Using Preliminary Hazard Analysis To Determine Equipment and Instrument Requalification Frequency

24/8/2018 Using Preliminary Hazard Analysis To Determine Equipment And Instrument Requalification Frequency
Guest Column | August 17, 2018
Using Preliminary Hazard Analysis To Determine

Equipment And Instrument Requali cation
Frequency
By Melissa Stappen, ValSource, LLC
During the course of your career in

the pharmaceutical industry, you
will likely face the question, “How
often should [given task or
activity] be performed?” I was
asked this question earlier in my
own career, when I was tasked
with developing an equipment
qualification program. I knew the
necessary steps to perform the
initial qualification of equipment
and instruments, and yet the nature of the equipment and instrument lifecycle was, at
the time, elusive. I knew that the equipment should be periodically requalified if its
consistent performance was deemed necessary to ensure the quality of products. This
article explains how I developed a requalification decision-making framework based on
the use of the preliminary hazard analysis (PHA), a tool used in quality risk
management.
An Introduction To Equipment Qualification
Equipment qualification is a critical step in overall process validation (PV), typically

referred to as Stage 2a of the PV lifecycle outlined in many regulation and guidelines,
including the FDA’s 2011 Process Validation Guidance1 and Annex 15 of the EU GMPs2,
among others.
https://www.pharmaceuticalonline.com/doc/using-preliminary-hazard-analysis-to-determine-equipment-and-instrument-requalification-frequency-0… 1/7
A robust equipment qualification program should require that all new equipment, prior
to use in production or quality control testing, pass through all stages of qualification —
including design qualification (DQ), installation qualification (IQ), operational
qualification (OQ), and performance qualification (PQ) — as appropriate based on the
uses and risks of the equipment. The activities of each of these qualification steps
should be well documented, to provide evidence that the equipment is fit for its
intended purpose, and those records should be available for review by request.
Figure 1: Stages of equipment and instrument qualification3
As illustrated in Figure 1, the equipment qualification program should speak to the

periodic requalification of equipment once it has been initially qualified — and as part of
implementing any changes (through a defined change control process) that may impact
the qualified state of the equipment. The extent of the requalification should be based
on the criticality of the equipment used in production or on the quality control testing of
products and the extent of the change. A documented periodic review of pertinent data
should also be performed to confirm that a process/method/system continues to
consistently produce a result meeting predetermined acceptance criteria.4
ICH Q9 On Preliminary Hazard Analysis (PHA)
Returning to the personal example I shared at the beginning of this article, as I began to
outline the necessary steps to perform the periodic review and requalification, I
wondered, “When or at what frequency should the periodic review be performed?” I was
stumped. How should I structure the program to help the user determine when to
perform the review? What guideline should I follow to create this aspect of the
qualification program? Where do I find the answer? After a few minutes of racking my
brain, I reached for ICH Q9 (Quality Risk Management) and found my answer in Annex
I — the risk management tool PHA.
ICH Q9 defines PHA as “a tool of analysis based on applying prior experience or

knowledge of a hazard or failure to identify future hazards, hazardous situations and
events that might cause harm, as well as to estimate their probability of occurrence for a
given activity, facility, product or system.”5
The tool consists of the following components: 1) identification of the possibilities that
the risk event happens, 2) qualitative evaluation of the extent of possible injury or
damage to health that could result, 3) a relative ranking of the hazard using a
combination of severity and likelihood of occurrence, and 4) identification of possible
remedial measures.5
I realized that by building a worksheet to organize the analysis and assist with
facilitation of the activities, the PHA tool could essentially address all the
aforementioned questions, as well as correlate the risk priority ranking to a periodic
review frequency for the subject equipment. (See Figure 2 for an example PHA
worksheet.) A team consisting of equipment owners, process owners, and quality
assurance could then be identified to perform the analysis. Each member should
possess a strong understanding of the quality risk management process, how to use the
PHA tool, scoring criteria, and key definitions.6
Figure 2: PHA worksheet example
The inputs to the worksheet are directed by each column and provided by a two-step
triage approach using risk blocks scored against criteria as high, medium, and low
rankings (see Tables 1, 2, and 3).7
Table 1: Severity Rankings
Table 2: Probability (Occurrence) Rankings
Table 3: Detectability Rankings
The preliminary risk class based on severity and probability (or occurrence) was first
determined (Figure 3) and then further evaluated against detectability, resulting in a
risk priority ranking (Figure 4) that correlates to the periodic review frequency for the
subject equipment (Table 4).
Figure 3: Risk class determination
Figure 4: Risk priority ranking
Table 4: Example of Periodic Review Frequency
Once the worksheet is completed with input from team members, the periodic review
frequencies should be reviewed and agreed to by the team members.
The following PHA worksheet (Figure 5) provides an example of a completed analysis

activity.
Figure 5: PHA worksheet example — completed analysis activity
My experience using the PHA tool enabled me to build a useable worksheet that allowed
all members of the team to participate in the risk analysis activity. It provided each
member the ability to provide subject matter expertise, voice concerns, and promote
issues for further discussion. Additionally, by facilitating the team meetings, time
schedules were managed and those issues that were a challenge were tabled and
discussed offline. At the end of each completed worksheet, team members provided
positive comments regarding the risk analysis activity, noting the efficient use of time,
effective use of risk management tools, and delivery of risk priority rankings for subject
equipment that correlated to a periodic review frequency.
In conclusion, using a risk management tool such as preliminary hazard analysis, a

periodic review frequency can be identified and applied to qualified equipment. This
will enable a timely review of the equipment by means of pertinent data such as
manufacturing performance trend data, change history, and/or deviation history to
confirm consistent production results meeting the predetermined acceptance criteria.
References:
1. FDA. Process Validation: General Principles and Practices. January 2011.

2. EU. EudraLex - Volume 4, Good Manufacturing Practice (GMP) guidelines, Annex
15: Qualification and validation. October 2015.
3. Choudhary, A. Qualification of System and Equipment in Pharmaceuticals.
Pharmaceutical Guidelines. December 2010.
4. PDA. Technical Report No. 54-5: Quality Risk Management for the Design,
Qualification, and Operation of Manufacturing Systems. May 2017.
5. ICH. ICH Q9: Annex 1: Risk Management Methods and Tools. June 2005.
6. PDA. Technical Report No. 54-2: Implementation of Quality Risk Management for
Pharmaceutical and Biotechnology Manufacturing Operations, Annex 1. June
2013.
7. GAMP 5 Guide. Compliant GxP Computerized Systems. February 2005.
8. MHRA. ‘GxP’ Data Integrity Guidance and Definitions. March 2018.
About The Author:
Melissa Stappen, consultant with ValSource, LLC, has over 20 years of

experience in the pharmaceutical, medical device, biotech, and
clinical/healthcare provider settings. During her career, she has
provided support to quality assurance, quality control, and compliance
departments as a subject matter expert relating to endotoxin and
microbial contamination control. Her current role of validation
consultant emphasizes risk management based programs for
laboratory instrumentation, methods, and equipment. You can email
her at mstappen@valsource.com or connect with her on LinkedIn.

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24/8/2018 Using Preliminary Hazard Analysis To Determine Equipment And Instrument Requalification Frequency

Guest Column | August 17, 2018

Using Preliminary Hazard Analysis To Determine

During the course of your career in

An Introduction To Equipment Qualification

Equipment qualification is a critical step in overall process validation (PV), typically

Figure 1: Stages of equipment and instrument qualification3

As illustrated in Figure 1, the equipment qualification program should speak to the

ICH Q9 On Preliminary Hazard Analysis (PHA)

ICH Q9 defines PHA as “a tool of analysis based on applying prior experience or

Figure 2: PHA worksheet example

Table 1: Severity Rankings

Table 2: Probability (Occurrence) Rankings

Table 3: Detectability Rankings

Figure 3: Risk class determination

Figure 4: Risk priority ranking

Table 4: Example of Periodic Review Frequency

The following PHA worksheet (Figure 5) provides an example of a completed analysis

Figure 5: PHA worksheet example — completed analysis activity

In conclusion, using a risk management tool such as preliminary hazard analysis, a

1. FDA. Process Validation: General Principles and Practices. January 2011.

About The Author:

Melissa Stappen, consultant with ValSource, LLC, has over 20 years of

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