OTC Cosmetics Drugs regulation and Good Practices

OTC Cosmetics Drugs regulation and Good Practices

2020-08-30T09:37:05+00:00February 14th, 2015|

Background and history

In 1938, the FFDCA (Federal Food, Drug and Cosmetic Act) granted FDA cosmetic products and ingredients regulation authorization.

The statutory provisions of the FFDCA addressing cosmetics includes adulteration and misbranding provisions. In addition to the FFDCA, cosmetics are regulated under the Fair Packaging and Labeling Act (FPLA) and related regulations.

The Cosmetics provisions were amended by the Color Additive Amendments Act of 1960 and the Poison Prevention Packaging Act, but remain basically the same as the provisions in the 1938 FFDCA.

Cosmetics products are not subject to the same regulation efforts, complexity, time, registration and approval as drugs products. Moreover, Cosmetics products manufacturered in general and Cosmetics OTC products manufactured in particular, will need to upgrade their manufacturing facility, Quality Assurance and documentation system, machinery and in addition, to adopt Good Manufacturing (GMP) documentation (GDP), storage (GSP), engineering (GEP) practices and validations in order to register the facility and enter the Cosmetics-Drugs combination products. As part of the Cosmetic Drug and OTC products, manufacturers will have to report their product’s adverse effects to the FDA.

The FD&C Act (Federal Food, Drug and Cosmetics Act) restricted adulterated and /or misbranded Cosmetic products and strongly recommends to follow GMP (Good Manufacturing Practice) standards, self and/or external inspections and audits in addition to an effective Quality System, in order to minimize these kind of risks and to assure Cosmetic products meet the quality and their intended use consistently.

Cosmetic Vs. Drug product

Cosmetic product definition

Based on FD&C Act (Federal Food, Drug and Cosmetic Act) Cosmetic is defined as cleansing, beautifying, promoting attractiveness or altering the appearance. Products intended to be rubbed, poured, sprinkled, or sprayed on, introduced into or otherwise applied to the human body. Cosmetic products include skin moisturizers, perfumes, lipsticks, fingernail polishes, eye and facial makeup preparations, cleansing shampoos, permanent waves, hair colors, deodorants, as well as any substance intended for use as a component of a Cosmetic product.

Drug product definition

Based on FD&C Act (Federal Food, Drug and Cosmetic Act) Drug is defined as product intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease and products affect the structure or any function of the body of man or other animals.

Pharmaceutical/drug Cosmetic and OTC products combinations

Cosmetic products and ingredients, with the exception of color additives or Active Pharmaceutical Ingredients (API), do not require FDA submission or approval.

There are products which are Cosmetic products containing Drug ingredients (cosmetic drugs) and as such, fall into both definitions; Cosmetics and Drugs. There are products that have multiple effects (Cosmetic and Pharmacological) and are Cosmetic product that contain Active Pharmaceutical Ingredient (API) that have a pharmacological effect. For example, an anti-dandruff shampoo is a Cosmetic and Pharmacological (drug) product because it is being used to clean the hair as well as to treat dandruff. Additional combinations of Cosmetic and Drug products are anti-aging facial creams, fluoride toothpastes, antiperspirant deodorants and Sun Protection Factors (SPF) moisturizers and makeup.

Cosmetics Drugs and OTC products require FDA pre market approval via New Drug Application (NDA) procedure or conform to a “monograph” as specified by FDA’s OTC (Over The Counter) Drug Review. These monographs define the analysis process of OTC drug ingredients which will be identified for assuring safe and effective and not misbranded cosmetic OTC product.

Cosmetic  and Drug intended use

Product intended use is determined based on product label claims, consumer perception of the product based on product and/or brand reputation and API (Active Pharmaceutical Ingredients) which have a therapeutic effect.

Cosmetic product regulation and registration

According to the FD&C act Cosmetic products do not require FDA approval before marketing, unless they contains color additives or may contain restricted ingredients. Drugs, however, require registration in the U.S including NDA (New Drug Application) submission to the FDA. Monograph testing used for Drug ingredients identification, safety, effectiveness and misbranded avoidance as established by FDA’s OTC (Over-the-Counter) Drug Review (for more information refer to article New drug development and regulation).

Cosmetic-Drug combination products are subjected to Cosmetic and Drug FDA regulation and should comply with OTC and Drug-Cosmetic labeling requirements. The determination of whether a Cosmetic is also a Drug and therefore subject to the additional statutory requirements that apply to drugs, is based on the distributor’s intent or the intended use. The intended use of a product may be established in several ways such as claims on product labeling or in advertising /promotional materials or through the inclusion of ingredients that will cause the product to be considered a Drug because of a known therapeutic use.

The FDA has published several Over The Counter (OTC) categories monographs of nonprescription Drugs treatments such as acne, dandruff, seborrheic dermatitis, psoriasis medications and sunscreens.

Cosmetic products formulation registration is not mandatory but for cosmetic OTC products manufacturers are obligated to register their Drug products (FDA) including Drug active material being added to the Cosmetic product.

Cosmetic products manufacturers are solely responsible for both ingredients and finished Cosmetic products safety before marketing. Ingredients safety can be tested on several animal models using the Cosmetic ingredients and monitoring irritation (skin, eye), allergic and toxicity following ingredients exposure in order to prove the Cosmetic product is safe for use.

In the past decade, Cosmetic products safety on animal models is less common due to animal rights advocates which has affected public opinion. As a result, the FDA offers alternative safety tests and scientific models as much as possible in order to minimize animal models usage.

Cosmetic Ingredient Review (CIR) program is expert panel that review the most common Cosmetic ingredients which are being used in the Cosmetic industry in order to determine whether:

  • The ingredient is safe for use in the relevant ingredient concentration
  • The ingredient not safe and therefore should not be used in cosmetic product formulation
  • The ingredient is safe with qualifications and therefore can be used under specific conditions
  • The ingredient that has insufficient data or information for clear determination

Although CIR review reports are being published, Cosmetic products manufacturers are recommended and not obligated to follow these findings.

Color additives

Cosmetic products’ color additives include any dye, pigment or substance that may impart product color on the human body. All kinds of color additives are supposed to be defined as “safe for use”. Petroleum derived color additives should be certified by the FDA before usage. Cosmetic products that contain color additive will be registered and receive FDA approval before marketing. Cosmetic product will be considered adulterated in cases of contain non-certified color additive or contain certified color additive which was not comply with the applicable FDA regulation.

Mineral plant or animal sourced color additives do not require FDA certification.

Voluntary Cosmetic registration program

FDA’s VCRP (Voluntary Cosmetic Registration Program) exist since 1974. VCRP program encourages local Cosmetic manufacturers and packaging companies to register their facilities 30 days before operation. Moreover, every Cosmetic products manufacturer and packagers (outside the U.S) that are interested in exporting their products to the U.S market should register their facilities and product formulation ingredients.

 Cosmetic Drug product adulteration, misbranding and mislabeling

Cosmetic Drug product adulteration

Cosmetic Drug product will be defined as adulterated in the following circumstances:

  • Product contains poisonous or deleterious substances which may cause consumer injury under the conditions of use detailed on the Cosmetic Drug product label
  • Product consists filthy, contaminated, putrid or decomposed substances
  • Product was manufactured, packaged, stored or distributed under insanitary and/or non-controlled conditions that may result in product contamination, low quality and/or consumer risk
  • Product container composed of poisonous or deleterious materials which may render product content that may risk patient health
  • Product contain unsafe color additive (except for hair dyes)

In order to decrease adulteration risks, the FDA established a restricted poisonous or deleterious material list for specific usage that can cause Cosmetic product adulteration.

Cosmetic drug product misbranding and mislabeling

The FFDCA restrict adulteration or misbranding of Cosmetic products including introduction, receipt and delivery of adulterated or misbranded Cosmetics into interstate commerce. In cases where adulterated or misbranded Cosmetic product is being introduced or held for sale, FDA may take enforcement actions.

According to FFDCA, Cosmetic Drug product will be defined as “misbranded” in the following circumstances:

  • False or misleading label
  • Partial information on the label
  • Information on the label is not prominently placed and/or conspicuousness and as result may mislead to consumer usage
  • Container design or forming may mislead consumer usage
  • Usage of color additives was made but required information on packaging and labeling does not conforms regulatory requirements
  • Packaging or labeling violates does not conform regulations poison Prevention

Cosmetic products adverse events

Currently, consumers can report to the FDA on negative reactions and adverse events as results of cosmetic products usage via “MedWatch” website. The FDA can use the adverse events reports in order to identify repeatable adverse events, consumer complaints and low quality Cosmetic products in order to take legal action if needed.

Good Manufacturing Practices (GMP) and GxPs


In the past decade, GMP was adopted into the Cosmetic industry for maximizing the assurance that Cosmetic products are consistently manufactured in the required quality that is proper for their intended use. In order to achieve the required product quality, both manufacturing and quality controls aspects should be followed.

ISO 22716 established initial basic GMP (Good manufacturing Practices) guideline at 2007.Since then, the FDA published a draft guidance for Cosmetic Good Manufacturing Practices that includes updates, clarifications that included also data from ICCR (International Cooperation Of Cosmetic Regulations) and ISO 22716.

The FFDCA main concerns are related to:

  • Cosmetic drug product adulteration with substances which may risk consumer
  • Cosmetic drug product that contain contaminated, filthy, putrid, or decomposed substances
  • Low quality product that may harm the consumer

Documentation & records

SOPs, batch records, policies, protocols, Risk Assessments and other controlled documents should be written and include all the internal procedures, methodologies and instructions in a controlled and effective manner.

All tasks and day to day activities should be described, documented, trained and approved by all relevant functions, managed and retained in a controlled manner in order to assure the following:

  • All different processes follow quality and GxP principles
  • All products manufactured will be tested and meet the required quality aspects
  • Human errors prevention as result of lack of information and misinterpretation
  • Traceability improvement following Good Documentation Practices
  • Improved deviation investigations and root cause analysis
  • Critical process parameters should be controlled and monitored
  • Utilities and process equipment should be validated

Documents will include all current relevant information and should be retained in either electronic or paper format.

Batch records should be detailed enough and include all information related to raw material identity and quantities, production steps, process and environmental parameters, process yield, limits, sampling, in process controls, storage and batch status.

Controlled documents should be reviewed, approved and trained periodically by relevant company personnel in order to verify the information in the document is updated and reflects the actual procedures being performed.

Internal quality audits and supplier audits

In addition to supplier GMP and quality audits, the Cosmetic manufacturer/company should periodically perform internal GMP and quality audits and inspections. These audits/inspections should be performed either by objective personnel inside the company (not from the same audited or related department) or using external auditors/inspectors. It is always recommended to use external auditors, as they usually have a much more objective point of view.

The main target of the internal quality/GMP audits/inspection is to ensure that the Cosmetic company follow and implement all quality and GMP standards detailed in this article, to assess the compliance of the company and most importantly, to identify gaps to be closed using the appropriate corrective and mitigation actions. The internal audit observations and summary report should be presented to the company senior management and corrective actions implementation should be documented, followed, tracked (usually via CAPA mechanism) and reported to senior management as part of management review.

The company should audit it’s suppliers periodically in order to ensure that the purchased and supplied raw materials, printed material, packaging material, equipment and or other components meet the quality and standards required by the company and that these materials/components are being manufactured and supplied according GMP principles and standards.

Building and facilities

Cosmetic drug and OTC products should be manufactured in facility that complies with all current Good Manufacturing Practices (cGMP). The facility should be designed according to GMP standards including proper construction material and facility design. Material and personnel flows, sufficient space for manufacturing and maintenance as well as proper segregation should be covered under facility conceptual design in order to minimize the risk for mix-ups, contamination and cross contamination.

The Cosmetics GMP facility will have pest control that should be monitored routinely according to a detailed procedure.

Raw material, intermediate and final product should be exposed only in clean rooms and/or controlled areas. The inlet air should be filtered to the required cleanness level and supplied in the required temperature and relative humidity values.

Walls, ceiling, floor, windows, doors and other relevant items should be Pharmaceutical grade materials that will be smooth, easy to clean, resistant to cleaning agents and will not shed particles.

The process and storage environmental conditions such as temperature, relative humidity and other relevant working conditions should be controlled, monitored and validated.

Gowning policy as well as cleaning and maintenance procedures for machinery, systems and equipment should be written and followed in order to keep the cleanness and operational state of the facility and to allow sanitary operation.

Proper fixtures, ducts, pipes, drainage, air breaks and back flow pretension mechanisms should be installed in order to prevent contamination of the product.


Equipment that is being used for OTC and Cosmetic-Drug products should be designed for its intended process use include sanitary design and should be constructed from Pharmaceutical grade materials such as stainless steel, glass etc. for corrosion and dirt accumulation prevention and clean ability improvement minimizing the risk of contamination, cross contamination and process problems.

Equipment should be qualified and validated prior to usage. All critical parameters should be identified,  measured and monitored using calibrated instrumentation, displayed and controlled along the entire OTC/Cosmetic Drug product manufacturing process.

Equipment and utensils should be maintained periodically (preventive maintenance) and kept in a clean and orderly condition. Equipment should be stored in clean and controlled areas, kept sealed as much as possible (maintain the cleanness state) to prevent contamination, microbial proliferation and corrosion.

Equipment instrumentation that measure, control and monitor critical process parameters should have the required accuracy level and be in calibrated state.

Equipment and utensils that are not in validated state and/or defective or does not meet the required tolerances should not be used for production purposes.

Raw materials

Raw material should be purchased from certified suppliers that have an official GMP compliance certification. Supplier GMP and Quality System audit/inspection should be performed at least once in two years. Raw material should be supplied with an official and signed COA (Certificate Of Analysis). All raw material release specifications should be tested by the company QA (Quality Control) and assured to meet release specifications.

Raw materials should be stored and transported in a controlled manner according to the specific storage conditions such as temperature, RH (Relative Humidity) and lightning, detailed in manufacturer material label.

Raw material packaging should not be defective and should be clearly labeled in order to identify clearly the stored raw material name, lot number, expiry date and status (rejected/release/quarantine).

Received raw material should be transferred immediately into its intended controlled storage areas and exposure to sunlight/rain or other non-controlled conditions is forbidden.

Received raw materials should be identified and tested in order to ensure it meets specifications declared by the supplier.

Raw material should be stored in such way that will prevent mix ups, contamination from the outer environment and cross contamination from other raw materials. Raw material packages should be sealed, placed on racks or trays and should have no contact with the floor.


Color additives should be approved for Cosmetic usage according to 21CFR parts 73, 74 and 82.

Prohibited cosmetic ingredients such as Bithional, Vinyl Chloride, Chloroform and others should not be used in the Cosmetic Drug product formulation.

Cosmetic OTC product labeling

A cosmetic product must be labeled according to Cosmetic product labeling regulatory requirements (detailed in the cosmetic labeling manual). OTC products must be labeled according to OTC drug regulations, including “Drug Facts” labeling as described in the 21CFR.

Combination OTC Drug/Cosmetic products must have combination OTC Drug/Cosmetic labeling which includes active and inactive Ingredients list.

OTC Drug products monographs will include information to be labeled on the product package in order to assure the product will not be misbranded. Label will contain Drug facts panel such as list of active ingredients, Drug purposes, uses and applicable warnings, directions, inactive ingredients, consumer service telephone number and other relevant information.

Cosmetic Drug ingredients should be listed alphabetically as “Active Ingredients” followed by Cosmetic ingredients or in a descending order of predominance as “Inactive Ingredients” as or listed as “Inactive Ingredients” divided into groups such as concentrations of greater than one percent of color additives.

In addition to the FFDCA, Cosmetics products are being regulated under FPLA (Fair Packaging and Labeling Act) which is focused on packaging and labeling of “consumer commodities” that includes Cosmetic products manufactured or distributed for sale through retail sales agencies or individual.

In case a restricted ingredient was added to the Cosmetic product, a warning statement should be printed on product label.

 Cosmetic Drug manufacturers FDA audits and inspections

As with the Pharmaceutical industry FDA inspections, FDA can audit/inspect Cosmetic Drug manufacturers with no prior notice. Main focus in the Cosmetic drug industry FDA audits is on product safety, adulteration and misbranding violations. As part of inspection, FDA may collect product samples for analysis including at the manufacturing, storage, transportation and import stages. In cases of historical consumer complains, adverse effects and/or product recalls, FDA will follow up on adverse events complaints related to a specific Cosmetic product. In addition to FDA, U.S distributors may require Qualified Person approval before product marketing approval.

Qualification and Validation

Validation and Qualification is required for a variety of Cosmetic product stages such as utilities, equipment, cleaning process, manufacturing process, analytical methods, software, computerized system, storage and shipping Validation.

Utilities Validation- Critical utilities will be validated for Installation and Operational Qualification (IQ and OQ). Non-critical utilities that have no impact on product quality and/or GMP can have commissioning qualification only.

Process equipment Validation – Process equipment such as vessels, tanks, homogenizers, pumps, filling and packaging machines will be validated for Installation, Operational and Performance Qualification (IQ, OQ and PQ) under worst case conditions.

Process equipment cleaning Validation- Equipment that is in product contact such as tanks, vessels, homogenizers, filling machines, small equipment and others will be validated for Cleaning Validation and Clean Hold storage time under worst case conditions.

Analytical equipment and system Validation- Will be validated for Installation and Operational Qualification (IQ, OQ) as well as for software and Computerized System Validation (CSV).

Analytical methods Validation- Analytical methods in usage such as active raw material analysis, product detection, monograph, impurities, cleaning agents and microbial detection will be validated.

CIP (Clean In Place) skids Validation – Will be validated for Installation, Operational and Performance Qualification including spray device Qualification (spray devices installed on equipment).

Control panel and HMI Validation – Equipment and skids control panels and HMIs will be validated for software and Computerized System Validation (CSV) according to Annex 11, 21CFR part 11 and GAMP 5 requirements. For more information refer to article  FDA/CE compliant computerized and software Validation.

Shipment Validation- Final product shipment and supply chain should be validated for Installation, Operational and Performance Qualification (IQ , OQ and PQ) for transportation system as well as for transportation routes. For more information refer to article Good Storage and Distribution Practice, cold chain safety and Validation.

About the author:

Eran Yona Bio-Chem CEO and GxP consultant


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