Top 10 news of Medical Device (IVD) Market in China in 2020

1. Decree of the State Council No. 739, 2021

In Dec, 2020, it was revealed that state council in China approved the State Council Ordinance 739 in 2021, which was since years in opinions collecting -, correcting - and revising phase. This most important legislative of medical device in China will replace Decree of the State Council No. 680, 2017. The new publised decree has the order number 739 in 2021.

There will be many speculations to chase, follow and understand by implementing:

·        Simplified clinical evaluation with real world post market data

·        Enhancement of the role of Chinese agent (authorised representative)

·        Strengthening of post market requirement as PMCF

·        Expansion of third party labs conducting type testing

Topic: legislative

Relevance: high

Complexity: moderate

2. Chinese Product Code, Guideline and Standard ALL-IN-ONE database

The Chinese authority NMPA established a database with product code, product-specific guideline and standard.

The precondition to use this database is to know the first 4 digits of product code. Then you can search linked product-specific guideline and standard, in Chinese language. The product requirements are described in product-specific guidelines and standards covering the key elements at technical review by CMDE. These requirements should be reflected in submission dossier and in details at labelling, type testing, risk management, verification and validation, clinical evaluation, post market as well as clinical trial.

We show one medical software as example bearing product code 21-02-XX:

Product code:   21-02 Image processing software

Guidelines:

Guidelines for technical review of registration of medical image storage and transmission software (PACS)

Standards:

GB/T 36108-2018 Technical requirements for CAD software for fixed oral restoration

YY/T 0457.1-2003 Characteristics of photoelectric X-ray image intensifiers for medical electrical equipment Part 1: Measurement of incident field size

YY/T 0457.2-2003 Characteristics of photoelectric X-ray image intensifiers for medical electrical equipment Part 2: Determination of conversion factor

YY/T 0457.3-2003 Characteristics of photoelectric X-ray image intensifiers for medical electrical equipment Part 3: Measurement of brightness distribution and non-uniformity

YY/T 0457.4-2003 Characteristics of photoelectric X-ray image intensifiers for medical electrical equipment Part 4: : Determination of image distortion

Topic: regulatory database

Relevance: high

Complexity:  moderate

3. Manufacturing of overseas medical device in China

Article 34 in new Regulations on the Supervision and Administration of Medical Devices (2021/739)

In Sep, 2020, NMPA issued a special guidance “Manufacturing of overseas medical device in China”.

It applies to overseas manufacturers whose class II and III medical device are already approved in China. In guidance is meant a simplified registration process if this medical device will be produced by an authorised manufacturing partner with equivalent GMP in China.

This guidance offers following options to foreign legal manufacturers:

I. Overseas manufacturer could have additional manufacturing site in China und place medical device in two channels. → Made overseas and in China

II. The manufacturing site could be absolute transferred to an authorised manufacturing partner in China.

→ Made in China

This might be another alternative for Private Label Manufacturer (PLM) as in Europe due to increasing accountability aligning with MDR. Benefiting from this legal regulation in China, company with core R&D could outsource manufacturing products easily in China if medical device was already approved there. It would even leverage the complex supplier chain management and production manpower.

It seems on the one side to be tricky to transfer device master record to manufacturing partner. On the other side it gives a new chance to outsource production, registration and sales of an outdated, maybe in home country obsolete products to a reliable Chinese partner.

For some manufacturers who would scale up the production number and accelerate logistic steps to end user, it is a unique polity to follow and practice.

Topic: outsourced production in China

Relevance: moderate

Complexity: moderate

4. Requirements of supplementary reply at technical review

This notification refers to supplementary reply by legal manufacturer after technical review by  Chinese authority. It refers to initial -, change -, extension registration of medical device and IVD, as well as application of clinical trial. In the fact, legal manufacturer has one year time to address the deficiency and gives supplementary reply in electronic format.

It is wise to have a smooth contact with reviewer after “deficiency letter” notification and address EACH deficiency in supplementary reply. The spirit at this reply to CMDE should at least contain points below:

1) Description of understanding of the deficiency

2) Description of response ideas or argumentation logic

3) Basis for supplementing and correcting data

4) Special objective evidence, documents, data or information 

5) Explanation of special circumstances

Even if the answers doesn’t meet supplementary request, a brief clarification should be summarised. There are often misunderstanding deficiencies from authorities site.

Topic: technical review

Relevance: moderate

Complexity: high

5. Dossier requirements at acceptance review

The requirements of "Acceptance Checklist" at acceptance review were new in 2019 after new table of content format. With time of uploading dossiers in electronic regulated product submission (eRPS), the problems turned up at many legal manufactures in 2020. More and more submission dossiers are refused by CMDE.

Before introduction of table of content via eRPS, legal manufacturers submitted all info in one dossier in paper. Now the documents must be uploaded selectively to dozens of CH-folders. It is not surprised that non-experienced manufacturers left some un-applicable folders un-filled which is not compliant to dossier requirements for official reviewers. 5 days after acceptance review by CMDE, deficiency reply results from proving completeness of submission dossiers in accordance with table of content.

It is actually a Chinese version of “Acceptance Checklist” from FDA. It is primary for authorities’ reviewer to examine dossier though this checklist with general folder requirements and completeness of 2th subfolder CHX.Y and 3th subfolder CHX.Y.Z. We recommend you to prove all eRPS folders before submitting the whole dossier to NMPA with help of checklist of dossiers.

Topic: registration review

Relevance: high

Complexity: moderate

6. Periodic Risk Evaluation Report

After the requirement of incident reporting was strengthened in China, the new requirements of Periodic Risk Evaluation Report in term of risk assessment were into force last year. NMPA provided in guidance even a template of PRER for legal manufacturers and accepted the first series of annual PRER of 2019 and 2020 by deadline in Sep, 2020.

It applies to class II and III medical device in first 5 years “Chinese life” after initial registration since 2019. Each year a PRER should be submitted electronically. After 5 years legal manufacturers can keep the record internally. PRER of class I is not necessary to be submitted, however one report in first 5 years after initial registration should be documented internally as well.

See the deep analysis in Easy regulation where we evaluate new regulation and clear essential registration step.

Topic: post market activity

Relevance: moderate

Complexity: moderate

7. UDI implementation of some class III medical device

Article 39 in new Regulations on the Supervision and Administration of Medical Devices (2021/739)

As of 01, 01, 2021, UDI is obligatory for legal manufacturers of some class III medical device who want to place products into Chinese markets. UDI is indispensable at submission dossier, on all size of packaging, product itself (disposable and re-sterilised device exempted), at sales activities after approval, at incident reporting and medical reimbursement. Info of UDI should be uploaded via eRPS at Chinese authority by legal manufacturers.

UDI is applicable for medical device which is produced after 01, 10, 2021. The change of UDI is not significate change which triggers new registration of medical device.

There are so far three UDI issuing organisations: GS1, ZIIOT and alihealth. In general, the UDI issued by GSI is in China accepted compared to other infamous providers.

Here is the list of class III medical devices which need UDI in China up to date :

Topic: labelling

Relevance: high

Complexity: moderate

8. New Chinese industrial standards

Every year NMPA published new industrial standards of medical device and IVD which are valid in the next year.  It is better for legal manufacturers to understand the new requirements in Chinese standards precociously.

By significant change of requirements, either obligatory industrial standard YY or non-binding industrial standard YY/T, it applies to upcoming product registration. The action of this change can be new verification or validation test, revision of product technical requirements, revision of labelling and new onsite type testing.

In 2020 there are 43 industrial standards published which will be valid in 2021.

The standards of medical device can be found also in database of product code, guidelines and standards, see top 2 regulation above.

Topic: Chinese standards

Relevance: moderate

Complexity: moderate

9. Real world clinical data used at clinical evaluation

The real world clinical data guidance is due to long clinical trial period in China, complex acceptation of overseas clinical trial data and little likelihood to get permission of competitor to use clinical date of similar products at clinical evaluation in China. It makes clinical data in term of real world data up which is collected with best practise at field in use of medical device by health care users and patients.

The source of real world data: incident reporting data, medical record data, registration data and medical insurance data, medical insurance data, health records, public monitoring data, patient self-reported data and data generated by mobile device. In addition, real-world data can also include data generated during the production, sales, transportation, storage, installation, use, maintenance, delisting and disposal of medical devices.

It means that legal manufacturers need to have all network with legal manufacturers, logistics, distributors, all hospitals where medical device is used, insurance company and access of public database. It can be explained that for some medical device, legal manufacturers can catch up clinical data at post market after product approval. Otherwise it is more than a theory to systematically evaluate so much different clinical information. Let’s await the first successful real world case in China.

Topic: clincial evaluation

Relevance: moderate

Complexity: high

10. Unapproved medical device in Hainan province

NMPA issued a new regulation that innovative imported medical device with unique intended use can be placed in Hainan province, without approval by centre authority NMPA in Beijing. The pre-conditions is that there is no similar medical device with same intended use and technical characteristics which was approved and medical device has a unique urgent clinical needs.

The aim of authority is clear to attract innovative medical device early in China. If the benefit versus risk dealing with life-threatening disease can be provided, the potential risk can be measured at post market activity e.g. with real world clinical data. This policy is in context with long term process of approval of innovative medical device which needs Chinese patent and clinical trial in China.

This new policy in Hainan sounds attractive however it should be observed in a long term. It might bring not unexpected after-tax returns for sponsors of innovative medical device if it can be only used in Hainan island. The most excited follow up story how to establish a standard product registration afterwards in mainland remains unmentioned. Without big number of patients at multi clinical centres, it fails to serve as safety evidence as clincal data. Even it was solved with enough clinical cases, it remains a question whether the use of clinical date can compensate lost time in clinical use in Hainan province plus extensive type testing later at product registration to prove effectiveness requirements.

Regardless of “unapproved risk analysis” above, derived from an approved list of rehabilitation medical device using this rapid channel, this policy should be interested at least for medical device manufacturers of rehabilitation. Hainan can be likely a hot spot of reha island.

Definitely it is nevertheless worthy for a “free feasibility test“ of subject medical device on Hainan island.

Topic: product commercialization

Relevance: low

Complexity: low

Conclusion

In 2020 it happens a lot at Chinese market of medical device. While in difficult Corona lockdown time Europe extended transition time of MDR one year more and in US Donald Trump was replaced by a new president, Chinese authority NMPA made no break and brought some meaningful new regulations into force.

With the introduction of Decree of the State Council No. 680 in 2021, we look forward to the path of NMPA, change of Chinese medical device market, alignment and actions of domestic and overseas manufacturers.

Contact us if you would like to

• Follow the Chinese regulatory update
• Register medical device in China
• Start clinical trial and write clinical evaluation
• Manufacture medical device in China
• Search Chinese partners in distribution and in supply chain
• Outsource UDI controlling in the whole product life in China
• Solve compliance troubles, strive and approach perfection in customer need with Easychinapprov in China
• Have medical device registration over the world