the registration license will be cancelled; - Apply Vigilance System; - Adhere to vigilance requirements; - Print on the device the following QR code, which shows the internet link for reporting to EDA any problems to patients or users or problems related to use or quality.

8. Annexes

9. Glossary

CE: Conformity European DOC: Declaration of conformity EDA: Egyptian Drug Authority EPVC: Egyptian Pharmaceutical Vigilance Centre FSCA: Field Safety Corrective Actions FSNs: Effective Field Safety Notices GMP: Good Manufacturing Practice HEPA Filter: High-efficiency Particulate Air Filter HVAC System: Heating, Ventilating, and Air Conditioning System ISO: International Organization for Standardization MDSD: Medical Device Safety Department MIRs: Manufacturer Incident Reports MSDS: Material Safety Data Sheets PMS: Post-Market Surveillance PSRs: Periodic Summary Reports RO: Reverse Osmosis SMH: Summary of Marketing History SOP: Standard Operating Procedure Version number/year:02/2025

10. History Table

Summary of Changes Issue date Version no. 20/07/2022 Version 1 The name of the Central Administration for Operations has been updated to become the Central Administration for Inspection on pharmaceutical institutions or the Central Administration of Licensing of pharmaceutical institutions whenever they are mentioned in the guideline, depending on the specialization. 01/09/2025 Version 2