Accessing the medical devices market in Egypt and Saudi Arabia: a systematic review of policies and regulations.

ABSTRACT Introduction: Despite the significant medical devices market size in Egypt and Saudi Arabia, information regarding policies and regulations for medical devices market access is highly deficient. Areas covered: The aim of this paper is to provide a systematic review on market access policies and regulations in both countries, to allow safe and timely access to medical technology. The following databases were searched: PubMed, Science Direct, Scopus, and Al Manhal Arabic database. Additionally, the web portals of regulatory authorities of both countries were searched. There are 34 records included in the qualitative synthesis of this review. Expert commentary: Main findings include; adopted regulatory framework from reference countries, and interim main regulatory documents, In conclusion, the market access schemes are relatively structured. However, some recommendations are put forward to navigate towards a more comprehensive policy framework in both countries.


Introduction: health systems and the four phases of the medical devices life cycle
According to the World Health Organization (WHO), medical devices have a life cycle that consists of four phases ( Figure 1). When effectively implemented, these phases enable improved access to safe, high quality, and costeffective medical devices [1]. The research and development phase is guided by input parameters like identified population needs. Nevertheless, another important parameter is the national policy on health technology research and development. According to the WHO, national policy should incentivize manufacturers to innovate solutions to those needs in the form of health technologies [1]. The regulations phase is in place to protect the public. It ensures that the health technology in question meets the minimum safety and effectiveness standards prior to placement on the market, as well as offering continuous supervision over its safe use [2]. Consequently, the assessment phase which includes Health Technology Assessment (HTA) is in place to inform potential payers with clinical outcomes and costeffectiveness when selecting medical devices for procurement. Finally, the management phase, which refers to Health Technology Management (HTM), covers a wide range of functions. This includes; procurement, completing inventory of assets, maintenance, and matching timely the safe high quality devices with their users and with health services provided ( Figure 1) [1].

Rationale
Despite the significant market size of medical devices in the Middle East, and its substantial potential for growth, information regarding policies and regulations for accessing this market is highly deficient. Consequently, the state and the progress level of the region's respective regulatory systems and their abilities to provide safe, timely, and effective access to medical technology remains unclear.
Egypt and Saudi Arabia are considered to be pivotal states in the Middle East that continue to hold a notable role in the region. Egypt has been taking on the role of political and cultural leadership in the Arab world, while Saudi Arabia remains a main dominant economic power within the region. Deep political and economic ties are strongly present between the two countries [3].
From the industrial perspective, Egypt and Saudi Arabia hold substantial medical devices market size (Table 1) [4][5][6][7]. Both countries have numerous market features in commonmainly the fact that both are heavily relying on medical devices importation. From the economic perspective, such countries' selection allowed taking into consideration the different country income levels and their effect on establishment of market access policies and regulations. Considering the leadership role held by the two countries in the region, their extensive economic relationship, and their considerable market size, one can highlight their significance in terms of impact on the Middle East medical devices market. The authorities' health policy choices can widely impact the choices of other developing authorities in the region, and may eventually have a trickle-down effect toward the development of the region's regulatory ability to guard patient's safety and allow timely access to medical technology.

Aims and objectives
This review is an attempt toward exploring the regulatory systems of Egypt and Saudi Arabia as two major exemplars of the regulatory systems in the Middle East region. The goal of this review is to study the market access processes, their governance and implementation in the context of medical devices. The main focus is on the regulations phase (phase 2; see Figure 1). The paper's scope is on the pre-market access process. Although some information highlighted in this report relate to the post-market surveillance, yet such information remains within the context of the initial market access framework. An in-depth focus of the post-market stage is beyond the scope of this review.
The intention is to provide analysis based on the findings and put forward some recommendations for strengthening the regulatory phase, hence paving the way toward proper integration of the upcoming phases to achieve a more comprehensive medical devices policy framework. According to the WHO, a comprehensive policy framework is one that is able to fully implement official national policies on access, quality, and use of health technologies. This is done throughout the entire phases of the medical devices life cycle [1].
The core value of this review is emphasized through two main angles. The first is a descriptive focus that attempts to explore and collate in a systematic manner the information on market access policies and regulations in these countries ( Table 2). Such information is currently highly fragmented and in some cases available in Arabic language only. This is done to allow more informed market access process by the interested stakeholders.
The second angle is an analytical focus, which allows critical visualization of the status quo of the regulatory schemes. This offers a unique opportunity for corrective actions toward current insufficiencies, and lays a foresight on how the regulatory schemes are likely to develop over time, in light of regional and international changes as well as knowledge transfer in the healthcare policy field.
The collective approach of this review offers the advantage of identifying the challenges faced by both systems, since both belong to similar market and geo-political conditions. Additionally, this approach identifies opportunities in the context of regional and global harmonization efforts of medical devices regulations. To our knowledge, several   [4,5,[8][9][10][11][12]. GDP: gross domestic product.
reviews on different medical devices regulatory systems have been carried out [13,14], yet no previous systematic reviews have attempted to explore and analyze any of the medical devices regulatory systems of the Middle East.

Methods
Following PRISMA guidelines for systematic reviews [15], a systematic search was performed in academic journals and relevant regulatory authorities' web portals.

Results
This review identified a total of 160 documents that were potentially relevant, of which 116 papers are from scientific databasessix studies from PubMed, 104 from Science Direct and EMBASE, and six from SCOPUS. There were 42 records identified from authorities' web portals; websites, repository portals, and documentations, and two additional records through snowball citation and gray literature.
No matching records where retrieved from country data of medical device profiles provided by the WHO medical devices portal, the WHO Eastern Mediterranean Health journal, or Al Manhal database.
After removing duplicates, a total of 54 records were screened by reviewing the abstracts. After which, a total of 37 articles were retrieved for full text screening. The full text assessment excluded three articles with reasons including; article that was focusing on specific technology only, an article with exclusive emphasis on patency, and an article focusing on Middle Eastern culture in regulatory environment. Finally the review included a total of 34 records for qualitative synthesis. Four studies from scientific databases, 28 records from authorities' databases, and two from gray literature and snowball citation [18,19] (Figure 2; Results references :).
For clarity, result details are divided in two main parts: Governance; highlighting main topics related to regulatory authorities, type of regulations, and main elements of regulatory system.
Process and implementation; involving details relating to the actual process of market access, and implementation of regulations in Egypt and Saudi Arabia.

Regulatory bodies
The EDA is the pharmaceutical regulatory body of the Ministry of Health and Population (MOHP) in Egypt. Medical devices unit is included within the spectrum of this pharmaceutical regulatory body as a sub function [20]. The main bulk of regulatory processing is done through the Central Administration for Pharmaceutical Affairs (CAPA) [21]. CAPA handles a whole range of activities including; pre-market authorization, customs release, post-market inspection, and licensing and registration of importers, Authorized Representatives (ARs), and establishments. CAPA is assisted by the National Organization for Drug Control and Research (NODCAR), and other specific technical committees for checking the technical specifications of medical devices facilities and products [22].
Similarly, the SFDA is an independent authority with a primary function of ensuring safety, quality, effectiveness and performance of medical devices according to their intended purpose [23]. The SFDA has an entire sector dedicated solely for the regulation and organization of medical devices. Unlike the EDA, the SFDA uses electronic databases to handle the entire processes of medical devices registration, post-market surveillance, custom release, and listing/ licensing of establishments and ARs [24]. (Further information on regulatory bodies can be found in the supplementary material).

Medical devices classification
The EDA fully adopts the European Directive of the Medical Devices 93/42/EEC and its amendment 2007/47 in defining and classifying the medical devices [25,26]. Accordingly, medical devices are classified into four Classes; I, IIa, IIb, and III. The classification depends on the duration of usage, invasiveness, and special rules [26]. Despite adopting the European classification system of medical devices, the Egyptian MOHP reserves the right to modify any classification based on the technological progress of devices. In cases of disputes on classification between MOHP and the manufacturer, the MOHP refers to decisions of committee on standards and technical regulations [27].
On the other hand, SFDA does not have a specific medical device classification system. Nevertheless, using its Medical Devices Classification (MDC) e-system, the classifications are set according to the medical device's country of original authorization. This has to be within the jurisdictions of one or more of the International Medical Device Regulators Forum (IMDRF) countries namely; European Union (EU), United States of America (USA), Australia, Canada, and Japan [28]. A unique regulatory governance advantage in this case is the fact that the majority of medical devices (70%) in Saudi Arabia are imported from IMDRF members, namely USA and Germany [29].

Regulatory documents
The Main regulatory policy documents are interim in both countries; the Egyptian Regulation for Medical Devices (ERMD), issued in 2010, and the Saudi Medical Devices Interim Regulations, issued in 2008 [27,30]. The ERMD is further aided by a regulatory document called, updates of provisions in the rules of registration of medical supplies (issued in 2014) and by The Egyptian Guideline for Medical Device Vigilance system. The latter outlines the concept of post-market surveillance vigilance system, in context of responsibilities of the manufacturers, distributers and users of medical devices [31,32].
The SFDA has a more extensive set of documents expanding on the main regulatory one. This includes a set of eight Implementing Rules (IRs) documents. These documents have been issued to specify and refine the provisions of the Medical Devices Interim Regulation [33,34]. Additionally, the SFDA has National Provisions and Requirements for Medical devices. This is a unique regulatory document that mandates some Saudi specific national provisions to ensure safety of medical devices. This includes provisions related to; electrical safety, electrical coding, medical gases, electromagnetic compatibility, labeling and packaging requirements [33,35]. Such parameters are tested against standards set by the Saudi Arabian Standards Organization (SASO), International Organization for Standards (ISO), and International Electro-technical Commission (IEC) [35] . This regulatory feature is deficient in the Egyptian system, which has developed only standards for measuring devices [18]. Furthermore, there are 10 guidance documents aimed at manufacturers, ARs and distributors. Thereby, ensuring coherent application of the IRs and the interim regulations especially in the processes of market authorization, post-market surveillance, licensing, and listing purposes of medical devices [36].

Authorized representatives (ARs)
According to the SFDA, the AR is any natural or legal person, who is established within the state and has received a written mandate from the manufacturer to act on his behalf for specified tasks [37]. Both countries necessitate the presence of ARs for manufacturers who have no local establishments within their territories. Regulatory documents of both countries necessitate this legal obligation [27,37].

Medical devices national registry
SFDA has a comprehensive database for all establishments, products and devices in the field of medical devices. This database is called the Medical Device National Registry (MDNR). The aim of the MDNR is to obtain a profile of the Saudi medical devices industry, and to measure the readiness of medical devices and establishments to comply with medical devices regulation [38]. Other databases exist for reporting of medical devices and importation. However, the MDNR is considered to be a medical devices database rather than a medical devices patient registry [39]. No similar databases were found for the EDA.

Premarket authorization (PMA)
According to the EDA, the PMA process takes 70 working days before a final decision is made. The full process is described in details in Figure 3 in accordance with official EDA registration flowchart [40].
According to consultations with a medical device expert from the EDA, non-sterile devices of Class I from reference countries are granted direct entry into the Egyptian market. In order for all the other classes of medical devices to be granted PMA, they have to be manufactured in a reference country or certified by notified bodies of a reference country. In addition, the device has to be freely sold in one of the reference countries. Certificate of Conformité Européenne (CE), ISO and free sale are the main mandatory documentations required by the EDA. The US FDA certificate is considered enough as a certification and waives the requirements of the three previous main documents. Declaration of Conformity (DOC) is provided by manufacturers in all cases. In some cases, the sterile and non-sterile devices that are not from reference countries, or non-sterile devices in dosage form require a specialized scientific committee consultation [41].
The fee for the process of medical devices registration was not obtainable via the website or any other source on the EDA web portal. However, according to correspondence with an EDA personnel, a unified set fee is indicated for all types of medical devices, amounting to 3500 Egyptian pounds ($458.6) [41].
Regarding Saudi Arabia, the SFDA as specified by a royal decree regulates the pre-market authorization of all medical devices on the national level, irrespective of the classes of the product or their level of safety [42]. Manufacturers or ARs apply through the electronic Medical Device Market Authorization system (MDMA). The PMA process is guided by articles of Implementing Rule of Market Authorization (MDS-IR6) [43]. The lead time for such a process is 35 working days irrespective of the medical device type [44]. The full process is described in Figure 4.
The SFDA applies a four tiered fee system for medical device marketing authorization. The processing fees depend on the class and the type of the device ranging from 15 The EDA assesses both local and imported product standards and risks through the CE, ISO 13485, and the FDA certificates. All medical devices require a proof that they are freely sold in the country of origin. Devices which are from a non-referenced country are required to obtain a documentary proof stating that it is currently being freely sold in one of the reference countries [45]. Other reports like stability study, sterility and test reports are also mandatory documents in the dossier [20]. (The full documents checklists are in the supplementary material).
On the other hand, SFDA recognizes the product standards of medical devices that have been granted PMA by at least one of the IMDRF members. Obtaining a CE mark alone would be sufficient for market access. However SFDA and all regulatory bodies within the Gulf Cooperation Council (GCC) require safety data, including; information on intended use, warnings, precautions, and potential adverse events associated with this use [46]. Some of these requirements are mandated by the

Scientific committee.
In some cases the EDA consults a scientific committee as a third party to further examine the applicant's dossier and may even test the device if necessary. Accordingly, the scientific committee issues a recommendation to the EDA and a final decision on PMA is issued [27]. This committee consists of leading medical professors (approximately 10 in number) from various medical specialties in addition to pharmacist managers from CAPA and the NODCAR [19].
Similarly, the SFDA holds the right to designate a thirdparty organization known as Conformity Assessment Body (CAB), for assistance in the process of PMA [47]. The role of the CAB is specialized examination of the documents to verify conformity with the IMDRF and Saudi National provisions [37].

Local manufacturers.
Local medical device production is relatively limited in both countries. In Egypt, the medical device industry is largely confined to the production of consumables, and other medical devices such as furniture and basic dialysis products. It is estimated that only 10% of medical device market is supplied by local production. Complex technology as diagnostic imaging is a large import product area due to the low local production capabilities [4].
Local manufacturers have their facilities licensed by both the Industrial Ministry and the MOHP, to control the quality from both public health and industrial quality control perspectives. Application of local medical devices is subjected to another modified checklist. However, in terms of medical devices' technical requirements, the same regulations apply [45].
In Saudi Arabia, less than 3% of the total expenditure on medical equipment is for local products [46]. Local manufacturers in Saudi Arabia are expected to comply with the relevant regulatory requirements of one or more of the IMDRF member's jurisdictions, in addition to the national Saudi provisions. However, It is not required for medical devices designed and constructed by health  facility staff for internal use within that facility to acquire a PMA [23].

Customs release. In Egypt, the General Directorate of Pharmaceutical Monitoring for Custom Release on Medical
Devices is the entity in charge of custom releases [48]. Custom release is granted for registered medical devices. It is also possible to approve unregistered free samples of medical devices for registration and research purposes. Normally, this is requested by universities, research centers, and central laboratories of the MOHP [48]. (More information on custom release checklist is available in the supplementary document). Similarly, medical devices presented to the Saudi customs have to be accompanied by all the necessary documentation to be released from the port of entry. This includes; DOC and Market Authorization issued by the SFDA. It is noted that charities, diplomatic, and military institutions are normally exempted from custom tariffs on medical devices [49].

Refusal of PMA.
Refusal of PMA by the EDA can occur pursuant to applications not satisfying the ERMD. Any refusal should be communicated without delay to the manufacturer or the AR. According to article seventeen of the ERMD, corrective actions should be presented to the manufacturer or the AR, as well as time allowed for such corrective actions to be implemented. The manufacturer or the AR is allowed to put forward their views as a part of a consultation process. However, consultations on the decision may depend on the urgency of the measures being taken and their impact on the public health [27].
In Saudi Arabia, applicants getting refusals on their PMA are entitled to know the reasons and the means of appeal by the SFDA. There are no further clarifications on means of appeal demonstrated in the regulatory documentation [33].

Placing on the market
A unified clear regulatory document illustrating the specific labeling requirements of the medical devices was not retrievable for Egypt. However, labeling requirements are derived as separate provisions from various regulatory sources. Generally, the regulatory threshold of labeling and packaging requirements is set in accordance with their relevant adopted legislations. These are the legislations adopted by the EDA from reference countries including their respective ISO, CE, or FDA standards systems. As such, a master label of the device from the country of origin is required by the EDA [50]. According to the labeling provisions in the ERMD, labeling and packaging of the medical devices must be made available to the user and the patient in Arabic language [26,27].
On the other hand, the SFDA has an established system for labeling of medical devices. SFDA requires copies of all labeling that were submitted and approved by the relevant authority in the country of origin of the medical device. In terms of content, all information of the device name and data, power supply, environmental factors, and any precautions, warnings or limitations has to be clearly placed on the label of the medical device. The Information For Use (IFU) should indicate the intended purpose, performance, and handling conditions according to the Saudi National Provisions [51].

Post-market surveillance
The Medical Device Safety Department (MDSD) of the EDA is the entity responsible for handling the post-market medical device vigilance system. The MDSD handles the medical device vigilance data in a way compatible with the IMDRF and the European commission guidelines for medical devices [31].
Incidents reported are normally related to malfunctions, unanticipated adverse events, interactions with other substances or products and degradation of the device. Incidents caused by patient conditions or abnormal use are not required to be reported. Reporting is the responsibility of manufacturer, user, and the MDSD [31].
Post-market surveillance system is done via random inspection carried out by EDA on the medical devices, and the manufacturers' establishments. The MDSD responsibilities include receiving incidents reports, risk evaluation, and monitoring of manufacturers' subsequent actions. Consequently, the MDSD gather further information, consult with a relevant notified body or medical devices registration department, and then issue recommendations to users and manufacturers. Updated information is disseminated accordingly within the EDA [31].
The manufacturer on the other hand, is required to have suitable vigilance systems in place for their devices. They are responsible for notifying the MDSD with incidents when the reporting criteria are met according to the Egyptian guidelines for pharmacovigilance. This is in addition to submitting trend reports, periodic summary reports, and notifying the MDSD with the field safety corrective actions of their products. The manufacturer is responsible for keeping ARs, and any other agents on the market informed [31].
The SFDA maintains a web-based system for medical device reporting, called the National Center for Medical Device Reporting (NCMDR). The purpose of which, is to execute key aspects of the SFDA's post-market activities, and allow dissemination of information reducing the likelihood of adverse events [33].
Reportable adverse events are divided into two main categories; those occurring within Saudi Arabia and others occurring outside. In case of incidents occurring outside, measures have to be taken to assess whether such incidents are liable to occur in Saudi Arabia as well. A field safety notice is issued to the users and manufacturer to take precautionary actions.
On the other hand, for incidents occurring within Saudi Arabia; a similar procedure takes place with a corrective action that is agreed by the SFDA. Corrective actions include; notifying the IMDRF country of origin, as well as drafting and completing a field safety corrective action plan. The reported incidents can happen as sporadic events or during the postmarketing surveillance process [33].

The need for a comprehensive regulatory framework
Aiming for a comprehensive medical devices regulatory framework can impose immense financial burden on regulatory authorities [52]. However, ensuring safety of medical devices entails the presence of such regulatory framework that leaves no room for regulatory gaps. Both EDA and SFDA have their main policy framework for medical devices regulation still labeled draft or interim, since 2010 for Egypt and 2009 for Saudi Arabia. Moreover, both rely on adoptive regulatory framework from reference countries [27,33]. However, this does not waive the need for legislating national provisions, to adapt these frameworks accordingly to fit within the local environments of both countries. The EDA regulatory system shows some degree of vagueness concerning the regulations of medical devices. This is probably pertaining to the draft nature of the ERMD, the relatively low number of implementation policy documents, and the lack of transparency in dissemination of regulations via regulatory databases and web portals. On the other hand, the SFDA has already taken an initial step by issuing the national provisions regulating electrical safety, electrical coding, medical gases, electromagnetic compatibility, and labeling and packaging of medical devices [35].
It is also noted that the EDA's interim regulation only deals with medical devices generally and inspires its legislation from the EU directive 93/94/EEC. Nonetheless, there is no indication of adoption of other legislative work with respect to active implantable medical devices or in vitro diagnostic medical devices, both of which formally have separate directives in the EU. The EDA specifies that the ERMD policy document is not applicable on these two types of devices, yet does not mention other alternative regulative schemes for them or clarify sources for regulations of such devices [27,31].

Centralized governance
Both EDA and SFDA centrally handle the registration of any kind of medical devices prior to granting access to the markets. This model is in contrast to less centralized regulatory systems such as China, a system that has delegation of authority to provincial authorities on the regulation of some classes of medical devices [13].
Centralized governance can greatly burden both regulatory systems from the financial and the organizational perspectives given both systems' developing nature. This raises the question of whether these developing regulatory systems are capable of effectively handling such rapidly expanding markets [4,5].

Harmonization
Despite the similarities between the EDA and the SFDA regulatory systems like relying heavily on medical devices importations and adoption of foreign regulatory frameworks, regional harmonization on the Eastern Mediterranean level is still relatively low [53]. Pooling the financial, knowledge, and the human resources can alleviate the regulatory burden at a single country level and unify the market access process for the manufacturers.
On the international level, adopting regulatory framework from the IMDRF countries allows a great level of harmonization, since these countries are also major manufacturers of medical devices worldwide [52].

Patient's safety
Medical devices regulations are in place to guarantee medical devices safety for patients. Whether the product will be safe to use and perform in an effective way depends on three elements that need to be covered comprehensively in the relevant regulations. These elements are; the product itself in terms of its standards, the use of the product and the product representation to the user [52].
With regards to product standards, PMA pathways in Egypt and Saudi Arabia recognize products standards of PMA from reference countries' systems. According to the WHO, adopting standards of PMA allows the governments to establish low cost programs that promote safety performance of medical devices. This is done by taking advantage of what other more experienced systems have already achieved on the level of product standards [52]. Nevertheless, a certain degree of threat to patient's safety in Egypt and Saudi Arabia relatively persist in the light of the current market access regulatory framework.
Two main PMA reference systems as revealed by this review are the ones from the US and the EU [27,33,52]. These two systems present greatly different approaches to approving devices for use in patients [14]. Devices subject to the EU process may be available to patients sooner compared to the US, although with less clinical experience prior to use [54]. This consequently means, devices accepted and allowed access to Egypt and Saudi markets are resultants of varying degree of scrutiny of different approval systems. Such heterogeneous adoptive approach does not allow a uniform overall impact assessment on patient's safety. Furthermore, both the US and the EU systems are faced with variable dissatisfaction and criticism levels [55][56][57]. For instance, since 2012 the EU has been forced to revise the medical directives in place after being faced with scandals of medical devices safety issues [58]. A famous 2012 US FDA report cited 12 examples of high-risk medical devices that were approved in the EU and then later deemed ineffective or dangerous [59]. On the other hand, quality problems in pre-market submissions in the US have been evidently found by several studies. There are several claims of lack of hallmarks of well-designed clinical trials, and unfair results reporting, raising questions on the empirical basis for device approval in the US [54]. As such, in the light of these developments, serious questions can be raised on the current state of heavy reliance on US and EU standards by Egyptian and Saudi PMA systems.
Although a full analysis on patient's safety is not possible given the scope of this review, the advantages of regulations adoption by regulatory systems as stated by the WHO do not come risk-free. Patient's safety in such systems can be highly dependent on understanding the nature of the adopted systems, and their main challenges. Moreover, a robust post-market system that takes into account the heterogeneity of the approved medical devices, can be of great significance in guarding patient's safety. Judging by the more advanced e-system of Saudi Arabia compared to the Egyptian counterpart, threats on patient's safety can be more eminent in Egypt.
Finally, the lack of national provisions on labeling and on environmental related mandates in Egypt is another limiting factor that further hinders the safe representation, and usage of medical devices. Based on this review's findings, an indepth analysis of post-market surveillance in both countries is highly encouraged; this is to assess how patient's safety in both countries can be guarded based on their current market access systems.

Electronic-databases and medical devices registries
There is considerable gap between Egypt and Saudi Arabia in terms of electronic database services (e-services). Such capabilities are significant to both the manufacturers and the regulatory authorities alike. Manufacturers can view regulatory requirements clearly and can interact better with regulatory authorities in the presence of such e-services [36]. Saudi Arabia has a 5 year National e-Health Strategy, aiming to position e-Health as a primary transformation agent and enabler toward improving standards, availability, and quality of care in the Kingdom [60]. On the other hand, the EDA services are comparably traditional in nature. The application for the Medical Devices PMA is initiated by manual procedures. This could be related to the longer procedural time by the EDA [61].
On another note, establishing medical devices registries should be considered. Medical device registries are used for the study of medical devices outcomes. They can be used to bridge the gap between the devices' performance in clinical trials and their use in regular practice, in addition to laying preliminary grounds for HTA of medical devices [39].

Fee systems and sustainable financing
Sustainable financing is one of the main sources of maintaining a strengthened National Regulatory Authority (NRA). Governments need to revise their legislation and introduce fee systems in addition to other funding mechanisms that reflect the real costs of the NRA activities [62].
One of the interesting findings of this review is the huge discrepancy between fees charged in Egypt and Saudi Arabia for PMA. The SFDA charges a fee which is roughly 11 times greater than the EDA's [41,44]. This substantial discrepancy is an interesting point for further investigations and research. More resourceful regulatory authorities are more able to provide tools like e-services databases, possibly leading to more effective and less bureaucratic PMA processing. Moreover, the lack of tier-based fee system that reflects devices classification is a major weakness in the EDA compared to the SFDA. This is because high-risk devices may require more regulatory work done for their assessment than lower risk ones.

Time to market
From a manufacturer's point of view, time needed to access the Egyptian and Saudi markets is dependent on several factors. Initial selection of the EU PMA regulatory process as a reference system may make devices available on the market sooner compared to the US's PMA system [54]. This fact may encourage international manufacturers to pursue faster referenced PMA systems to gain faster access to the Egyptian and Saudi markets.
An interesting finding of this review is the time discrepancy between the two regulatory systems. Although both the EDA and SFDA carry out similar PMA processes, the time to market in Egypt is much longer compared to that of Saudi Arabia. The official SFDA timeframe of application reviews are typically 35 business days, while the EDA timeframe can take up to 5 months for application reviews [61].

Expert commentary
The findings of this review highlight the significant association between the expanding market and the developing regulatory infrastructure of the Egyptian and Saudi Arabian systems. A desirable market growth entails a simultaneous proportionate development of regulatory systems. Regulatory programs for health technologies, more specifically for medical devices can be developed in stages, as suggested by the WHO's Global Overview of Medical Device Regulation [52]. Recommendations for developing further the regulatory infrastructure of both countries can encompass long-and shortterm actions ( Figure 5). Long-term actions can be done through strengthening and capacity building of the existing NRAs. However, the notion of patient's safety cannot be withheld until NRAs are fully strengthened. This is why short-term actions are highly significant.
Short-term actions include imposing import planning and control strategy, since both systems are heavily reliant on importation. This can ensure that imported devices are of required standards, and of priority to the healthcare needs. Customs authorities and medical devices regulatory authorities may need to cooperate more effectively to successfully meet these objectives. This includes a clearer display of regulatory requirements to interested stakeholders overseas. Moreover, the establishment of databases and medical devices registries, especially in the Egyptian system can help ease the burden on the centralized governance structure adopted by the authorities. This allows better handling of data and minimizes unnecessary delays in the market access process, as well as laying foundation for HTA and HTM capabilities.
Advertising control is essential in maintaining a proper presentation of medical devices, which is one of the main critical elements of medical devices safety suggested for developing regulatory systems [52]. Post-market surveillance and problem reporting needs further research to allow proper enforcement mechanisms. This is needed to ensure that the post-market vigilance system is in coherence with the heterogeneous nature of the adopted PMA regulatory frameworks.
On the other hand, long-term strategies to strengthen NRAs should not be omitted. Active stakeholders' engagement is a key factor to stronger NRAs. Regulations that result from inclusive stakeholder involvement will likely yield better implementation [52]. Other strategies include re-assessing organizational structure of current governing bodies, and aiming for human resources empowerment. These provide the means for highly alert and responsive regulatory systems. Having the perfect regulations in place will not guarantee patient's safety unless such regulations are executed skillfully by the proper workforce [62]. Last but not least, sustainable financing mechanisms need to be set to empower all these corrective measures. Strategies for fee systems are needed, to allow a sustainable effective function of regulatory enforcement and supervision.

Five-year view
The medical devices markets in both Egypt and Saudi Arabia are expected to grow tremendously. In Saudi Arabia, the markets' expected growth is estimated to exceed US$ 1.6 billion by 2018, with a compound annual growth rate of 9% [5]. Similarly, the Egyptian market is expected to double in size by the year 2018, it is forecasted to reach an estimation of US$ 1.009 billion [4].
The main findings highlighted in this review indicate a relatively fast regulatory track for market access of medical devices. These findings when combined with deficient national strategies for HTA and HTM may lead to uninformed procurement strategies. On the large scale this may lead to unplanned industrial influx of medical devices into both markets. From the industrial perspective, this can be a good market opportunity. Nonetheless, the risk of influencing the market toward a supply induced demand exists under the current circumstances [63]. Consequently, problems of resources allocation in the public or private sector may arise, reducing their ability to respond to population needs in the longer term. Therefore, governments are urged to formulate as appropriate, national strategies and plans for the establishment of systems for the; assessment, planning, procurement and management of health technologies as per the 60th World Health Assembly's resolution WHA60.29 [63].

Limitations
Available data on market access of medical devices in the Middle East is highly limited. An extensive database search was performed, in addition to hand searching relevant web portals, institutions, and gray literature. Although all efforts were done to undergo this complex research in a systematic and accurate manner, the authors cannot rule out the possibility of missing some data, especially in the complex hand search segment.

Conclusion
Market access policies of both Egyptian and Saudi Arabian regulatory systems are relatively structured. There are major similarities between the two countries including; adopting regulatory frameworks of reference countries, interim nature of regulatory documents, centralized governance, and necessitating the presence of ARs. However, regarding process and implementation more progress is seen in Saudi Arabia, due to the presence of national provisions of medical devices regulations, faster processing time of PMA, and more established e-system capabilities.
The status quo of both regulatory systems poses several implications. Both markets are not directly accessible by new technologies that are unauthorized in reference countries. Furthermore, the growing market potential highlights the need for developing more comprehensive national strategies, which eventually may need to encompass the other phases of medical devices lifecycle. This includes HTA, and HTM of medical devices.
Finally, further research work is needed by both systems to assess the compatibility of post-market strategies within the context of the current regulatory frameworks. Further work is needed by both regulatory systems to look for means of strengthening their NRAs collectively to allow safe, timely, and effective access to medical technologies.

Key issues
• Despite the significant market size of medical devices in Egypt and Saudi Arabia, and its substantial potential for growth, information regarding policies and regulations for accessing this market is highly deficient. • Although a full analysis of patient's safety is not possible given the scope of this review, serious questions can be raised on the current state of heavy reliance on the US and EU regulatory frameworks by the Egyptian and Saudi Premarket Authorization systems. • The status quo of the Egyptian and Saudi systems offer a relatively fast regulatory track for market access of medical devices. These findings when combined with deficient national strategies for health technology assessment (HTA), and health technology management (HTM), may lead to unplanned industrial influx of medical devices into both markets. • A desirable market growth entails a proportionate development of regulatory systems. Short term actions are needed to guard patient's safety, while long term ones are needed to strengthen existing national regulatory authorities.