2014 was a year of major strides in streamlining regulatory processes around the globe. The International Medical Device Regulators Forum launched its single-audit pilot program, letting participating companies prove compliance in the U.S., Canada, Australia and Brazil based on one third-party assessment. China and Japan rolled out new regulatory frameworks aimed at speeding access to new devices, and Australia began accepting the CE mark for low- and medium-risk devices. In Europe, lawmakers and EU officials advanced proposals on medical device and in vitro diagnostics regulation, but couldn’t reach agreement on a premarket scheme for the highest-risk devices, reuse of single-use devices and other key issues. Legislation to create a regulatory framework for devices also resurfaced in South Africa during 2014, while India took steps to improve device quality and impose international GMPs. Below, International Devices & Diagnostics Monitor recaptures some of the main events of the year gone by.
Regulatory Reform. EU lawmakers and members of the European Commission and Council of Ministers continued to debate the merits and shortcomings of proposed regulations on medical devices and in vitro diagnostic devices, with controversy centering around whether high-risk devices be subjected to intense premarket review — à la the U.S. Food and Drug Administration.
EU-Level Expert Panel Urged
Industry group Eucomed urged that the scrutiny of notified body procedure in the draft device regulation be replaced by a “reinforced control procedure” featuring more frequent and rigorous checks by Medical Device Co-ordination Group audit teams and the Commission of the Notified Bodies. To ensure the quality of conformity assessments, the group suggested a new EU-level expert panel be created to independently vet companies’ clinical evidence as part of the review process.
As the new Parliament got underway this past fall, following May elections, it was decided to move medical devices and IVDs from the health directorate to the Directorate for Industry and Trade. Industry largely welcomed the change, saying it put a greater focus on competition and the needs of small businesses.
Across the channel in the UK, the government announced a major review of how devices and diagnostics are developed, with the aim of speeding new products to market.
New Rules in China, Japan
On the other side of the world, a two-month transition time for five new regulations in China stoked concerns that supplies of products might be disrupted. The regulations, released in August, changed the way devices and in vitro diagnostics are registered in China, the rules on instructions for use and labels and supervision of device manufacturing and distribution. The regulations are part of a major regulatory overhaul that took effect June 1. Among other things, the risk-based reforms require that clinical trials be conducted in China for all Class II and III devices, unless they can show they are equivalent to a device already listed in the country.
In Japan, the Pharmaceutical and Medical Devices Agency launched a comprehensive regulatory framework for medical devices in late November, but devicemakers were still awaiting many of the implementing regulations as that deadline drew near, raising fears that products might be temporarily blocked from that market as well. The law, adopted in 2013, also creates a new category for cellular and tissue therapy products and calls for a provisional approval pathway to speed access to promising therapies. Separately, the PMDA eased its standards for use of biological raw ingredients in medtech products.
Elsewhere, Malaysia continued to implement its 2012 device regulations, issuing five notices on how to comply with the new law and a 12-step guideline on IVD registration submissions. The former included details on authorized representatives, conformity assessment procedures for products authorized by recognized countries and good manufacturing practice certification to support an establishment license.
In Australia, the Therapeutic Goods Administration announced it will now accept CE mark certifications issued by European notified bodies for low- and moderate-risk devices, relieving companies of the need for a TGA assessment. Meanwhile, Brazil’s Anvisa issued draft resolutions that would ease registration of low- and medium-risk devices and diagnostics, and there were signs of renewed life in South Africa’s long-overdue device regulations bill.
Inspections and Audits. The International Medical Device Regulators Forum successfully launched its Medical Device Single Audit Program with two audits in which the devicemakers were found to have only minor nonconformances. Participating companies were assured they wouldn’t receive warning letters unless there was an imminent threat to the public health. Under the MDSAP pilot, slated to run through the end of 2016, an assessment performed by a single third-party auditor is sufficient to prove compliance in Australia, Brazil, Canada and the U.S.
Meanwhile in the U.S., the FDA announced a sweeping reorganization of its inspectorate that will include dedicated device investigators, eliminating the existing region-based model. Over time, investigators will be extensively trained in specific types of devices. CDRH has already identified one area that it intends to carve out as a subspecialty: radiological and mammography devices.
The specialized inspectorate is one piece of a larger plan to improve CDRH services, which includes creation of more metric-driven inspections and a five-year review of all compliance and policy guides.
And in the EU, notified bodies began conducting unannounced quality audits of companies that hold CE certificates for Class IIa and higher-risk devices. The surprise visits apply to all manufacturers that have products in the European Economic Area, regardless of where their manufacturing plants are located and come at a time when EU regulators and the U.S. FDA are moving toward sharing inspections data.
Halfway around the world, India took steps to improve device quality, proposing that manufacturers be required to follow international good manufacturing practices, while a private initiative took shape that will begin self-certifying companies’ best practice.
Harmonization. During the year, IMDRF also finalized a risk-based framework for software as a medical device and documents on device and in vitro diagnostic submission tables of content. Meanwhile, the Asian Harmonization Working Party issued draft guidance on adverse event reporting timelines and a white paper on classifying and qualifying device software.
Also in the Pacific-Rim area, Australia and New Zealand abandoned plans to create a joint regulatory authority, but said they would continue to explore regulatory harmonization. New Zealand’s health minister also promised to continue in-country regulatory reforms. Devicemakers in both jurisdictions welcomed the news, saying the potential benefits would not have offset the costs of setting up the new agency.
Also in Asia, South Korea’s Ministry of Food and Drug Safety announced it was amending its electromagnetic safety standards for medical devices to align them with international standards.
Research and Development. During 2014, the FDA issued several guidance documents focused on improving device clinical trials. One, issued in March, explained best practices in designing studies for devices intended for use by pediatric patients. In August, the FDA published final guidance and an action plan on gender differences in clinical research. The agency wants sponsors to enroll patients in numbers proportionate to the disease prevalence and track those numbers throughout the trial.
South of the equator, the Brazilian government clarified criteria for participation in a program to expand access to affordable technologies through public-private R&D partnerships.
Transparency. On Sept. 30, the U.S. government began publishing devicemaker payments to physicians, the latest provision of the Physician Payment Sunshine Act to take effect. Industry complained that the Open Payments Database lacks context, making it difficult for the public to gauge whether a payment was appropriate or not. The Centers for Medicare and Medicaid Services further riled industry by not including a reporting exemption for payments made to continuing medical education programs in final guidance.
Across the pond, the European Parliament advanced major data privacy legislation, but not before removing a provision that would have allowed clinical research subjects to demand that personal data be erased from all records, even after they were incorporated in regulatory filings. Lawmakers also carved out exemptions to data usage rules to allow devicemakers to share anonymized trial data for research purposes.
Health IT. Concerns over safety and security of device software and medical apps remained high last year. A U.S. FDA report, mandated by the 2012 FDA Safety and Innovation Act, proposed a three-tiered, risk-based framework for categorizing software: products with administrative health IT functions; products with health management IT functions; and products with medical device health IT functions. The agency would closely regulate only the last category, which would include software that duplicates functions now performed by FDA-regulated devices. The proposal echoed legislative attempts to keep most types of software out of the FDA’s purview, but still faced pushback from critics who believed it gave the agency too much discretion.
On the security front, the FDA finalized guidance requiring manufacturers of medical software and apps to describe cybersecurity efforts in premarket submissions. Topics to address include hazard analysis, updates and maintenance throughout the device’s lifecycle, and software integrity.
Laboratory-Developed Tests. The U.S. FDA signaled its intention to move forward on regulation LDTs with a July report to Congress and October guidance. The agency proposes classifying LDTs as low-, moderate- or high-risk within 18 months of issuing final guidance. Registration, listing and adverse event reporting requirements for Class II/III LDTs would take effect six months after the framework is finalized, with premarket requirements for Class III LDTs commencing six months later.
While supported by AdvaMed, the proposal faces notable opposition. The American Clinical Laboratory Association has asked the FDA to withdraw the draft and has retained attorneys for a possible court fight. Lawmakers have also asked the agency for clarification on how plans to regulate the tests.
Pricing and Reimbursement. Concerns about rising healthcare costs and patient access fueled technology assessments in the U.S. and EU. A voluntary network of European HTAs called for greater cooperation to avoid duplicating work related to device coverage decisions in individual EU countries, while the pan-European EUnetHTA proposed a framework to harmonize coverage decision guidelines in EU member states.
In the UK, the National Institute for Health and Care Excellence called for medtech cost-benefit assessments to include burden of illness. During the year, the watchdog agency also updated its guidance on cardiac devices and gave a positive nod to intrabeam radiotherapy for early breast cancer.
Meanwhile, India’s National Pharmaceutical Pricing Authority set its sights on price controls for a group of notified medical devices regulated under the country’s drug law. NPPA wrote to 10 manufacturers and importers in December demanding immediate pricing information, in response to media reports claiming that drug-eluting stents were being sold at exorbitant prices.
Device tax. In the U.S. the 2.3 percent medical device excise tax remained firmly in place, despite continued efforts by industry and some lawmakers to repeal it. The Internal Revenue Service reported that revenues from the tax were more than $250 million shy of expectations in the first half of 2013. The Republican-led House of Representatives passed a tax repeal measure in September, but it never gained traction in the Senate. With Republicans gaining control of the Senate in November, repeal seems a real possibility this year. — Jonathon Shacat, Elizabeth Orr