Eliminate hidden dangers of medication, try our best to solve the problem of children's medication shortage

On the eve of International Children’s Day, the website of the Drug Evaluation Center of the State Drug Administration (hereinafter referred to as the Center for Drug Evaluation) quietly changed-the "Children's Drug Column" was officially opened.
The column gathers information on policies, regulations, technical guidelines and other information in the field of children's medication.
In the future, it will become an important window for enterprises, doctors, and the public to understand national policies and regulations on children's medication, grasp R&D technical requirements, and interact with the drug regulatory authorities.

   "Since this year, the Center for Drug Evaluation has taken'supporting the development of children's medicines' as one of the practices of'Deep Chemistry History and I will do practical things for the masses'.
The column is set up to encourage and promote the development and innovation of children's medicines.
" According to Kong Fanpu, director of the review center, in recent years, the drug regulatory department has taken active steps to introduce a series of policies and measures to encourage children's drug application and priority review and approval.
After nearly three years of reform and practice, a stage result has been achieved: children's drug review The standard system and evaluation methods are gradually improved, and the R&D vitality has been significantly improved; revised and supplemented the information on children's drug use in the drug inserts on the market to guide the rational use of pediatric clinical drugs; a batch of clinically urgently needed children's drugs have been approved for marketing first, which better meets the needs of pediatric clinics Medication needs.

  Responding to urgent clinical needs

  According to Wang Xiaoling, director of the Department of Pharmacy at Beijing Children’s Hospital affiliated to Capital Medical University, the clinical dilemma of “children’s medicine depends on breaking, and the amount depends on guessing” has a long history: children’s special medicines are not abundant enough, and children’s acceptance is poor, suitable for young children Lack of dosage forms and specifications—"Entrusted by the former Department of Pharmaceutical Affairs of the Ministry of Health in 2011, Beijing Children’s Hospital joined 15 large children’s hospitals across the country to investigate the current situation of children’s medications.
The results showed that there were only 46 types of special drugs for children, accounting for 15 4.
37% of the common catalogue of pediatric medicines in hospitals; less than 30% of the suitable dosage forms for children under 2 years old.
Project data from Beijing Children's Hospital from 2011 to 2019 show that at least 45% of the drug inserts lack the usage and dosage for children.
"

  In order to solve the problem of the shortage of medicines for children, in 2014, six departments including the former National Health and Family Planning Commission, the National Development and Reform Commission, and the former State Food and Drug Administration jointly issued the "Several Opinions on Protecting Children’s Drugs".
Various links such as ensuring production and supply put forward specific requirements for ensuring the use of children's medicines.
In 2016, the former National Health and Family Planning Commission, the Ministry of Industry and Information Technology, and the former State Food and Drug Administration organized pediatric clinical and pharmaceutical experts to formulate the first batch of "List of Children's Drugs Encouraging Research and Development" (hereinafter referred to as "List") according to clinical needs; 2017 , In 2019, the second and third batches of "Lists" were released successively.

   "The Center for Drug Evaluation continues to encourage the declaration and review of the varieties in the "List".
The second-class improved new drug chloral hydrate/syrup combination package approved for marketing at the end of March this year is the first batch of varieties in the "List".
" Yang Zhimin, director of the Department of Clinical Medicine, said that this product is a sedative drug, approved for sedation and hypnosis before examination and operation of children.
For many years, my country has only this variety of medical institution preparations, and lack of marketed drugs.
The product approved for marketing this time is improved on the basis of the overseas marketed chloral hydrate oral liquid and the preparations of medical institutions in my country, and it has realized the children's dosage.
Accurate measurement improves taste suitability.

   "As of now, 12 "list" varieties have completed the technical review and approved for marketing, 11 "list" varieties are under review for marketing applications, and another 5 "list" varieties have been approved for clinical trials.
" Kong Fanpu Introduction, especially since the implementation of the newly revised "Administrative Measures for Drug Registration" on July 1, 2020, review resources have further returned to clinical urgent needs, in accordance with the "Priority Review and Approval Work Procedures for Drug Marketing Authorization (Trial) issued by the National Medical Products Administration" ", "New varieties, new dosage forms, and new specifications of children's drugs that meet the physiological characteristics of children" can apply for the priority review and approval procedures.
To this end, the Center for Drug Evaluation has opened up an independent review channel for children's drugs, established a special label for "children's drug", and proactively served in communication, acceptance, review and other links to improve the efficiency of variety processing and ensure that high-quality children's drugs are listed as soon as possible.

  The data shows that up to now, the total number of children's drugs approved for marketing through the priority review channel has reached 32.
Since 2021, 12 children's drugs have been approved for marketing, and the number of completed and review speeds have been significantly improved.

  Eliminate hidden dangers of medication

  The incomplete specifications and small dosage forms for children have caused the clinically to divide the adult dosage forms and specifications for use in children.
"In 2018, the Beijing Children’s Hospital ward pharmacy oral drug division survey showed that there were 99 types of tablets in the inpatient pharmacy.
79 types need to be divided into doses, and individual varieties for premature infants need to be split to 1/25 or even 1/50.
” Wang Xiaoling introduced that the split of drugs can easily lead to a series of problems such as decreased efficacy, inaccurate doses, and contaminated drugs.
Children's health poses risks.
In addition, the lack of clinical trial data for children's drugs, the lack of instructions for the usage and dosage of children's indications, the small number of pediatric clinical guidelines starting late, and the lack of evidence-based guidelines for children's drug use are also potential safety hazards for children's drug use.

  In order to solve the pain points of pediatric clinical medication, ensure the safety and effectiveness of children's medication, and solve the lag in the revision of drug instructions in the clinical work of children's medication in my country, especially the indications, usage and dosage, precautions, and adverse reactions for children that have been researched.
Issues such as the inclusion of the instruction booklet cannot be delayed.
To this end, the Center for Drug Evaluation and the National Children's Medical Center worked closely to set up the "China Children's Drug Instructions Standardization Project" to jointly organize research and advancement.

  Yang Zhimin introduced that in June 2018, the standardization and supplementation of children's medication information in the drug inserts on the market was officially launched.
The Center for Drug Evaluation uses data resources from children’s medical institutions and adopts real-world research methods to improve children’s application information as soon as possible to guide clinical rational use of drugs.
It has successively reviewed and screened two batches of the list of varieties and specific revisions for the proposed revision of the instructions, and made them public to the public solicit opinions.
The first batch of marketed drug inserts with increased indications and usage and dosage for children was officially released on May 31.

  Stimulate research and development vitality

   “To solve the problem of children’s drug shortage, we must first solve the dilemma of insufficient dynamism in children’s drug research and development.
It requires the joint efforts of relevant departments to create a better industrial development environment.
" The review center has issued a number of technical guidelines specifically for children's drug research and development, and through policy guidance and the establishment of a standardized evaluation system, it attracts enterprises to pay more attention and investment in children's drug research and development.

   “Benefiting from the review policy support and the growth in demand for children’s medicines, domestic children’s medicine R&D platforms have been built, R&D investment has been continuously strengthened, and corporate R&D capabilities have also increased.
However, children’s medicines have long R&D cycles, high costs, low profits, and insufficient corporate R&D motivation.
The phenomenon has not been completely changed.
" Hong Liping, vice president of Kangzhi Pharmaceutical Co.
, Ltd.
, said that compared with adult preparations, the selection of excipients and their safety in the research and development of children's medicines, young animal experiments, and key technological breakthroughs in children's medicine research, etc.
Faced with no small challenge.
The return on investment of enterprises is not high, which objectively hinders the research and development of children's medicines for a long time.

  But Hong Liping, who is in charge of the company's new drug research and development, is heartened that the above-mentioned problems have received the attention and attention of the review department.
“In recent years, the Center for Drug Evaluation has successively issued a series of technical guidelines specifically for children’s drug use.
This shows that the review department attaches great importance to children’s drug R&D and technical evaluation.
This is the same for children’s drug R&D and even the entire children’s drug industry.
The big news is good, and the enthusiasm for research and development of enterprises is high.
” Hong Liping said that the release of the technical guidelines has brought hope to companies that have been deeply involved in the children's medicine industry but have encountered market and policy bottlenecks.

  In order to further understand the actual needs and development difficulties of children's medicines, on May 27th, Kong Fanpu led the review team once again to investigate a children's medicine research and development company in Shandong, and carried out on-site communication and guidance based on the actual situation of the company's research and development.
"As a drug review department, we are very willing to maintain good communication with companies regarding the actual difficulties and solutions in the development of children’s drugs, and do our best to provide support and assistance, so as to ensure the effectiveness and safety of the drugs.
We will make every effort to promote the research and development of Chinese children's medicines.
" Kong Fanpu said.

  Innovative research model

  In 2017, the “Thirteenth Five-Year Plan” major new drug creation and technology major special project “Children’s Drug Varieties and Key Technology Research and Development” was established, and Ni Xin, director of the National Children's Medical Center and dean of Beijing Children's Hospital, served as the project leader.
He introduced that in response to the characteristics and clinical needs of children’s medicines, the research group will combine production, learning, research, and medicine to build key technologies and improve product research capabilities as the core, and use new formulation technologies, new concepts and new methods to develop urgent clinical needs.
Innovative preparations and multi-dose forms of children's medicines.
After more than 3 years of hard work, the project has achieved initial results and will be completed in the near future.

   “Clinical research on medicines for children is very difficult, and the recruitment, safety and benefit protection of children are far more difficult than adults.
” When introducing the research results of the subject, Ni Xin said that many pediatric clinical preparations have been used in medical institutions for many years, and the efficacy is Excellent and widely acclaimed, but due to the high cost of application and registration, it has been difficult to achieve conversion.
After the Drug Approval Center releases technical documents supporting the development of children's drugs with real-world evidence, hospitals can collect past clinical application data and use real-world data research results to bring medical institution preparations to the market.
"After the establishment of a mechanism for real-world data for drug registration, the pediatric system will benefit the most.
" He said happily.

  However, the clinical application data of preparations in medical institutions are basically real-world data.
Compared with the randomized controlled trial data of evidence-based medicine research, real-world data lacks strict quality control of recording, collection, storage and other processes in most cases.
This causes problems such as incomplete data, missing key variables, and inaccurate records, which brings difficulties to subsequent registration.
"It is gratifying that during the research and development period, the Center for Drug Evaluation has actively communicated with us many times to guide us on how to transform real-world data into real-world evidence that can support drug registration, effectively accelerating the product launch process.
" Ni Xin said.