Posted 16 January 2014
By Alexander Gaffney, RAC
The European Medicines Agency (EMA) has formally issued a call for a reflection paper on methods to compare quality attributes in drug development, saying that regulators need to settle on established criteria for determining acceptable ranges of "similarity criteria" in biosimilar products.
The draft of the concept paper was released in May 2013, and explained that EMA has received several requests in recent years regarding the adequacy of data meant to compare the quality of two products, such as an innovative biological product and a follow-on biologic, otherwise known as a biosimilar product.
If a biosimilar product is of insufficient quality relative to the reference product, it could be rejected by regulators. The problem for regulators: How do you define "similarity" on a consistent, quantifiable and scientific basis?
EMA's most recent iteration of the concept paper notes that "several different methodological approaches [have] been proposed to define comparability" with respect to biosimilar products and their biological reference products.
To date, EMA said it and its review committees have been considering these questions on a case-by-case basis, but that significant challenges need to be addressed in nearly all cases.
"The diversity of candidates of critical quality attributes within specific developments, as well as the usually low or unbalanced number of drug batches available for the drug compounds to be compared, had been identified as the most limiting factors, rendering the use of statistical routines usually performed on basis of clinical patient-data inappropriate most of the time," EMA wrote. "Despite these limitations, it seems important to identify and discuss methods which may be adequate to serve for comparative purposes."
Toward a Reflection Paper and a Guideline
The concept paper explicitly calls for a reflection paper to discuss these issues in depth in the hopes of eventually resulting in a guideline capable of being used by regulators and members of industry.
Regulators are slated to explore how two--"or even more"-biologics can be compared to one another, how versions of a drug change over time (such as during scale-up and post-approval changes during and after clinical testing), factors affecting batch-to-batch variability, and how small batch sizes can impact comparability protocols.
EMA added that it believes the primary benefit of the reflection paper will be to advance biosimilar development, but that it could also stand to benefit other scenarios in which comparative evaluation is useful, such as analyzing in vitro assays or small-molecule chemical drugs.
EMA said the reflection paper should be available in approximately six months' time, followed by an additional six months of industry and public consultation. A guideline is expected to be generated out of that process, though it is unclear exactly when it might be published.
EMA: Concept paper on the need for a reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development