Cosmetic Products Stability Overview According to ANVISA- BRAZIL(Vol. 1)
Cosmetic Products Stability Overview According to ANVISA- BRAZIL – Volume 1
Priscilla, Lima Viana Palhano(GPKOL Consultant)
컨설팅 분야 : RA, PM
거주국가 : 브라질
- Argo Consulting (2018~) / CEO
- Vital Brazil Institute/Regulatory Affairs an Special Project Department/ Biomedicine Specialist/(2016-2017)
- Vital Brazil Institute/Biomedicines Department/Biomedicine Specialist/ (2013-2015)
- Technological Life Science Park/Business Incubator/New Business Specialist/ (2010-2013)
* 세부 전문분야 및 컨설팅 내용
- Regulatory affairs: Register of products in ANVISA, including the obtaining of necessary license and certificates
- PM: Technology transfer project in pharmaceutical industry
The goal of this paper is to present an overview rational of ANVISA recommendations for cosmetic products stability evaluation, emphasizing the importance of such studies which are initiated at the development stage and should accompany the product at least until the end of its estimated period of validity. This is the first one of a series of 3 complementary papers.
According to the definition established by the current legislation, Cosmetics, Personal Hygiene Products and Perfumes “are preparations composed of natural or synthetic substances for external use on the many parts of the human body, skin, capillary system, nails, lips, external genital organs, teeth and mucous membrane of the oral cavity, with the exclusive or main objective of cleaning, perfuming, changing the appearance and or correcting corporal odor and or protecting or keeping them in good condition”.
In order to facilitate the reading of this guide, the expression “personal hygiene products, cosmetic and perfumes” will be substituted by the expression “cosmetic products” comprehending all the previously designated classes.
Stability studies on cosmetic products supply information that indicates the relative stability level of a product under the various conditions that it can be subjected to from the moment it is manufactured until the end of its validity.
This stability is relative as it varies with time and in response factors that accelerate or retard alterations in the parameters of the product. Modification within established limits do not necessarily constitute a reason for withdrawing approval of the product.
The study of cosmetic products stability contributes towards:
Guiding the development of the formulation and of adequate containing material;
Supplying subsidies for formulation improvement;
Estimating the validity term and supplying information to confirm it;
Assisting in the monitoring of organoleptic, physical-chemical and microbiological stability, by producing information about the trustworthiness and safety of products.
2 Factors that Influence Stability
Each component, active or not, can affect the stability of a product. Variables related to the formulation, to the fabrication process, to the containing material and the environmental conditions as well as transportation can influence stability. According to their origin, the alterations can be classified as extrinsic, when determined by external factors; or intrinsic, when determined by inherent formulation factors.
2.1 Extrinsic Factors
These are related to external factors to which the product is exposed, such as:
The drawing near of the expiry date of the product can lead to alterations in the organoleptic, physical-chemical, microbiological and toxicological characteristics.
High temperatures accelerate physical-chemical and chemical reactions, generating alterations in: component activity, viscosity, appearance, color and odor of the product. Low temperatures accelerate possible physical reactions such as turbidity, precipitation and crystallization. Problems created by high or very low temperatures can also derive from non-conformity during the manufacturing process, storage or transport of the product.
c) Light and Oxygen
Ultraviolet light along with the oxygen leads to the formation of free radicals and sets in motion oxidation- reduction reactions. Products that are sensitive to light action must be conditioned away from light, in opaque or dark flasks and must also have antioxidant substances added to the formulation for the purpose of retarding the oxidation process.
This factor affects mainly the solid cosmetic forms, such as powder, bar soap, eye shadow, bath salts, among others. Some alterations may occur in the physical appearance of the product, making them soft or sticky or modifying weight or volume as well as leading to microbiological contamination.
b) Containing Material
The materials used for the containing cosmetic products, such as glass, metal and plastic, can influence their stability. Suitability tests must be carried out between the containing material and the formulation, with the view to determining the best relation between them.
The cosmetic products most susceptible to contamination are those which present water in the formulation, such as emulsions, gels, suspensions and solutions. The adequate and validated use of additive substances (Challenge Test of the additive system) as well as the accomplishment of the Good Manufacturing Practice are necessary for the adequate conservation of the formulation.
Vibration during transportation may affect the stability of the formulations, causing a division of the phases of emulsions, solidification of suspensions, alteration of viscosity, among others. A factor which aggravates the vibration factor is the alteration of temperatures during the transportation of the product.
2.2 Intrinsic Factors
These are factors related to nature of the formulations themselves and above all to the interaction of the ingredients among themselves or with the containing material. They result in physical or chemical incompatibilities which may, or may not be apparent to the consumer.
Alterations occur in the formulation’s physical appearance, visible as: precipitation, phase separation, crystallization, formation of cracks, among others.
Three different aspects related to pH values must be compatible: stability of the formulation ingredients, effectiveness and safety of the product.
b) Reactions of oxidation-reduction
Oxidation or reduction processes occur leading to alterations in the activity of the active components and in the organoleptic and physical characteristics of the formulations.
c) Hydrolysis reactions
These occur through interaction with water. Esters and Amines are more susceptible to them. The higher the percentage of water in the formulation, the more likely the occurrence of this kind of reaction becomes.
d) Interactions among formulation ingredients
Undesirable chemical reactions that can occur among the ingredients of the formulation, annulling or altering its activity.
e) Interaction between formulation ingredients and the containing material
Chemical alterations that can result in alterations at the physical or chemical level to the containing material components and the ingredients of the formulation
Physical: the original physical properties must be conserved, such as appearance, color, odor and uniformity, among others;
Chemical: properties such as the integrity of the chemical structure, the percentages of the ingredients and other parameters must be maintained within specified limits;
Microbiological: microbiological characteristics must be maintained in accordance with specifications.
The accomplishment of Good Manufacturing Practices and the preservative systems used in the formulation can guarantee these characteristics.
Aside from these appearances, it is also necessary to consider the maintenance of the product’s characteristics in the questions of:
Functionality: the attributes of the products must be maintained unaltered in relation to the effects originally proposed.
Safety: significant alterations must not occur that may influence the safety of product use.
During the development of new formulations and of laboratory and factory pilot-batches.
When significant changes occur in the manufacturing process.
To validate new equipment or production processes.
When significant changes occur in the raw material being used.
When significant changes occur in the containing material that comes into direct contact with the product.
5. The Fundamentals Of Stability Testing
The tests must be conducted under conditions that allow them to supply information on the stability of the product in the least time possible. For this, samples must be stored in conditions that accelerate the changes that may occur during the validity term. Care must be taken that the conditions are not so extreme that instead of merely accelerating the aging process, they provoke alterations that would not occur under market conditions.
The suggested study sequence (preliminary, accelerated and “on shelf”) has the aim of evaluating the formulation by steps, looking for signs that could lead to conclusions on stability.
6. Stability Evaluation Parameters
The parameters to be evaluated must be defined by the formulator and depend on the characteristics of the product that is being studied and on the ingredients being used in the formulation. Generally, the evaluation is:
Organoleptic parameters: appearance, color, odor and flavor, whenever applicable;
Physical-chemical parameters: pH value, viscosity, density, and in some cases, the monitoring of formulation ingredients;
Microbiological parameters: microbial count and challenge test of the preserving system.
7. Statistical Analysis
A Statistical analysis can be one of the tools used in the interpreting of data obtained during the stability studies, for the diverse aspects evaluated and at the different stages of testing.
It is necessary to adequately delineate the test, defining the variables that will be controlled and that influence the results, ex: cycles, time and temperature. Besides the factors related to studies there are other variables that are not controlled and that can influence the result. It is important to take these variables into account making sure that their influences do not affect information obtained in relation to the factors of real interest.
The data obtained in a specific stability study can be qualitative and quantitative, remembering that previous information and the histories of other products can assist in interpreting it.
The various statistical tools available must be carefully selected for use in the analysis and in the interpretation of data according to the stage of the study (selection of the formulations, accelerated stability, normal, shelf and process validation). As examples:
Significance evaluation of the difference between two data series: Hypothesis test – T test;
Determination of the capacity of a sample result and estimating real value: Estimation by trustgap
Tolerance limits determination of the specific characteristics: tolerance limits;
Incorporation of previous information in future event predictability: Bayes Theorem;Evaluation of the relations between two or more variables through an equation to estimate a result: Linear regression.
It is also relevant to consider that, although there are several statistical tools and softwares that facilitate the analysis of the results, the experience and knowledge of the formulator are fundamental in the correct interpretation of the data. On many occasions statistically significant results may not be analytically relevant. On the other hand, there is the inverse situation, in which results, statistically non-significant, can be very relevant from the analytical viewpoint and should not be disregarded.
8. Approval Criteria for Product Stability
The interpretation of the data obtained during the Stability Test depends on criteria established in accordance with the formulator’s experience. The samples are evaluated in comparison with the standard sample and with products that are considered as “references” submitted to the same test conditions. Generally limits of acceptance are defined for the evaluated parameters, and the standard sample must remain unchanged during the whole life cycle of the product.
The correspondence between the data and its interpretation must be relative as in practice, the objectives and the characteristics of each product or category are quite distinct.
Generally the following criteria are considered:
Appearance: the product must keep itselfentire during the whole of the test, maintaining it’s initial
appearance under all the conditions except high temperatures, freezer conditions or cycles in which small alterations are acceptable.
color and odor: must remainstable for at least 15 days when exposed to sunlight. Smallalterations are acceptable at high temperatures.
Viscosity: the limits of acceptability must be defined by the formulator, considering the visual and sensorial perceptions caused by alterations. The possibility of the consumer’s also noticing them must be considered.
Compatibility with the containing material: the integrity of the package and the formulation must be considered, evaluating the weight, the sealing and the functionality.
In cases where the monitoring of the active ingredient percentage is necessary, the quality and performance parameters of the product must be considered.
Other parameters can be established according to the formulator and the products’ specifications.
9. Expiry Date of the Cosmetic
In Brazil, the obligatoriness of the indication of the expiry date on the packaging of cosmetic products where it can be seen by the consumer, is established in specific legislation, Resolution 79/00 and its updates and Law 8.078/90 – Consumer Protection and Defense Code.
The expiry date – characterized as the life span, in which the product maintains the original characteristics – rather than being a mere legal requirement, is, above all, a technical quality requirement as a product that is unstable from the physicalchemical, microbiological or toxicological point of view not only loses effectiveness but can also cause damage and impair consumer confidence.
Due to the peculiar nature of the formulations of cosmetic products, it is accepted as a general rule that it is impossible to elect one isolated ingredient separated from the rest of the formulation. Thus it is difficult to apply the relation between kinetic constant, temperature and a direct correlation of these variables with the estimated expiry date. However, the expiry date can be estimated by means of the Stability Studies and it must be
firmed using the shelf test.
10.Conclsion Report on Stability Studies
At the end of the Stability Studies, the elaboration of a report with the following information is suggested:
Identification of the product
Containing material used in the test
Study conditions (sample storage conditions, test time period and periodicity of the evaluations)
Results (can be registered in a chart, relating the storage conditions, time and periodicity of the analysis)
Conclusion (evaluate the obtained results, report if the product was approved or not, conditions that the test was conducted and estimate the expiry period)
The signature of the person responsible for the study
Stability studies are aimed at evaluating the capacity of a product maintain the same organoleptic, physical- chemical, microbiological characteristics as well as its safety and effectiveness. Thus the stability study must be seen as a necessary requirement for the product’s quality guarantee and not merely as a requirement of the regulatory agency.
In Brazil, it’s responsibility of the National Health Surveillance Agency – Anvisa / MS to regulate, inspect and control the production and the commercialization of cosmetic products, in order to offer safe products and with quality, on the market; contributing in this way towards the protection of the population’s health.
In this way, foreign companies that wish to market their products in Brazilian territory must follow all the rules of this regulatory agency for such products can be registered in Brazil.
BRASIL. ANVISA. Agência Nacional de Vigilância Sanitária. Guia de Estabilidade para Cosméticos, publicada em http://portal.anvisa.gov.br/
BRAZIL, ANVISA - Brazilian Health Surveillance Agency. Cosmetic Products Stability Guide, published in http://portal.anvisa.gov.br/
Priscilla Viana Palhano Lima was Manager of Regulatory Affairs and Special Projects of the Brazilian public laboratory. He was directly in charge of the legal compliance of technology transfers with foreign companies from France, Poland, the United States and South Korea. He has experience in dossier analysis and elaboration of Partnership for Productive Development projects for the Ministry of Health. She is currently a consultant in Regulatory Affairs and Project Management of Partnership Projects for Productive Development for the Ministry of Health. Priscilla is the founder of the Argo Consulting company that promotes consulting in the areas of regulatory affairs, business development, project management international partnerships and technology transfers in partnership with MM Assessoria Industrial company.
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