Over the past several years, Chinese regulatory authorities have signaled an increased awareness of the need to improve quality standards for both generic and biosimilar drugs. In 2015, the China Food and Drug Administration (CFDA) (now NMPA, National Medical Product Administration) issued technical guidance on the development and evaluation of biosimilars,
and in 2016, the State Council General Office issued the Opinion on Conducting Evaluations of the Quality and Efficacy Consistency of Generic Drugs, which laid out an industry-wide overhaul of generic drug quality by requiring a retroactive and ongoing generic consistency evaluation (GCE).
What will these and other reforms mean to the Chinese generics and biosimilars landscape?
Regulatory Reforms for Generics
Bioequivalence studies had been required for generic drugs since 2007 regulatory revisions. However, these bioequivalence studies were often unreliable due to a lack of an official reference drug list and a lack of Good Clinical Practice (GCP) and regulatory oversight, calling into question the quality of generic drugs approved prior to the 2016 reform. Now, legacy generics as well as new generics must be demonstrated to have the same quality as, and be biopharmaceutically equivalent to, the officially listed reference drug, which is typically the innovator or branded version of the generic drug.
According to Jifeng Lei, CEO of Anbison Inc., Chinese pharmaceutical companies now fully understand the regulatory and technical requirements that are in line with the FDA and the European Medicines Agency (EMA) in terms of pharmaceutical equivalence and bioequivalence. Essentially, the generics applicant must demonstrate that their product becomes available at the site of drug action at the same rate and to the same extent as the reference product when administered at the same dose and under the same administration route. Bioequivalence studies are conducted in NMPA-qualified hospitals, with sample analysis occurring at qualified analysis organizations according to GCP guidelines. An intensive site inspection is conducted for every application for those sites by NMPA inspectors, and the bioequivalence requirement is referenced to the FDA-published general guidance as well as the specific product bioequivalence guidance. This increased focus on generics quality may help to account for a growing global demand for China-produced generic drugs. In 2017, Chinese drugmakers won approval for 38 generics, up from 22 in 2016.
As generic quality increases as a result of the Generic Drug Quality and Efficacy Consistency Evaluation policy, competition for off-patent branded drugs will no longer draw premium prices. At the same time, companies that are unable to keep up with these new rigorous standards will be left behind, resulting in consolidation of the sector.
According to Lei, many Chinese pharmaceutical companies are now focusing on pharmaceutical redevelopment to make their marketed drug products bioequivalent and pharmaceutically equivalent to the reference product so they can survive in the marketplace. Product and process design, process performance monitoring, process qualification, bioequivalence, and the Common Technical Document are becoming hot topics within the Chinese pharmaceutical industry. At the same time, according to Lei, the NMPA is cracking down on false data in the application dossier, and top management and scientific talent in the industry are now more likely to be focusing on the technical side—development and manufacturing—rather than on the sales side.
There is still a significant need for more contract research organizations focusing on pharmaceutical development and bioequivalence studies.
