Sharing experience, tips and examples for

getting through the pharmaceutical

qualification nightmare
July 6, 2020

At Sensum, we interact with many pharmaceutical quality assurance teams on the topic of qualification and validation.
Credit: Sensum

B y Dr Miha Možina

Buying equipment does not also give you permission to use it in a pharmaceutical
environment; quali cation and validation are still in your way. Their primary goal is
not to prevent you from using your equipment or to increase its costs, but to help
you ensure consistent quality of nal products.

At Sensum, we interact with many pharmaceutical quality assurance teams on the

topic of quali cation and validation, as we develop and provide solutions for
automatic visual inspection of end products, which need closer supervision by
quality assurance than quality control systems. For more than 15 years, we have
experienced different quali cation scenarios, which allowed us to identify several
good practices. In the following paragraphs, you can nd practical insight into the
process of quali cation with some useful tips that might help you with any
quali cation project.

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First things first; What is validation and what is qualification?

Validation is a larger concept than quali cation and is related to processes such as
the manufacturing process. It can be simply explained as a systematic approach
that checks and helps processes to have expected and consistent results. Validation
does not involve only equipment, but also various supplementary systems, software
and people, which are part of the process.

Validation breaks down to several activities and one of those is the quali cation,
which is related to introducing systems to the process. The job of quali cation is to
make sure that a particular system is meeting regulatory requirements, industry
standards and expected performance.

The (in)famous V-model

The extent of quali cation depends on the complexity of the equipment. For
example, the quali cation of an intermediate bulk container should require less
effort in comparison to a visual inspection system. We shall take a look at the
quali cation of a con gured computerised system, which covers all typical
quali cation steps. The quali cation procedure for the example is presented in the
V-model below with two phases, speci cation and veri cation.

Specification phase: from URS to DQ

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User Requirements Speci cations (URS) are prepared by the nal user who lists
their expectations and requirements for their process. URS is a basic document that
streamlines the entire quali cation process.

SENSUM TIP: At Sensum, as a supplier, we come across many URS. Most of the URS
documents have many requirements with 20+ pages, but actual requirements relevant
for the speci c project are written in barely one or two short points. This happens
because the URS are prepared from a template or from another project’s URS without
critical modi cations and corrections. URS has an impact on the whole quali cation
procedure and cutting corners here is not helpful. For example, we recommend to
remove general requirements that are not applicable; such requirements will invoke
unnecessary discussion or even extend quali cations. Furthermore, do not forget to
add important data. Consult your production experts so the requirements will cover
the actual process needs, such as throughputs, quality of operation, ef ciency, waste
generation, machine settings, part assembly, downtimes, cleaning, calibration,
maintenance, skills required to use the machine etc.

After the URS are agreed and approved, they are typically shared with several
potential suppliers. Each supplier replies to URS with a quote, as well as Functional
Speci cation (FS) documents, which are dif cult to read and often impossible to
link with each URS point.

SENSUM TIP: For faster evaluation of suppliers’ offers, make room in URS document
for their comments and name the new column Functional speci cation, because, in
fact, their comments are functional con rmations and descriptions of their machine.
In this way, you can completely avoid reading through the supplier’s design
documents.

Once the suppliers provide their feedback, it is time for Design Quali cation (DQ).
As mentioned in the introduction, the scope of quali cations depends on the
system’s complexity. In this example, the DQ has three steps – proposal evaluations,
risk analysis and setting up tests, which sounds problematic with a huge amount of
work, but with proper setup, it is manageable.

In the rst step of DQ, the user has to check if the supplier meets the requirements
described in URS. Needless to say, if a supplier cannot meet all requirements, talk to
them and nd acceptable solutions for both or choose more appropriate

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supplier/solution. If you appended URS with FS as proposed in this article, a major
part of the DQ can be done by commenting back to the supplier’s comments.

SENSUM TIP: Simply do DQ within the URS/FS document by justifying your decisions
as in the example.

The second step of DQ is risk analysis and is started only after the rst step is
agreed between the user and the supplier. The outcome of risk analysis is risks and
speci cations, which need to be tested and addressed during quali cations.

SENSUM TIP: Risk analysis is a dif cult task, especially if the technology is new for
the user. Do not try to fabricate a possible risk for each URS point. Use experience and
common sense. If risks are too hard to de ne for any reason, the supplier should be
able to help you with risk analysis. The supplier knows the solution in-depth better
than anyone.

The last step of DQ is setting up quali cation tests for the veri cation phase of the
V-model. The tests should check whether the supplier is providing everything as
agreed and should address any risk that was above the risk threshold.

SENSUM TIP: Supplier’s IQ/OQ document will include tests for most of the required
points and risks. Check those tests rst before starting to set up any new tests. Also,
try to justify general requirements and risks with functionality to simplify your
quali cation protocols and minimise redundant testing. As an example, let’s assume a
risk: “A camera in the inspection system is not working.”. Do not make a special test to
check, if a camera is installed, connected to power and is working. Assign the risk to a
general test, such as “machine start-up”, which you will do anyway, and justify, that
you could see live images on HMI after start-up, and therefore, the system has a
functional camera. In another example, let us now assume a user requirement on
audit trail: “All actions on the machine must be recorded in the audit trail.”. Don’t
make a special test “check audit trail”. Try to assign the requirement to any
operational test, where batch report with audit trail will be checked for any other
reasons.

The nal result of DQ is Traceability matrix, which links risks and requirements
with tests.

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SENSUM TIP: Traceability matrices are known for many things. To save the project
team’s time is not one of those things. The challenge is to make connections between
URS, risks and tests clear and as simple as possible. By experience, there will always
be more URS points than risks in number. For that reason, assign URS points to risks
and not vice versa. Some URS points might even go un-assigned, which will only
indicate that un-assigned URS points are not risky for the project.

Verification phase: Finally, the IQ, OQ and PQ

When the speci cations phase is nished and the supplier is ready for the
installation, the veri cation phase begins. The user and supplier will follow IQ/OQ
protocols and the user will conclude quali cations with PQ.

SENSUM TIP: User and supplier should agree on the exact protocol and scope of tests
during DQ to minimise making up new tests during the quali cation, which is risky
for both parties.

IQ/OQ is typically done twice. First, it is done at supplier place as part of factory
acceptance tests (FAT). During FAT, any changes to the system due to requirement
changes (oh, those happen often) or due to possible deviations are not as expensive
as later, when the system is outside of manufacturing facilities.

SENSUM TIP: FAT is usually the user’s rst experience with the machine. Spend time
on OQ as much as possible, because OQ consists of tests, where the machine is
performing its job. It is hard to imagine a worse deviation as safety or functional
deviation. However, IQ is still prerequisite for OQ, so try to get it done as quick as
possible by only doing necessities and by skipping more administrative tests with
“N/A at FAT” or “Not risky, to be tested at SAT” to get to OQ as fast as possible.

Second, IQ/OQ is repeated with the same products after nal installation at the
user’s site as part of site acceptance tests (SAT).

SENSUM TIP: Send the nal user (operators from production) to FAT / SAT. If
operators perform the tests, FAT and SAT become very ef cient training at the same
time. In addition, try to make operational tests from OQ feel like real operation by
including tests for the set-up of hardware and software, tests for feeding/discharging,
tests for long term operation, performance evaluation, waste generation evaluation,
throughput checks and downtime tests, such as cleaning tests and

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assembly/disassembly tests. OQ experiences will be highly welcome when preparing
for PQ.

Performance Quali cation (PQ) is performed by the user after a successful SAT. The
user should have prepared a Standard Operation Procedure (SOP) and follow it
during the PQ. Products made/processed at successful PQ can be already used
commercially.

SENSUM TIP: The supplier can help you optimise your SOP, which will be used for
many years. Optimisation and modi cation at this early point will improve the
success rate of PQ and will improve the success rate of all later runs.

Download URS, Risk analysis with traceability matrix, IQ, OQ examples from the link
in the company logo at the beginning of the article.

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