Posted: 23 Aug 2015 07:22 PM PDT
By James C. Shehan –
We’ve all been told that consistency is a virtue and some recent developments have AbbVie’s consistency on display while that company questions FDA’s biosimilar labeling morality, or at least decision-making. In a citizen petition supplement recently submitted to FDA, AbbVie renewed its efforts to change FDA’s policies on biosimilar labeling by assailing the logic behind FDA’s reliance on the Purple Book in response to a Congressional inquiry, by citing FDA’s own recent statements in the Amarin off-label matter and by continuing to assert the needs of prescribing physicians to be fully informed about biosimilars.
AbbVie’s specific requests are that the labeling of all biosimilars contain “clear statement[s] that the product is a biosimilar, that the biosimilar is licensed for fewer than all the reference product's conditions of use (if applicable), … that the biosimilar's licensed conditions of use were based on extrapolation (if applicable), [and] that FDA has not determined that the biosimilar product is interchangeable with the reference product (if applicable).” AbbVie also asks for “[a] concise description of the pertinent data developed to support licensure of the biosimilar, along with information adequate to enable prescribers to distinguish data derived from studies of the biosimilar from data derived from studies of the reference product.”
The original AbbVie citizen petition was submitted by AbbVie in June in reaction to the Agency’s removal from a final guidance document on “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product” of requirements that the labeling of a biosimilar biological product indicate that it is biosimilar to a reference product, and also to call out whether or not it is interchangeable with a reference product, two requirements that did appear in the 2012 draft version of the document (see our previous posts here and here).
AbbVie’s supplement references FDA’s response to an April 30th letter from Lamar Alexander and eight other Republican senators that questioned FDA’s decision to make the labeling of the first approved biosimilar, Sandoz Inc.'s Zarxio (filgrastim-sndz) almost identical to that of its reference product, Amgen Inc.'s Neupogen (filgrastim). The letter noted that Zarxio’s labeling “does not even include the word "biosimilar," which could further increase consumer confusion about how this product relates to the reference biologic.”
AbbVie zeroes in on FDA’s June 22 response to that letter, in which FDA stated that information about biosimilarity and interchangeability did not need to be included in biosimilar labeling because it was in the Purple Book: “The Purple Book enables a user to see whether a biological product has been determined by FDA to be biosimilar to, or interchangeable with, a reference product.” The Purple Book is the biologics analog to the Orange Book drug listing guide (see our post here). The Purple Book lists licensed biological products and contains information about reference product exclusivity, biosimilarity and interchangeability.
AbbVie notes that FDA also states in the June 22nd letter that "health care professionals should have product labeling that includes the essential scientific information necessary to make informed prescribing decisions for their patients," while the 2012 draft guidance said that information "regarding biosimilarity or interchangeability" is needed for informed prescribing decisions. This leads AbbVie to conclude that “The proposition that the Purple Book could cure a material omission in the labeling for a biosimilar is indefensible, FDA regulations explicitly state that prescription drug labeling found "on or within the package" (in other words, the package insert) must contain all of the information that prescribers require to administer the drug to their patients safely and effectively. For decades, FDA, industry, and the medical profession have all understood that package inserts must provide ‘full disclosure.’ If information is necessary for prescribing decisions, it must appear in the package insert. That is a foundational principle of FDA law—and one that FDA fought long and hard to vindicate.”
AbbVie also notes two other pieces of information that are not in the Purple Book but are needed to make informed prescribing decisions- information about the indications and routes of administration for which a biosimilar has been found to be biosimilar to its reference product. AbbVie asserts that this information will become increasingly important as more biosimilars are approved and the market evolves into “a highly complicated landscape of products with varying scopes of biosimilarity and interchangeability," and concludes that “The only way to convey that nuanced information to prescribers is through product-specific disclosures in the labeling of each biosimilar.”
In a separate section of the citizen petition, AbbVie cites FDA’s own statements in support of AbbVie’s position that biosimilar labeling should make clear which supporting clinical studies were conducted by the reference sponsor and which by the biosimilar sponsor. In the Amarin case, which involves a challenge to FDA’s regulation of off-label statements by drug companies, (see our post here), Amarin included a letter to it from Janet Woodcock, the Director of FDA’s Center for Drug Evaluation and Research, concerning what Amarin could and could not say, in FDA’s opinion, about its Vascepa (isocapent ethyl) product. Dr. Woodcock states: “[A] communication should not state or imply that studies conducted using products other than Vascepa were studies of Vascepa itself .... Rather, to ensure that your communications are not false or misleading, we recommend that they expressly disclose when studies were conducted using products other than Vascepa (in particular when those other products contain active ingredients that are different from the isocapent ethyl—an ester of EPA—that is contained in Vascepa) and that the results of the studies may not be applicable to Vascepa.
AbbVie also quotes the government brief in the Amarin case as saying that it would be "misleading for Amarin to suggest or imply ... that studies using products other than Vascepa were studies of Vascepa itself."
AbbVie points out that these FDA statements stand in contrast to FDA's current approach to biosimilar labeling, at least in the case of Zarxio. “As explained in the Petition, a biosimilar and its reference product are – like Vascepa and related products — similar, but not the same active ingredients or products. But, the labeling that FDA approved for Zarxio relies entirely on studies involving a different product without acknowledging that the studies were not conducted with Zarxio. As both FDA and DOJ have now represented to a federal court, a failure to "expressly disclose when studies were conducted using [other] products" is misleading.”
A third section of the AbbVie supplement concerns growing “stakeholder support for more transparent biosimilar labeling.” AbbVie' cites three recent letters to FDA’s Acting Commissioner, an important conference on Capitol Hill, additional survey evidence, and a recent statement from the biosimilar industry.
Our two earlier posts on this topic analogized the issue of whether biosimilar labeling should or should not indicate that a product is a biosimilar to the affixing of a scarlet letter to Hester Prynne in Hawthorne’s classic novel. Having completed a blog trilogy and seeing no end in sight for the issue of biosimilar labeling issues, we may need to move on to new references – perhaps Fast and Furious 8 will suffice.
We’ve all been told that consistency is a virtue and some recent developments have AbbVie’s consistency on display while that company questions FDA’s biosimilar labeling morality, or at least decision-making. In a citizen petition supplement recently submitted to FDA, AbbVie renewed its efforts to change FDA’s policies on biosimilar labeling by assailing the logic behind FDA’s reliance on the Purple Book in response to a Congressional inquiry, by citing FDA’s own recent statements in the Amarin off-label matter and by continuing to assert the needs of prescribing physicians to be fully informed about biosimilars.
AbbVie’s specific requests are that the labeling of all biosimilars contain “clear statement[s] that the product is a biosimilar, that the biosimilar is licensed for fewer than all the reference product's conditions of use (if applicable), … that the biosimilar's licensed conditions of use were based on extrapolation (if applicable), [and] that FDA has not determined that the biosimilar product is interchangeable with the reference product (if applicable).” AbbVie also asks for “[a] concise description of the pertinent data developed to support licensure of the biosimilar, along with information adequate to enable prescribers to distinguish data derived from studies of the biosimilar from data derived from studies of the reference product.”
The original AbbVie citizen petition was submitted by AbbVie in June in reaction to the Agency’s removal from a final guidance document on “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product” of requirements that the labeling of a biosimilar biological product indicate that it is biosimilar to a reference product, and also to call out whether or not it is interchangeable with a reference product, two requirements that did appear in the 2012 draft version of the document (see our previous posts here and here).
AbbVie’s supplement references FDA’s response to an April 30th letter from Lamar Alexander and eight other Republican senators that questioned FDA’s decision to make the labeling of the first approved biosimilar, Sandoz Inc.'s Zarxio (filgrastim-sndz) almost identical to that of its reference product, Amgen Inc.'s Neupogen (filgrastim). The letter noted that Zarxio’s labeling “does not even include the word "biosimilar," which could further increase consumer confusion about how this product relates to the reference biologic.”
AbbVie zeroes in on FDA’s June 22 response to that letter, in which FDA stated that information about biosimilarity and interchangeability did not need to be included in biosimilar labeling because it was in the Purple Book: “The Purple Book enables a user to see whether a biological product has been determined by FDA to be biosimilar to, or interchangeable with, a reference product.” The Purple Book is the biologics analog to the Orange Book drug listing guide (see our post here). The Purple Book lists licensed biological products and contains information about reference product exclusivity, biosimilarity and interchangeability.
AbbVie notes that FDA also states in the June 22nd letter that "health care professionals should have product labeling that includes the essential scientific information necessary to make informed prescribing decisions for their patients," while the 2012 draft guidance said that information "regarding biosimilarity or interchangeability" is needed for informed prescribing decisions. This leads AbbVie to conclude that “The proposition that the Purple Book could cure a material omission in the labeling for a biosimilar is indefensible, FDA regulations explicitly state that prescription drug labeling found "on or within the package" (in other words, the package insert) must contain all of the information that prescribers require to administer the drug to their patients safely and effectively. For decades, FDA, industry, and the medical profession have all understood that package inserts must provide ‘full disclosure.’ If information is necessary for prescribing decisions, it must appear in the package insert. That is a foundational principle of FDA law—and one that FDA fought long and hard to vindicate.”
AbbVie also notes two other pieces of information that are not in the Purple Book but are needed to make informed prescribing decisions- information about the indications and routes of administration for which a biosimilar has been found to be biosimilar to its reference product. AbbVie asserts that this information will become increasingly important as more biosimilars are approved and the market evolves into “a highly complicated landscape of products with varying scopes of biosimilarity and interchangeability," and concludes that “The only way to convey that nuanced information to prescribers is through product-specific disclosures in the labeling of each biosimilar.”
In a separate section of the citizen petition, AbbVie cites FDA’s own statements in support of AbbVie’s position that biosimilar labeling should make clear which supporting clinical studies were conducted by the reference sponsor and which by the biosimilar sponsor. In the Amarin case, which involves a challenge to FDA’s regulation of off-label statements by drug companies, (see our post here), Amarin included a letter to it from Janet Woodcock, the Director of FDA’s Center for Drug Evaluation and Research, concerning what Amarin could and could not say, in FDA’s opinion, about its Vascepa (isocapent ethyl) product. Dr. Woodcock states: “[A] communication should not state or imply that studies conducted using products other than Vascepa were studies of Vascepa itself .... Rather, to ensure that your communications are not false or misleading, we recommend that they expressly disclose when studies were conducted using products other than Vascepa (in particular when those other products contain active ingredients that are different from the isocapent ethyl—an ester of EPA—that is contained in Vascepa) and that the results of the studies may not be applicable to Vascepa.
AbbVie also quotes the government brief in the Amarin case as saying that it would be "misleading for Amarin to suggest or imply ... that studies using products other than Vascepa were studies of Vascepa itself."
AbbVie points out that these FDA statements stand in contrast to FDA's current approach to biosimilar labeling, at least in the case of Zarxio. “As explained in the Petition, a biosimilar and its reference product are – like Vascepa and related products — similar, but not the same active ingredients or products. But, the labeling that FDA approved for Zarxio relies entirely on studies involving a different product without acknowledging that the studies were not conducted with Zarxio. As both FDA and DOJ have now represented to a federal court, a failure to "expressly disclose when studies were conducted using [other] products" is misleading.”
A third section of the AbbVie supplement concerns growing “stakeholder support for more transparent biosimilar labeling.” AbbVie' cites three recent letters to FDA’s Acting Commissioner, an important conference on Capitol Hill, additional survey evidence, and a recent statement from the biosimilar industry.
Our two earlier posts on this topic analogized the issue of whether biosimilar labeling should or should not indicate that a product is a biosimilar to the affixing of a scarlet letter to Hester Prynne in Hawthorne’s classic novel. Having completed a blog trilogy and seeing no end in sight for the issue of biosimilar labeling issues, we may need to move on to new references – perhaps Fast and Furious 8 will suffice.
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