Industry requirements Flashcards
1
Q
Sterilisation Industry requirements
A
Cleaning, disinfection, sterilization, and assurance of maintained sterility are critical considerations to ensure the safety and success of implants and devices.
- The term “sterile” refers to the presence or absence of microorganisms and is essentially a binary state; a material is either sterile or it has microorganisms.
- From a regulatory perspective, the term “sterile” is used to indicate the probability of an implant or device having a bioburden.
- The current expectation for patient safety is that less that one out of a million devices or implants can be nonsterile.
- This expectation is known as the “sterility assurance level” (SAL) and the one out of a million is defined as having an SAL of 10−6.
- A vast majority of the sterilization practices in use today are terminal processes where the products are sterilized after the entire process of manufacture has been completed.
2
Q
Radiation Based Sterilisation Techniques
A
- Sterilization by means of radiation is commonly used for mass- produced medical devices because of its simplicity and convenience in terms of large-scale processing.
- Terminal sterilization is achieved by exposing prepackaged devices to the appropriate dosage of radiation.
- The radiation will emit electrons or pho- tons that penetrate the packaging and destroy cells, bacteria, and viruses on devices.
- Radiation causes DNA damage in bacteria and viruses preventing pathogens from reproducing and thus inactivating them.
- The two most common methods used in industrial sterilization are gamma and electron beam.
3
Q
Radiation Based Sterilisation Techniques (Safety Concerns)
A
- Sterilisation by radiation carries two main safety concerns: possible lethal exposure to radiation and ozone.
- The lethal dosage of radiation to humans is about 0.01kGy with an exposure time of less than a second in some cases.
- Radiation sterilisation occurs at dosages ranging from 8 to 35 kGy.
- Understanding the bioburden on the materials prior to radiation sterilisation is critical for determining dose and validating sterilisation. As eg. the radiation dos-age required for bacteria and spores is lower than that for viruses.
- Thus, to prevent lethal exposure to workers, safety measures such as considerable amounts of shielding and robust interlocks are implemented in radiation processing.
- Ozone is a toxic gas that is formed when radiation comes into contact with oxygen, causing first the formation of free oxygen radicals and successively ozone.
- Appropriate safeguards to ozone inhalation include ozone monitors and adequate ventilation.
- Most industrial-scale radiation sterilisation occurs in closed rooms with safety precautions, and prepackaged products are usually loaded on conveyor systems that keep product containers in the path of the radiation for sterilization.
4
Q
Radiation Based Sterilisation Techniques
GAMMA STERILISATION
A
Gamma radiation takes its form in short electromagnetic wavelengths and therefore is more energetic.
- The gamma rays sterilise a product by providing adequate energy to break down DNA and prevent reproduction.
- The most common source of radiation is from radioactive cobalt-60, accounting for ∼80% of commercial radiation sterilisation.
- To process devices for gamma sterilisation, devices are placed in containers, generally made from aluminum, termed totes.
- Devices are placed in the totes and moved to the processing room to be sterilised (Fig. 3.1.4.1).
- Regardless of the amount in the tote, the product will be sterilised due to the lack of charge on 60Co particles, which allows the gamma particles to penetrate evenly and across long distances, thus making gamma sterilisation an attractive option since the amount does not limit sterilisation conditions.
5
Q
Radiation Based Sterilisation Techniques
ELECTRON BEAM STERILISATION
A
- Electron beam sterilisation refers to the application of electrons that are accelerated to form a beam of electrons with an energy of 5-10MeV, which are then scanned across the devices to be sterilised.
- These electrons are produced from electron accelerators, the two most common being DC accelerators and radio- frequency power-based accelerators.
- Unlike GAMMA STERILISATION, distances between devices and radiation source is a limitation since the beam has limited penetration distance.
- Thus, extra care and planning are required to determine load placements that take penetration depth into consideration, with less dense objects being placed ahead of objects with greater density.
- The process of electron beam sterilisation is faster (seconds to minutes) than gamma sterilisation (minutes to hours) because of a very high delivery rate of dosage.
- The short exposure time of the electron beam is also beneficial in that it decreases any material degradation that may occur to the product.
- From an application perspective, unlike gamma irradiators, electron beam sources have had relatively low commercial availability, resulting in electron beam sterilisation becoming a contract commercial sterilisation option only.
6
Q
Chemical Sterilisation Techniques
A
- Sterilisation by chemical means is more involved and specific to the product and chemical used than methods such as irradiation.
- The most popular chemical method is Ethylene Oxide Sterilisation
7
Q
Chemical Sterilisation Techniques (Safety Concerns)
A
- For sterilisation purposes, EO gas must be administered and stored at highly concentrated quantities.
- Under these conditions, EO is toxic, carcinogenic, and very explosive.
- Tools and equipment must be carefully chosen to prevent the possibility of accidental sparks in the vicinity of EO chambers.
- Even after an EO process is complete, personnel must take appropriate measures to avoid exposure to the toxic gas.
- These precautions include the use of personal protective equipment as well as respirators when working with products that have not been fully aerated to dissipate the gas and its residual by-products.
- Finally, any manufacturer of EO - sterilised products is responsible for abiding by the international standards that allow for adequate aeration to minimise EO residual levels below permissible limits for distribution, which is governed by ISO 10993-7.
8
Q
Chemical Sterilisation Techniques
ETHYLENE OXIDE STERILISATION
A
- Functions on the basis of its strong alkylating property, which causes disruption of cellular processes, including clotting of proteins, inactivation of enzymes, and disruption of DNA, resulting in preventing the replication of microorganisms.
- The alkylation reaction occurs on the amine side chains of the proteins, enzymes, and nucleic acids.
- Since this reaction is facilitated by moisture, it is essential that EO sterilisation be carried out in a humid environment.
- The basic EO sterilisation cycle involves five stages: preconditioning and humidification, gas introduction, exposure, evacuation, and aeration.
- Compatibility with most materials and excellent solid matrix diffusion properties have resulted in EO being used as the preferred sterilisation method for almost half the medical device manufacturing market.
- In addition to being a low-temperature process, EO can sterilise moisture- and radiation-sensitive materials without compromising product integrity.
- In addition, complex product architectures and designs can be sterilised by adjusting EO concentration and duration of exposure.
9
Q
Thermal Sterilisation Techniques
A
- Thermal sterilisation is the oldest class of sterilisation technique.
- This method can be used with moist or dry heat, which both have many characteristics in common.
- The high temperature in both techniques is the main principle of microbial inactivation.
- Thermal processes kill microorganisms by coagulation of proteins, including structural components of the cells, as well as by rupturing cell walls.
- The nature of the process is strongly impacted by the presence of water or humidity, in terms of the penetration of the heat, the exposure time of the surface of the material, as well as bio-burden sensitivity to dry or moist heat.
- For example, Bacillus subtilis var niger is less sensitive to dry heat, while Geobacillus stearothermophilus is less sensitive to moist heat or steam; thus each bacterium is used as the biological indicator to test the efficacy of the corresponding sterilisation treatment.
- Action and efficacy are also impacted by the ability of the materials being sterilised to high temperatures and to steam at high pressures.
10
Q
Thermal Sterilisation Techniques (Safety concerns)
A
- The hazards associated with the thermal sterilisation technique include heat, steam, and pressure.
- While this technique is the simplest sterilisation technique, following the protocols, regular maintenance, using a proper validation indicator, and controlling the exhaust would reduce the hazards.
- In addition to the regular safety considerations, choosing a suitable thermal technique plays an important role in the efficiency of the sterilisation.
- The dry heat technique is the most convenient method for heat stable materials such as non-aqueous materials, oil-based injectable pharmaceuticals, powders, glassware, and metallic surgical instruments.
- Whereas, high temperatures with moisture has advantages over dry heat such as reduced sterilisation time.
11
Q
Thermal Sterilisation Techniques
DRY HEAT
A
- The dry heat technique, one of the simplest sterilisation techniques, relies on only two parameters: temperature and exposure time.
- The simplicity of this technique has made it favorable for clinical and industrial applications for materials that can survive temperatures above 170°C with no deleterious effects.
- Convection, conduction, and thermal radiation are the major principles of dry heat sterilization.
- Generally, the dry heat technique includes thermal exposure at high temperature (160–330°C) for up to 3h; however, lower temperatures (e.g., 105°C) may be effective on some microorganisms if applied for a longer period of time.
- Dry heat is the most logistically convenient method for devices/ components that are not temperature sensitive. - - The simplest dry heat technique is the use of an oven
12
Q
Thermal Sterilisation Techniques MOIST HEAT (STEAM)
A
- Moist heat requires significantly reduced heat exposure time compared to dry heat and is nontoxic, rapid, penetrating, and energy efficient.
- However, this technique is not effective at destroying endotoxin (depyrogenation).
- Moreover, high temperature, humidity, and high pressure may lead to the softening, degradation, and hydrolysis of polymer-based materials.
- This technique is widely used in industrial sectors and hospitals for sterilisation of pharmaceuticals in glass ampules, plasticware, and metallic surgical instruments intended for reuse by applying saturated, pressurised steam.
- The regulatory preference is that steam sterilisation be used for terminal sterilisation where possible. Steam sterilisation is generally carried out at 120°C for only 20min and under a pressure of 121kPa.
- Autoclaves are widely used for this technique, which are similar to a pressure cooker with computer control for cycle monitoring.
13
Q
Ways that materials may fail
Patient–Implant Interactions Causing Clinical Complications
A
THROMBOSIS
- Thrombotic occlusion (blockage/closing of blood vessel)
- Thromboembolism (obstruction of vessel by a clot dislodged from another site in circulation)
- Anticoagulation-related haemorrhage (owing to therapy to prevent thrombosis) (escape of blood from a ruptured vessel)
INFECTION
- Inappropriate healing (too little or too much)
- Structural Failure Due to Materials Degeneration (wear, fracture/fatigue, calcification, tearing)
- Adverse Local Tissue Interactions (Inflammation, toxicity, tumor formation)
- Migration (Whole device, Embolisation or lymphatic spread of materials fragments)
- Systemic/Miscellaneous effects (Allergy, heart valve noise)
14
Q
The process for implant retrieval and evaluation
A
- Concerned with the documentation of problems that dictate modification of design, materials, or use of the implants in patients.
- Makes use of systematic, multilevel assessment protocols documented in international standards (ASTM F561 and ISO 12891) and the medical/scientific literature.
- The standards generally describe relevant conditions to document at the time of explantation, methods for analysing the tissue– implant interface and isolating particulate debris, and stages of progressively destructive analysis of the implant.
- STAGE 1 analysis consists of routine device identification, documenting the device description, and macroscopic examination for any evidence of failure modes.
- STAGE 2 analysis is more detailed and time consuming, and includes photography, optical microscopy, and nondestructive failure analysis.
- STAGE 3 analysis includes material-specific techniques for metallic, polymeric, and ceramic materials, many of which are destructive. (SEM, TEM etc.)
- In addition to specific analysis protocols for the implant–tissue interface and implant biomaterials, unraveling a cause of failure usually requires systematic integration of clinical and laboratory information pertaining to the patient, and careful pathological analyses.
- Evaluation of the implant without attention to the patient factors and clinical conditions will produce an incomplete evaluation, and limit understanding of the failure mode(s).
15
Q
What needs to be considered in the manufacture of medical devices (device failure and retrieval)
A
- Explant analysis is complementary to both preclinical assessments and postmarketing surveillance.
- Quantitative endpoints generated from implant retrieval and evaluation and related failure mode analysis aid the implant development process and contribute to patient safety as they bridge the gap between in vitro performance assessments and the effective clinical behavior of implants.
- Registry-based surveillance should be utilised where available when manufacturing devices as it offers the unique strength of reflecting the clinical reality (e.g., outcomes in routine clinical practice) and thus provide a high level of external validity of the proposed medical device.
