Prerequisites for

Successful Validation
Charlie Neal
Diosynth-RTP (an Akzo Nobel Company)

❖
alidation was hinted in the Each are presented and dis-

V 1960s, almost four decades

ago. What has changed
over the last 30 to 40 years? Has the
❝A firm derives
little benefit if a
thorough
cussed in the following sections of
this article.

overall understanding of the term 1. Understanding

improved? Have all responsible understanding
firms truly embraced validation? of validation
Are they doing everything within
their power to make validations a remains within
success? Unfortunately not. While the validation
validation is a very necessary ele-
ment of any firm that falls under the department, and
scrutiny of the governing regulatory there is
agencies – both United States and
foreign – it has not received the re-
absolutely no
cognition it deserves. concept of the
So often, departments charged term within the
with conducting validations are
forced into an exiled status, as op- department
posed to being embraced. responsible for
• How can validation profes- approving the
sionals bring about a change? validation
• How can they assure that prop-
er events occur to achieve suc-
budget. ❞
cessful validation?
• Why has validation been so misunderstood for
the last four decades?
• How can validation resources go about planning
and executing validations?
• How can a firm be assured that its resources have
what it takes to successfully complete a valida-
tion? There are thirteen tools or elements that are
required for conducting effective validations.
Perhaps the single most impor-
tant element required is a good un-
derstanding of what validation is.
This understanding actually goes
beyond the basic definitions of val-
idation, beyond the concept of
“requiring a minimum of three
runs.” This understanding must be
anchored by sufficient years of
practical experience and knowl-
edge. It will permit sound and logi-
cal decisions, even under the most
intense situations.
Given the fact that regulated drug
manufacturers must perform valida-
tions, it is very important that this
understanding be shared throughout
the organization. Afirm derives little
benefit if a thorough understanding
of validation remains within the val-
idation department, and there is ab-
solutely no concept of the term within the department
responsible for approving the validation budget.
So often, validation becomes alienated from the
rest of the company due to a lack of thorough under-
standing. Why can’t the laboratory use the piece of
equipment undergoing validation? Why can’t the
facility be used before the laboratory has completed
analysis of the microbiological data? Why are vali-

240 Journal of Validation Technology


dations so expensive? Naturally, if the entire compa-
ny is fairly educated on what validation entails, less
time will be required defending validation’s actions.
Good understanding has to be disseminated
throughout the entire organization. Of course, it has
to begin with the group charged with performing
validations. In the end, it is up to the firm to realize
the importance of assuring that this understanding is
shared among the key groups.
2. Communication
One of the best methods of improving environ-
mental understanding is through communication.
Communication is essential for any activity that re-
quires more than one resource to complete. Hopefully
this point is understandable considering that conduct-
ing effective validations involve multi-departments.
• When is validation of unit xyz scheduled to begin?
• How many resources will be required?
• When do protocols have to be approved?
• At what sites will sampling occur?
These are typical questions that can best be an-
swered through communication. One of the keys to
proper communication is locating the right commu-
nication vehicle. Most organizations communicate
through one or more of the following methods:
• Conversations
• Memos
• Periodic meetings
• Training sessions
While adequate communication can be obtained
through either one of the above, the ideal environment
would have all of the above. The point is that some
communication is better than no communication.
3. Experience
A firm must have resources with solid validation
experience in order for their validation program to be
successful. Can the average person be expected to
perform open heart surgery without proper study/pre-
paration? More simply, can the average person be
expected to win a bike race if they have not yet learn-
ed to ride a bike? If one has not shouldered the re-
sponsibility of performing an Installation Qualifi-
Charlie Neal, Jr.
cation (IQ) on a pump, will they be able to execute
the Operational Qualification (OQ)? Well, this same
concept holds true for a person charged with plan-
ning or executing validations.
The point is that the more responsibility a person
has shouldered for validation, the greater his experi-
ence will be. Likewise, the greater his knowledge,
understanding and logic will be. For example, a sea-
soned validation resource, in the midst of completing
a validation, encounters a failure that will necessitate
validation to be repeated in its entirety. Working
through this series of events will undoubtedly provide
the resource with experience in dealing with failure
and resolving problems.
Now, is it reasonable to expect an inexperienced
staff to perform a solid validation? In most cases, no.
However, with proper coaching and consultation,
some successes can indeed be realized.
4. Cooperation and Focus
Why is there a need for cooperation in order for per-
sonnel to conduct effective validations? Let us first
understand the “multitude” of departments that some-
times interact during the course of executing validation-
Program/Project Management, Accounting, Validation,
Quality Control (QC), Project Engineering, Process
Engineering, Quality Assurance (QA), Metrology, Fa-
cilities, Regulatory, etc. It is safe to assume that these
departments have an array of priorities, and typically
they are not the same as validation’s.
Let us focus on the example of a professional bas-
ketball team. Their objective parallels that of a multi-
disciplined/inter-departmental validation team-both
strive for success. The assumption is that each team
member is critical to the overall success of the team.
Assume that both teams are in the fourth quarter or
final phase of their event-the basketball team in the
championship game, and the validation team execut-
ing the final event prior to initiating product com-
mercialization. If the center on the basketball team
loses his desire to play defense, and/or pass to his
teammates, how successful will that team be? The
same concept applies to the validation team. If some-
one fails to approve the protocol or to sample per the
protocol, the cost of validation will undoubtedly
increase. Why? Simply because more time will be
spent seeking approvals. Likewise, time will be spent
justifying and writing the explanation for why a
May 2003 • Volume 9, Number 3 241
Charlie Neal, Jr.

sample was not initially collected. Cooperation is • Investigate/acquire information

essential and critical. Therefore, each member must • Conduct meetings
be focused on the overall tasks, and willing to coop- • Plan
erate 100%. • Put the plan into words (protocol)
• Execute the plan
5. Resources • Troubleshoot and/or resolve problems
In reality, it does not matter how much knowl- • Summarize the effort
edge, experience, and understanding a firm has, if
they don’t allocate the proper resources for conduct- Consider how projects are funded within corpo-
ing effective validations. What do we mean by re- rations. Each department has to prepare an annual
sources? By resources, we of course mean personnel budget for anticipated expenses. It is very important
who will plan and execute, equipment on which val- that the anticipated costs are shared with upper man-
idations will be performed on, materials, with which agement to assure that ample support-or funding-
to conduct validations, laboratories that will perform exists. Now consider validation and the bulleted
necessary analyses, funding to pay
for the validations, and TIME in ❝So often, the wait for the receipt
which to perform validations. Val-
idations can often begin, but cannot of analytical results causes the
be completed if any one of these re- entire validation project to come
sources are missing.
As an example, consider an auto- to a halt. Why? Because
clave on which a new load configu- validations are based upon
ration requires validation. A window
has been created by the equipment the results obtained. ❞
owner (time, equipment), the owner’s
department has provided all the human resources activities listed above. From a corporate standpoint,
required (personnel), and the lab is ready for samples each one of these elements require time, and there-
(laboratories). However, the validation team has fore have an associated cost.
been advised that the laboratory does not have the re- Thus, it is essential that they are reflected in the
quired spore strips (materials) in inventory. Can val- validation budget.
idation be completed? No, since spore strips are
required in order to assess the efficacy of the cycle. 7. Plan
The same holds true for any resource required for A professional sports team cannot be expected to
validation. win the championship without a plan. Most of these
teams refer to their plans as plays. Without plays, a
6. Budget good offensive football team cannot hope for suc-
It is important to understand that a successful val- cess against another good team’s defense. For exam-
idation must be done to completion. Typically, it ple, if the quarterback does not know where his
should not be limited by a budget assembled by per- receivers will be, how often would he be able to
sonnel who have no appreciation for what is required complete a pass? If a running back did not know his
to successfully complete validation. Further, it is im- team’s blocking strategy, how many yards would he
portant to understand that validations cost money. A average per play? Per game? Per year?
rule of thumb has been that equipment qualifications, Bear in mind, that conducting validations within
which are integral parts of validations, are typically most companies will involve a number of depart-
10-20% of the cost of the capital equipment. Where ments and disciplines. These disciplines need a plan
do these charges come from? Typically, these charges in order to get good team synergy. Further, this plan
are related to the time to execute the following cost must be communicated in order to be accepted and
initiatives: successful.

242 Journal of Validation Technology


• When should the analytical laboratory receive
the samples?
• How should a deviation be handled?
• How will chamber temperatures be monitored?
• When will the first event occur?
• Will manufacturing assistance be required to
execute the validation protocols?
It is essential that the lead validation resource
know the answer to each of the above questions, and
assure that they are shared in pre-validation plan-
ning sessions.
8. Training
Training is essential for any successful valida-
tion. Even though the group charged with gathering
routine Water-for-Injection (WFI) samples from the
plant distillation system knows how to collect regu-
lar samples, chances are they will not inherently
know how and when to gather samples in support of
a new sample port. Thus, the need for training.
Typically, this training initiates within the validation
group. It is essential that the lead validation resource
for a given validation project initiate, facilitate,
coordinate, and/or communicate the need for
resource training. In some companies, the expecta-
tion is that validation resources provide training as
required by the validation event.
Actually, the requirement for training goes beyond
the act of mere teaching. The regulating bodies re-
quire proper documentation be assembled and main-
tained to serve as proof that key resources have under-
gone required training. Proper documentation should
minimally include employee identification, a descrip-
tion of the training course, and the date on which train-
ing occurred.
9. Standard Operating Procedures (SOPs)
SOPs capture activities that routinely occur within
an organization. Departments charged with abiding by
or following these SOPs must first be trained against
these SOPs. Many SOPs are typically the offspring of
a successful validation. In most cases, equipment op-
eration SOPs are drafted for use during the initial
phases of qualification. These SOPs often are not
finalized until after the equipment’s OQ event. A case
in point would be an SOP for the set-up and operation
of a new piece of equipment. Often, the vendor manu-
Charlie Neal, Jr.
als or the specifications will convey how the equip-
ment is operated. In the OQ phase, this information is
usually transcribed for use in the form of a draft SOP.
Once the OQ steps are completed, the result should be
an SOP that is finalized, approved, trained upon, and
implemented for routine use.
The expectation is that these SOPs are finalized before
the equipment is used to support process validation.
10. Solid Quality Control (QC)/Lab Support
During most validations, some laboratory testing
will be required. In most cases, this testing is handled
by the QC group. In most organizations, QC will
shoulder the responsibility to develop and validate
the analytical methods used. QC is also expected to
provide results in a timely manner. So often, the wait
for the receipt of analytical results causes the entire
validation project to come to a halt. Why? Because
validations are based upon the results obtained.
In addition, QC input is required during protocol
preparation. If the QC lab lacks organization, maturi-
ty, technical competency, appropriated methods, etc.
an initiative has to be undertaken to attain laboratory
support through a contract laboratory.
11. Solid QA Support
All validation resources may not be the best for ad-
hering to compliance procedures. It is therefore up to
QA to thoroughly police the protocols before, during,
and after execution.
This policing must be against internal SOPs and ex-
ternal regulations. The expectation is that QA will en-
force any relevant compliance issues, and will thereby
prevent an unwanted discovery by auditing bodies. If
an auditor uncovers a number of compliance issues, the
department that will often be held accountable is QA.
It must be understood that a good QAresource often is
not a resource that most other operating departments
would choose as their best buddy during working
hours. However, their value to the success of the or-
ganization’s validations must not be minimized.
12. Permission to Conduct Preliminary Runs
(Trials/Engineering Runs, Demonstrations, etc.)
Could one be expected to drive from Maine to
California without a map? Would a map exist without
some preliminary explorations? Why does an infant
crawl before walking? Why do they undergo a period
May 2003 • Volume 9, Number 3 243
Charlie Neal, Jr.
where they will make only one to three steps? With
time, they of course, progressively make more steps
until they ultimately learn to walk. Walking then be-
comes natural, and for the most part, faultless. When
a system undergoes validation, the desire is that its
operation is then faultless. Like walking, validations
require practice. Given the fact that validations are
typically expensive, it should be understood that any-
thing that would assure that the costs are minimized
would be an asset. Therefore, it is advisable that per-
mission be attained to perform some form of prelimi-
nary runs. These runs can be used to provide operator
training, to investigate values recommended by spec-
ifications or vendor equipment manuals, and/or to ex-
plore any limits proposed for validation.
These trial runs have to be factored into the vali-
dation budget. While each will bear a cost, the focus
should be the cost of the overall or entire validation
program. Consider the OQ effort. Assume that the re-
quisite specifications are generated, and the protocols
are then assembled and approved. During execution,
it is discovered that the specifications are incorrect,
and therefore, multiple deviations will be generated,
each requiring time to resolve. Each resolution will
minimally require QA’s approval. Each approval will
require time for explaining the “fix” to QA (and/or
other approving departments). Typically, the result is
a budget that is severely over spent and a black eye
for validation.
Abenefit of a dry run is less time and money spent
troubleshooting or explaining issues. This is true be-
cause the debugging is planned on the front end and
the impact to the manufacturing schedule should be
minimized.
13. Realistic Completion Dates
Typically, the expectation is that once the requi-
site time has been allotted to complete three (3) runs,
the system under validation is released and ready for
use. Unfortunately, this is rarely the case. For exam-
ple, a cleaning validation activity will require time
to complete the following activities, including:
• Training
• Conducting cleaning events
• Gather cleaning samples (swabs or rinse samples)
• Obtain the microbial challenge results
• Evaluate results,
244 Journal of Validation Technology
• Write conclusions
• Seek and attain post-execution approval
Therefore, it should be relatively easy to see that it
requires much longer than the three, basic runs.
This is where a Gantt Chart or other time manage-
ment tool is assembled. Validation resources typically
provide input on validation tasks. The firm must un-
derstand that this is often a lose/lose situation because if
the (validation) planning resource is overly optimistic,
disappointment will result when the completion date is
not met. Oftentimes, commercial campaigns are plan-
ned, based upon the projected completion date. These
campaigns may involve contractical commitments. If
the dates are not met, money will be forfeited.
If the resource is overly pessimistic, chances are
that the environment will not be ready to react when
validation is completed well before the projected date.
In this case, campaigns may not be pursued in a time-
ly manner, and therefore, the opportunity to earn
money may be lost. Either one of these extremes
causes some degree of disarray. Thus, it is the respon-
sibility of the lead validation resource to accurately
plan, communicate, and realistically reflect the time
required to complete validation.
Conclusion
Validation has been, and continues to be, greatly
misunderstood after approximately four decades.
Thirteen remedies have been discussed that can help
make validations more successful within any organi-
zation possessing a desire to be compliant with the
regulatory agencies. While some of these tools may
appear to be insignificant, all are necessary. It is there-
fore important that firms seeking to properly execute
validations, conduct a self-assessment to determine
which of these tools exist within their organization,
and which of these could use some form of improve-
ment. Once this self-assessment has been completed,
the firm can then take the necessary steps to bring
about an improvement in the manner that validations
are conducted. The time required to affect change
within the organization will be dependent upon the
amount of interest that exists within the corporation’s
upper management team. This is, after all, the team
that is ultimately responsible for allocating and fund-
ing validation resources. ❏
 Charlie Neal, Jr.

About the Author

Charlie Neal, Jr. is the Equipment Validation and
Requalification Manager for Diosynth-RTP (an Akzo
Nobel company), located in Research Triangle Park,
North Carolina. He has been involved with valida-
tion for over 22 years, and has authored articles for
both the Journal of Validation Technology and the
Journal of cGMP Compliance. He can be reached
at 919-678-4387.

Article Acronym Listing

IQ: Installation Qualification
OQ: Operational Qualification
QA: Quality Assurance
QC: Quality Control
WFI: Water-for-Injection
SOP: Standard Operating Procedure

May 2003 • Volume 9, Number 3 245