LC•GC INTERNATIONAL - APRIL 1996 1

Questions of Quality

TEN STEPS TO HEAVEN?

The ten steps of a Laboratory Information capable of doing.
Management System (LIMS) project are The ten stages of a LIMS project are:
outlined, but are you walking the road to • analyse needs
heaven or hell? • specify user requirements
• write a validation plan
• devise a transition plan
What is a LIMS? • select a supplier
In the last Questions of Quality column • develop functions
we discussed the boundaries and scope • pilot a system
of a LIMS. It can be defined as a • qualify or validate the system
computer application that is capable of • train users
capturing, analysing, reporting, and • roll out the system to users.
managing data and information using a The SDLC can be represented as a V, as
database. The key components of a shown in Figure 1. The first eight stages
LIMS are the computer hardware, the will be covered in this month’s Questions
communications network, and the of Quality. The training and roll out of the
software (operating system, software system to the users and their involvement
tools, programming languages, in the whole of the SDLC will be discussed
database, and data). The problem is to in the next Questions of Quality.
fit a commercial LIMS into your
laboratory and the way you work. How Will the System Operate in a
do you do this? The answer is to follow Regulated Environment?
the systems development life cycle The first question you should consider
(SDLC). before starting a LIMS project is “will the
system operate in a regulated
Systems Development Life Cycle environment?” Such an environment is
This instalment of Questions of Quality Good Laboratory Practice (GLP), Good
and the next will look at the Manufacturing Practice (GMP), or
development and implementation of a International Standards Organization
system that follows the traditional (ISO) Guide 25; all of which have specific
computer SDLC. It is this approach requirements for the validation of
that chromatographers will find computer applications. Therefore, if the
unusual. Normally, equipment is answer to the question is yes, then the
purchased off-the-shelf and used with development of the system should be
little or no modification. However, a documented to demonstrate the quality
different approach is necessary with of development. It is my experience, and
complex laboratory automation such that of others, in these environments that
as a LIMS. In this instance, the users development is evidenced through
must state what tasks they want the documentation. The absence of
system to undertake. This often places documents suggests that no activities
the chromatographer in a difficult took place.
position because he/she is not certain If the system will not operate in a
R.D. McDowall what the system should be, or is, regulated environment, there is no
2 LC•GC INTERNATIONAL - APRIL 1996

F1

Concept Operate

Fit? Validate/
Specify
Qualify
User

Supplier
Fit?
Design Test

Build

Figure 1: Systems development life cycle. N.B. When specifying a design it is necessary to consider testing and validation/qualification before
operation can proceed.

requirement to document the This can result in some documents. validated. The LIMS matrix, described in
development. However, this is contrary to • Needs Analysis Report: This describes the the last Questions of Quality column,
the principles of Good Computing basic problems that the proposed system can be used as the basis for drawing up
Practice, in which each stage of should solve, such as replacement of an the user requirements. The requirements
development should be documented. By older system or expansion of existing may be phased (Table 1, step 4)
not documenting the development of the facilities to overcome a bottleneck that is provided there is a core working system.
LIMS, you will considerably increase the rate-limiting for the laboratory. If the LIMS is to be validated, the
risk of failure. Therefore, even if there is no • Project Proposal requirements specification is mandatory:
requirement for documenting the • Preliminary Budget Proposal A system cannot be validated without
development, I strongly suggest that you • Initial Project Plan: The project plan an up-to-date requirements
do so. If you don’t want to formalize should be updated as the project specification. When the requirements
development in this way, may I suggest progresses. Planning in the early stages change, the system requirements
that you just send a cheque for the time of a project is not detailed enough and specification must be updated to reflect
and money that you would have spent on as the project unfolds this is corrected. these changes. Why all the fuss about
the system, made payable to my eldest The size and significance of the system this document? Validation is currently
daughter, Jennie, to me, care of LC•GC to be acquired will determine how much defined as “establishing documented
International? She will waste the money documentation is needed. For a small evidence which provides a high degree
just as quickly, but the difference is she will LIMS, a preliminary budget proposal may of assurance that a specific process will
enjoy herself far more than you will during be sufficient to document this phase. consistently produce a product meeting
the failure of your LIMS project. An For the acquisition of a larger system its predetermined specification and
additional benefit is that my wallet will (e.g., for a site or an international quality attributes” (1). Note the phrase
rest easy. multi-site system), a project proposal “predetermined specification” — this is
Quality development will usually add a with an outline project plan and an the requirements specification.
further overhead to the project of up to extensive needs-analysis report will When the requirements specification
10%. However, this is effort well spent probably be required. is complete, a Request for Proposal (RFP)
because approximately 50% of LIMS A decision should be made at this is written, detailing the information that
projects fail, or fail to meet initial point — whether the project should be the department requires to make a
expectations; the additional effort will approved with money and resources selection. The RFP also helps the supplier
help ensure that the system will meet made available. format its tender or proposal. The
business and user requirements. A rather requirements specification and RFP
novel idea really. Step 2: Specify User Requirements should be separate documents, because
When budgetary approval is given, the if there are changes in the user
Step 1: Analyse Needs acquisition phase can start. The first requirements, only one document needs
The work in this stage establishes the stage is to write a Requirements to be updated. As well as defining the
reason for the system. During this process, Specification, which describes the user functions, the requirements
a needs analysis is undertaken which functions that the system needs to specification should identify the
defines the nature of the LIMS to be perform. This fixes the baseline against preliminary configuration of the system.
acquired and describes its goals and risks which prospective systems will be See Table 1 for an outline RFP.
within business and technical constraints. assessed and the installed system will be
 LC•GC INTERNATIONAL - APRIL 1996 3

Step 3: Write a Validation Plan should be planned at this stage to problem that will take much effort to
As soon as the user requirements are manage user expectations. This is overcome. We will discuss this in more
defined, the validation plan should be essential to forewarn the detail in the next instalment.
written. Validation is not the last stage chromatographers who will be affected
of the life cycle — it should be an by the implementation of the LIMS. For Step 5: Select a Supplier
integral part of the project. The old instance, who among the user The first stage in this process is to
saying that you cannot test quality into a community will be the first group of prioritize the functions in the
system is very true; only by designing users? The credibility of any LIMS can be requirements specification. The detailed
quality into the LIMS from day one of easily lost during the roll-out to users listing of the functional requirements will
the project will you succeed. If the and it is vital that the first users are enable the laboratory to define its
validation is considered from the start of sympathetic to the system. Poor criteria for selecting the new system.
the project (prospective validation) rather planning and management of the user Each requirement should be listed as
than as an afterthought (retrospective expectations from the start will cause a either mandatory or optional.
evaluation), this will save you
considerable work.
The validation plan will outline the
aims of the system and, most T1

importantly, the deliverables that should Table 1: Selected Sections in a Request for Proposal (RFP). The Twelve Sections of the RFP for a
be produced from each stage of the life LIMS are Described as Follows:
cycle to demonstrate that the work
was actually done. Producing the Description of the laboratory and the work undertaken:
documentation may sound like hard This should start with a brief description of the organization and the industry sector it is in, fol-
work, but with a little thought, the lowed by the function of the laboratory and how it helps the organization meet its aims.
documents can be produced within a Staff numbers and organization:
standard and structured format relatively The number of staff, levels of qualification (technician, academic, etc.), and how they are orga-
quickly. This is in contrast to nized. It may be appropriate to insert an organizational structure to help the description. What are
retrospective evaluation, in which these the roles of the functional elements of the laboratory?
documents or statements have to be Analytical instrumentation:
constructed some time after the events. Describe the main analytical instruments used in the laboratory: makes and models and overall num-
Memories can often be bad. bers. Will instruments be connected directly to the system or interfaced using a network? Do you
have sufficient volumes going through the instrumentation to justify on-line connection to the LIMS?
Step 4: Devise a Transition Plan Level of automation:
It is important early in the project to plan How automated is the laboratory: autosamplers for instrumental automation? Are other types of
the transition from the current way of automation used, such as robotics or sample processor apparatus?
working to the new LIMS. This is a Sources and volumes of work:
crucial part of any LIMS project and is Who are the main customers of the laboratory? What types of samples are submitted and the total
often neglected, resulting in problems later. numbers involved? The type and number of tests applied to each sample should be described.
If you have a manual system in your Speed of turnaround:
laboratory, the transition should not be The turnaround time required by the laboratory may influence the nature of the hardware and its
too complex or involved. Sometimes, the configuration or the integration with other computer systems.
new LIMS may replace an existing system. Further processing of results:
Therefore, planning should start early for How is the final report compiled? Will this be part of the LIMS or is the system to be interfaced to
the retirement of the old system and another system that is responsible for the further processing?
deciding what to do with any existing Past, present, and projected workload:
data that is stored on the system. Historical numbers of the workload for the past three or more years and a projection based on today's
Regardless of the current working knowledge is important to help size the LIMS hardware, including the disks, with a degree of confidence.
practices, the new LIMS should deliver Corporate computing policy:
some immediate benefit to its users to Software, hardware, and communications at local and corporate levels. This is an area of varying
encourage them to learn the system. For design constraints that have an impact on the tools and hardware to implement the system.
the first roll-out of the LIMS, do not Data input from other systems:
attempt to deliver a complete system. If the LIMS is to be connected to another system, describe it, and also what data, in which format,
Aim instead for a core system that meets will be transferred. Estimate the data volumes to establish the bandwidth required.
the major needs of the user community. Data output to other systems:
Note that the user community, as shown The same applies to the output from the system.
by the LIMS matrix, is inside and outside Integration with networks and communications:
the laboratory. Details of acceptable network protocols are essential. What is the e-mail system if integration is a
The overall plan for the implementation requirement to transmit results to clients?
of, or changeover to, the new system
4 LC•GC INTERNATIONAL - APRIL 1996

• A mandatory function is one that must decision right, otherwise you won’t requests for enhancements or
be present for the system to operate know whether you have made the extensions. Negotiations will continue
properly and meet regulatory correct choice of system until until both parties agree on the initial
requirements. 6–12 months, and a lot of time and configuration of the system. Thus, any
• An optional function is desirable if it is effort, later. specific points will be included in a
a standard operation on a system but Tests should be devised and contract between the LIMS vendor and
the basic functioning of the data performed for each selected LIMS. The the laboratory. We discussed the
system is not affected if the function is results of these tests, together with the contract in a previous Questions of
not present. comments of users on subjective Quality column (4).
The list of mandatory requirements elements of the system, should be used
establishes the base for selecting a to select a final supplier. Step 8, Part I: Qualify or
particular system and supplier, and this is When a final supplier has been Validate the LIMS
a key document. The selection tests can selected, or if you have the time Yes, I can count and the sequence of
be devised from the prioritized concurrently with the testing of the numbering is deliberate; but you can’t
mandatory functions. In addition, they systems, the quality procedures of each develop a system until it has first been
can be used in the acceptance and vendor should be investigated. This installed at your site. Therefore, the
qualification test plan and test scripts. involves assessing how the system was system has to be installed properly, not
Training is a key component of developed and tested, and how just thrown off a truck at your front
successful implementation of the new problems are recorded, tracked, and door. So, this part of the qualification or
system and must be considered as early resolved (including the help desk). validation of the system is concerned
as possible in this step. Training Alternatively, a vendor audit can be with the installation.
requirements need to be discussed with undertaken. The initial system configuration, the
the suppliers and modified to the A vendor audit is becoming RFP, and an outline of where the system
specific circumstances and type of increasingly important to regulatory components are to be sited and
system. Training should not just cover agencies. The Organisation for Economic connected are used to write an
the use of the system but also the Cooperation and Development (OECD) installation plan for the new LIMS. The
development of functions using the GLP guidelines for computerized systems installation of the major system
programming language and how to (2), specifically mention that users components is usually undertaken by the
manage and maintain the system. should ensure that a vendor has vendor’s staff and the job completed and
During the process of preparing the produced the system under a quality tested by them. However, when
RFP, a number of LIMS suppliers should procedure. These state that components are connected to the
be selected based on any previous “computerized systems should be organization’s infrastructure (such as a
experience, discussion with other system designed to satisfy GLP principles and network or other computer applications),
users, or on information from trade introduced in a pre-planned manner. the roles and responsibilities should be
adverts. For practical reasons, the There should be adequate discussed and agreed between all parties
number of suppliers should be kept documentation to recognized quality (again this might be an area for inclusion
relatively low (approximately six to eight and technical standards… For under contract discussions). The tests to
initially). The RFP is sent to the selected vendor-supplied systems it is likely that be performed on each module of the
vendors and a tender should be received much of the documentation created system as it is installed are described in
within a defined timescale (usually, during the development is retained at the Installation Plan. These tests may often
approximately six weeks after receipt). the vendor’s site. In this case, evidence be the standard ones that the vendor
Tender responses are reviewed against of formal assessment and/or vendor uses in all installations; occasionally they
the selection criteria and those systems audits should be available at the test may include some specific ones from your
that meet all, or the majority of, facility.” laboratory or organization. The output of
mandatory requirements should be The United Kingdom Pharmaceutical this process is an Installation Plan for the
selected for actual testing. Industry Computer Validation Forum installation qualification stage.
Testing two systems allows you a (UKPICVF) has produced the Good The Installation Plan is used by the
degree of choice in selecting the final Automated Manufacturing Practice appropriate personnel to install the
LIMS. If more systems are tested, this will (GAMP) guidelines (3) which outline the purchased hardware and software.
increase the choice, but also the time steps to be taken in the acquisition of a When a module of the system has been
and effort involved. This is computer system from a vendor, tested correctly, it is signed off and the
particularly important when a small including an emphasis on auditing the next module is installed and checked. As
laboratory is considering a LIMS; you will vendor’s quality procedures. components are installed, a configuration
not have the time and resources that are Before the purchase order is issued, log is completed to establish the
available to a medium-sized or large contract negotiations should take place components that comprise the initial
laboratory and may only be able to test to cover items such as price, payment configuration of the system. The outputs
one system. However, it is vital that you schedule, and what the supplier will do of the process are an Installation Report
spend time on this phase to get the about missing items or how to handle and a Configuration Log.
 LC•GC INTERNATIONAL - APRIL 1996 5

The second part of the qualification written the user documentation. You evaluation, and training system. This can
occurs after you have developed the were going to write down how to use be used effectively before transfer of
system to your requirements. the system, weren’t you? programs and trained users to the
When you have written and tested the operational computer. A modification of
Step 6: Develop Functions additional LIMS functions, you can give the LIMS licence may be required to
It is unlikely that you will find a LIMS it to the users. Or can you? operate in this manner.
that matches your requirements fully.
There will be some basic functions that Step 7: Pilot the System Step 8 Part II: Qualify or
every LIMS will perform, but some you Rather than roll the system out to the Validate the LIMS
will have to make or develop yourself. whole laboratory and watch it fall flat on This column is starting to look like a title
LIMS vendors provide tools to help you its face, I would suggest that you first from a Shakespeare play. The second
achieve these functions and these come pilot the system with a group of phase of qualification is the operational
in two main types: specific laboratory- sympathetic and computer-literate users. qualification or validation of the
oriented programming languages that The rationale with this approach is that completed system. This requires a test
allow you to develop laboratory-based any problems can be recognized and plan and test scripts written under the
functions; and programming tools that resolved before credibility is lost. For validation plan for the system. The test
are available with the database used in instance, new ways of working that look plan will investigate the critical areas of
the LIMS. attractive on paper can be tried out on a the system, such as data acquisition,
When additional functions are small scale to see if they are effective. It manipulation, and calculation, and also
required they need to be specified in is unlikely that a system designed on reporting of results. A number of test
writing, then written and tested by paper will work well at the first attempt. scripts should be written, based on the
laboratory staff, in-house computer Something is usually forgotten and it is current requirements specification, the
staff, or the LIMS vendor. If you do this these details, sometimes large and prioritized functions, and the tests used
in-house, by whatever means, it sometimes small, that make or break the to evaluate prospective systems. The
should be done in a quality way and system. number of test scripts will depend on
you should have documented
procedures. An alternative approach to
the traditional specification of the I WOULD SUGGEST THAT YOU
functions is to use prototyping. This
starts with the specification; however, FIRST PILOT THE SYSTEM WITH A
the user funtions are developed in an
iterative manner with the programmer GROUP OF SYMPATHETIC AND
working in close collaboration to
develop the functions. COMPUTER-LITERATE USERS.
Prototyping is an effective approach
but it must be managed effectively,
otherwise, functions can be developed Another facet of a pilot system is to size the complexity of the LIMS, the number
and modified because “the screen does the operational computer correctly. and type of instruments linked to it, and
not look right”. Equally important with Vendors will size the computer hardware the number of other computer
prototyping is that the requirements based upon an “average” laboratory (this applications interfaced with the system.
specification is updated to reflect the is the well-known laboratory in Outer The test scripts should cover the way the
latest version of the prototype. Mongolia, analysing yak’s milk). This system will normally be used and how to
You have two approaches with approach may be a start, but I would resolve common problems encountered
prototyping, either hacking code to advise that performance requirements are during the laboratory operation. You
achieve the functions or structured written into the contract with the vendor, should look at testing with normal,
programming. The former is fast but providing an upgrade path if they are boundary, and out-of-limits data.
when the desired system is reached, wrong. Alternatively, you purchase the It is important to realize that the
the operational system must be smallest computer you can run the LIMS validation must be performed in the
programmed from the start for a on to develop the system and test its same way that you use the system. As
robust and maintainable system. Of performance to size an operational you have purchased a configurable
course, when the management hears computer accurately. This second system, you may have developed a
that the system is ready, there is approach has a number of advantages: LIMS that is unique. For this reason,
pressure to roll out a prototype that is hardware prices are falling and you can never purchase a validated
not intended for operational use. The performance is rising, therefore you LIMS, or any system for that matter. If
latter approach is slightly slower but should save some money going along this you use the LIMS without any custom
allows the programming effort to be route. You will also have two computer programming, you will have to
maximized and the operational system systems at the end of the project; the populate the database with your own
to be ready to go when you have smaller system can be a development, methods and analytical approaches;
6 LC•GC INTERNATIONAL - APRIL 1996

again this may be unique.

You should be able to rely on the
work done by the vendor in developing
a system (subject to an audit), but never
rely on a validation certificate from a
vendor. It is, in my opinion, misleading
and wrong to sell software in this way.
Systems can be certified or verified by a
vendor but never validated. That is the
end-users’ responsibility.
When the testing has been
completed, a summary report is written
about the qualification testing and the
whole life cycle, summarizing all the
validation activities performed during
the project. Inputs are all the documents
produced during the projects, such as
the requirements specification, the RFP,
the review of the vendor’s quality
procedures, and the test scripts and
reports produced during the
qualification process. Note that I use the
phrase summary report; this is
deliberate. Too often validation is used
as an excuse to fell large areas of forest;
a summary report should be exactly that
— a summary of the validation or
qualification effort.
The summary report is authorized by
management and should contain a
statement that a system is released for
use in a GXP (a summation of GMP, GLP,
and GCP) environment.
That’s all there is to a LIMS project
really, except for the users. The next
instalment will look at reasons why “user”
is more that just a four-letter word.

References
(1) Guideline on General Principles of Process
Validation, Food and Drug Administration,
May 1987.
(2) Good Laboratory Practice Consensus
Document: The Application of the Principles of
GLP to Computerised Systems, Environment
Monograph Number 116, Organisation for
Economic Co-operation and Development
(OECD) Series on Principles of Good Laboratory
Practice and Compliance Monitoring Number
10, Paris, France, 1995.
(3) GAMP, Good Automated Manufacturing
Practice, Pharmaceutical Industry Supplier
Guidance for Validation of Computer Related
Systems in Pharmaceutical Manufacture, UK
Pharmaceutical Industry Computer Systems
Validation Forum, 1995.
(4) R.D. McDowall LC•GC Int. 7(7) 386–388 (1994).