JVT

Risk Considerations for Installation of a New Autoclave in a Pharmaceutical Manufacturing Facility | IVT

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

  1. Sandle, T. (2013). Sterility, Sterilisation and Sterility Assurance for Pharmaceuticals: Technology, Validation and Current Regulations, Woodhead Publishing Ltd.: Cambridge, UK, pp93-110
  2. Hugo WB (1991). A brief history of heat and chemical preservation and disinfection. J. Appl. Bacteriol. 71 (1): 9–18
  3. 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
  4. 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
  5. ICH Q9:  Quality risk management.  International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH, Geneva (November 2005)
  6. 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.

 




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