New Measures Relating to the Registration of In Vitro Diagnostic Reagents

The Measures related to the Administration of Registration of In Vitro Diagnostic Reagents(“Measures”) issued on 30 July 2014 by the China Food and Drug Administration (“CFDA”) entered into force on 1 October 2014. The Measures replace the Pilot Measures related to the Administration of Registration of In Vitro Diagnostic Reagents effective as of 1 June 2007 (“Pilot Measures”). 

How will the new provisions impact the current practice of registration of In Vitro Diagnostic Reagents (“IVDs”), and more importantly, how will the new provisions affect the registration of IVDs for foreign companies? 

These Measures are one of several important pieces of legislation governing medical devices that have been introduced as a consequence of the modification of the new Regulation on the Supervision and Administration of Medical Devices, effective since 1 June 2014. 

In order to ensure the efficient implementation of these Measures and provide more clarity during the period of transition from the previous regime, the CFDA also published a Circular dated 1 August 2014 (Shi Yao Jian Xie Guan (2014) No.144) (Circular related to the Matters of the Implementation of the Measures related to the Administration of Registration and Filing of Medical Devices and the Measures related to the Administration of Registration of In Vitro Diagnostic Reagents). 

The main changes introduced by the Measures are set out below: 

 1. Registration and filing 

The Measures divide IVD ‘registration’ into two separate procedures: registration and filing. An IVD is subject to either a registration or filing procedure depending on its risk class, as set out in the table below. 

Fast track registration is also available for innovative IVDs. 

The Measures clearly provide that an applicant may not carry out a clinical trial until the registration test has been completed. Such registration test requirements were not provided for in the Pilot Measures. The CFDA Circular dated 1 August 2014 (Shi Yao Jian Xie Guan (2014) No.144) sets out transitional arrangements applicable to clinical trials that had already started prior to 1 October 2014.

For clinical trials that had already started before this date, for which the relevant registration test requirements imposed by the Measures have not been done, the clinical trial report can still be used for the purpose of registration, provided that a clinical test agreement is submitted at the same time.

2. Filing obligation for clinical trials 

The Measures provide that before starting any IVD clinical trial, the applicant must file an application with the FDA at the provincial level. The provincial FDA office which receives the filing must circulate the filing information to the relevant FDA office and the local Health and the Family Planning Commission in charge of the clinical trial institution or laboratory. 

Although legislation governing the registration of other medical devices states that approval is required predominantly for Class III medical devices, this special provision for IVDs requires a filing for both Class II and Class III IVDs. Since the new Measures make it more difficult to change a clinical trial institution or laboratory once this filing has been made, applicants are likely to devote more effort to choosing such institutions or laboratories, in order to ensure that they do not incur unnecessary costs or delays in having to submit a new application. 

3. Clinical trial institutions

The Measures provide that clinical trials must be carried out by qualified clinical trial institutions. The Pilot Measures on the other hand, provided that clinical trials could only be conducted by medical institutes at the provincial level. The Measures therefore have the effect of increasing the number of clinical trial institutions available for carrying out IVD trials. 

A list of qualified clinical trial institutions will be issued by the CFDA. Before this list is issued, the CFDA circular dated 1 August 2014 (Shi Yao Jian Xie Guan (2014) No.144) states that the applicant must still carry out clinical trials at provincial medical institutes.

4. Elimination of IVD loophole for research

Under the Pilot Measures, if an IVD was used for the purpose of research and not for clinical diagnosis, no registration was required, provided that the following notice was included on the package insert and label: “for research purpose only, clinical diagnosis prohibited”. 

This provision is no longer included in the Measures, eliminating the loophole under which companies were able to manufacture IVDs without registration. 

5. Change of manufacturing address 

If the manufacturing site of an imported IVD changes, a foreign manufacturer must apply to the relevant FDA office for approval. However, if the manufacturing site of an IVD manufacturer located in China changes, only registration is required which is a less time-consuming procedure. 

The Pilot Measures provided that if the manufacturing site of an IVD changes, the applicant must apply for the quality management system examination of the new manufacturing site before applying to the FDA to register a change of address. Although such a provision no longer exists in the Measures, quality management system examination is nevertheless still required by the Measures on the Supervision and Administration of Manufacturing of Medical Devices, which have been in force since 1 October 2014. 

6. Change of main supplier of an antigen or antibody

The Measures provide that in order to change the main supplier of an antigen or antibody, approval must be obtained from the original registration authority. 

The new provision is much stricter than that contained in the Pilot Measures, under which only the change of the actual antigen or antibody itself required approval by the registration authorities. 

As a result, IVDs manufacturers are likely to be discouraged from changing antigen or antibody supplier after approval has been obtained.

In summary, the Measures impose more stringent regulatory requirements for imported IVDs relative to those manufactured in China. Further, the Measures also strengthen the administration of registration test, clinical trial process and eliminate some grey areas in the Pilot Measures.