PHARMACEUTICAL VALIDATION.



Pharmaceutical Validation Introduction.

Bio-Med and Pharmaceutical Validation is more than just raising an IQ and OQ. It requires an understanding of the the overall quality requirements as detailed in 21 CFR Part's 820, 211, 210 and 11. The process starts at the procurement stage with the VP, and continues through the URS - DQ - VRA - IQ - OQ - PQ and is achieved with the completion of the process qualification (PQ). The equipment must then be controlled throughout its working life by Change Control, which is there to guarantee that its validated status is maintained and never compromised. Incorporation of any updates or modifications requires a thorough understanding of both the business processes being supported and the associated regulations GLP - GCP - GMP - GDP.


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

1

Operating

Systems

Record Version

2

Measuring Devices bespoke software.

Record Configuration & calibration

3

Configurable

Packages

Review supplier & validate functionality and any bespoke code.

4

Large Configurable Systems

Audit supplier, validate system functionality and review code IAW full life cycle requirements.

5

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.

This Pharmaceutical Validation graphic depicts the documentation required for revalidation.
This Pharmaceutical Validation graphic depict the document flow for relocation activities.



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 can’t be started unless there is an approved User Requirements Specification (URS), in place to define the requirement that are to be validated.


This Pharmaceutical Validation diagram illustrates the sequential flow of documents that the regulators expect.

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 company’s 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 company’s 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.


This graphic represent the relationship between the pharmaceutical validation documentation train.

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 adulterated.


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 don’t.

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 don’t 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.



PHARMACEUTICAL VALIDATION



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SOP for Spreadsheet Creation.

Why does something as simple as a spreadsheet figure in so many regulatory citations? Good question; and at times a difficult one to answer. When you ask a group of compliance personnel the same question you will be informed that Excel cannot be validated because it does not seal the original copy (of the spreadsheet), allows the original to be modified and has an audit trail that can be disabled. All true, but none of these problems interfere with your ability to validate that the spreadsheet is fit for purpose. They only preclude you from using the spread sheet as a compliant repository for any data that has to be store in compliance with 21 CFR Part 11.
If the spreadsheet is signed off and dated by the user, their supervisor and QA, it becomes regulatory acceptable data stored in hardcopy, and Part 11 does not apply.
After numerous requests for this, we have launched our brand new SOP for Spreadsheet Creation to cover these and other known target points that the regulators consistently hone into as soon as they find that spreadsheets are being used. Use this Spreadsheet Creation SOP to ensure that you create spreadsheets that are validatable. Then use our spreadsheet validation pack to validate them.

SOP for Spreadsheet Creation. -- $125.00

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SOP Equipment Validation.

The SOP for Computer Equipment Validation continues to be an extremely popular document. This document leads you through the validation process, from the URS to the final P2Q.


Purchase your copy now at Special Price of $22.00.

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Validation Risk Assessment (Issue11.) -- $125.00

The Risk and Part 11 Validation Risk Assessment (VRA) protocol is becoming the most important document in the validation train. The VRA reassures the regulators that you have looked at specific equipment functionality and considered the appropriate level of validation that is required. You have also considered various aspects of its use and the implications of any malfunctions. From the results of this exercise the scope of all validation activity can and must be justified. This is a robust and simple to execute document, one that will lead you through the process and deliver a result that can be used as the foundation for your validation activities.
This VRA now includes the assessment table for categorizing and documenting the new 21 CFR Part 11 guidance ruling on what predicate data must be stored in a Part compliant system, along with the new broadsheet to establish your new database of part 11 records. (now mandatory).

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Equipment combined IQ/OQ/PQ Protocol.

This combination protocol has been produced in response to several hundred reader suggestions we received in our ‘Suggestions Section’. It has been carefully designed to make it the preferred choice for Process and Laboratory stand alone equipment. It is interactive, easy to use and suitable for all mixes of equipment with and without software.
The IQ section establishes documented verification that key aspects of the equipment adhere to approved design intentions and that the recommendations of the manufacturer have been suitably considered. The OQ section establishes that there is documented verification that the installed system functions as specified and that there is sufficient documentary evidence to demonstrate this. The PQ section gives documented verification that the equipment performance in its normal operating environment is consistently exactly as specified in the URS.

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