This client alert is the third of a three-part series that discusses hot topics to come out of the 2015 BIO International Convention.

During the BIO 2015 Convention in Philadelphia, there were several sessions directed to biosimilars. Biologic medicines now account for about one-third of annual drug approvals in the US (according to the Pharmaceutical Research and Manufacturers of America) and it is estimated that in the next year or two, 80 percent of the top-selling medicines will be biologics. One panelist, stated that, in the biosimilar world, structure determines everything. It is one of the reasons the quality of the structure determinations and the similarity of the structure of the biosimilar candidate to the innovator reference product is emphasized. The biosimilar must be highly similar in structure and must function the same way. According to another panelist, quality data on the structure and function of the biosimilar are needed to show similarity, and clinical trials confirm biosimilarity.

Many of the panelists stated that the lack of clarity in regulations is one of the major roadblocks to advancing biosimilars.  A concern is that existing statutes regulating “generic drugs” could be applied incorrectly to biosimilars.  This has led to a recent move to amend state laws to address biologics and biosimilars. More than 30 states have at least considered legislation establishing state standards for biosimilars.  Among the topics being addressed are labeling, dispensing and substituting a biosimilar to replace the innovator biologic product.  Issues regarding switching (done by the physician) versus substitution (done by a pharmacist), prescriber notification of any substitution, patient notification that a switch or substitute has been made, and whether a biosimilar must be approved as “interchangeable” by the FDA before it can be substituted for the innovator biologic medicine are among the hot topics being discussed in state legislatures.  No other global regulatory agency makes a distinction between biosimilarity and interchangeability.

In the US, a biosimilar would be considered interchangeable if, for the same clinical purpose as an innovator product, it can be switched back and forth without any significant change in efficacy and be expected to produce the same clinical result as the innovator reference product in any given patient.  Such interchangeability is similar to that  expected for generics of name-brand prescription medicines.  What stands in the way of this goal are difficulties in determining similarity, and the herculean task of developing state and federal regulations for this growing field of medicine.  So far, the FDA has not issued specific recommendations on interchangeability.  The FDA has said that interchangeability is considered a higher standard than biosimilarity, and indicated a preferred approach is for a company to first prove “biosimilarity” before requesting an “interchangeability” designation.

In international emerging markets, there are additional challenges.  In some international markets that have not adopted regulations for biosimilars, biosimilar products are inaccurately labelled as “generic” drugs.  As part of its mandate to establish and promote international standards with respect to pharmaceutical products, the World Health Organization (WHO) has published advisory guidelines for regulating and evaluating biosimilars by international regulatory authorities.  Unlike the FDA, the WHO is not a regulatory authority, and has no enforcement authority in member states.  One panelist, a medical doctor , stated that, to increase adoption of international standards by member states, the WHO collaborates with other agencies, including the Asia Pacific Economic Cooperation (APEC) and the International Pharmaceutical Regulators Forum, to promote and develop international standards.  The FDA is following some of the WHO guidelines regarding biosimilars.  The WHO also participates in regional workshops to support regulators and manufacturers in emerging markets.  The next workshop will occur in September 2015 in Ghana.

As the industry and state, federal and international governments strive to support this new field of medicine, a number of questions still need to be answered.  How similar must a biosimilar be in order to be highly similar?  Is automatic substitution appropriate for biological medicines, or should substitution occur only under the direct supervision and with the consent of the treating physician?  Should biologics be prescribed only by brand name to avoid automatic substitution?  How can we avoid any stigma or adverse message being sent to pharmacists and patients that substitutions are somehow not as good as the innovator biologic?  How fast will state legislatures be able to update their pharmacy practice acts to allow for substitution of interchangeable biologic products?  How can industry work with state, federal and international regulators to promote the growth of this new frontier in medicine?