Shutdowns. The window of opportunity for the hard-working production team to take a breath after months of intensive manufacturing, and for the facility and equipment to get some much-needed attention before production restarts. 

Of course, it’s also the window of opportunity for QA to chase us down for those overdue Quality Records!

From a microbiologist’s perspective, shutdowns often bring a wave of anxiety. With all the engineers and maintenance crews in and out of our controlled areas, how on Earth will we get back into a state of control? How many deviations will I have to write for all the action limit breaches? But more importantly, I hope the mold doesn’t rear its fuzzy-haired head back into our facility like last time...

Looking back, I’ve learned that the key to a successful restart begins long before the shutdown even starts. In this article, I’ll share some lessons learned, practical insights and best practices to bring your cleanrooms back under control. What I wish I had known before a facility shutdown.

Planning for the Planned and Unplanned

Whether a shutdown is planned or unplanned, the primary objective is the same – preserve the integrity of the facility as much as possible. In my experience, the greatest chances of a ‘Right First Time’ (RFT) facility restart comes from careful planning, thorough risk assessment(s) and robust protective measures.

Risk assessments should involve a multi-disciplinary team, including Production, QA, Validation, Microbiology and Engineering, to identify the relevant activities and contamination risks associated with the shutdown. I have seen many complications (and disasters) that stem from poor planning, such as:

• Increased Microbial Contamination: Due to the lack of control from the influx of engineers and maintenance workers, alongside their respective tools and equipment.
• Increased Presence of Physical Contamination: Activities such as drilling or disabling of the HVAC within controlled areas can introduce massive particulate loads, spread widely if not contained appropriately with even basic measures such as sheeting or disabling doors. The presence of dust, dirt and debris can increase the challenge to remove microbial contamination by creating barriers to shield the microorganisms from any disinfectants during the facility cleaning and disinfection activities.
• Contaminated Equipment: Airborne viable and non-viable contamination can settle onto the surfaces of production equipment, and as many have high surfaces and/or intricate designs it makes it difficult to reach some parts or areas and can result in severe contamination events.

With careful planning, I have learned that proactive protective measures can be implemented to reduce the impact of contamination on the facility:

• Operator Gowning: As we know, people are the biggest sources of contamination. To mitigate the increased risk of contamination, an appropriate level of gowning and training should be provided for all visitors, including gowns, overshoes and mob caps.  This may be preferable to a full gowning amnesty or free for all during any shutdown.
• Tools and Equipment: Maintenance tools and equipment may be covered in greases, lubricants and oils. Requirements for cleaning and disinfection of tools and equipment during the shutdown period should be well defined to remove gross contamination. Engaging with contractors early to establish protocols and procedures allows them to better meet the restrictions and requirements within controlled areas.
• Clear Signage: Access permissions and gowning requirements should be clearly visible on cleanroom doors (basically keep people out of rooms and restrict access where possible).
• Manufacturing (Cleanroom) Equipment: Secure coverings, plastic or Tyvek® is sheeting, bagging and storage should be considered to protect equipment from contamination.

In summary, my experiences have highlighted that successful shutdowns and restarts hinge on diligent preparation, clear communication, and thorough, multi-disciplinary risk assessments.

Restoring the Facility to a State of Control

After maintenance wraps up, there’s always that urgency to get production running again. But for microbiologists, waiting for Environmental Monitoring results is a nerve-wracking phase. Delays often happen due to poor results which require cleaning and disinfection to be repeated, so robust contamination controls addressing physical, chemical, and microbial threats are essential. Having seen countless facilities delay facility release in the original time scales, here are some of the more common reasons why delays happen:

Physical Contamination

A common pitfall I’ve seen is neglecting thorough cleaning practices. Shutdowns can introduce dirt, dust and chemical residues into the facility; physical contamination will create occluded surfaces that act as barriers to protect microorganisms from disinfectants. Residues from chemical contaminants can also have a similar effect but in addition may also interfere with the effectiveness of the disinfectant. This highlights the importance of cleaning the facility prior to subsequent disinfection steps – HEPA filtered vacuums can be used for dust, and detergents can be used for greases and oils.

Microbial Contamination

The type of antimicrobial product used is also a crucial point. Bacterial and fungal spores are comparatively difficult to kill and will require sporicidal products, applied either manually or with automated processes, such as Hydrogen Peroxide Vapour (HPV) bio decontamination. Any failure or lapse in the surface treatment steps can lead to delays.

Admittedly, I used to be unaware of automated decontamination services. We had put a lot of time designing and validating our manual cleaning and disinfection programme, so I knew our disinfection programme worked – it’s what we always used. The idea of bringing in a third-party to decontaminate our classified areas felt unnecessary and over the top, but there was one shutdown that changed my mind. Despite our best efforts, we had persistent recoveries of mold from our environmental monitoring following a shutdown.

Faced with either extending the shutdown indefinitely to scrub every nook and cranny again or trying something new, we opted to call an automated hydrogen peroxide vapour (HPV) decontamination service provider – Ecolab’s Bioquell Rapid Bio-Decontamination Service (RBDS).

Mold was always a recurring challenge, as we often recovered low levels of mold during our facility monitoring. Despite countless hours of investigations and deviations, we struggled to nail the source of the mold, however one eagle-eyed microbiologist in our team spotted a trend of increased recoveries within our lower graded areas after shutdowns and engineering works. After this particular shutdown, our post-shutdown monitoring showed a widespread proliferation of Penicillium and Aspergillus species across our facility at alarming levels.

Our post-shutdown procedure consisted of manual disinfection. We always suspected that our facility design, with the high ceilings and odd crevices, had something to do with the recurring mold recoveries as it was always a struggle to disinfect these areas. Despite our repeated best efforts to spray, wipe and mop our facility, our fluffy haired ‘friends’ continued to aggressively reappear on our post-shutdown monitoring.

Initially, I was worried that contract service providers wouldn’t know our facility’s ‘quirks’, but the RBDS service provider’s technicians assessed our facility and identified potential challenges. We were put at ease as the contractors guided us through the necessary steps to prepare us for decontamination. We certainly learned a lot from them.

The service providers also informed us that we were able to expand the scope of what gets disinfected because the hydrogen peroxide vapour can reach those hard-to-reach areas. Engaging such experts eliminated a lot of our worry and doubt for us, and their speed and effectiveness were a huge advantage.

Following the pre-decontamination site visit, a date for decontamination was agreed and the contractors arrived on site, the generators were strategically positioned to ensure good distribution of the hydrogen peroxide vapour. They placed Biological Indicators (BIs) containing a population of 106 Geobacillus stearothermophilus spores in various locations to verify the effectiveness of the decontamination service. For every Biological Indicator placed, a chemical indicator was placed as well. These chemical indicators looked different to the ones we usually used for our isolators – it turns out that Bioquell’s Chemical Indicators (Cis) had reactive ink that were calibrated with the BI log reductions to give us an instant indication on whether the gassing cycle is likely to achieve a 6-log sporicidal reduction, based on a colour change.

After the gassing cycle was completed, the indicators were retrieved and processed by the decontamination team. Thankfully, the chemical indicators showed promising results indicating that we had achieved the desired 6-log reduction throughout the treated areas in the facility. This was subsequently confirmed following the 7-day incubation of the Biological Indicators.

Seeing that level of sporicidal kill* in places where our arms and mops couldn’t quite reach, was impressive, but we had a ‘trust but verify’ philosophy on site. We wanted to confirm its effectiveness with our own eyes, so our team of Microbiologists performed intensive Environmental Monitoring. Our post-shutdown environmental monitoring showed no action or alert limit breaches, and more importantly, no mold recoveries! Through the lens of a microbiologist, the decontamination service was a complete success.

Another benefit of the decontamination service was the ability to re-allocate internal resources to other areas. Due to the size of our facility, most of our production team were required to support with the facility manual cleaning and disinfection – each round of disinfection usually took place over 2-3 days, which was repeated several times due to the recurring mold recoveries. By bringing in a third-party decontamination service, this freed up our personnel for other important start up tasks.Whilst there was some initial resistance in our organisation about spending money on a contracted decontamination service, it’s important to remember that shutdowns are already expensive, particularly in terms of lost productivity when the manufacturing team are necessarily engaged in time consuming cleaning and disinfection, and then often delays and repeats of the process to mitigate any recoveries. If we hadn’t eradicated the recurring mold issue, we would have extended the shutdown by weeks, possibly months. That means weeks of no production, delayed product shipments, potential stock-outs for patients, and a lot of extra overhead costs as everyone works overtime to troubleshoot.

It’s no secret that the regulatory landscape within the pharmaceutical industry is increasingly focused on contamination control; we were once faced with an inspector who scrutinized our Contamination Control Strategy (CCS) and questioned our ability to effectively respond to excursions due to repeated contamination events that were observed. This prompted us to re-visit our CCS and identify ways that we could strengthen our response to contamination and identify ways that we could be proactive to prevent the contamination events from happening.

As the Bioquell Rapid Bio-Decontamination Service had helped us out of a few tricky situations since our ‘mold infested’ shutdown, we decided to strengthen our response to more routine contamination by proceduralizing the bio-decontamination service as a ‘Plan B’ to ensure that we could always effectively return our facility into a state of control.

Final Thoughts: From Confession to Confidence

Facility shutdowns are often seen as a necessary pause in operations, but for microbiologists, they can feel like a high stake balancing act between risk and readiness. What I’ve learned through experience is that success doesn’t come from luck, it comes from preparation, collaboration and the willingness to embrace new solutions.

Automated decontamination services, once viewed skeptically as ‘expensive’ and unnecessary, had become a trusted ally in our contamination control strategy. They helped us reduce downtime and eliminate persistent issues, allowing us to move into our manufacturing campaigns with confidence. More importantly, they allowed us to shift our focus from firefighting to forward planning.

If I could go back and advise my past self, I’d say: don’t wait for a crisis to rethink your approach. Invest in the right tools, lean on expert support, and treat every shutdown as an opportunity to strengthen your facility’s microbiological resilience.

*When used according to the label instructions, Ecolab Bioquell systems utilize Bioquell Hydrogen Peroxide Sterilant-AQ (EPA Registration Number:1677-277). “A sterilant destroys or eliminates all forms of microbial life in the inanimate environment, including all forms of vegetative bacteria, bacterial spores, fungi, fungal spores and viruses” per the code of Federal Regulations Title 40 Chapter I Subchapter E Part 158 Subpart W § 158.2203.