Domestic generic drugs: "Youth is better than blue"

After the patent period of the original drug can be copied to reduce the price of the drug

A generic drug is a drug that is identical or similar to the original drug in terms of active ingredient, dose, potency, action and indication. Chang Feng, dean of the International Medical Business School of China Pharmaceutical University, explained that drugs that have passed the patent period have obtained considerable profits by maintaining high prices during the patent period, recovering the research and development costs, so other companies can reduce the price of drugs through imitation after the patent protection period.

In other words, the original drug is protected by intellectual property rights during the patent period, and high pricing helps the pharmaceutical company that created the drug recover the cost of innovative drug research and development and supports the research and development of new innovative drugs. As the cost of innovation is recovered, post-patent drug prices should fall off a cliff so that more patients can afford them.

Taking Entecavir for the treatment of hepatitis B as an example, the original drug Entecavir was developed by the international pharmaceutical company Bristol-Myers Squibb and was listed in China in 2006 with a price of tens of yuan a piece. After the patent protection period of the original drug Entecavir, because the original research enterprises have patent layout on the raw material synthesis route and preparation method, it is not easy to imitate this drug.

Relying on the Jiangsu Engineering Technology Research Center for New Liver Drugs and the Jiangsu Key Laboratory of Antiviral Targeted Drug Research, with the support of the national Major New drug creation special, through more than ten years of systematic technological innovation, Zhengda Tianqing has broken through the key technical bottlenecks and crossed the patent barriers of original drug synthesis methods. A series of research and development achievements have been made in drug crystal form, synthesis process route and drug preparation method. Based on the above technological innovation, the first imitation of the domestic market Entecavir dispersible tablets (Runzhong) was listed in 2010, solving the problem of domestic hepatitis B patients.

Public data show that in 2018, the price of the national postharvest hepatitis B special drug Entecavir dropped from 10.55 yuan/tablet to 0.62 yuan/tablet, a drop of 94%. The collection of "purchasing with quantity and exchanging price with quantity" further contributes to the reasonable return of drug prices, saves the expenditure of medical insurance fund, and greatly reduces the burden on patients.

The investment in the first and difficult-to-mimic drugs still needs to be increased

"We recently analyzed the prices of 150 unselected original drugs in the first seven batches." Chang Feng said that before the collection, up to 73% of the original drug prices in China are higher than the international median price. After the collection, affected by the price reduction of selected generics, the price of original developed drugs has decreased, but the price of 69% of unselected original developed drugs in China is still higher than the international median price.

After the patent period of the original drug, if the lack of generic drugs brought about by the "competitive pressure" is difficult to self-price. "It is unreasonable to maintain high prices beyond the patent period." Chang Feng said.

Blacksmithing also needs its own hard, and the imitation ability of China's pharmaceutical industry is also a key ability to maintain the safety of people's drugs. "It is necessary to promote the transformation of the development model of generic drug companies and promote the high-quality development of the generic drug industry." In the past, pharmaceutical companies spent heavily on marketing and underinvested in innovation and research and development, said Zhang Ming, head of the price recruitment expert group at the National Healthcare Security Administration.

Data released by the National Health Commission also shows that from 2012 to 2016, a total of 631 patents expired in the world, many of which did not apply for generic registration. Zhang Ming said that it is necessary to create an environment for the cultivation of enterprise innovation ability, guide pharmaceutical companies to shift from heavy sales and heavy channels to heavy research and development, heavy quality, and increase investment in the first imitation drugs and difficult imitation drugs.

The development of first and difficult-to-mimic drugs also requires a lot of biotechnology innovation. In 2018, the "Opinions on Reforming and Improving the Policy of Generic Drug Supply Security and Use" issued by The General Office of the State Council clearly pointed out that the technical research of generic drugs should be strengthened, and the key common technology research of key chemical drugs and biological drugs in the drug catalog should be encouraged to be included in the relevant national science and technology plans. Using the same mechanism as exenatide, the original drug for the treatment of type 2 diabetes, the domestic innovative drug focuses on improving the oral use of diabetes from multiple perspectives such as humanization and long-term effect. Through the construction of advanced technology platforms such as gene engineering tandem technology, polypeptide protein drug preparation technology, and biological drug long-acting preparation technology, Chinese pharmaceutical enterprises have recently made a series of breakthroughs in the development of such drugs.

In the imitation of domestic Entecavir tablets, the innovative construction technology of purine rings is also adopted to effectively avoid complicated chromatographic separation, simplify the post-treatment process, and further reduce production costs while improving product quality.

Consistent evaluation ensures that generic drugs are good and affordable

There has been such a saying on the network: "The purity of the active ingredients of the original and generic drugs is different, one may be 80%-90%, and the other can only achieve 30%-40%." In response to such remarks, Zhang LAN, director of the Pharmaceutical Department of Xuanwu Hospital of Capital Medical University, responded that such rhetoric is completely irresponsible.

"Pharmaceutical equivalence evaluation is an important part of generic drug consistency evaluation in China." Pharmaceutical equivalence requires that generic drugs must have the same active ingredients, content, route of administration and dosage form as the original drug, and meet drug quality standards, Zhang LAN said.

In order to improve the overall level of China's pharmaceutical industry and ensure drug safety and effectiveness, The General Office of the State Council issued the Opinions on carrying out the Consistency Evaluation of the Quality and Efficacy of generic Drugs in 2016, requiring generic drugs to carry out the evaluation of the quality and efficacy consistency of original drugs. Bian Xiaolan, director of the Department of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, said that the consistency evaluation focuses on verifying that generic drugs are equivalent to the original drugs in terms of design, biological absorption and metabolism, etc. China's generic drug quality and efficacy consistency evaluation has a high starting standard.

On the basis of carrying out consistency evaluation to improve the quality of domestic generic drugs, the state carries out volume collection, so that domestic generic drugs can obtain a fair competition with the original drug. "The drug collection will put generic drugs that pass the consistency evaluation on the same open platform and compete fairly with original drugs." Zhang Ming said that high-quality generic drugs are in great need of a chance to prove themselves in clinical applications.

Data show that after eight batches of national collection, the proportion of patients using high-quality drugs such as original drugs and generic drugs that have passed consistency evaluation has increased from 50% before collection to more than 95%, and the overall quality level of clinical drugs has been improved.

Chang Feng believes that in recent years, China's generic drug industry has made great progress in terms of quality, production capacity and market position. The consistency evaluation policy strictly adheres to the "quality pass" of generic drugs in the approval process, and the number of generic drugs going to sea in China is increasing, and the improvement of international recognition also indicates the improvement of the level of generic drugs in China.

"At present, China is in the stage of leapfrogging from a generic-drug power to a generic-drug power." Chang Feng said that companies on the market that have not passed the consistency evaluation and do not have the advantages of scale production and product pipelines are being eliminated, generic drugs are gradually realizing the high-quality replacement of original drugs, and the concentration of the pharmaceutical industry is constantly improving. On this basis, the quality of medication for Chinese patients will be further improved.