China Updates Drug Registration Rules and the Measures for Monitoring Drug Production – Part 2

The restating of the expedited review pathways, and the recently published work procedures, appear to be a step toward improving a process that has seemingly changed numerous times over the years. While there are several positives to the new provisions, the notable exclusions of any IP and data exclusivity rights (including provisions for new drug monitoring period, data exclusivity and patent infringement declaration) highlights the gaps and inconsistencies in the regulatory and IP framework for pharmaceuticals that has been discussed for several years. It is anticipated that these important regulatory and IP protections will be expanded on in future updates to IP laws, (note the Patent Linkage provision in the new draft Patent Law), but there still remains little indication as to when other changes may be implemented.

In this second part of our review of the new "Drug Registration Rules" ("DRR") (SAMR Order No.27) and new "Administrative Measures for Monitoring Drug Production" ("AMMDP") (SAMR Order No.28), both of which came into force on 1 July 2020, we will consider the mechanisms in the DRR that allow for expedited review and also review the previous sections related to IP that have been removed from the previous DRR.

Mechanisms for Expedited Review

There are four mechanisms for expedited MA review:

1. Innovative therapeutic drug (must be requested at clinical trial ("CT") stage)

May be used for:

a. A new drug that can prevent/treat severe or life-threatening diseases with no currently sufficient treatment options, or that improves significantly on current treatment options.

For this pathway the applicant is provided with specific support during the application process, notably:

i) Ability to communicate with the CDE during key stages of the drug's clinical trials (the CDE will assign evaluators for communication).

ii) CDE can review current research information and provide advice/suggestions on the next stage of the research plan.

2. Conditional approval (must be requested at CT stage)

May be used for:

a. A new drug that can: prevent/treat severe or life threatening diseases with no currently sufficient treatment options, or that improves significantly on current treatment options.

b. Drugs urgently needed for public health, with CTs expected to confirm the clinical effect.

c. Vaccines urgently needed for major public health emergencies, or other vaccines that are confirmed by the National Health Commission to be urgently needed and have positive benefit versus risk profiles.

(NB – the CDE can determine during the review that the drug does not meet the criteria for conditional approval and ask the applicant to submit a regular MA application)

For this pathway, the drug registration certificate will state the validity period of such a conditional approval, the post-market surveillance required and the time limit for completing the surveillance, plus any other requirements considered necessary. The MAH shall take the appropriate post-market risk management measures, complete the required drug clinical trials within the stipulated time limit, and file a post-market application. If the MAH fails to complete the required research within the stipulated time limit or fails to prove that benefits outweigh risks, the NMPA can, amongst other things, revoke the conditional approval or even deregister the drug.

This pathway has already been utilised. Zhejiang Hisun Pharmaceutical Co received conditional approval on 15 February 2020 for favipiravir tablets. This product is indicated for the treatment of new or re-occurring flu in adults (can be used only when other antiviral drugs have no or inadequate therapeutic effect). As favipiravir is considered to have a potential effect against COVID-19, the tablets have been offered for compassionate use in a small range of clinical trials.

3. Priority review and approval

May be used for:

a. Clinically needed drugs, and for innovative or improved new drugs that are used to prevent and treat major infectious diseases and rare diseases.

b. New varieties, dosage forms and specifications of the paediatric drugs that cater to children's physiology.

c. Vaccines and innovative vaccines that are badly needed for disease control and prevention.

d. Drugs that are satisfactory for the innovative therapeutic drug procedure.

e. Drugs that are approved conditionally.

f. Other situations stipulated by the NMPA where the priority evaluation and approval can be applied.

For this pathway, the applicant can enjoy certain priorities:

1) The time limit for review of the MA application is 130 days.

2) The time limit for review of drugs that are urgently needed for rare diseases and have been marketed outside of China but not marketed in China is 70 days.

3) The processes for inspection, product test and approval of the generic product names will be given priority over the standard approval pathway.

4) The applicant can submit supplemental technical materials after communication with, and confirmation from, CDE.

4. Special approval

May be used for:

a. "Needed" drugs during a period of unexpected public health threat

For this pathway, the government must determine such a threat exists.

In January 2020, 31 provinces in China all initiated a first-level response to the public health emergencies caused by the COVID-19 pandemic (as per the PRC Emergency Response Law, National Emergency Plan for Public Health Emergencies). Thus, COVID-19 is considered in China as an unexpected public health threat, enabling drugs for treatment of COVID-19 to apply for the special approval pathway. For this pathway, the applicant can enjoy a timely response from the NMPA and CDE throughout the review process. This applies to elements such as the technical review, on-site inspection and sample verification processes.

For further guidance, the NMPA released on 8 July 2020 some procedures to assist with applications made under the first three expedited review pathways:

i. Work procedures for review on innovative therapeutic drug

ii. Work procedures for review and approval on drug for conditional approval

iii. Work procedures for drug priority review and approval

The documents are for trial implementation but include more detailed information about how to make applications under the relevant pathway.

Notable Exclusions

While there are some obvious changes to the new DRR, there are also some notable exclusion. In particular, data exclusivity and certain IP protections have been removed from the new DRR. Unlike the previous DRR (October 2007), the new DRR has removed the requirement that an MA applicant make both, a statement of the relevant patents associated with the drug product, plus a declaration of non-infringement to those patents. While they have been removed from the text of the document, the application process for registration still requires a declaration of patents and non-infringement. In addition, the new DRR does not include the provision from the previous version of the DRR (October 2007) that stipulated approval of a drug MA could only occur within two years of patent expiry. This requirement has not seemingly appeared in any subsequent documents. The new DRR is also silent on any required new drug monitoring period and the previous regulatory data exclusivity ("DE") provisions have also been removed (although the new drug monitoring period and DE provisions remain in the currently effective "Implementing Regulations of the Drug Administration Law (March 2019)).

Summary

The restating of the expedited review pathways, and the recently published work procedures, appear to be a step toward improving a process that has seemingly changed numerous times over the years. While there are several positives to the new provisions, the notable exclusions of any IP and data exclusivity rights (including provisions for new drug monitoring period, data exclusivity and patent infringement declaration) highlights the gaps and inconsistencies in the regulatory and IP framework for pharmaceuticals that has been discussed for several years. It is anticipated that these important regulatory and IP protections will be expanded on in future updates to IP laws, (note the Patent Linkage provision in the new draft Patent Law), but there still remains little indication as to when other changes may be implemented.