The enthusiasm for the import of generic drugs has gradually increased: Overseas data sharing is good!

Medical Network July 26th The spring of overseas generic drugs has arrived.

On July 10, 2018, the State Drug Administration issued the Circular on the Technical Guidelines for Accepting Clinical Clinical Trial Data for Drugs (No. 52 of 2018). The data on overseas clinical trials covered by the guidelines include applicants' approval. Innovative medicines are simultaneously developed for clinical trial data obtained overseas and have fully measurable bioequivalence data. This will promote more and more overseas generic drugs (ie, 5.2 drugs, non-original research on overseas listings) Drug application for domestic listing) Declaration and listing.

Foreign data is liberalized, you must first pass the 'race' mark

As shown in Table 1, the data of overseas clinical trials approved by the State Drug Administration are mainly considered from three aspects: First, the authenticity, completeness, accuracy and traceability of the data of overseas clinical trials. Second, the overseas clinical trials. The validity and safety of the data, and third, whether there are ethnic differences in the data of overseas clinical trials.

Among them, racial difference analysis requires racial sensitivity analysis of regional and ethnic aspects of clinical pharmacology data to determine whether overseas clinical trial data is applicable to the Chinese population; and follow the ICH's racial influence factors on receiving foreign clinical data ( E5) Requirements, confirm the validity and safety of the Chinese subgroup and the overall population of the world.

In summary, Class 1 imported new drugs (innovative imported drugs that are not listed at home or abroad), if there are multi-center clinical trials for Chinese and foreign synchronization, 5.1 drugs (original listed drugs for overseas listing), and 5.2 imported generic drugs The corresponding original drug has products for clinical trials in the East Asian population, especially the Chinese subgroup, and will be expected to benefit from the policy of “Technical Guiding Principles for Accepting Overseas Clinical Trial Data”.

In addition, certain characteristics of the drug (chemical classification, metabolic pathway or pharmacological classification) itself determine whether it is susceptible to racial factors.

Some drug properties will most likely indicate an insensitivity to racial factors. Drug properties that are not sensitive to racial factors include: linear pharmacokinetics (PK); flat efficacy within recommended doses and dosing regimens Kinetic curve (PD) (shows that the drug is well tolerated); a wide range of doses indicates that the drug is well tolerated (rare dose changes do not cause a dramatic change in drug action); Metabolized in multiple ways (not increasing the possibility of drug interactions due to only a single pathway of metabolism); high bioavailability (not affected by dietary absorption); low protein binding rate; drug-drug, drug-diet , drug-disease interaction is small; non-systemic mode of action; low probability of being inappropriately used (prone to inappropriate use of drugs such as analgesics and tranquilizers).

Correspondingly, drugs such as prodrugs, especially those with potentially racial differences, are sensitive to ethnic factors.

Drawing on ICH, China will strictly monitor overseas data in the short term.

In addition, according to E5 of ICH, China accepts clinical trial data from abroad, and may also consider the following parts:

1) Clinical trial data of special subpopulations, such as patients with hepatic insufficiency and renal insufficiency;

2) Adaptation of dosage and method of administration according to ethnicity or according to local treatment methods;

3) Drug interaction research.

According to the experience of ICH, with the increase of regional recognition experience of clinical data in foreign countries, the drug regulatory department will be better in the case of the need to supplement the safety and efficacy of the study, the pharmacodynamics of the dose and dosage regimen will be better. The understanding of the need for supplementary research between regions will gradually decrease.

In view of this, China's Food and Drug Administration may strictly monitor overseas test data in the short term, and the listed places of imported drugs are US, Japan, UK, Germany, etc. Regulation Countries with higher requirements are relatively easier to recognize.

According to the data of Xianda Yaohai Tour, after the reform of chemical registration regulations, the import registration declaration before 2017 is mainly based on the clinical declaration of category 5.1 and the clinical declaration of category 1 new drugs. The clinical declaration of category 5.2 in the first half of 2018 has increased.

Currently, only the 5.2 class approved for the import of cefazolin sodium for injection can be regarded as the consistency evaluation. 5.2 The declaration refers to the generic manufacturers in India, Taiwan, Europe and America, and the domestic third-party registration agency Main. For example, Novartis has reported the inhalation of salmeterol, dexamethasone tablets, levetiracetam tablets, mometasone furoate nasal spray, escitalopram oxalate tablets and voriconazole tablets. Sildenafil orally disintegrating tablets, rivaroxaban tablets, fulvestrant injection, sevelamate tablets and abiraterone acetate tablets.

The recent approval of the import is mainly from the 5.1 category, that is, the original drug listed overseas is applied for domestic listing. In 2017, 15 imported drugs were approved in 5.1 categories, and in the first half of 2018 there were 8.

Takeda's first-line treatment of multiple myeloma drug oxazide citrate capsule was approved in 2018. In 2017, it started clinical phase III in China. Although it has not been listed, it has been approved for marketing. Gilead's sophophos bweeviparvavir tablets.

These two products are expected to be released on May 23, 2018. 'National Drug Administration National Health health Committee on optimization Drug registration The announcement of the review and approval of related matters' (No. 23 of 2018) mentioned that 'the prevention and control of the listed products abroad is seriously life-threatening and there is no effective treatment. disease As well as rare disease drugs, if the applicant for imported drug registration believes that there is no ethnic difference, it can submit the clinical trial data obtained overseas to directly apply for drug listing registration. 'In other words, for these cases, before May 23, 2018 Accepted and proposed to reduce the above-mentioned imports of clinical trials drug If the clinical trial application meets the requirements of the Drug Registration Management Measures and related documents, it may be approved for direct approval and approved for listing.

In the first half of 2016 to the first half of 2018, Pfizer's Dacomitinib was the only one to import a new class 1 drug. It was submitted in the first half of 2018 to treat patients with advanced non-small cell lung cancer (NSCLC). 2. The second generation of human epidermal growth factor receptor ( HER ) inhibitors was developed.

Product introduction also needs to consider the domestic market status, market size and price. From the perspective of the national drug structure, only the imported generic drugs that have no generic drugs and relatively low prices, and the critical drugs that are not listed in the domestic market are currently imported. Diseases, rare diseases, pediatrics and imported generic drugs that lack effective treatment are more likely to accelerate the introduction.