Gamma globulin, the so-called immunoglobulin, is a blood product prepared from healthy human plasma through the process of separation, purification, virus inactivation, etc. It is the passive immunity preparation, of which the most widely used product in the clinical practice is the human immunoglobulin for intravenous injection, referred to PH4.
In terms of the mechanism of action, PH4 plays a therapeutic role in a variety of diseases mainly through the antibody supplementation and immunomodulation. In February 2017, the Chinese version of the National Directory of Drugs Covered by the Basic Medical Insurance, Industrial and Commercial Insurance, and Maternity Insurance (2017 Edition) was issued by the Ministry of Human Resources and Social Security, with human immunoglobulin for intravenous injection in the Category B. The diseases are the following six major categories: primary immunoglobulin deficiency, neonatal septicemia, heavy primary immunologic thrombocytopenic purpura, Kawasaki disease, generalized myasthenia gravis and acute Guillain-Barre Syndrome.
Long History of Traceability and Wide Range of Applications
In the 1890s, the diphtheria in Europe and the United States became one of the major killers threatening the health of children, with the mortality rate of over 10% at one point. German physiologist, Emil vonBehring, and his colleagues extracted serum from animals infected with diphtheria bacilli or from recovering patients and injected it into diphtheria patients, allowing many of them to be cured. In 1901, Behring was awarded the first Nobel Prize in Physiology or Medicine for the invention of this serum therapy.
In fact, the active ingredient in the fight against diphtheria bacilli is immunoglobulin in the serum, which can probably be considered as an early example of the use of this drug against the disease. For more than 100 years, immunoglobulins have been used in several major global outbreaks of infectious diseases, including Spanish influenza, SARS, H5N1 avian influenza, H1N1 influenza A, Middle East respiratory syndrome, Ebola, and SARS-CoV-2 in these years.
Whether based on serum or plasma, the active ingredient that actually works is the immunoglobulin. We have found that this therapy is not new and has a wider range of applications. In case of the current COVID-19 infection, to some extent, the root cause of the demand for gamma globulin is that there are no drugs that can specifically combat SARS-CoV-2 in high-risk groups such as the elderly or immunocompromised, making gamma globulin an alternative treatment option to deal with the current infection.
Previously, some regional epidemic prevention and control authorities have included human immunoglobulin for intravenous injection in the recommended list of the guideline catalog of drugs for the treatment of COVID-19, which is used to assist in the treatment of confirmed cases of COVID-19, especially critical cases. However, the actual treatment efficacy of gamma globulin against COVID-19 infections remains to be further scientifically validated in the clinic and may not be appropriate for every infected patient. Following the laws, the future pathogenic power of the SARS-CoV-2 will eventually weaken, and the current demand for gamma globulin will gradually decrease. The demand for drugs corresponding to patients with rigid needs should be mainly met.
Limited Short-term Capacity Supply and Expected Increasing Trend during the 14th Five-Year Plan
In the first 11 months of 2022, the major manufacturers of blood products in China with an increase in the number of PH4 batch issuances were Taibang Biologic, Tiantan Biological Products, Hualan Biological, Pacific Shuanglin Bio-pharmacy, Green Cross, Shenzhen Weiguang Biological Products Co., Ltd., Xinjiang Deyuan Biological Engineering Co., Ltd., Sichuan Yuanda Shuyang Pharmaceutical Co., Ltd., and Nanyue Biopharming Co., Ltd.
Currently, all immunoglobulins in the Chinese market are made in China, which are not yet allowed to be imported because of several perspectives, such as the safety of China. The production materials for the immunoglobulin is the healthy human plasma, and the amount of plasma collection is the main factor determining its production capacity. According to statistics, the amount of plasma collection in China is 9,455 tons in 2021 and roughly estimated to be about 10,000 tons in 2022. Conservative estimates suggest that China's actual plasma demand exceeds 15,000 tons. This gap in demand will further increase as the popularization of PH4 in COVID-19 infection and the expansion of indications in the future.
In China, the collection and use of raw plasma should follow strict regulations, and the amount of plasma collected will not be greatly increased in the short term. At the same time, negative factors such as epidemic containment and the increase in the number of infected people in society have restricted the development of plasma collection activities to a certain extent, which directly affects the supply of raw plasma.
China's 14th Five-Year Plan has increased the construction of plasma stations, and several provinces, including Yunnan, Inner Mongolia, and Henan, have made clear their plans to expand the construction of subsequent plasma stations. It can be predicted several Chinese blood product companies are expected to see significant growth in the number of plasma stations during the 14th Five-Year Plan.
In addition, in terms of supporting capacity construction, a number of Chinese blood product manufacturers have made early plans, including Tiantan Biological, Weiguang Biological Products Co., Ltd., Bohui Innovation, and Sichuan Yuanda Shuyang Pharmaceutical Co., Ltd, have invested in new production capacity, aiming to expand the production capacity of blood products, some of which have already been put into use. In line with the construction efforts of plasma stations during China's 14th Five-Year Plan, the capacity of blood products made in China is expected to rise even higher in the future from an overall perspective.