A biosimilar product is essentially a non-inferior ‘twin’ of the reference biologic with similar clinical efficacy and safety. Biosimilar development is a fairly new and evolving landscape with many unique operational challenges. This blog explores some of these challenges and ways to overcome the barriers.
The regulatory approval requires biosimilar developers to establish similarity of the potential biosimilar to its reference biologic. The direct comparative analysis requires a biosimilar developer to create a quality target product profile, QTPP, for its biosimilar product by determining the inherent variability in the reference biologic with respect to the key quality attributes. Comparator sourcing therefore is critical to biosimilar development and poses a challenge as the innovator companies release only few batches of commercial stock over a prolonged time-period. The biosimilar developer must procure multiple batches of comparator (reference biologic) with varying expiry dates to create a robust QTPP. An even larger quantity of comparator is required for the head-to-head clinical trials. The cost of sourcing the reference biologic is a significant share of the total cot of biosimilar development. This overall study budget can further increase, if reference treatment is not procured in a timely manner. Sourcing of reference biologic can prove to be a “bottle-neck” in the biosimilar development and hence, should be addressed strategically.
The commercial supply of reference product does not always come with certificate of analysis or CoA, which is a key document for regulated import of IMP (Investigational Medical Product) in many countries. In absence of CoA, from qualified personnel and/or institution, the biosimilar developer will have to generate one thereby impacting both timelines and cost.
The design of a similarity trial for biosimilars is also not straightforward. The aim of the phase 3 similarity study is to establish that there are no clinically meaningful differences between the biosimilar and its reference product. While designing the non-inferiority trial for biosimilars, sensitive patient population and assay sensitivity to differentiate between effectiveness of two, is of greatest importance. Additionally, the trial design has to account for any change in treatment paradigm for smooth regulatory approval.
Patient recruitment is the most significant contributor to clinical spends. Not only that it also impacts the trial timelines. Recruitment for biosimilar study is particularly challenging due to the general lack of awareness. A lot of effort is still need to communicate the value of biosimilars to clinical trial investigators and prospective participants. Biosimilar guidelines are fairly new in most regions and therefore clinical trial site staff’s education is a critical step towards quick and successful study completion. Prospective participants should also be communicated the benefits of biosimilars as there is no placebo arm in biosimilar clinical study. Messages around the economic impact of biosimilars may also encourage participation.
Biosimilar clinical study typically requires biologic naïve patients for most sensitive comparison of effectiveness. This requirement puts developers in direct competition against new biologic treatments for patient recruitment. Country and site selection is therefore crucial. South-East Asia and Latin America regions may be more attractive for patient recruitment due to high biologic-naïve patient population. Eastern European countries should also be preferred due to low access of innovator biologic and a price-sensitive patient pool. Consideration should also be given to regulatory requirements of countries of interest. There are a number of countries which require study data in local patient population e.g. Mexico, China, Russia, etc.