Stability Testing

The laws regulating expiration dates and other aspects of medical drugs protect consumers from ineffective drugs. Expiration Date Rules Drug expiration dates are meant to indicate the date at which the drug’s potency begins to diminish. The drug does not usually become harmful after the expiration date listed on the box or bottle, but rapid degradation of certain drugs, such as insulin or liquid antibiotics, is possible. Any drug that contains an organic compound is also susceptible to decay. However, most drugs in pill form remain effective beyond the expiration date. The purpose of this expiration date is to inform consumers about the potency and effectiveness of the drug at the time of purchase. A closed-container system is used by these companies to study how the drug ages. Scientists observe the rate at which the drug remains chemically potent. The closed-container environment must mimic the containers the drugs are bought and sold in.

Regulatory Considerations for Forced Degradation Studies

E-mail One of the most common questions people ask health care providers is, Can I use my old drugs past their expiration dates? In the late s, the FDA first began requiring expiration dates on both prescription and over-the-counter medications. The legal code adopted by the FDA also notes that manufacturers must account for storage conditions and reconstitution conditions for certain drugs in the expiration date.

The expiration date of most medicines is 12 to 60 months after manufacture, reports Pharmacy Times. According to Pittsburgh-Post Gazette , pharmacists further shorten the time a medicine can be used when they add their own “discard after” or “beyond-use” date to the prescription label itself. From manufacturer to FDA to pharmacist, the underlying principle is maximum safety.

ity testing for new drug substances and products and provides directions on what studies, data evaluation, and expiration dating for parenteral products—with an emphasis on intravenous RTU drug prod – ucts in plastic containers. Stability Study Design For U.S. new drug applications, typically RTU DRUG PRODUCTS: PART II Stability study.

Supportive Stability Data Number and Size of Batches Initial stability testing by accelerated testing may be performed on a batch smaller than the normal production size as long as the batch is produced by similar equipment as would be used for regular production. Generally, the placing of three initial batches into the long term stability program is considered minimal to assure batch uniformity for establishing an expiration date.

Since a dosage form is a complex unit and there are continued variables in the production process, such as change in personnel, raw material lots and suppliers, and equipment, it is imperative that stability studies are not limited only to initial production batches but a portion of annual production batches be the subject of an ongoing stability program. Accelerated Studies When accelerated stability studies are performed, one batch may be adequate in order to establish a tentative expiration date.

This is acceptable since it is not the purpose of an accelerated test to determine batch uniformity but rather to test for kinetic degradation. The use of accelerated testing data to establish a tentative expiration dating period of greater than three years is discouraged when it is based solely on accelerated data. Combining data compiled at room temperature and at accelerated temperature is possible to justify an expiration dating period of over two years.

This can be done, as an example, by taking a sample product that has been at room temperature for one year and subjecting that sample to accelerated temperature conditions. The expiration dating period used would then be the sum of that justified individually at each storage condition. We do not believe it is reasonable to perform accelerated testing at very high temperatures for a very short time and expect to extrapolate results to a very long expiration dating period since the actual mechanism of degradation at high temperature may be different than at room temperature.

Test Intervals It is commonly recommended that stability testing be performed initially, than every three months for the first year, then every six months for the second year, and then annually thereafter.

CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS

Proper utilization will be helpful in gathering information on product stability and leading to an optimized formulation. API stability must also be determined in final forum as it is necessary to ensure efficacy and safety of the finished product. Testing procedures must include a stability indicating test which will distinguish the active ingredient from any degradation products and be able to make a reliable estimate of the quantity of any degradate.

The primary reason for stability testing is to ensure the safety of the patient through establishing the expiration dating period of the pharmaceutical product. Understanding the stability of an active pharmaceutical ingredient (API) or drug formulation is one of the most important factors in determination of the viability of a drug product.

Storage Temperature for various types of products. Performing an effective sampling plan and utilizing the appropriate sample size for a stability testing program. Performing a compliant sample analysis, handling and effecting the appropriate test specification for the product type. Attendees will gain an understanding in the following key areas: Case Study 1 and Suggested Resolution 4. Breakfast and Registration Session 1: The Attendees will gain an understanding in the following key areas: Choice of methods with meaningful data or stability indicator Analytical Assay Test Method Attributes

Early Development GMPs for Stability (Part IV)

Available online 30 January 30 January Publisher Summary The drug substance—active pharmaceutical ingredient API —is the most important component in a drug product. During the early phase of development, the number of API batches is relatively limited, the batch size is usually very small, and manufacturing experience is beginning to evolve. The primary emphasis in setting specifications for a new drug substance is on safety, based on the purposes of clinical studies at this stage.

– Section – Testing and approval or rejection of components, drug product containers and closures (OTC) human drug products – Section – Expiration dating – Section – Testing and release for distribution – Section – Stability testing.

These methods include both classical and state-of-the-art technologies as well as new technologies as they emerge over time. During the life cycle of a product, several reasons can arise for making changes in existing analytical methods: Note that replacing an existing method is not the same as adding a new method to a release or stability test panel. Thus, significant changes in the method can create a substantial discontinuity between past and future data sets.

Also, specification acceptance criteria that were based on historical data from the existing method could be affected by the measurement capabilities of the new method. So it is necessary to conduct an appropriately designed method-bridging study to demonstrate suitable performance of the new method relative to the one it is intended to replace. Note that a method-bridging study is distinctly different from a methodtransfer study.

Method transfers demonstrate comparable performance of a method that exists in one laboratory in another. Neither is method-bridging the same as adding a new assay to an existing analytical testing regimen. A method introduced de novo is not linked to an existing data set generated by an older method that is being discontinued.

In January , a CASSS Chemistry, Manufaturing, and Controls Strategy Forum explored technical and quality issues associated with replacement of existing analytical methods by new methods during development — how that transition could be achieved smoothly while maintaining phase-appropriate regulatory compliance. They also provided highlights of relevant examples. Additional regulatory perspectives were contributed by Health Canada representatives during panel discussions.

HUMAN DRUG CGMP NOTES June

Fifteen years ago, the U. The testing, conducted by the U. Food and Drug Administration, ultimately covered more than drugs, prescription and over-the-counter.

itg subject: expiration dating and stability testing for human drug products. Publishing of 21 CFR Part – Current Good Manufacturing Practice for. PHARMACEUTICAL MANUFACTURING HANDBOOK Production and Processes SHAYNE COX GAD, PH.D., D.A.B.T. Gad Consulting Services Cary, North Carolina CONTRIBUTORS.

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FDA Drug Expiration Date Rules

Labeling and packaging materials shall be representatively sampled, and examined or tested upon receipt and before use in packaging or labeling of a drug product. Any labeling or packaging materials that do not meet such specifications shall be rejected to prevent their use in operations for which they are unsuitable. Access to the storage area shall be limited to authorized personnel. Such examination shall be performed by one person and independently verified by a second person.

There shall be written procedures designed to assure that correct labels, labeling, and packaging materials are used for drug products; such written procedures shall be followed. These procedures shall incorporate the following features:

Direct accelerated stability tests for cosmetic products by an innovative technology Arnold Uhl, LUM GmbH, Berlin, Germany The NEXT STEP® in analysis of cosmetic products Stability Analyser Direct_accelerated_stability_tests_for_cosmetic_p roducts_by_an_innovative_technology_LUM_in-cosmetics_

Each drug product may be a unique article because of, for instance, differences in 1 chemical and physical properties of the active ingredients or the excipients, 2 manufacturing procedures, 4 containers and closures, 5 proposed storage conditions, and 6 the stability of the article to maintain its quality or purity through the use of antioxidants or preservatives.

Because of the uniqueness of each drug product, it is virtually impossible to provide one set of rules that can apply to all situations. The CGMPs were purposely written broadly to allow for such unique differences. Absence of an Expiration Date The absence of an expiration date on any drug product packaged after September 29, , except for those drugs specifically exempt by Exemptions OTC drug products meeting the exemption of Information obtained from old stock, not previously the subject of stability studies, may also be utilized.

Products Intended for Reconstitution Any drug product intended for reconstitution and not bearing an expiration date for the unreconstituted product and another expiration date for the product after reconstitution is considered to be out of compliance with There must be separate stability studies to support each expiration date. Supportive Stability Data Number and Size of Batches Initial stability testing by accelerated testing may be performed on a batch smaller than the normal production size as long as the batch is produced by similar equipment as would be used for regular production.

Generally, the placing of three initial batches into the long term stability program is considered minimal to assure batch uniformity for establishing an expiration date. Since a dosage form is a complex unit and there are continued variables in the production process, such as change in personnel, raw material lots and suppliers, and equipment, it is imperative that stability studies are not limited only to initial production batches but a portion of annual production batches be the subject of an ongoing stability program.

Accelerated Studies When accelerated stability studies are performed, one batch may be adequate in order to establish a tentative expiration date. This is acceptable since it is not the purpose of an accelerated test to determine batch uniformity but rather to test for kinetic degradation. The use of accelerated testing data to establish a tentative expiration dating period of greater than three years is discouraged when it is based solely on accelerated data.

ST101 Lecture 2: Regulations on Stability Program Global Stability Requirements