Medical Device Link.

Originally Published PMPN December 2001

REGULATORY FOCUS

Manufacturers now have a tool clarifying a 1997 rule on labeling statements regarding geriatric use of drugs and biologics.

FDA has released a new guidance on how to submit information for the "Geriatric Use" subsection of the labeling for prescription drugs and biologicals.

In the August 27, 1997, Federal Register [62 FR:45313], the agency published a rule establishing a special labeling section to provide elderly patients with relevant information regarding a product's use. It is part of the Precautions section, which would be combined with the Warnings section should FDA's proposed changes to the overall format be adopted. For more information on the agency's proposed changes, see the "Regulatory Focus" column in the March 2001 edition of PMP News.

As a result of the rule, manufacturers of many drugs and biologics must submit geriatric labeling supplements under 21 CFR 314.70 or 601.12. Agency approval is required prior to implementation, except in cases where insufficient data exist to determine whether geriatric responses to a drug are different from those of younger patients, or when a precaution or dosage administration instruction is added or strengthened.

The new guidance, published October 4, 2001, outlines the content and format of geriatric labeling submissions and delineates who should submit them and when. The full text can be viewed at www.fda.gov/cder/guidance/3636fnl.htm.

Manufacturers of previously approved drug and biologic products must submit revised labeling and data supporting the revision. For generic drugs, revised labeling should be submitted based on the approved geriatric labeling of the reference-listed drug product in the Orange Book when that drug's labeling is changed to include a Geriatric Use subsection. However, if a particular generic drug is the reference-listed drug, then revised labeling and supporting data must be submitted.

Submissions are not required for over-the-counter drugs, marketed drugs for which there is no approved application, and prescription drugs approved but not marketed. In the latter case, if the manufacturer resumes marketing the product, a geriatric labeling supplement must be submitted prior to marketing.

Several categories were given priority implementation: psychotropic drugs, anticoagulants, quinolones, oral hypoglycemic agents, digoxin, antiarrythmics, and calcium channel blockers. Submissions for these were due by August 27, 1998. Deadlines for other drugs depend on the approval date. Drugs submitted for approval after August 27, 1998, must have geriatric information in their submission. For other drugs, the older the drug, the later the implementation date.

If a drug product is unlikely to be used by the geriatric population, the manufacturer may submit a request for the omission of the section or an alternative, with reasons supporting the request.

The rule is not applicable for most topical ophthalmic drug products. This is because clinical differences in responses between geriatric and younger populations have not been demonstrated to occur in clinical studies of topical ophthalmic drug products. Systemic absorptions are minimal, thus systemic interactions are unlikely. In these cases, the applicant should request an alternative statement, such as "No overall differences in safety or effectiveness have been observed between elderly and younger patients" in lieu of a Geriatric Use subsection.

The submission should begin with a cover letter indicating that it pertains to geriatric labeling, citing the relevant paragraphs in the regulation. The user fee identification number, or a reason for exception if there is no number, must also be included. Few geriatric labeling supplements are expected to require the payment of user fees because they will not require clinical data for approval. Only supplements for which clinical data are required for approval are assessed fees. However, if data supporting the removal or lessening of a warning, precaution, or contraindication meet the definition of clinical data for purposes of assessing user fees, the supplement will likely be assessed a user fee.

After a table of contents comes the revised labeling draft. This should include a marked-up copy of the last approved labeling, showing all additions and deletions and where the supporting data are located in the submission.

Next comes a statement from the applicant about which specific paragraphs in 21 CFR 201.57(f)(10) (i) through (vi) are applicable to the revision and an explanation of how the regulation applies. Following that is the user-fee cover sheet.

Last comes the supporting data and an analysis of it. The sources must be described. Safety data should include the extent of exposure, duration of exposure, and adverse events. If there is voluminous pertinent data, the applicant should contact the relevant FDA division where the application resides to discuss what should be submitted. The applicant must state how and when the medical literature was searched and include a complete listing of literature reports searched.

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