China Medical Device Registration & Regulatory Consulting | GRP

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China / MEDICAL DEVICES CONSULTING

REGULATORY STRATEGY

The regulatory process from product design to market entry for a new medical device or IVD is oftentimes complicated and unclear. Most of the Chinese regulations are in Chinese and are changing continuously. The

GRP RA team stays current with the latest legislation, regulatory requirements and interpretations and industry initiatives in China. GRP’s team makes sure that its clients are kept informed of changes in the regulatory environment that may impact their regulatory and business strategies in China.

Our regulatory team in China has the expertise in developing effective and tailored regulatory strategies for medical device companies that helps them get their products successfully registered in China, in timely manner and with minimum risk.

PRODUCT REGISTRATION

Although China’s medical regulatory bodies are becoming more harmonized with international standards, the Chinese registration process still poses significant difficulties for Western medical device and pharmaceutical firms.

Device should be approved in original country before it is registered in China. Every medical device should be registered with CFDA for getting access to Chinese market. If you require assistance with obtaining approval for your medical device in China, at GRP, we can help you prepare the necessary documents and register your product with the Chinese regulatory authorities.

Classification of medical devices in China:

Device Class Description
Class I Devices The safety and effectiveness of the device can be ensured through routine administration.
Class II Devices Further control is required to ensure the safety and effectiveness of the device
Class III Devices The device is implanted into the human body; used for life support or sustenance; or pose potential risk to the human body, and thus must be strictly controlled in respect to safety and effectiveness.

REGISTRATION PATHWAYS

Device Class Clinical Trial Requirement Description
Class I Devices Not required Class I medical devices no longer need to be registered with the CFDA; instead, a notification must be filed with the relevant local level Chinese FDA. However, for the notification application, more documents will be required than there were for Class I registration.
Not required Required
  • Chinese Specification Drafting (Dossier Preparation and Specification Drafting): 1 month
  • Sample Testing: 6 Months
  • Filing to the CFDA- Preliminary review and acceptance notice: 1 Month
  • CMDE Review- Supplementary notice: 60-90 Business days (2-3 months)
  • Supplementary Dossier preparation: 1 year
  • CMDE Review:  60 Business days (2 months)
  • CFDA Final review- Registration approval:  30 Business days (1 month)

Exceptions For clinical trials:

  • The product has a clear working mechanism, finalized design, and mature production technology. A medical device of the same variety is already on the market and has been used in clinical practice for many years without any record of serious adverse events. There will also not be any changes to the product’s conventional usage.
  • The safety and efficacy of the product can be proven through non-clinical evaluations.
  • The safety and efficacy of the product can be proven through the analysis and evaluation of data obtained from clinical trials or clinical application of other medical devices of the same variety.

Application Requirements

Class I medical device:

Section Description
1 Product Risk Analysis Document
2 Product Technical Specification
3 Product Testing Report (Company’s self-testing report or third party report)
4 Clinical Evaluation Report
5 Key Manufacturing Information (process, flowchart, material, etc.)
6 Design/ Artwork of IFU and product label for the minimum selling unit
7 Legal Documents:

  • Legal qualification of the foreign manufacturer (i.e. ISO 13485)
  • Market authorization approval at the country of origin (i.e. CFG+510k or CE)
  • Authorization letter to the agent in China.
8 Self-Declaration Letters

  • Letter to declare that the documents submitted meets the CFDA’s regulation for Class I Medical device notification.
  • Letter to declare that the product conforms to the Class I Medical Device classification catalog.
  • Letter to declare that the product conforms to the National and/or Industry standards (GB/YY) in China, and the list of these conformed standards.
  • Letter to declare that all submitted documents are true.

*Chinese translations of all the documents are required. Both original and notified copies of the legal documents are required.

Class II and III Medical Devices:

Section Description
1 Application Form
2 Legal Documents
3 Main safety and Efficacy Specification List
4 Summary Data

  • Overview
  • Product description
  • Product model
  • Description of the package
  • Intended use and contraindications
  • Predicated device (if applicable).
  • Other Information
5 Research Data:

  • Product performance evaluation data
  • Biocompatibility evaluation data
  • Biosafety research data
  • Sterilization and disinfection process validation data
  • Shelf and package evaluation data
  • Animal research data
  • Software validation data
  • Other data if necessary
6
  • Manufacturing process description for active/inactive device
  • Manufacturing site description
7 Clinical Evaluation Data
8 Product Risk Analysis Data
9 Product Technical Specifications
10  Registration Testing Report

  • Testing report issued by a CFDA certified lab
  • Preliminary evaluation comment from the testing lab
11  Artwork for the IFU and Product Label

  • Instructions for use (IFU)
  • Artwork of the product label for the minimum selling unit
12 Self-Declaration Documents

TYPE TESTING REQUIREMENTS:

In almost all situations for Class II and Class III devices, the CFDA will request samples for type testing. The testing centers will use the product standard to determine what tests to conduct.

  • For Class II and Class III devices, the CFDA will request samples for type testing. For Class I products, CFDA will accept a company’s foreign testing data.
  • Testing centers will test all specification items listed in the Product Technical Specifications (YZB Product Standard which is drafted by the company).
  • For each specification item, testing centers will utilize the testing method described in the Product Technical Specifications.
  • While conducting the tests, the CFDA requests that testing centers provide comments on the company’s drafted Product Technical Specifications.
  • The comments from the testing center should be submitted together with the testing report to avoid repeats and additional testing, which occurs frequently, leading to long delays in the registration process.

The testing report will be issued by a CFDA certified national testing center, which can be freely selected from the CFDA list. It is only valid for 1 year, and once it expires, a company must start again to obtain a new valid testing report.

QUALITY COMPLIANCE

  • The CFDA has issued various regulations to strengthen management and organization at medical device manufacturing sites. This includes implementing Good Manufacturing Practice (GMP) standards for all medical devices, a more stringent adverse events and recalls system, additional on-site inspections, and other new industry standards. In addition to the CFDA, the General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ) also carries out safety, certification, and inspection of certain medical devices to ensure adherence to quality standards.
  • However, despite the improving standards and implementation of GMP regulations for medical devices in China, there are still many scandals regarding defective products due to poor quality systems. Foreign companies will need to conduct audits in order to ensure that their Chinese operations or partners are performing according to expected standards.
  • There are two types of on-site audits that are required in China: a one-time quality management system (QMS) audit for registration that domestic and foreign manufacturers must complete, and a GMP audit for a manufacturing license after registration that local manufacturers must complete annually. Requirements for these audits include an on-site audit checklist as well as multiple company meetings.

CHALLENGES TO MEETING GMP STANDARDS IN CHINA

  • In some Chinese factories, there are no organized or centralized quality manuals that employees can readily access.
    As a result, quality control in Chinese factories may be minimal. Thorough audits can help locate the areas that are deficient and update the quality systems to meet Western standards.
  • There may be poor document control and reporting inconsistency in Chinese factories.
    In some factories, if procedures change, the changes are usually not documented. When a device is reported as having failed, some factories do not investigate or report the adverse events. Having the factory audited can help identify post-market surveillance issues and set up systems for reporting adverse events.
  • Even after a factory is GMP compliant and a good quality system is set in place, problems will still arise if employees are not invested in the process.
    It essential that those employed by the medical device factory upkeep the maintenance required to guarantee an effective quality system. Many do not understand (or care about) the ramifications of poor quality control or intellectual property theft.

Local Representation

When marketing a drug or medical device in China, it is important to have an independent in-country representative for your products that is a legal entity registered in China, even if you are marketing through a Chinese distributor.

This representative serves as the required local entity that deals with the China Food & Drug Administration (CFDA) regarding product registration and renewal, adverse event reporting, etc. There are three local agents required:

  1. Registration Agent: The company that registers the product is the registration agent.
  2. After Sales Agent: The after sales agent provides technical service and support for the medical device product. The business scope described in the business license of the local legal Chinese entity must include a provision stating that the after sales agent will provide such services.
  3. Legal Agent: The legal agent’s key responsibilities include: a) reporting any adverse events regarding the medical device that occur inside or outside China to the CFDA; and b) handling any recall issues as they arise, as well as other regulatory matters.

Having an independent third party allows for confidentiality of technical information and less reliance on a distributor, whose primary motive may only be sales. In cases where your distributor is acting as your local agent, if your distributor does not perform well and you wish to end the relationship, the distributor may attempt to charge a large fee to transfer the existing registrations or refuse to transfer them at all.

CLINICAL TRIALS

Medical Device clinical trials in China must comply with China’s GCP requirements. It is important to determine if the device requires the clinical trials. This can be decided based on the classification of the device.

As is the case in many countries around the world, a local clinical trial is almost always required for the registration of drugs in China. Since drug registration in China follows global International Conference on Harmonisation (ICH) guidelines, data requirements in China are like those in the United States and other developed countries. However, companies may encounter difficulties if they want to keep sensitive data confidential from copying competitors.

In some cases, as an alternative to local clinical studies, a bioequivalence (BE) study will be required instead. The BE study will test similarities between two drugs believed to have the same active ingredients and use.

The filing process for clinical trials in China begins with submitting a Clinical Trial Application (CTA) dossier to the CFDA. The Center for Drug Evaluation (CDE) reviews the submission dossier, test report, and verified specification, and requests a panel meeting if any concerns or questions are raised. The CDE may issue supplementary requests if any additional documents are needed from the applicant. The National Institute of Food and Drug Control (NIFDC) tests and analyzes the quality of the drug samples, while the Center of Food and Drug Inspection (CFDI) inspects sponsors and manufacturing sites.

After the CDE’s review, a recommendation on whether to grant the applicant a Clinical Trial Permit (CTP) is submitted for confirmation to the CFDA. The CTP approval requires an extensive length of time—about 18 months after the initial CTA dossier is submitted to the CFDA. The CFDA prioritizes which clinical trial proposals to review first according to the product’s level of importance. Drugs that aim to cure serious diseases, such as AIDS and cancer, are normally fast tracked to get clinical trial approval.

After obtaining a CTP, the company is free to initiate clinical trials at any approved site in China, as long as they follow Good Clinical Practices (GCP) throughout the clinical trials.

CFDA Clinical Trials China

The CFDA’s Drug Regulatory Department oversees local clinical trials and affirms compliance with GCP. Generally, clinical trials in China involve four phases:

  • Phase I – an initial review of the drug’s safety to humans
  • Phase II – an evaluation of the effectiveness of the drug
  • Phase III – a confirmation for the effectiveness of the drug
  • Phase IV – a post-marketing study

The clinical trial’s sample size must meet statistical requirements by satisfying the minimum number of subjects outlined by the CFDA. If the institution is unable to reach the minimum sample size because of the rarity of a disease, the institution should appeal to the appropriate provincial-level FDA (PFDA) to reduce the sample size.

The trial must be carried out by an organization certified to conduct drug clinical trials, using drugs from manufacturing facilities that follow Good Manufacturing Practices (GMP).

If there is a serious adverse event, investigators must notify the PFDA and applicants within 24 hours, and the ethics committee thereafter. If an event is serious, the PFDA may suspend or terminate the trial. A trial may also be terminated due to fraud, ethical concerns, and failure to report adverse events.