One of the biggest changes to food and drug law changes by the 2010 passage of the Patient Protection and Affordable Care Act (PPACA), better known by most as Obamacare, was its provisions for the creation of a "biosimilars" pathway under Section XII of the law. But now one of the most influential states in the US is moving to restrict their eventual use, conceding arguments made by innovative biopharmaceutical manufacturers that physicians should be able to restrict the substitution of biological drugs with biosimilar equivalents approved by the US Food and Drug Administration (FDA).

Background

Previous efforts to create a pathway for biosimilars under the 2009 Biologics Price Competition and Innovation Act (BPCI) were ultimately combined into the PPACA, which established the 351(k) pathway for FDA to approve biosimilars much in the same way as generic pharmaceutical get approved via the 505(j) pathway.

The tradeoff is thus: Innovative biological products receive 12 years of market exclusivity for products, while subsequent biologics which reference the studies used to approve the former are then able to obtain approval more easily since they would require less data.

But as Regulatory Focus has explained before, the biggest issue of all may well be whether a biosimilar product is interchangeable with the original reference listed drug (RLD). Unlike chemical drugs, which can generally be closely-if not exactly-approximated and be found to be therapeutically equivalent based on bioequivalence and pharmacokinetic/pharmacodynamics data, biologics are altogether a great deal more complicated.

Since many are formed using complex biological processes (e.g. in bioreactors), generic manufacturers would find it nearly impossible to create an exact copy of the RLD's protein structure due to either a slightly different starting biological material, a different manufacturing process, and a variety of other factors that could affect uptake of the drug.

Thus, the major question faced by regulators will almost certainly be threefold:

1. Is the biosimilar product therapeutically equivalent to the RLD for the purposes of approval?
2. Does the biosimilar product demonstrate an identical safety profile as the original?
3. Assuming the drug is equivalent in both safety and efficacy, is it substitutable for the RLD (as a generic would be)?

State Legislative Efforts: California Edition

While FDA has yet to approve any biosimilar products (though it has released numerous guidance documents and received several investigational new drug applications for eventual 351(k) filings), that hasn't stopped some state legislators from moving to pre-emptively ban the practice of substituting biosimilar drugs.

The latest of those bills is California's SB 598, which would prevent a biosimilar from being substituted in place of the RLD by a pharmacist unless FDA has specifically found the two products to be interchangeable. It would also allow a physician to prevent a pharmacist from substituting a biosimilar product for its biosimilar equivalent even if they are found to be interchangeable-a boon to innovative companies which could leverage the measure to stifle generic competition.

The bill has already seen overwhelming approval in the California Senate and Assembly, and now awaits Gov. Jerry Brown's signature.

"SB 598 is timely legislation that provides a balanced framework governing the use of biosimilars and gives doctors and patients more and better choices," said Joseph Panetta, president of BIOCOM, a California-based life sciences organization. "California policymakers recognize that biosimilars may be approved for the U.S. healthcare market as early as 2014 and without an update to state law patients will not have full access to them."

Pushback from FDA, GPhA

The bill, however, has received sharp rebukes from both FDA and the Generic Pharmaceutical Association (GPhA), who say it undermines confidence in biosimilar drugs as a whole by implying that non-interchangeable drugs are less safe or effective than the original RLD.

"Efforts to undermine trust in these products are worrisome and represent a disservice to patients who could benefit from these lower cost treatments," said FDA spokeswoman Lisa Kubaska to In-Pharma Technologistlast week. "It is important for everyone to approach these issues with an understanding of both FDA's expertise in this area and what the 2010 law requires for approval of biosimilar and interchangeable products."

Kubaska notes that the PPACA already set a "very high bar" for biosimilar approvals and expressly allowed for substitution.

In a statement released on 4 September 2013, GPhA noted its "disappointment" in the impending passage of the law.

"The bill would create unnecessary barriers between Californians and newer, lower-cost versions of biologic therapies, known as biosimilars, particularly interchangeable biosimilars," it wrote. "For the sake of California patients, the California budget, and California taxpayers, GPhA calls on Governor Brown to veto SB 598."

GPhA also argued the bill would increase costs for taxpayers, noting that the inability to substitute for lower-cost drugs would raise costs for CA's state Medicaid plan, known as CalPERS.