Espicom View: Indiana has become the latest state to endorse legislation regarding biosimilars. The legislation has been signed into law despite there being no biosimilars approved in the US, and with the FDA having not yet finalised its guidance. The legislation is part of a wider debate about the safety of biosimilars that has seen opponents of the industry act to sow doubt, whilst proponents fight to reassure politicians and the public alike. This debate will continue even after the first biosimilars are introduced in the US as the two sides battle to shape the emerging industry.
On March 25, Indiana Governor Mike Pence signed Indiana Senate Bill 262 into law. The legislation was one of many state-level bills so far introduced across the US concerning biosimilars, but was amongst the few introduced to date that have become law. The bill was introduced to the Indiana Senate on January 13 2014, authored by Republican Senator Brandt Hershman. The bill allows pharmacists to substitute an interchangeable biosimilar for a prescribed biological product if certain conditions are met. It requires the Indiana Board of Pharmacy to maintain a website that lists biosimilars that are determined by the FDA to be interchangeable; as yet, the FDA has not made any such determinations and no biosimilars have been approved in the US. The bill passed through the Senate quickly, being approved on January 28 with a 38 to 11 majority. The same day it was referred to the state's House for consideration. On February 25, the Indiana State House of Representatives passed the bill with an 87 to five majority.
The bill was welcomed by the Biotechnology Industry Organization (BIO), which commented that the legislation was aligned with its principles on biologic substitution. These are that:
substitution should occur only when the FDA has designated a biologic product as interchangeable;
the prescribing physician should be able to prevent substitution;
the prescribing physician should be notified of the substitution;
the patient, or patient's authorised representative, should, at a minimum, be notified of the substitution; and
the pharmacist and the physician should keep records of the substitution.
Commenting on the legislation, BIO noted that it had enjoyed the support of a broad coalition of biologic and biosimilar manufacturing companies. According to BIO, the bill included transparent communication on all biologics dispensed in order to maintain a consistent and complete medical record. The organisation noted that whilst the FDA oversees approval of biologics and designations of interchangeability, policies governing whether one product may be substituted in place of a doctor's prescription and whether a pharmacist must inform patients and doctors are covered by state law. BIO argued that the Indiana bill sought to properly preserve patient access to accurate prescription information, maintain incentives for innovation and promote a competitive market for biologics.
However, not all groups with an interest in the subject matter supported the bill. After the bill was sent to the Governor, the Academy of Managed Care Pharmacy (AMCP) sent a letter to Governor Pence, dated March 6, urging that the bill be vetoed. The AMCP argued that the bill would place unnecessary administrative burdens on the substitution of biosimilars determined to be interchangeable, and further considered the bill to be premature, as the FDA has yet to finalise its guidance for approving biosimilars, determining their interchangeability with reference products or determining their naming. The letter commented that until this guidance is finalised, states will not know if additional steps are warranted prior to substitution of an interchangeable product or dispensing a biosimilar.
The AMCP explained in its letter that it believed Senate Bill 262 was problematic for three reasons:
In sections 2 and 3, the uniform definitions of 'biosimilars' and 'interchangeable' established by the FDA are revised. Since the FDA has not completed its review and rule-making on biosimilars, it seems untimely for a state to revise definitions in this manner.
In Section 5, an undue administrative burden is placed on pharmacists by requiring additional patient and prescriber notification if a biosimilar is dispensed. The proposed requirements are limited only to biosimilars and are not required for any other prescription dispensed.
These additional administrative requirements have the potential to make patients, without cause, question the safety of these prescriptions.
For these reasons, the letter continued, the AMCP believed that the legislation would discourage substitution, which in turn would potentially increase medication costs to patients and payers and thus threaten patient access to more affordable treatments. The AMCP further argued that the legislation did not recognise the value that biosimilars offer to patients and payers by enhancing access to safe and lower cost medications. The organisation noted that since the introduction of biosimilars in 2006, the EU had experienced an average price reduction of 30% for products with competition from biosimilars. It argued that it was reasonable to expect a similar impact in the US.
The FTC's Biosimilars Workshop
Issues revolving around state-level legislation with regard to biosimilars were raised in a workshop sponsored by the FTC that was held on February 4. The public comment period for the workshop ended on March 1. The FTC has originally planned to hold the workshop on December 10 2013, but weather concerns and the closure of the federal government for the day led to its postponement. The event covered arguments for and against state-level legislation in considerable depth, with speakers representing both those in favour and against state-level legislation given an opportunity to make presentations.
A growing number of states have considered or introduced biosimilars legislation, and whilst each bill has differed somewhat, they so far have all broadly followed the pattern seen in the Indiana legislation requiring an ability to substitute biosimilars and keep specific records. According to one speaker at the workshop, Jessica Mazer, Assistant Vice President of State Affairs at the Pharmaceutical Care Management Association (PCMA), in 2013, 28 bills were introduced in 18 states. The legislation was rejected in ten states, enacted in five states and carried over in three. Amongst the ten states to reject the legislation was California. In this instance, the legislation was passed by California's legislature, but in contrast to the situation in Indiana it was subsequently vetoed by California's Governor. The PCMA is opposed to the legislation and has worked with a variety of organisations and companies to oppose bills. Ms Mazer noted that the PCMA was particularly concerned that the proposed legislation was premature, a point raised by Governor Edmund G Brown Jr when he vetoed the California bill, and by the AMCP in Indiana. Ms Mazer commented that the PCMA is worried that such legislation will cause confusion and essentially attempts to undermine public confidence in biosimilars. Much of the debate over the various state-level legislative initiatives has revolved around reporting requirements in the legislation. In general terms, the bills tend to require pharmacists to notify patients and/or prescribers upon dispensing an interchangeable biosimilar in a specified amount of time, and for pharmacists and prescribers to keep records of products dispensed for a specified amount of time.
A second issue to be raised in the workshop, which was echoed in the comments surrounding the Indiana legislation, was that of definitions. In the workshop presentations, Susan DeSanti, formerly the Director of the FTC's Office of Policy Planning but now an attorney with the FTC's office in San Francisco, CA, explained that federal law describes two types of follow-on biologics. One is biosimilars; the FDA is required to determine amongst other things that biosimilars are highly similar to the original biologic. However, biosimilars will still require a separate prescription, as federal law does not provide that biosimilars can be automatically substituted for a biologic. The second type is interchangeable biologics, which federal law does specify can be automatically substituted for a biologic. Federal law has more stringent requirements for a biosimilar to be approved as interchangeable.
Momenta Pharmaceuticals' Bruce Leicher made an interesting observation regarding this in his presentation. Mr Leicher argued that a common denominator in the various state-level bills was a commercial marketing campaign to make interchangeable biologics look like non-interchangeable biosimilars. The effect of this would be to make interchangeable biologics look like they are not interchangeable, but instead are different, in an effort to discourage state-level substitution. Mr Leicher argued that this was part of a long-established campaign against biosimilars.
Organisations such as BIO are at pains to stress that biosimilars are not generics, and indeed this is true. Welcoming the Indiana legislation's passage into law, BIO's President and CEO, Jim Greenwood, stated: 'Even slight changes to a biologic drug can change its properties entirely. Unlike conventional generic medicines, interchangeable biologics are not the same as the drugs they seek to substitute. In fact, two biologics made using different cell lines and different manufacturing processes will rarely, if ever, be exactly the same. Those suggesting interchangeable biologics and generics are the same are wrong.' Mr Greenwood's assertions arguably underscore Mr Leicher's point. It is true that, unlike conventional generics, no two biologics will be exactly identical, but the language used, putting biosimilars, interchangeable biologics and generics together, creates a picture that proponents may well argue is false. An interchangeable biologic will not be identical to its reference product, but the FDA will have determined it to be close enough. A product defined by the FDA to be a biosimilar will not be interchangeable and thus will require a separate prescription.
Mr Leicher also noted that originator biologic products are often manufactured in different plants, something he referred to as 'planned products drift'. As a result, even branded biologics are manufactured in different plants, and consequently there can be manufacturing differences, something that undermines the arguments about interchangeable biologics not actually being interchangeable. According to Mr Leicher, state-level legislative proposals reflect the next tactic in the battle against biosimilars: a campaign that argues there is a problem with pharmacovigilance, thus requiring particular record keeping. Mr Leicher argued that historically there are problems with systems, but that there is nothing necessarily unique about these problems to either biosimilars or interchangeable biologics. Such problems need to be addressed, but should not be used as anticompetitive tools.
Record Keeping Requirements
Geoff Eich, Amgen's Executive Director for Research and Development Policy and a member of Amgen's Biosimilars Policy Group, also spoke at the workshop. Amgen has been a major proponent of state-level biosimilar legislation, so it is not surprising that Mr Eich supported the initiatives in his speech. Mr Eich endorsed the record keeping requirements, broadly arguing that it is important to be able to see exactly what products a patient has been prescribed as all biologics and biosimilars are different. Consequently, the ability to trace and identify any adverse reactions will be essential, particularly once situations occur where patients may be prescribed different products.
However, as other speakers at the conference argued, the record keeping approach is flawed. Speaking after Mr Eich was Dr Steve Miller, the Chief Medical Officer with Express Scripts. Dr Miller told the conference that his career started as a transplant kidney doctor. Dr Miller commented that patient medical records are ambiguous, depending on a number of factors. For example, with chemical drugs doctors will often use brand names to prescribe, rather than the international non-proprietary name, but a generic will be dispensed. Consequently, patient records are not necessarily accurate, and certainly not to the point that record keeping proponents would like.
The workshop showed that the debate over what should perhaps be termed follow-on biologics still rages in the US despite the absence of any such products in the market. Proponents and opponents of the emerging industry are fighting to determine the size and shape of the industry, and both sides are using the experiences provided by how the Hatch-Waxman Act shaped the generics industry as the starting point. These are still very early days and the debate will continue to rage even after the first products are introduced. The Hatch-Waxman Act was introduced 30 years ago this year, but it still took another 15 or 20 years before the generics industry really took off. A similar lengthy path is very likely for the biosimilar industry, providing ample room for debate.