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The US Food, Drug and Cosmetic Act defines a drug as an article intended for the diagnosis, cure, mitigation, treatment or prevention of disease and intended to affect the structure or any function of the body of man or other animals. Drugs are commonly separated into two categories; Prescription (Rx) Drugs and Over-the-Counter (OTC) Drugs.
A Prescription Drug is one that requires formal approval by the FDA prior to launch. The process to obtain FDA approval for a Prescription Drug is quite extensive, requiring many years of research and data collection, and tremendous resources.
All of these efforts and dollars culminate in the submission of a New Drug Application (NDA – for new drugs) or Abbreviated New Drug Application (ANDA – for generic drugs) to FDA. In either case, a New Drug Application includes extensive information about the drug substance and the specific product for which approval is sought.
It is not uncommon for a new Prescription Drug to cost hundreds of millions of dollars and eight years (on average) or more to bring it to market. All this to demonstrate the safety and efficacy of a new Prescription Drug product.
In contrast, Over-the-Counter Drug products do not require pre-approval by the FDA, meaning that there is no requirement for submitting a New Drug Application or conducting extensive research. As a result, the investment of time and resources needed to launch an OTC Drug is a small fraction of that required to launch a new Prescription Drug.
In spite of these greatly relaxed requirements, there still remain specific steps that must be followed in order to legally launch an OTC Drug product in the U.S.
For OTC Drug products, the first requirement is that the product complies with the OTC Drug Monograph to which the product is assigned.
The purpose of having an OTC Drug Monograph System in the U.S. is to streamline the introduction of well-known and well-studied drug products to the marketplace, and especially those which contain active ingredients that have a long and safe history of effectively preventing and/or treating specific health conditions.
IMPORTANT NOTE: An OTC Drug Product which fails to meet the requirements of the applicable OTC Drug Monograph is considered to be a ‘new drug’ by FDA. If such a product were to be launched without prior FDA approval, FDA would seek immediate removal of the product from distribution on the grounds of it being an ‘unapproved drug’.
While there is a separate OTC Drug Monograph for each drug category, all Monographs are structured in a similar manner. Each defines a specific drug category, lists the active ingredients that are permitted (singly and in combination), the quantity of each active ingredient that is permitted in the product, efficacy testing requirements (where applicable) and labeling requirements.
If a new OTC Drug product fully complies with OTC Drug Monograph requirements, there is no need for FDA approval prior to launch. It may simply be launched, once it is verified that all Current Good Manufacturing Practice (cGMP) requirements have been met.
It is important to note that any Organization which engages in the manufacturing, packaging, testing, storing, holding or distributing of a drug product is required to register with FDA and is subject to the cGMP regulations as published in 21 CFR Parts 210 and 211.
Even if the owner of a drug product is a ‘virtual’ company that outsources all of the above-described activities to service providers, that drug owner is still required to register with FDA and bears the responsibility of ensuring that each of the service providers has performed their services in full compliance with cGMP.
In order to successfully and legally launch a new OTC Drug Product within the US, a number of requirements must be met prior to and after launch.
Although the order of events may vary, the important fact remains that FDA expects all requirements to be met. An example of an OTC Drug launch sequence that would satisfy current cGMP requirements may be described as follows:
Once an Organization makes a business decision to develop and launch a new OTC Drug Product, the first step in the process is product conceptualization.
At this stage, the product concept is decided upon. This includes the selection of which active ingredient(s) will be utilized, their respective potencies, and comparison with the applicable OTC Drug Monograph to ensure that the product concept does not violate the Monograph.
Once the product concept has been established, the next step is to develop a formula, select raw materials to be included in the formula, and identify raw material vendors.
This stage typically involves the making of experimental product batches and a significant amount of lab testing for the purpose of ensuring that the product exhibits the desired attributes.
Upon successful completion of this stage, the product formula is finalized.
Having finalized the product formula, the next step is to select the container/closure system for the new OTC Drug Product. This must be decided upon prior to conducting stability studies since expiration dating of a drug product is based upon the stability of the product and its compatibility with the container/closure system in which it will be distributed.
It is important to note that the United States Pharmacopeia (USP) now requires that plastic container systems be tested for the presence of undesirable elements and compounds which have been shown to leach into some drug products after they have been filled into their primary packaging.
Plastic container testing requirements may be found in USP General Chapter <661> Plastic Packaging Systems and their Materials of Construction. This is the current requirement until December 1, 2025 at which time new Chapters <661.1> Plastic Materials of Construction and <661.2> Plastic Packaging Systems for Pharmaceutical Use will replace Chapter <661>.
cGMP requires that formal specifications be established for raw materials, container components, and finished drug products.
Such specifications are used to assess the suitability of the drug product, the raw materials from which it is manufactured, and the components in which it is packaged. Stability specifications are also required.
cGMP requires that analytical methods employed in the testing of drug products and their critical components must be validated.
This ensures the accuracy and suitability of testing methods with respect to the drug product in question.
Having finalized the product formula and selected the container and closure system, the next step is to establish the expiration date that will be used for the product launch.
This is achieved by making a “stability batch” and conducting stability testing at appropriate intervals. The batch must be at least 1/10th the size of a production-scale batch of the new product and it must employ processing equipment that is of similar design to that which will be used in production scale batches.
Stability testing must be conducted in each package configuration in which the product will be distributed. If Accelerated Stability Studies are employed to extrapolate (“estimate”) an expiration date for the launch, it is required that Real-Time Studies be conducted concurrently, so as to confirm the date arrived at through extrapolation.
NOTE: Expiration dating cannot be based solely upon the results obtained from Accelerated Stability testing. Expiration dating must be confirmed through the conducting of Real-Time Stability testing.
Artwork for labeling must be created and carefully reviewed for accuracy and compliance with the applicable OTC Drug Monograph and also general rules for the labeling of drug products. Once approved, labeling materials must be printed in time for the product launch.
cGMP requires that the process used to manufacture drug products must be validated, so as to ensure that process equipment and operating parameters are appropriate, and that the resulting product will meet all specifications and acceptance criteria.
Typically, process validation is conducted over three (3) batches and includes verification of process parameter limits that appear in the Master Batch Record.
Although OTC Drug Products do not require FDA approval prior to launch, the FDA must be notified of new OTC Drug Products prior to their launch. This notification takes the form of Drug Listing. Instructions for completing the Drug Listing process may be found in 21 CFR 207 Subpart D – Listing.
The basic requirement is for owners of OTC Drug Products to complete and submit a Drug Listing Form (found on FDA’s website) for each OTC Drug Product that it intends to launch. Samples of product labeling must also be provided at the time the Drug Listing Form is submitted.
Once an OTC Drug product has been launched, the drug owner has an ongoing cGMP commitment to conduct stability testing on the first three (3) commercial batches, and also to initiate stability testing on at least one batch of the product that is manufactured within each calendar year, for each year that the product continues to be manufactured and distributed.
This ensures that the drug product and the manufacturing process remain in a state of control. Any change that is made to the product formula, container and closure system, the manufacturing process or any other critical parameter must be assessed for the possibility of having to reestablish expiration dating for the product after that change has been made.
cGMP requires that drug owners conduct an annual review of each of its OTC Drug Products, so as to verify the continuing appropriateness of the product formula, its specifications, testing methods and the manufacturing process.
Non-conformances such as testing failures, consumer complaints and Adverse Events reported from the field must also be tabulated and assessed. This APR must be fully documented and made available to FDA upon their request.
When it comes to launching a new OTC Drug product in the U.S., CPT℠ Labs can provide expert testing and consulting assistance nearly every step of the way.
This includes early-stage consulting assistance in assuring that your new product complies with the correct OTC Drug Monograph; raw material and container/closure system testing; In-process, Product Release and Stability testing; Method Development and Method Validation services; Process Validation and Cleaning Validation testing; OTC Monograph efficacy testing (SPF, for example).
You can rely upon our expert capabilities to assist you in bringing your new OTC Drug product to market in the most efficient and compliant manner.
Based on the individual needs of our clients, we offer a wide range of support across various departments. Since initial product testing can be fairly complex in terms of a high-quality, safe and trusted product, our clients typically explore the benefits of numerous departments and areas of expertise, including:
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