Medical Device
Stabilty Studies -
Ensuring product
reliability
Vincent RIETSCH
BU Manager – Medical Device Testing & Consulting
Sylvain DARONDEL
BU Manager – Storage & Logistics
29.02.2024
Introduction
Regulatory & normative framework
Study design & protocol
Data collection & analysis CONFIDENTIAL AND PROPRIETARY - © Eurofins Scientific (Ireland)
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Introduction
Definition of stability studies for Medical Devices
Safety
Efficacy
Reliability
Stability studies
(various environmental conditions)
4
Importance of stability studies for Medical Devices
Key reasons for Medical Devices stability studies :
1. Patient safety
2. Regulatory compliance
3. Product quality
4. Product shelf-life determination
5. Management of supply chain
6. Product development and optimization
7. Patient and professionals' confidence
5
Medical Devices, Combined MD and Sterile Barrier Systems
Combined Medical Sterile Barrier
Medical Device
Device Systems
- shelf-life - ingredient stability
- storage, shipping, and - interaction between
distribution packaging system and - packaging performance
product and integrity
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Regulatory
framework
MDR - Annex I: GSPR
Medical Device Regulation (2017/745) requires:
➢ Devices shall be designed, manufactured and
packaged in such a way that their characteristics
and performance during their intended use are not
adversely affected during transport and storage by :
• Contaminants and residues to patients
(chemistry)
• Microbial ingress and packaging integrity
(microbiology and physics)
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MDR - Annex II: Technical Documentation
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Regulatory Framework - ISO 13485 / FDA 21 CFR part 820
Both QMS standards requires to manage medical
devices stability, but very few information available :
➢ document procedures in the context of storage
and transport operations
➢ ensure the maintenance of the sterile barrier
system
However, no method of evaluating the lifecycle is
provided.
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Regulatory Framework - ICH guideline
ICH Q1A guideline for new Drug Substances and
Products
Not applicable to Medical Devices, but define
applicable storage conditions, ie thermal stability
and sensitivity to moisture
Study Storage condition Minimum time period
Long term 25°C (± 2°C) / 60% RH (± 5% RH) 12 months
or
30°C (± 2°C) / 65% RH (± 5% RH)
Accelerated 40°C (± 2°C) / 75% RH (± 5% RH) 6 months
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Normative
framework
ASTM F1980:2021 - Standard Guide for Accelerated Aging of
Sterile Barrier Systems and Medical Devices
2007 version 2021 version
Applicability Sterile Barrier Sterile Barrier
Systems for Systems and
Medical Medical Devices
Devices
Provide sufficient evidence for expiration date claims for medical devices and
sterile barrier systems (SBS), until data from real-time aging studies are
available
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ASTM F1980:2021 - Scope and goals
➢ Develop accelerated aging protocols to model the effect of time and
physical properties
➢ Not in the scope :
• Real-time aging protocols studies (ISO 11607-1:2019) shall be
performed to confirm the accelerated aging test results using the same
methods of evaluation
• Interaction compatibility between the SBS material and device
• Performance validation (environmental challenge, distribution, handling,
and shipping)
• Label storage conditions
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ASTM F1980:2021 - Main concepts
➢ Physical properties of the materials and adhesive or
cohesive bonds degrades over time by dynamic (shipping
and/or handling) or static (storage) events
➢ To get new products to market in the shortest possible time,
real time aging studies do not meet this objective.
Accelerated aging studies can provide an alternative
means of screening for possible aging-related failure
mechanisms in the SBS or medical device.
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ASTM F1980:2021 - Accelerated aging theory
➢ Principle : material is subjected to conditions which accelerate the reaction
kinetics of possible degradation pathways
➢ Chemical reactions follow Arrhenius reaction rate function : 10°C increase in
temperature of a homogeneous process results in a two-fold increase in the
rate of a chemical reaction (Q10)[1].
➢ Not only the accelerated aging temperature conditions but also the ambient
relative humidity during that accelerated aging
➢ Knowledge of the materials used, and their relevant degradation mechanisms,
is important in the proper design of an accelerated aging protocol
[1]: Hemmerich, K. J., “General Aging Theory and Simplified Protocol for Accelerated Aging of Medical Devices,” Medical Plastics and Biomaterials,
July/August 1998, pp. 16–23
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Study design &
protocol
ASTM F1980:2021 - How to design an accelerated aging study ?
➢ Characterization of materials (composition, morphology, thermal transitions,
additives, moisture absorption characteristics, degradation mechanisms…)
➢ Selection of appropriate temperatures (based on materials and intended
storage conditions) :
• Room or Ambient Temperature (TRT), between 20°C to 25°C
• Accelerated Aging Temperature (TAA), ≤ 60°C
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ASTM F1980:2021 - How to design an accelerated aging study ?
➢ Determination of the Accelerated Aging Factor (AAF) by the following
equation :
AAF = Q10 [(TAA – TRT)/10]
➢ Determination of the Accelerated Aging Time (AAT) by the following equation :
AAT = TRT / AAF
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ASTM F1980:2021 - Accelerated aging protocol steps
The protocol should define :
➢ Test sample determination, including the SBS
➢ Q10 value (in general, Q10 = 2)
➢ Desired shelf life
➢ Aging test time intervals, including time zero (T0)
➢ Test conditions, room temperature (TRT), and accelerated aging
temperature (TAA)
➢ Relative humidity conditions and allowable tolerances
➢ Calculate the Accelerated Aging Time (AAT) using Q10, TRT and TAA
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ASTM F1980:2021 - Accelerated aging report
The report should define :
➢ written test report specifying the accelerated aging conditions
➢ temperature and relative humidity of the chamber used
➢ If the sterile barrier system is evaluated :
• test standard references and methods
• equipment used for physical and microbial testing
➢ Document the post-aging test results
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ASTM F1980:2021 - Post-Aging Testing Guidance
Very few information available :
➢ Tests selected for evaluation should challenge the material
functionality that is most critical or most likely to fail because of aging
➢ SBS should be evaluated for both physical properties and integrity (ISO
11607-1:2019)
Main endpoints to address :
➢ Sterile barrier and micro-organisms impermeability
➢ Biocompatibility and toxicological properties
➢ Physical and chemical properties
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Storage &
Logistic
Storage condition management (Ishikawa) 1/3
Environment
➢ Access and video surveillance
➢ Anti-intrusion security system
➢ Temperature regulation
➢ Pest control
Methods
➢ SOPs in place (sample flow, metrology,
maintenance)
➢ Training support
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Storage condition management (Ishikawa) 2/3
Manpower
➢ Training
➢ Habilitation
Materials
➢ Stability study Protocol and Report
(ICH Q1D : bracketing and matrixing)
➢ Safety data sheet
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Storage condition management (Ishikawa) 3/3
Machines
➢ Fully qualified (IQ, OQ, PQ) with mapping
➢ Backup (double engines or empty qualified machine)
➢ Maintenance program
➢ Spare part on stock
➢ Power back-up generator
Measurements
➢ Continuous monitoring (temperature and humidity) 21 CFR Part 11
➢ Alarm system with on-call system 24 hours a day, 7 days a week, 365
days a year
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Shipment management
➢ Shipment condition
➢ Courier selection and qualification
➢ Vehicle and parcel validations
➢ Custom clearance for international shipment
➢ Delivery reporting and tracking
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Case studies
Eurofins European largest ICH Stability Storage capacity
In operation for One hour from Paris Dedicated team to Dedicated building
20 years airports and storage and logistic 3,200m3 of storage
International train
station
5,000+ ICH, ATEX,
Stability Studies cycling, customized
> 70 storage areas From -80°C to 120°C From 15 to 85%RH
API, RM, FP, MedDev photostability studies
Safe and qualified Shipment under
TAT 24 hours eLIMS BPT
storage conditions controlled conditions
LabAccess
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Case studies #1 - Accelerated aging
Surgical implants :
- accelerated aging of 2 boxes (30 x 10 L,
57 x 1.5 L)
- 55°C/50%HR
- 2-time intervals (T91 and T228, 1- and 5-
years simulation)
- boxes sent by carrier at the end of
aging (visual inspection and functional tests)
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Case studies #2 - Combined Medical Device
Dermal filler :
- combined stress, real-time and accelerated aging (4 batches)
- Precondition study : -20°C 7 days, 40°C 3 days, cycling (-20°C, 40°C) 12 days
- 25°C/60%HR (real-time) and 40°C/75%HR :
- 7-time intervals (T3, T6, T9, T12, T18, T24 and T36, + back-up)
- 2-time intervals (T3 and T6, + back-up)
- boxes sent by carrier to several testing sites (mechanical, chemical and
microbiological tests)
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Take-home
Message
Take-home Message
➢ Proceed with a risk analysis
➢ Carefully select aging temperature and relative humidity
➢ Define aging time intervals corresponding to the desired shelf life
➢ Build the test samples in accordance with a validated production process
➢ Shelf life is validated when accelerated aging and real-time results meet the
acceptance criteria
➢ Take PMS data into account
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