China’s National Medical Products
Administration (NMPA) has stepped up overseas inspections in recent years, and
manufacturers looking to market products in China must be prepared for
potential visits from Chinese inspectors. Gert Bos, PhD, FRAPS, executive
director and partner with Qserve Group, addressed the topic during a session at
the recent RAPS Regulatory
Conference Europe in Brussels. Bos and his Qserve China colleague, Michael
Yan, answered some questions about China’s inspections program in the following
led China to increase foreign inspections over the past few years?
In the past, the limited availability of
foreign inspectors forced China to focus on large companies and companies
making high-risk, long-term implants. With an increased budget allowing for
rapid increase of the available inspector pool, we see the scope widening, and
many more companies are and will be subject to overseas inspections. As other
leading agencies around the world have similar oversight systems in place,
China intends to pick up this work as well in their rapid progression in the
field of regulatory compliance, and to ensure the imported products are safe
for the Chinese population.
NMPA has performed quality system audits and
good manufacturing practice (GMP) inspections for many years within China. According
to regulations, overseas manufacturers are supposed to have the same level of oversight.
As China’s government is now significantly building up their professional
inspection team, both domestic and overseas manufacturers are expected to
receive more frequent and stricter inspections in the future. The published
regulation has adjusted some details to be aligned with domestic practice , but
there would continue to be some differences in practice. For example, the
“double blind” arrangements of unannounced inspections performed in China will
be very difficult to implement for overseas inspections due to the need for
visa applications and logistic arrangements.
significant changes did China make to its foreign inspection process with the
release of its updated guidelines in December 2018?
In principle, the guidance did not add
further requirements. It just regulates the procedure that gives an
interpretation on the regulatory requirements.
If we analyze some details of the
regulatory framework that is being followed up by the guidance, the following
might be worth mentioning:
The China agent’s responsibilities
were added in article 10, the specific requirements of the authorization and
its documentation requirements listed in Annex 2, and the adjustment to keep
alignment with coming new regulation via China agent.
Scope extension: overseas sites
or subcontractors for domestic products will now also need to follow this
The site-master file (SMF) is
separated into a pharmaceutical version and a medical device version.
A new Annex (5) has been added covering
the format of the “oversea inspection advanced notice.” It is to be issued
after reviewing the SMF and is used to notify the manufacturer of the
inspection plan, including location, timing, etc. An application for delay
(with proper reason) must to be submitted by the manufacturer within 10 working
days after receiving the notice.
Complaints, whistleblowing or similar
clues that might indicate a violation might also lead to an inspection.
The number of inspectors per
visit might be increasing.
Some adjustments have been made
to the response timelines.
A result of minor non-conformities
will no longer be classified as “meeting the requirement.”
Refused or unable to notarize
documents has been added to the scenario of noncooperation, which will be
classified as “not meeting the requirement” directly.
A traceability system
requirement is now clearly required in article 32.
criteria does China's NMPA use to select sites for foreign inspection?
Until there are sufficiently trained personnel
available to inspect all companies exporting products to China, it will be a
risk-based decision considering the risk factors identified from registration
approval—surveillance inspection, testing, complaints and whistleblowing,
are the possible results of an inspection?
If there’s something wrong, it could lead
to “risk control measures” taken. These include interviewing the holder,
ordering corrections within a specified time limit, issuing warning letters,
suspending import customs clearance filing, suspending importation of the
medical device, suspending sales and use, supervising product recall and even
revoking the import approval. In addition, NMPA may schedule further
information, if any, is made publicly available about inspection results?
The inspection result, of which mainly the
content in Annex 6, will be shared with the public on the NMPA/CFDI website, mainly
about the defects and manufacturer/agent information, but in quite a
do we know about results of previous inspections and what issues have been
identified as problematic?
The results of individual assessments are
available in Chinese on the website of the NMPA. At this moment, it is a bit
early in the process to analyze trends in the dataset.
are the most important things companies need to know about NMPA's procedure for
For overseas inspection, NMPA will notify
the China legal agent in advance and give a rough timeline. As the time for the
inspection approaches, final dates will be confirmed between NMPA and foreign
companies through discussions. Key elements for companies to consider in
Start learning China’s
regulations and standards as soon as possible, and do not leave this solely in
the hands of your China team or China agent!
Facilitate teamwork among the
quality, regulatory affairs, R&D and clinical teams, as well as the China
Staff responsible for managing the
supply chain need to be involved, and they also will have to accept the
inspections; this needs to be contractually agreed upon.
are the key differences between NMPA inspections and inspections conducted by
European and US authorities?
First of all, one needs to consider the
different culture, regulations and different understanding of the standards.
Next, the scale and focus might differ. For example:
Three or more inspectors,
possibly with additional observers, will perform the inspection in parallel. Make
sure you have enough translators and moderators onsite.
The inspection team is expected
to have a thorough knowledge and relevant background, including tech-file reviewer,
testing engineer, etc., in addition to the GMP inspector. And don’t forget the
bigger team behind the audit. Inspectors may check in with the headquarters team
after the day’s work if they’re not sure of some issues, so be sure to give
reasonable justifications for anything that may be seen as questionable.
Inspectors may take pictures or
videos for use as evidence.
Inspectors may take samples themselves
or ask manufactures to ship them to NMPA for further testing.
can device makers address language and cultural differences with Chinese
The inspections will be performed in the
Chinese language, although some inspectors may speak fluent English. It is
necessary for manufacturers to be well prepared and to make sure the key
resources are available, including good translators with proper QA/RA/R&D
and relevant device backgrounds. Be well prepared in advance with necessary documents
and logistics accounted for. Mock inspections combined with on-site training
typically help a lot.
are some key "dos and don'ts" for companies selected for inspection
The top eight might look as follows:
Don’t take the inspection
Don’t be adversarial.
Don’t try to control the
inspection—it is the regulators’ inspection.
Communicate any special
circumstance or needs.
Ask questions if you are unsure
Make corrections if possible. If
the inspector(s) can’t find documents, try to locate and present them. If you
can’t find something, say so.
If you can’t make corrections,
let it be.
Be mindful that the Chinese cultural
expectation is to respect the auditor.
should companies do if they don't pass the inspection?
If non-conformities are raised:
Provide a statement or
explanations within 10 working days after receiving the result notice from NMPA
if there’s any disagreement.
Provide the progress of the corrective
action preventive action (CAPA), or detailed CAPA plan if it is not possible to
finish correction in time, within 50 working days after receiving the result
Apply for relieving the risk
control measures taken by NMPA after CAPA is performed.
Prepare for the additional
inspection if needed.
Recall products where
Ensure knowledgeable support to
work on closure of CAPAs, and to smooth communication with the inspection team
during follow up.