It is evident that biologic drugs are playing an increasingly important role in the global medicinal market. However, the Economic Institute of the China Food and Drug Administration (CFDA) has predicted a large number of these biologic drugs will lose their patent protection in the next five years and, as a result, biosimilars are expected to increase market share rapidly, in the same manner as we have seen in the block buster small molecule patent cliff of the last few years.
There exists a constant debate as to the best way to boost the biological drug and biosimilar market in China. In contrast to small molecule drugs, biologic antibody drugs account for a only a small proportion of the available and approved drugs in China largely because of their higher price and the lower reimbursement price in the internal health insurance system. In addition, under current practice, approval of biosimilar drugs follows the same process as those required of new drugs, which is time consuming and expensive.
On 4 March 2015, the CFDA released a Guidance on the Development and Evaluation of Biosimilars (For Trial Implementation) which for the first time proposes a regulatory framework for the abbreviated approval of biosimilar drugs. The Guidance has been welcomed by industry and proposes a framework which could allow for biosimilars to undertake an abbreviated approval process. The Guidance sets out a step by step process in order for the CFDA to determine whether a candidate biological product is biosimilar to its reference product approved in the Chinese market.
Under the Guidance, the CFDA sets out three types of comparability testing that may be required in order to evaluate biosimilarity, namely:
- Pharmaceutical data, including the structure, purity, biological activity, stability, cell substrate, dosage, and package material study data;
- Nonclinical evaluations data, including the pharmacokinetic (PK) and pharmacodynamics (PD), immunogenicity, and toxic data; and
- Clinical pharmacology data, including the human PK and PD studies, clinical immunogenicity testing, and clinical safety data.
The Guidance proposes that this data should be collected in a step by step manner . Where no or little difference in comparability testing is demonstrated this could allow subsequent comparability tests to be skipped..
Whether a product is determined as being not different, slightly different or uncertain will be decided by the results of each of the studies, and in turn the results will determine to what extent further studies, if any, are required. A biosimilar which is assessed as ideal need not undertake some of the comparative studies, while those biosimilars where differences to the comparator biological are identified will be required to undertake studies which will investigated the biosimilar further.
Although the Guidance sets out detailed scientific considerations of the studies required, it fails to specifically define the degree of similarity necessary in order for subsequent comparability steps to be skipped. Despite the lack of clarity in this respect, the industry has welcomed the Guidance as an abbreviated approval process for biosimilars will certainly increase the accessibility of biosimilars and reduce the cost of bring biosimilars to market.
The CFDA will adjust the Guidance according to the situations and the problems encountered during the stage of trial implementation. We will keep you updated on the progress of the Guidance, particularly in respect of whether the CFDA introduces a defined similarity standard.