Validation Without Tears Getting Started
Validation Without Tears Getting Started
Validation Without Tears Getting Started
Getting Started
By Tanya Fletcher & Melvin R. Smith
Almedica Services Corporation
❖
A
lthough there are many Why Validation?
articles and treatises on the ❝This article is
various aspects of val- For discussion’s sake, let’s say
idation, very few, if any, address devoted to the your company has been finally
the people who are getting the job forced to commence validation
done. The validation person often
subject of
activity. Forced is the operative
find themselves in a hostile envi- getting started, word today, not only because of the
ronment faced with overwhelming changes in the new cGMPs and
demands, unrealistic expectations, organized and CFR’s, but also because of the in-
and expected to accomplish tasks creased sophistication and know-
within a totally impossible time launching ledge in the field. Many senior field
frame. This is often coupled with validation staff of the FDA (the enforcement
an almost total lack of support and compliance staffs) have recent-
staff, appropriate test equipment, activity.❞ ly retired and moved into senior
and inability to identify the mov- QA industry staff positions. Their
ers and shakers who can lend sup- experience and training have increased the auditor
port in accomplish tasks. inspection acumen, and validation status is at the top
Often too, this individual(s) finds a culture ini- of their list.
tially hostile to their activities, not understanding, Validation activities, as with all quality activities,
nor accepting that regulatory and cGMP valida- must be supported from the top. Every level of man-
tions are often requirements. Validation is often agement must permit and support your activities.
seen as an intrusion on production, and something Validation is the company’s responsibility, not an
extra to do, in addition to the normal workload. individual, or department.
Since validation efforts do not initially produce
any additional profits, they may be seen as a cost Whom Do I Report To?
center.
Often, the problem of, “but we’ve always done it Interestingly, whom the validation person should
that way” inertia is seen as an obstacle that must be report to is of great interest, and even subject to con-
overcome. When the firm sees how that new troversy. Should it be QA? Regulatory affairs?
methodologies can accomplish goals, resistance will Operations? President of the company?
crumble. More staff will want to get involved, and Because of various levels of bureaucracy that can
climb on the validation bandwagon. exist in a firm, and the Byzantine reporting struc-
This article is devoted to the subject of getting tures that may exist, the validation person might
started, organized, and launching validation activity. want to have defined, in writing, to whom he/she
produce any major benefits. The same goes for The Journey
attacking those types of validations which are near
and dear to your heart, and which in other situations, The first thing you need to have is a master valida-
you may have done well. As this is a new situation, tion plan (MVP) in place. Although there is no regula-
let your superiors outline, with your input, a reason- tion or guideline that requires this document, it is cru-
able prioritization. Remember, your supervisor cial. With the master validation plan in hand, one can
needs to demonstrate results to the next reporting then approach the reporting supervisor for assistance in
level. Furthermore, your supervisor probably knows developing strategies, priorities, as well as budgeting.
the firm better than you, knows what the short and The best MVP and priorities, however, are sub-
long term goals are, and knows the department’s role ject to changes and other exigencies existing in the
in meeting them. organization. This requires flexibility, so don’t be
too rigid against changing the MVP. Remember, you
Get The Proper Training are working for a commercial firm, where facility,
computer system, and equipment changes and addi-
It would be nice if there was a single format, and tions are commonplace.
single approach, to validation activities. Sadly, there The master validation plan should not be viewed
is not. But there are guiding principles and general by management, or presented by the validation staff,
approaches that can help you sort out what you have as causing interference in work flow, or other nega-
to do, how you’re going to do it, and what your work tive connotations. It should also not be seen as being
product will be. intrusive on other department’s turf. The plan should
Therefore, besides education and training, love of view validation as codifying, rationalizing and legit-
detail and documentation, you must be able to write. imizing the current equipment, methods, processes
Written communication skills are developed by and products for all to see and understand.
practice and use. You must communicate with all Once you have completed a master validation plan,
employee levels. Succinct writing is a skill to be listed your job priorities, realize a possible time line
developed. Not only must data be accumulated, may be altered by exigencies within the firm, with a
entered, analyzed and reviewed, but trends, forecasts promise of support and backing, you are ready to start.
and proof statements must be able to be drawn or At this point, you need a format to do the work.
inferred from them. No one format works for every task, but there are
Next, it would be useful to hone your valida- some general guidelines to follow.
tion skills by registering for courses on basic val-
idation principles. Join professional organiza- Format
tions, and order journal subscriptions to organiza-
tions that specialize in addressing validation For the most part, when dealing with equipment
issues. A deep working knowledge of all cGMPs, and computer system validation, one relies upon the
ISO9000 series, and other laws and regulations IQ-OQ-PQ (installation qualification, operational
must be possessed. You are operating not as an qualification and performance qualification). As a
isolated worker, but rather as part of the larger guideline, IQ is everything you do before powering
system professionally, as well as company-wise. the equipment or system. OQ is what you do after you
There is much help out in industry. Seek it out. power it to determine parameter limits of operation,
Network. and demonstrate that the equipment or system works.
Now that the skills, knowledge of your milieu, PQ is where the equipment or system software is sub-
your reporting strategies and knowledge of the jected to the stresses of “everyday” production use.
organization chart are all in hand, and knowing The documents or protocols must be pre-approved
where you want to get to (validated products, before executing them.
processes, and equipment) let us see how we will For equipment, computer system validation and
take the first step in validation and what you will other validations, the best approach, and the one
do on the journey. most easily executed is the “fill in the blanks” pro-
Figure 1
Approvals
Document Prepared by:
Printed:
Signature: Date:
Approved By:
Individual Department(s):
Printed:
Signature: Date:
Quality Assurance:
Printed:
Signature: Date:
tocol. Here you determine what you have to do, and protocol and determine a tentative schedule for com-
have it reviewed and approved by management and pletion. Your schedule is dependent on details, such
QA. They must sign off before you perform the as testing time and turn-around of laboratory results.
study (see Figure 1). They sign off in designated Also, allow downtime on equipment or processes.
approval sections of the documents individually. Proceed step-by-step through the protocol and
It is best to construct the protocols based on user record the results. Any noteworthy observations
manuals, drawings and formalized design specifica- should be documented in your protocol. If a test fails,
tions. The needs of your firm, and intended use also this should be noted as a deviation. A deviation is
dictate the content of your documents. A well con- where you report those findings or results which are
structed protocol is the easiest one to execute. Take at variance with what you expected or predicted. This
the time and expend the effort here. In fact, construct- may be anything from a constant tripping of electric
ing the format, will be the most time consuming. breakers, to negative pressure in your clean room.
There are many articles and courses available that Perhaps, inadvertently you discover that the capsule
detail how to go about writing a validation protocol filling machine has difficulty counting black colored
for equipment, computer systems, cleaning, facility, capsules. A distinction must be made as to what devi-
product and process validation. Research them and ations are critical and non-critical. Critical deviations
find the style you are most comfortable with. affect the operational status. Deviations must be
reviewed and approved by appropriate personnel. For
Execution an example of a formal deviation form, see Figure 2.
With the protocol completed, and deviations
Armed with a well thought out, written and ap- addressed, you are ready to summarize your find-
proved protocol, you are ready to execute the proto- ings. Your summary should compare the goals that
col and record results. Carefully read through the were set out in the protocol against the results.
Figure 2
By: Date:
Action plan approved by: Date:
Date of implementation:
Person responsible for implementation:
recovery studies must be performed. Therefore, it is tic, temperature or humidity controlled conditions? If
necessary to employ the services of a laboratory. It they do, then these will be the critical aspects of your
is strongly advised to do research via other profes- facility commissioning. If the facility is aseptic, the
sionals, courses and articles before embarking on a HVAC system must be designed to effectively filter
cleaning validation program. Laboratory costs are clean air and remove dirty air. If aseptic, the cleanest
expensive. area must have the lowest traffic.
Once recovery studies and sampling plans have As with equipment validation, adequate test
been researched and performed, a cleaning validation equipment must be utilized. To continue the example
protocol can be written and subsequently approved. of an aseptic area, test equipment, such as a particle
Cleaning validation typically is performed for three counter, or manometer need to be utilized.
lots or batches of the same product in contact with Equipment, such as a DOP detector, can be used to
the same equipment. After the typical three lots or determine the efficiency of a HEPA filter. As stated
batches are complete, and results are returned from in the previous section, test equipment needs to be
the laboratory, a summary report can be written. As initially and then continually calibrated in a sched-
discussed, the summary should include results and uled manner.
any deviations found. The report should express if
the validation was successful or not, based on the Product Validation
goals set forth in the cleaning validation protocol.
In this type of validation, a history of product
Facility Qualification/Commissioning development must be developed. It is initially
assumed the equipment used and environmental con-
Commissioning involves identifying and verify- ditions are validated. For example, in experimental
ing the facility floor plan, utilities, maintenance pro- batch #1, we mixed x with y in the following amounts
gram, security/alarms system, and back up systems. with a total weight of, and kneaded it in a plastic bag.
The existing facility and support programs must be After that step was completed, we attempted to tablet
compared against design specifications, drawings it, and it fell apart. We noted the results and destroyed
and standard operating procedures. the mix. We then proceeded on to experimental batch-
Floor plan verification involves documenting es two through as many as needed. Your final experi-
walls, ceilings, floor finishes, room dimensions and mental batch will yield the desired results, and should
lighting. This verification is based on drawings and be ready for initial scale-up.
design specifications. Utilities verification will veri- Also included is a discussion of the final compo-
fy use points for electricity, water systems, com- nents, their sources, reasons for inclusion and intrin-
pressed air systems and HVAC systems. “As-found” sic quality (USP, NF, etc.), as well as their relative
information should be compared against design mixing proportions and contents.
specifications. Maintenance and routine testing of The final product must be described in its physi-
these systems should also be documented. The oper- cal, chemical and laboratory test results. The equip-
ation of back-up systems must be documented, and ment (validated) must be described, as well as
tested for response time. required operating parameters.
Alarm systems must be verified for entry, as well The ultimate goal is describing a validated prod-
as out of range environmental conditions. For exam- uct based upon source and quality of components,
ple, if a humidity controlled room rises above its method of mixing, processing and blending, final
specification of 50% or less relative humidity, processing to get it into its dosage form testing to
appropriate personnel must be contacted. This alarm assure meeting its pre-determined required specifi-
and response system must be verified and docu- cation, and capability of being scaled up and manu-
mented on a scheduled basis. factured on a routine and repetitive basis.
When planning to commission a facility, it is criti- Once again, we work with a predetermined and
cal to identify the crucial processes carried out in the signed off protocol, which is then filled in, and a
facility. Do the processes in the facility require asep- summary is written. The history of development is
one of the major differences, as will be a discussion responsible for documentation, retesting or even
of the laboratory testing. But it is basically the same revalidation.
methodology used; plan, write, approve, execute, Whomever you hire, it is important to assess their
write, and approve. technical proficiency, and capabilities to perform
your validation tasks.
Process Validation
Conclusion
This is often a variation of equipment validation,
coupled with a product validation. Process validation When we started on this journey, the aim was to
assumes all equipment, process rooms and storage remove the mystery of validation, and encourage
areas are validated. In order to perform a successful staff not to be afraid of it. Validation is here to stay,
process validation, the process must be broken down and its requirements will continue to expand through
into discrete steps. Critical parameters of the process industry.
steps must be determined and then tied together. A Validation is not difficult when critical equip-
process validation typically involves three lots of the ment, systems, processes are identified, broken
same product exposed to the same equipment and down and prioritized. Once you determine your for-
process. Once again, approve the protocol, fill it in and mat, focus on critical content, and get input from
summarize. Document any deviations. Where required, individual departments as well as QA, this will help
determine a set of laboratory measured parameters. the validation run more smoothly.
Once you have a basic understanding of valida-
Things To Remember tion and its role in industry, you will embark on
effectively determining your company’s needs and
In conducting validation you have to decide on successfully fulfilling them. ❏
many things which are currently taking place, as well
as future considerations, such as:
■ Change control and distribution notifications. The opinions expressed in this article are strictly
■ What triggers revalidation? those of the authors. They in no way represent the
■ SOPs that legitimize what you are doing, and views of Almedica Services Corporation.
what is required to maintain a validated state.
■ Training requirements and re-training needs.
■ Where is the library of manuals (operator,
repair/maintenance, schematics) located?
■ When will you periodically review the state of
validations done? A recommendation might be
two years after the original or restudy was done.
Staffing