How to Know when to Toss your Prescription Drug or Refrigerate it

Stability Studies Provide the Answer

Posted: June 28, 2017

API Manufacturing and Pharmaceutical Manufacturing

Check the label on any prescription you fill and chances are it will have a label with an expiration date, as well as instructions on whether to keep your drug out of sunlight, refrigerated or another instruction.  This information is designed to provide you with a date for when to discard your medication, as well as a way to keep your prescription safe and effective.

The information and instructions provided on these labels don’t come easily, but involve rigorous testing early in the drug manufacturing process through stability testing.

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Stability testing is an important part of the drug development and approval process, determining the safety and integrity of the drug and also its shelf life and storage conditions. Contract Manufacturing Organizations (CMOs) and their sponsoring pharmaceutical companies invest significant time and effort into stability testing

What is Stability Testing?

Stability testing assesses how the quality of a drug substance or drug product, and it’s packaging, varies with time under the influence of environmental factors, including temperature, humidity and light. The process determines whether any physical, chemical or microbiological changes affect the efficiency and integrity of the final product.  This ensures that a pharmaceutical product is safe and effective, regardless of where in the world it will be supplied. Stability testing establishes the shelf life and recommended storage conditions of a finished pharmaceutical product and the retest periods for a drug substance.

What Role Does the FDA Play?

The FDA provides recommended guidelines in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), which outlines the frequency and types of conditions that should be performed on any drug entity wishing to apply for FDA approval.

A key recommendation is to perform stress testing of the drug substance, which can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic stability of the molecule and validate the stability-indicating power of the analytical procedures used.

PCI Synthesis conducts stability study programs according to ICH guidelines Q1A (R2) under cGMP for both drug Substance and Drug Product.

How is Stability Testing Conducted?

The most suitable approach to gathering data to determine product stability and the stability of its packaging is to conduct real-time stability studies.  However, since this approach is time-dependent, forced degradation studies are conducted to determine product stability over time.  These studies not only provide vital information about the product, but they also determine if the analytical method is a stability-indicating one.

Drug Substance and Drug Products are typically studied under at least two different storage conditions:  long-term ambient storage and accelerated conditions.  Each stability program is conducted based on an approved protocol, and testing includes the product’s physical and chemical characteristics which may be susceptible to change during its storage, potentially impacting its strength, quality, purity, and ultimately, safety.

Each protocol describes the packaging, storage conditions and the tests that will be performed, along with stability test dates, test durations, etc.  Stability tests are conducted using the same container closure system and packaging materials that are intended for the final product.

How much of the product should be tested?

Typically, three validation batches of a product are placed under a formal stability study, and it’s recommended that an informal study be conducted on development batches before initiating the formal study, so you can design a better packaging configuration for the product.

Batches manufactured for additional validation, such as process scale-up, are also often added to the stability study, and typically one batch per year is added to demonstrate ongoing material stability.

The purpose is to provide evidence about the quality of materials over time under the influence of various environmental factors.

How much does it cost?

When working with a CMO, stability testing is typically an add-on project, which can cost in the range of $40-60K.  At PCI Synthesis, we have three people dedicated to the stability testing program for current clients at any given time.

Want to know more about stability studies?  Contact us at 978-462-5555 or http://info@pcisynthesis.com.

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About the Author

Ed Price CEO of PCI Synthesis
Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).

Do you have questions? Talk to Ed.