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Answer:Foreign nationals planning to work in the Philippines are required to secure a work visa, which can be obtained from the Philippines’ Bureau of Immigration (BI), as well as an Alien Employment Permit (AEP) issued by the Department of Labor and Employment (DOLE).Alien Employment PermitAn Alien Employment Permit (AEP) authorizes a foreign national to work in the Philippines. Though not a work permit, AEP is an important legal document required to secure a work visa in the country.Some foreign nationals are exempted from obtaining an AEP. These include:All members of the diplomatic service and foreign government officials;Owners and representatives of foreign principals whose companies are accredited by Philippines Overseas Employment Administration (POEA); andPermanent resident foreign nationals and probationary or temporary resident visa holders under the Philippines’ immigration law.Reference: August 18, 2017Posted by ASEAN Briefing

The development of medical device starts with the need realized by a physician or surgeon. The device development is usually the result of this need and communication between him and engineer from a medical device supplying company. Although large medical device companies typically develop successive iterations of existing devices, most new device categories are typically developed by venture-backed start-up companies. Typically, a physician and/or engineer inventor conceives of a device solution to an unmet clinical challenge, initiates the patent process, and builds preliminary device prototypes. Preliminary bench and animal testing may be performed using the inventor’s or an acquaintance’s personal funding (angel investors). Further development typically requires engaging a team of engineers who work closely with physician advisors to bring the concept through the “design-build-test-redesign” cycle of bench and animal testing. This preclinical stage typically takes 2 to 3 years and depending on the nature of the device may consume US$10 to $20 million before the device is ready for clinical testing. These capital requirements exceed the means of most angel syndicates and are typically obtained from venture capital firms in the form of equity financing.A small percentage of device ideas are conceived in academic medical centers using federal or other grant funding. Few academic centers have the intrinsic capabilities to develop the device beyond the early prototype stage. Intellectual property is typically out-licensed to an existing company or start-up for further development. To facilitate the development of ideas that emerge out of federally funded programs, Congress passed the Bayh-Dole Act that assigns all intellectual property rights to the academic medical center.Initial Clinical TestingA start-up company’s survival is dependent on reaching milestones efficiently (in terms of time and money) to successfully raise additional funding. First clinical use is perceived by many as a key milestone, so that delays in the initiation of clinical testing programs can threaten a company’s viability. Companies will therefore seek the quickest path to first clinical use. US regulatory requirements are more extensive and require additional time and resources compared with those of other countries. It is estimated that obtaining Food and Drug Administration (FDA) approval to initiate clinical studies in the United States adds 3 to 6 months to the process of device development. In addition, subsequent review by the institutional review board (IRB) at the clinical site can add an additional 3 to 6 months to this timeline. Because of these factors, initial clinical device testing has shifted largely to outside of the United States. It is thus estimated that more than 75% of first clinical use cardiovascular device testing is now outside the United States, saving what may be 6 to 12 months when compared with US clinical initiation. When initial clinical testing is performed within the United States, it is estimated that only 25% of the work occurs at academic institutions. This is due in part to the bureaucracy associated with large academic institutions for both IRB approval and contract negotiations .Clinical testing of an unapproved significant-risk medical device requires FDA approval in the form of an Investigational Device Exemption (IDE). The IDE application provides information to the FDA on device design and qualification, as well as on the study protocol. The FDA is mandated to respond to the IDE application within 30 days.1 An IDE may also be required for studies in which an approved device is used for a purpose distinct from its approved indication.2 This is typically the case when a trial is sponsored by a company for the purpose of expanding the indication of a device or making significant changes in the instructions for use.Regulatory Approval Process (United States)Medical devices are regulated in the United States by the Center for Devices and Radiological Health (CDRH) of the FDA. The FDA/CDRH mandate is to promote and protect the public health by making safe and effective medical devices available in a timely manner. The standard for demonstrating safety and effectiveness is determined in part by the risk associated with the device in question. Devices are classified according to their perceived risk using a 3-tiered system (class I, II, or III).Class I devices (lowest risk) are subject to general controls, which are published standards pertaining to labeling, manufacturing, post-market surveillance, and reporting. Devices are placed into class I when there is reasonable assurance that general controls alone are adequate to assure safety and effectiveness. The general controls that typically apply to class I devices include prohibitions against adulteration and misbranding, requirements for establishing registration and device listing, adverse event reporting, and good manufacturing practices. Furthermore, remedies including seizure, injunction, criminal prosecution, civil penalties, and recall authority are provided to FDA. Formal FDA review is not required for most class I devices before their market introduction.Class II devices are those higher-risk devices for which general controls alone have been found to be insufficient to provide reasonable assurance of safety and effectiveness, but for which there is adequate information available to establish special controls. Special controls may include performance standards, design controls, and post-market surveillance programs. In addition, most class II devices require FDA clearance of a premarket notification application (PMA or 510[k]) before the device may be marketed. In the 510(k) application, the medical device manufacturer must provide data to demonstrate that the new device is “substantially equivalent” to a legally marketed device. Although substantial equivalence can usually be demonstrated on the basis of bench and animal testing alone, approximately 10% of 510(k) applications include clinical data.Class III devices, such as heart valves, pacemakers/implantable cardioverter-defibrillators, and coronary stents, are judged to pose the highest potential risk. These devices are either life-sustaining/supporting, of substantial importance in preventing impairment of human health, or present a high risk of illness or injury. Consequently, general and special controls alone are inadequate to provide reasonable assurance of safety and effectiveness. Most class III devices require FDA approval of a PMA before they can be legally marketed. Approval of the PMA generally requires clinical data demonstrating reasonable assurance that the device is safe and effective in the target population.The Human Device Exemption (HDE) is a new pathway to allow for commercialization of class III devices designed to address small markets, ie, diseases or conditions that affect fewer than 4000 patients in the United States each year. Approval of an HDE requires demonstration that the device is safe and the probable benefits outweigh the probable risks. Although the process may require smaller clinical trials, an HDE device must continue to operate under local IRB approval at each participating institution and must continue to collect case report forms akin to an ongoing clinical trial. The PMA process typically involves a series of studies starting with first clinical use and culminating in a multicenter, prospective randomized control trial (pivotal trial). The complexity and extent of the clinical testing program is dictated by the nature of the device and its proposed use. The clinical study program is developed by the company in conjunction with clinician investigators, all in close collaboration with FDA/CDRH.The first and arguably most important step in this process is the pre-IDE meeting, in which the company, often accompanied by the lead clinical investigator(s), meets with FDA/CDRH to present data about the device, its clinical development program, and its intended use after approval. The FDA/CDRH staff reviews existing bench and animal data (as well as any outside-the-United States clinical data) and makes informal non-binding suggestions regarding the need (if any) for additional pre-clinical data (bench and animal), as well as the study design. The sponsor then submits an IDE application to FDA/CDRH (Medical Devices) for formal review.Clinical development of a new class III device is typically divided into pilot and pivotal trial phases. The purpose of the pilot phase (starting with first clinical use) is to establish safety and to assist in design of the pivotal trial. Pilot-phase testing is typically limited to fewer than 100 patients treated at a few centers. The purpose of the pivotal trial is to generate data that define patient populations in which use of the device is safe and effective. The dialogue initiated during the pre-IDE meeting continues and intensifies between FDA/CDRH and the company over the specifics of the pivotal trial and includes the patient population, the control group against which the new device will be evaluated, and the primary and secondary end points of the evaluation. For first-in-class devices, eg, drug-eluting stents, where there are few data regarding short- or long-term outcomes, FDA/CDRH requires prospective randomized controlled studies. Though high profile, devices that require randomized data for approval are the exception rather than the rule. The vast majority of device clinical trials are case series that carefully document product performance. Still more products are approved as “tools.”Most devices currently in testing are similar to well-characterized approved devices, eg, next generation bare metal stent, angioplasty balloon, etc. When FDA/CDRH has substantial data on the device class metrics, comparisons may be made to historical data or objective performance criteria. When few data on existing standards are available, the FDA typically requires randomized rather than single-arm studies, in which the new device is compared against concurrent controls treated with current best medical practice. That comparison may be powered to show that the new treatment is superior to prior approaches, or that it is non-inferior (equivalent or better) compared with a previously approved device in a new area. The issues relating to the type of trial are discussed below.The specifics regarding study design may have profound impact on the time and cost of bringing a new device to market. Though the primary mission of the FDA/CDRH is to ensure safety and effectiveness of commercially available devices, when exerting regulatory oversight the agency must balance its primary mission with the costs of introducing new technologies to the clinical marketplace. This has been codified by the FDA Modernization Act and the FDA Modernization Act-II, which require the agency to pursue the “least burdensome means” available to establish device safety and efficacy. Although surrogate end points, eg, angiographic restenosis rather than recurrent cardiac events, may be allowed as secondary end points, the primary end point of a pivotal trial for a first-in-class class III (Classify Your Medical Device) device is usually a clinical end point (or a well-established surrogate such as infarct size in a myocardial infarction treatment device). Depending on the end points negotiated, such pivotal trials may require enrollment of 1000 or more patients at 30 to 50 sites over a period of 1 to 2 years, with appropriate follow-up frequently to 1 year after treatment. The trial must be conducted according to good clinical practices standard, with the approval of the local IRB at each participating center.Clinical Site (IRB, Contract, Conflict of Interest)Once the FDA/CDRH has approved the IDE, the sponsor must formally recruit as many as 50 sites to ensure patient enrollment in a timely fashion. Each site has its own rules regarding participation in clinical studies, which typically can be divided into 3 components: Human research, contract, and conflict of interest.Every clinical site is federally mandated to have an IRB responsible to ensure the protection of the rights, safety, and welfare of research subjects. Regulation of the IRB review of protocols involving medical devices is under the purview of the FDA. The Office of Protection From Research Risks (OPRR) is responsible for oversight regarding all human research and is in direct communication with the FDA/CDRH. Studies involving human subjects that do not involve products regulated by the FDA fall under the direct purview of the OPRR. Both the FDA and the OPRR are in the Department of Health and Human Services. Each IRB must meet standards for the composition, leadership, and processes set forth by that department. IRBs are subject to periodic audits by the FDA to ensure that records and procedures are in compliance with regulations.Working with the sponsor, the principal investigator prepares an application to the IRB at his/her institution that includes the consent form describing in lay language the device, the proposed clinical study, the inclusion and exclusion criteria for the trial, and a draft consent form describing the risks and benefits of participation in the study. The IRB then formally reviews the application and frequently requests changes, particularly to the informed consent. The IRB process typically requires approximately 3 months, but at times can take considerably longer.The company must also negotiate agreements with each clinical site addressing the many issues associated with the clinical trial. In addition to the study costs/reimbursement (per-patient enrolled and overhead), these agreements typically include indemnification and the assignment of ownership rights of new discoveries (intellectual property) made in the course of the study. The resources required at each center to perform the high quality research necessary for a PMA protocol are formidable. In addition to resources required to maintain an excellent clinical program (physician, nursing, and technical staff coupled with state of the art facility), the study center must dedicate additional resource, primarily research nurses to perform high-quality clinical research. The role of the research nurse is critical to all phases of the trial, including general study management, IRB process, patient recruitment, and accurate completion of case report forms. The sponsor is responsible for accrediting each clinical site to document that the necessary resources are in place to fulfill the demands set forward in the protocol. The clinical research staff do not provide clinical care and are thus not part of the hospital’s salaried clinical nursing staff. The per-patient costs include all additional charges the patient incurs for the study, including procedures (therapeutic and diagnostic), clinic visits, and diagnostic studies, as well as research nurses’ salaries. It is estimated that it takes 3 to 6 months to formally recruit each clinical site.Device development from the earliest stages requires active involvement of practicing clinicians. Clinician/inventors are frequently involved in creation of the device concept and are often integral members of the design team performing the majority of the early animal studies. Through this involvement, the clinician/inventor obtains intimate knowledge of device performance and failure modes. Safety concerns during first clinical use and pilot phase mandate participation by these clinician/inventors. The clinician/inventors frequently take leadership roles and have equity positions in the company developing the device. These interests present important conflicts of interest which must be addressed to ensure patient safety, data integrity, and public trust in the process. Many institutions have set up formal processes to address these conflicts of interest, potentially adding more time to the institutional recruitment process.Pivotal studies required for a PMA application are typically large multicenter randomized trials and often represent the largest commercial risk and expense in the device development process. In addition to obtaining an IDE from the FDA and formally recruiting clinical sites, the sponsor must also put into place an extensive infrastructure that typically includes engaging a contract research organization (CRO), core laboratories, formation of a data safety monitoring board (DSMB), and an executive committee. The CRO provides the infrastructure required to recruit, qualify, and audit sites. Core laboratories evaluate primary data, eg, angiography, ECG, and ultrasound results, in a uniform and blinded manner. An executive committee is typically composed of the clinician investigators, company representative, CRO, and core laboratories. The DSMB, composed of a group senior clinical investigators and statisticians with no other involvement in the study, periodically reviews trial data at specified intervals. The DSMB has the mandate to stop or modify a study, eg, discontinue randomization to one of the groups if complications associated with the study device are in excess of anticipated rates, if differences between study groups reach statistical significance, or if further patient enrollment will not impact study outcome.Regulatory Approval Process (European Union)Though there are many similarities in the regulatory process in the United States and countries within the European Union, there are important differences that impact the time and cost associated with the introduction of a new medical device.I have identified 3 illustrative examples: Use of notified bodies, criteria for approval, and local site (IRB/site negotiation).The European Union system relies heavily on notified bodies (NBs), which are independent commercial organizations to implement regulatory control over medical devices. NBs have the ability to issue the CE mark, the official marking required for certain medical devices. NBs are designated, monitored, and audited by the relevant member states via the national competent authorities. Many functions performed by the FDA/CDRH within the United States are performed by NBs, including medical device certification, device type designation, assessment and verification of quality systems, and review of design dossiers for high-risk devices. Currently, there are more than 50 active NBs within Europe. A company is free to choose any notified body designated to cover the particular class of device under review. After approval, post-market surveillance functions are the responsibility of the member state via the competent authority. NBs typically function in a closed manner, providing little visibility on criteria required for approval. This dynamic allows for a high degree of variation as well as competition among NBs. As a result, NBs are perceived by industry to be less bureaucratic organizations that can respond more quickly and efficiently than the FDA. These potential benefits may be offset by a system that is intrinsically more fragmented and highly variable and has resulted in the approval and continued marketing of devices, eg, abdominal aorta stent grafts, in Europe that failed efficacy trials in the United States.Criteria for approval of high-risk devices are different in the European Union. To receive approval to market a class III high-risk (and some class II) device in the United States, the manufacturer must demonstrate the device to be reasonably safe and effective, which typically requires a prospective, randomized controlled clinical trial. To receive approval to market a device in the European Union, the manufacturer must demonstrate that the device is safe and that it performs in a manner consistent with the manufacturer’s intended use. This difference has a profound impact on the size and scope of the clinical studies for regulatory approval. This significant difference is illustrated by examining the introduction of distal protection systems. The GuardWire developed by PercuSurge, Inc (later acquired by Medtronic) is a specialized coronary guidewire with an elastomeric balloon mounted at the tip. During an angioplasty/stent procedure, the operator crosses the lesion with the GuardWire and inflates the balloon. Stent placement is then performed, after which a specialized catheter is used to evacuate any arterial debris that may have become dislodged during the procedure. The GuardWire balloon is then deflated. Demonstration of safety and performance, ie, ability to aspirate material during the stenting procedure, was demonstrated in a 22-patient single-arm study. In contrast, in the United States, this device was designated class II (requiring 501[k] clearance and clinical data). To satisfy US criteria for clearance, the standard of safety and effectiveness required in this case was defined as the ability to reduce complications associated with stenting of saphenous vein grafts. To meet this criterion, an 800-patient multicenter trial randomized trial comparing distal protection to usual care (no protection) was performed. At 30 days, a 42% relative reduction in major adverse cardiac events (primarily myocardial infarction) was observed. A trial of this type is estimated to cost US$10 to $12 million and may take 24 months to perform.

The election of 1996 was the first Presidential Election I was able to vote in.I did not vote for H. Ross Perot. I despised the man. You see when I was in highschool I was involved in several extra curricular activities only one of which was a University Interscholastic League activity.UIL has a “No Pass No Play” rule, which was the brain child of H. Ross Perot, but that is just information for you and not the specific reason I despise him.My Junior year of high school, I was elected Area 5 Region 1 President for Business Professionals of America. This organization is not part of UIL.I had an English teacher that year which I disagreed with. She required lots of memorization of useless texts from a variety of book. When asked what good this would do for a growth adult her only answer was it would make you well rounded. I had the same problem with my senior year English teacher. Consequently, after 30 years, and three college degrees, I have never used a single bit of information I memorized in either of those classes.This means I struggled to pass those classes, not because I didn't know the content, but because I criticized the teacher and their demand for memorizing useless information. Information they were incapable of demonstrating any future use for.Well, thanks to Ross Perot most Texas schools extend UIL rules to organizations that aren't UIL, because Ross pushed UIL to focus on punishing schools and students. Basically, a school could lose their UIL accreditation if a student participated in an extra curricular activity, even if the activity wasn't associated with UIL.My main problem with this rule is that it really doesn't affect most students. In my school, only 30% of students were involved in UIL activities. An additional 10% were involved in non-UIL activities. The remaining 60% of the students were not involved in any extra curricular activities at all. Now, this wasn't a small highschool. This was one of the wealthier highschools in the Texas with around 2500 students.So basically, thanks to Ross Perot, I was punished for disagreeing with a couple of highschool English teachers and unable to participate in school activities.That is really just a long way of saying I didn't vote for Ross Perot. I voted for Bob Dole and I voted consistently Republican until 2012 when the GOP chose an elitist as their candidate. That is the only time I voted for the Democratic candidate. Then 2016 election rolled around. The GOP nominated a lying, chearing, clueless elitist, and the Democrats nominated a two-faced candidate. I couldn't in good conscience support either candidate. I voted Libertarian that year.This year the only thing that matters is removing the current GOP elitist from the office. Any vote I give must be for that purpose. For the second time in my life, I'll vote for the Democrat.