Single anti-biopharmaceuser clinical application "multi-point flowering", experts remind: pay attention to the real world to add preservatives potential risks

Biomedicine has entered a new era.
to the fastest-growing sub-sector - mono-resistance, for example, after 2010 China's large molecular drug research and development is on the rise, coupled with drug review reform, capital market heat, domestic antibody new drug research and development rapidly erupted.
statistics, the number of new antibody drug declarations since 2015 has reached double digits, in 2017 and 2018 have exceeded 40, in 2020 the number of declarations is broken records reached 81, compared with 2013 the number of new antibody drug declarations in China has a qualitative leap. Although the above
declarations include some fusion protein drugs such as antibody fusion protein, IL-15, VEGF/FGF and other new drugs, but the domestic 260 polymer drug declaration, single resistance has 178, accounting for 68% of the number of new drugs received.
2020, the FDA has approved a total of 96 antibody drugs, of which 61, or two-thirds, were approved in the five years 2016-2020.
in China, there are currently 23 domestic antibodies on the market, plus 39 approved imported monoantibodies, a total of 62 antibody drugs approved.
, including beva bead mono-resistance, curt-bead mono-resistance, Adamo single-resistance, lytoxi-single-resistance and other star products of biosynthic drugs have been listed.
" domestic biological medicine starting point is high, rapid development.
, however, innovative monoantygens are still clinically lacking.
" authoritative expert Dr. Xu Zengjun recently for the domestic biopharmaceutical industry praise at the same time also do not forget to remind the industry to further innovation and upgrading.
2021 and the next decade, the global biologics sector continues to have patents for heavy varieties expired, providing greater structural opportunities for biologics.
"14th Five-Year Plan" clearly includes biomedicine in the special project.
new era, biomedicine will focus on key core technologies and products, focus on effectively solving the "neck" problem, for the development of high-quality biomedicine to provide strategic support.
, the wave of cluster innovation will have an unprecedented and profound impact on the biopharmaceity industry chain, supply chain and value chain.
only if you understand the trend will it become part of it.
years, the domestic biological medicine has laid a solid foundation.
the new decade, what kind of new vision will it usher in? 1 Industry shift speed up, clinical use of the proportion of sharp rise with a new round of scientific and technological revolution and industrial changes continue to deepen and accelerate, the past people respected the "noble" drugs gradually civilian, and single anti-drug specificity is high, toxic side effects are small, for a variety of malignant tumors have significant efficacy, greatly improve the clinical access of biological drugs.
Such as Fuhong Hanyu's Adam single anti-"Handayuan" December 7, 2020 by the State Drug Administration approved the listing, for the treatment of rheumatoid arthritis, strong straight spina bifida and plaque-like psoriasis.
This is Fuhong Hanxuan in the domestic market the first bio-similar drug lytoxidan resistance, the first Central European double batch of domestic bio-similar drug querceto-pearl mono-resistance, successfully won the third single anti-biological drug.
Hengrui, Xinda, Sansheng Guojian, Kangfang, Tianyuan Biological and other front-line soldiers on the lytoxi mono-resistance, beva-pearl single-resistance and other clinically demanding star products are laid out, and the research and development pipeline is quite distinctive;
the domestic market, "Chinese" bio-similar drugs have also begun to fight overseas.
Fuhong Hanxuan's Quto Zhudan successfully landed in the European market, has been listed in the United Kingdom, Germany, Portugal, Spain, and won the recognition of the British National Health Service, has entered London's world-renowned top general hospitals and cancer specialist hospitals, including the Royal Marston Hospital, King's College Hospital, University Hospital of London, St. George's Hospital and so on.
China's biological medicine has formed a "competitive internationalization" of the new pattern.
drug shows the obvious advantages that traditional drugs do not have, and brings new drug choice and cure hope to the treatment of clinically incurable diseases.
80% of the top 10 drugs in global sales in 2019, biopharmaceders account for more than 80%, mostly antibody drugs.
in the past five years, the proportion of biological drugs represented by monoantials at home and abroad in clinical use has increased significantly.
meters net recently released "China's public hospital terminal drug pattern" report more intuitively pointed out that in 2015-2019 public hospital terminal anti-tumor drug single-year sales (in terms of the average retail price of the terminal) growth rate of 20% to 40% range, especially in 2017 began to surge, just three years out of all the shareholders most want to see the curve.
affected by medical insurance factors, many anti-tumor drugs borrowed DTP pharmacies and other forms in the retail side.
2017-2019, the proportion of sales of single anti-drug drugs increased from 24.02% to 40.49% among end-of-line anti-tumor drugs in urban retail pharmacies in China.
industry experts have said, "the single resistance as the representative of biological drugs can be described as the rise of the counter-trend."
such high growth is affected by the epidemic, in the first half of 2020 China's three terminals in the six major markets drug sales increased by -10.7% YoY, the proportion of drugs in public hospitals fell to 33.3% in the environment.
curt bead monoanti, beval bead single resistance, lytoxi single resistance 3 varieties occupy more than 90% of the domestic single anti-market, indicating that the safety and effectiveness of these biological drugs advantages, in clinically has been more and more recognized by doctors, patients and family members.
if the variety of health care negotiations further increased, demand release, technology iteration, compared with the United States biological agent market share accounted for more than half of the scale, the domestic biological drugs still have a huge space to dig.
from the development trend of the world biopharmaceutical industry, is currently in the beginning stage of large-scale industrialization of biopharmaceuticals.
industry expects that the global biopharmaceutical industry will gradually become the guiding industry of the world economy.
However, China's biopharmaceuticals and biosynthics market share accounts for only 1% of the world, with the strong support of China's biopharmaceutical industry policy, the industrial scale continues to grow, research and development innovation investment continues to increase, driven by intelligent technology, the biopharmaceutical industry is a gathering trend, the next decade is a rare window period.
the above-mentioned experts, "at the policy level, the three medical associations promote effective supply."
from the last three years of the domestic terminal best-selling brand TOP20 changes can be seen in the industry is accelerating the shuffle.
top 10 best-selling brands in 2017 without monoantial drugs, and by 2019 three monoantrants have entered the top 10.
, the proportion of clinical use of biological drugs will gradually increase.
"2 In the real world, the potential risk of benzoyl alcohol as a preservative is increasing with the increasing depth and breadth of clinical use of biologics, and real-world cases are attracting more and more industry attention.
scientific understanding of biological drugs is also improving, and through practical summary to fully understand the treatment benefits and risks of different populations.
In the past few years, U.S. clinical experts have found more than a dozen serious adverse reactions to the death of newborns caused by the physiology of the central vascular catheter, which contains benzoyl methanol, in real-world clinical use.
, it is understood that biological agents are protein, peptides and other large molecule injection preparations.
General single-dose injections are sterile by sterilization, while non-sterilized injections and multiple doses of injections are prescribed or diluted with antibacterial preservatives to prevent possible microbial contamination during manufacture, storage and use.
as one of the components of preparation prescription, the correct use of preservatives plays an important role in ensuring the quality of medicines.
, however, many preservatives themselves have certain toxic side effects, which can cause hidden dangers in terms of drug safety.
EMA has issued a number of guidance documents specifically on benzoyl alcohol as a pharmaceutical preservative, focusing on the risk of neonatal death due to the drug's phenylethanol content.
U.S. clinical case study found that infants, pregnant and lactating women need to be careful about the use of phenyl methanol-containing drugs, and to guard against the accumulation of toxicity from long-term use.
many clinical experts worry that the toxicity of preservatives is much unknown, due to the lack of relevant research, clinically lack of effective prevention management.
is often overlooked clinically, " says Professor Zhao Zhigang of the Department of Pharmacy at Tiantan Hospital in Beijing, affiliated with Beijing Capital Medical University.
removal of benzoyl alcohol in the body is affected by factors such as age (metabolic development), polymorphism of ethanol dehydrogenase in different races, and it is difficult to determine its threshold dose.
the consequences of ignoring this issue? According to Zhao Zhigang: "In addition to causing the risk of neonatal death, the clinical use of benzoyl alcohol as a preservative intravenous infusion may cause adverse reactions including: hemolytic effect, bruising at the injection site;
comprehensive foreign clinical experience, with the continuous progress of science and technology, try to avoid adding preservatives to drugs has become a new clinical appeal.
In addition, relative to Chinese medicine, chemical drugs, biological drugs in the domestic clinical use of the time is not long, in the real world, the vast number of clinicians (especially primary doctors), patients to its understanding and understanding need to continue to improve, similar to this addition of preservatives caused by adverse reactions will also be paid attention to.
"3 regulatory upgrade, standardized use of the urgent face of social concerns, domestic and foreign regulatory agencies to strengthen the preparation of antimicrobial preservatives control requirements.
from the EMA-related guidance documents, regulators encourage the use of technological innovation to protect against preservatives.
China's concept of supervision is also in line with international standards.
the 2020 edition of the Chinese Pharmacopoeia and other regulations on the use of antimicrobials in drugs tend to be strict.
" injections should avoid adding antibacterial agents, especially mercury-containing anti-bacterial agents, to intermediates and finished products as far as possible.
shall not be added to the freeze-dried preparation for single-dose injection, unless otherwise specified, and no antibacterial agent shall be added to single-dose injection.
For multi-dose products, the use of antimicrobials should be shown to not affect the safety and ability of the product, depending on the contamination that may occur during use and the recommended maximum time of use after opening the lid.
addition of antibacterial agents should be in the effective antibacterial range of the use of a minimum amount, and should set the control range.
" carefully tasted the new version of the Chinese Pharmacopoeia, clearly feel the domestic regulatory layer in strict management to add preservatives.
is also easy to ignore, but equally important: the clinical standardization of the use of preservatives biological drugs.
In practice, intravenous infusion drugs with preservative thinners in multiple doses and packaging are often taken home by the patient for safekeeping after the drug is opened due to the actual conditions of the hospital (e.g. refrigerator capacity, quantity).
, is there a potential risk of patients being taken back to the hospital for infusions at the next treatment? "There are certain risks in patient self-storage management, and it is desirable to raise the awareness of doctors, nurses and patients about the relevant norms to avoid adverse events caused by improper storage of drugs, reduced effectiveness of drugs and disputes between doctors and patients," Zhao said.
," he points out, "even if dilution is carried out with a dilution containing preservatives, the standard storage conditions for biological drugs are still very strict, and it is difficult for the average patient to ensure that infusion drugs are stored strictly in accordance with the regulations on the way back and forth to the hospital and at home."
if not properly preserved, it may cause adverse events in subsequent infusions.
, doctors, patients, nurses need to pay more attention to the poorly preserved drugs due to reduced effectiveness of the patient's condition can not be effectively controlled.
Because of the characteristics of the tumor itself, the progression of the disease after treatment may be judged as normal disease progression, and it is not possible to effectively determine whether the real-world drug storage is due to the reduced effectiveness of the drug and missed the opportunity for effective control."
, in the new era, the state demands a strong and effective solution to the pain point problem.
With the continuous development of technology, anti-preservative-free mono-anti-biological drugs have become the dominant, the current domestic market of single-anti-drugs, in addition to imported querceten beads monoanti, are not containing preservatives.