Guidance for Geriatric Labeling
Supplements intended to clarify geriatric drug use.
FDA has released a draft of guidelines for the content and format of special geriatric labeling. The draft stems from a final rule published by FDA in the August 27, 1997, Federal Register (62 FR:45313), establishing the geriatric use subsection in 21 CFR 314 for prescription drug and biologic labeling. FDA recognizes that some drugs should be used differently by different age groups and wants industry to address that with labeling. As a result, some companies may have to rearrange or add new information to their labeling.
The rule took effect August 27, 1998, and the guidelines are to be finalized later this year. According to the proposal, many companies that submit new drug applications will also need to include geriatric labeling supplements with their submissions, which require FDA approval before implementation, except when the labeling changes strengthen instructions for use according to 21 CFR 314.70(c)(2) or 601.12(f)(2). Agency approval is also not required if insufficient data exist that show whether geriatric patients react differently from younger patients. Labeling for topical ophthalmic drug products, specifically, should include a statement indicating that there are no differences in safety and effectiveness between elderly and younger patients.
The rule does not apply to over-the-counter drugs, unmarketed but approved drugs, or drugs approved before 1938. Generic prescription drugs must conform to the labeling of the corresponding brand-name drug. FDA's Office of Generic Drugs plans to inform generic drug makers of their responsibility to provide geriatric labeling supplements if their labeling does not already conform to that of the respective brand-name drug.
The following classes of drugs, which FDA says pose potential problems for geriatric patients, were required to have their labeling changes approved prior to the rule's effective date: psychotropics (such as antidepressants), nonsteroidal antiinflammatories, digoxin, antiarrhythmics, calcium channel blockers, oral hypoglycemic agents, anticoagulants, and quinolones.
For all other classes of currently marketed drugs, the geriatric-use labeling supplement must be submitted by August 27 of an upcoming year, depending on how long ago the drug was approved. For instance, for a drug approved between 1975 and 1981, a supplement must be filed by August 27, 2001. The more recent the drug, the quicker the submission is needed.
Geriatric-use labeling supplements must be based on at least one of the six formats described in 21 CFR 201.57 (f)(10). The first format includes a specific geriatric indication, with more detailed discussion in the appropriate sections, such as the one on warnings and precautions.
The second format states that geriatric indications are the same as those for younger adults. If not enough geriatric subjects (fewer than 100) are studied, or if there is no difference in geriatric response to the drug, that should be noted. If there are differences, they should be described with more details in the appropriate sections.
The third format recommends that information from a pharmacokinetic or pharmacodynamic study on elderly patients be briefly described, with reference to more detailed discussion in appropriate sections. If the drug is substantially excreted by the kidney, the supplements should include standard language for that occurrence.
The fourth format mentions any specific hazards relevant to the elderly, with references to the appropriate sections for more detailed discussions.
The fifth format lists a statement that encourages safe use of the drug based on good clinical practice.
The sixth format states that if none of the above five formats are applicable, the sponsor must explain why and may propose an alternative statement.
Submissions should be sent to FDA using form 356h for drugs or form 2567 for biologics. The cover letter should explain that the submission is a geriatric labeling statement, specify the format(s) applicable to the product, and include a user-fee identification number (or an explanation why no user fee is required). Not many user fees are expected for these submissions because they will not require clinical data for approval.
Included in the submission should be a draft of the revised labeling, an indication of the applicable regulatory format and an explanation of how it applies, and a marked-up copy of the last approved labeling clearly showing all additions, deletions, and locations of the supporting data.
The supporting data should also be included and the source should be noted. Safety data should note any adverse events and the extent and duration of exposure. If any change from currently approved labeling is necessary, relevant analysis and source data should be enclosed. If the labeling will merely relocate existing information, reference to the original data is not needed.