U.S.-based Biotechnology Industry Organization (BIO) and the China-based R&D Pharmaceutical Association Committee (RDPAC) want changes in the China FDA's most recent biosimilar approval guidelines, particularly a provision that allows for additional assessment of a biosimilar candidate if a comparability study showed differences between the candidate and its reference product.
On March 3, in CFDA issued its first guidelines to be followed in researching, developing and evaluating biosimilars of biologicals that have marketing approval in the country. Drugmakers now are allowed to register their generic version of a biological drug and similar treatments. The releases also included comments and feedback from various parties, including industry groups.
The agency said that with what it termed "guiding principles" in place, China should be able to meet the demand for the biotechnology drugs, improve accessibility and lower their prices. The guidelines also are expected to reduce development costs for the companies. According to the CFDA, the guidance has been amended, taking into consideration the comments that were submitted on the draft, which focused primarily on product evaluation criteria.
The guidance lays out the basic principles of biosimilar drug development and evaluation, such as recommended non-clinical and clinical studies and quality control. Moreover, the agency believes the guidance will reduce corporate R&D time and biosimilar development costs.
The CFDA noted it was joining more than 20 nations or organizations that have developed biological medicine guidelines. The push for guidelines follows growing demand in China by patients for new therapies, though cost is a central focus of the exercise as well.
The agency action puts in place much of a draft that was circulated for comment last October. Among its final provisions is a requirement that biosimilar tests be conducted simultaneously with the reference drug at each stage.
According to a mid-December report by the Generics and Biosimilars Initiative (GaBI), discrepancies at the chemistry, manufacturing and controls level and at the preclinical level should mean the candidate should not be considered a biosimilar.
"BIO is currently reviewing the recently published final draft of the guidelines. BIO has reviewed and commented on the CFDA's earlier Guidelines on Development and Evaluation of Biosimilars published by the Center for Drug Evaluation and applaud the development of guidelines that are generally consistent with WHO, U.S. FDA, and EMA," said Joseph Damond, BIO's Senior Vice president for International Affairs in an email.
"However, as we noted, there are areas of the guidelines that need to be further clarified to ensure the proper and safe regulation of a large molecule biologic or biosimilars versus a small molecule drug. BIO hopes that its comments on reference products, R&D and evaluation, immunogenicity, multiple indications, and interchangeability continue to be considered as CFDA implements their new guidelines. As always, BIO stands ready and eager to provide the relevant global expertise to help develop a world-class biotherapeutics market in China."
In addition, RDPAC said that if the candidate drug is considered unsuitable, the maker should be allowed to change directly to new drug development and registration pathways. Both organizations joined in saying approved biosimilars should then be allowed to serve as a reference product for other candidates. In a 2014 report, RDPAC said China's therapeutic biologics industry stands at RMB 18 billion ($2.9 billion), representing less than 2% of the global total.
BIO also recommended in its draft comments that the CFDA insert in its guidance a reference to intellectual property protection for reference drugs. Except for those problems, BIO praised the draft guidelines as consistent for the most part with WHO, U.S. FDA and EMA guidelines.
But according to these guidelines, the CFDA seems to be looking for biosimilars which are exact copies of the reference drugs. Developers are encouraged to keep the same amino acid sequence, produce similar packaging and also obtain ingredients from the same place as the reference drug. All discrepancies need to be backed up by evidence from tests and trials.
- for the releases from CFDA: here and here (in Chinese)
- for the CFDA's draft guidelines (in Chinese)
- here are industry comments on GaBI
- and background materials