10 steps to consider before qualification protocol execution

Self Inspection (internal audit) Training

10 steps to consider before qualification protocol execution

Last week, my colleague Kate Wild wrote an interesting blog on GMP SOP writing, and it prompted me to think about how we weoin hanley technical manager pharmoutrite, review, approve and execute qualification and validation protocols, so all about qualification protocol execution.

In essence, an approved protocol is used to record the relevant details from the successful testing of a facility, system, equipment (termed as “FSE”) or a process, to ensure that it is “fit for use”. Sometimes the protocol execution does not go to plan. To avoid some basic pitfalls, ask yourself these 10 questions before putting pen to paper:

1. Is the protocol ready for approval?

Sometimes a protocol is rushed through the approval stages to meet project timelines. Proper planning and allotted time to effectively review the protocol against the specification is key to achieving a “right first time” approach in protocol generation.

2. Is the FSE operationally ready and are all processes well understood?

If after protocol approval, items such as operational parameters and settings are still not fully understood, protocol execution should not begin. Qualification and validation stages are not the time for trials, development and investigation.

3. Is the executor suitable to carry out and document the work?

It is possible that the protocol executor has not been involved in earlier stages of design, FAT/SAT and/or commissioning. The executor may also be a vendor/supplier who arrives on your site just for execution. If so, the execution should involve input and support from all Subject Matter Experts (SMEs), as applicable. The executor should have a clear understanding of the Good Documentation Practices and be appropriately trained in all applicable procedures.

4. Does the executor understand the supporting Quality Management System (QMS)?

A vendor/supplier may execute the protocol for you, and may use their documents. This is acceptable, but all parties need to be clear about the QMS procedures that need to be followed before, during and after execution. The applicable SOPs generally include management of deviations, change control, documentation requirements, reporting and training, to name a few.

5. When will the protocol be effective and ready to use?

Depending on site procedures, the protocol should be issued and effective when the FSE or process is ready to be qualified. Time should also be allowed to check prerequisites and carry out training on the protocol, as applicable. Control on the issue, use, tracking, copying, distribution and storage of the protocol and associated documentation should also be defined in a site procedure.

6. Can I bring my protocol and the items I require for testing into the cleanroom?

Check and follow your site procedures. When working in Grade A or B areas, cleanroom paper should be used for the protocol as it generates less particles. All items brought into a graded room should be cleaned/sanitised accordingly, and should not be a source of contamination.

7. What do I do if a page of my protocol gets damaged or lost during execution?

Procedures at your site should provide instruction for these situations. For example, if a page has been water damaged, the QA department may decide to keep the original document, but allow the executor to raise a deviation and re-print the page and re-execute the step. If a page has been lost and it contained data that cannot be verified, the protocol step must be re-executed.

8. What if I encounter protocol errors during testing?

It is beneficial to have a procedure that categorizes the type and criticality of protocol non-conformances. The procedure could categorise errors as “minor” (typographical error) and “major” (incorrect acceptance criteria/acceptance criteria not met) at its most basic, but also include instruction on how to determine the impact of the error, the root cause, and the corrective & preventative actions, as applicable.

9. Once I finish protocol execution, when can I move to the next qualification stage/phase?

Qualification progression approaches differ from company to company. For example, it may be applicable to move from Installation Qualification (IQ) to Operational Qualification (OQ) based on a number of tests being completed, but the protocol or associated report may not be approved. Progression should be detailed in the Site Validation Master Plan and applicable qualification & validation procedures, and comply with local regulations.

10. Will my protocol be acceptable to show to an inspector?

If the protocol was executed and approved correctly, meeting all of its acceptance criteria and in accordance with GMP, you should be confident that it will stand up to scrutiny by an inspector. After all, that is why you considered the 9 steps above before it was executed. All of the evidence gathered during the testing should be attached to the protocol in a logical format, and should not be attached to the associated report. The report should stand alone as a clear and concise document that summarises all of your good work. This report document should be presented during an inspection, unless the protocol is also requested.

(4) Comments
  1. A great blog.
    Further to item 4, it may also be a requirement to officially train the vendors/suppliers on your qualification related SOP’s if they will be performing validation execution. Training records for all parties involved with validation may need to be presented should an auditor request them.

  2. Hi Eoin,

    One point I would make is for the drafting of the protocol itself. The approach to drafting the protocol should also take into account that it may/will be reviewed during a regulatory inspection and therefore the purpose, scope and test descriptions must be clearly defined so that the intent of the protocol is clearly understood during the inspection which may be some years after the protocol is executed.
    With this in mind the aim should be to have a good auditable package with the protocol, results and test evidence clear as to the intent of the protocol and each individual test performed. The author must keep this in mind when drafting the protocol, to write the sections in a manner so that others could complete or re-execute the protocol as intended is a good approach for protocol writing. In my experience this will lead to a better definition of the purpose, a clearer scope section and more clearly written test descriptions.
    If the protocol can be understood by someone outside of the qualification activity and not just the author then it should still remain as a good audible package during an inspection years after its execution.


  3. Just to add: Vendor Qualification Documentation should be under control, Staff should be trained, SOP written, equipment should be calibrated, P&ID ready…

  4. A good blog. Very concise and to the point. This could serve as a good guide for those looking to perform qualifications. Something that I feel people may want to consider adding to a qualification protocol are required steps to assure all related documentation and systems are addressed, such as the SOP(s) associated being in place and effective, proper systems for PM/Calibration are set, cleaning requirements addressed, etc. It has been proven useful to address these segments at the time of qualification so that they are no overlooked. If there are other in-house systems to track these things then a reference to them in the protocol may be adequate.

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