The qualification of equipment is a GMP requirement. Qualification is the documented evidence of the verification that a pharmaceutical machine meets the pre-determined requirements.
The definition varies per guideline. For more information you can check the following documents;
- Annex 15 of Eudralex Volume 4 – LIFE CYCLE APPROACH
- EMA Process Validation Guideline for Finished Products (27 Feb 2014)
- Guidance to Process Validation (FDA, January 2011)
- WHO guideline on non-sterile Process Validation QAS/13.527 (draft, Jan 2013)
- ICH – Q 2, 8, 9, 10 & 11
Other than these aspects, you can find a lot of information with the following organizations;
- GAMP 5 (for computerized systems validation)
- ASTM-2500 (uses the term “verification”)
When you are qualifying equipment in the pharmaceutical industry, make sure you develop knowledge of the qualification process and the equipment itself. You should be able to defend your choices during the qualification process in the future. Besides this, it is always good to develop Subject Matter Experts (SME’s) on all your equipment. They will provide guidance when equipment fails or when you make decisions on your (preventative) maintenance program.
Do not limit your qualification team to the process / equipment owner. Involve a multidisciplinary team. Not only will this boost regulatory confidence but increase the quality of your qualification as well.
Most would say that a risk assessment or team composition are the first steps in the qualification process. This isn’t the best approach.B
efore you start writing any qualification protocols you must first understand what you are going to qualify. Do you fully comprehend what the equipment does, how it works and what it’s parameters are? This is the most common pitfall of validation/qualification studies.
But where does this knowledge come from? You can not just Google how your specific type of equipment works and what its configuration is. Rather, seek input from peers/communities or from R&D-work, risk assessments, guidelines, education, SME’s and professional literature. And last but not least, the vendor itself. They should be your number one source for input.
AUTOClave QUALIFICATION EXAMPLE
As an example, we are going to perform the validation/qualification of an autoclave for penetrable loads.
We start with a team of experts on the autoclave we are going to buy. The team should involve experts on your process as well. This group of experts will thoroughly examine each supplier’s offer and the process in which the autoclave will be used. Are the autoclaves of a right quality? Are the vendors well-known suppliers of pharmaceutical equipment? What documentation do the vendors have available? Etc.
Subsequently, we determine autoclave loads and write a URS detailing what we want and how the supplier should meet those terms. The vendors respond to our URS with a renewed offer, which is again reviewed. When the review has concluded, a vendor has been selected.
Using their documentation a DQ (Design Qualification) is carried out. Then we proceed with two other Q’s; IQ and OQ (installation qualification and operational qualification). Once those have been completed we move to the practical part; cycle and load development.
These are followed by a study on the WCL/WCS; the worst-case-locations and worst-case-situations. Only after completing the previous activities we perform the last Q; PQ (performance qualification).
You are encouraged to use information from third-parties (if qualified) during qualification and validation, but always remember that inspections will examine your qualification, not the qualification of (any) third parties.
Calibration and Maintenance
During your qualification you need to make sure that your equipment stays operable and calibrated.
A preventive maintenance system that includes calibration must be implemented by the end of Operational Qualification at the latest (OQ). This includes: A Maintenance Plan, Maintenance Procedures and Maintenance Records
According to the GMP’s calibration and (preventive) maintenance are;
CALIBRATION –The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements.
PREVENTIVE MAINTENANCE –A program to ensure equipment and control systems remain fit for use with the aim to reduce the following risks:
- Risk to product integrity due to contamination or malfunctioning of equipment,
- Risk to production through poor equipment availability,
- Risks associated with health, safety and the environment,
- Regulatory risks arising from an inability to demonstrate that adequate maintenance controls are in place.
cleaning GMP equipment
Keeping the equipment clean is a GMP requirement. Cleaning is an important factor during qualification (and validation). Whether there is manual or automated cleaning, there are a number of factors to pay attention to.
For manual cleaning:
– A detailed procedure
– Trained operators (qualified)
– Good documentation
– Pre-validation data
For automated cleaning:
– A defined recipe
– Equipment must be qualified
– The process must be monitored
– Pre-validation data
But how do you determine what your cleaning/validation needs are?
Risk assessments and a risk matrix will help you determine what type of cleaning applies to what. We have made an example of a matrix used by an API manufacturer:
Setting limits for your cleaning is an important step. You are going to have to have some sort of tolerance/acceptable limits. Without it you will be cleaning forever (and qualifying/validating forever). When we help clients with setting their cleaning limits we use the following rules/considerations;
- Regulatory Authorities do not set limits for specific products
- Limits must be justified based on risk assessment (nothing detected -> 100 ppm)
- Limit must be achievable and verifiable
- High potency products versus low potency products
- Different limits for campaign changeover versus intra-campaign
- Different limits for “early” equipment versus “late” equipment