PDA New England Chapter Inspection Trends Event

ICQ will be participating as a sponsor at the next PDA meeting, “Regulatory Inspection Trends”.  Please stop by and visit our table and say hello.  The event features presentations by Edmund Mrak, David Sencabaugh and William Frisch and will run from 5:30 – 9:00 PM.  This event takes place on November 18, 2015 at the Hilton Boston in Woburn, MA and includes a buffet dinner.  We look forward to seeing you all there!

Logo for Parenteral Drug Association.  (PRNewsFoto/Parenteral Drug Association)

Register Here

Wednesday, November 18, 2015

5:30 – 9:00 PM

Hilton – 2 Forbes Road, Woburn, MA 01801

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Rouge Corrosion in High Purity Systems

It can be disheartening to design and build a new pharmaceutical facility with shiny new stainless steel process vessels and tubing only to see what appears to be rust appearing exactly where you don’t want it. However there is hope and you are not alone. Rouging in process equipment is very common and in some cases is considered quite stable. This blog post will not pretend to present the various chemical reactions in the rouging process. Nor will there be any definitive statement of what course of action a company should take given that each process, effect on product and severity of occurrence is unique.

What causes Rouge?

There are many positions on what causes rouging. One thing that everyone can agree on is that Rouge is a form of Iron Oxide. Yes, this means it is a form of rust, not what you want to hear when you need to assure your process to not be Reactive, Additive or Absorptive to protect product Safety, Identity, Strength, Quality and Purity (SISQP) (CFR21 Subchapter C, Part 211 Subpart D Section 211.65).

Rouge can begin to form on surfaces that have been damaged from cavitation (pumps and turbulent tubing arrangements), dented tubing, impingement (from sprayballs), improper surface Ra (roughness) and from plain old scratching and gouging of surfaces during routine maintenance and processing.

Rouge Classifications

There are three types of rouge;

Class 1:  Limonite, FeO (OH). Rouge that originated outside of the system where it was discovered. This type of rouge can then migrate to the affected system through process streams and more commonly WFI and Clean Steam. This type of rouge is your typical reddish-orange.


Photo Credit: Ateco Tobler AG

Class 2: Hematite, Fe2O3.  This type forms in place, within the affected system.  This can be the result of surface damage within a stainless steel vessel or associated stainless steel tubing.  Hematite is brownish in color.

Class 3: Magnetite, Fe3O4.  This is the type that typically forms in high temperature steam systems.  This class of rouge is blackish in color an can be powdery or glossy.




Photos Credit: CPP Chemical Plants and Processes

Where to Expect Rouge

For the rouging process to occur you must have water present. This means that high purity water systems often are the source of Class 1 rouge found throughout processing systems. The distributed nature of Water for Injection (WFI) means that rouge can quickly migrate throughout multiple processing areas. Other sources of Class 1 rouge can be improper Material of Construction (MOC) fittings upstream from a system or from improper surface finish such as surfaces with an Arithmetic Average Roughness (Ra) measurement above 15-20 Ra. In some cases a process requires Electro-Polished (EP) surfaces which in conjunction with surface roughness are expressed as RaEP. Electro polishing is a process by which the “peaks” of a surface are removed through the use of an electric current and electrolyte. This provides a surface that has less surface area for reaction and fewer crevices for migrating rouge to take hold.

Turbulent water flow and cavitation can also damage the surface finish in tubing and pump housings resulting in a surface where the chromium oxide layer has been removed and exposure of the stainless steel surface higher in iron. As could be expected, rouge will form in these situations and this will also find its way into your process vessels.

Class 2 rouge is often the result of a damaged, previously passivated surface. CIP sprayballs can be the culprit in pinpoint rouge spots within a vessel as a result of high flow rates. Often times these spots will occur on the dome of the process vessel where they are not visible from sight glasses. This gives them time to form undetected and it’s not until rainbow-colored streaks of discoloration are noticed making their way down the vessel walls that their presence is discovered.


Photo Credit: Spray Balls by John C. Tverberg March 26, 2012

The air/liquid interface is also a prime location for rouge development as you have air and water, the key contributors. This is something to keep an eye out for in processes that require long wet vessel hold times and for vessels that are held for long periods of time prior to CIP post use and or are left wet post use.

Another scenario can be rouging from a damaged vessel wall or bent process tubing. Bent tubing may not be appear as an immediate concern however when one considers the surface of the tubing inside at the bend point, there could well be a change in the surface character by which underlying stainless steel layers are now exposed along with the higher iron content. A damaged surface example could be when a sight glass is being removed and a nut falls into the vessel and pings around a bit. The bottom outlet is removed and the wayward nut is removed from the vessel. This may seem like the problem is solved however the surface where the nut made impact is most likely damaged and no longer meets the required surface finish specification. An Ra measurement should be obtained or at a minimum this event should be recorded. Doing so will aid in the investigation should rouge begin to appear at the bottom of the vessel. If damage has occurred and the surface is not re-electro polished then pitting can occur that will require more extensive corrective measures such as grinding and filling with 316L rod followed by electropolishing.

Class 3 rouge is common in clean steam systems and less alarming that class 1 or class 2 rouge as it often in the stable form of Magnetite. Unless there is a powdery nature to the rouge, these systems can be operated for years with this rouge present without negatively impacting your process.

Rouge Remediation

Removal of rouge should be decided on a case by case basis. Some companies choose to establish monitoring programs by which the presence of rouge is observed and recorded for any changes in appearance or proliferation. This coupled with quality testing of product can often be sufficient to ensure that the presence of the rouge is not impacting product Safety, Identity, Strength, Quality or Purity.

Another approach has been to aggressively pursue the removal of all visible rouging from process systems. This should only be attempted after thorough investigation including classification of rouge present and best determination of sources. If the sources can be identified, in cases such as improper MOC fittings or pump cavitation due to non-optimal operating parameters, then it goes without saying that these identified causes should be addressed prior to overall system remediation.

Once the path of remediation has been decided on, there is really only one preferred method, Citric Acid Passivation. Other options exist such as Nitric Acid passivation and possibly even manual cleaning coupled with De-rouging CIP cycles. These latter two options have their drawbacks however.

Both Citric and Nitric acid passivation effectively remove surface contaminants from stainless steel and increase the Chromium Oxide to Iron Oxide ratio. However, Nitric Acid passivation can release toxic gases and must be disposed of as hazardous waste. Citric Acid on the other hand is organic and safe to use and does not require that it be treated as hazardous waste. Furthermore, with temperature elevation, Citric acid can accomplish passivation in a shorter period of time while Nitric Acid is more dangerous at high temperatures.

With regards to manual cleaning, this choice is not optimal as it subjects the vessel to possible damage. The process of entering a vessel for manual cleaning can be abrasive to the surface and increase the potential for scratching and gouging. This option is often chosen regardless of the drawbacks when there is substantial rouging that requires removal.

De-Rouging CIP cycles can all be used utilizing higher percentages of acid in the cycle. These ~5% acid cycles have proven to be effective in milder cases of rouging and as part of a preventative rouge program.


Despite our best efforts, rouging is here to stay. Though we decide on differing approaches to how to handle its presence, the fact remains that we can expect to see this uninvited guest in our process equipment and utilities. At least we can take comfort in knowing that this is happening industry wide and we can potentially learn from each other’s efforts.


Written B: Joe Herrick, Managing Consultant

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The Importance of Donating Your Time

In, 2014 there were over 610,000 homeless men, women and children in the United States and another 45 million people, that’s 15% of the total U.S. population, living below the poverty line. These statistics demonstrate a need for help, a need for volunteers to make a difference and support those that are disadvantaged.  Volunteering has proven to have positive benefits for the volunteer as well as for the person or community served.  Volunteering efforts, when organized properly, can help strengthen and repair communities, build lasting relationships and offer support to those in need.  Volunteering is a concept that has been around for centuries that has grown some of the largest organizations in the world.1

Volunteering has a history that spans across centuries and cultures.  The word volunteering stems from the French word voluntaire which means “one who offers himself for military service.”  In the 19th Century the United States experienced a turning point in American history known as The Great Awakening.  During this time, people started to become aware of the large disparities between the rich and the poor and developed a focus on the disadvantaged.  The Great Awakening gave birth to volunteer organizations such as The Salvation Army, the YMCA and The American Red Cross.5

On an individual level volunteering can enhance one’s hands-on skill sets, provide opportunities to meet new people and help give back to the community. Volunteering creates a visceral feeling and instills altruistic qualities that can last a life time.  The intentions of volunteering are to improve human quality of life and encourage goodness in others.  Volunteering does not require a large organized effort and could be as simple as shoveling a sidewalk for a disabled neighbor or helping someone carry their groceries.4

Company driven volunteering is a type of volunteering in which a company or an organization makes an investment in the employees, the company and the community for philanthropic purposes.  Company driven volunteering events can bring employees together to promote team work and encourage them to give back to the community.  It can provide team work activities, employee/management training and skill building, allow for leadership opportunities and allow companies to show their key values.  Common types of company driven volunteering may include organizing items at a food pantry, sending care packages to deployed troops, volunteering at a homeless shelters or cleaning a town park.

Integrated Commissioning and Qualification (ICQ) is a fast growing company that strongly values unique family dynamic that was established early on in an effort to maintain the culture we are rolling out programs like Company Driven Volunteering.  As a locally grown business originally from Rhode Island, ICQ has expanded both its reach and its horizon past the borders of RI, past the borders of the North East and past the borders of the United States.   As our corporate reach expands so must our efforts to maintain our core values.


ICQ’s first volunteering effort of 2015 involved assembling and sending care packages to deployed service members overseas.  On Saturday, February 21, 2015 over 20 ICQ employees and family members came together to assemble 50 military care packages.  Company driven volunteering events such as this are only successful due to the participation and effort from everyone involved.

Written By: Tyler Hassenpflug, Consultant I


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Method Transfer

h-pharmaMethod transfer is a regulatory requirement that is performed between two sites. It is a documented process to verify a certain laboratory’s capability of performing the analytical testing method’s intended use. Method transfers are performed for validated methods for which complete analytical methods and validation data are available.


Method transfer between laboratories and different company sites is needed throughout all pharmaceutical testing. Results have to be consistent throughout all testing being performed no matter where the testing takes place. For results to be considered valid all methods and test plans must be validated. As an example transferring a method from research and development to the quality group for a new a new product that will shortly be produced in manufacturing. It is important to properly have all acceptance criteria developed. After bringing the new method to your lab criteria on validating the method to ensure that it will work as planned must be determined. Once the new method is transferred to the new laboratory for testing all personnel that will be executing the method must be trained in the procedure.

ICQWritten By: Daniel Gabrault, Consultant

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Laughter, the Shortest Form of Meditation

Laughter, humor and smiling in the workplace can have a tremendously positive affect on a company’s culture. The use of humor, and the ability to produce and make humor, is associated with intelligence and creativity – two things highly valued in the workplace.

Smiling and laughter are free! They boost health, mood, longevity and success. When you smile, endorphins are released. We feel happier and less stressed, are able to think more clearly and creatively because our attention is widened, opening us to multi-tasking and insights that come from the fringes of our perception and subconscious.


Laughing is good exercise. It expands the lungs, stretching body muscles and stimulating homeostasis (maintenance of equilibrium). The added oxygen released by laughing replenishes and invigorates cells improving blood vessel function and increasing blood flow. A good bout of laughter can burn as many calories as rowing intensely for 10 minutes! Smiling – the universal sign of happiness – makes you appear more approachable, attractive, self-confident, self-assured and allows for easier interaction with others. When you smile you exude confidence and the ability to cope during stressful situations. Smiles use from 5 to 53 facial muscles, naturally lifting your face. Studies have shown smiling makes people appear younger. Smiling instantly improves spirits and reduces blood pressure. nita2 Infectious laughter and humor binds people together by promoting better teamwork, higher productivity (“whistle while we work”) and increased job satisfaction. Laughter is one of the most effective tools for keeping relationships fresh and exciting. When you’re in good spirits, learning ability is optimal because your mind opens to new ideas. When a learner breaks out of learning malaise, something unexpected is provided increasing the uptake of information; a neurological benefit occurs when emotion is experienced at the same time learning.


Written By: Nita Wilding, Assistant Controller

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A little about Cleaning Validation…

Cleaning Validation (CV) is driven by regulatory expectations to ensure that residues from one product will not carry over and cross contaminate the next product. Regulatory scrutiny is more rigorous in a multi-product facility compared to a single product establishment. Companies are usually cited either for not having a sound cleaning validation or not meeting the protocol acceptance criteria. Because failing protocol acceptance criteria is considered a substantial regulatory risk, companies tend to spend money and resources even though there is minimal or no product risk.


Visual inspection is a tool commonly used during cleaning validation. Visual inspections are used to verify there is no residue or excessive water pooling etc.


Cleaning Validation is handled by taking rinse water samples and by taking Total Organic Carbon (TOC) swab samples of the equipment. There are four different samples taken to be tested by Quality Control (QC) and they are Bioburden, Endotoxin, Conductivity and Total Organic Carbon (TOC).

Written By: Tim Cronin, Consultant II

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Season’s Greetings!


Everyone here at ICQ Consultants would like to wish our employees and colleagues a very happy holiday season and new year.  Thank you, everyone, for your hard work and dedication.  We appreciate all you do to assist in the success of our company.  We have had the pleasure to work with a multitude of outstanding professionals including both our employees and our clients.  Here is looking forward to a successful 2015!


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ICQ Consultants, Engineering Better Solutions



Integrated Commissioning & Qualification Corporation (ICQ) is a leading provider of commissioning, qualification and verification services to companies in the life sciences and pharmaceutical industries. We develop programs and procedures that promote, facilitate and ensure compliance with stringent regulatory standards and our clients’ own internal quality standards. During our history, teams of ICQ consultants have played a central role in the commissioning and qualification of multiple manufacturing plants in the New England area as well as North Carolina. ICQ consists of eighty plus employees all qualified in the different areas of the industry that we as a company specialize in.

We thrive on the long-term success of our clients. We at ICQ make every effort to establish strong continuing relationships. Our company strives to blend in at the client site and become an extension of each client company we work with. ICQ offers many services from the start-up and commissioning of new facilities, utilities, process equipment and processes to decommissioning or project planning. No matter which service you require we have an experienced professional to place into our client sites.

◊ Equipment/Facilities CQ &V ◊ Process Engineering ◊ Process Validation ◊ Manufacturing Operations ◊ Quality Systems and Remediation ◊ Consent Decree Remediation ◊ Construction and Program Management ◊ Project Planning and Scheduling ◊ Compliance Support ◊ Quality Control and Assurance ◊ Re-Qualification ◊ Decommissioning ◊ Commissioning Activities (IV, OV, IQ & OQ) ◊ Engineering Change Management ◊ Cycle Development (CIP & SIP) ◊ Engineering Test Plans ◊ Start-Up and Turn-Over ◊ Shake Down Activities ◊ Project Execution ◊ Cleaning Validation (CIP/COP) ◊ Sterilization Validation (SIP/SOP) ◊ Process Validation ◊ Mixing Validation ◊ Clean/Dirty Hold Validation ◊ Expiry Validation ◊ Cleaning Verification (CV) ◊ Validation Maintenance ◊ Assistance with Compliance Audits ◊ Development and Management of Compliance Action Plans ◊ Regulatory Readiness Inspections and Training ◊ Response to Regulatory Citations and Warning Letters ◊ Design of Quality Systems for New Facilities or New Process Lines ◊ Ongoing QA/QC Support ◊ Preparation of Regulatory Filing and Review Documents ◊ Implementation of Quality by Design (QbD), ICH-Q9, ICH-Q10, ASTM E2476, ASTM E2500 Principles and Approach ◊ Project Managers ◊ Project Leads ◊ C&Q Technical Leads ◊ C&Q Consultants ◊ C&Q Engineers ◊ C&Q Specialists ◊ Documentation Specialists ◊ Construction Managers


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The Process Validation Life-Cycle


Guidance on Process validation began in 1987 to address consumer recalls and complaints and assure consumers that their products were consistently made with the utmost quality. This guidance underwent some significant fundamental changes in 2011. If processes were “validated” as prescribed by the FDA guidance then why were products being recalled? Why were customers complaining about their products? Why was this happening? When something happens we ask why and get to the root cause(s).

The traditional approach for process validation was a snapshot in time. At a point in time a process demonstrated that it could achieve and maintain a state of control and consistently manufacture a particular product within prescribed acceptance criteria and quality standards. Controls were established to monitor the process and critical operating and performance parameters were identified and reproduced for a prescribed number of batches.

The FDA wanted to see more emphasis on process monitoring and demonstrating statistical control after you “validated” a process. An enhanced approach – a life-cycle approach was implemented and traditional process validation was divided into three stages/phases. Traditional process validation would correspond to Stage 2 activities. The transition from Stage 2 to Stage 3 is analogous to technology transfer to commercial routine manufacture. Stage 3 is the continuous process verification/validation of the commercial process.

process validation

Stage 1 Process Design, ensuring the work is down upfront to characterize and consistently reproduce within certain operating and performance parameters.

Stage 2: Process Qualification, qualifying equipment and utilities, performing process performance qualification (traditional process validation) ensuring the process is able to meet predetermined operating and performance parameters.

Stage 3: Continued Process Verification, ongoing monitoring of the process to ensure it continues to operate within established operating and performance parameters.

Validation is no longer a snapshot in time, it is composed of three stages, and each builds upon the other yet remains fluid. There is constant interplay between stages. Systems and process should be periodically evaluated to verify that they are still operating in a valid state. As experience is gained in commercial routine manufacturing, opportunities for improvements should be sought based on periodic review and evaluation, operational and performance data, and root-cause analysis of failures.

To maintain and control the manufacturing process, the focus had to become on process knowledge and process understanding throughout the life-cycle of the product. Understand and measure inherent product/process variability. A control strategy has to be developed to explain and justify how the product quality is managed and ensuring the operating and performance parameters remains in statistical control. Process control generates product consistency and quality. Process monitoring will provide the information needed to further understand the product/process and give you the information to refine your control strategy. In a feedback process, the continuous process verification is a key component assuring the ongoing effectiveness of the control strategy.

Some of my sources.

For the full article on Why did FDA change their Guideline on Process Validation? Click on http://www.gmp-compliance.org/eca_news_2600.html

Pharmaceutical Engineering Jan/Feb 2012   Control Strategy as the keystone of the product life-cycle, from product/process understanding to continuous process verification and improvement.

PV guidance, check the CDER guidance page at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, the CBER guidance page at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or the CVM guidance page at http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm

Written By: Lisa Conti, Senior Consultant

ICQ Consultants, Corp.


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Let’s Be Perfectly Clear

nitas word bubble

“The single biggest problem in communication is the illusion that it has taken place.”

-George Bernard Shaw

So, what is effective communication? And, how do I as an individual become an effective communicator?

Effective communication is about the exchange of information so that everyone gets something valuable out of the exchange (whether it be a conversation, an email, a presentation). To be an effective communicator requires just a few simple guidelines:overreacting beakers

  • find common ground and make a connection
  • be positive and friendly
  • actively listen and observe
  • be clear and concise
  • be aware of your body language
  • don’t overreact

Practicing effective communication skills in the workplace creates a positive and encouraging atmosphere for everyone. It helps reduce stress and frustration and increases productivity and moral.

Making sure rules and expectations are clearly understood and making work fun helps keep workers motivated and productive. Setting challenging and reasonable expectations and practicing openness and compassion shows you are human.

Honest interest and curiosity about the potential in everyone you encounter during the “communication” process demonstrates approachability. Speaking with positive sentence structures encourages people to be more interested in what you have to say.

Listen to others, don’t just hear them. Acknowledge and observe others and consider the situation fully by understanding, gathering and confirming information before making decisions. Make your message timely and effective.

Professionalism is very important. Remove emotions from the equation and don’t overreact. Clear and concise instructions, rephrasing and repeating, posing questions and the use of visual aids helps to ensure your message is understood.

Managers need to share the big picture – be transparent – and let employees know what goals you are aiming for. Be sure employees have the tools they need for the job. Trust your people, build trust by treating everyone s as individuals with different needs and personalities. Autonomy breeds innovation and job satisfaction.

Written By: Nita Wilding, Assistant Controller


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