External analgesic drug products are regulated as OTC monograph drugs by FDA primarily used as topical medications applied to the skin for pain relief under OTC monograph system 21 CFR part 348.
As per 21 CFR part 348, the drug product manufactured with FDA permitted active ingredients within specific concentration limits and follows strict labeling rules, it is Generally Recognized as Safe and Effective (GRASE). It does not require individual FDA approval to market the product.
The FDA divides external analgesics into categories based on how they work to relieve pain, itching, or irritation:
- The most common permitted allowed active ingredients menthol (1.25–16%), methyl salicylate (10–60%), and capsaicin (0.025–0.25%).
Counterirritants: These ingredients create a cooling or warming sensation to distract the brain from pain.
- Menthol, camphor, and capsaicin.
Local Anesthetics: These numb the skin by blocking nerve signals.
- Lidocaine (maximum allowable concentration of 4% for OTC use).
Topical Corticosteroids: Used to reduce inflammation and itching.
- Hydrocortisone (up to 1%).
Antihistamines: Primarily used to relieve itching from bug bites or rashes.
- Diphenhydramine hydrochloride.
Manufacturers must follow strict cGMP regulations in the manufacturing process.
Drug Facts Label: All packaging must feature a standardized “Drug Facts” panel detailing active ingredients, purposes, uses, and warnings.
Required Warnings: Labels must clearly state “For external use only” and warn against applying the product to broken, irritated, or heavily bandaged skin.
Facility Registration: Establishment must register and list the drug under their own NDC number. Every year they must renew their registration and drug listing.
Liberty Management Group , as a leading FDA consultant will provide assistance with drug establishment registration, drug listing and label review.
Sudha S
Regulatory Consultant
Email: office@libertymanagement.us