What stability tests with climate chambers reveal about medicines

Significance of the durability tests (stability test)

The safety, efficacy and quality of medicinal products are essential pillars of modern pharmacy. A central element in ensuring these parameters are so-called shelf life tests - also known as stress tests or stability tests. They are used to assess the stability of a medicinal product under different environmental conditions and thus determine the shelf life.

With the increasing complexity of modern active ingredients and ever-growing regulatory requirements, stability studies are becoming increasingly important. From biotechnologically produced proteins to temperature-sensitive vaccines - stable drug development requires sound know-how and carefully planned tests.

Such studies help to determine suitable packaging, storage conditions and test intervals. They are central to the approval and determination of the expiry date - the date until which a medicinal product can be used safely. They are carried out in accordance with international standards such as the ICH guidelines and accompany the product throughout its entire life cycle - from development to market surveillance.

History of the expiry date

The introduction of a standardized expiry date is a comparatively recent achievement of modern pharmacy. Until well into the 20th century, medicines were often sold without any information on shelf life - especially in pharmacies that produced medicines themselves. This led to considerable uncertainty regarding the efficacy and safety of preparations, especially if they were stored for long periods.

It was only with advances in pharmaceutical science and the industrialization of drug production that awareness of the importance of the chemical and physical stability of active ingredients grew. Regulatory authorities around the world began to recognize the need for binding specifications to guarantee the quality and safety over the entire life of a drug.

The first specific regulatory requirements for stability studies were developed in the 1970s and 1980s - by the US FDA and the European drug authorities, among others. The introduction of internationally harmonized guidelines by the ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) marked a milestone: it defined standards for carrying out stability tests in order to determine an expiry date in a scientifically sound manner.

The expiry date itself now indicates the time until which a medicinal product retains its specified quality, safety and efficacy under the defined storage conditions. It is determined on the basis of extensive stability data collected as part of shelf life tests. It is therefore not just a label on the packaging, but an expression of a complex analytical and regulatory process that makes a key contribution to patient safety.

International and national standards & guidelines

The performance of stability tests is clearly regulated today - both at national and international level. The most important regulations include the ICH guidelines, national requirements such as the German Medicinal Products Act (AMG) and the European Pharmacopoeia.

Increasing complexity

The demand for stability studies is growing continuously - due to increasing regulatory requirements and the growing complexity in the development of modern medicinal products. This has led to the establishment of a market of specialized service providers who offer comprehensive and individually tailored solutions in this area. With in-depth expertise in development support and life cycle management, they support pharmaceutical and biotech companies with experienced project teams.

Modern storage infrastructures are available for carrying out stability studies. This includes walk-in climate chambers that can be flexibly adapted to different, customer-specific storage conditions. This enables a high degree of flexibility in the planning and implementation of a wide range of study requirements.

Criticism and programs for reassessment

The shelf life of a medicinal product - often referred to as shelf life - indicates the period during which a product remains stable under defined conditions. Stable means that there is no unacceptable chemical, physical or microbiological instability and that the therapeutic effect is still guaranteed.

Average shelf life

Looking at all approved medicines as a whole, the average shelf life worldwide is between 24 and 36 months. This value varies depending on the dosage form and active ingredient class:

• Tablets and capsules: usually 2-5 years
• Liquid preparations (e.g. juices, drops): 6-24 months
• Parenterals (injection solutions): 1-3 years
• Augen-/Nasentropfen: häufig <12 Monate, insbesondere nach Anbruch

These values are based on the results of the respective long-term stability tests. In practice, safety margins are often taken into account to compensate for slight deviations due to transportation or storage.

Criticism and programs for reassessment

Although the concept of the expiry date has become established, there are critical voices from specialist circles. Some experts criticize the fact that many drugs could still be effective and safe after the official expiry date. This criticism led to the introduction of a unique program in the USA: the Shelf Life Extension Program (SLEP) of the USA

• Initiator: U.S. Department of Defense in cooperation with the FDA
• Objective: To extend the shelf life of medicines in large government stocks
• Results: Many tested drugs showed sufficient stability even years after the expiry date
• Significance: Potential savings in the billions and impetus for a more differentiated view of shelf life information

Despite such findings, the legal validity of the expiry date remains unaffected - particularly with regard to patient safety, product liability and quality assurance.

Stability of consequences: What happens after opening?

Another important aspect is the stability of a medicine after it has been opened for the first time. This applies to eye drops, ointments and liquid dosage forms, among others. After opening, external factors such as humidity, temperature and microbiological contamination can influence stability. Therefore, manufacturers often give specific instructions for use after opening, such as "use within 30 days after opening".

What equipment is needed for durability tests?

Stability test rooms, also known as climatic chambers , provide optimal conditions for stability studies in areas such as pharmaceuticals, medicine, personal care and scientific research. These chambers allow precise control of temperature, humidity and lighting in accordance with applicable guidelines to ensure reliable test results.

Special FDA-compliant software may also be required for pharmaceutical tests. Climatic chambers are also often used in accelerated ageing tests to simulate and accelerate the natural ageing process under controlled conditions. FDM stability chambers provide a constantly controlled environment in terms of temperature and humidity and have an intuitive control system that increases ease of use and ensures a smooth test procedure without unexpected problems. These chambers are particularly well suited for stability testing according to ICH Q1A, expiry date testing, packaging testing, accelerated ageing testing and many other applications.

Stability method - overview

Generally speaking, there are different types of stability tests, which vary in duration and conditions:

1. Long-term stability test
   • Is carried out over the intended storage period (e.g. 12 to 60 months) under recommended storage conditions.
   • Objective: To demonstrate that the product remains safe and effective throughout its shelf life.
2. Accelerated stability test (short-term or accelerated test)
   • Takes place over a shorter period (typically 6 months) under less favorable conditions (e.g. higher temperature and humidity).
   • Objective: Early indications of possible stability problems and estimation of durability.
3. Intermediate stability test (Intermediate Test)
   • Used when conditions of the accelerated test are not sufficient or to check stability under medium conditions.
   • Often at 30 °C and 65 % RH for several months.
4. Photostability test
   • Testing of resistance to the influence of light, as prescribed by ICH Q1B.
5. Freeze-thaw test (for some products)
   • Test of stability during repeated freezing and thawing.

Process according to ICH guidelines (e.g. ICH Q1A(R2))

The general procedure of a stability study includes:

1. Planning and design of the study
   • Selection of the batches to be tested (ideally at least 3 representative batches).
   • Determination of the test conditions (temperature, humidity, light, duration).
   • Determination of the test times (e.g. 0, 3, 6, 9, 12 months).
2. Carrying out the tests
   • Products are stored under defined storage conditions.
   • Samples are taken at fixed times and analyzed (e.g. active ingredient content, appearance, solubility).
3. Evaluation of the data
   • Analysis of the results in terms of product specifications and trends.
   • Determination of shelf life and storage conditions.
4. Report and documentation
   • Preparation of a final report with all results and recommendations.

Solutions in practice: climate chambers from Aralab

Pharmaceutical companies require precise technological infrastructure to carry out reliable stability tests. This is where climate chambers come into play - especially the high-precision solutions from Aralab.

Aralab offers a wide range of climate chambers specifically designed for stability testing in the pharmaceutical industry. These chambers allow precise control of temperature, humidity and light conditions to meet the requirements of ICH guidelines. Aralab's FitoClima series is available in various sizes, including 600 l and 1,200 l models, which are ideal for different test volumes. Aralab also offers walk-in climate chambers for large-volume applications.

Some of the outstanding features of the Aralab climate chambers are:

• Precise control of temperature (15 °C to 45 °C) and humidity (35 % to 90 % rH) with high uniformity.
• Compliant with ICH Q1A and Q1b Guidelines
• FDA 21 CFR Part 11 compliant software for data recording and management.
• Modular design with customizable shelving and lighting options.
• Energy-efficient components and user-friendly ClimaPlus touchscreen control.

By using Aralab climate chambers, pharmaceutical companies can ensure that their stability tests are carried out under controlled and reproducible conditions, which ultimately contributes to the safety and efficacy of the drugs.

Product overview

Aralab

Constant climate rooms

• Temperature and climate controllable
• Ideal for stability tests
• Use in pharmaceuticals and food

Aralab

Stability chambers
"REACH-IN"

• 600/1200 liter chambers
• Flexible shelf configurations possible
• Precise temperature/humidity control

Aralab

WALK-IN" stability chambers

• Constant climate conditions
• For medicines and cosmetics
• Suitable for bearings and tests

Aralab

Photostability test

• Suitable for photostability tests
• ICH Q1b-compliant
• Flexible, adjustable interior

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What role does Vitaris play?

Vitaris is a proud trading partner of Arlaab and your competent contact in Switzerland when it comes to sales, installation, maintenance, repair and qualification (IQ/OQ/PQ) of Arlaab appliances.

Thanks to our many years of experience and in-depth expertise in the field of laboratory technology, we ensure that you not only receive high-quality devices, but also comprehensive technical support - local, personal and reliable.

Whether commissioning, regular maintenance, troubleshooting or the qualified validation of your systems: With Vitaris, you have a partner at your side who professionally supports all phases of the device life cycle - in accordance with regulatory requirements and always with a focus on quality and operational safety.

Why professional stability studies pay off

Stability studies enable a realistic simulation of environmental influences such as temperature, humidity and light, allowing chemical, physical and microbiological instabilities to be detected at an early stage. On this basis, well-founded storage conditions and shelf life periods can be determined. The logarithmic progression of chemical reactions is taken into account in order to create precise time models. Legally compliant documentation ensures the traceability and quality of the product throughout its entire life cycle. At the same time, stability studies support the optimization of product development and contribute to risk minimization in the approval process.