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CLIMET CHRONICAL

Rev. 1.0 (Jan 2016)

Celebrating Over 50 Years In Business!

January 2016 Newsletter www.climet.com

sales@climet.com

Tel. +1 (909) 793.2788

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Table of Contents Regulatory Corner .................................................................................................. 3

Being ready for ISO 14644-1: 2015 ........................................................................ 3

Biopharmaceutical Warning: Aseptic Monitoring ................................................... 4

Another Example of Climet’s Unparalleled Customer Support ............................... 5

Aseptic Monitoring in Biological Safety Cabinets and Isolators .............................. 5

Product Update: CI-90A and CI-95A Microbial Samplers ........................................ 7

Product Update: New DataPro 2.5E Software ........................................................ 7

ISO 9001 Certification ............................................................................................ 8

Firmware and Software Revision Updates .............................................................. 8

Suggestions, Comments and Recommendations .................................................... 8

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Regulatory Corner By Jim Strachan, General Manager Dave Chandler, Engineering Manager Climet Instruments Company

This section of our newsletter is dedicated to the answering or discussing any regulatory questions or pertinent issues.

In December 2015, the ISO 14644-1 and ISO 14644-2 standards were ratified.

These changes include:

1. 95% UCL calculation for 1 to 9 locations is no longer required. All locations now use a simple average. This eliminated room failures because of a wide variance in counts, even though all areas are well below limits for the class. This may affect reporting requirements.

2. Number of sample locations for certification (not monitoring) has increased, and is now provided on a table in ISO 14644-2, B.7.

3. Specification for 5 μm counts have apparently been removed from class 5 and 6 areas, because there are too few particles to be statistically significant in those areas. However, the ISO standard refers to footnote (f), which refers to ISO/DIS 14644-1.2, Annex C (e.g., Macroparticles). This does not eliminate 5 μm classifications where there are “specific process requirements”, such as biopharmaceutical production. ISO 14644-1/2 is in harmony with EU GMP, Annex 1 (e.g. Manufacture of Sterile Medicinal Products).

4. Certification interval for ISO Class 5

clean areas has, in accordance with

ISO 14644-2, gone from a six month

maximum time interval to:

Periodic classification testing shall be

undertaken annually. This frequency can

be extended based on risk assessment, the

extent of the monitoring system, and data

that are consistently in compliance with

accepted limits or levels in the monitoring

plan.

However, we do not generally

anticipate changes from the prior six

month certification interval in

applications related to the manufacture

of sterile medicinal products due to the

generally high financial impact that

might potentially occur as a result of

product or API scrapping. Individual risk

assessments should be considered.

Generally speaking, companies subject to FDA or GMP have 18 months to comply with the new ISO 14644-1/2 industry standard.

Being ready for ISO 14644-1: 2015 By Dave Chandler, Engineering Manager Climet Instruments Company

The cleanroom classification standard ISO

14644-1 was first published in May of 1999.

This standard covers the classification of air

cleanliness by particle concentration. After

more than 10 years of review, ISO published the

first revision to the standard on December 15,

2015. Companies who currently use ISO 14644-

1 for classifying their cleanrooms can

immediately begin using the new current

version.

Climet portable counters dating back to the

CI-500 have had the ability to generate

PASS/FAIL reports for ISO 14644-1. We have

created new firmware versions for the CI-x5x

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Series of counters, which will contain new

formulas for reporting PASS/FAIL according

the new standard ISO 14644-1:2015.

The main differences in the new ISO 14644-

1:2015 vs 1999 are as follows:

The limit for 5 µm particles is removed for ISO

Class 5.

ISO Class 5 no longer has a limit for 5 µm

particles. The GMP 2008 reports continue to

include the same limits for 5 µm particles as

before and the formulas are not changing for

GMP 2008 reports.

The minimum number of sampling locations

is different.

In the 1999 standard, the minimum number of

locations was equal to the square root of the

area in square meters. This has been replaced

with a table and more locations will be required

in most cases. A new formula can be used for

areas greater than 1000 square meters.

The 95% UCL calculation has been

eliminated.

The 95% UCL (upper confidence limit) is no

longer calculated for sampling areas with 2 to 9

locations. Every location must pass individually.

The new higher minimum number of locations

provides at least 95% confidence that at least

90% of the clean room or clean zone does not

exceed the class limits.

Coming soon.

Starting in February or sooner, all CI-x5x units

will ship with new firmware compliant with ISO

14644-1: 2015. It will be possible to upgrade old

CI-x5x portable counters with new firmware.

Unfortunately, firmware upgrades are not

possible on CI-500’s, CI-550’s and CI-450’s

(which have all been discontinued for over 10

years).

New versions of DataPro 2.5E and DataPro 3

will also be providing reports compliant with

the ISO 14644-1:2015. Users with DataPro 2.5

can obtain upgrades to DataPro 2.5E. Please

contact the sales department for details.

Biopharmaceutical Warning: Aseptic Monitoring By Jim Strachan, General Manager

Climet Instruments Company

Biocontamination refers to biological contamination of products by bacteria and/or fungi, as well as the toxic by-products of these microorganisms, such as endotoxin and mycotoxins from Gram-negative bacteria and fungi, respectively.

To ensure biopharma operations are aseptic, monitoring is conducted in the industry primarily through active air sampling, and more particularly, impaction samplers.

Operational Quality of an air sampler is measured in accordance with ISO 14698-1. The following equation provided in Annex B.3 is how “Sampling Efficiency” is calculated:

Sampling = Test sampler count x 100 Eff. (%) Reference sampler count

Essentially, the ISO standard compares the viable sample count of the device under test against another “reference” sampler. Simply, it is not a Sampling Efficiency rate, as much as it’s a Comparison Efficiency rate.

As a result, the “Sampling Efficiency” of a microbial sampler is really a function of how well it performed against a reference sampler.

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Subsequently, all organizations that perform aseptic monitoring should know their instrument’s “Sampling Efficiency,” as well as the reference sampler, its collection efficiency, and why the manufacturer chose this reference device.

The collection efficiency of the reference sampler very much matters, considering the device under test is being compared against it.

Climet’s testing is discussed in this newsletter in the article concerning the upgrade to our CI-90A and CI-95A models on page 7.

Another Example of Climet’s Unparalleled Customer Support A large pharmaceutical manufacturer located in

Juarez, Mexico (name intentionally withheld)

was experiencing difficulty communicating

between their portable particle counters

manufactured by a competitor, and their LIMS

(Laboratory Information Management

System).

According to the end-user, the other

manufacturer gave virtually no support in

resolving the problem, and as a consequence

the large pharmaceutical producer purchased

Climet particle counters as replacements.

Unfortunately, the customer experienced the

same data communications failure with their

newly purchase Climet particle counters.

In an example of superior customer service,

Climet sent one of our Engineers, Joe Allison, to

their site to determine the root cause of the

problem.

After confirming the Climet particle counter’s

RS-232 serial port was functioning properly, Joe

discovered the customer was using a 3rd Party

RS-232 to Ethernet converter between the

Climet particle counter, and their LIMS system.

Joe was able to quickly determine the adapter

was the root cause of the problem, and was in

short order able to configure it properly in order

to allow sample data to be transmitted to their

LIMS.

Needless to say, the end-user was very upset

with our competitor, because they gave them,

“No help to solve the same problem with their

particle counters.”

Customer Service is one of those things that’s

difficult to quantify, and it is perhaps even more

difficult assigning a dollar value. That said,

Climet customers can rest assured that we are

committed to exceeding their expectations,

and providing the highest level of quality

support and assistance to their specific

application needs.

Aseptic Monitoring in Biological Safety Cabinets and Isolators By Jim Strachan, General Manager Climet Instruments Company Biological Safety Cabinets (BSC) and isolators are often used in the manufacture of sterile medicinal products.

From a regulatory standpoint, biotech and pharmaceutical companies must demonstrate to regulatory authorities (such as the FDA and GMP, and increasingly, to the public) that their processes and procedures are adequate with respect to microbial monitoring, enumeration, culturing, and species identification.

Both BSCs and isolators use a unidirectional or laminar air flow as major element of a system that mitigates or more preferably, eliminates the risk of biocontamination.

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Obviously, disruption of this laminar flow, given the micro-environment, can significantly increase the risk of biocontamination.

Unfortunately, unidirectional air flow is disrupted when a microbial sampler is brought into a micro-environment, as well as when it is removed. More importantly, the exhaust from the microbial air sampler causes a further disruption in the laminar air flow, resulting in an increased risk of biocontamination.

In micro-environments such as isolators or BSCs, industry best practices are to use a remote sample head, which can be mounted inside the BSC or isolator.

The above is a Climet CI-95A microbial air sampler, with an adapter head connected to autoclavable silicon braded tubing, which is then attached to a stainless steel remote sample head.

The material making up the sample head and the enclosure of the microbial sampler are very important.

With regards to the sample head, it must be autoclavable.

The sample head consists of a screen, or slit pattern, and the width of the material is generally 3mm or 3,000µm thick. Given a unicellular influenza virus is 0.43µm, it is imperative each hole be sanitized.

Obviously, the easiest way to do this is by autoclaving the sample head.

Polished Stainless Steel, by a very large margin, provides the best protection against biological contamination.

Steel is one of the rare materials that are known to have static neutral characteristics. This is important as static charges will attract particles of all sizes.

Particle carrying microbes will subsequently be highly attracted to plastics and to a much lesser degree, aluminum, which gives up a small amount of positively charged electrons.

Plastics are also susceptible to biodegradation when exposed to moisture, bacteria, enzymes, UV light, and aggressive chemicals often found in cleanroom sanitation or disinfection fluids.

As biodegradation occurs, plastics will slowly release inert particles into the environment, and therefore contribute to the particle burden of the clean area.

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Additionally, micro-fractures and cracking will occur as biodegradation progresses. These microscopic cracks make perfect hiding places for bacteria and other contaminants, and are difficult to clean and sanitize.

Therefore, use of plastics is never recommended in biopharma manufacturing, and stainless steel is always preferred over aluminum.

Sterility failures are rare, but their occurrence carries disastrous consequences for biomanufacturers of sterile products, as scrapping of finished product and/or API can be extremely expensive.

We must conclude that a small investment in quality, can have a substantial positive impact on profitability, and return on investment.

Product Update: CI-90A and CI-95A Microbial Samplers By Jim Strachan, General Manager

Climet Instruments Company

As our may already be aware, Climet’s CI-9x Series of microbial samplers have been in manufacture for over 10 years.

The Biological Efficiency of our CI-9x Series of microbial samplers was tested and compared against the SKC BioSampler. According to an article in Aerosol Science and Technology (32:184-196, 2000), the SKC BioSampler has the industries highest collection efficiency at 100% for sizes 1 µm and larger. Its performance in unparalleled when compared to all impaction samplers commonly used in biopharma monitoring.

Although the SKC BioSampler has excellent biological collection efficiency, it is a glass impingement sampler with a low 12.5 LPM flow rate, making it completely inappropriate for

monitoring biopharmaceutical industrial manufacturing applications.

Climet’s original CI-9x Series of microbial air samplers had good biological collection efficiency performance (83%) when compared to the SKC BioSampler.

However, due to significant research and development conducted throughout 2015, Climet engineers identified two unique design elements, that when incorporated improve the Biological Collection Efficiency of the CI-9xA Series to 101.4% when compared to the SKC BioSampler.

Climet has filed patents for this new technology, and effective January 2016, the model number CI-9x Series will be appended with the letter “A” to reflect the improved performance with the new technology.

Customers can rest assured that the performance of the CI-9xA Series is unparalleled among other impaction samplers.

Current customers with prior models may have their instruments upgraded at a nominal fee. Please, contact Climet’s Sales Team for additional details.

As always, customers may request a copy of the biological efficiency report by contacting our sales team: sales@climet.com

Product Update: New DataPro 2.5E Software By Jim Strachan, General Manager Dave Chandler, Engineering Manager Climet Instruments Company

DataPro 2.5 Software is used with Climet portable particle counters for facility monitoring. It provides trend analysis, graphs, and creates compliance reports.

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In January 2016, DataPro 2.5 is being upgraded to DataPro 2.5E. The new version of the software will:

Calculate reports to the new ISO 14644:2015 standard, GMP reports, and FED 209e standard;

Push sample data to a user-defined directory on the computer network via a standard Ethernet connection;

Support Wifi sample data transfer;

Allow users to upload a floor map; and

Allow users to monitor multiple CI-x5x portable counters on a network.

ISO 9001 Certification By Jim Strachan, General Manager

Climet Instruments Company

As of January 7, 2016, Climet is ISO 9001:2008 Certified. The audit was conducted by NSF International Strategic Registrations, who is accredited by the ANSI-ASQ National Accreditation Board (ANAB), and the International Accreditation Forum (IAF).

Our Certificate Number is C0262283-IS1. You can obtain a pdf copy of our certification by clicking the logo at www.climet.com

Firmware and Software Revision Updates By Dave Chandler, Engineering Manager Climet Instruments Company

The update of DataPro 2.5E is discussed in an article on the facing column..

As of 14 January 2016, DataPro 3 supports reporting for the new ISO 14644-1:2015 standard. DataPro 3 is monitoring software used with Climet CI-3100 Ethernet OPT continuous monitoring particle counters.

For customers who require information on previous firmware or software versions, please create a login to our website at www.climet.com/partners/join/

Suggestions, Comments and Recommendations We are always looking for relevant topics, and welcome your comments, suggestions, and feedback. Please contact our Sales & Marketing Team +1 (909) 793-2788 sales@climet.com

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Copyright © 2016 All Rights Reserved.

Climet Instruments Company, a Division of Venturedyne, Ltd. www.climet.com +1 (909) 793.2788

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efforts have been used in this document to present accurate information, but inadvertently may contain typographical errors, omissions, or

other inaccuracies. The author disclaims liability from any unforeseen errors and omissions; and we reserve the right to correct any errors,

inaccuracies or omissions and to change or update information at any time, without prior notice. We do not generally undertake to update,

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