WHAT IS VALIDATION?.

Bio-Med and Pharmaceutical Validation can be very simple and straight forward, and then
again at times, it can be complex and difficult. A great deal depends on the contents of the
company Corporate Quality Manual. This is where all company approved bio-med and
pharmaceutical validation regulatory Practices and Procedures must be defined and documented.
Failing this being in place, the VMP and VP must document the validation procedures that the
company has decided are required. The protocol writers and executers must then follow these
instructions.
It can; at times, be almost impossible to split such systems into computers and or equipment;
therefore the system must be considered, taking note of the specifics of each and the overall
functionality achieved by the system. While recognizing that the diversity of software, as defined
in GAMP 4 & 5 is vast, you have to remember that the typical operating systems (windows or
similar) because of the vast number in service, are taken as standard, and do not require to be
qualified. Therefore when you come to application programs; that run on these standard
operating systems (STS), your system qualification effort does not have to include the STS; just
the application program itself.
Gamp
Class

Category

Pharmaceutical Validation Scope

Operating
Systems

Record Version

Measuring Devices
bespoke software.

Record Configuration & calibration

Configurable
Packages

Review supplier & validate functionality and any bespoke

code.

Large Configurable
Systems

Audit supplier, validate system functionality and review

code IAW full life cycle requirements.

Systems Specifically
written for Owner.

Audit supplier, validate all code IAW full life-cycle

requirements.

Contentious Points.
The EU GMP Annex 11 on Bio-Med and Pharmaceutical Validation of equipment, requires that
there should be "adequate alternative arrangements for systems that need to be operated in the
event of a breakdown". These arrangements should provide for alternative workaround
procedures to be implemented and followed, to replace the absent system functionality and allow
safe

continuation

of

business

during

the

failure.

Regulators, and internal / external auditors, require evidence that Business Continuity Plans have
been created and rehearsed, including records that the alternative processes have been suitably
documented and personnel adequately trained. Companies should be able to demonstrate that
they can ensure that critical services and processes can continue, that the restoration of
workforce, facilities and equipment occurs in a timely fashion and that there is a timely
resumption of essential business functions.

occurs in a timely fashion and that there is a timely resumption of essential

business functions.

DEFINE VALIDATION.
In pharmaceutical validation regulators require documents to be based on agreed and approved
policies and procedures. That means you can't start writing an Installation Qualification (IQ),
without having an approved Pharmaceutical Validation Plan (VP) in place to scope the IQ

activities, and of course the VP cant be started unless there is an approved User Requirements
Specification (URS), in place to define the requirement that are to be validated.

Management Control.
The VP, or in major or new systems, VMP, should be the document that starts the bio-med or
pharmaceutical validation process. The VP/VMP must give management's reason for requiring
the validation task, along with documenting the justification and scope. It must further delegate
responsibilities for all the qualification activities, and set the scope of these actions. At this stage
a Risk Assessment (VRA) should be used to set this scope. Once these high level decisions are
made, the VP must be signed off as a working document that has now set the companys
validation requirements for this piece of equipment.
Once proposals to satisfy the URS have been received, they are required to be qualified by the
execution of a Design Qualification (DQ), which must confirm that the design proposal, if

proceeded with, will satisfy the requirements as detailed in the URS. Personally, I cannot over
emphasize the importance of the DQ. I have seen some horrendous blunders perpetuated by
some really clever dedicated individuals, just about all of these blunders would have been caught
at DQ level, if there had been one.
Protocol authors can now write the IQ OQ P1Q P2Q documents, in accordance with the
companys approved practices and procedures. Whether Performance Qualification P1Q and
Process Qualification P2Q are both required depends on your VP. A machine can have a range
of settings and functions, perhaps you only want to validate one process perhaps you want to
validate the entire functionality - perhaps your product is too expensive to waste and you intend
to use a placebo to validate the actual process settings.

Document Justification.
There are many consultants that would argue; that you must start at User
Requirements Specification level (URS), since your P2Q is based on verifying that
the URS has been satisfied. This is where the justification for your approach must
be documented in the VP, without the end user documenting what the equipment is

required to do (the exact measurable process and specifications), how can you
scope a P2Q?

When a P2Q that is carried out using equipment that has not been the subjected to
the above procedures, (or a very near justified equivalent), it has no standing and
all product subsequently produces would be considered by the regulators, as
adultered.

Good Manufacturing Practices.

CAPA remains the single most cited subject in the Bio-Med and Pharmaceutical industries, with
50% of FDA warning letters being concerned with CAPA problems.
Why does this not surprise me? Because having worked in the industry for many years I I have
worked with many companies who paid scant regard to the subject. Yes, there are companies
around who do the job properly, but according to statistics, half dont.
I think most persons who have worked in the industry for any length of time, have seen the
occasion when production output has taken priority over the proper investigation of customer
problems and or complaints.
The catch-22 is always cost, is it more cost effective to have a compliant CAPA system, that is
not only keeping you compliant with regulatory requirements, but also producing data that
enables you to reduce customer complaints and quality deviations; or is it more cost effective to
pay lip service to CAPA requirements on the bases that you dont have many customer
complaints.
We have just released a CAPA AUDIT document, which should be used to verify that your
CAPA system, whether manual or electronic is being used in a compliant manner.
Our most popular purchase still remains the Package 3. This contains all the protocols and
associated procedure documents required to carryout a validation task.

Our most common technical enquiry is still the question asking; Does a validated piece of
equipment, that is moved from one area to another, require to be revalidated, even if the move is
only across a room.