The development of generic drugs: Bolar exception patent rights of the patent system and the approval procedures for generic drugs

From the perspective of patent rights, drugs can be roughly divided into patented drugs and generic drugs. The investment of patented drugs is large, risky, difficult and long, but at the same time, the benefits that can be obtained are also very amazing. Generic drugs generally refer to drugs that are put on the market after administrative approval after the patent of the patented drug expires.

The generic drug should have the same active ingredients, route of administration, dosage form, specifications and the same therapeutic effect as the generic drug. Although the difficulty of research and development of generic drugs is greatly reduced, considering that drugs are directly related to the health and life safety of users, their placing on the market is still strictly controlled by the state, and all countries generally have specialized drug regulatory agencies for the proposed listing of drugs. Drugs undergo complicated procedures for marketing review. The acceptance, review, and approval of the registration of generic drugs will still take a long time to complete.

Therefore, if the generic drug manufacturer can only start the development and registration application of the generic drug after the expiration of the patent right protection period, the generic drug can be truly introduced to the market after a lengthy approval process. In this way, despite the termination of the patent right, there was still no similar generic drug on the market for a long period of time. This is equivalent to extending the patent protection period, which is obviously unreasonable to the public and generic drug manufacturers. Is not in line with the spirit of the patent system.

Therefore, many countries have introduced Bolar exception clauses in their patent law systems. This clause allows generic drug manufacturers to use patented inventions before the expiration of patent protection without the consent of the patent owner, and obtain marketing approval from the public health management agency. Once the patent protection period expires, cheap generic drugs can be put on the market as soon as possible.

The origin of the Bolar exception

The Bolar exception originated from the U.S. Court of Appeals for the Federal Circuit in Roche v. Bolar in 1984.

In this case, the plaintiff Roche had a patent for fluazepam hydrochloride, the active ingredient of a sleeping pill, and the patent expired in 1984. The accused infringer, Bolar, imported a small amount of the sleeping medicine from abroad in order to launch its imitation products when the patent for the ingredients of the sleeping pill expired. In order to make the generic medicines pass the examination and approval, the Bolar company passed the inspection of these medicines. Clinical trials to obtain the data required for approval. Roche believed that Bolar's actions infringed its patent rights and filed a patent infringement lawsuit in the Federal District Court of New York. The court of first instance held that Bolar’s conduct was a research experiment, and the number of patented products involved was small, and that it did not constitute an infringement of the pharmaceutical patent owned by the plaintiff Roche.

Roche refused to accept the first-instance judgment and appealed to the U.S. Court of Appeals for the Federal Circuit. After review, the Court of Appeal held that Bolar’s actions were clearly for commercial purposes, and that the experimental use exception should not be extended to applications with commercial purposes. Therefore, the experimental use exception principle cannot be applied. Therefore, the second instance ruled its infringement. The Court of Appeal recognized that the process of waiting for approval by general drug manufacturing companies actually extended the patent protection period, but pointed out that this issue should be resolved by Congressional legislation, and the court is not the appropriate place to debate the issue.

The verdict in this case prompted generic drug manufacturers to carry out a series of activities and pushed the US Congress to take action. In 1984, the "Drug Price Competition and Patent Term Restoration Act" was passed. The bill solves the problem that generic drugs cannot be listed in time for a long time after the expiration of the patent term, resulting in the illegal extension of the patent term; and it also compensates the patentee for the delay in the patent term due to the FDA's approval of the drug patent application. It is the Bolar exception clause in the United States.

The impact of the Bolar exception

In recent years, the sales of generic drugs have continued to rise, and their share in drug sales has also increased year by year. Corresponding to the increasing sales of generic drugs, the number of generic drug applications received by the United States and the European Union each year is also increasing.

The system established by the "Drug Price Competition and Patent Term Recovery Act" in the United States not only promotes the accelerated listing of generic drugs, but also encourages generic drug companies to challenge related patents of patent drug manufacturers. The world’s largest generic drug companies Israel Teva Pharmaceuticals ( Teva, Mylan, Canada, Apotex, and Novartis, Switzerland, have all put forward a large number of Orange Book category IV patent challenges.

The continuous development of the generic drug industry has given birth to a number of international generic drug giants, and pharmaceutical companies that have advantages in the patented drug industry have also developed their own generic drug departments. Israel Teva Pharmaceuticals and Mylan Pharmaceuticals of the United States are among the leaders.

In 1997, the patent for ranitidine, one of Glaxo Wellcome’s best-selling drugs, expired. After that, generic companies such as Mylan Pharmaceuticals quickly put its alternative drugs on the market. In fact, they entered the market from generic drugs. From the beginning of the market to October of that year, the sales of Glaxo Wellcome’s ranitidine dropped sharply by 55%, and 60% of patients chose generic drugs, which caused a lot of trouble for Glaxo Wellcome. .

Pfizer's patented blood lipid-lowering drug Lipitor (atorvastatin) was granted a patent in 1997, and it was the world's first drug with a sales volume of over 100 billion U.S. dollars. In 2004, the Indian company Ranbaxy filed an invalidation lawsuit against Lipitor's two US patents in response to a patent infringement lawsuit filed by Pfizer against its generic drug application, thereby obtaining a license to market its generic drug. Finally, Pfizer and Ranbaxy reached a settlement agreement, and Ranbaxy delayed the listing of its generic drugs to November 2011. It is estimated that during the 180-day exclusive sales period, Lipitor generic drugs will bring Ranbaxy’s sales revenue of US$650 million.

China's Bolar exception clause

China is the world's third largest pharmaceutical market and has deep growth potential. However, it cannot be denied that China's pharmaceutical industry is relatively backward, and the chemical drug industry is still in the stage of imitating innovation, and its independent innovation capability is still relatively weak. Therefore, the development of the generic drug industry is an inevitable choice for my country.

Many international pharmaceutical companies have targeted the Chinese market and have continued to expand their business in China. German Bayer Pharmaceuticals commissioned Shandong Xinhua Pharmaceutical Co., Ltd. to produce a variety of generic drugs. In 2008, it acquired the anti-cold drug business of Dongsheng Technology, including The "white plus black" best-selling in China. And Merck chose to cooperate with Simcere Pharmaceuticals to enter China's generic drug market. In order to provide the public with cheaper drugs, we encourage generic drugs to be marketed in time after the patent expires to reduce medical expenses.

Before the current patent law was amended, Article 63 stipulated that the use of relevant patents exclusively for scientific research and experiments does not constitute patent infringement. It emphasizes that it is designed for scientific research and experimental purposes. The exemption provisions on the liability for patent infringement in the patent law before the amendment did not include the information required to provide administrative approval. As a result, domestic courts are in a dilemma when encountering similar disputes in Bolar litigation.

Known as the "First Bolar Exception Case in China", the Japanese Sankyo Co., Ltd. v. Beijing Wansheng Pharmaceutical Co., Ltd. was one of the top ten intellectual property cases in Beijing in 2006.

Japan's Sankyo Co., Ltd. owns the patent right for Olmesartan Lipid Tablets, which was granted on September 24, 2003. In July 2005, during the period when Sankyo Pharmaceutical Company applied to the State Food and Drug Administration for the production of the patented drug, Sankyo Pharmaceutical Company discovered that more than a dozen companies in China had applied to the State Food and Drug Administration for clinical approval of a new drug suspected of infringing the plaintiff’s patent. Beijing Wansheng Pharmaceutical Co., Ltd. has entered the new drug application and approval stage. On February 16, 2006, Sankyo Co., Ltd. and Sankyo Pharmaceutical Company sued Wansheng Company for infringement of its patents in Beijing No. 2 Intermediate People's Court. The Second Intermediate People’s Court of Beijing held that although Wansheng Company used the patented method to manufacture the drugs involved in the case for the purpose of conducting clinical trials and applying for production licenses, the defendant Wansheng Company’s manufacturing behavior was to satisfy the relevant national authorities’ The need for administrative examination and approval of registration is not directly for the purpose of sales, and does not belong to the act of implementing patents for the purpose of production and operation as stipulated in the Patent Law.

Regarding this case, although the court ruled that the defendant did not infringe, it is debatable. The defendant’s actions in this case had commercial purposes, that is, they had production and business purposes. Therefore, in order to avoid this difficulty in the application of the law caused by the lack of direct provisions of the law, in the third revision of my country’s "Patent Law", a paragraph was added that is not considered as patent infringement, as the sixth patent law. Article 19, Item 5, namely: manufacture, use, or import of patented drugs or patented medical devices in order to provide information required for administrative examination and approval, as well as those specially manufactured or imported for patented drugs or medical devices, this article is called Bolar in our country is an exception. It is worth noting that the Patent Law not only added a fifth Bolar exception clause in Article 69, but also retained the original fourth scientific research experiment exception clause. This provides clear legal provisions to resolve similar previous drug patent infringement cases, and avoids falling into the embarrassing situation of vague application of legal provisions.

Since the revised "Patent Law" was formally implemented on October 1, 2009, generic drug manufacturers have used the Bolar exception clause and the related drug patent link system to apply for drugs in advance within 2 years before the expiration of the drug patent protection period. Registration, when the drug patent expires, you can immediately enjoy the opportunity to seize the drug sales. Although China's Bolar exception clause is not perfect, with the continuous establishment of related supporting systems, I believe that Bolar exception can form a complete system in China, which is more in line with China's national conditions and can better serve us.