I. How should the terms "undisclosed," "self-obtained" and "reliance" as defined in the Implementation Measures be understood?

Undisclosed: With the development of industry and the need to safeguard the public’s right to know, drug regulatory authorities in major countries and regions worldwide generally require the disclosure of information such as summaries or reports of clinical trial results. The term not previously disclosed as defined in the Implementation Measures refers to regulatory data that has not been disclosed in full; that is, if only a portion of the regulatory data has been disclosed, the regulatory data as a whole is still considered undisclosed.

Self-obtained: This includes drug regulatory data obtained by the drug registration applicant through research conducted in-house, research commissioned from third parties, or data acquired through purchase or exclusive licensing.

Reliance: Typically, the marketing authorization of a new drug requires the submission of complete data on pharmaceutical studies, nonclinical studies and clinical trials in order to obtain approval. In contrast, modified new drugs and generic drugs use the originator drug as a reference; they generally do not require the repetition of clinical trials, but instead employ a comparative approach against the originator drug to provide supplementary evidence of safety and efficacy demonstrating clinical advantages, or use bioequivalence (BE) studies and other methods to indirectly demonstrate pharmaceutical consistency and therapeutic equivalence with the originator drug.

The term "reliance" as defined in the Implementation Measures refers to situations where other applicants apply for marketing authorization for a modified new drug or a generic drug by citing or referring to regulatory data submitted by the marketing authorization holder of an already marketed originator drug to demonstrate the drug’s safety and efficacy, without repeating the same trials.

II. Why does the data protection system not apply to traditional Chinese medicines?

Traditional Chinese medicines are governed by the Regulations on the Protection of Traditional Chinese Medicine and supporting documents.

III. What does all regulatory data used to demonstrate the safety, efficacy and quality control of a drug in Article 5 of the Implementation Measures encompass?

According to the Provisions for Drug Registration and ICH guidelines, regulatory data used to demonstrate the safety, efficacy and quality control of a drug generally covers the following categories:

(i) Pharmaceutical data, including but not limited to active pharmaceutical ingredient (API)/drug product studies, manufacturing processes, specifications and method validation studies, stability studies, and packaging material compatibility studies.

(ii) Nonclinical study data, including but not limited to pharmacodynamics studies, pharmacokinetics studies, toxicology studies, and safety pharmacology studies.

(iii) Clinical study data, including early-phase (Phase I/II) data and pivotal (Phase III) data.

IV. Should new data protection be granted for new indications, new patient populations or concomitant therapies for drugs that have already been granted data protection? Is data protection granted for bioavailability, bioequivalence and vaccine immunogenicity data?

The core of drug regulatory data protection lies in protecting original regulatory data generated to demonstrate the safety and efficacy. Therefore, new data protection can only be granted if new data demonstrating the safety and efficacy of the drug is generated.

For drugs that have already been granted data protection, where new indications or patient populations are added, data protection may be granted for this portion of clinical trial data provided that new, original clinical trial data can be supplied; however, new combination therapy regimens require a case-by-case assessment, and data protection may only be granted where entirely new data is required.

As clinical data relating to bioavailability and bioequivalence does not generate new evidence of safety or efficacy, it is not within the scope of data protection.

Given that the purpose of data protection is to encourage pharmaceutical innovation, protective efficacy clinical trials are the gold standard for evaluating innovative vaccines, whilst immunogenicity serves as a surrogate endpoint for vaccine efficacy evaluation; therefore, such data is not protected.

V. If the active ingredient of a drug has been marketed overseas but not yet marketed within the territory, and the new indication for which a marketing authorization is first applied within the territory has not been marketed either within the territory or overseas, how should data protection be provided in such circumstances?

For the originator drug that has been marketed overseas but not yet marketed within the territory, if the indication for which a marketing authorization is first applied within the territory has not been approved for marketing either within the territory or overseas, although it is classified as a modified new drug under the registration category, the applicant must submit all regulatory data used to demonstrate the drug’s safety, efficacy and quality control, in addition to submitting drug clinical data relevant to that indication. In other words, the data requirements for such drug registration applications are consistent with those for innovative drugs and originator drugs that are already marketed overseas but not yet marketed within the territory. To encourage the simultaneous development of new indications both within the territory and overseas, whilst taking into account the fundamental principles governing the scope of drug regulatory data protection, the Implementation Measures stipulate that in such circumstances, Article 5 of the Implementation Measures shall apply, granting a data protection period of 6 years. The scope of data protection includes all regulatory data in the marketing authorization dossier used to demonstrate the drug’s safety, efficacy and quality control.

However, where additional indications are subsequently added for such drugs, only the data required for the approval of the new indication need be submitted; there are no special considerations compared to other applications for new indications. Therefore, Article 6 of the Implementation Measures applies, granting a data protection period of 4 years. The scope includes new clinical trial data demonstrating a clear clinical advantage over drugs with known active ingredients (marketed biological products), but excludes bioavailability, bioequivalence and vaccine immunogenicity data.

VI. If the manufacturing of a drug is transferred from overseas to China, can the original data protection period of an overseas-manufactured drug be retained?

Yes. To improve access to medicines and meet clinical needs, overseas enterprises are encouraged to transfer the manufacturing of originator drugs marketed in China to domestic facilities. If the originator drug has already been granted data protection, the National Medical Products Administration (NMPA) will not grant approval for marketing authorizations or supplementary applications submitted by other applicants who rely on data from the imported originator drug or the originator drug manufactured within the territory without the consent of the holder, during the period of data protection. The aforementioned holders include holders of imported originator drugs and originator drug manufactured within the territory. To obtain the aforementioned protection, holders of domestically-manufactured drugs must obtain the consent of the originator drugs holder.

VII. For conditionally approved drugs that have been granted data protection, will new clinical trial data generated after marketing be granted new data protection?

Conditionally approved drugs that meet the conditions for data protection are granted a data protection period upon marketing authorization. New clinical trial data obtained from studies conducted post-marketing to fulfil the conditions attached to the approval serve as supplementary evidence to the prior approval conclusions; they do not constitute new data demonstrating clinical safety or efficacy, and therefore no new data protection period shall be granted. However, during the data protection period for the drug, other applicants shall not rely on these new clinical trial data to obtain a marketing authorization without the consent of the holder.

VIII. How is the data protection period handled for Category 5.1 chemical drugs, Category 5.2 chemical drugs and Category 3 chemical drugs?

To encourage the early entry of overseas-marketed originator drugs into China and meet the clinical needs of Chinese patients, once a Category 5.1 chemical drug has been granted a data protection period, the data protection periods for Category 5.2 and Category 3 chemical drugs that have already been granted such periods shall remain valid; for Category 5.2 and Category 3 chemical drugs that have already been accepted for review, those meeting the criteria will continue to undergo review and approval, but will no longer be granted a data protection period; for new marketing authorization applications and supplementary applications relying on such data, the provisions of Article 12 of the Implementation Measures shall apply.

IX. Following the issuance of the Implementation Measures, how will the regulatory requirements for clinical trials of generic versions of originator drugs that have been marketed overseas but not yet marketed within the territory -where a product of the same product is already marketed, be optimized and adjusted?

The term “the first approved generic versions of originator drugs that have been marketed overseas but not yet marketed within the territory” in Article 8 of the Implementation Measures refers to the first approved generic drug of the same product. For generic versions of originator drugs that have been marketed overseas but not yet marketed within the territory, where a product of the same product was already approved prior to the issuance of the Implementation Measures, other newly submitted generic applications for the same category are not required to repeat safety and efficacy clinical trials once two years have elapsed since the first product was marketed.