Key Strategies for Successfully Passing NMPA Inspections for Medical Device Manufacturers
Part 5. Verification of the QMS for Medical Device Production (Manufacture) based on GMP (Good Manufacturing Practice for Medical Device) Requirements (CFDA order No. 64 2014)
In our previous
blog post, we highlighted the importance of understanding and complying with the regulatory requirements outlined in the NMPA Guidelines for Inspection of the Quality Management System (QMS) for Medical Device Registration (2022 No. 50) for the inspection of the QMS for medical device registration, covering various aspects such as QMS principles, personnel, facilities, documentation, design and development, purchasing, production, quality control, outsourced production, and product authenticity. This blog aims to explore the well-known GMP (Good Manufacturing Practice for Medical Devices) Requirements (CFDA Order No. 64 2014) and provide some insights into the differences between ISO 13485 and the Chinese GMP requirements.
In China, the ISO 13485:2016 standard, which is internationally harmonized, has been incorporated into a recommended industrial standard known as YY / T 0287-2017. Importantly, it's worth noting that compliance with YY / T 0287-2017 is not mandatory. Instead, the mandatory QMS regulation in China, which serves as the basis for overseas on-site audits, is the "
Good Manufacture Practice for Medical Devices." (China GMP) This regulation covers various aspects, including the design, manufacturing, sales, and after-sale services of medical devices intended for the Chinese market (
Table 1).
Table 1. Notice No. 64 Good Manufacturing Practice for Medical Devices
| Chapter No. | GMP 章节 | China GMP Chapter Name |
| Chapter I | 总 则 | General Provisions |
| Chapter II | 机构和人员 | Institution and Personnel |
| Chapter III | 厂房与设施 | Buildings and Facilities |
| Chapter IV | 设备 | Equipment |
| Chapter V | 文件管理 | Document Management |
| Chapter VI | 设计和开发 | Design and Development |
| Chapter VII | 采购 | Procurement |
| Chapter VIII | 生产管理 | Production Management |
| Chapter IX | 质量控制 | Quality Control |
| Chapter X | 销售和售后服务 | Sales and After-sales Service |
| Chapter XI | 不合格品管理 | Control of Nonconforming Products |
| Chapter XII | 不良事件监测、分析和改进 | Adverse Events Monitoring, Analysis and Improvement |
| Chapter XIII | 附则 | Supplementary Provisions |
As it was already mentioned in our previous blog, for manufacturers of the implantable, sterile medical devices, independent software, custom dentures, and in-vitro diagnostic reagents the following additional China GMP annexes shall be considered:
In most cases, the requirements specified in the China GMP align well with both ISO 13485 and Good Manufacturing Practices (GMP). It's important to highlight that the on-site audit is carried out selectively, especially for initial applications for the registration of imported medical devices. In such cases, the National Medical Products Administration (NMPA) in China will acknowledge the QMS qualification issued by the foreign applicants' home country.
The NMPA recognizes an ISO 13485 certificate for overseas manufacturers as sufficient evidence of the manufacturer's qualifications. However, it's essential to give particular attention to any China-specific requirements that must be integrated into the QMS to ensure compliance with regulations when marketing medical devices in China. This is similar to many other countries with additional regulatory requirements next to or on top of ISO 13485.It's noteworthy to point out that all local Chinese medical device manufacturers are required to undergo on-site QMS audits before they can submit applications for their products.
In contrast, most medical device manufacturers from overseas have not been subjected to on-site audits by the CFDA (China Food and Drug Administration), now - NMPA.
Currently, China has not expressed any intentions to participate in "Mutual Recognition Agreements" or accept audit reports issued by conformity assessment bodies from other countries. While in practice, on-site audits for overseas manufacturers are conducted selectively pre- or post-market, it remains the responsibility of these medical device manufacturers to adhere to Chinese regulations when they market their products in China.
Therefore, the importance of identifying and adhering to Chinese regulations should not be solely based on the "risk" of being chosen for an on-site audit overseas.
What portion of the additional requirements needs to be addressed to achieve compliance with China's GMP?
To determine the extent of additional requirements that must be met to align with China's GMP standards, the manufacturer, who has already implemented a QMS in accordance with the ISO 13485:2016 standard, needs to conduct a comprehensive gap analysis. This analysis involves a detailed examination of the existing QMS against the specific criteria and expectations set forth in China's GMP regulations. By doing so, the manufacturer can identify the areas where adjustments, enhancements, or additional measures are needed to ensure full compliance with China's GMP requirements.
The table below shows a selection of the requirements within each chapter of the ISO 13485:2016 standard versus similar requirements in China GMP and highlights the differences between the two QMS regulations.
Table 2. Differences between ISO 13485:2016 and China GMP
| ISO 13485:2016 | China GMP | China GMP-specific requirements |
| 4. Quality Management System | I. General provision | |
| 4.1.1 The organization shall document a quality management system and maintain its effectiveness in accordance with the requirements of this International Standard and applicable regulatory requirements. The organization shall establish, implement and maintain any requirement, procedure, activity or arrangement required to be documented by this International Standard or applicable regulatory requirements. | Article 3
Manufacturers shall establish and improve the quality management system adapted to the medical devices manufactured in combination with product features according to the requirements in the GMP and ensure its effective operation. |
The Manufacturer has to provide the objective evidence that its QMS is adapted to the medical devices manufactured in combination with the product features (for instance, sterile, implantable, etc.) and it complies with all requirements in the China GMP.
The evidence of the established process that ensure the effective QMS operation shall also be demonstrated. |
| 4.1.2 The organization shall: b) apply a risk based approach to the control of the appropriate processes needed for the quality management system; | Article 4
Manufacturers shall conduct risk management through the whole process of design and development, manufacture, sales and after-sales service and take the measures adapted to product risks. |
China GMP specifies that risk-based thinking shall be incorporated through the whole process of design and development, manufacture, sales and after-sales service, while ISO 13485:2016 requires that the Manufacturer applies a risk-based approach to the appropriate process, basically defined by the Manufacturer. |
| 5. Management Responsibility | II. Institution and personnel | |
| 5.1 Management commitment Top management shall provide evidence of its commitment to the development and implementation of the quality management system and maintenance of its effectiveness by: a) communicating to the organization the importance of meeting customer as well as applicable regulatory requirements; b) establishing the quality policy; c) ensuring that quality objectives are established; d) conducting management reviews; e) ensuring the availability of resources. | Article 6 The principal of manufacturer is the main responsible person of the quality of medical devices and shall fulfill the following responsibilities: (1) Organize the formulation of quality policy and quality objectives of manufacturers; (2) Ensure the human resources, infrastructures and working environment required for the effective operation of quality management system, etc.; (3) Organize the management review and carry out periodical evaluation on the operation of quality management system, and continuously improve it; (4) Organize the manufacture in accordance with laws and regulations. | The organization has to review the top management responsibilities and ensure that, for example, the top management is responsible for human resources, infrastructures and working environment required for the effective operation of QMS, carry out the periodical evaluation of the QMS and organize the manufacture with respect to the laws and regulations. |
| 6. Resource Management | II. Institution and personnel | |
| 6.4.1 Work environment
The organization shall: a) document requirements for health, cleanliness and clothing of personnel if contact between such personnel and the product or work environment could affect medical device safety or performance; | Article 11 Manufacturers shall manage the health of the personnel: (1) engaged in the work affecting the product quality and (2) establish health records. | China GMP mandates that manufacturers must manage the health of personnel whose work impacts product quality, including the establishment of health records, which may entail providing proof of health examinations for these employees. In contrast, ISO 13485:2016 stipulates that health requirements must be documented, signifying that they should be clearly defined and outlined. |
| 6. Resource Management | III. Factories and facilities | |
| 6.4.1 Work environment The organization shall document the requirements for the work environment needed to achieve conformity to product requirements. If the conditions for the work environment can have an adverse effect on product quality, the organization shall document the requirements for the work environment and the procedures to monitor and control the work environment. | Article 15 For the design and installation of buildings and facilities, necessary measures shall be taken in accordance with the product features so as to effectively prevent the insects or other animals from entering. The maintenance and repair of buildings and facilities shall not affect the product quality. | China GMP requires the implementation of the pest control and the Manufacturer shall be able to provide the objective evidence of evaluation that the repair of the buildings and facilities does not affect the product quality. |
| 6. Resource Management | IV. Equipment | |
| 6.3 Infrastructure The organization shall document requirements for the maintenance activities, including the interval of performing the maintenance activities, when such maintenance activities, or lack thereof, can affect product quality. As appropriate, the requirements shall apply to equipment used in production, the control of the work environment and monitoring and measurement.
Records of such maintenance shall be maintained (see 4.2.5). | Article 22 Manufacturers shall establish usage records of inspection instruments and equipment, including the usage, calibration, maintenance and repair, etc. | A manufacturer shall document the usage records of the inspection instruments and equipment which is not required by ISO 13485:2016 standard. The evidence of the usage records can be found in the inspection records where a reference to the equipment/instrument is made. |
| 7. Product Realization | VII. Procurement | |
| Not included. | Article 42 Manufacturers shall conclude and sign Quality Agreement with the suppliers of main raw materials clarifying the quality responsibilities of both sides. | ISO 13485 requires that the Manufacturer controls outsourced process including the written quality agreements according to 4.1.5. China GMP requires that Quality Agreement shall be in lace with the supplier of main raw materials. |
| 7. Product Realization | X. Sales & After-sales Service | |
| Not included. | Article 63 The manufacturer, which sells or retains a medical device distributing enterprise to sell any products manufactured by it, shall comply with the relevant medical devices' regulations and rules. Upon their awareness of any distributing activities by such medical device distributing enterprise in violation of any laws or regulations, the manufacturer shall promptly report to the local food and drug regulatory authority. |
No such a requirement exist in ISO 13485, although it applies for manufacturer who undertake the role of distributor under China GMP. In this case additional regulations may apply: - Order No. 54 Regulation of Medical Device Distribution (No. 8 previously)
- Notice No. 58 Good Supply Practice for Medical Devices
|
| 8. Measurement, Analysis & Improvement | IX. Quality control | |
| Not included. | Article 61 Manufacturers shall formulate administrative provisions for sample retention according to product and process features, retain the samples according to relevant provisions, and maintain the observation records of retention samples. |
In addition to the in-house procedures for sampling, a manufacturer shall have a process that defines the sample retention requirements as well as the process for observation of the retention samples and managing the relevant records. |
In summary, while there may be some overlapping requirements between China's GMP and ISO 13485:2016, it's important to recognize that China GMP introduces a host of new Quality Management System (QMS) requirements that manufacturers are obligated to adhere to. These new requirements encompass a wide spectrum of elements, ranging from product quality and safety to personnel health and operational practices. As such, manufacturers need to not only navigate the familiar territory where ISO 13485:2016 applies but also proactively address and integrate the novel elements introduced by China's GMP into their QMS to ensure comprehensive compliance.
Becoming curious about what the NMPA inspection process entails?
Read our blog series - 7 parts:
Part 1. China NMPA inspection types
Part 2. China NMPA inspection process
Part 3. Preparation for China NMPA inspection
Part 4. Verification of the QMS for Medical Device Registration
Part 5. Verification of the QMS for Medical Device Production
Part 6. Verification of the QMS for Medical Device Distribution
Part 7. China NMPA Inspection Results and Common Findings
If you need assistance with the preparation to upcoming NMPA inspection, mock-inspection, gap assessment of QMS compliance with China regulations, or need subject-matter expertise contact us.