ABSTRACT
This paper addresses some of the risk considerations that must be evaluated when replacing a steam sterilizing autoclave within a pharmaceutical processing facility. It demonstrates the application of Failure Modes and Effects Analysis (FMEA) for assessment of risk as part of quality risk management. Formal risk approaches normally share four basic concepts including risk assessment, risk control, risk review, and risk communication. Risk management is fundamentally about understanding what is most important for the control of equipment or design quality and then focusing resources on managing and controlling these aspects. Before risks can be managed, they need to be assessed. FMEA is a widely used risk assessment tools. Steps to perform FMEA are identified; questions to be asked are listed. Criteria for risk assessment must be defined. Either a numerical scoring system or marker phrases such as “high,” “medium,” “low” may be utilized. Three areas are evaluated: Severity of the hazard, likelihood of occurrence, and likelihood of detection. Tables for classifying these aspects are provided. A team approach to risk assessment is recommended. The risk assessment process is demonstrated using the example of a steam sterilizing autoclave replacement.
INTRODUCTION
This paper addresses some of the risk considerations that must be evaluated when replacing a steam sterilization autoclave within a pharmaceutical processing facility. A cast study format is utilized. In outlining the key risk considerations, the paper demonstrates a risk assessment approach – Failure Modes and Effects Analysis (FMEA).
An autoclave is a pressure chamber used to sterilize equipment and supplies by subjecting them to high pressure saturated steam (1). Autoclaves are used within pharmaceutical facilities to eliminate microbial cells and spores from within a given device. Autoclaves commonly use steam heated to 115–134°C (250 273°F). To achieve sterility, a holding time of at least 30 minutes at 115°C, 15 minutes at 121°C (250°F) or 3 minutes at 134°C (273°F) is required (2).
The validation and verification of the sterilization process is well monitored in the pharmaceutical industry. Operators must ensure that autoclaves comply with various regulatory guidances and regulations. Nonetheless, the purchase of a new autoclave and the assessment requires evaluation. An additional dimension is added when one autoclave is being used to replace another, as with the case study discussed here. To make such an evaluation, a formal risk assessment is required under the auspices of quality risk management.
Risk management and risk assessment principles should be applied as early as possible during the design and construction of steam sterilization devices. The most critical functions in a steam sterilization device are the steam sterilization of direct and indirect the product contact parts. A second important aspect relates to air removal. All of the trapped air must be removed from the autoclave before activation. Trapped air is a very poor medium for achieving sterility during the sterilization cycle.
Formal risk approaches normally share four basic concepts, which are listed below:
- Risk assessment
- Risk control
- Risk review
- Risk communication.
This paper considers the application of FMEA, failure modes and effects analysis, to the replacement of a steam-sterilizing autoclave in a pharmaceutical manufacturing facility.
FAILURE MODES AND EFFECTS ANALYSIS (FMEA)
Risk management is fundamentally about understanding what is most important for the control of equipment or design quality and then focusing resources on managing and controlling these aspects to ensure that risks are reduced and contained. Risks relate to a situation, event or scenario where a recognized hazard may result in harm. Before risks can be managed, they need to be assessed (3).
Risk assessment involves identifying risk scenarios. In relation to cleanroom and clean air design, this should ideally be a prospective exercise rather than in reaction to a failure. This process involves determining what can go wrong in the system and all the associated consequences and likelihoods. To achieve this, some kind of risk assessment tool is required (4).
Three key definitions are outlined in ICH Q9(5). These help to contextualize what is meant by “risks.”
- Risk: The combination of the probability of occurrence of harm and the severity of that harm
- Harm: Damage to health, including the damage that can occur from loss of product quality or availability
- Hazard: The potential source of harm.
For engineering systems, one of the most widely used tools for risk assessment is Failure Modes and Effects Analysis (FMEA) (6).
FMEA is a highly structured approach and can be undertaken through the following steps:
a) Setting the scope
b) Defining the problem
c) Setting scales for factors of severity, occurrence and detection (see below)
d) Process mapping
e) Defining failure modes
f) Listing the potential effects of each failure mode
g) Assigning severity ratings to each process step
h) Listing potential causes of each failure mode
i) Assigning and occurrence rating for each failure mode
j) Examining current controls
k) Examining mechanisms for detection
l) Calculating the risk
m) Examining outcomes and proposing actions to minimize risks.
STARTING THE RISK ASSESSMENT PROCESS
Before commencing a risk assessment, it is important to define the size and the scope of the assessment while remaining focused on what is to be achieved, to select the appropriate team (often an interdisciplinary team is best); selecting and reviewing the appropriate risk management tool; deciding upon any numerical scale to be used, and prioritizing the different problems to be addressed.
These steps can be broke down as follows:
- Gathering data through an audit and analysis
- Constructing diagrams of work flows
- Pin-pointing areas of greatest risk
- Examining potential sources of contamination
- Deciding on the most appropriate sample methods
- Helping to establish alert and action levels
- Taking into account changes to the work process / seasonal activities
- Using some type of scoring system so that the risk can be ranked and the level of risk determined.
In doing so the following questions should be asked:
- What is the function of the equipment?
- What are its performance requirements?
- How can it fail to fulfill these functions?
- What can cause each failure?
- What happens when each failure occurs?
- How much does each failure matter? What are its consequences?
- What can be done to predict or prevent each failure?
- What should be done if a suitable proactive task cannot be found?
These reflective questions help to structure the risk assessment activity.
RISK CRITERIA
It is important to establish the risk assessment criteria as part of the risk assessment exercise. This is necessary in order to place risks in proportion to one another and against a universal scale. Without this, it cannot be determined whether one risk is a greater or lesser problem compared with another, or if a given risk could potentially result in patient harm.
FMEA may utilitze either a numerical scoring system or marker phrases such as “high,” “medium,” “low’ for quantitation. Marker terms are used in the following case study.
These terms are applied to three aspects. These are the severity of the hazard; how likely the hazard is to occur; and whether there are any mechanisms in place to detect the hazard should it occur. Here:
- Severity is the consequence of a failure, should it occur
- Occurrence is the likelihood of the failure happening based on past experience
- Detection is based on the monitoring systems in place and on how likely a failure can be detected. Sometimes, a good detection system is described as one that can detect a failure before it occurs.
When these three are cross-compared, the overall risk can be established. The best means to do this is through the use of risk filters. These are illustrated in Tables 1 and 2 below.
Before looking at the risk filter tables, it is necessary to define each of the terms used to establish the overall risk.
Severity of Impact
- High = Patients safety will be impacted
- Medium = Potential patient safety issues
- Low = No impact on patient
Likelihood of Occurrence
- High = 1 failure per year
- Medium = 1 failure every 5 years
- Low = 1 failure every 10 years
For documentation, the likelihood is as follows:
- High = No Documentation
- Medium = Incorrect Documentation
- Low = Documentation present and correct
Probability of Detection
- Low = Will not be detected by in-place systems
- Medium = Only one mechanism for detection by existing systems
- High = More than one mechanism for detection by existing systems
RISK CLASSIFICATION AND RISK FILTERING
Record the risk classification based upon the impact and likelihood from the table (Table 1). This is established through the use of a filter (or matrix).
CLASSIFICATION OF RISK |
||||
Impact |
Likelihood |
|||
|
Low |
Medium |
High |
|
Low |
LOW |
LOW |
MEDIUM |
|
Medium |
LOW |
MEDIUM |
HIGH |
|
High |
MEDIUM |
HIGH |
HIGH |
TABLE 1: CLASSIFICATION OF RISK
Risk Priority
Record the risk priority based upon the risk classification and probability of detection from the table.
RISK PRIORITY |
|||
Risk Classification |
Probability Of Detection |
||
High |
Medium |
Low |
|
Low |
LOW |
LOW |
MEDIUM |
Medium |
LOW |
MEDIUM |
HIGH |
High |
MEDIUM |
HIGH |
HIGH |
TABLE 2: RISK PRIORITY
Risk Process
In formulating the risk assessment a group was assembled consisting of engineering, validation, microbiology, and the end-users. The process began by identifying the key risk factors and potential failure modes. These were described as “functional details.” Once these were defined, these primary categories were broken down into sub-steps that are termed “sub-functional details.”
Once these were selected and agreed, the steps were grouped together. The group then proceeded to assess the risk for each step, using the FMEA schema outlined above. This consisted of:
a) Considering the relevance of each sub-functional detail. For example, whether it could potentially impact upon product quality
b) The possible risk scenarios were considered
c) The severity of impact was then assessed as either “high”, “medium” or “low”, using the definitions outlined above
d) The likelihood of impact was then assessed, using the same descriptors
e) With the severity and likelihood assessed, the risk class was determined using Table 1 above.
f) The probability of detection was assessed next
g) Knowing the probability of detection allowed the overall risk priority to be determined using Table 2 above.
h) The penultimate step was to consider whether any controls or risk mitigation factors were in place
i) The final step was to reach a conclusion in relation to risk management.
The risk assessment process is outlined in Appendix I using the example of a steam sterilizing autoclave replacement.
Equipment preparation
The defined loading of the autoclave with equipment to be sterilized in an important sub-functional detail is in autoclave operation. The relevance of loading an autoclave incorrectly significantly impacts product quality. Here the risk scenario is an incorrect sterilization of the load. In this case:
a) The severity of impact would be high;
b) The likelihood of impact could be medium.
This produces, according to Table 1, a high risk class.
The probability of detection would be low, because the activity is operator dependent and there are no system aspects that prevent an incorrect load from being prepared. Therefore, using Table 2, the risk priority is high.
However, in terms of risk mitigation and risk management, a clear SOP can be put in place and operators can be trained in order to lower the possibility of an incorrect load being prepared. In addition:
- Photos of the loads can be prepared during the Operational Qualification
- Schematics may be included in the SOP
- Worst-case loads can be verified during both the Operational Qualification and Performance Qualification.
This example is included in Appendix I. Other sub-functional steps were derived using similar processes.
RISK EXAMPLE
Appendix I contains an example of risk assessment for a replacement steam-sterilizing autoclave. The table is arranged in a fashion to facilitate the risk assessment steps described above where functional and sub-functional steps are outlined. The case study was designed around a particular device and should be regarded as illustrative. Users embarking on a similar process may take note of the items covered. However, they should construct their own risk schematic and reach conclusions that are relevant to their own particular circumstances.
CONCLUSION
The final assessment of the FMEA risk exercise was that the new autoclave can be fitted and that the risks are adequately controlled. It was noted that although the new autoclave has newer control systems technology, the steam sterilization principles together with the load/ test cycles remain in line with the autoclave that is being replaced.
The FMEA risk assessment methodology was appropriate to the task. An alternative approach could have been to use a numerical risk assessment. However, the use of descriptor words like “high,” “medium,” and “low” proved adequate in relation to the activity.
REFERENCES
- Sandle, T. (2013). Sterility, Sterilisation and Sterility Assurance for Pharmaceuticals: Technology, Validation and Current Regulations, Woodhead Publishing Ltd.: Cambridge, UK, pp93-110
- Hugo WB (1991). A brief history of heat and chemical preservation and disinfection. J. Appl. Bacteriol. 71 (1): 9–18
- Sandle, T. (2011): Risk Management in Pharmaceutical Microbiology. In Saghee, M.R., Sandle, T. and Tidswell, E.C. (Eds.) (2011): Microbiology and Sterility Assurance in Pharmaceuticals and Medical Devices, New Delhi: Business Horizons, pp553-588
- Sandle, T. and Lamba, S. S. (2012) Effectively Incorporating Quality Risk Management into Quality Systems. In Saghee, M.R. Achieving Quality and Compliance Excellence in Pharmaceuticals: A Master Class GMP Guide, New Delhi: Business Horizons, pp89-128
- ICH Q9: Quality risk management. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH, Geneva (November 2005)
- Sandle, T. (2003). The use of a risk assessment in the pharmaceutical industry – the application of FMEA to a sterility testing isolator: a case study, European Journal of Parenteral and Pharmaceutical Sciences; 8(2): 43-49
FMEA KEY
BI - Biological Indicator
IQ - Installation Qualification
O&M - Operation and Maintenance
OQ - Operational Qualification
PQ - Performance Qualification
PC - Personal Computer
SOP - Standard Operating Procedure
SAT - Site Acceptance Test
UPS - Uninterruptable Power Supply
APPENDIX 1
Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment |
|||||||||||
Function Details |
Sub-Functions Details |
Assessment of Risk |
Controls In Place |
Risk Management |
|||||||
Relevance |
Risk Scenarios |
Severity of Impact |
Likelihood of Impact |
Class |
Probability of Detection |
Overall Priority |
|||||
Equipment |
Autoclave Operation And Maintenance Manuals |
cGMP |
Incorrect documentation supplied |
High |
Medium |
High |
High |
Medium |
SAT |
Documentation check during IQ. |
|
Equipment |
cGMP |
No documentation supplied |
High |
Medium |
High |
High |
Medium |
SAT |
Documentation check during IQ. |
||
Equipment
|
Drawings And Schematics (Including P&ID and General Assembly drawings) |
cGMP |
Drawings not the latest revision |
High |
Medium |
High |
High |
Medium |
Functional Specification |
Documentation review and approval of Functional Specification. |
|
Equipment
|
cGMP |
No drawings supplied |
High |
Medium |
High |
High |
Medium |
Functional Specification |
Documentation review and approval of Functional Specification. |
||
Equipment |
Equipment Inspection |
cGMP |
Poor Design and construction. Components not securely installed |
High |
Medium |
High |
High |
Medium |
SAT |
Equipment inspection during commissioning & IQ checks. |
|
Equipment |
cGMP |
Poor construction. Components damaged |
High |
Medium |
High |
High |
Medium |
SAT/ EN285 |
Equipment inspection during commissioning & IQ checks. |
||
Equipment |
Equipment Inspection |
cGMP |
Manufacture not performed according to a recognized standard |
High |
Low |
Medium |
High |
Low |
SAT
|
Documentation check to confirm that manufacturing according to BS5750 or equivalent. |
|
Control System |
Standard Operating Procedures |
cGMP |
SOP not in place |
High |
Low |
Medium |
High |
Low |
SAT/ Training |
To be created/ Approved post supplier training. |
|
Control System |
Standard Operating Procedures |
cGMP |
SOP followed incorrectly |
High |
Low |
Medium |
Medium |
Medium |
Training |
Supplier/ Training and SOP sign off. |
|
Equipment |
Maintenance Programme |
cGMP |
Maintenance requirements not identified |
High |
Low |
Medium |
High |
Low |
Asset register |
Asset Registration Form |
|
Equipment |
cGMP |
Maintenance procedure not produced |
High |
Low |
Medium |
High |
Low |
Asset register |
Asset Registration Form |
||
Operations |
Equipment Logbook |
cGMP |
Logbook not present |
High |
Low |
Medium |
High |
Low |
SOP |
Equipment Registration and Assessment |
|
Operations |
Equipment Identification |
cGMP |
Incorrect labeling |
High |
Medium |
High |
High |
Medium |
SOP |
Equipment Registration and Assessment |
|
Operations |
cGMP |
No identification |
High |
Medium |
High |
High |
Medium |
SOP |
Asset Number check during IQ. |
||
Operations |
Spare Parts And Consumables |
Business Critical |
Spare Parts List not available |
High |
Low |
Medium |
Medium |
Medium |
SOP |
Documentation check during IQ. |
|
Operations |
Business Critical |
Consumables not identified so not in stock |
High |
Low |
Medium |
Medium |
Medium |
SOP |
Equipment Registration and Assessment |
||
Equipment |
Materials In Product Contact |
cGMP |
Materials not suitable |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation check during IQ. |
|
Equipment |
cGMP |
Documentation not available |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation check during IQ. |
||
Equipment |
Lubricants |
cGMP |
Incorrect lubricants supplied |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation check during IQ. |
|
Equipment |
cGMP |
Lubricants not pharmaceutical grade |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation check during IQ. |
||
Equipment |
Filters |
Business Critical |
Filters not available |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation check during IQ. |
|
Incorrect filters supplied |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation check during IQ. Engineering Stores to stock critical filters. |
||||
Equipment |
Control System Hardware |
cGMP |
Incorrect components supplied |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation and Hardware check during IQ. |
|
Equipment |
Control System Software |
Business Critical |
Incorrect version of the software supplied |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation and Software check during IQ. |
|
EPROM failure |
High |
Low |
Medium |
High |
Low |
SAT |
Documentation and Hardware check during IQ. |
||||
Equipment |
Control System Software |
Business Critical |
No software backup disk supplied |
Medium |
Low |
Low |
High |
Low |
SAT |
Back up disk check during IQ. |
|
Equipment |
Monitoring System |
cGMP |
Back up battery failure in Chart Recorder |
Medium |
Low |
Low |
High |
Low |
SAT |
Battery checked during IQ. |
|
Operations |
Environmental Requirements |
Business Critical |
Plant room too hot for Autoclave control system to operate. |
High |
Low |
Medium |
High |
Low |
Preliminary works |
Plant room temperature to be controlled via extraction and additional cooling if necessary. |
|
Equipment |
Equipment Generated Particles |
cGMP |
Autoclave sheds dust/ particles into clean rooms. |
High |
Low |
Medium |
High |
Low |
SAT |
Material type compliance certs to be checked during IQ. |
|
Operations |
Utility Requirements |
cGMP |
The utilities supplied do not allow sterilisation conditions to be achieved. |
High |
Low |
Medium |
High |
Low |
Utilities to be tested IQ/ SAT |
The critical utilities will be designed to be tested at SAT. |
|
Operations |
Utility Requirements |
cGMP |
Services are not satisfactorily connected |
High |
Low |
Medium |
High |
Low |
SAT |
Services to be checked during commissioning and SAT. |
|
Equipment |
Operating Specifications |
cGMP |
Autoclave Operating Specifications are set-up incorrectly |
High |
Low |
Medium |
High |
Low |
SAT |
To be checked and documented during OQ |
|
Operations |
Maintenance works |
cGMP |
Maintenance work on the steam, water or piped gas services is performed after installation/ operational tests are completed |
Medium |
Low |
Low |
High |
Low |
SAT |
Tests must be repeated before commissioning starts. |
|
Equipment |
Calibration Information |
cGMP |
Critical instruments not identified |
High |
Low |
Low |
High |
Low |
SAT/ SOP |
Identification and classification of instruments during IQ |
|
Operations |
Critical Instruments |
cGMP |
Critical instruments not calibrated |
High |
Low |
Low |
High |
Low |
SAT/ SOP |
Identification and classification of instruments during IQ |
|
Operations |
Critical Instruments |
cGMP |
Calibration Certificates not available |
Medium |
Low |
Low |
High |
Low |
SAT/ SOP |
Documentation check during IQ. Calibration schedule updated. |
|
Operations |
Critical Instruments |
cGMP |
Calibration Laboratory not traceable to UKAS |
Medium |
Low |
Low |
High |
Low |
SAT/ SOP |
Documentation check during IQ. |
|
Operations |
Training |
cGMP |
Operators not trained |
High |
Medium |
High |
High |
Medium |
Supplier Training/ SOP |
Autoclave Supplier Training to be completed on site post commissioning and SOP to created and signed off for training. |
|
Operations |
Utility Requirements |
cGMP |
Equipment operation interferes with other equipment in the same room |
Medium |
Medium |
Medium |
High |
Low |
SOP |
Utility Impact Assessment/ Change Control/ SOP |
|
Equipment |
Operation |
cGMP |
Equipment is not safe to operate |
High |
Medium |
High |
High |
Medium |
SAT |
Commissioning Safety checks, and SAT checks to ensure safety. PUWER risk assessment. |
|
Operations |
Equipment Setup |
cGMP |
Setup incorrect |
Medium |
Medium |
Medium |
High |
Low |
Training/ SOP |
Training & Sign off against SOP. |
|
Equipment |
Power Failure Recovery |
Business Critical |
EPROM does not have the latest version of the software after SAT changes |
Medium |
Low |
Low |
High |
Low |
SAT/ Change Control |
Checks made during SAT and any changes/ or deviations noted in change control. |
|
Equipment |
Power Failure Recovery |
Business Critical |
Batch data lost when equipment power restored |
Medium |
Low |
Low |
High |
Low |
Training/ SOP |
SOP to train out process for recovery. |
|
Equipment |
Power Failure Recovery |
Business Critical |
Previous version of the software loaded after power restoration |
Medium |
Low |
Low |
High |
Low |
Training and Maintenance SOP |
SOP to train out process for recovery. |
|
Equipment Alarms |
Safety Devices |
cGMP |
Steam Valve failure |
High |
Low |
Medium |
High |
Low |
SAT/ Maintenance |
Checked during SAT and added to Maintenance schedule |
|
Equipment Alarms |
Sensors |
cGMP |
Temperature sensor failure |
High |
Low |
Medium |
High |
Low |
SAT/ Maintenance |
Checked during SAT and added to Maintenance schedule |
|
Equipment |
Interlocks |
cGMP |
Unloading door opens after a Bowie Dick Test |
Medium |
Low |
Low |
High |
Low |
SAT/ SOP |
Checked during SAT and regular SOP checks |
|
Equipment |
Interlocks |
cGMP |
Both doors open at the same time |
Medium |
Low |
Low |
High |
Low |
SAT/ SOP |
Checked during SAT and regular SOP checks |
|
Equipment |
Interlocks |
cGMP |
Unloading door opens after cycle failure |
High |
Low |
Medium |
High |
Low |
SAT/ SOP |
Checked during SAT and regular SOP checks |
|
Control System |
Algorithm Verification |
cGMP |
Algorithms used in the calculation of critical parameters is incorrect |
High |
Low |
Medium |
High |
Low |
Functional Specification/ SAT |
Checked at Functional Specification review and SAT |
|
Control System |
Operator Panel and Screen Navigation |
Operation |
Operator panel does not function as specified in the operator manual |
Medium |
Low |
Low |
High |
Low |
SOP/ Maintenance |
Checked during SAT and normal operation. |
|
Control System |
Security |
cGMP |
Security levels not set up on the software |
Medium |
Low |
Low |
High |
Low |
SOP/ Training |
Checked during SAT and set-up during Training and SOP created. |
|
Control System |
Report Generation |
cGMP |
The results on the printed report do not match the displayed values |
Medium |
Low |
Low |
High |
Low |
Calibration/ Maintenance/ Training/ SOP |
Checked during SAT and set-up during system Calibration. |
|
Control System |
Report Generation |
cGMP |
The values used for the display and printed reports are taken at different times in the cycle by the software. |
Medium |
Low |
Low |
High |
Low |
Calibration/ Maintenance/ Training/ SOP |
Checked during SAT and set-up during system Calibration. |
|
Control System |
Report And Data Archiving |
cGMP |
The data is lost when archived. |
Medium |
Low |
Low |
High |
Low |
Training/ Maintenance |
Checked during SAT and set-up during system maintenance. |
|
Control System |
Report And Data Archiving |
cGMP |
The data is corrupted or changed when retrieved |
Medium |
Low |
Low |
High |
Low |
System Maintenance/ Training |
Checked during SAT and set-up during system maintenance training. |
|
Control System |
Report And Data Archiving |
cGMP |
The report batch numbers are changed. |
Medium |
Low |
Low |
High |
Low |
System Maintenance/ Training |
Checked during SAT and set-up during system maintenance training. |
|
Control System |
Report And Data Archiving |
cGMP |
The software does not allow the retrieved file to be viewed |
Medium |
Low |
Low |
High |
Low |
System Maintenance/ Training |
Checked during SAT and set-up during system maintenance training. |
|
Control System |
Report And Data Archiving |
cGMP |
The software is not available for retrieval of data |
Medium |
Low |
Low |
High |
Low |
System Maintenance/ Training |
Checked during SAT and set-up during system maintenance training. |
|
Control System |
Recipe Loading |
cGMP |
The incorrect parameters are loaded in to the cycle |
High |
Low |
Medium |
High |
Low |
Training/ SOP/ O&M’s |
Checked during SAT and set-up during Training and SOP created |
|
Control System |
Recipe Changes |
cGMP |
The software does not store changes made to the recipe |
Medium |
Low |
Low |
High |
Low |
Training/ SOP/ O&M’s |
Refer to supplier O&M’s and SOP |
|
Control System |
Recipe Changes |
cGMP |
The parameters required to move from one phase to the next cannot be changed on the recipe screen. |
Medium |
Low |
Low |
High |
Low |
Training/ SOP/ O&M’s |
Refer to supplier O&M’s and SOP |
|
Control System |
Counter/ Sequence Verification |
cGMP |
The counter does not log all cycles |
Medium |
Low |
Low |
High |
Low |
Training/ SOP/ O&M’s |
Refer to supplier O&M’s and SOP |
|
Control System |
Counter/ Sequence Verification |
cGMP |
The counter does not log aborted or failed cycles |
High |
Low |
Medium |
High |
Low |
Training/ SOP/ O&M’s |
Refer to supplier O&M’s and SOP |
|
Control System |
Counter/ Sequence Verification |
cGMP |
The clock does not record the correct time (GMT) |
High |
Low |
Medium |
High |
Low |
Training/ SOP/ O&M’s |
Refer to supplier O&M’s and SOP |
|
Equipment Operation |
Operational Sequence |
cGMP |
The phase parameters in the software cause the cycle to abort |
Medium |
Low |
Low |
High |
Low |
SAT/ PQ |
Checked and documented during SAT and PQ. |
|
Equipment Operation |
Temperature Distribution |
cGMP |
The temperature in the chamber does not meet the specification in EN285 and HTM 2010 for Steam Sterilization. |
High |
Low |
Medium |
High |
Low |
SAT/ PQ |
Checked during Autoclave Commissioning, SAT & PQ |
|
Equipment Operation |
cGMP |
There is uneven heat distribution in the chamber |
High |
Low |
Medium |
High |
Low |
SAT/ PQ (Bowie Dick Tests) |
Checked during Autoclave Commissioning, SAT & PQ |
||
Equipment Operation |
Air Removal |
cGMP |
Air is not removed from the equipment |
Medium |
Low |
Low |
High |
Low |
SAT/ PQ
|
Checked during Autoclave Commissioning, SAT & PQ |
|
Equipment Operation |
Operation |
There is an air leak in the chamber |
Medium |
Low |
Low |
High |
Low |
SAT/ PQ |
Leak Rate Tests during commissioning, SAT & PQ |
||
Equipment Operation |
Steam Penetration |
cGMP |
Steam does not penetrate the equipment |
High |
Medium |
High |
High |
Medium |
Validation -PQ |
Checked and documented against current validated load profiles during PQ. |
|
Equipment Operation Equipment Operation |
cGMP |
There are high levels of particulates in the steam supply |
High |
Medium |
High |
Medium |
High |
Clean Steam Quality Testing
|
Clean Steam to be quality tested |
||
Equipment Operation |
Condensate Removal |
Operation |
The equipment orientation causes drainage problems i.e. Wet Loads |
High |
High |
High |
High |
Medium |
PQ testing and SOP |
To be checked and documented during PQ with current validated load profiles. |
|
Equipment Operation |
Bio-burden |
cGMP |
High levels of bioburden on the equipment. |
High |
Medium |
High |
High |
Medium |
PQ – BI testing |
To be checked and documented during PQ with current validated load profiles. |
|
Equipment Operation |
121°C Cycle |
cGMP
|
Sanitization Load cycle failure |
High |
Low |
Medium |
High |
Low |
SAT/ PQ |
To be checked and documented during PQ |
|
Loading conditions change each time |
High |
Low |
Medium |
High |
Low |
PQ testing |
PQ Testing to use worst case load on all cycles. |
||||
Sterilization Load cycle failure |
High |
Low |
Medium |
High |
Low |
SAT/ PQ |
PQ Testing to use worst case load on all cycles. |
||||
Sterilization Load does not sterilize |
High |
Low |
Medium |
High |
Low |
PQ testing |
PQ Testing to use worst case load on all cycles. |
||||
Sterilization conditions not achieved throughout the load |
High |
Low |
Medium |
High |
Low |
PQ testing |
PQ Testing to include thermometric testing and microbiological indicators |
||||
Cycle phase time out due to insufficient air removal |
High |
Low |
Medium |
High |
Low |
PQ testing |
To be checked and documented during PQ |
||||
Equipment Operation |
134°C Cycle |
cGMP |
Sanitization Load cycle failure |
High |
Low |
Medium |
High |
Low |
SAT/ PQ |
To be checked and documented during PQ |
|
Sterilization Load cycle failure |
High |
Low |
Medium |
High |
Low |
SAT/ PQ |
PQ Testing to use worst case load on all cycles. |
||||
Sterilization Load does not sterilize |
High |
Low |
Medium |
High |
Low |
PQ testing |
PQ Testing to use worst case load on all cycles. |
||||
Cycle phase time out due to insufficient air removal |
High |
Low |
Medium |
High |
Low |
PQ testing |
To be checked and documented during PQ |
||||
Cycle phase time out due to insufficient steam penetration |
Medium |
Medium |
Medium |
High |
Low |
PQ testing/ Bowie Dick test |
To be checked and documented during PQ |
||||
Equipment Operation |
Bowie Dick Test |
Quality Assurance |
Test cycle fails |
High |
Low |
Medium |
High |
Low |
Maintenance/ O&M |
To be tested and documented at SAT/ PQ. SOP to refer to trouble shooting and Supplier to provide technical support for new Autoclave |
|
Equipment Operation |
Water Intrusion Test |
Quality Assurance |
Test cycle fails |
Medium |
Low |
Medium |
High |
Low |
Maintenance/ O&M |
To be tested and documented at SAT/ PQ. SOP to refer to trouble shooting and Supplier to provide technical support for new Autoclave |
|
Step 1 Equipment Preparation |
Equipment Loading |
Product Quality |
Incorrect sterilization loads |
High
|
Medium
|
High |
Low |
High |
SOP Training |
Photos of the loads (OQ). Schematics to be included in the SOP. Worst-case loads to be verified in the OQ and PQ. |
|
Product Quality |
Incorrect sanitization loads |
High |
Medium
|
High |
Low |
High |
SOP Training |
Photos of the loads (OQ). Schematics to be included in the SOP. Worst-case load to be verified in the OQ and PQ. |
|||
Equipment Critical |
Chamber size incorrect |
Low |
Low |
Low |
Low |
Medium |
SAT |
Dimensional checks (IQ). |
|||
Product Quality |
Maximum load weight exceeded |
High |
Medium |
High |
Low |
High |
SAT |
Worst case loads to be verified in the OQ. |
|||
Step 1 Equipment Preparation |
Equipment Loading |
Product Quality |
Loading pattern incorrect |
High |
Medium |
High |
Low |
High |
None |
Photos of the loads (OQ). Schematics to be included in the SOP. Temperature Mapping Of The Loads. |
|
|
Equipment Loading |
Product Quality |
Equipment orientation incorrect causing ineffective air removal and condensate drainage |
High (Cycle failure) |
Medium |
High |
Low |
High |
None |
Photos of the loads (OQ). Schematics to be included in the SOP. B.Is to be put into the load to verify that there is sufficient air removal and steam penetration |
|
Process Critical |
Wrong autoclave used |
Medium (Not the final sterilizing step) |
Medium |
Medium |
Low |
High |
None |
SOP and training. |
|||
Step 2 Equipment Operation |
Cycle selection |
Product Quality |
Wrong cycle selected |
Medium (Not the final sterilizing step) |
Low |
Low |
Low |
Medium |
None |
SOP and training. The sterilization and sanitization cycles will be the same. |
|
Step 2 Equipment Operation |
Utilities |
Equipment Critical |
Compressed air failure |
Low |
Low |
Low |
Low |
Medium |
None |
The system aborts the cycle with critical alarms. Alarms will be verified in the OQ |
|
Step 2 Equipment Operation |
Utilities |
Equipment Critical |
Failure of modified steam supply |
Low |
Low |
Low |
Low |
Medium |
None |
The system aborts the cycle with critical alarms. Alarms will be verified in the OQ |
|
Equipment Critical |
Failure of new Steam valve |
High |
Low |
Low |
Low |
Medium |
None |
The system aborts the cycle with critical alarms. Alarms will be verified in the OQ |
|||
Equipment Critical |
Demineralized Water failure affecting the jacket temperature |
Low |
Low |
Low |
Low |
Medium |
None |
The system aborts the cycle with critical alarms. Alarms will be verified in the OQ |
|||
Equipment Critical |
Power failure |
Low |
Low |
Low |
Low |
Medium |
None |
The system aborts the cycle with critical alarms. They will be verified in the OQ. No UPS. Machine stops. Data downloaded via Ethernet connection to PC. |
|||
Step 2 Equipment Operation |
Utilities |
Equipment Critical |
Vacuum Failure |
Low |
Low |
Low |
Low |
Medium |
None |
The system aborts the cycle with critical alarms. Alarms will be verified in the OQ |
|
Step 2 Equipment Operation |
Measuring Instruments |
Process Critical |
Instruments not calibrated |
High |
High |
High |
Low |
High |
None |
All measuring instruments will be listed in the IQ and their criticality assessed. In-process Critical instrument calibration will be verified in the IQ. |
|
Step 2 Equipment Operation |
Measuring Instruments |
Process Critical |
Instruments calibrated to the incorrect specification leading to errors in the results |
High |
Low |
Medium |
Low |
High |
None |
A Calibration Specification will be prepared based upon the User Requirements. This is used to check for the correct calibration accuracy. controls, maintenance and calibration of instruments. |
|
Step 2 Equipment Operation |
Software |
Product Quality |
Data not logged by the software |
High |
Medium |
Medium |
Low |
High |
An independent chart recorder (cGMP) is attached to the system. |
Collection of data will be verified in the OQ. Data will be checked for each batch. |
|
Product Quality |
Software errors causing alarms or incorrect data |
High |
Low |
Medium |
Low |
High |
None |
Verified in the OQ |
|||
Step 2 Equipment Operation |
Hardware |
Product Quality |
Data not transferred correctly onto the printed report |
High |
Low |
Medium |
Low |
High |
None |
Verified in the SAT and OQ. The control system printout cannot be used as evidence of sterilization, it is for information only. The two reports will be compared during OQ. A CFR Part 11 assessment to be performed. |
|
Step 2 Equipment Operation |
Software |
Equipment/Process Critical |
Parameters changed on the cycle |
High |
Low |
Medium |
Low |
High |
None |
The software will be password protected with different access levels. Verified in the OQ. These will then be validated cycles and documented in the SOP. |
|
Step 2 Equipment Operation |
Software |
Equipment Critical |
Software not 21 CFR compliant |
High |
Low |
Medium |
Low |
High |
None |
A 21 CFR Assessment will be performed. |
|
Equipment Critical |
Software is upgraded during commissioning so parameters are changed. |
High |
Low |
Medium |
Low |
High |
Change Control/ Validation/ HTM 2010 |
Revision history to be covered under Change Control during the validation. |
|||
Product Quality |
Yokogawa Chart Recorder not started at the beginning of the cycle |
High |
Low |
Medium |
Low |
High |
None |
The procedure will be verified in the OQ. This will be included in the SOP and training. |
|||
Step 2 Equipment Operation |
Control System |
Product Quality |
Incorrect cycle selected |
High (Incorrect temperature selected) |
Low |
Medium (Not the final sterilizing step) |
Low |
High |
None |
SOP and training. There is an operator check, a second supervisor check and the cycle traces are also checked. |
|
Results changed on routine tests, for example, Bowie Dick, by manipulation of instrument readings |
High |
Low |
Medium |
Low |
High |
None |
The Engineering department controls access to the instruments, which are inside the unit. |
||||
Critical alarm not logged because of active non-critical alarm |
High |
Low |
Medium |
Low |
High |
None |
Verified in the OQ. |
||||
Cycle not aborted with active critical alarm because active non-critical alarm not acknowledged |
High |
Low |
Medium |
Low |
High |
None |
Verified in the OQ. |
||||
Step 2 Equipment Operation |
Filters |
Product Quality |
Vent Filter damaged causing contamination of the air supply
|
High |
Low |
Medium |
Low |
High |
None |
This will be included in the Planned Preventative Maintenance System. Integrity Testing Pre-filters in place. |
|
Step 2 Equipment Operation |
Filters |
Product Quality |
Pre-filters damaged causing contamination of the air supply |
High |
Low |
Medium |
Low |
High |
None |
Integrity Testing Pre-filters in place. |
|
Step 3 Cycle Completion |
Equipment Unloading |
Product Quality |
Dirty equipment removed from unloading side of autoclave |
High |
Low |
Medium |
Low |
High |
None |
SOP and training. |
Microbiology
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