Qualification of Aseptic Operators in GMP Environments

Working in a cleanroom under GMP isn’t easy, you have your gowning to consider, your movements, your equipment and then there’s the new operator who needs continuous monitoring.

Qualifying aseptic operators poses a significant challenge, not because it’s extremely difficult but because it requires great care and attention to detail. This blog post explores the qualification of cleanroom operators.

Training - General

Even though a lot can be trained, it is up to the HR department and management of the organization to ensure the soon-to-be aseptic operator has the right background and experience for the job. The more relevant experience the person has, the easier the training and qualification will be. You would ideally like to hire an aseptic operator with at least five years of experience in GMP production.

When a person is hired, he or she will enter into the training program. For new and existing aseptic operators, there should be a continuous training program on theoretical and practical GMP aspects, including microbiology and hygiene.

Training - Points to Consider

When performing GMP training, you must always make sure that the training is well documented. Proper training documentation serves multiple purposes, most notably as evidence that operators have indeed been trained, but the data also serves as valuable input for (management) reviews.
Secondly, you must make sure that the training is fit-for-purpose. Only having aseptic operators re-watch the same online training course every month is not a suitable curriculum for an aseptic operator.

Consider the trends, consider operator input; what are the problems at the moment? Any area’s for improvement? Any new techniques or equipment the operators should be aware of? Consider circumstances which are out of the ordinary as well, for example; If personnel work in more than one area, are the employees trained to ensure that they take adequate precautions to prevent cross-contamination when they pass from one area to another?
The GMP expects you to continuously update and adapt your training to the actual situation and real challenges.
Additionally, you will want to have an easily presentable training plan which considers frequency and the reason(s) for the GMP training. One aspect of training, which is often overlooked, is measuring the effectiveness; is it assessed, and how are the results communicated to employees? The same goes for the operator’s performance in the cleanroom.

Aseptic operations are challenging to perform; that’s why continuous feedback is needed as spontaneous feedback on performance usually comes too late. This feedback is required to enable operators to be more fluent in their operations. After all, the more fluent you can operate, the easier it is to perform it aseptically.

Other points to consider;

  1. Is there a differentiation between activities for more and less experienced personnel?
  2. Look at transfers between zones and evaluate “routine” operations frequently
  3. Do new employees practice operations (and how many times) outside the clean rooms before they perform them inside the clean rooms

 Gowning - General Principles

 So, you’ve got trained and qualified aseptic operators, they certainly know what they’re doing, now you have to make sure your operators look like they belong in a cleanroom. Operators must always wear gowning according to the appropriate area classification. Good personal hygiene is the foundation of proper gowning.

Even though it should be common knowledge we still see companies where employees wear jewelry or makeup in cleanrooms, these should not be worn in cleanrooms. Eating, drinking, and smoking are prohibited.

The danger with gowning is that it is a repetitive task. New operators will more quickly believe they have mastered it while this may not be the case. This phenomenon is known as the “Dunning–Kruger effect.” New operators with substantial, measurable deficits in their knowledge or expertise cannot recognize those deficits and therefore, despite potentially making error after error, tend to think they are performing competently when they are not, making them look confident. People perceive confident individuals as competent. Without proper supervision, other new operators will look to the confident operator for inspiration, amplifying the problem.

To mitigate these phenomenons make sure there is a cheat-sheet on gowning procedures in the gowning area and that it’s in line with the gowning SOP. Additionally, measure the qualification of gowning and re-train operators frequently.

Other gowning points to consider;

  1. How is assured that only qualified people enter the areas?
  2. Are all make-up and all jewelry removed?
  3. Is there a mirror in the dressing room so people can verify correct clothing from top to bottom before entering?
  4. How frequently are people resanitizing/changing their gloves?

Monitoring - General Principles

Monitoring frequently is a good idea in any GMP environment, but even more so in an aseptic GMP environment. Risk assessment should be leading here, what do you monitor, how frequently and where. There are, however, a few no-brainers such as gloves and gowns which should be monitored for microbial contamination.

 Typical locations for sampling include the glove fingers, face mask, forearms, and chest. Daily/lot related (whichever is more frequent) samples should be taken from each operator. When you find adverse trends or levels exceeding your limits, start an investigation. It is recommended to routinely check the quality of these investigation reports, do investigators often find the same root-cause? Is this conclusion converted into a CAPA? Has it been effective?

 Don’t forget to routinely train your monitoring staff on monitoring techniques and the latest industry standards/insights. One of the most critical aspects of this training program should be; “understanding the possible sources of contamination involved in sampling.”

Media Fill Qualifications

Media fills are a technique in which a liquid microbiological nutrient growth medium is prepared and filled in a simulation of a regular manufacturing operation and requires special attention in the qualification of aseptic operators in the pharmaceutical industry.

Participation in media fills should be a standard part of operator qualification. After the initial qualification, requalification should follow twice a year (in most organizations), per shift and per process.

Media fills are costly and labor intensive; as such, you don’t want to have to repeat them too often unnecessarily. Your qualification records, trends, and monitoring can provide valuable information when analyzing media fill failures. Does it fail with specific shifts or teams? Are there any adverse trends on an operator level, and how was this investigated? What are operators doing before they fail a media fill?

Behavior - General Principles

Proper cleanroom behavior should follow from adequate training. Anyone entering the cleanroom should exercise the general principles for behaving in a GMP cleanroom. People should move slowly and deliberately; body parts should be kept out of the laminar airflow, and gowns should be kept as clean as possible.

Necessary product manipulations should be approached in a way that avoids compromising sterility.

One way to check your training effectiveness and validity of your qualification program is by simply watching the aseptic handlings in the cleanroom.

Are people touching their clothing or face?

Are people touching sterile surfaces, equipment, products, etc. with their gloves or gown?

How are they manipulating the product, and how does this affect the airflow?

A quick touch of the face or shortly disrupting laminar air flow may seem like minor and split-second event, but we must always remind ourselves of the fact that people are the most important source of (microbial) containment in clean areas.

To provide you with a few statistics on the human body;

  1. Humans lose approximately 5 to 10 million skin cells every minute,
  2. Saliva 106 – 107 CFU (Colony Forming Units)/ml
  3. Sneezing once 104 – 106 CFU/ml
  4. Human feces 1011 CFU/ml

That’s under normal conditions; it is therefore highly relevant to have employees report any contagious illnesses, diseases, or open lesions immediately.

You should have such responsibilities detailed in an SOP, including contact information or the person responsible for dealing with such cases. Smokers should also be restricted from working in the cleanroom for a definable period of time after having taken a smoke break (if allowed).

In Summary 

Only qualifying your operators through a one-off training program is not accepted; many systems, people, and checks can make or break a cleanroom operator qualification trajectory. To reduce contamination risk, there must be a continuous feedback loop both top-down and between operators themselves.

In Summary - General Points

  1. Headcovers must cover all hair and, if applicable, mustache and / or beard and must be tucked into the clothing collar
  2. Mouth mask and glasses are a requirement
  3. Sterilized, non-powdered rubber / plastic gloves
  4. Sterilized / disinfected footwear is a requirement
  5. Pants must be tucked into the footwear
  6. Sleeves must be tucked into/under the gloves
  7. No outer clothing in the dressing room to A / B rooms
  8. Jewelry is notorious when it comes to contamination. Ridding yourself of all jewelry is the motto. Class A / B environments should be completely jewelry-free.
  9. Hair and mustache / beards are also notorious places (each hair log3-log5 mo's). That is why they must always be covered.
  10. When changing clothes, there is a risk of particles falling on clean clothing. This can amount to millions of particles, obviously because there is intensive movement during this procedure. Therefore, the hairnet must be worn first.
  11. Make-up and gels also release many particles and can, due to their composition (cosmetics), cause severe reactions in patients if they end up in the medicinal product.
  12. Floors, despite proper cleaning procedures, are always the most suspicious (most dirty). If we put on clean, or even sterile, cleanroom clothing, we must ensure that this clothing is not contaminated with dirt from the floor.

Cleanroom Gowning Guide

 Download a free copy of our cleanroom gowning guide for gowning principles in GMP environments here; download.