|
|
| IP Newsletter | Summer/Fall 2014 | |
Legal and Regulatory Pathway
Marketing authorization for a biosimilar product in Korea is based upon a regulatory assessment that an applicant has demonstrated the product's "comparability" to the reference biologic drug under the relevant guidelines. According to the Ministry of Food & Drug Safety (MFDS), the term "comparability" is defined as "a scientific comparison of a biosimilar product and a reference biologic drug with the goal of establishing that no detectable difference exists in terms of quality, safety, and efficacy." The MFDS will exercise discretion when assessing the comparability of a biosimilar product to the reference product. Further, while product-specific guidelines for demonstrating comparability are currently available only for some products, including somatropin, erythropoietins and recombinant granulocyte-colony stimulating factor, the MFDS reportedly is committed to updating its guidelines.
Products Currently Eligible for the Biosimilar Pathway
According to the MFDS, whether the biosimilar pathway applies to a certain biopharmaceutical product depends on the state of the art to which it is related, for example, analytical procedures, manufacturing processes and the availability of sensitive clinical endpoints and model conditions. Thus, although all biopharmaceutical products are theoretically eligible for approval under the biosimilar pathway, not all biological products currently may be eligible for approval as a biosimilar product.1 According to the MFDS, present technology can support findings as to the comparable quality, safety and efficacy of "recombinant DNA products" only.2 Therefore, the MFDS currently does not review any drug applications related to other types of biosimilar products.
International Non-proprietary Name (INN) Policy on Biosimilars and Drug Prices
While debates over whether a biosimilar product should share the same INN as its reference counterpart loom in other jurisdictions, especially in the U.S. (e.g., Amgen's Citizen Petition filed December 20, 2013 in response to GPhA and Novartis' Citizen Petitions regarding the U.S. FDA's INN policy on biosimilar products), the MFDS' current position is to grant the same INN for both the reference and the approved biosimilar products, as demonstrated with Remsima™ and Herzuma™. However, it is likely the MFDS' position, based on only these two cases, may undergo several permutations as the world biosimilar industry, based on science and familiarity, matures.
This INN policy has important commercial implications for drug pricing. In Korea, once a biosimilar drug with the same INN enters the market, the price of the original drug drops by 30%.
Trade Secret Protection for Reference Product Data
In Korea, information related to analytical, preclinical and clinical data as part of a reference product application submitted by innovators is considered trade secret information and protected from public disclosure, including from biosimilar applicants. However, the MFDS regulations, in reliance on reference product data, exempt biosimilar applicants from submitting some CMC, clinical and non-clinical data. The MFDS's examination practice raises certain questions, including:
|
Despite recognition of reference product data as trade secrets, how far may the MFDS legally rely on reference product data for approval of a biosimilar product? | |
|
|
What internal process will the MFDS implement to prevent any improper reliance on trade secrets during biosimilar examination (e.g., can biosimilar application reviewers also review the reference product's trade secret information)? | |
Implications of the Korean Patent Linkage System on Biosimilar Products
Under the Korea-U.S. Free Trade Agreement enacted in 2011 and effective on March 15, 2012, Korea is now enforcing a patent linkage system for all pharmaceutical products, both traditional "small molecules" and biologics. The Korean patent linkage system, mirroring the U.S. Hatch-Waxman Act, establishes a regulatory framework that seeks to balance incentives for continued innovation by innovator companies and opportunities for market entry by generic drugs.3
We should note that regulating both traditional "small molecules" and biologics under the same patent linkage system is a significant distinction from the U.S. system. Accordingly, a biological innovator may list a patent covering its product on the Green List (the Korean equivalent of the U.S. FDA's Orange Book) after the MFDS examination and will be able to seek a stay against biosimilar launch, as in a typical "Paragraph IV" litigation under Hatch-Waxman. According to the most recently announced draft legislation, the length of the stay will be 12 months. Conversely, a biosimilar manufacturer will be obligated to notify the reference product patent holder or market approval holder if the biosimilar manufacturer asserts that the listed patent or patents are not infringed or invalid.
Considerations for Industry
As in other jurisdictions, the current biosimilar pathway in Korea is intended to avoid unnecessary repetition of data production. However, many of the issues related to biosimilar products are still very new and the current regulations leave a number of critical questions unanswered. As the MFDS is confronted with more issues on biological products, it is expected to shape a more defined regulatory framework. Companies currently engaged in developing and marketing biological products will need to pay close attention to these developments.
| 1 | This guidance by the MFDS appears to be similar to that of the U.S. FDA, whose guidelines indicate that a certain product may be ineligible for approval due to science and experience with the particular product class. | |
| 2 | A "recombinant DNA product" is defined as a medical product containing peptides or proteins as a drug substance produced by recombinant engineering. Recently, the MFDS has established standards for non-clinical and clinical trials required for proving comparability to an approved monoclonal antibody drug (reference drug). The "recombinant DNA product" does not include vaccines, plasma-derived products or biological orphan drugs. | |
| 3 | The current version of the linkage regulations are subject to change until March 2015 when the regulations will be enacted. | |
|
Mee-Sung SHIM msshim@ip.kimchang.com |
H. Joon CHUNG hjchung@ip.kimchang.com |
Eun-Jung CHO ejcho@ip.kimchang.com |