Children's use of children's medicine, consideration of children's medicine research and development

Medicine is a magic weapon for saving people, but if it is not used properly, it can cause great harm
.
"It is a drug that is three-point poisonous".
For adults, improper use of drugs may cause harm, and if it is placed on children, it may cause more serious consequences
.
On May 26, 2021, the State Food and Drug Administration held the on-site promotion meeting of "deepen the history and practice, I will do practical things for the masses".
The meeting pointed out that it is necessary to focus on ensuring drug safety and do practical things, highlighting the key group of children, and using strong Supervision to ensure drug safety
.
And set up a column, but also to encourage and promote the research and development and innovation of children's medicine
.
In recent years, the drug regulatory department has taken active actions and issued a series of policies and measures to encourage children's drug application and priority review and approval.
Improve the research and development vitality significantly; Amend and supplement the information on children's drug use in the package inserts of listed drugs to guide the rational use of pediatric clinical drugs; A batch of clinically urgently needed pediatric drugs are given priority to be approved for marketing, which better meets the needs of pediatric clinical drugs
.
Figure 1.
Pediatric Drug Column 1 Top-level design and policy support for pediatric drug review and approval During the period from 2011 to 2022, the state has issued many policies to encourage pediatric drug application and priority review and approval, and gradually improve the supervision system for pediatric drug use.
For details, see Table 1 below
.
Table 1.
Pediatric drug policy support during 2011-2022 2 Insufficient types of children's drugs, "in short supply" China's children's drug supply is insufficient, showing the market characteristics of "three less and two more", namely: fewer varieties of children's drugs, fewer dosage forms, Fewer dosage specifications, more generic drugs, and more adverse reactions
.
Moreover, children's medicines have bad taste and poor medication compliance.
For a long time, there has been a situation of "medication depends on breaking, dosage depends on guessing", and "children's discretionary reduction".
Children's drug abuse seriously damages children's health.

.
The development of paediatric drugs in China started relatively late, and the technology research and development was relatively backward
.
At present, as a special group of medicine consumption, the types of children's medicines in China account for less than 10% of all medicines, and more than 90% of children's medicines in China are non-child-specific medicines
.
There is also a lack of suitable dosage forms and specifications for children, especially for young children and neonates
.
Figure 2.
The proportion of children's medicines to all medicines in China in 2020 According to relevant statistics, as of January 1, 2021, the number of approved products (chemical medicines, traditional Chinese medicines and biological preparations, etc.
) There are 228,448 drugs (8,487 according to the composition), of which the total number of approval documents for pediatric drugs (calculated by children, pediatrics, children, etc.
) is 3,826 (241 ingredients); in the field of chemical drugs, the total number of approval documents is 151,473 (2195 ingredients), and the total approval number for children's medicines is 1598 (55 ingredients)
.
According to the "2019 Statistical Bulletin of National Economic and Social Development", at the end of 2019, the national population aged 0-15 was 249.
77 million, accounting for 17.
8% of the total population
.
However, China's children's drug market currently accounts for about 5% of the total size of the entire pharmaceutical industry, reflecting that the children's drug market is far from saturated and the future market space is broad
.
3 To develop medicines for children, what should we do? 1 In terms of preparations, the basic principles of drug development for children are basically the same as those for adults.
Pediatric patients should be provided with drugs that have been evaluated and confirmed to be suitable, and children should be prevented from receiving unnecessary clinical trials
.
Considering the complexity of clinical research on children's drug use, it is necessary to consider relevant research applicable to children's drug use as early as possible during drug development
.
Based on differences in physiological characteristics, pharmacokinetics and pharmacodynamics, the pediatric population can be divided into the following age groups with reference to the recommendations of ICH E11(R1): Preterm neonates, term neonates (0-27 days) Infants (28 Days - 23 months) Children (2-11 years old) Adolescents (12-16-18 years old <depending on the region>) According to ICH Q8, the main points to consider in the development of paediatric pharmaceuticals include: API, excipients, route of administration and dosage form , dosing frequency, packaging system, patient acceptability, instructions, quality control, neonatal,
etc.
Figure 3.
Pediatric drug development strategy In addition, the selection of appropriate excipients is one of the key elements in pediatric drug development
.
When selecting excipients, the child's age, weight, developmental degree, frequency of administration, planned course of treatment, and commonly used concomitant medications may increase the exposure of excipients that may result in full consideration
.
Here are a few excipients that require extra attention in children
.
Table 2.
Safety risks of excipients 2 In terms of physiology, in addition to the formulation development, it is necessary to focus on the formulations developed and the excipients used, and the differences in physiology of children and adults should also be considered to ensure the tolerability of the drug in children.
effectiveness
.
① Biochemical differences lead to different ADME ② Different effect requirements on drugs, etc.
Children's medication is generally calculated according to body weight, and adult medication is generally calculated according to dose, such as "amoxicillin", a drug affected by gastric acid, 3-month-old infants have low gastric acid and absorption Fast, the required dose is small, 30mg/kg, once every 12h; for adults, 0.
5g/time, once every 8h
.
Conclusion Therefore, the pharmaceutical development of children's medicines is generally consistent with the methods of conventional drug development, focusing on the physiological and pathological characteristics of the children's population, rationally selecting the route of administration and dosage form, and ensuring the accuracy of measurement, convenience of administration, and patient availability.
acceptability,
etc.
References: [1] EMA (2019), Annex to the European Commission Guideline on 'Excipients in The Labelling and Package Leaflet of Medicinal Products for Human Use' (SANTE 2017 11668).
[2] Medicines for Children (Chemicals) Guidelines for Pharmaceutical Development [3] CDE official website