Cleanrooms are basically controlled spaces where particulate counts, temperature, relative humidity and pressure are controlled and monitored. While movies and the sci-fi genre may make these spaces seem very high-tech, they are actually quite basic in design and function. In fact, you can transform almost any existing space into a cleanroom, although the cost of doing so be quite high.

For companies who plan on completing short-term projects or production runs with specific products who do not have a working cleanroom, using a modular cleanroom, also known as a “portable cleanroom” can be a viable alternative.

Modular Cleanroom Benefits

A modular cleanroom can provide many benefits. The primary benefit is cost with flexibility and portability of processes following as a secondary benefit.  Below are just a few of the possible benefits of choosing a modular cleanroom over a “built-in” option.

Versatility: Most modular cleanrooms can be assembled on-demand, and be ready to use in a couple of days. These are generally complete solutions requiring no ancillary expenses.

Flexibility: With portable cleanrooms, the customer can benefit from nearly unlimited floor-plans and layout options; adhering to what makes the most sense for a particular process.  Alternatively, re configuring a built-in cleanroom to change the layout or design would require stopping processes and heavy construction costs.

Cost-efficient: A modular cleanroom is manufactured offsite; and can be custom built. They often cost a fraction of what permanent cleanroom construction would cost.

Renting and leasing: Most portable cleanroom builders have options to lease or rent the portable cleanroom. This makes sense for companies that know they have a short-term project.  They can rent or lease a cleanroom for a short term and then return it if they need something different for the next project.

Tax break: Since a modular cleanroom can be easily disassembled and is completely portable, and moved to a different location within the company, it is considered a piece of capital equipment; benefiting from the same tax regulations as other machinery and capital equipment.

Cleanliness: For cleanroom classification requirements of ISO 6 and above, a modular/portable cleanroom can be the better option; the materials used in modular cleanrooms do not face the same material degradation challenges faced with permanent cleanroom construction.

 

Types of Modular Cleanrooms

Hard wall Modular Cleanrooms: These portable cleanrooms are typically designed and built to customer specifications. They are delivered on-site and installed/assembled by a manufacturer representative. Hard wall modular cleanrooms are typically built using vinyl, aluminum, fiberglass or a combination of these materials. They can be configured with windows and doors placed according to the buyers specification.  They typically come complete with monitoring solutions for particle counts, temperature, pressure, and relative humidity. It is important to note, however, the monitoring instruments included in modular hardwall cleanrooms may not always be top-of-the-line, so it is important to consider using a third party, stand-alone solution for more accurate monitoring. Also included are HEPA filtration units that can be configured to meet ISO 5 – ISO 9 standards, in most cases.

Soft-wall Modular Cleanrooms: These are the most portable of all modular cleanroom designs. Customers can typically select the thickness of the plastic sheeting/enclosure, the level of filtration (and in some cases they can be outfitted to tie in to existing HVAC systems). The plastic sheeting is usually mounted on steel or aluminum frames complete with casters. While soft-wall modular cleanrooms offer the highest in portability factor, they may not reach the same cleanliness levels that hard-wall modular cleanrooms can. It all depends on the manufacturer and the cost the buyer is willing to bear.

 

Challenges

Perhaps the greatest challenge with any cleanroom, but particularity with a modular cleanroom, is maintaining mandated cleanliness and keeping the overall environment consistent. The best way to avoid contamination is to have an accurate particle counter on site, or to have your modular cleanroom bench tested regularly. Just as important as particulate counts and air exchange rates is maintaining air quality.  This generally means pressure, temperature and humidity. To monitor and maintain air pressure, temperature and relative humidity, a stand-alone cleanroom differential pressure, temperature and relative humidity monitor is essential. Differential pressure is what keeps pollutants out of a standard cleanroom (or keeps caustic chemical fumes and particles in when using a negative pressure isolation room). These highly precise cleanroom monitors are relatively inexpensive, and can be easily attached to your portable modular cleanroom. A number of these are available, each of which have different features.  Always check if the instrument you choose can alert local staff, as well as provide advanced alerts via SMS, email and/or automated phone calls.

Early detection in air quality issues will save a great deal of potentially lost time, money and contamination remediation.

 

 

 

Introduction

Annex 1 of the EU GMP is a guideline and set of specific rules describing the European Union’s requirements for the manufacture of sterile medicinal products, including what we refer in the USA as “compounding pharmacies.” EU MP Annex 1 guidelines are applicable to all EU nation states in regards to pharmaceuticals bought, sold and manufactured –  including those imported from non-member nations. The latest revision will be released in 2019, and is expected to have a greater reaching impact on QA/QC and all laboratory activities in the EU and abroad.

So, what exactly is Annex 1 of the EU GMP, and what does it mean for pharmaceutical companies operating in the USA? For the most part, USP regulations in conjunction with 21 CFR 11 dependencies satisfy EU GMP, especially Annex 1, however, it is important to ensure manufacturing processes are not simply performed within standards and regulations, but monitored thoroughly throughout the process as well.

Overview

On 20 December 2017, the European Commission published the long-awaited draft of Annex 1 “Manufacture of Sterile Medicinal Products.” In fact, it was published nearly three years after it was first announced. Many see the change over the previous (technologically outdated) versions as having a focus on Quality Risk Management (QRM)

A key driver for the change, the concept of risk management is hard to miss in the new document:

  • 92 instances of the word “risk” (only mentioned 20 times in previous version) total times mentioned is 600, so “risk” is huge.
  • 15 references to QRM specifically

The 2018 (and presumably 2019) update contains substantial additional detail on virtually every topic in the 2007 version. In addition to those noted above as potential game-changers, compliance personnel can look forward to new levels of detail on such subjects as: Trending of environmental monitoring results (meaning the existence of a dependable chart recorder/data logger of pressure differential, temperature, and relative humidity)

Two key areas of focus should be viable and non-viable environmental and process monitoring and environmental control of pharmaceutical clean rooms as the essential part of the manufacture of a quality product. Simply adhering to standards without documented, digital storage of ongoing process controls is an exercise in futility.

We are somewhat partial since we engineer and develop instruments to monitor environmental conditions in cleanrooms, and for monitoring and logging data of control processes during pharmaceutical manufacturing. However, this partiality comes form countless instances of customers, and manufacturers reporting occasions where they assumed a process control was operating within optimal standards, only to find out later in log reports there was an anomaly which compromised the process. If end-use retail products are being manufactured – there is an acceptable risk for these incursions, and worst case scenario is a product mail fail or operate undesirably. In the case of a pharmaceutical product, it may be a person’s health and wellness which is ultimately compromised.

While there is no specific language to dictate specifics on “annex compliant” negative and positive pressure monitoring, as there is for acceptable micron size in particulate monitoring, it is important to note that the language does reference the requirement to maintain environmental control process monitoring, logging data throughout the manufacturing process.

Compliance

There are many instruments on the market; some specialize in monitoring temperature. others focus on humidity. Some are standalone room air differential pressure monitors. The TV2 Cleanroom Monitor is the only instrument to perform all three actions with specifications which exceed EU GMP requirements, USP 787 requirements and provides data storage for one full year.

We are happy to consult with you regarding your temperature, relative humidity and room pressure monitoring needs – whether you re in the USA or adhering to new EU GMP Annex 1 compliance guidelines. We are here to help.

Here is a PDF of the EU GMP Annex 1

ec_annex1_20dec2017

 

 

 

Hygrometers are single purpose instruments that measure the amount of water in the air.  They actually measure the relative humidity, which is expressed as a percent of comparing the actual water in the air and the amount of water the air could contain if it was completely saturated. While we can at least try to guess what’s air temperature at the moment even without looking at a thermometer, it is much harder if not impossible to measure humidity without a hygrometer. Keeping a stable humidity level can be just as important as keeping the right temperature. High humidity can damage stored food, medicine, etc… just like high temperature can. The only difference is that without a hygrometer you really have no way of knowing that something’s wrong!

Older mechanical hygrometers show only the present relative humidity.  Some more expensive mechanical hygrometers record the humidity on a piece of paper so that you get an actual printed chart, increasing the hygrometers’ usefulness – chart recorders. But hygrometers alone generally only show the present RH level and, unless we spend all of our time watching the readout, they tell nothing about possible humidity fluctuations. So how do you determine that?  Analog chart recorders or digital data loggers record the RH level over time. They are great improvements over the older mechanical hygrometers.

Newer recording hygrometers can be chart recorders or data loggers. Using chart recorders or data loggers that record humidity you can determine if your stored inventory (i.e. food, medicines, electronic materials) are being stored in the proper environment. And If they have an alarm with them they will alert you if something goes wrong so you can take action.

Example: Consider this situation – your computer room is a subject to frequent humidity changes (due to improper air conditioning, for example). Everything’s all right most of the time but occasionally the humidity sharply rises and falls. If no one is present during these times you will never realize that the environment is changing. This can be a real problem for computers.  Too low humidity can lead to static discharges, and a static discharge can completely destroy a hard drive or microprocessor.

A recording hygrometer such as a chart recorder or data logger will keep a record of what happened but are not able to trigger alarms when a dangerous trend occurs.  For that you need a data viewer such as the TV2, so a text, Email or phone call can alert you if the humidity begins to drop.