In Part I and Part II of this series, we discussed the regulatory approval processes for medical devices in the US and in Europe. The markets in these countries are significant and are often given priority consideration when medical device companies form their overall regulatory strategies. However, developed and developing countries in Asia and Latin America are gaining increasing importance as emerging markets in the medical device arena. Anglophone countries such as Canada, Australia, and New Zealandalso represent important medical device markets. In Part III of this series, we will look at some of the unique features within the regulatory processes in some of these markets.
European or American regulatory approval of a medical device can facilitate device approval in other countries. Demonstrating compliance to internationally-recognized medical device standards such as IEC 60601-1, often already achieved for a CE marked device, can bolster the acceptance of a device in many other international markets. Registration dossiers for many countries contain similar elements to those one would find in a CE Technical File or a 510(k). Having a quality system implemented per ISO 13485 and/or FDA GMPs can also support regulatory submission files in other countries.
Nevertheless, a CE marked or FDA approved device does not remove all roadblocks in the quest for world market presence of your product. Despite efforts to harmonize regulation of medical devices via international collaborative groups such as the Global Harmonization Task Force (GHTF), some factors hamper progress. Many countries are in the process of implementing regulatory requirements for medical devices for the first time.Language barriers and cultural differencescan stymie technical understanding and garble collaboration, even between countries sharing a common border. Local authorities may not operate with the same information as regional or country regulatory authorities. Import and export regulations vary from country to country, as do distribution and product reimbursement practices. All of these elements can affect the time to approve and commercializeyour medical device in the international market.
Canada, Australia, and New Zealand
The MedicalDevices Bureau of the TherapeuticProducts Directorate (TPD) is Canada’s regulating body for medical devices. Medical devices are categorized into four risk classes (Class I, Class II, Class III, and Class IV); all Class II, III and IV devices must procure a Medical Device License (MDL) prior to commercialization. The amount of information required as part of the regulatory submission depends on the device class; Class III and IV devices must also provide a Premarket Review Document which includes a summary of safety and effectiveness studies, including clinical studies if applicable. Canadian regulationsrequire class II, III, and IV device manufacturers to furnish a CAN/CSA ISO 13485 quality system certificate issued by special third party auditors which are recognized by Canadian Medical Devices Conformity Assessment System(CMDCAS). Review time for approval depends on device class; target times range from 15 days for Class II devices to 90 days for Class IV devices. Device manufacturers must provide a list of known open software issues when a product is released onto the market.
The Therapeutic Goods Administration (TGA) is responsible for medical device regulation in Australia. Approval of medical devices in Australia is similar to the process in Europe. Medical devices are divided into four risk classes (Class I, Class IIa, Class IIb, and Class III), and implementation of a quality system compliant with ISO 13485 (or equivalent) is necessary. Product conformance to the Essential Principles specified in the Australian regulation must be demonstrated; for most devices, a conformity assessment is performed by the TGA or by an EU Notified Body for a fee. A CE Technical File (or Design Dossier) is commonly used to show compliance. A local sponsor must be appointed to manage the manufacturer’s submission to the TGA.
New Zealand’s medical device regulator is called MedSafe, and is a business unit of the Ministry of Health. Devices must be registered on MedSafe’s database, Web Assisted Notification of Devices (WAND). There is no pre-market approval process in New Zealand. A local sponsor that has the legal responsibility for the medical device must be identified by the manufacturer. The sponsor ensures that a medical device is notified to the WAND database within 30 days of the product being placed on the market. A manufacturer must ensure that appropriate documentation (e.g., certification from FDA, EU or Australia’s TGA) demonstrating device safety can be furnished to MedSafe upon request.
There are some common elements that comprise the approval process and required submission documentation for medical device approval in many Latin American countries. These include:
- A Technical File or Report similar to a CE Technical File (technical description, device safety test results, biocompatibility data, labeling, etc). The required amount and type of information varies depending on the country.
- A Certificate of Free Sale (CFS) issued by the public health authority in the country of origin, whichdemonstrates that the device is cleared for sale in the US, Europe, or another country which has an established trade agreement with the country where registration is desired.
- Product registration in most countries is valid for 5 years
- Most countries divide devices into four risk classes (I, II, III, and IV or similar), ranging from low risk to high risk.
- Many countries require certain regulatory documents to be translated by a qualified individual into Spanish or Portuguese, as applicable, and notarized.
In recent years, efforts have been made to harmonizelegislation in Latin American countries in a manner similar to the European Union. However, no legislative agreements have yet been definitively established, and local laws continue to vary. As a result, some countries may require minimal information for device registration, while others require substantial supplemental technical information for the same device. It is helpful to have local representatives as part of one’s regulatory team who are knowledgeable about the local cultures and laws to facilitate preparation of documents for submission, and to aid in navigating importation and distribution requirements.
Brazil represents the largest medical device market in Latin America. Brazil is one of the most recent Latin American countries to adopt medical device regulation. Nevertheless, Brazil’s device approval process is notoriously lengthy and submission costs are the most expensive in Latin America. Brazil’s regulatory agency, ANVISA, generally employs ahigher level of scrutiny during the review process compared to other Latin American countries. Device approval requires certification to Brazil’s Good Manufacturing Practices (B-GMP, similar to FDA GMP), which can take up to 2 years to obtain due to the enormous backlog in facility auditing. After device approval, follow up B-GMP inspections are conducted every 2 years. Recent regulation has established an abbreviated registration process called “Cadastro” for lower risk devices, which permits circumvention of GMP inspection.
Documents required for submission in Brazil include a Trade Permit issued by the State, samples of labels and instructions for use translated into Portuguese, and a description of all manufacturing and quality control process steps. A Technical Report is required which includes a list of safety relevant components translated into Portuguese.
Like Brazil, Mexico’s traditional approval process for medical devices is notably long (12-18 months). In 2010 a simplified equivalency process was implemented in Mexico for devices that are cleared for sale in the U.S. or in Canada, which can shorten the review process to as few as 30 days. The fast track process requires technical documents to be translated into Spanish, and includes the following elements (among others):
U.S.fast-track required documentation (all must be translated into Spanish and notarized):
- Certificate to Foreign Government (CFG), a FDA issued document for export of products that can be legally marketed in the U.S.
- Establishment Inspection Report (EIR) –an FDA site audit report;
- A copy of the 510(k) or PMA documentation
- Canadian fast-track required documentation:
- A copy of the Medical Device License (MDL) (notarized Spanish translation);
- CAN/CSA ISO 13485 quality system certificate;
- ISO 17021 Certificate (Proof of CMDCAS accreditation of third party quality system auditor)
Argentina’s device registration time currently averages 4-6 months. Required documentation for registration includes, among other elements, a Certificate of Free Sale (CFS), a notarized declaration of Good Manufacturing Practices translated into Spanish by a qualified translator, and instructions for use translated into Spanish.
Venezuelan law specifies 20 working days for the device approval review process. Because the Venezuelan Ministry of Health is currently working with reduced hours of operation, actual turnaround time for product registration is 1 to 3 months. Registration requirements include provision of 3 letters of recommendation from physicians that have used the device in another country where the device is approved. Sterilized devices must also be tested by a local accredited institution as part of the approval process.
Device registration in Peru requires a Certificate to Foreign Government (CFG) (FDA issued document for export of products that can be legally marketed in the U.S) and a Letter of Authorization.
Currently a medical device may be sold in Chile without governmental authorization, as there are no registration requirements.
Japan is one of the largest markets in Asia for medical devices. Medical devices must be registered with Japan’s medical device regulatory agency, Pharmaceuticals and Medical Devices Agency (PMDA). Japan classifies devices into four risk categories (Classes I, II, III, and IV). In addition to implementing an ISO 13485 compliant quality system, manufacturers of high risk medical devices (Class III and IV devices and some Class II devices) mustundergo a rigorous quality system audit by the PMDA. Higher risk devices also require submission of a Summary Technical Document (STED) to demonstrate safety and performance.
Historically, the Japanese review process has tended to take anywhere fromabout 8 months to 21 months for approval, depending on whether a device is determined to be substantially equivalent, improved, or a brand new medical device per the Japanese regulation. Recently,PMDA has implemented an action program with the intention of accelerating the review process. Activities include hiring more device reviewers, allowing for more subcontracting of clinical studies, and an overall reorganization of the review department within PMDA. Review time for device approval in 2011 was reduced to between 5 and 10 months, depending on device type.
Development and reform in China are causing medical device regulations to evolve at a rapid pace. China’s medical device regulatory authority, the State Food and Drug Administration (SFDA), classifies devices into 3 risk categories.Device approval includes submission of a dossier to the SFDA as well as type testing. For Class II and III products, SFDA does not accept Notified Body or CB Scheme product safety test results; type testing must be conducted by a SFDA recognized test laboratory on Chinese soil to the Chinese safety standard (which is similar to the IEC 60601-1 standard). There is generally a large back log for type testing. Manufacturers wishing to import medical devices must also submit a notarized quality system certificate demonstrating compliance with ISO 13485 or FDA GMPs. Class III products manufactured outside of China are subject to an onsite product audit prior to registration approval. Class III devices are also likely to require clinical studies conducted in China prior to approval, in particular for devices which contact the central nervous system. For devices which do not require clinical studies, the total product registration time can take approximately 12-18 months.All regulatory submission documents must be in both Chinese and English; translation costs can be significant.
As in Japan, Korea’s regulatory authority, the Korea Food and Drug Administration (KFDA), classifies devices into four risk categories (Classes I, II, III, and IV). For Class II, III, IV devices, registration is obtained by submitting a Technical File and conducting type testing by a third party. For some higher risk devices, the technical file may also require clinical study data as part of the submission. Companies must also obtain certification to Korean Good Manufacturing Practices (KGMP) via a third party organization which works together with KFDA to conduct a compliance evaluation.
In India, medical devices are classified as drugs. Only some devices are regulated; the government supplies a list of about 40 categories of products which require product registration. It is expected that more products will require registration in the future. Registering a device in India requires, among other things, an ISO 13485 certificate for the manufacturer’s quality system and an authorization letter from the Indian government. A meeting with the government for a fee prior to applying for this authorization can help pave the way for approval.
Regulations in Singapore have recently changed to require product registration for most medical devices. Devices are classified into four risk categories (A, B, C, D). Products which have already been approved in another market such as the U.S., Canada, or Europe may follow an abbreviated registration process.
Hong Kong does not currently require medical devices to be registered in order to be commercialized. While registration is voluntary, it is likely that registration will be required in the future.
While U.S. or European approval of a medical device can substantially ease the burden of registration and approval in other countries around the world, harmonization of medical device regulation is still far from being realized. In developing countries in particular, the regulatory approval process is evolving and dynamic. In Latin American and in Asia, language and translation efforts impart a cost and schedule impact to the registration process, and should be considered in regulatory strategy planning. In such markets, installing a local presence to work closely with regulators and to facilitate importation and distribution of product is an important asset for successful approval and commercialization of medical devices.
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Karen Brentnall is senior quality engineer at Stratos Product Development. She has 16 years of experience in product development and quality engineering, during which she developed expertise in class II and III medical device product development. Prior to joining the quality and regulatory world, she worked for eight years as a mechanical design engineer. She has played an active role in the design, development and manufacture of numerous medical devices including the SuperSonic Imagine Aixplorer diagnostic ultrasound system, the Boston Scientific Rotablator rotational artherectomy system, several therapeutic catheter devices and LVADs, and a hemodialysis machine. Her expertise includes development and maintenance of documentation to support medical device regulatory submissions, including risk management, quality planning and verification. Her capabilities also include implementation and maintenance of quality management systems per the FDA medical QSRs and ISO 13485.