SHANGHAI – Six Chinese government agencies with authority over health matters, including the CFDA and the National Health and Family Planning Commission, have issued a joint opinion on pediatric drugs in an attempt to address the problem of medicine safety for children in China.

The document sets out the government's future direction and points the way for what changes can be expected. This is a first step to comprehensive legal reforms for children's drug safety, reforms that the country has not made in a decade.

In a follow-up statement, the government recognized that "the safety of medication for children faces challenges" and that "we must be keenly aware that pediatric drugs in terms of dosage and specifications are inadequate, that companies lack motivation to do R&D and manufacture drugs and there is irrational administration of drugs."

The opinion points to a host of issues to tackle, many of which stem from the fact that drugs are rarely if ever clinically tested on children here. All too often drugs that are tested in adults are prescribed to children at lower doses, while drugs specifically for pediatric indications are lacking.

This is not surprising since China has no specific incentives for pediatric drug development, such as market exclusivity, nor does it require pediatric clinical trial data for market approval.

According to legal experts at Covington & Burling LLP, while the details of the policy objectives will become clearer after specific regulations or implementation guidance is announced, the opinion is important to be prepared for the new regulatory proposals likely to emerge.

Given the wide scope of reforms that are sorely needed, the proposed changes bode well for companies with pediatric drugs already approved elsewhere looking to license drugs for the China market.

The verdict is still unclear for developers of new and innovative medicines for pediatric indications.

"I think the CFDA guidelines could be very similar to the current U.S. FDA guidelines, to develop marketed drugs for pediatric indications, but it won't necessarily help the development of novel drugs," Jim Wu, CEO of Ark Biosciences Inc., of Shanghai, told BioWorld Asia.

Ark is working to develop a new pediatric drug candidate for respiratory syncytial virus (RSV). (See BioWorld Today, June 20, 2014.)

"The CFDA is cautious and I doubt they will push for novel pediatric drug development," said Wu. "Although, never say never. In our case, when we have the phase I data from Australia, we will set up a meeting with the CFDA to have a discussion to find out how they really feel about developing a novel drug for pediatric indications."

HOLDING OUT THE CARROT OF EXPEDITED APPROVAL . . .

At the top of the to-do list the opinion sets out three main areas to encourage corporate investment by promoting research and development and promising an accelerated drug review.

A special approval pathway will be established for "pediatric formulations already approved and marketed in foreign jurisdictions and meet an urgent medical need in China," writes Covington & Burling. Lacking in specifics, it is expected that the government intension is to provide a shortcut through the regulatory jungle.

The document also calls for encouraging more pediatric clinical trials. The government will explore a requirement for pediatric clinical trial data and information on pediatric use to be included on future new drug applications.

This could lead to a substantial shift from the current situation. According to Wu's observations, "to my understanding, some pediatricians at some leading childrens' hospitals in China have done phase III clinical trials for pediatric indications, but not for novel pediatric drugs and not for phase I or II."

Academics from West China Second Hospital at Sichuan University went further and looked at the quantity and quality of pediatric randomized controlled trials in China between 2002 and 2011 and concluded that the quantity of RCTs did not increase over the decade and "quality improvements were suboptimal in the later five years."

AND THE STICK . . . OF TIGHTER RULES

Another issue the government is keen to rein in is widespread off-label drug use in children.

For drugs already on the market, often used for pediatric indications, but lacking specific dosage guidance, it may come to pass that they will have to supplement their dossiers with pediatric clinical trial data.

Given that the metabolic rates and drug pharmacokinetics affect children of different ages, it is important for doctors to have age-specific dosage guidance included in drug inserts, Wu said.

Currently physicians have the right to prescribe the drug based on need and, in many cases, are left using guess work to cut down on dosage for a pediatric illness similar to the adult one the drug was approved for.

To further encourage cutting-edge research, development and innovation, the government is proposing a catalog of pediatric drugs will be developed. This would be included in the plan for new protein-based biopharmaceuticals and vaccines under China's Significant New Drug Innovation Project, a major component of the National 12th Five-Year Plan.

BALANCING INNOVATION, COST, SUPPLY AND SAFETY

The government continues efforts to keep drug costs low and the supply adequate. Policies targeting the production and supply of medicines include bringing more pediatric formulations into the insurance system for reimbursement.

To better control adequate supply, the government is exploring implementing price and purchase controls, setting production and reserve quotas, and an early warning system for drug shortages in coordination with manufacturers.

With an eye to improve clinical use, the government also proposed greater clinical evaluation with databases for usage, dosage, efficacy, pharmacokinetics and drug interaction data. The database will focus on the essential drug list composed mostly of generic drugs.

There will be greater emphasis on regulatory oversight of quality and control and safety issues. In 2013, a pediatric volume of the National Formulary was introduced and there will be greater expectations that this will be followed.

At the end of the shopping list, and a departure from many U.S. type reforms, the government also is encouraging research into the pediatric use of traditional Chinese medicines "to harness the advantages of both Chinese and Western medicine."