The EU has lead the charge with its biosimilars pathway, which has resulted in 18 approvals, though the WHO “has become the yardstick by which to measure new countries looking to adopt biosimilar regulations,” Andrew Robertson, director of global regulatory policy at Merck, told attendees at DIA’s 50th annual conference in San Diego.
Robertson noted that the WHO offers three key messages in its guidelines, including the need for companies to demonstrate similarity to a suitable reference biologic, promote stepwise comparability exercise – “meaning the more work you do in preclinical analytics, the less work you’ll have to do in clinical studies,” and finally the need to stress that similar biologics are not generics, which is “a point that gets lost quite often.”
The US, which is expected to have the biggest market for biosimilars in the coming years, has been slow to approve any, though work is progressing and four more FDA biosimilar guidelines are expected in 2014.
Twenty-four countries now have biosimilar pathways or have approved follow-on biologics, though for some countries -- such as Russia and China, which are not WHO-compliant -- they are adapting generic-like pathways to approve biosimilars, Robertson said.
Sonica Batra, director of clinical development of biologics at Dr. Reddy’s Laboratories, also noted that China’s FDA does not have a specific definition, guidance or pathway for biosimilar approvals, and registration can take 6 years or longer. In addition, if the products are not manufactured domestically, it can take almost two years to get a GMP certification to produce them.
Batra also noted that South Korea has seen rapid growth in the past few years for biosimilars, with a clearly delineated approval pathway and 11 development companies and 13 approvals as of 2012.
Japan, which has five biosimilar approvals and guidance in place, and Australia are both in the process of adopting biologic qualifier standards, and have expressed a willingness to conform with a global standard.
Canada, meanwhile, has guidance in place governing biosimilars and two approvals. Turkey and Norway are looking to take a page out of the US law governing biosimilars – the BPCIA (Biologics Price Competition and Innovation Act) -- and are interested in seeing interchangeable biologics standards adopted.
INNs and Doctors
As far as naming is concerned, which has been a hot topic recently in the US, an INN (international non-proprietary name) is required in China, Colombia, Latvia, encouraged in India and Netherlands, and proposed in Russia.
The majority of EU member states, however, recently said no to INNs for biosimilars, charging that the products should be closely aligned with their reference biologics.
Distinguishable INNs can aid pharmacovigilance and avoid a single point of information failure, as well as to increase manufacturer accountability, according to Richard Dolinar, chairman of Alliance for Safe Biologic Medicines.
Dolinar helped conduct a survey of 470 prescribers from France, Germany, Italy, Spain and UK, which found that doctors were largely unfamiliar with biosimilars. According to the survey, 54% said they only basically understand biosimilars, while 20% could not define them, “which is high considering they’re on the market,” he added.
“Doctors don’t understand the difference between generics and biosimilars and we need doctors who know about these drugs,” Dolinar said.
He also noted that small changes in manufacturing techniques can result in adverse events for biosimilars.