The Over-the-Counter (OTC) Drug Review was established to evaluate the safety and effectiveness of OTC drug products marketed in the United States before May 11, 1972. It is a three-phase public rulemaking process (each phase requiring a Federal Register publication) resulting in the establishment of standards (drug monographs) for an OTC therapeutic drug class.
The first phase was accomplished by advisory review panels. The panels were charged with reviewing the active ingredients in OTC drug products to determine whether these ingredients could be generally recognized as safe and effective for use in self-treatment. They were also charged with reviewing claims and recommending appropriate labeling, including therapeutic indications, dosage instructions, and warnings about side effects and preventing misuse.
The agency published the panel’s conclusions in the Federal Register in the form of an advanced notice of proposed rulemaking (ANPR). After publication of the ANPR, a period of time was allotted for interested parties to submit comments or data in response to the proposal.
According to the terms of the review, the panels classified ingredients in three categories as follows:
Category I: generally recognized as safe and effective for the claimed therapeutic indication;
Category II: not generally recognized as safe and effective or unacceptable indications;
Category III: insufficient data available to permit final classification
The second phase of the OTC Drug Review is the agency’s review of active ingredients in each class of drugs, based on the panel’s review of ingredients, on public comment, and on new data that may have become available. The agency, in turn, publishes its conclusions in the Federal Register in the form of a tentative final monograph (TFM). After publication of the TFM, a period of time is allotted for interested parties to submit comments or data in response to the agency’s proposal.
The publication of final regulations in the form of drug monographs is the third and last phase of the review process. The monographs establish conditions under which certain OTC drug products are generally recognized as safe and effective. Products containing active ingredients or indications that are nonmonograph require an approved New Drug Application for marketing.
After publication, a final monograph may be amended, either on the Commissioner’s own initiative or upon the petition of any interested person. OTC drug monographs are continually updated to add, change, or remove ingredients, labeling, or other pertinent information, as needed.
Combination products are defined in the Code of Federal Regulations Title 21 (21 CFR 3.2(e)) as follows:
– A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity
– Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;
– A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or
– Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect.” (1)
– Validation Procedures for Combination Product Type are as follows:
– Value code system is 2.16.840.1.1138220.127.116.11.1
– Value comes from the Combination Product Type list.
– Display name matches the value code
– If the document type is for bulk ingredient (53409-9), OTC animal drug (50577-6), OTC type A (50576-8), OTC type B (50574-3), OTC type C (50573-5), prescription animal drug (50578-4), VFD type A (50575-0), VFD type B (50572-7), VFD type C (50571-9), Cosmetic (58474-8), Dietary Supplement (58476-3), Medical food (58475-5), Human compounded drug (75031-5), Licensed Vaccine Bulk Intermediate (53406-5), Drug for Further Processing (78744-0) or Animal Compounded Drug Label (77647-6) then there is no combination product type characteristic on any package.