Technical documentation in Chinese eRPS format (table of content)

nIVD MA ToC, IMDRF

a)           Information regarding the packaging of the devices, including, when applicable, primary packaging, secondary and any other packaging associated;

b)          Specific packaging of accessories marketed together with the medical devices shall also be described;

c)           If the user needs to package the medical device or its accessories before they perform sterilization, information about the correct packaging (e.g. material, composition, dimension) should be provided.

eRPS requirements, NMPA

Packaging description. Information on the packaging of the product and the packaging of accessories sold with the product; for sterile medical devices, information on the initial packaging appropriate to the sterilization method should be stated.

The requirements at nIVD MA ToC in IMDRF focus on different levels of labels, specific packaging of accessories and packaging info before sterilization. The requirements in eRPS format at NMPA require the general packaging description, packaging of accessories and packaging information of sterile medical device.

The conclusion is that the manufacturer should check the original regional requirements in Chinese eRPS guidance. The extent of documents could be more simple, however a bit different. The authority has its own preference and also traditional review thinking from former submission structure with only 12 chapters and without sub-chapters. 

VIP chapter

Besides the submission structure in given table of content, it hides the requirements behind each chapter of which legal manufacturer should take care.  Besides it, the manufacturers should pay attention to product specific guiances and standards. The requirements in details are derived from there regarding the specific verification and validation (software, shelf life, usbility, bocompatibility etc.), risk management and clinical evaluation etc.

Which one is under sharp view of Chinese authority after introduction of eRPS format?

If clinical study is not applicable to subject medical device, the eRPS chapter 3 NON-CLINICAL EVIDENCE is the most challenging part to provide verification and validation test. We would accompany you to go through the detailed requirement by NMPA.

As seen below there are 8 second level chapters (CH03. XX) under NON-CLINICAL EVIDENCE. 

Among CH03.05, these chapters in figure 3 squared have same sub-structures:

study description, study identifier, date of initiation, summary, full report and statistical data (if applicable) 

It means that manufacturer should pay attention of these topics by providing convincing testing report and understandable summary. So far all tests can be done in home country without additional Chinese requirements despite existing Chinese standards. For summary it should include the (1) purpose, (2) methods, (3) acceptance criteria, (4) results and (5) discussion and conclusions.

V&V requirements in details

3.05.01 Physical and Mechanical Characterization 

3.05.02 Chemical/Material Characterization

3.05.03 Electrical Systems: Safety, Mechanical and Environmental Protection, and Electromagnetic Compatibility 

3.05.04 Radiation Safety

Information on product performance studies and a description of the study and preparation of the technical requirements of the product should be provided, including the basis for the determination of functional and safety indicators and other indicators relevant to quality control, the standards or methods used, the reasons for their use and the theoretical basis.

The requirements behind above 4 verification aspects are often written in product-specific guidances and standards. The applied standards, requirements and testing methods should be described.

3.05.05 Software/Firmware

For products containing software, a separate medical device software description document should be provided, including basic information, implementation process and core algorithms, the level of detail depending on the level of security and complexity of the software. At the same time, a statement on the naming rules for the software version should be issued, specifying all the fields and field meanings of the software version, identifying the full version of the software and the identification version used for distribution.

As seen beforehand in figure, the given subfolders` names reveal a complex software file in accordance with corresponding software guidances and standards.

3.05.06 Biocompatibility and Toxicology Evaluation

The biocompatibility of the materials in the finished product that come into direct or indirect contact with patients and users should be evaluated.

The biocompatibility evaluation study information should include:

1. the basis and methods of the biocompatibility evaluation;

2. a description of the materials used in the product and the nature of the contact with humans;

3. the rationale and justification for performing or exempting biological tests;

4. an evaluation of the available data or test results

For these 2 subfolders you have to provide a summary of biocompatibility, testing report and GLP certificate of testing labs. The test should fulfil guidance of biocompatibility of medical device.

3.05.08 Safety of Materials of Biological Origin (human/animal)

For products containing products with biosafety risks such as homologous materials, materials of animal origin or bioactive substances, information on biosafety studies of the relevant materials and bioactive substances should be provided. Include a description of the process of obtaining, processing, preserving, testing and handling of tissues, cells and materials; a description of the source (including details of donor screening) and a description of validation tests of the method of removal or inactivation of viruses, other pathogens and immunogenic substances during production; and a brief summary of the process validation.

3.05.09.01 End-User Sterilization

End-user sterilisation: the recommended sterilisation process (methods and parameters) and the basis for the determination of the recommended sterilisation method should be specified; for products that can withstand two or more sterilisations, information on the study of the tolerance of the recommended sterilisation method associated with the product should be provided.

3.05.09.02 Manufacturer Sterilization

Sterilisation by the manufacturer: the sterilisation process (methods and parameters) and the sterility assurance level (SAL) should be specified and a sterilisation confirmation report should be provided.

3.05.09.03 Residual Toxicity

Residual toxicity: If the method used for sterilisation is prone to residues, information on residues and the treatment methods adopted should be specified and research information provided.

3.05.09.04 Cleaning and Disinfection Validation

End-user sterilisation: the recommended sterilisation process (method and parameters) and the basis for the determination of the recommended sterilisation method should be specified.

3.05.10 Animal Testing

Pre-clinical animal test study information includes the purpose, results and records of the animal test study.

3.05.11 Usability/Human Factors

Fortunately the usability test is still not obligatory. It would be surprising requirements when manufacturer have to clarify the population difference. If not, a potential third local testing with Chinese user after type testing and conditional shelf life testing might be in reality.

3.07.01 Product Stability

Determination of expiry date: If applicable, a validation report of the expiry date of the product should be provided.

The validation report should comply with shelf life of active medical device guidance. Either you can let medical device undergo accelerating aging test, or you provide an analysis report regarding all critical components in storage, transportation, sterilization and usage conditions. Another literature reference is ASTM 1980-2.

3.07.02 Package Validation

1. For medical devices with a limited number of repeated uses, information on the verification of the number of uses should be provided.

2. Packaging and packaging integrity: the basis for maintaining the integrity of the packaging during the declared expiry date and under the conditions of transport and storage.

The requirement of packaging validation is according to  Chinese standard YY/T 0681.

Matching MDR

Let`s concentrate on the key chapters with verification and validation (V&V) requirements again. We have to choose Annex II, 6 at MDR in EU to compare to.

Let`s assume that the legal manufacturers with marked medical device in Europe had a solid technical documentation matching Annex II, 6. Product Verification and Validation, how can we match requirements to Chinese eRPS structure?

Do you know that for registration needed technical documentation is just a part of iceberg of design history file at development? Communication in cross discipplin and entity can be struggling.

Contact us if you need

• interim regulatory affairs or project manager in Chinese (international) registration
• have full traning how to register a product in all markets in a one year online university
• a unique interactive workshop from gap analysis of technical document based on MDD or MDR to feasibility of Chinese registration

Summary

It might take decades for authority to introduce the next generation of documentation structure. In our opinions, the first level of table of content would include 12-16 chapters (CH.XX). The 7 first level CH-chapters in the second generation of international submission format are short as overview. However, to arrive to deepest 6. level of CH-Subfolder, you have to click 5 times. It is supposed that most manufacturers prepare the dossiers by filling, searching, editing, revising the folders. As searching in drawer the fewer clicks RA specialists choose folder, the more selectively individuals can handle the submission dossier in aduring and after product registration.

We just hope that one day a harmonised TOC in all globe markets of medical device will be accepted. Keeping to dream that, let regulatory affairs experts for Chinese medical device market firstly face to understand the developing requirements behind Chinese eRPS folder.

With Easychinapprov, all requirements of technical documentation are in control.