Stability and transport validation of sterile medical devices

Validating the stability and transport of sterile medical devices is an essential process for ensuring the safety and efficacy of healthcare products throughout their lifecycle. With increasing regulatory requirements, including those of European Union Medical Device Regulation 2017/745, manufacturers need to demonstrate that their products maintain their integrity and performance, from manufacturing through to clinical use. This article explores the issues, methods and best practices for ensuring effective validation.

The regulatory framework

European Union Medical Device Regulation 2017/745 stipulates that medical devices delivered sterile must remain “sterile under the conditions of transport and storage recommended by the manufacturer” (Art. 11.4, Chapter 2 of Annex 1) and that they must be “designed, manufactured and packaged in such a way that their characteristics and performance during their intended use are not altered during transport and storage” (Art. 7, Chapter 1 of Annex 1). For manufacturers of medical devices, this means demonstrating that the product remains sterile and retains its claimed performance from the site of release all the way through to clinical use.

To meet these requirements, ISO 11607-1, which specifies requirements and test methods for packaging and sterile barrier systems for medical devices is applied. This standard describes the tests for maintaining the integrity of packaging systems, and refers to the various standards that need to be followed to simulate the distribution cycle of the medical devices (ASTM D4169, ISTA series 1 to 3) or to carry out accelerated aging of the medical device for stability studies (ASTM F1980). 

Stability testing: accelerated and real-time aging 

Stability testing is based on performance evaluation of packaging systems and/or products that have exceeded the shelf life claimed by the manufacturer. When a new product is launched on the market, or when consequent changes require a reassessment of this shelf life, ageing under accelerated conditions makes it possible to obtain data rapidly to guarantee reasonable time-to-market.

The standard ASTM F1980:2021 “Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices” specifies the parameters that will enable to establish an accelerated aging protocol adapted to the devices being tested. It is based on the assumption that the chemical reactions involved in material degradation follow Arrhenius’ law (or the Q10 rule), and that a 10°C increase in temperature approximately doubles the rate of reaction (and vice versa). In this case Q10 = 2 (i.e. a doubling of the ageing rate every 10°C), which is the commonly accepted factor for first-order chemical reactions, but not all materials strictly speaking follow this rule, and the Q10 value can thus vary from 1.8 to 3 (Figure 1).

Relationship between Q10 (Δ 10°C at constant reaction rate) and accelerated aging duration (adapted from ASTM F1980-21)

For example, some resorbable materials will have a Q10 value greater than 2, while a stable polymer such as polyethylene may have a Q10 of 1.8. Irrespective of the Q10 value, the higher the temperature, the faster the accelerated aging. However, by analyzing the medical device’s constituent materials and their transition temperatures, it is important to ensure that the temperature applied does not give rise to phenomena that cannot occur at room temperature. ASTM F1980 recommends a threshold temperature of 60°C, which should not be exceeded unless appropriate data are available to justify doing so.  

Control of aging temperature is therefore a key element of control, but the latest edition of ASTM F1980 also reinforces the importance of controlling and monitoring relative humidity. Indeed, as temperature rises, the relative humidity decreases for a given quantity of water. As physico-chemical changes during aging are highly dependent on water, particularly in the case of adhesives, which can hydrolyze, or alloys, which can corrode, it is essential to maintain a constant relative humidity that is representative of actual storage conditions, or risk obtaining non-compliant results. Thus, when it is determined that humidity can affect the aging of a product, ASTM F1980 recommends testing at a constant relative humidity set between 45 and 55%, corresponding to the relative humidity measured at 25°C in a temperate environment.

Accelerated ageing tests are therefore a major tool for obtaining solid stability data in a relatively short timeframe, but they require prior work based on a risk analysis and taking into account the composition of the device. However, ISO 11607-1 states that accelerated aging tests must always be confirmed by real-time aging tests on products stored under the conditions claimed by the manufacturer. 

Packaging system performance testing: transport simulation

ASTM D4169 and the ISTA 1 to 3 series provide a test protocol simulating the extreme conditions to which medical devices and their packaging systems may be exposed during a representative distribution cycle. The choice of which standard to follow can be complicated, as certain tests are more or less restrictive. The manufacturer must therefore clearly and exhaustively define the targeted distribution cycle (pallet or single carton transport, maximum load, rail, air or road transport, targeted geographical areas, etc.) and identify which standard is best suited to their needs.

The DC-13 distribution cycle of the ASTM D4169 standard is often followed by manufacturers of medical devices. This test cycle is in some respects comparable to the tests required by ISTA 2A, and subjects the test sample to drop, stack, vibration, low pressure and concentrated impact tests. Prior to testing, the test sample can be pre-conditioned for the extreme temperatures and relative humidity encountered in certain geographical zones (e.g. desert or tropical).

Conclusion

Validating the stability and transport of medical devices is essential to ensuring safe and effective healthcare. Faced with increasingly stringent regulatory requirements, including those of the Medical Device Regulation 2017/745, manufacturers must adopt rigorous methods to ensure that their products maintain their integrity and performance throughout their lifecycle. Standards such as ISO 11607-1, ASTM D4169 and ASTM F1980 provide important and instructive frameworks for carrying out aging tests and transport simulation, enabling the risks associated with device degradation to be anticipated and minimized. By integrating accelerated aging protocols and realistic simulations of transport conditions, manufacturers can not only meet regulatory requirements, but also reinforce the confidence of healthcare professionals and patients in the reliability of their products. In this way, a proactive and methodical approach to medical device validation is essential to guaranteeing the safety and quality of healthcare products.

Need help?

Our experts can help you draw up detailed protocols, justifying the choice and number of representative samples (cartons, primary and secondary packaging, products, etc.), the tests to be carried out and the parameters to be applied. Our experts can also advise you on the selection of certified testing laboratories and the drafting of validation reports.

We can also provide you with our expertise in your dealings with notified bodies, carry out literature reviews and draft rationales justifying the conformity of your tests, where appropriate.

Our technical teams are at your disposal for all your projects, and can be contacted at onedt@efor-group.fr.