Similarities and Differences of Regulation of Plasma Used in the Production of Blood Products at Home and Abroad※
At present, the raw material plasma of blood product enterprises in China is low in plasma volume and in comprehensive utilization. It is suggested the current situation of the shortage of plasma protein products in China be alleviated by implementing the system of listing permit holders, promoting the centralized detection of raw material plasma and comprehensively utilizing the surplus plasma separated from clinical samples.
In Europe, around 70% to 80% of blood plasma used by blood product manufacturing companies comes from clinically recovered plasma, while 20% to 30% is sourced from plasma collection stations. In contrast, in the United States, approximately 80% to 90% of raw plasma is obtained from plasma stations, with the remaining 10% to 20% coming from voluntary blood donation organizations.
In the United States, there are no restrictions on setting up plasma collection centers. It operates purely based on market mechanisms. The FDA's main role is to ensure that these centers meet certain standards. To be recognized, companies must comply with federal laws and pass FDA inspections. They can then plan their own plasma collection activities accordingly.
All blood collection organizations are required to obtain a license from the FDA. The FDA conducts random inspections of these organizations every two years. During an inspection, the organization being inspected must provide all necessary materials requested by the inspector. The FDA inspectors have the authority to conduct inspections at any time and can order a center to cease operations or make improvements if necessary.
Blood product companies audit these plasma centers once every three years. In the United States, individual plasma collection centers do not perform testing on collected plasma samples themselves; instead, they send them for centralized testing and storage elsewhere.
In China, the blood plasma used by blood product manufacturing companies is sourced exclusively from plasma collection stations. These stations operate as independent legal entities, typically as wholly-owned or majority-owned subsidiaries of the blood product companies. Each plasma collection station is authorized to supply raw plasma to only one blood product manufacturer with which it has signed a quality responsibility agreement. It is strictly prohibited for them to supply raw plasma to any other entities.
The country maintains a centralized planning and establishment system for plasma collection stations, ensuring that within a designated plasma collection area, only one station is permitted. The administrative management of these stations falls under the jurisdiction of health and wellness regulatory authorities, which are responsible for approval and conduct quarterly supervisory inspections. Additionally, the blood product companies are required to perform on-site audits of their affiliated plasma collection stations at least twice a year. It is mandatory for plasma collection stations in the country to test each unit of collected plasma to ensure quality and safety standards are met.
In the United States, eligible plasma donors are those who have successfully passed the donor screening process—comprising a health inquiry, physical examination, and blood sample testing—on two separate occasions, with the interval between the two being greater than the minimum required but not exceeding six months. Donors are allowed to donate plasma twice a week, with at least two days between donations. The volume of plasma donated is determined by the donor's weight, typically not exceeding 880 mL per session, and donors must be under the age of 69. If a donor has undergone procedures like tattooing or acupuncture, and cannot provide proof of the use of sterilized needles, they must wait for one year before donating plasma.
The "Chinese Pharmacopoeia" 2015 edition, Volume III, sets clear guidelines for plasma donors: the age range is from 18 to 55 years old, with the possibility of extending up to 60 years old for regular donors. Donors are required to undergo physical examinations and plasma testing, and can only donate after passing these assessments. The maximum volume of plasma collected from a donor in a single session should not exceed 580 mL (including anticoagulant solution, with a calculated mass ratio not exceeding 600 g), and the interval between donations must be no less than 14 days.
In developed countries like the United States, a common method for screening viruses in raw plasma is through enzyme-linked immunosorbent assay (ELISA) combined with nucleic acid amplification testing (NAT). If no disqualifying information is received about the plasma donor within 60 days, the collected plasma from before that period can be used for production. This is known as a 60-day quarantine period.
According to the regulations, the quarantine period for raw plasma is set at a minimum of 90 days. This means that after collecting and testing qualified raw plasma, it must be stored for 90 days. After retesting the plasma samples from the donors and confirming their virus-free status, only then can the qualified raw plasma collected 90 days ago be used in production. In 2008, further regulations were introduced stating that if blood product manufacturers add virus nucleic acid amplification testing to their enzyme-linked immunosorbent assay (ELISA) method for screening plasma samples, the time limit is set at a minimum of 60 days from the day of plasma collection.
东海2023※
At present, China collects about 10,000 tons of plasma each year and has 287 plasma stations in operation. However, when compared to the United States, there is a significant gap of four to five times in our blood plasma supply.
Currently, China only offers 14 different types of blood products. This puts us at a relatively low level in terms of product variety, per capita usage, and application areas.
Albumin is the most popular type, with about 60% of it being imported. However, there's a great opportunity for domestic human serum albumin to replace these imports. Immunoglobulin has the highest market share worldwide, but in China, its usage per person is much lower than in the United States due to limited academic promotion and clinical awareness. This indicates significant potential for growth.
Plasma makes up approximately 55% of the total blood volume and contains 90% water and 7% plasma proteins. Among these proteins, albumin accounts for 60%, immunoglobulin for 15%, clotting factors for 4%, and other protein components make up the remaining 21%.
Most blood products cannot be manufactured through recombinant methods and can only be extracted from healthy human plasma. The global annual plasma collection volume is around 60,000 tons. In terms of regional distribution, the United States ranks first in plasma collection volume, accounting for over 60% of the total.
Plasma donors can only donate plasma at the single plasma collection station designated within their registered residence area. They are not allowed to donate plasma across different collection areas or through mobile plasma donation. The interval between two plasma donations must not be less than 14 days. The total number of plasma donations within one year must not exceed 24 times. Each plasma donation should not exceed 600 grams (including anticoagulants). Blood test items: blood type, hemoglobin content, serum total protein content, alanine aminotransferase, hepatitis B virus surface antigen, hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV-1 and HIV-2) antibody or antigen antibody combination test, syphilis spirochete antibody, serum/plasma electrophoresis. Physical examination: 18-55 years old, the age limit for regular plasma donors can be extended to 60 years old; weight: men greater than or equal to 50KG, women greater than or equal to 45KG; blood pressure; pulse, etc.
Plasma collection station can only supply raw plasma to a blood product manufacturing unit that has signed a quality responsibility agreement with it, and it is strictly prohibited to supply raw plasma to any other units. Quarantine period: Enterprises should establish a traceability system for raw plasma to ensure that each unit of plasma can be traced back to the plasma donor and can be traced back at least 60 days prior to the last collection of plasma from the donor.
China has had restrictions in place since 1985 on importing blood products, with the exception of human albumin. In 2002, China expanded these restrictions to include a ban on importing human albumin from areas affected by mad cow disease. However, in November 2007, we made an exception and started allowing the import of recombinant human clotting factor VIII. It's worth mentioning that imported coagulation factor VIII derived from human plasma is still not allowed.
Batch issuance: a mandatory inspection and review system for each batch of blood products before they are released or imported. Products that fail the inspection or do not receive approval during the review process shall not be allowed to be sold on the market or imported.
The production of blood products in China is still mainly based on the low-temperature ethanol method, and the products are limited to more abundant or easily purified albumin, immunoglobulin, fibrinogen, coagulation factor VIII and other more than 10 kinds of products in plasma.
There are over 100 types of proteins and factors in the blood, and large foreign companies are able to separate more than 20 varieties using chromatography. Intravenous Immunoglobulin (IVIG) is the most widely used immunoglobulin product.
