A similar bill was passed in Massachusetts, requiring pharmacists to record substitution of interchangeable biologic products in an interoperable EHR system, if available, and to report such substitutions to the prescriber [ 53].
We considered three different ways of computing residue mutability: 1) using only SNAP scores of to-Ala substitutions, 2) computing the arithmetic mean of all SNAP scores for the 19 nonnative substitutions at each position, and 3) computing the arithmetic mean of the SNAP scores for substitutions of interchangeable residues at each position.
The generic drug association and insurers do not object to limiting substitution to drugs declared interchangeable by the F.D.A.
Substitution and Interchangeability: If a product is interchangeable with another, the implication is that both have been shown to have similar safety and effectiveness.
Gross substitution implies that goods are interchangeable.
However, given that the N-terminal regions of harmonin and Cip98 are not functionally interchangeable (Pan et al., 2009), any functional substitution of harmonin by Cip98 in the photoreceptor must not rely on protein interactions in the N-terminal region.
The pharmacist is obliged to suggest substituting the prescribed pharmaceutical product for the cheapest interchangeable generic unless the physician has marked on the prescription that substitution should not take place.
It is also possible that the patient may be switched back and forth between the biosimilar and the originator, either due to poor record keeping as a result of automatic substitution or because the drugs are considered interchangeable.
Unlike generics, initial approval may not include interchangeability, as additional evidence may be required before a biosimilar could be approved as interchangeable with its reference product; interchangeable designation could allow pharmacy-level substitution without prescriber intervention.
Although studies in prokaryotes suggest that the polyamine network is functionally interchangeable and loss of an important enzyme can be mitigated by substitution (Tholl et al., 1998), the situation in eukaryotes seems to be more complex.
A number of factors explain biosimilars' failure to launch in the United States, including: confusion about what it means for a biosimilar to be "highly similar" or "interchangeable" with a branded biologic, more than 40 state laws that prohibit automatic substitution of brand-name biologics with biosimilars, a lack of federal guidelines on biosimilar substitution, and confusion over naming.
