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08/31/2010

DRAFT
GUIDELINE FOR INDUSTRY THE STABILITY TESTING OF COSMETICS

TABLE OF CONTENTS

I.

INTRODUCTION (1)

A. Objectives of the Guideline (1.1).2 B. Scope of the Guideline (1.2)....2 C. General Principles (1.3)...2
1. Product Development Considerations (1.3.1)...2

II.

GUIDELINE (2)

A. Cosmetic Product (2.2)...3

1. 2. 3. 4. 5. 6. 7. 8. 9. General (2.2.1)..3 Photostability Testing (2.2.2)....3 Selection of Batches (2.2.3) ..3 Container Closure System (2.2.4)..3 Product Attributes (2.2.5)...3 Testing Frequency (2.2.6)..4 Storage Conditions (2.2.7).4 Evaluation (2.2.8).....5 Statements/Labeling (2.2.9)....5

III. IV.

GLOSSARY (3).......5 APPENDIX (4)..8

Guideline for Industry Stability Testing of Cosmetic Products

I. INTRODUCTION The purpose of stability testing is to ensure that the cosmetic product maintains its intended physical, chemical and microbiological quality, as well as functionality and aesthetics when stored under appropriate conditions. Historically, companies have developed their stability testing programs based on practical application and local market conditions. The guideline presented herein supplements both the preceding general document on stability testing prepared jointly between CTFA and Colipa in 2004, and the updated Colipa annex to that general document. Objectives of the Guideline (1.1) This guideline is intended to provide a resource for manufacturers in the development of a stability testing program. It illustrates the industrys current thinking on this topic, and identifies a stability data package that is acceptable for marketing. The guideline outlines key stability parameters for cosmetic products, but leaves sufficient flexibility to encompass the variety of different practical situations that may be encountered due to specific scientific considerations and characteristics of the materials being evaluated. Alternative approaches or variations of these guidelines can be used (e.g., where there is scientific justification or to satisfy requirements within a particular jurisdiction) providing the basic intention of the program is maintained.

A. Scope of the Guideline (1.2) The guideline addresses the information that may be collected for cosmetic products to demonstrate effective stability. The guideline is not intended for products that have been designated as drugs or pharmaceuticals by regulatory agencies (for the U.S., see the definition of a cosmetic and a drug in the Federal Food, Drug and Cosmetic Act: http://www.cfsan.fda.gov/~dms/cos-218.html).

B. General Principles (1.3) Microbiological, physical and chemical attributes, as well as functionality and aesthetics, of a cosmetic product may change over time and under the influence of factors such as temperature, light, humidity and packaging. The test conditions chosen for stability testing should take into account those factors relevant to the product. The purpose of the stability study is to establish, based on testing a minimum of one batch of the cosmetic product, an expected use life and label storage instructions applicable to future batches of the cosmetic product manufactured and packaged under similar circumstances. The degree of variability of individual batches affects the confidence that a future production batch will remain within specification throughout its expected use life.

This guideline does not establish legally enforceable responsibilities. Voluntary guidelines describe the current thinking and should be viewed as recommendations. Wherever specific regulatory or statutory requirements exist, they must be followed. The use of the word should in a guideline means that something is suggested or recommended, but not required.

1. Product Development Considerations (1.3.1) Companies may have a product development stability screening process. It is not the intent of this document to address such processes. During the investigative development stage of a formulation, various stability indicating test methods and procedures may be used to screen formulations that move forward in the development process to formal stability studies. Chemists have long used exceedingly high temperatures such as 50 C or 60 C from 48 hours to two weeks to accelerate potential physical changes and/or chemical reactions that may challenge longer term viability of a formula to meet consumer requirements.

II. GUIDELINE (2) A. Cosmetic Product (2.2) 1. General (2.2.1) The design of formal stability studies for cosmetic products should be based on knowledge of the behavior and properties of the raw materials and experience gained from formulation studies. The likely changes on storage and the rationale for the selection of attributes to be tested in the formal stability studies should be stated. 2. Photostability Testing (2.2.2) If appropriate, photostability testing should be conducted on at least one batch of the cosmetic product. Standard conditions for photostability testing can be found in ICH Q1B. 3. Selection of Batches (2.2.3) Data from stability studies should be available on at least one batch of the cosmetic product. The batch should be of the same formulation and packaged in the same container/closure system(s) as the marketed product. The manufacturing process used should simulate that to be applied to production batches and should provide product of the same quality and meeting the same specification as that intended for marketing. Batch sizes that are smaller than production scale may be used if justified. It is up to the manufacturer to determine which container size is to be stability tested. 4. Container/Closure System (2.2.4)

Stability testing should be conducted on the cosmetic product form packaged in the container/closure system(s) that is proposed for marketing. Any available studies carried out on the cosmetic product outside its immediate container or in other packaging materials can form a useful part of the stress testing of the cosmetic product or can be considered as supporting information, respectively. 5. Product Attributes (2.2.5) Stability studies should include testing of those attributes of the cosmetic product that are susceptible to change during storage and are likely to influence quality, safety, and performance characteristics. The testing should cover, as appropriate, the physical, chemical, and microbiological attributes, preservative system (e.g., preservation attributes through appropriate microbiological and/or chemical testing), and packaging functionality tests. Analytical procedures should be verified, stability indicating, and be conducted in accordance to a preapproved protocol. . Whether and to what extent replication should be performed will

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depend on the results of verification studies. For further information about specifications, consult the CTFA Quality Assurance Guidelines, Annex 18, Specifications. Expected use life acceptance criteria should be derived from consideration of the available information and the desired market target for stability. Additional guidance is available in ASTM E2454 Standard Guide for Sensory Evaluation Methods to Determine the Sensory Shelf Life of Consumer Products. It may be appropriate to have justifiable differences between the expected use life and release acceptance criteria based on the stability evaluation and the changes observed on storage. 6. Testing Frequency (2.2.6) Frequency of evaluations should be sufficient to establish the stability profile of the cosmetic product. Data from accelerated stability testing may be used to establish a tentative expected use life in cases where room temperature data is not available at product launch. In cases where long term data are not available, long term room temperature studies should be conducted to confirm the expected use life of the marketed product. At the intermediate storage condition, a minimum of three time points, including the initial and final time points (e.g., 0, 1, and 3 months), from a 3-month study is recommended. Reduced designs (i.e., matrixing or bracketing), where the testing frequency is reduced or certain factor combinations are not tested at all, can be applied if justified. For example, intermediate conditions could be justified in place of 25C for long-term testing as a reduced design. If changes are made to the formula, the manufacturing process or container closure system, the manufacturer should determine whether these changes are likely to affect product stability and, if so, additional testing should be performed to support the changes.

7. Storage Conditions (2.2.7)

In general, a cosmetic should be evaluated under storage conditions (with appropriate tolerances) that show its thermal stability and, if applicable, its sensitivity to moisture. The storage conditions and the lengths of studies chosen should be sufficient to cover storage, shipment and subsequent consumer use. Long term testing should cover a minimum of 12 months duration on at least one representative batch. Alternative storage conditions can be used if justified. 2.2.7 General case Study Long Term Intermediate Accelerated Storage Condition 25 2 C RH* 30 2 C RH* 40 2 C RH* Minimum Test Period Suggested 12 months 3 months 1 month

*It is up to the manufacturer to decide appropriate humidity conditions based on package type and formulation.

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Alternative conditions to those listed above may be used if justified. See Appendix I for additional scientific references regarding stability conditions. 8. Evaluation (2.2.8) A systematic approach should be adopted in the presentation and evaluation of the stability information, which should include, as appropriate, results from the physical, chemical, and microbiological tests, including particular attributes of the product form (e.g. viscosity) as well as aesthetic of packaging and packaging functionality tests. It is the manufacturers responsibility to justify what degree of change would be considered significant to the quality of the product package form.

9. Statements/Labeling (2.2.9) A storage statement should be established for the labeling in accordance with relevant national/regional requirements. The statement should be based on the stability evaluation of the cosmetic product. Where it is applicable, specific instruction should be provided, particularly for cosmetic product that cannot tolerate freezing. Generic terms such as ambient conditions or room temperature should be avoided.

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GLOSSARY (3) The following definitions are provided to facilitate interpretation of the guidance. Accelerated testing: Studies designed to increase the rate of chemical degradation or physical change of a cosmetic product by using exaggerated storage conditions as part of the formal stability studies. Data from these studies, in addition to long-term stability studies, can be used to assess longer term chemical effects at non-accelerated conditions and to evaluate the effect of short-term excursions outside the label storage conditions such as might occur during shipping. Results from accelerated testing studies are not always predictive of physical changes. See Appendix I for additional published information on accelerated testing. Acceptance Criteria: use guideline Pre-established target and/or acceptable ranges for variation of performance criteria ASTM International: 100 Barr Harbor Drive PO Box C700, West Conshohocken, Pa., 19428-2959 United States of America. Batch: A specific quantity of a material that is intended to have a uniform character and quality, within specified limits, and is produced according to a single manufacture order. Bracketing: The design of a stability schedule such that only samples on the extremes of certain design factors (e.g., strength, package size) are tested at all time points as in a full design. The design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested. Where a range of formulation variants is to be tested, bracketing is applicable if the variants are identical or very closely related in composition (e.g., for a pressed powder range made with different compression weights of a similar basic granulation, or a capsule range made by filling different plug fill weights of the same basic composition into different size capsule shells). Bracketing can be applied to different container sizes or different fills in the same container closure system. Container closure system: The sum of packaging components that together contain and protect the cosmetic product. This includes primary packaging components and secondary packaging components if the latter are intended to provide additional protection to the cosmetic product. A packaging system is equivalent to a container closure system. Expected use life: The time period during which a cosmetic product is expected to remain within the approved product specification, provided that it is stored under the conditions defined on the container label. Intermediate testing: Studies conducted at 30 C/60% RH and designed to moderately increase the rate of chemical degradation or physical changes for a cosmetic product intended to be stored long-term at 25 C. Long-term testing: Stability studies under the recommended storage condition for the expected use life proposed (or approved) for labeling. Matrixing: The design of a stability schedule such that a selected subset of the total number of possible samples for all factor combinations is tested at a specified time point. At a subsequent time point, another subset of samples for all factor combinations is tested. The design assumes that the stability of each subset of samples tested represents the stability of all samples at a given time point. The differences in the samples for the same cosmetic product should be identified as, for example, covering different batches, different sizes of the same container closure system, and, possibly in some cases, different container closure systems. Specification: A list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described. It establishes the set of criteria to which a cosmetic product should conform to be considered acceptable for its intended use.

Stability studies: Long-term, accelerated and intermediate studies undertaken on a primary batch according to an established evaluation process to confirm the expected use life of a cosmetic product. Also see Appendix I
for additional scientific references regarding stability conditions.

Storage condition tolerances: The acceptable variations in temperature and relative humidity of storage facilities for formal stability studies. The equipment should be capable of controlling the storage condition within the ranges defined in this guidance. The actual temperature and humidity (when controlled) should be monitored during stability storage. Short-term spikes due to opening of doors of the storage facility are accepted as unavoidable. The effect of excursions due to equipment failure should be addressed and reported if judged to affect stability results. Excursions that exceed the defined tolerances for more than 24 hours should be described in the study report and their effect assessed.

Appendix (4)

A number of references exist that may be consulted when determining appropriate conditions for the stability testing of cosmetic products. The following is provided for informational purposes and lists conditions that are described in several published references. Each manufacturer must determine the conditions appropriate for their products based on knowledge of the formulations, of similar formulations and of the market.

1. IFSCC Monograph 2 1 Temperature Control Room Temp Accelerated Accelerated Accelerated 4C 20 - 25 C 37 C 37 C 45 C 80% Humidity Duration Shelf life Shelf life 3-6 months 1 month 1-3 months

2. Cosmetic Regulation in a Competitive Environment Ch 11 Stability Testing of Cosmetic Products2 Room Temperature: 24-25C Accelerated testing: 37, 45 and 50C Freeze-thaw cycling: 0 or -5C Elevated Humidity: 80% RH

International Federation of Societies of Cosmetic Chemists, IFSCC Monograph, Number 2: The Fundamentals of Stability Testing, Micelle Press, 1992 2 Estrin, Norman F. and Akerson, James M., eds., Cosmetic Regulation in a Competitive Environment, chapter 15 Stability Testing of Cosmetic Products by Philip E. Minor