Pediatric Drug Approval and Efficiency



"In the past, it usually took about 2 years to get the clinical approval documents for children's drugs, but now it only takes 4-6 months. Since 2016, we have got 3 clinical approval documents for children's drugs, and enterprises have really felt the acceleration of the review and approval of children's drugs." Ding Yang, deputy general manager of the R & D center of Sichuan Baili Pharmaceutical Co., Ltd., said.

The latest statistics from the Drug Evaluation Center of the State Food and Drug Administration (hereinafter referred to as the Drug Evaluation Center) show that up to now, 353 registration applications (based on the acceptance number) have been included in the priority review process, of which 40 are children's drugs, and children's drugs account for 11.33 per cent of the priority review and approval drugs. The drugs for children that have been included in the priority review involve a total of 12 indications, of which endocrine system drugs for the treatment of childhood diabetes are the majority, and others are also involved in the treatment of critical diseases such as childhood leukemia, hemangioma, and neonatal apnea. Some children's drugs with clinical value and urgently needed by patients have completed the pre-marketing technical review, such as McGastat capsules for the treatment of rare disease type C Niemann-Pick disease, tocilizumab injection for the treatment of systemic juvenile idiopathic arthritis, and A- glycosidase for injection for the treatment of Pompe disease.

Why is it difficult to develop drugs for children?

In recent years, drugs for children have received social attention. From the point of view of the commercial value of drug manufacturers, the number of patients after the listing of new adult drugs is large, the commercial return is fast, while the number of patients with children's drugs is small, the commercial return is low, often input and output upside down. Therefore, the research and development of children's drugs is not enough.

"The development of drugs for children is a worldwide problem. In most cases, it is more difficult for children to participate in clinical trials than for parents to participate in clinical trials themselves." Yang Zhimin, director of the Clinical Department of Drug Review Center, said, "The difficulties in recruiting subjects, the many ethical issues involved, the many safety concerns and the high requirements of evaluation methods for pediatric research all need to be resolved."

In addition, the research and development of children's drugs in China also faces special problems. There are no domestic R & D institutions specializing in the research and development of children's drugs, and even the vast majority of R & D institutions do not have children's drug R & D personnel, resulting in low R & D capabilities. Compared with European and American countries, the innovation ability of pediatric clinical trials in China is insufficient. Even if the drugs for children have been listed in Europe and the United States, the imitation ability of our country needs to be improved. The relevant person in charge of

Drug Examination Center said that in the face of the new situation of the liberalization of the comprehensive two-child policy, it is urgent to solve the problem of drug use for children. Since the State Council initiated the reform of the drug review and approval system, the Drug Review Center has adhered to the clinical needs-oriented approach, actively improved the priority review system for children's medication, and responded to social concerns.

How to speed up and improve the quality of the review?

"Shenzhen Children's Hospital received an 8-month-old child with red rash and joint inflammation. He was diagnosed with systemic juvenile idiopathic arthritis. Fortunately, tocilizumab injection has been approved for listing through priority review, and the child was rescued in time. The drug in 2016 to encourage children's drug priority review policy landing, officially entered the green channel, only eight months to be approved for listing." Shanghai Roche Pharmaceutical Registration Director Yang Hong introduced.

Drug Review Center has implemented a series of new policies for children's drug priority review since 2015. "As an important part of the reform of drug review and approval, the Drug Review Center attaches great importance to children's medication and strives to solve the problem of children's medication." Yang Zhimin said.

Establish a sound and scientific technical review system. The Drug Review Center has successively issued four technical guidelines, including the "Technical Guidelines for Pediatric Population Drug Clinical Trials", and gradually established and improved a scientific technical review system for children's medication. "In the past, there were no guiding principles and enterprises had no sense of direction. Now the 'rules of the game' have been clarified. The declaration of enterprises is more predictable in time and quality, and the efficiency and confidence are greatly improved." Yang Zhimin said.

Children's medication review line up separately. "In the past, children's drugs were reviewed together with adult drugs, and there was a backlog. Now children's drugs are separated and reviewed first." Yang Zhimin said, "While insisting on giving the green light to review the varieties of children's drugs that are" timely help ", we should" cooperate "with the team of research and development scientists to promote the research and development process of enterprises, so that children's drugs that are urgently needed clinically and in short supply in the market can be put on the market as soon as possible to serve children patients."

Inspired by the policy of priority review of children's medication, the enthusiasm of pharmaceutical giants that were reluctant to do clinical trials in China in the past has increased, and the number of approved clinical trials for children has risen sharply.

The speed of review has been raised. Is the quality of review guaranteed? Ding Yang believes that the speed-up is mainly due to the optimization of the system. The review experts of the Drug Review Center participated in the whole process of the priority review of children's medication, saving a lot of time and investment for enterprises, not only not sacrificing the quality of the review, but also helping enterprises. It has improved the level of clinical research and promoted the sound development of children's medication research and development. Children in my country are gradually bidding farewell to the era of "lack of medicine.

What will be the change of children's medication?

"My son has diarrhea. The doctor said that it is OK to take some rehydration salts, but most of the drugstores in Beijing are adult rehydration salts. There is no rehydration salts for children. It is difficult to control the proportion and dosage if you need to use water by yourself." Zhou Jun, a young mother in Chaoyang District of Beijing, said, "later, I bought children's rehydration salt from abroad. There is no need to mix it. The lid is a measuring cup, and there are strawberry, watermelon and other flavors, which are more acceptable to children."

Children's medication needs to be "delicious". Improving the dosage form is one of the important contents of the evaluation of children's medication in China. There is a lack of suitable dosage forms for children in China, which are specially designed for children of different ages. Some compounds have special physical and chemical properties. When developing dosage forms for children, especially for infants and young children, they have special safety requirements in terms of excipients, which makes it difficult to achieve technically. "Some foreign children's drugs not only have dosage forms and tastes suitable for children, but also design cartoon dropper to help parents accurately quantify, so that children's drugs are not only safe but also interesting, which is worth learning from." Yang Zhimin said.

Children's medication needs to be quantified. "Pediatric discretionary reduction" is a common medication guide on drug use instructions. "In fact, infants, young children, adolescents, the amount of drugs used is completely different. To guide families to regulate the use of children's medication, the instructions need to have more detailed information on children's medication." Yang Zhimin said, "In the future, if a drug's foreign instructions have instructions for children, we will also improve the Chinese instruction system after scientific evaluation."

Children's medication needs innovation. The drug examination center actively set up a platform, implemented the mode of "early intervention and service innovation", and held an exchange meeting with the declared drug enterprises to jointly discuss the safety indicators and schemes of the declared varieties. Yang Zhimin called for further strengthening international exchanges and cooperation, speeding up the introduction of new drugs and new clinical research methods for children, and gradually realizing the synchronization of drug review and listing for children with the international market, so that children in China can benefit from the latest research results of the world at the same time, and truly provide health protection for the next generation.