INTA’s Health Policy and Trademark Rights Subcommittee of the Emerging Issues Committee was given a mandate to create a Task Group to further review laws and regulations that limit the use of trademarks and brand imagery on pharmaceutical products. The mandate came in light of the previous work conducted by the Task Group on Unaddressed Issues in Health and Safety, which highlighted the recent headline-grabbing advent of plain packaging requirements for tobacco products in the trademark field. The Pharmaceuticals Task Group researched the situation in Canada, Europe, and the United States, and developed a series of three articles which will touch on the historical intrusion of governments into the branding of pharmaceuticals and highlight recent developments that are changing the landscape in these jurisdictions. We begin with the U.S. situation.
Before 1990, the U.S. Food and Drug Administration (FDA) did not significantly consider the role of pharmaceutical trademarks in possible medication errors. Then, around 1990, the FDA’s Labeling and Nomenclature Committee (LNC) started evaluating proposed pharmaceutical trademarks and making recommendations to the FDA’s Center for Drug Evaluation and Research (CDER) as to whether a proposed pharmaceutical trademark would be acceptable from the perspective of patient safety. Since then, the review and evaluation of trademarks has moved from LNC to other FDA offices or divisions, and now resides within the Division of Medication Error and Prevention Analysis (DMEPA). The FDA’s authority to conduct a review of the proposed trademark arises from the fact that proprietary names are used in a pharmaceutical product’s labels and labeling, as well as in other promotional materials, and so, is based on the “misbranding” section within the Food, Drug and Cosmetic Act (FDCA), where, at Section 502(a) (21 U.S.C. § 352 (a)) the FDCA states: “… a drug, including a biologic, is misbranded if its labeling is false or misleading
in any particular (emphasis added).” In addition, Section 351(b) of the Public Health Service Act (42 U.S.C. § 262(b)) prohibits falsely labeling or marking any package or container of a biological product.
The most significant early milestone that prompted the FDA to review proposed pharmaceutical trademarks more rigorously occurred around 1999, when the Institute of Medicine (IOM) published a report called To Err Is Human
. According to that report, health care in the United States was not as safe as it should or could be. Specifically, it was alleged that between 44,000 and 98,000 people were dying in hospitals each year because of preventable medication errors. This was a wake-up call. In the years following publication of this report, as well as further independent reports and learned papers, the U.S. government and the FDA enacted new laws and regulations and developed various draft guidance documents with the goal of minimizing potential medication errors, including those alleged to occur because of confusion between a proposed trademark being considered for a pharmaceutical product and the trademark of an existing pharmaceutical product.
FDA Guidance: Lack of Predictability, Uncertainty of Safety
In April 2016, after a number of years of various draft guidance documents, the FDA issued a final guidance titled “Contents of a Complete Submission for the Evaluation of Proprietary Names—Guidance for Industry
” (Contents Guidance). This guidance should be read in conjunction with the FDA’s draft guidance for industrytitled “Best Practices in Developing Proprietary Names for Drugs
,” first launched in 2010, relaunched in 2014, and which continues to be draft guidance (Best Practices Guidance). As stated by the FDA, the Best Practices Guidance is the third guidance on best practices for developing and selecting proprietary names and is intended to complement the Contents Guidance, the FDA’s existing guidance for industry. This statement represents the only connection between the guidances.
The Contents Guidance is directed to an “applicant or sponsor” and applies to proprietary name (trademark) submissions for: (1) prescription drug products, including biologics, that are the subject of an investigational new drug (IND) application, a new drug application (NDA), an abbreviated new drug application (ANDA), or a biologics license application (BLA); and (2) nonprescription drug products that are the subject of an IND, NDA, or ANDA. An applicant or sponsor, however, is only required
to make a submission of its proposed proprietary name as part of an NDA, ANDA, or BLA. If the sponsor or applicant wishes to have an earlier evaluation, the FDA will provide a preliminary review of a proposed name while the product is under an IND, but only after phase two clinical trials for the drug have been completed.
Even if the proposed name is reviewed during an IND and is deemed conditionally accepted, the acceptability status may change because the FDA still has authority to review the proposed trademark during NDA review. If the proposed name is approved conditionally during an NDA review, based upon representations by the FDA in 2014, the acceptability status should not change unless there is a material change to the NDA by the sponsor or applicant.
The FDA, however, has not yet formalized that representation in any of the referenced guidances or its “Manual of Policies and Procedures” (MAPP). Thus, it’s still possible that a conditionally approved proposed trademark could be rejected any time during the NDA review, including before final approval of the product.
Within the Contents Guidance, the FDA states that each submission should be identified as either a request for proprietary name review (or if an amendment, an amendment to a request for proprietary review) or a request for reconsideration of proprietary name (following an initial rejection of a proposed proprietary name). The FDA further states that sponsors or applicants should include up to two proposed proprietary names for review and the applicant should specify its first choice, i.e., primary and alternate. However, the FDA will not evaluate the alternate name unless the primary name is determined to be unacceptable and the applicant has confirmed with the FDA in writing that it would like the alternate proposed proprietary name to be reviewed. In addition, the intended pronunciation of the proposed proprietary name, and the derivation of the proprietary name should be included in the submission.
In connection with these three elements (the proposed proprietary name, pronunciation, and derivation of the proposed name), a sponsor developing a proposed product name is well advised to carefully consider the factors outlined in the “FDA’s Approach to the Evaluation of Proposed Proprietary Names” found in the Contents Guidance (p. 5, Section II.D). Included is reference to the tools and methods the FDA uses (outlined in Section IV.A of the Concept Paper) for its analysis which are contained in the FDA concept paper titled “PDUFA Pilot Project Proprietary Name Review” (Concept Paper
Many of the elements described in the Concept Paper are reproduced and continued in the FDA’s Best Practices Guidance. As such, the Contents Guidance and the Best Practices Guidance, plus the Concept Paper form the landscape of content to be considered with respect to requesting a proprietary name. Although the Contents Guidance doesn’t mention the Best Practices Guidance, the Best Practices Guidance does refer to the Contents Guidance.
Additional content that the FDA says sponsors and applicants should include in their submission is further set out in the Contents Guidance at page 10, Sections IV.B, C, and D and consists of:
- Intended meaning of the proprietary name’s modifiers;
- Pharmacologic/therapeutic category;
- Proposed label and labeling if available at the time of filing, or, if the product label and labeling is not available, information that is expected to form part of the label; and
- Information about product dispensing and delivery
Since a modifier (prefix or suffix) might suggest different meanings to health care professionals and consumers, to minimize product confusion, the submission should include the intended meaning of the modifier, the rationale for the modifier, and any studies that have been conducted to support the use of the modifier. As well, in connection with information expected to be part of the label, this is the requirement if the request for review is filed during the IND when the final label is not available. As such, this requires information that will be found in the label, such as established name, prescription status, dosage form, product strength, proposed indications for use, routes of administration, etc.
The Contents Guidance also sets out a final element, which is the “Applicant’s Assessments of Proprietary Name, Packaging, and/or Labeling” (Contents Guidance, p. 15, Section IV.E). To support its position that the proposed name is not similar to existing drug names and therefore approvable, a sponsor or applicant may submit safety review data, simulation studies, Failure Modes and Effects Analysis (FMEA) results, etc., based on what studies and analyses appear to be important according to the high-level descriptions provided in the Contents Guidance, Best Practices Guidance, and Concept Paper.
The Best Practices Guidance attempts to provide objective and quantifiable measures to sponsors or applicants. It also places emphasis on the FDA’s Phonetic and Orthographic Computer Analysis (POCA) tool. Specifically, the FDA established the following three ranges of scores (Best Practices Guidance Appendices D, E, and F) so sponsors or applicants can predict with greater certainty whether a proposed pharmaceutical trademark would be “approvable” by the FDA.
Unfortunately, the POCA tool is only one factor considered by the FDA. The Best Practices Guidance makes it clear that the FDA will conduct its own internal safety review even if a sponsor or applicant has conducted a safety review and submitted its results under the “Applicant’s Assessments” section of the Contents Guidance. Unpredictability continues in the face of a sponsor’s safety review since prescription simulations (safety reviews) are, among other things: (1) lacking scientific validation; (2) open to subjective interpretation; (3) not representative of actual prescribing and dispensing situations; (4) not reproducible; and (5) not free of false positives.
Although the content for the “Applicant’s Assessments” section of the Contents Guidance addresses the primary inquiry of the Best Practices Guidance, namely whether the proposed trademark is too similar to existing drug brand names, it is noteworthy that any information provided under “Applicant’s Assessments” is not required: “FDA [will not] consider a submission incomplete because this information is not provided.” Therefore, because the FDA does not require that data, and, conducts its own safety review, study, and analysis, the FDA reserves the right to make that determination based on its own data. Indeed, it isn’t clear to what extent, if any, the FDA considers the data submitted by the sponsor or applicant. Thus, even though a sponsor or applicant may have a favorable safety review, FMEA result, a POCA score identified as “low similarity” or “moderate similarity,” etc., all of which would suggest an “approvable” proposed trademark, any one, or more, of the previously enumerated items could lead to a different result when the FDA conducts its own internal safety review and overall assessment. Stated differently, the FDA does not make it clear how it conducts its assessments and arrives at its conclusions, other than referring to the general principles set out in the Contents Guidance, the Concept Paper, and the Best Practices Guidance, and to say all of the factors outlined in each of these documents are taken into consideration. This lack of transparency helps to explain the DMEPA-proposed trademark approval data within the table below:
*Center for Biologics Evaluation and Research
This data is from an FDA Update: Proprietary Name Review Program PhRMA presentation given on July 24, 2017; thus, the 2017 information is from data from October 1, 2016 to June 14, 2017, and the data does not provide specific insight about whether the approved trademarks were the primary or secondary mark, or whether there were re-filings of name approvals because of a rejection prior to final regulatory approval of the drug product.
Regardless, whether you are a pharmaceutical trademark owner or a health authority reviewing proposed brand names, patient safety remains paramount. Thus, sponsors or applicants must continue to work with the FDA to minimize the role of pharmaceutical trademarks in medication errors. Working together, it may be possible to develop and/or further refine objective tools like POCA, and provide greater insight as to how different factors are considered and the weight they are given in making decisions, with the hope of providing greater predictability for sponsors or applicants, and at the same time, ensure greater safety for patients.
Although every effort has been made to verify the accuracy of items in the INTA Bulletin, readers are urged to check independently on matters of specific concern or interest.
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