According to the Regulations on Supervision and Administration of Medical devices (Order 739), the Administrative Measures for Registration and Filing of Medical Devices (Order 47) and the Administrative Measures for Registration and Filing of IVD (Order 48), new e-filing catalogue (eRPS) will be effective since Jan 1, 2022.
More dossiers will be required for registration submission through NMPA e-filing system since Jan 1, 2021. The below table lists the major amendments on current eRPS catalogue.
BradyKnows held a webinar to describe more details: Revisiting Order 739 – Significant Updates for Medical Device Registration in China: Dossier Prep, Self-Testing, CER, and PMS. Please email to info@inspirativemed.com to get a copy of webinar slide and visit the record from this link.
On Sep 27, 2021, NMPA published a new Review Guideline of Animal Studies for Medical Device Registration: Part 1 Determination Criteria (2021 Amendment) and Part 2 Animal Study Design and Conduct Quality Assurance, which have been effective since Sep 18, 2021.
Background
Animal study for medical device is to select animals that meet the study requirements, according to the study purpose, carry out product feasibility and / or safety and / or effectiveness research under the provisions of the pre-designed study protocol, observe and record the reaction process and results of animals, so as to confirm the role and impact of medical devices on life activities. In the risk management activities of design and development, the effectiveness of risk control measures shall be verified / validated after the implementation of risk reduction control measures. Animal study is one of the means to validate the effectiveness of risk control measures and an important evidence module to evaluate the safety and effectiveness of medical device.
Key Issues for This New Animal Study Guideline:
1.Applicable Scope
This Guideline is not applicable to the study on non-living animals, isolated tissues or organs, and in vitro diagnostic reagents regulated as medical devices.
2.General Principles of Animal Study
The animal study for medical devices shall comply with the principle of 3R + DQ. The 3R principle (Replacement, Reduction and Refinement) is the welfare protection of animals. The scientific protocol design (Design) is the software and scientific basis for the realization of the 3R principle, and the conduct under the effectively operating quality management system (Quality) is the hardware and engineering basis.
The 3R + DQ principle is the principle guarantee to avoid excessive animal study and obtain scientific, reasonable, objective and reliable animal study data and evidence.
3.Determining Whether an Animal Study Is Necessary
There are many kinds of medical devices, and not all products need to carry out animal studies. The applicant should make rational use of the decision-making principle in the design and development stage, and give priority to non-living research, computer simulation and other methods to replace animal studies, make full use of the existing animal study data of similar products or use performance comparison with similar products on the market and other evidences to reduce the animal study sample size.
4.Purpose of Animal Studies
The purpose of animal study is generally divided into feasibility study, safety study and effectiveness study. In an animal study, the feasibility, effectiveness and safety of the product can be evaluated at the same time. When there is no clear study purpose, animal study should be avoided.
5.The Relationship Between Animal Study and Biological characteristics
This Guideline does not replace the technical documents related to biological evaluation of medical devices such as GB / T 16886 series standards. Some biological risks can be evaluated in animal studies, but the evaluation contents shall meet the requirements of biological evaluation related technical documents such as GB / T 16886 series standards.
6.Attachments of this Guideline
The attachments of the guideline lists “examples of products that may need to carry out animal study”, which is not a list of products that must carry out animal study. The applicant should follow the “flow chart of decision-making to carry out animal study” to make a scientific decision on whether to carry out animal study.
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7.Animal Study Protocol Design
The applicant should take the purpose as the guidance, scientifically design the protocol, then strictly control the quality according to the protocol for study conduct, truthfully record the study results, and systematically evaluate the results by professionals.
7.1 Study Device
The study device shall be the sample produced under the effective operation of quality management system, which is generally the final product designed and finalized. Due to the influence of animal anatomical structure and other factors, alternative samples can be used. In the process of animal study, the product design can be changed. It is necessary to analyze the impact of the change on the animal study process, test results and conclusions, and carry out animal study again if necessary.
7.2 Study Animals
Study animals are very important for the evaluation of the feasibility, safety and effectiveness of medical devices. It is recommended to give priority to study animals. The following factors (including but not limited to):
7.2.1 Meet the requirements of study purpose
7.2.2 Structure (such as anatomical structure and size),function, metabolism, disease characteristics,biological response, etc. similar to human body
7.2.3 Sensitive to evaluation indicators
7.2.4 Basic animal elements such as gender and specifications will not affect the results and conclusions of animal study.
7.3 Animal Sample Size
The animal sample size should fully ensure the reliability of the study results and comply with the 3R principle. It is possible not to use statistical methods for estimating sample size.
If the evaluation results presented by individual animals under the same study conditions have great variability, it is necessary to analyze the causes of variability, such as operation methods, product quality, etc., and increase the sample size of animals when appropriate to obtain more scientific and objective conclusions.
7.4 Observation Time
The applicant should set sufficient and different observation time points in combination with product study purpose, working principle, expected contact mode and time with human body, time required to achieve biological response steady-state and other factors, generally including preoperative, intraoperative, immediate postoperative, short-term postoperative, medium / long-term postoperative, etc.
7.5 Evaluating Indicator
The specific evaluation method, observation time point and frequency of specific evaluation indicators shall be defined in the study protocol. The evaluation indicator should have scientific and objective evaluation criteria.
8. Animal Study Conduct and Quality Assurance
Animal Study shall be carried out under an effective quality management system, and the regulatory department shall inspect the system if necessary.
Animal welfare protection shall be ensured during the whole process of animal study conduct, and the study protocol shall be approved by the animal ethics committee before conduct.
All data generated by the study shall be recorded in strict accordance with the study protocol and corresponding operation specification documents, and ensure that the data record is timely, direct, accurate, clear and difficult to eliminate. As the first responsible person, the applicant shall ensure that the study data are complete, true, reliable and traceable, and the results are credible.
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According to the requirements of the established quality management system, sufficient quality assurance personnel shall be allocated to take charge of quality assurance and ensure the independence of quality assurance. The quality assurance personnel shall review the animal study items and issue a quality assurance statement to confirm whether the study methods, procedures and results are accurately and completely described, truly and comprehensively reflect the original data of the study, and confirm that the study meets the requirements of the Guideline.
The Administrative Measures for Registration and Filing of Medical Devices (Order No. 47) and the Administrative Measures for Registration and Filing of IVD (Order No. 48) (hereinafter the Measures) have been issued and take effective since October 1, 2021. In order to implement the related measures, NMPA published the notices on the relevant matters of technical review during the transition period. Some key issues are listed as below.
1.NMPA Acceptance
1.1Acceptance adjustment
Since October 1, 2021, the application on designated type testing of medical device for registration will no longer be accepted.
Since October 1, 2021, if there is any change in the original IFU after review, the registration applicant shall, in accordance with the requirements of Article 16 of the Provisions on the Administration of Instructions and Labels of Medical Devices, modify the IFU or handle the notice of IFU change according to the change document.
1.2Modification registration and modification filing
Since October 1, 2021, if the registered products have changed as specified in the Measures and need to
conduct modification registration and modification filing, the registrant shall apply for modification registration and filing separately.
1.3Legal agent of overseas medical devices
Since October 1, 2021, overseas registration applicants and filling applicants shall designate an enterprise based in China as legal agent to handle the registration and filing of relevant medical devices. Representative offices established in China by overseas registration applicants and filling applicants shall not act as legal agent.
1.4Renewal
For renewal of medical device certificate, the registrant shall apply the renewal 6 months ahead of expiry date on certificate, and submit related dossiers.
2.NMPA Review
2.1During NMPA review on the accepted registration of medical device before the implementation of new mandatory standards, NMPA will remind the applicant in the supplementary notice about new mandatory standards effective soon, and recommend the applicant to implement new standards, modify product technical requirement (PTR), supplement type testing report and research documents.
If the applicants accept the recommendations from NMPA and submit supplementary documents, NMPA will review as per new standard; if the applicants do not accept the recommendation and not submit related documents, NMPA will review as per old standard. If NMPA review as per old standard, but the product upgrade to new standard is the modification mentioned in the Measures, the applicant shall conduct modification after approval of medical device certificate.
2.2During the renewal, if the renewal was accepted before Oct 1, 2021, NMPA will notify to supplement the dossiers for new mandatory standards.
Since Oct 1, 2021, if new mandatary standards have taken effective, and the products upgrade to new standards is mentioned in the Measures, the applicant shall conduct modification first before renewal.
Date: Thursday, Nov 18, 2021, 8:00-9:00 AM Pacific Time (US)
2021 is a big year for medical devices in China. Issued by the State Council, Order 739 (“Regulations on the Supervision and Administration of Medical Devices”) was officially effective in June 2021, which has brought significant changes to medical device registration, testing, clinical evaluation, and post-marketing surveillance. By November 2021, NMPA has issued several finalized regulatory documents such as eight Guidelines for medical device clinical evaluation, Provision for in-house type testing, updated registration dossier requirements, etc. By the end of 2021, it is time for us to revisit the regulation updates and assess the impact of such changes on foreign manufacturers who wants to bring their products to the Chinese market in a practical and least-burdensome approach.
Agenda
Overview of Order 739 vs. 680
Significant changes in dossier preparation for imported Class II & III medical devices
Modification registration under Order 739
Renewal registration under Ordre 739
How to submit a self-test report for type testing? How to entrust a third-party testing lab? What are the qualifications and limitations
Stricter Post-Market Surveillance requirements and MAH’s responsibilities under Order 739
According to the Regulations on Supervision and Administration of Medical devices (Order 739), the Administrative
Measures for Registration and Filing of Medical Devices (Order 47) and the Administrative Measures for Registration
and Filing of IVD (Order 48), new e-filing catalogue (eRPS) will be effective since Jan 1, 2022.
More dossiers will be required for registration submission through NMPA e-filing system since Jan 1, 2021. The
below table lists the major amendments on current eRPS catalogue.
BradyKnows held a webinar to describe more details: Revisiting Order 739 – Significant Updates for Medical Device
Registration in China: Dossier Prep, Self-Testing, CER, and PMS. Please email to info@inspirativemed.com to get a
copy of webinar slide and visit the record from this
link.
On Sep 27, 2021, NMPA published a new Review
Guideline of Animal Studies for Medical Device
Registration: Part 1 Determination Criteria (2021
Amendment) and Part 2 Animal Study Design and
Conduct Quality Assurance, which have been effective
since Sep 18, 2021.
Background
Animal study for medical device is to select animals
that meet the study requirements, according to the
study purpose, carry out product feasibility and / or
safety and / or effectiveness research under the
provisions of the pre-designed study protocol,
observe and record the reaction process and results of
animals, so as to confirm the role and impact of
medical devices on life activities. In the risk
management activities of design and development, the
effectiveness of risk control measures shall be verified
/ validated after the implementation of risk reduction
control measures. Animal study is one of the means to
validate the effectiveness of risk control measures and
an important evidence module to evaluate the safety
and effectiveness of medical device.
Key Issues for This New Animal Study Guideline:
Applicable Scope
This Guideline is not applicable to the study on non-living animals, isolated tissues or organs, and in vitro
diagnostic reagents regulated as medical devices.
General Principles of Animal Study
The animal study for medical devices shall comply
with the principle of 3R + DQ. The 3R principle
(Replacement, Reduction and Refinement) is the
welfare protection of animals. The scientific protocol
design (Design) is the software and scientific basis for
the realization of the 3R principle, and the conduct
under the effectively operating quality management
system (Quality) is the hardware and engineering
basis.
The 3R + DQ principle is the principle guarantee to
avoid excessive animal study and obtain scientific,
reasonable, objective and reliable animal study data
and evidence.
Determining Whether an Animal Study Is Necessary
There are many kinds of medical devices, and not all
products need to carry out animal studies. The
applicant should make rational use of the decision-making principle in the design and development stage,
and give priority to non-living research, computer
simulation and other methods to replace animal
studies, make full use of the existing animal study data
of similar products or use performance comparison
with similar products on the market and other
evidences to reduce the animal study sample size.
Purpose of Animal Studies
The purpose of animal study is generally divided into
feasibility study, safety study and effectiveness study.
In an animal study, the feasibility, effectiveness and
safety of the product can be evaluated at the same
time. When there is no clear study purpose, animal
study should be avoided.
The Relationship Between Animal Study and
Biological characteristics
This Guideline does not replace the technical
documents related to biological evaluation of medical
devices such as GB / T 16886 series standards. Some
biological risks can be evaluated in animal studies, but
the evaluation contents shall meet the requirements of
biological evaluation related technical documents such
as GB / T 16886 series standards.
Attachments of this Guideline
The attachments of the guideline lists “examples of
products that may need to carry out animal study”,
which is not a list of products that must carry out
animal study. The applicant should follow the “flow
chart of decision-making to carry out animal study” to
make a scientific decision on whether to carry out
animal study.
Animal Study Protocol Design
The applicant should take the purpose as the
guidance, scientifically design the protocol, then
strictly control the quality according to the protocol
for study conduct, truthfully record the study results,
and systematically evaluate the results by
professionals.
Study Device
The study device shall be the sample produced under
the effective operation of quality management
system, which is generally the final product designed
and finalized. Due to the influence of animal
anatomical structure and other factors, alternative
samples can be used.
In the process of animal study, the product design can
be changed. It is necessary to analyze the impact of
the change on the animal study process, test results
and conclusions, and carry out animal study again if
necessary.
Study Animals
Study animals are very important for the evaluation of
the feasibility, safety and effectiveness of medical
devices. It is recommended to give priority to study
animals. The following factors (including but not
limited to):
Meet the requirements of study purpose
Structure (such as anatomical structure and size),
function, metabolism, disease characteristics,biological response, etc. similar to human body
Sensitive to evaluation indicators
Basic animal elements such as gender and
specifications will not affect the results and
conclusions of animal study.
Animal Sample Size
The animal sample size should fully ensure the
reliability of the study results and comply with the 3R
principle. It is possible not to use statistical methods
for estimating sample size.
If the evaluation results presented by individual
animals under the same study conditions have great
variability, it is necessary to analyze the causes of
variability, such as operation methods, product quality,
etc., and increase the sample size of animals when
appropriate to obtain more scientific and objective
conclusions.
Observation Time
The applicant should set sufficient and different
observation time points in combination with product
study purpose, working principle, expected contact
mode and time with human body, time required to
achieve biological response steady-state and other
factors, generally including preoperative,
intraoperative, immediate postoperative, short-term
postoperative, medium / long-term postoperative, etc.
Evaluating Indicator
The specific evaluation method, observation time point
and frequency of specific evaluation indicators shall be
defined in the study protocol. The evaluation indicator
should have scientific and objective evaluation criteria.
Animal Study Conduct and Quality Assurance
Animal Study shall be carried out under an effective
quality management system, and the regulatory
department shall inspect the system if necessary.
Animal welfare protection shall be ensured during the
whole process of animal study conduct, and the study
protocol shall be approved by the animal ethics
committee before conduct.
All data generated by the study shall be recorded in
strict accordance with the study protocol and
corresponding operation specification documents, and
ensure that the data record is timely, direct, accurate,
clear and difficult to eliminate. As the first responsible
person, the applicant shall ensure that the study data
are complete, true, reliable and traceable, and the
results are credible.
According to the requirements of the established
quality management system, sufficient quality
assurance personnel shall be allocated to take charge
of quality assurance and ensure the independence of
quality assurance. The quality assurance personnel
shall review the animal study items and issue a quality
assurance statement to confirm whether the study
methods, procedures and results are accurately and
completely described, truly and comprehensively
reflect the original data of the study, and confirm that
the study meets the requirements of the Guideline.
The Administrative Measures for Registration and Filing
of Medical Devices (Order No. 47) and the
Administrative Measures for Registration and Filing of
IVD (Order No. 48) (hereinafter the Measures) have
been issued and take effective since October 1, 2021.
In order to implement the related measures, NMPA
published the notices on the relevant matters of
technical review during the transition period. Some
key issues are listed as below.
NMPA Acceptance
Acceptance adjustment
Since October 1, 2021, the application on
designated type testing of medical device for
registration will no longer be accepted.
Since October 1, 2021, if there is any change in
the original IFU after review, the registration
applicant shall, in accordance with the
requirements of Article 16 of the Provisions on
the Administration of Instructions and Labels of
Medical Devices, modify the IFU or handle the
notice of IFU change according to the change
document.
Modification registration and modification filing
Since October 1, 2021, if the registered products have
changed as specified in the Measures and need to conduct modification registration and modification
filing, the registrant shall apply for modification
registration and filing separately.
Legal agent of overseas medical devices
Since October 1, 2021, overseas registration applicants
and filling applicants shall designate an enterprise
based in China as legal agent to handle the registration
and filing of relevant medical devices. Representative
offices established in China by overseas registration
applicants and filling applicants shall not act as legal
agent.
Renewal
For renewal of medical device certificate, the registrant
shall apply the renewal 6 months ahead of expiry date
on certificate, and submit related dossiers.
NMPA Review
During NMPA review on the accepted registration
of medical device before the implementation of new
mandatory standards, NMPA will remind the applicant
in the supplementary notice about new mandatory
standards effective soon, and recommend the
applicant to implement new standards, modify product
technical requirement (PTR), supplement type testing
report and research documents.
If the applicants accept the recommendations from
NMPA and submit supplementary documents, NMPA
will review as per new standard; if the applicants do
not accept the recommendation and not submit related
documents, NMPA will review as per old standard.
If NMPA review as per old standard, but the product
upgrade to new standard is the modification
mentioned in the Measures, the applicant shall conduct
modification after approval of medical device
certificate.
During the renewal, if the renewal was accepted
before Oct 1, 2021, NMPA will notify to supplement
the dossiers for new mandatory standards.
Since Oct 1, 2021, if new mandatary standards have
taken effective, and the products upgrade to new
standards is mentioned in the Measures, the applicant
shall conduct modification first before renewal.
Date: Thursday, Nov 18, 2021, 8:00-9:00 AM Pacific Time (US)
2021 is a big year for medical devices in China. Issued by the State Council, Order 739 (“Regulations on the
Supervision and Administration of Medical Devices”) was officially effective in June 2021, which has brought
significant changes to medical device registration, testing, clinical evaluation, and post-marketing surveillance. By
November 2021, NMPA has issued several finalized regulatory documents such as eight Guidelines for medical
device clinical evaluation, Provision for in-house type testing, updated registration dossier requirements, etc.
By the end of 2021, it is time for us to revisit the regulation updates and assess the impact of such changes on
foreign manufacturers who wants to bring their products to the Chinese market in a practical and least-burdensome
approach.
Agenda
Overview of Order 739 vs. 680
Significant changes in dossier preparation for imported Class II & III medical devices
Modification registration under Order 739
Renewal registration under Ordre 739
How to submit a self-test report for type testing? How to entrust a third-party testing lab? What are the qualifications and limitations
Stricter Post-Market Surveillance requirements and MAH’s responsibilities under Order 739
Founded in 2007, BradyKnows is a China Market Entry Consulting Firm for both medical device and In Vitro Diagnostic (IVD) companies. In 2021, we established Inspirative Medical in the United States to better multi-culturally communicate with global clients and overcome gaps in R&D/standards/regulations/QMS/PMS between China and other countries.
VISION & MISSION
BradyKnows offers market entry strategy, regulatory and quality consulting, clinical strategy/CER/trials, local testing, legal representation, and commercialization.
We build elite teams for our clients with the full participation of project managers, regulatory/clinical/quality consultants, and technical engineers. The elite team will accompany our clients in the entire product life-cycle and help them overcome challenges and achieve every milestone in China.
