[quick news] 10 billion biological products were modified, affecting 26 enterprises

Recently, the State Food and Drug Administration issued a notice to revise the instructions for intravenous human immunoglobulin (pH4) and freeze-dried intravenous human immunoglobulin (pH4), mainly adding warning words, and revising the [adverse reactions], [precautions], [elderly medication] and other items There are two kinds of human immunoglobulin: intramuscular injection and intravenous injection Intravenous injection of human immunoglobulin is mainly used to treat primary immunoglobulin deficiency, secondary immunoglobulin deficiency and autoimmune diseases In the catalogue of basic medical insurance drugs in Beijing, the reimbursement scope of immunoglobulin products is also strictly defined: severe infection rescue, severe autoimmune diseases, and limited to hospitals above grade II According to the database of drug intelligence assistant and key monitoring drugs, intravenous immunoglobulin was listed as assistant drugs in qianfushan Hospital of Shandong Province, and as key monitoring drugs in Gushi County and Dengzhou city of Henan Province In addition, according to the domestic drug database of pharmaceutical intelligence, 26 domestic enterprises hold the approval documents for the production of intravenous human immunoglobulin (pH4), and 11 domestic enterprises hold the approval documents for the production of freeze-dried intravenous human immunoglobulin (pH4) The annual batch sales of the two drugs are shown in the figure below, in which intravenous immunoglobulin (pH4) ranks the second among all batch biological products, with a total sales of 46.207 billion yuan In the annual sales, the peak sales reached 6.804 billion yuan, with a minimum of 1.253 billion yuan In 2018, the sales reached 6.247 billion yuan, and Chengdu Rongsheng Pharmaceutical Co., Ltd was the best selling enterprise; frozen immunoglobulin (pH4) ranked the second among all batch biological products The total sales of human immunoglobulin (pH4) for dry and intravenous injection reached 1.361 billion yuan, with a peak of 236 million yuan per year, a minimum of 21 million yuan, and a sales volume of 136 million yuan in 2018 Guangdong wellen bio Pharmaceutical Co., Ltd was the best company for sales Figure 1: Top 10 in the sales ranking of biological products issued in batches Figure 2: annual statistics of sales of human immunoglobulin (pH4) for intravenous injection Figure 3: annual statistics of sales of human immunoglobulin (pH4) for intravenous injection Figure 4: annual statistics of sales of human immunoglobulin (pH4) for freeze-dried intravenous injection figure 5: annual statistics of sales of human immunoglobulin (pH4) for freeze-dried intravenous injection In order to further ensure the safety of drug use by the public, the State Drug Administration decided to add warning words to the instructions for intravenous injection of human immunoglobulin (pH4) and freeze-dried intravenous injection of human immunoglobulin (pH4), and revise the [adverse reactions], [precautions], [elderly drugs] and other items The relevant matters are hereby announced as follows: 1、 All manufacturers of intravenous human immunoglobulin (pH4) and freeze-dried intravenous human immunoglobulin (pH4) shall, in accordance with the measures for the administration of drug registration and other relevant regulations, put forward the supplementary application for the revision of the instructions according to the revision requirements of the instructions for intravenous human immunoglobulin (pH4) and freeze-dried intravenous human immunoglobulin (pH4) (see the annex), and report to the Institute before March 15, 2019 Local and provincial drug regulatory authorities for filing If the revised contents involve drug labels, they shall be revised together; the instructions and other contents of the labels shall be consistent with the original approved contents Replace all drug instructions and labels that have been delivered within 6 months after the supplementary application is filed Each enterprise producing intravenous immunoglobulin (pH4) and freeze-dried intravenous immunoglobulin (pH4) should carry out in-depth research on the mechanism of new adverse reactions, take effective measures to do well in the publicity and training of drug use and safety issues, and immediately notify the drug distributors and users in an appropriate way of changes in the content related to drug safety, and guide doctors and pharmacists in the rational use of drugs 。 2、 Clinicians and pharmacists should carefully read the revised contents of the instructions for intravenous injection of human immunoglobulin (pH4) and freeze-dried intravenous injection of human immunoglobulin (pH4), and make full benefit / risk analysis according to the newly revised instructions when selecting drugs 3、 Patients should strictly follow the doctor's instructions 4、 The provincial drug regulatory authorities are requested to supervise and urge the enterprises to do a good job in the revision of relevant product instructions and the replacement of label instructions in the daily supervision It is hereby announced Appendix of State Food and Drug Administration on January 11, 2019: revised requirements of instructions for intravenous injection of human immunoglobulin (pH4) and freeze-dried intravenous injection of human immunoglobulin (pH4) (1) warning words added: Because the raw materials are from human blood, although the raw plasma is screened for related pathogens, and the measures to remove and inactivate the virus are added to the production process, there is still a potential risk of spreading some known and unknown pathogens in theory, so the advantages and disadvantages should be considered in clinical use 2、 [adverse reactions] items [adverse reactions] add the following contents: 1 Foreign clinical trials The following common adverse reactions were observed in more than 5% of the clinical trial subjects of the same foreign products: headache, chills, fever, pain, fatigue, back pain, nausea, vomiting, abdominal pain, diarrhea, reaction of infusion site, rash, pruritus, urticaria, hypertension, hypotension, tachycardia, etc 2 The following adverse reactions / events have been detected in the domestic post marketing monitoring products and similar domestic products Because these adverse reactions / events are reported spontaneously in the population that cannot be determined, the incidence cannot be estimated accurately: (1) systemic damage: chills, high fever, chest pain, discomfort, paleness, fatigue, periorbital edema, edema, systemic pain, etc (2) Damage of skin and its accessories: maculopapular rash, erythematous rash, localized skin reaction, epidermolysis, multiple erythema, dermatitis (such as bullous dermatitis), increased sweating, etc (3) Immune dysfunction and infection: allergic reaction, anaphylactic reaction, transfusion reaction, anaphylactic shock, etc (4) Cardiovascular system damage: cyanosis, palpitation, hypertension, arrhythmia, etc (5) Nervous system damage: dizziness, coma, loss of consciousness, tremor, involuntary muscle contraction, hypoesthesia, etc (6) Respiratory system damage: dyspnea, shortness of breath, apnea, wheezing, laryngeal edema, respiratory insufficiency, transfusion related acute lung injury, hypoxemia, etc (7) Vascular damage and coagulation disorders: flushing, phlebitis, etc (8) Mental disorders: agitation, mental disorders, drowsiness, etc (9) Metabolic and nutritional disorders: hyperglycemia (Note: if sugar is contained in drug ingredients, please indicate this item) (10) blood system damage: leucopenia, neutropenia, granulocytopenia, etc 3 The following adverse reactions / events are also detected in the similar products on the market in foreign countries Because these adverse reactions / events are reported spontaneously in the population with uncertain total number, the incidence cannot be accurately estimated: (1) skin and its accessory damage: Stevens Johnson syndrome, etc (2) Nervous system damage: epilepsy, aseptic meningitis, etc (3) Respiratory system damage: acute respiratory distress syndrome, pulmonary edema, bronchospasm, etc (4) Vascular damage and coagulation disorders: thrombosis, etc (5) Blood system damage: increase of plasma viscosity, hemolytic reaction, etc (6) Urinary system damage: renal function damage, etc 3、 [precautions] items [precautions] add the following contents: 1 Monitor the renal function of patients with acute renal failure, including blood urea nitrogen, blood creatinine and urine volume For patients with renal insufficiency or failure, infusion should be performed at the minimum rate The use of this product in susceptible patients may cause renal dysfunction The patients with sucrose are more likely to cause renal dysfunction and acute renal failure 2 Possible thrombotic events Patients with known risk factors for thrombotic events were monitored; blood viscosity was assessed at baseline in patients at risk of hyperviscosity For patients at risk of thrombosis, slow infusion at a minimum dose is required 3 Aseptic meningitis syndrome may occur, especially in high dose or rapid infusion 4 Hemolytic anemia may occur To monitor the clinical signs and symptoms of hemolytic and hemolytic anemia patients 4、 [geriatric medication] item [geriatric medication] item was revised as: this experimental study was not conducted, and there was no systematic and reliable reference In patients over the age of 65, the recommended dose should not be exceeded and infusion should be done slowly (Note: if other contents of the manual are inconsistent with the above revision requirements, they shall be revised together.) 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