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Periodic Reviews of Computerized
Follow Spectroscopy for the latest updates:
Spectrometry Systems, Part I
Sep 01, 2011 By R.D. McDowall
Spectroscopy
Volume 26, Issue 9
In the first of a two part series, this month's column looks at interpreting the
Annex 11 regulations and understanding the principles of a periodic
Quantum Mechanics
review. The second part will discuss how to carry out the review and report
it. This series of installments from David Balls
excellent Baseline column discusses the
In my last Focus on Quality column we looked at the new European Union relevance of quantum mechanics for spectroscopy
Good Manufacturing Practice (EU GMP) regulations, fousing on Annex 11 and why it is important for spectroscopists to know
(computerized systems) and Chapter 4 (documentation) (1) that became the basics.
effective on June 30 of this year. A new requirement in Annex 11 (2) is for
Read more.
periodic evaluation or periodic review. The regulation states in clause 11,
"Computerized systems should be periodically evaluated to confirm that Author Guidelines
they remain in a valid state and are compliant with GMP. Such evaluations
Spectroscopy welcomes manuscripts that describe
should include, where appropriate, the current range of functionality,
techniques and applications of all forms of
deviation records, incidents, problems, upgrade history, performance, spectroscopy and that are of immediate interest to
reliability, security, and validation status reports." users in industry, academia, and government.
Some of the interpretations of this clause are We cover molecular spectroscopy techniques, atomic
spectroscopy techniques, laser-based spectroscopies,
and mass spectrometry. We accept review articles,
You have to conduct periodic reviews of computerized systems. technical articles, and tutorials. For more information,
There are no exceptions to this regulation (for example, only critical please see our author guidelines.
systems need to be evaluated); all systems must be reviewed.
The frequency of the review is determined by the company's quality
assurance or laboratory management and justified where necessary to
an inspector. Implicit in this statement is that you should apply a risk
assessment to determine the frequency. Also, it is explicitly stated in
clause 1 of Annex 11 that risk assessment is conducted throughout the
life cycle of a computerized system.
http://www.spectroscopyonline.com/periodicreviewscomputerizedsystemsparti 1/3
The aim of any review is to ensure that the system is compliant with the
applicable regulations and that it remains in a validated state over the
Current Trends in Mass
time period since the last review. Spectrometry
The scope of the periodic review can cover the last full validation,
March 2017 Edition
change control records since the last validation, problems and their
resolution, user account management, user training, and IT support
such as data backup.
What is not stated in the regulation however, is the formality of the process.
So how can we demonstrate to an inspector that periodic reviews have
been carried out? Unless the reviews are formally documented, then you
can't; it's as simple as that. So we will look at the overall process of a
periodic review in this column and then in the next installment we will
examine the practicalities of performing and reporting such a review.
View the Articles Here>>
A Small Regulatory Problem
Why perform a periodic review? This is probably one question that you may
ask when reading the section above. In life, it is always better to use real Recent Special Issues
examples to illustrate points you are trying to make because it
Applications of ICP & ICP-MS Techniques for
demonstrates that other organizations can sometimes make bigger
Today's Spectroscopists
mistakes than you do. Take, for example, the following citation from a Food
and Drug Administration (FDA) warning letter (3):
6. Your firm failed to check the accuracy of the input to and output from the
computer or related systems of formulas or other records or data and
establish the degree and frequency of input/output verifications [21 CFR
211.68(b)].
For example, the performance qualification of your <redacted> system

software failed to include verification of the expiration date calculations in
the <redacted> system. In addition, there is no established degree and View the Articles Here
frequency of performing the verification. Discrepancy reports have
Advances in Portable and Handheld
documented that product labeling with incorrect expiration dates have
Spectroscopy
been created and issued for use.
Your response states that you opened Investigation T-139 and you provide
a January 29, 2010 through February 26, 2010 completion timeline. You
have not provided a response to correct this violation and establish a
corrective action plan to assure that computer systems are properly
qualified.
The point is that the initial validation failed to check calculations in a

computer system resulting in drug labels that were printed with incorrect
expiry dates on them. Who picked up on the problem? The inspector! If the View the Articles Here
company had conducted a periodic review, this problem should have been
identified by the reviewer, since it is an explicit requirement of the US GMP FT-IR Technology for Today's Spectroscopists
regulations, as noted in the warning letter. It is an obvious point for potential
problems with any computerized system and the issue should have been
identified and resolved long before the inspector strolled through the door
for tea and cookies.
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Volume 26, Issue 9
What's in a Name?
Although the Annex 11 regulation talks about a periodic evaluation (I have

called it a periodic review), there are also laboratory audits carried out by
the quality assurance departments. So are periodic evaluations, periodic
reviews, or audits the same, or are they different? In my opinion, periodic
reviews or periodic evaluations are one and the same, and are focussed on
a computerized system, the process it automates, and the support
processes for it. In contrast, an audit can cover a computerized system, a
laboratory process, quality system, or a subset of any portion of the
laboratory. Therefore, an audit can be the same as a periodic review or
evaluation, but can also be a wider check of laboratory operations to
Quantum Mechanics
ensure compliance with regulations and internal procedures. An audit also
can cover computerized systems that are part of the process, but generally This series of installments from David Balls
the scope of an audit is wider than a periodic review. Therefore, looked at excellent Baseline column discusses the
from another perspective, periodic reviews are a subset of laboratory relevance of quantum mechanics for spectroscopy
and why it is important for spectroscopists to know
audits. Thus, in this column I will refer only to periodic reviews but this will the basics.
include periodic evaluation and general audits that include computerized
systems. Read more.
Overview of a Periodic Review Author Guidelines

The topic of a periodic review that we will discuss is shown in Figure 1 and Spectroscopy welcomes manuscripts that describe
consists of two phases: planning and execution. techniques and applications of all forms of
spectroscopy and that are of immediate interest to
So we have established that the periodic users in industry, academia, and government.
review is an independent audit of a We cover molecular spectroscopy techniques, atomic

computerized system to determine if the spectroscopy techniques, laser-based spectroscopies,
system has maintained its validation status and mass spectrometry. We accept review articles,
technical articles, and tutorials. For more information,
and, as said before, it is also a planned and please see our author guidelines.
formal activity. The first requirement for
conducting a review is a standard operating
procedure (SOP) covering the whole
Figure 1: Flow chart for a periodic
review or audit of a computerized
process. As a periodic review is a subset of
system. an audit, the audit SOP should be relatively
simple to adopt for a computerized system
or you can use an existing audit SOP with a subsection for periodic
http://www.spectroscopyonline.com/periodicreviewscomputerizedsystemsparti?id=&sk=&date=&pageID=2 1/3
reviews. The whole process should be described in the audit/review SOP

and is shown in Figure 1.
Spectrometry
I have depicted the process as two parts:
March 2017 Edition
The planning phase (covering all systems). This links the inventory of
computerized systems for the laboratory with a risk classification of
each system (the figure suggests critical, major, or minor, but this is
only a suggestion) to the SOP for periodic reviews and audits and the
annual self-inspection schedule. The principle is that the critical
systems are reviewed more frequently than major or minor systems,
and major systems are reviewed more frequently than minor ones.
The periodicity of review for each type of system is determined by
your company.
The execution phase (for each system reviewed). For each system
selected for review there is a common process that consists of View the Articles Here>>
planning and preparation for the review, the opening meeting,
performing the audit, including a check on the effectiveness of
corrective actions from a previous review, the reviewer's closed
Recent Special Issues
meeting where the observations are examined to determine if there Applications of ICP & ICP-MS Techniques for
are any findings or noncompliances, the closing meeting where Today's Spectroscopists
findings and observations are discussed, and finally the writing of the
review report and an action plan for any corrective actions or
preventative actions.
In this installment, we will focus mostly on the planning phase and will
present the execution phase in an overview. The next installment will cover
the execution phase in more detail.
Objectives of a Periodic Review
There should be two main goals for a periodic review of a computerized View the Articles Here
system:
To provide independent assurance to the process owner and senior Spectroscopy
management that controls are in place around the system being
reviewed and are functioning correctly. The system is validated and
controls are working adequately to maintain the validation status.
To identify those controls that are not working and to help the
process owner and senior management improve them and thus
eliminate the identified weaknesses. The impact of a finding may be
applicable to a single computerized laboratory system or all systems
in a laboratory.
It is the second objective that is the most important, in my view. Moreover, it View the Articles Here
is an important outcome from any periodic review for senior management to
realize that some controls may require systematic resolution. If a problem is FT-IR Technology for Today's Spectroscopists
found in a procedure that is used for all systems, the resolution of this may
affect all computerized systems used in the laboratory rather than just the
one being reviewed.
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Volume 26, Issue 9
Who Performs a Periodic Review?
Annex 11 does not say who should carry out the periodic review. So let's
consider the possibilities:
The process owner (the laboratory person who is responsible for the
system)
The system owner (the person responsible for the availability and
support of the system)
Quality assurance (QA)
Hmmm, I can guess some of your answers. The point I want to make is that
people directly involved with a computerized system have a vested interest Quantum Mechanics
in their system and cannot make an objective decision if an activity is under
control and in compliance or not. QA may be appropriate to conduct a This series of installments from David Balls
periodic review, but the individuals have to know about computerized excellent Baseline column discusses the
relevance of quantum mechanics for spectroscopy
system validation and understand the regulations and company and why it is important for spectroscopists to know
procedures in relation to computerized systems; not many in QA fit these the basics.
criteria.
Read more.
So to help us answer the question, what do the regulations say about this?
European Union GMP chapter 9 (4) discusses self inspections (for Author Guidelines
example, audits and periodic reviews) in about two-thirds of a page, and
the key elements of these regulations can be summarized as follows: techniques and applications of all forms of
Regulated activities should be examined at intervals to ensure users in industry, academia, and government.
conformance with regulations.
We cover molecular spectroscopy techniques, atomic
Self inspections must be preplanned. spectroscopy techniques, laser-based spectroscopies,
Self inspections should be conducted by independent and competent and mass spectrometry. We accept review articles,
persons.
please see our author guidelines.
Self inspections should be recorded and contain all the observations
made during the inspections.
Where applicable, corrective actions should be proposed.
Completion of the corrective actions should also be recorded.
So, from the perspective of the European regulations, we need a periodic

review to be independent to ensure an objective and not subjective
approach to evaluating your computerized spectrometer system. Indeed,
the definition of independent is "not influenced or controlled by others;

thinking or acting for oneself" (5). If a person who knew the system well
were to perform a periodic review there is the possibility that he or she Spectrometry
could miss something because it was familiar, that an independent
March 2017 Edition
reviewer could find. There is also the human tendency of a person involved
in a system to focus on what they were doing well rather than the
independent person who would be focusing on finding activities that were
not compliant or could be done in a more efficient way. Therefore,
independence of the person conducting a periodic review is of prime
importance.
Skills and Training of the Reviewer
There are a number of requirements necessary for a person to effectively

conduct a periodic review. These are
Knowledge of the current good laboratory practice (GLP) or good
manufacturing practice (GMP) regulations and the associated
guidance documents issued by regulatory agencies or industry Recent Special Issues
bodies. At a minimum, this knowledge needs to be in the same good
practice discipline that the laboratory works to, but knowledge of the Applications of ICP & ICP-MS Techniques for
other requirements of good practice disciplines is an advantage Today's Spectroscopists
because one discipline can be vague on a specific point that another
might have more detail on. For example, in GMP there are no
regulatory agency guidelines for the SOPs required for a
computerized system, but the FDA has issued one for clinical
investigations (6), where a minimum list of procedures can be found
in Appendix A.
Note that the knowledge of regulations above said "current." This
criterion is included because the regulations and guidelines are
changing at an increasing rate, especially in the European Union, View the Articles Here
where it is easier and quicker to change the regulations, as we have
seen with Annex 11 itself (1). Advances in Portable and Handheld
Experience working with computerized systems and knowing where Spectroscopy
(noncompliance) "bodies" can be buried and where bad practices
can occur.
An understanding of the current procedures used by the company,
division, or laboratory for implementing and operating validated
computerized systems. This is the interpretation of the regulations
and guidance for the laboratory staff to work with that need to be
both current and flexible.
An open and flexible approach, coupled with the understanding that
there are many ways of being in control. Therefore, the reviewer's View the Articles Here
ways of validating a computerized system and maintaining its
validated state, or indeed those in the good automated FT-IR Technology for Today's Spectroscopists
manufacturing practice (GAMP) guide (7) and GAMP Good Practice
Guide, Risk Based Approach to the Operation of GXP Computerized
Systems (8) are not the only way of working. As Judge Jenkins stated
in the case of the FDA versus Utah Medical, "Many roads lead to
Rome"; the fact that a laboratory does something different to what you
think it should do should not preclude it from being compliant (9). We
will return to this point again when we discuss planning the audit.
Finally, good interpersonal skills coupled with a hide as thick as an
elephant's. The reviewer needs to ask open questions to understand
what process is being carried out and investigate with pertinent
questions to indentify if the work is adequate or if there are Raman Technology for Today's Spectroscopists
noncompliances. Persuasion may be required to change ways of
working and a hide as thick as an elephant's may be needed to
ignore any personal remarks or insults that may come your way.
So that outlines a periodic reviewer's skill set. Now the reviewers have to
perform the review, which we will discuss in part II of this series.
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Volume 26, Issue 9
How Critical Is Your System?
Putting the heading in a different way: Do we need to do a periodic review

for all computerized systems? Well, the simplest answer to that question is
to go back to clause 11 of Annex 11, quoted at the start of this column. It
says "computerized systems," not critical ones or selected ones but all
computerized systems. Therefore, this implies the need for categorization
of computerized systems according to risk. Figure 1 shows the planning
process, from the inventory to the annual schedule of periodic reviews to
be conducted within an organization.
The starting point is the inventory of computerized systems contained in the

laboratory validation master plan (10) that should be categorized according Quantum Mechanics
to risk. Some of the risk categories include critical, major, minor, no impact
This series of installments from David Balls
on good x practice (GxP), or high, medium, and low. You will want the most excellent Baseline column discusses the
critical systems to be reviewed most often, as they pose the highest risk, relevance of quantum mechanics for spectroscopy
and the lowest priority systems will be reviewed less frequently, as they and why it is important for spectroscopists to know
the basics.
pose the lowest risk. Most of the laboratory computerized systems featured
in FDA warning letters are networked systems with multiple users, because Read more.
they have the greatest impact.
From the inventory there will be developed a listing of the most critical
Author Guidelines
systems: These will have the most frequent reviews to ensure that they are Spectroscopy welcomes manuscripts that describe
in control, with decreasing frequency for the major and minor systems. A techniques and applications of all forms of
review schedule for all computerized systems in the laboratory would be users in industry, academia, and government.
drawn up for the coming year. Typically, the schedule for the year will be
written by the person responsible in QA the previous year and will list all
systems to be reviewed and the months in which this will happen. and mass spectrometry. We accept review articles,
When to Perform a Review? please see our author guidelines.
In my opinion, there are three or four possible times to review a

computerized system:
Before operational release of a system. This is to ensure that system

development has been undertaken according to corporate standards
and the validation plan. You may think that with all the planning and
documentation produced in a validation, this is the last time to
perform a review. However, I believe that this is the right time, for the
simple reason that if something has been missed from the validation
of a critical system, such as checking that a calculation works
correctly, do you really want to operate a system for a year or so and Spectrometry
then discover it? I thought not.
March 2017 Edition
Periodically, ensure that the operational system still remains
validated. This will be a planned and scheduled activity and will be
carried out on a regular basis for each computerized system in the
laboratory while it is operational. There may be occasions when the
review schedule is changed to link to a planned upgrade of the
system, but this is typically performed after the system has gone live
and is in operation.
Before an inspection. Occasionally some companies may review a
system before an inspection to ensure that there are no major
compliance issues. However, if this approach is taken, ensure that
the time between the audit and the inspection is sufficient to ensure View the Articles Here>>
that the remedial activities are implemented and work before the
inspection. Personally, I believe that if a computerized system is truly
critical it will be reviewed on a frequency that does not require a Recent Special Issues
special review like this. Applications of ICP & ICP-MS Techniques for
When a system is retired and the data are migrated. I will not discuss Today's Spectroscopists
this topic further in these two columns.
Although you can conduct a periodic review at these times during the
lifetime of a spectrometer system, the principles of what a review consists
of and the way one is conducted are the same.

Spectroscopy
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Volume 26, Issue 9
Health Warning: Periodic Reviews Only Sample
Periodic reviews and audits should carry a health warning. It is important to

realize that all reviews and audits are sampling exercises. The reviewer will
select the procedures, documents, or records to examine and draw
conclusions based on them that are applicable to the whole process being
examined. Therefore, it is important to realize that noncompliances may
exist where none have been found and reported, simply because the
sample taken by the reviewer did not contain any problems. Trained
reviewers and auditors know this and will inform the process owner of this,
especially at the end of the review and also in the report. This is also known
by GLP and GMP inspectors, and the FDA puts virtually the same text into
Quantum Mechanics
all warning letters to deserving organizations:
The deviations detailed in this letter are not intended to be an all-inclusive excellent Baseline column discusses the
statement of deviations that exist at your facility. You are responsible for relevance of quantum mechanics for spectroscopy
investigating and determining the causes of the deviations identified above and why it is important for spectroscopists to know
the basics.
and for preventing their recurrence and the occurrence of other deviations.
There are two points to note: First, the specific statement indicating that the Read more.
inspection is a sampling process and that the list of deviations from the
Author Guidelines
regulations is never complete and cannot ever be unless the whole
laboratory is reviewed. Second, and most important, is that the users, Spectroscopy welcomes manuscripts that describe
laboratory management, and quality assurance have the responsibility for
ensuring regulatory compliance. If you find a problem, it is your job, and users in industry, academia, and government.
not that of QA or the inspectorate, to resolve it.
Therefore, if you want to hide behind a clean periodic review report, but spectroscopy techniques, laser-based spectroscopies,
know that noncompliant working practices are going on that the reviewer
has not picked up on them, you are deceiving yourself. Moreover, it means please see our author guidelines.
that if an inspector identifies a problem, especially one that you have
known of and done nothing about, it means that the subsequent corrective
action will be more stringent than if you had found the problem yourself and
fixed it under your terms. It is better for you to have found the problem and
be in the process of fixing it, rather than for an inspector to find it, as it
demonstrates that you are doing your job responsibly and diligently.
Slicing and Dicing: Defining the System Scope
It is important to get the scope of the audit

correct and not to miss anything that
could be significant in an inspection or Spectrometry
could lead to questioning the quality of the
March 2017 Edition
results generated by the system (for
example, unvalidated or incorrect
calculations). Figure 2 shows an example
of a computerized system used for Figure 2: Scoping the periodic
quantitative bioanalysis in a GLP- review of a computerized system.
regulated laboratory. The system consists
of three high performance liquid chromatography (HPLC) systems with
mass spectrometry (MS) detectors; each instrument has the MS software
installed on a workstation to control the instrument and then acquire and
interpret the chromatograms. Data are acquired directly to a central server View the Articles Here>>
that is supported by the IT department. In addition, there is a single
workstation used by analysts to interpret chromatograms and relieve
congestion on the instruments themselves for processing data. Recent Special Issues
The question is, How should a periodic review be scoped? From Figure 2 Applications of ICP & ICP-MS Techniques for
we can see that the system scope can be broken down into two parts. The Today's Spectroscopists
breadth of the scope could include the portion of the system in the
laboratory and the portion operated by the IT department. So the breadth of
the audit needs to be decided: just the laboratory, just IT, or the whole
system? As an aside, if the system had a server that is operated and
maintained by the laboratory, then the whole system scope is the
responsibility of the laboratory.
Then we need to determine the depth of the scope and determine how far
to go reviewing the instrument and software aspects of the system. In the
situation shown in Figure 2, each workstation has a separate installation of View the Articles Here
the MS software. Therefore, does the review take a sample from a single
workstation and the attached instrumentation? From two, or all three
Spectroscopy
installations? This is where risk management comes in. As the architecture
of the overall system relies on three individual instances of the MS software
that have to be set up (for example, users, access privileges, and software
configuration) independently, do you want to know if the software instances
are the same or not? How do you know that the three are the same?
Although the installation and configuration documentation may say they are
the same, has anything changed since then on one or more of the software
instances? So, the depth of the review can depend on the technical
aspects of the system for example, individual installations of software
with multiple software configurations versus a client server architecture View the Articles Here
where there is just a single configuration. Do not forget the data processing
workstation as well, because it will be another individual installation and
software configuration to consider.
Expressing a personal view, I would have a wide system breadth that

would include both laboratory and IT aspects. The depth depends on the
time available; in the case of Figure 2, I would review all instances to
ensure equivalence, both on paper and in the software, but, again, this is
dependent on the time available.
What is not shown in Figure 2 is whether the system has additional

installations of the software for validation and training. When these are View the Articles Here
present, then the periodic review also needs to check them to see that they
are correctly set up and equivalent to the operational system. Raman Technology for Today's Spectroscopists
Also, consider an alternative to the system

configuration in Figure 2: If the three
systems were standalone with no
reprocessing workstation, then the
periodic review could cover three
independent standalone systems. In this
Figure 3: Types of audit or periodic case, one aim of the review would be to
review.
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Volume 26, Issue 9
Types of Periodic Review
Ok, we now have the scope of the audit defined in terms of breadth and
depth; what we now have to decide is how we will approach the review.
There are three basic ways you could conduct a periodic review or audit,
shown in Figure 3. These include the horizontal, vertical, and diagonal
approaches:
Horizontal audit or review: A horizontal review is conducted across

the breadth of the system documentation; it attempts to cover all
areas but at a low depth. It is typically undertaken if there is little time
available to perform the review or if the system has not been
reviewed before. The aim of this type of review is to give the Quantum Mechanics
confidence that all the major computer validation requisites are in
place, but there may not be enough time to look in depth at how the
various areas integrate together. Note that a horizontal audit can turn relevance of quantum mechanics for spectroscopy
into a vertical audit if a problem is found during the review and the and why it is important for spectroscopists to know
problem is required to be investigated in more detail. the basics.
Vertical audit or review: In contrast to a horizontal audit, a vertical
Read more.
audit takes a very narrow perspective, selecting one or more areas to
review and then going into a lot of detail, for instance checking that Author Guidelines
the controlling procedure has been followed. As an example, a
vertical review could look at the change control procedure, and all Spectroscopy welcomes manuscripts that describe
the change requests for a specific system could be examined in spectroscopy and that are of immediate interest to
much more detail than possible with a horizontal audit. users in industry, academia, and government.
Diagonal audit or review: As the name suggests, a diagonal review is
a mixture of the horizontal and vertical audits. The purpose is to see
that all the major validation elements are in place, operate correctly, and mass spectrometry. We accept review articles,
and that all applicable processes work and are integrated together. technical articles, and tutorials. For more information,
Therefore, when examining the defining user requirements in the
horizontal portion of a review, the diagonal audit will assess the
traceability of requirements from the uniform reporting system (URS)
to the rest of the life-cycle documents. In addition, the review can
also take a test script and trace it back to the URS. As you can see,
the diagonal audit examines the system more thoroughly than a
horizontal audit.
In practice, all three types of auditing can be used effectively during a

periodic review, depending on how much time there is available.
Spectrometry
As mentioned above, a horizontal review can turn into a vertical one. For
example, during a horizontal review of change control, the reviewer may March 2017 Edition
ask to see three change requests selected at random from the list of
change control requests; note the sampling process in the request. When
examined and compared with the procedure, it may be found that two out
of three requests did not follow the correct procedure. So the reviewer asks
for three additional requests, again selected by the reviewer at random.
When examined, two comply with the SOP and one does not. The reviewer
now has a situation in which six change control requests have been
reviewed and half comply with the procedure but, more worryingly, half do
not. So what should the reviewer do? One alternative is to leave the change
control process and complete the audit. The second is to dig further into View the Articles Here>>
the change control requests and the procedure to find out what is the true
picture and leave the rest of the audit until the problem is investigated
further. Because change control is such a vital mechanism for ensuring
continued validation status, the archaeological excavation of the change Applications of ICP & ICP-MS Techniques for
control records should take precedence over the rest of the audit, in my Today's Spectroscopists
opinion. Also, consider that there might be a systematic issue with change
control that could affect all computerized systems in the laboratory.
Therefore, the horizontal review turns into a vertical audit to discover how
deep the problem goes: Has it been a consistent problem since the last
review or has the problem only recently started?
Writing the Periodic Review Plan
Returning to the execution phase outlined in Figure 1, let's look at the

various tasks in order, starting with writing the plan for the periodic review. View the Articles Here
This consists of a number of activities that cumulate in the plan:
Agree on the date or dates for the review. When a system is due to Spectroscopy
be reviewed, the reviewer will contact the process owner to agree on
dates for the review to take place. How long the review will take
depends on the size and complexity of the computerized system, but
typically it takes between 13 days. It is important that when dates
are agreed on that key personnel will be available to discuss their
specialist subject areas with the reviewer; otherwise the benefit of the
review could be lost and noncompliances could be missed due to the
lack of specialist knowledge. Smaller systems can be audited in a
day but if the IT department needs to be included or a larger system
is being audited, then it is more likely that 23 days will be required. View the Articles Here
Agree on the scope of the review. The reviewer should ask for
information about the system (if not known already) to determine the
scope of the review. This is particularly important for systems for
which the laboratory and IT each have responsibilities. In such cases,
the involvement of the two departments in the review needs to be
coordinated. If the IT department is outsourced, then the outsourcing
company needs to be contacted to ensure staff are available for the
review.
Write the periodic review plan. A review plan is written that contains
the name of the system to be reviewed, agreed dates of the review,
the department and location where the system is sited, and the View the Articles Here
regulations and procedures that the review will be based upon (for
example GMP or GLP regulations and industry guidance
documents). Included in the plan should be a timetable of activities of
when the reviewer wants to discuss specific subjects. This is
important to inform the laboratory and any other staff when their
participation will be required. It helps them plan their own work for the
day of the audit and avoids people hanging around waiting
unneccessarily.
Approval of the review plan. The periodic review plan is a formal
document that needs to be signed by the reviewer as the author and
a separate person as an approver. Depending on the company

policies, the process owner may also need to sign the plan to
acknowledge that he or she approves it and also to implement any
corrective actions if there are any findings or noncompliances.
Preparation for a Periodic Review
What, I need to prepare for a periodic review? Yes! From the perspective of
the reviewer, the individual needs to read up about the system and refresh
his or her knowledge on any relevant SOPs that the system is validated and
operates under. This means reading key documents such as
computerized system validation SOPs

validation plan for the last full validation of the system to be reviewed
and the corresponding validation summary report
user requirements specification for the current version of software
that is installed
organizational charts Sponsored Links
list of applicable procedures as a minimum and copies of some of
the key SOPs, if possible, such as change control SOP and user Editorially-driven audio PODCASTS
SOPs. designed to keep industry
professionals connected
This approach allows the reviewer to have an understanding of the system
and procedures before arriving to perform the review and to be able to do
some research, if required, before the review starts, thus saving time while
on site. A reviewer could ask for more documents than listed above, but
there is always a balance between the quantity of material and time used to
prepare for the review and the time on site; personally I prefer to prepare
using the key documents and procedures.
The spectroscopists who will be subject to the audit also need to prepare.
At the most basic level, tidy up the laboratory (you will be surprised how
many laboratories do not do this). Also, check that all documents are
current and approved. If there are any unapproved or unofficial documents,
they must be removed from desks and offices and destroyed. There are
also other areas where the laboratory can prepare for example, by
reading the current procedures and ensuring that training records are up to
date.
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Volume 26, Issue 9
Activities During the Periodic Review
After the review plan has been written and approved and the reviewer has
prepared for the review, the great day dawns and the review takes place.
As can be seen in Figure 1, the activities that take place consist of the
following steps:
The opening meeting: This should be the shortest part of the periodic
review, where the reviewer and the laboratory and, when appropriate,
IT and QA staff who will be involved with the audit, are introduced to
each other. The reviewer will outline the aims of the review along with
a request for openness, as it is an internal audit designed to identify if
the system is under control and remains validated or not. It is Quantum Mechanics
important that the head of the laboratory attend both the opening and
closing meetings to see if there are any issues to resolve. The
importance of the laboratory head attending must not be relevance of quantum mechanics for spectroscopy
underestimated. If this key individual is not present, it sends a and why it is important for spectroscopists to know
subliminal message to all, including the reviewer, that the individual the basics.
has no interest in the validation status of the computerized systems. I
Read more.
certainly would document his or her absence in the review report.
How do you work around here? I mentioned earlier that the person Author Guidelines
conducting a periodic review should not have fixed views of how a
computer validation should be conducted, as there are many ways to Spectroscopy welcomes manuscripts that describe
be compliant. The key point in a periodic review is to keep asking the spectroscopy and that are of immediate interest to
question, "Is the laboratory in control?" To orient myself for an audit or users in industry, academia, and government.
periodic review, after the opening meeting I prefer that the victims,
sorry, auditees, give a short presentation of how validation is
conducted in this laboratory. This approach is very useful as it allows and mass spectrometry. We accept review articles,
the person conducting the periodic review (for example, me) to technical articles, and tutorials. For more information,
understand the terminology used by the laboratory and the overall
validation strategy used for the system under review. In the long run,
it helps to avoid misunderstandings and miscommunication between
the two parties.
Carrying out the periodic review. This is the heart of the periodic
review where the last validation, organization, staff training records,
change control, backup, and recovery operation of the system and
associated procedures, and so forth will be assessed. We will look at

this in more detail in the second part of this column.
Reviewer's private meeting. This is the time for the person conducting Spectrometry
the review to look over his or her notes and documents provided by
March 2017 Edition
the laboratory to see if any observations are identified as findings or
noncompliances. Also, some outline notes for the closing meeting are
prepared; these must include all major issues to be discussed with
the process owner and laboratory management the reviewer
should not omit bad news and then add these little gems to the report
so that it comes as a surprise to the laboratory.
Closing meeting. This is where the reviewer will inform the laboratory
staff about initial findings so that there will be no surprises when the
draft report is issued for comment. All findings should be based on
objective evidence, such as noncompliance with a procedure or
regulation. There may be occasions when a difference comes down View the Articles Here>>
to interpretation of regulations. In that case, the auditor should seek
information in industry guidance documents to support the finding.
Write and approve the periodic review report and action plan. At the Recent Special Issues
conclusion of the on-site portion of the review, the reviewer now has Applications of ICP & ICP-MS Techniques for
to draft the report, which will contain what the reviewer saw and the Today's Spectroscopists
findings or noncompliances. Contained either in the report or as a
separate document will be the action plan for fixing the
noncompliances.
Implementing corrective and preventative actions. Any findings and
their associated corrective and or preventative action plans are
implemented and monitored ready for review when the system comes
due.
All the activities listed in this section will be discussed in more detail and
the second part of a periodic review will be addressed in the next "Focus View the Articles Here
on Quality" column.
Summary Spectroscopy
In this installment, I have looked at a periodic review or evaluation for

computerized systems. The function is an independent audit to confirm that
a system maintains its validated status and to identify any areas of
noncompliance. In the next installment, I will discuss conducting the
periodic review, who is involved, and reporting the observations and
findings.
R.D. McDowall is principal of McDowall Consulting

and director of R.D. McDowall Limited, and the editor
of the "Questions of Quality" column for LCGC Europe,
Spectroscopy's sister magazine. Direct FT-IR Technology for Today's Spectroscopists
correspondence to: spectroscopyedit@advanstar.com
References
(1) R.D. McDowall, Spectroscopy 26(4), 2433 (2011).

R.D. McDowall
(2) EU GMP Annex 11, Computerized Systems.
(3) FDA Warning letter, AVEVA Drug Delivery Systems, Inc., 21 May 2010.
(4) EU GMP Chapter 9, Self Inspections.

(5) Webster's Dictionary ( http://www.merriam-webster.com/dictionary/).
(6) FDA Guidance for Industry, Computerized Systems in Clinical Raman Technology for Today's Spectroscopists
Investigations, 2007.
(7) GAMP Guide, version 5, 2008, Appendix 08, Periodic Reviews.
(8) GAMP Good Practice Guide: Risk Based Approach to Operation of GXP
Computerized Systems, 2010, Section 12: Periodic Reviews.
(9) C. Burgess and R.D. McDowall, QA Journal 10, 7985 (2006).
(10) R.D. McDowall, Spectroscopy 23(7), 2629 (2008).
6/9/2017 PeriodicReviewsofComputerizedSystems,PartII|Spectroscopy
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Spectrometry Systems, Part II
Nov 01, 2011 By R.D. McDowall
Spectroscopy
Volume 26, Issue 11
This column, which is the second of a two-part series, looks in more detail
at a periodic review. Here, we will discuss how to conduct the review, the
Quantum Mechanics
use of checklists, and reporting the outcome.
In part I of this column (1), we discussed what a periodic review is, how to excellent Baseline column discusses the
define the scope of a system scheduled for a review, and the main relevance of quantum mechanics for spectroscopy
elements in the planning and execution of a review. In the second part of and why it is important for spectroscopists to know
this discussion on periodic reviews, I want to focus on the execution phase the basics.
of a periodic review and discuss in more detail the following activities:
Read more.
the opening meeting Author Guidelines

carrying out the periodic review
reviewer's closed meeting Spectroscopy welcomes manuscripts that describe
the closing meeting spectroscopy and that are of immediate interest to
writing and approving the periodic review report and action plan users in industry, academia, and government.
implementing corrective and preventative actions.
Who Is Involved and What Do They do?
Who should be involved with a periodic review, apart of course, from the
person who is conducting the review (as we discussed in part I of this
column)? Ok, here is a list of potential people. Some of these roles may be
combined depending on the size of the system being reviewed and
especially if the laboratory is responsible for the whole system including the
IT support, if the system is relatively small, or if there are only a few users.
Other persons may be involved, depending on the roles and
responsibilities for the system:
http://www.spectroscopyonline.com/periodicreviewscomputerizedsystemspartii 1/3
Laboratory manager: Although the laboratory manager may not be Current Trends in Mass
directly responsible for the system itself, the system operates in the
Spectrometry
laboratory for which the manager is responsible and accountable. At a
minimum, the laboratory manager should be present at the opening March 2017 Edition
and closing meetings to introduce him or herself and listen to the
review conclusions and discuss any findings.
Process owner: The individual in the laboratory who is responsible for
the system. For a standalone spectrometry system, this may be the
spectroscopist who runs the system. For larger systems, say the high
performance liquid chromatographymass spectrometry (HPLCMS)
networked system that was discussed in the first part of the column (1),
it may be that the process owner is the laboratory manager.
System owner: The system owner is the person responsible for
supporting the system from an IT perspective. If the system is View the Articles Here>>
standalone (where IT support comes from within the laboratory), the
role of system owner can be taken by the process owner. If the the
system is networked, the system owner may be an individual in the IT Recent Special Issues
department. In the latter situation, the system owner could be from an
external company if IT operations have been outsourced. Applications of ICP & ICP-MS Techniques for
Power user or laboratory system administrator and users: Depending Today's Spectroscopists
on the size of the system, these roles could be taken by a single
person or by many individuals. However, the reviewer needs to have
access to somebody within the laboratory who knows the system in-
depth from a technical perspective (the power user or system
administrator) and may also require an experienced user to discuss
procedures and use of the system.
Computer validation: Because the periodic review will examine the last
validation of the system, there needs to be a person available to
answer the reviewer's questions on this topic. Depending on how the View the Articles Here
work was performed, this could be the system administrator from the
laboratory or a member of the computer validation group within the Advances in Portable and Handheld
organization. Spectroscopy
Quality assurance (QA): A member of QA who is responsible for the
laboratory may also be involved with the periodic review. Depending
on the depth of this person's knowledge, his or her involvement may
range from interested observer to full participant.
Here is where the timetable for the periodic review comes in. Instead of
having everybody hanging around waiting to be called, a timetable for the
review should state what topics will be covered and roughly when they will
take place. This allows individuals to carry out their normal jobs and turn up
at an appointed hour. There may be some variation in the timetable View the Articles Here
depending on what the reviewer finds, so prepare to be flexible with the
timing.
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Volume 26, Issue 11
Types of Computerized Systems to Be Reviewed
Typically, there are two types of

computerized systems that will be
covered by a periodic review: hybrid
systems (electronic records plus paper
printouts with handwritten signatures) and
homogeneous systems (electronic records
Table I: Advantages and
with electronic signatures where the only
disadvantages of paper, hybrid,
printouts will be summary sheets or at the and electronic auditing systems
request of an inspector or reviewer). Let's
look at the advantages and disadvantages of each, starting with a Quantum Mechanics
completely paper-based system as shown in Table I. Paper is a medium
that we are all familiar with; it is tangible, we can handle it and pick it up.
Also, the audit trail is apparent because the paper is written or printed in a relevance of quantum mechanics for spectroscopy
linear fashion. However, the poor reviewer has a disadvantage as he or she and why it is important for spectroscopists to know
the basics.
must wade through piles of paper to understand what was done, by whom,
and when. Read more.
Moving to a hybrid computerized system, we have the same advantages Author Guidelines
and disadvantages of the paper plus the complication and correlation of
electronic records. It is the correlation of the paper with the electronic Spectroscopy welcomes manuscripts that describe
records that provides the biggest challenge in an inspection or periodic spectroscopy and that are of immediate interest to
review of heterogeneous or hybrid systems. The failure by Food and Drug users in industry, academia, and government.
Adminstration (FDA) inspectors to cross check the paper printouts with the
corresponding electronic records in a chromatography data system
allowed Able Laboratories (Cranbury, New Jersey) to conduct fraud on a and mass spectrometry. We accept review articles,
large scale for a long period of time (2). If an electronic (homogeneous) technical articles, and tutorials. For more information,
system is audited, the reviewer needs to ensure first that the computerized
system itself is validated and has remained so from the last full validation to
the time of the periodic review. However, the reviewer needs an
experienced user when checking the way the system operates and how the
electronic records are produced to implement the requests from the
reviewer through the system. Often, the system used for part of the review
may use the validation or training instance and the reviewer needs to
ensure that the operational and other instances are equivalent. However,
http://www.spectroscopyonline.com/periodicreviewscomputerizedsystemspartii?id=&sk=&date=&pageID=2 1/4
the great advantage when reviewing an electronic system is the speed of

the audit; a lot of ground can be covered relatively quickly because of how
the system supports the business process. What also needs to be Spectrometry
addressed are the technical controls within the system to ensure data
March 2017 Edition
integrity, for example, checking the audit trail to make sure that results have
not been manipulated to pass. As an electronic system can cross
organizational departments, the review scope may be wider than normal
and if networked will also include the IT department responsible for
supporting the system.
Are Computerized Systems Designed to Help Periodic Reviews?
No, is the simple answer to a simple question. Let us explore the reason
why we want systems to help us with periodic reviews.
(Turn on moan-mode). Much of the emphasis in the design of the majority View the Articles Here>>
of computerized systems used in the analytical laboratory has focused,
unsurprisingly, on providing new functions for users and incorporating
regulatory compliance, such as audit trails when requested by regulated Recent Special Issues
users. However, as we are moving toward electronic systems with minimal
paper output, we really do not have the functions in software to allow Applications of ICP & ICP-MS Techniques for
effective and efficient second-person review of the data on a day-to-day Today's Spectroscopists
basis and also for periodic reviews on a 13 year frequency. It is the need
for second-person review that we need to concentrate on because the
periodic review will use the same functions. Both the second-person check
and the periodic reviewer need to assure themselves that the data quality
and integrity are good and have not been compromised. This is also a
concern for regulatory agencies, especially the FDA, which recently
launched an initiative on ensuring data integrity (3).
The United States good manufacturing practices (US GMP) regulations

require, in section 211.194(a), that laboratory records include complete View the Articles Here
data derived from all tests necessary to assure compliance with
established specifications and standards, including examinations and Spectroscopy
assays, as follows:
(4) A complete record of all data secured in the course of each test,
including all graphs, charts, and spectra from laboratory instrumentation,
properly identified to show the specific drug product, and lot tested.
(8) The initials or signature of a second person showing that the original
records have been reviewed for accuracy, completeness, and compliance
with established standards (4).
These two clauses are important because the regulation requires that all
data be collected. This includes the checks carried out on the
spectrometer before sample analysis commences, as well as any rerun FT-IR Technology for Today's Spectroscopists
samples. The checks performed by the reviewer (second person) must
include complete data, including audit trails of hybrid and electronic
computerized systems.
Referring to Table I, the complete data should be present in the laboratory

notebook or uniquely numbered laboratory sheets and instrument printouts.
Built into the paper will be the cellulose audit trail that is, where mistakes
that have been identified and corrected will have the original entry struck
through with replacement data entered by the side, the initials of analyst
who made the change, and the date of the change. The correction may View the Articles Here
also include a reason for change as per the applicable good X practice
(GxP) regulation that the laboratory works under.
When we consider hybrid systems, our data integrity problems start

because the audit trail becomes jumbled and the linkage between
electronic records and the corresponding paper printouts is not always
obvious. Often, the audit trail is not very good as there is just a single audit
log with little or no search function. By its nature, an audit trail will normally
contain a multitude of entries: user access, failed attempts for access by
users, additions, modifications, and deletions to data, user account
management and access control, and so forth. Many of these entries are
routine events, but unless there is a simple and easy means of separating
different types, the audit trail can be useless.
Similarly, when fully computerized systems are used, the linkage between
records and reports is usually easier and more straightforward. However,
the key requirement is an effective audit trail, which may not be the case.
Typically, systems are not designed to work electronically: The business
process may be fine but the Achilles heel of the majority of systems is the
audit trail as it is the key to ensuring data integrity. What is required are
data filters that can be configured by users to identify when changes to
data have been entered into the audit trail that will allow effective second-
person review and, by implication, periodic review. In addition, there is the
new European Union (EU) GMP requirement (5) for review of audit trails
and few if any systems have the ability to demonstrate that this has been
done. So, we are left with systems that are typically not designed to
facilitate reviews of data, audits, or inspections. Welcome to the periodic
review world of hybrid and electronic computerized systems! (Turn moan- Sponsored Links
mode off.)
Editorially-driven audio PODCASTS
Opening Meeting designed to keep industry
So having moaned about the systems you have to review, let's begin the professionals connected
process. This starts with the opening meeting, which is typically a short
session where the reviewer meets the key people who will be involved with
the review. It allows introductions to be made and for the reviewer to
explain what the aims of the periodic review are and set expectations from
the individuals who will be contributing from the laboratory side. It also
provides an opportunity to fine-tune the schedule to take into account any
last-minute availability of staff and to move items around. The point here is
that the reviewer should be flexible and, so long as the main topics are
covered, the order of review should not matter.
One item that is important is at the end of the opening meeting and before
the start of the review, the reviewer should ask for a short presentation of
the system by the process owner or validation manager to outline the main
functions and how the system was validated. This allows the reviewer to
understand the context of the material he or she has read before the review
starts and also to pick up and understand terminology.
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Volume 26, Issue 11
With Cat-Like Tread?
I want to consider how you actually carry out a periodic review. In my view,
you have two basic options:
Static: Sit in a room and read and evaluate system documentation or

logs against procedures and polices. At this point, the more
intelligent readers among you may be wondering if watching paint
dry is a more intellectually stimulating option.
Dynamic: Look at the system and see how the software and
instrument operates, examine the IT support, and have discussions
with users and IT staff. You will be amazed at what you can find out
by simply being observant, which we will discuss later in this column. Quantum Mechanics
In reality, the periodic review is a mixture of the dynamic and static options. This series of installments from David Balls
Walking around the laboratory and seeing the system in its operational excellent Baseline column discusses the
environment allows a reviewer to put the documentation into context and and why it is important for spectroscopists to know
see the reality rather than what is portrayed in policies and procedures. So, the basics.
the reviewer should not just sit in an office and read walk around and
see the system in operation in the laboratory. Therefore, the review Read more.
schedule should contain time for a tour of the laboratory and system and, if
applicable, the IT department.
Author Guidelines
Conducting the Periodic Review
You will need to obtain information from the people that you will interview
users in industry, academia, and government.
and have discussions with during the audit. The best way to do this is to
ask open-ended questions (for example, when? who? where? how? why? We cover molecular spectroscopy techniques, atomic
and what?) to get people talking. Then, of course, comes the question that
makes you ask if all periodic reviewers are from the state of Missouri. technical articles, and tutorials. For more information,
Because the answer to the open questions listed above is usually followed please see our author guidelines.
by the infamous "show me" to verify that what has been stated actually
occurs and there is documented evidence available to demonstrate this. To
verify the information provided, the reviewer should use closed questions
that the responder can respond to with either yes or no answers. Another
technique that allows a reviewer to understand information is to ask
questions such as, "What happens if ?"
Some of the dos and don'ts of conducting

periodic reviews are shown in Table II,
and many of these are derived from how Spectrometry
to manage people correctly during the Table II: The dos and donts of
March 2017 Edition
review. Part of the role of a reviewer could conducting a periodic review
be to persuade users and IT staff to
change their way of working if
noncompliant practices are observed; you can't do this if you have put their
backs up when you conduct the review.
I've Got a Little List
If you want to strike terror into the individuals involved in a periodic review,
a very good way at the opening meeting is for the reviewer to casually open
a briefcase and pull out the most devious instrument of torture imaginable.
Like a magician pulling a rabbit from a hat out comes the checklist!
Moreover, the thicker the checklist and the louder the sound it makes when
it hits the table, the greater the terror perceived by the victims. Recent Special Issues
Seriously though, a checklist has a number of advantages for a reviewer. It
should have been generated from the applicable regulations,
pharmacopeial general chapters, company procedures, and regulatory
and industry guidance documents. However, as the regulations are
changing at a rapid rate, the checklist should be a living document and be
versioned and dated to ensure that the current version is being used by the
reviewer. As such, the aim of the checklist is to ensure consistency across
the company, as well as between sites and reviewers, and that all aspects
of the review have been covered. From the perspective of the reviewer, a
checklist is a memory aid to help them cover all the points.
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Volume 26, Issue 11
Death by Checklist?
There is also a downside to a checklist: A reviewer can be a slave to it.

Imagine, if you can, the scene during a periodic review where the reviewer
asks the following: "Question 107: Have you got a backup SOP? Question
108: Have you kept a log of backups performed? Question 109: " and so
forth. At this point, the poor individual on the receiving end of this
inquisition is mulling over the philosophical question: Which is better,
murder or suicide?
This situation can be real if a reviewer takes the checklist literally. Instead,
the checklist should be used as a guide and, if structured correctly, will be
broken up into different subject areas that, when taken together, will cover Quantum Mechanics
all applicable topics. When a specific topic is covered, the reviewer should
ask questions and discuss with the individuals involved. The reviewer just excellent Baseline column discusses the
needs to refer to the checklist to ensure that everything has been covered relevance of quantum mechanics for spectroscopy
before moving on to another topic. and why it is important for spectroscopists to know
the basics.
Furthermore, as mentioned in part I of this series, the reviewer needs to be
aware that if something important is found during the review, it may warrant Read more.
a more detailed investigation. In such a case, a portion of the review may
Author Guidelines
be expanded and other parts not covered.
Options for Checklists: Working Smarter Not Harder techniques and applications of all forms of
Let me ask you a personal question: Are users in industry, academia, and government.
you lazy? We have looked at checklists,
but we also need to consider how to use
them effectively throughout the periodic Table III: Advantages and and mass spectrometry. We accept review articles,
review process. Rather than just having a disadvantages of auditing paper, technical articles, and tutorials. For more information,
list of questions that are ticked off as the hybrid, and electronic systems
review progresses, we need to think how
we can link the checklist with the review report. Indeed, can a checklist
form the basis for the audit report? The answer is yes. One way of doing
this is shown in Table III. Here, in the left-hand column are the checklist
questions and in the right-hand column is space to write in the observations
and any findings or recommendations (we will return and define these
terms later in this column). However, you can see that with a little planning,
the checklist and report can be integrated easily and the checklist
becomes the basis for the periodic review report.
Spectrometry
Review of the Last System Validation
March 2017 Edition
It is ironic that computer systems that are supposed to automate operations
and streamline processes generate mountains of paper. So if a system
subject to a periodic review has been validated since the last review, the
current review should start with the last system validation. Depending on
the size and complexity of the computerized system, this could take a short
time or last at least a day. So where do we begin?
Rather than list my ideas, let's hear from the GMP inspectors who do this
for a living. Sections 23 and 24 of PIC/S guide PI-011, called computerized
systems in GXP environments (6), are devoted to the inspection of
computerized systems in regulated environments. This guide has also been View the Articles Here>>
adopted by the good clinical practice (GCP) inspectors in the EU (7), rather
than write their own. This is great, except that the PIC/S guide is outdated,
being based on good automated manufacturing practice (GAMP) 4 (8) Recent Special Issues
instead of GAMP 5 (9), leading to very little risk-based computerized
system validation and little flexibility in the approach. Applications of ICP & ICP-MS Techniques for
However, PIC/S PI-011 section 24 (6), entitled "Inspector's Aide Memoires,"
contains six checklists for inspecting a computerized system although the
main focus of these checklists is on the application, there is little on the IT
infrastructure and services supporting it. Section 23, entitled "Inspection
Considerations," is more interesting from the perspective of a periodic
review and how to conduct one, although clause 23.4 notes that this
guidance, much the same as any checklist, should not be used as a blunt
instrument when inspecting a computerized system, but used selectively to
build up an understanding of how computerized systems are validated and
operated by a company. However, we can learn and adapt the approach View the Articles Here
outlined here. Advances in Portable and Handheld
Spectroscopy
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Volume 26, Issue 11
Preparation Before the Review
As mentioned in the first part, the reviewer needs to do a little homework by

reading some key documents before he or she starts the periodic review.
The PIC/S guide suggests starting with the validation summary report (6);
however, in my view this is only adequate, and a better approach is to read
the following documents:
Validation plan the last full validation plan of the system will detail
the activities and documented evidence that were intended to be
performed and written, respectively.
Validation summary report to see what was actually done and
understand the reasons for the differences and the justification for the Quantum Mechanics
changes made to the plan.
User requirements specification (URS) to define the intended use
of the system and to assess the quality of the requirements: Are they relevance of quantum mechanics for spectroscopy
testable or verifiable? and why it is important for spectroscopists to know
the basics.
The rationale for reading these documents

Read more.
is shown in Figure 1. It checks the quality
of the validation control by comparing Author Guidelines
both the intent and delivery of the
validation effort and asks if they match; techniques and applications of all forms of
this provides a good foundation to begin spectroscopy and that are of immediate interest to
the review of the validation of the system. Figure 1: Preparatory reading
If the validation is suspect, then the quality before a periodic review. We cover molecular spectroscopy techniques, atomic
and accuracy of the results produced by the system will be suspect as spectroscopy techniques, laser-based spectroscopies,
well. Reading the URS determines how well the intended purpose of the technical articles, and tutorials. For more information,
system has been defined and, hence, how well the rest of the validation, please see our author guidelines.
shown with dotted boxes in Figure 1, is likely to have been performed.
Reviewing Requirements: Role of Traceability
You may remember that I discussed the

role of a traceability matrix in validation in
a two-part column a few years ago
(10,11). These articles will provide you
with the background to what I'm going to

discuss now from the perspective of a
periodic review. The traceability matrix Spectrometry
should allow a reviewer to trace
March 2017 Edition
requirements from the URS to where the
requirement is either verified or tested Figure 2: The importance of being
later in the life cycle or vice versa (test or able to trace requirements to
verification back to the requirements). So, testing.
what if there is no traceability matrix? Well
in essence, I ask the questions and then watch you wade through a sea of
paper to find the answer. This is a form of entertainment for the reviewer but
only if he or she can keep from smiling.
Regardless of how traceable the requirements, I always wonder how they

were written: For example, were they written to document the intended use View the Articles Here>>
of the system or to impress the reviewers of the URS? Let's look at two
examples of requirements, quality and traceability. Unfortunately, these are
both real-life examples.
In one periodic review, I wanted to trace a user acceptance test for the Applications of ICP & ICP-MS Techniques for
audit trail back to the URS. The URS was eventually traced to the section Today's Spectroscopists
on "Backup and Retrieval." Requirement 5.1.3 stated "The entire system is
to adhere to GXP requirements on the tracking of information. Therefore, it
will be required to demonstrate the status of the system at any nominated
point in time." This implies some form of audit trail is readily available. This
requirement is not testable or verifiable as it does not define the actual
functions of the audit trail. Interestingly, there was no mention of backup or
retrieval in this section.
Here's another example of how not to write requirements (for a

spectrometer system): "6.2.4.1. Report production at least every one page View the Articles Here
every 10 s at modest network utilization." Note that the requirement is Advances in Portable and Handheld
numbered, which is good for traceability. If we look at the first part of the Spectroscopy
requirement: report production of one page every 10 s, this is testable.
However, then come the four words to snatch defeat from the jaws of
victory: "at modest network utilization." This makes a testable requirement
untestable. What is a modest network? Don't even go there! Does this
mean a test is conducted at night when there are no users on the network
or when they are all on a break?
These are just two examples of the rubbish requirements that the poor
reviewer has to sift through.
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Volume 26, Issue 11
Other Areas for Review
I do not have sufficient space to cover some other aspects of the review of
the validation, such as
Configuration of the software: Is it the same as installed or has it been

changed? If yes, where is this documented and how is it tested?
Reviewing vendor documentation critically, especially in light of my
comments on vendor material (12)
Installation documentation for the IT, instrument, and software
components of the system.
Operational Review Quantum Mechanics

In this section of the periodic review, we'll be looking at the different types
of users, the system security (for example, look closely at the number of excellent Baseline column discusses the
characters in a user's password as they log on do the access privileges relevance of quantum mechanics for spectroscopy
on paper match those in the system?), the procedures for the system, and and why it is important for spectroscopists to know
the basics.
use of the system in operation. Typically, you'll get out into the laboratory
and talk with users and system administrators. Read more.
Depending on the scope and use of the system, this part can vary from Author Guidelines
relatively simple to very extensive, so advice here is very generic rather
than detailed. Check that users' training records are current and that users Spectroscopy welcomes manuscripts that describe
have been trained on the current versions of procedures. Furthermore, do
the procedures for the system describe how to use it in sufficient detail or users in industry, academia, and government.
are they vague?
A Picture Is Worth a Thousand Words spectroscopy techniques, laser-based spectroscopies,
A digital camera can be very useful during a periodic review to provide technical articles, and tutorials. For more information,
supporting photographic evidence to reinforce written observations. For please see our author guidelines.
example, it can record an untidy or unsafe laboratory and also avoid

"unofficial" corrective actions, such as tidying up the facility and then
denying that a problem ever existed. If a reviewer writes in the audit report
that the user name and password were written on the front of the
spectrometer PC (it's a bit dry and the reader needs to imagine the
situation), but if you have the section of the report as shown in Figure 3 it
carries more impact. Furthermore, the reviewer can leave the reader to
think, "What were those idiots thinking?" rather than leave the report to
hammer the point home. You will note that the photograph in Figure 3 does
not have a time and date stamp. This is deliberate because it is from an Spectrometry
auditing course that I run, and it is one of the mistakes in an audit report
March 2017 Edition
that attendees have to identify.
Observation: "The user name and

password were written on the front of the
spectrometer PC. See the photograph
below."
Regulatory Compliance The Final

Figure 3: Example of photographic
Frontier?
evidence used to support an
It will be inevitable that at some stage you observation in an audit report.
will need to include the IT department in a View the Articles Here>>
periodic review to see how activities such as backup, change, and control
are carried out. Again, IT will need to be notified and have staff available
according to the schedule in the plan. If the IT department activities are Recent Special Issues
outsourced, then agreement with the outsourcing company may also have
to be sought. Applications of ICP & ICP-MS Techniques for
The principles here are the same as for the users: Is there a procedure, is it
followed, and is there evidence of this? One issue is that some IT
procedures may be written under sufferance and may be fairly basic and
never read from the day they were written. However, look at the procedure
to see what is written and ask the IT staff to talk about or demonstrate what
is done and where the records are to demonstrate it was followed. Do they
match? If yes, this is fine; but if not, then you have findings to consider.


Spectroscopy
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Volume 26, Issue 11
Reviewer's Closed Meeting
The optimist in me thinks that if I allow an hour for the closed meeting, I can
take my time and review what I have seen and identify the findings, and, if
time allows, classify them as to their severity. The pessimist in me knows
that regardless of the timetable I will overrun the review and this will reduce
the time for my closed meeting. Regardless, the reviewer's closed meeting
is a quiet period where audit notes and observations can be reviewed and
any findings identified and classified as outlined below.
Observations, Findings, and Recommendations
What's in a word? The heading above lists observations, findings, and Quantum Mechanics
recommendations, but what do they mean? Again, each company will have
its own definitions but these are mine: This series of installments from David Balls
Observation: This is what the reviewer saw during the periodic review. and why it is important for spectroscopists to know
Dependent on the company requirements these can be detailed or the basics.
summary. However, consider that the same reviewer may not conduct
the next periodic review of this system and there needs to be sufficient Read more.
detail to enable another person to follow what was done in the current
review. For example, a reviewer should list a standard operating
Author Guidelines
procedure (SOP) with its version number so that the next reviewer can Spectroscopy welcomes manuscripts that describe
see what has changed since the last review. Note that observation as techniques and applications of all forms of
used here is not in the same context as an FDA 483 observation, it is
simply what the reviewer saw during the review.
Finding: A noncompliance with regulations or procedures equivalent to We cover molecular spectroscopy techniques, atomic
a 483 observation where there is a noncompliance with the regulations
or company procedures. However, are all findings or noncompliances technical articles, and tutorials. For more information,
the same? For example, is a missing signature from a document the please see our author guidelines.
same as not validating a computerized system? No. Therefor,e we
need to have a classification scheme. One that could be used is
presented in Table IV, in which each finding is classified in ascending
order of severity between 1 and 4.
Recommendations: This is something that I am occasionally asked to
do by some clients. Recommendations are not noncompliances, but
simply nonbinding recommendations to the process owner by the
reviewer that a working practice or way of performing a task could be

improved. Whether or not the recommendation is implemented is the
choice of the process owner. Spectrometry
The Closing Meeting March 2017 Edition
After the reviewer's closed meeting, the

review is concluded by the closing
meeting. Here, all involved with the audit
will be present. The reviewer will lead the
meeting by presenting the conclusions of
the audit and the findings, and this should Table IV: A classification of findings
or noncompliances
be done without interruption. One problem
with reviews and audits is that the highest level of praise is "adequate,"
which means little to the people on the receiving end. The reviewer should
include areas where good work has been done and say so. If there are
findings, then the major ones as a minimum need to be covered. If the
reviewer has been open, the laboratory staff will know where the problems Recent Special Issues
are but not the classification.
After the reviewer has presented the initial observations and findings, the Today's Spectroscopists
meeting is open for comment. This is important because the reviewer may
have misinterpreted something that can be corrected while still on site by
going through the procedures or other documented evidence. It is
important for the reviewer to cover all major findings and issues directly
with the laboratory staff so that there are no surprises in the report.
Otherwise, they will feel aggrieved that bad news was not passed on face-
to-face.
Documenting the Periodic Review
A draft report of the review is the formal outcome that will present the View the Articles Here
observations and findings, as we have discussed earlier in this column. The Advances in Portable and Handheld
laboratory has an opportunity to comment on the report and feed these Spectroscopy
observations back to the reviewer. Associated with the report is a
corrective action plan in which the findings (moderate and above) are listed
and the laboratory is asked to complete the corrective and preventative
actions against the findings. After the report and corrective action plan are
agreed on, then they are finalized.
To demonstrate that a review has taken place, some organizations produce

an audit certificate signed by the reviewer. This is shown to an inspector.
Previous 1 2 3 4 5 678 Next View the Articles Here
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Volume 26, Issue 11
Summary
These two installments have discussed in some depth what is involved in a

periodic review of a computerized system: the regulations, the scope of the
review, and how to conduct and report one. It is the means of ensuring that
computerized systems remain in control throughout their working life and
must be undertaken on a regular basis.
R.D. McDowall is the principal of McDowall Consulting

and the director of R.D. McDowall Limited. He is also
the editor of the "Questions of Quality" column for LCGC
Europe, Spectroscopy's sister magazine. Direct Quantum Mechanics
correspondence to: spectroscopyedit@advanstar.com
References excellent Baseline column discusses the
(1) R.D. McDowall, Spectrosc. 26(9), 2838 (2011). and why it is important for spectroscopists to know
R.D. McDowall
the basics.
(2) R.D. McDowall, Qual. Assur. J. 10, 1520 (2006).
(3) M. Cahilly, presentations at the ISPE GAMP Conference, Somerset, New Read more.
Jersey, 2011.
Author Guidelines
(4) US Food and Drug Administration, Current Good Manufacturing
Practice regulations 211.194(a) (US Dept of Health and Human Services, techniques and applications of all forms of
Rockville, MD). spectroscopy and that are of immediate interest to
(5) EU GMP Annex 11 on Computerised Systems, (2011).
(6) PIC/S PI-011 Computerised Systems in GXP Environments, PIC/S spectroscopy techniques, laser-based spectroscopies,
(2004). and mass spectrometry. We accept review articles,
(7) Annex III: To Procedure For Conducting GCP Inspections Requested By please see our author guidelines.
The EMEA: Computer Systems.
(8) Good Automated Manufacturing Practice guidelines version 4

(International Society of Pharmaceutical Engineers, Tampa, FL, 2001).
(9) Good Automated Manufacturing Practice guidelines version 5,

(International Society of Pharmaceutical Engineers, Tampa, FL, 2008).
(10) R.D. McDowall, Spectrosc. 22(11), 2227 (2008).

Spectrometry
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6/9/2017 PeriodicReviewsofComputerizedSystems,PartI|Spectroscopy

For example, the performance qualification of your <redacted> system

The point is that the initial validation failed to check calculations in a

View the Articles Here

Raman Technology for Today's Spectroscopists

Although the Annex 11 regulation talks about a periodic evaluation (I have

Overview of a Periodic Review Author Guidelines

review is an independent audit of a We cover molecular spectroscopy techniques, atomic

reviews. The whole process should be described in the audit/review SOP

Objectives of a Periodic Review

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View the Articles Here

Raman Technology for Today's Spectroscopists

Who Performs a Periodic Review?

So, from the perspective of the European regulations, we need a periodic

the definition of independent is "not influenced or controlled by others;

There are a number of requirements necessary for a person to effectively

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How Critical Is Your System?

Putting the heading in a different way: Do we need to do a periodic review

The starting point is the inventory of computerized systems contained in the

In my opinion, there are three or four possible times to review a

Before operational release of a system. This is to ensure that system

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View the Articles Here

Advances in Portable and Handheld

View the Articles Here

FT-IR Technology for Today's Spectroscopists

View the Articles Here

Raman Technology for Today's Spectroscopists

Health Warning: Periodic Reviews Only Sample

Periodic reviews and audits should carry a health warning. It is important to

Slicing and Dicing: Defining the System Scope

It is important to get the scope of the audit

Expressing a personal view, I would have a wide system breadth that

What is not shown in Figure 2 is whether the system has additional

Also, consider an alternative to the system

Types of Periodic Review

Horizontal audit or review: A horizontal review is conducted across

In practice, all three types of auditing can be used effectively during a

Writing the Periodic Review Plan

Returning to the execution phase outlined in Figure 1, let's look at the

a separate person as an approver. Depending on the company

Preparation for a Periodic Review

computerized system validation SOPs

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Activities During the Periodic Review

associated procedures, and so forth will be assessed. We will look at

In this installment, I have looked at a periodic review or evaluation for

R.D. McDowall is principal of McDowall Consulting

(1) R.D. McDowall, Spectroscopy 26(4), 2433 (2011).

(4) EU GMP Chapter 9, Self Inspections.

(7) GAMP Guide, version 5, 2008, Appendix 08, Periodic Reviews.

(9) C. Burgess and R.D. McDowall, QA Journal 10, 7985 (2006).

(10) R.D. McDowall, Spectroscopy 23(7), 2629 (2008).

the opening meeting Author Guidelines

View the Articles Here

Raman Technology for Today's Spectroscopists

Types of Computerized Systems to Be Reviewed

Typically, there are two types of

the great advantage when reviewing an electronic system is the speed of

Are Computerized Systems Designed to Help Periodic Reviews?

The United States good manufacturing practices (US GMP) regulations