China's domestic black market in illicit active pharmaceutical ingredients (APIs) is being fuelled by increasingly desperate cancer patients attempting to manufacture their own medicines, as well as a persistently slow drug-approval process for innovative overseas treatments, according to Chinese newspaper the Global Times.
Implications | Cancer patients are increasingly turning to home drug-making – including of Tagrisso (osimertinib; AstraZeneca, UK), and potentially of PD-1 inhibitors – after local authorities cracked down on the importing of drugs from overseas that have not been approved in China. |
Outlook | While there are few data on the scale of home-made-drug manufacturing in China, the growing trend is indicative of the large number of severe challenges faced by China as the country attempts to modernise its pharmaceutical market – the world's second largest. |
China, prohibits the sale of unapproved treatments purchased abroad, and locally-manufactured active pharmaceutical ingredients (APIs) of treatments not approved by the China Food and Drug Administration (CFDA). In the past, patients would reportedly seek assistance from contacts or intermediaries to purchase treatments on foreign trips; however, the high-profile arrest in 2014 of businessman Lu Yong – who was suffering from chronic myelocytic leukaemia – for illegally importing drugs from India has discouraged this practice. At the time, thousands of terminally ill patients signed a petition against the arrest. According to Sohu.com.cn, "This shows that people have been pushed to breaking point by the high cost of patented and imported drugs" (see China: 10 March 2016: China's NHFPC indicates future price cuts for oncology treatments and imports).
Consequently, Chinese patients have increasingly turned to purchasing APIs online from illegal traders, and manufacturing their own medicines. According to Global Times, cancer groups distribute articles instructing patients on the equipment and methods required for manufacturing specific medications, as well as potential side effects. The equipment for weighing and processing APIs is available for purchase on national e-commerce website taobao.com, and social media platforms QQ and WeChat are typically used to facilitate the illegal API trade. Patients are asked to provide API dealers with proof of cancer diagnosis, as well as clinical records.
According to the source, the illicit APIs are sourced from laboratories and scientific institutes, as well as some pharmaceutical companies. Prices vary according to the "purity" of the API – with an API of average purity costing approximately CNY500 (USD75) per gram, while an API with a purity of over 99.7% can earn CNY1,000–1,500 per gram. The APIs are reportedly typically Chinese-made copies of medicines developed abroad, using the publicly-available molecular structure as a blueprint. In China, such APIs copied from drugs developed overseas can be used legally for research, but selling these for medical use in humans (prior to regulatory approval) is illegal.
According to the source, frequently requested APIs among cancer-patient support groups have included "9291" – an abbreviation for AZD9291 – which is the development code for UK firm AstraZeneca's cancer treatment Tagrisso (osimertinib); other popular APIs include codes 2992 and 4002. In addition, patients are now seeking to purchase APIs in order to manufacture PD-1 inhibitors (such as Opdivo [nivolumab; Merck & Co, US] or Keytruda [pembrolizumab; Bristol-Myers Squibb, US]), which have yet to receive approval at the national level in China (although Keytruda has reportedly received some form of backdoor listing in Hainan Island – see China: 26 September 2016: Merck's Keytruda becomes first imported treatment approved under Hainan Island's pilot medical tourism programme).
Despite ongoing reforms, China's drug-approval process is significantly lengthier than in other countries, with new imported medicines taking up to seven years to receive marketing approval in the world's second largest pharmaceutical market.
According to Global Times, patients who willingly turn to home drug-making understand the risks: "They [patients] don't care whether it's safe or not. The side-effects of the APIs are much less of a problem compared to them taking no drugs at all. If they don't take medicine, they are just waiting to die," Li Yinghuan, a lecturer at Capital Medical University, was quoted as saying.
Outlook and implications
While few data on the scale of home-made drug manufacturing in China exist, the growing trend is indicative of the large number of severe challenges China is facing as the country attempts to modernise its pharmaceutical market – the world's second largest.
First, in terms of the implications for pharmaceutical multinationals, the growing illicit trade in APIs poses a threat not only to patient health, but also to the intellectual property of innovative drugs developed outside China. Despite government crackdowns and the illegality of the practice, it is likely that the sheer scale of the unmet need for innovative cancer treatments will mean that the illegal copying of patented drugs will increase.
Second, the report underlines the Chinese authorities' huge challenge in terms of monitoring China's vast and fragmented pharmaceutical distribution industry. Intermediaries in China have often been criticised as the weak links in distribution chains, leading to widespread corruption and kickbacks. Despite attempts to rein-in illegal practices, China's recent vaccine scandal is also indicative of this weakness (see China: 26 July 2016: China launches national inspection of vaccines after counterfeits scandal). The same lack of oversight and control can be seen in the area of social media with regard to healthcare (see China: 6 May 2016: China emphasises ban on unapproved use of cancer immunotherapies after student's death provokes new outcry): in April, 21-year-old student Wei Zexi died of synovial sarcoma, after claiming that false advertising from a Chinese search engine led him to take an illegal immune-oncology treatment.
Third, China's lengthy drug-approval process has been a longstanding issue for overseas drug makers, as well as for patients. The slow pace of regulatory reform – as well as persistently high drug prices – has led to an outflow of patients and patients' contacts to seek out drugs on the grey market in neighbouring Hong Kong, which operates under a different legal system (see Hong Kong: 9 October 2015: High price of oncology treatments creates cut-price drugs trade in Hong Kong).
Perhaps most importantly, the report underscores the sheer desperation of a large number of Chinese patients who lack access to effective treatment. This ongoing unmet need ranges from shortages of basic vaccines to astonishing news reports – including of one man who kept himself alive for 13 years with a home-made dialysis kit in his bathroom. While China continues to push healthcare reforms, the poorest sections of the population are expected to see the slowest improvement in treatment of their chronic diseases.