The Enterey Blog

Enterey's On Cloud 9. Happy Friday!

Posted by Tita Tavares on Fri, Aug 02, 2013 @ 01:16 PM

Enterey Word Cloud
 Enterey's On Cloud 9 with We're having a fun Friday in the office. Have a great weekend everyone!

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Top Priorities of a Successful Inspection by Mark Tucker

Posted by Tita Tavares on Fri, Mar 09, 2012 @ 08:56 AM

All companies talk about conducting successful inspections but how many have clearly defined what a successful inspection is?  In this blog, I will talk about what I feel are key attributes in order for a company to deem their inspections a success.  


First and foremost, a successful inspection must allow you to obtain or maintain your right to manufacture and distribute a product.  Whether this is your first pre-approval inspection or a general GMP inspection, there are significant consequences for failing to get approval or to be found “out of a state of control.”  The inability to sell and market products caused by a failed PAI GMP inspection, affects not only your bottom line but the patients that need your products. 

The second priority for a successful inspection is to avoid less severe but still damaging regulatory or market actions, which include product withdrawals, product recalls, warning letters and even seizures.  While not as severe as losing the right to operate, these actions still affect the company financially by potentially causing a loss of revenue, a loss of market share, and a loss of stock value while also damaging your company’s reputation and opening the possibility for litigation.  

The above two priorities are critical to the success of the company.  However, there are other, less critical but still important, goals for managing inspections.

Minimize the number and scope of the findings:  I believe that many companies err in making this a critical outcome for an inspection to be considered successful.  While this goal is certainly important, it is more important in my mind to look at the bigger picture.  While you definitely want to minimize the number, scope and significance of findings, in some instances, it might be better to accept a finding rather than to continuing to “discuss” the issue during the inspection.  Inspectors are human, too, and if they feel you are arguing without merit (and if the goal is zero observations, this can occur), the tone of the inspection can be negatively impacted harming your ability to influence the outcome of a more significant issue later in the inspection. 

Maintain the confidence of the health authorities: You can damage your image with health authorities by the way you handle an inspection. Regardless of the outcome of the inspection, you need the health authorities to perceive you as being open and cooperative rather than closed and secretive. You need the health authorities to feel your company is committed to quality and doing “the right thing.”

Have few or no surprises during an inspection: If you have implemented a robust inspection management system that includes regular updates to Senior Management,   no one should be surprised by the inspection findings and outcome.  However, if there are surprises, it is important to review and assess your inspection management system to understand where there are still gaps and improve the system to try and ensure there is no recurrence.

Maintain good inspection logistics: By implementing a robust inspection management system, there should be good communication between the inspection room and preparation rooms.  Documents should flow smoothly and as requested after being appropriately vetted; presenters should be well-trained and informed of the current issue under discussion before interacting with the inspectors; and the right people should be available at the right time with the right information.  If you do this really well, you can minimize the effect of the inspection on your site’s operations. 

By defining what a successful inspection is for your company, you can ensure everyone is working together to meet those goals, which in turn, will increase the probability of having a successful inspection outcome.  At Enterey, in partnership with Mark Tucker, LLC, we can help you in all aspects of inspection management to help ensure you meet your inspection outcome goals.

Comments?  Questions?  We want to hear from you.


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Published by Mark Tucker | Inspection Management & Auditing Expert, Enterey and Mark Tucker, LLC

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Tags: Enterey, FDA, Inspection Management, Inspection Readiness, Inspection Management Systems, Mark Tucker, Enterey News, Drug Manufacturers, Life Sciences Industry News Life Sciences News & H, Communication, Pharma, PAI, Pre-approval Inspections

Process Improvement Award Winner with Global 500 Biotech Company

Posted by Tita Tavares on Thu, Feb 23, 2012 @ 10:58 AM


Austin Srejma Enterey Senior Consultant

Austin Srejma, Enterey Senior Consultant


"Enterey Project Wins Process Improvement Award From Global 500 Biotech Company"

See how we introduced a more efficient change control process to help the growth of a current biotech client. Congratulations to Austin Srejma for being awarded a process improvement award. 

"Austin Srejma has served as Senior Consultant with Enterey since July 2009. This is the second time one of her projects has received a process improvement award. Enterey Life Sciences Consulting, founded in 2002, provides Life Sciences Consulting expertise across both process and system-related projects. Enterey provides solutions for a wide range of client needs, from strategic planning to business-integration activities, implementation and specialized efforts, such as clinical and commercial facility start-ups. Enterey has a proven track record for successfully delivering projects within the biotech and pharmaceutical space"

Read further current press details highlighted in LA Daily News.



Tags: Enterey, Enterey News, Life Sciences News & Hot Topics, Facility Start-up, Life Sciences, Process Improvements, Life Sciences Communication, Life Sciences Consulting

Agency Inspections Are on the Rise

Posted by Tita Tavares on Thu, Jan 19, 2012 @ 11:44 AM

Inspections by the FDA and foreign regulatory agencies have significantly increased since 2003 as manufacturing becomes more global and other countries regulate drug products. Between 2003 and 2005, the number of foreign inspections performed by the FDA ranged between 218 and 252. By 2007, that number had increased to over 450 per year and by 2009, it was up to nearly 550, dropping to 522 in 2010. In 2008, joint inspections began between regulatory agencies. That process continues today:

 Enterey Agency Inspection Rise

With the current leadership at the FDA stressing enforcement (as opposed to repeated warnings) for any violations or irregularities, 2010 saw the following actions:

  • 10 seizures
    (5 CFSAN, 3 CDER and 2 CDRH)

  • 17 injunctions
    (the highest rate since 2006)

  • 673 warning letters
    (171 CDER, 204 CDRH, 15 CBER & 191 CFSAN ).  This was the highest rate in warning letters since 2004.

  • 3,799 recall events
    (1,881 CBER, 258 CDER, 876 CDRH & 738 CFSAN) resulting in 868 different drug products being recalled from the market.

As demonstrated by the data collected by EFPIA, Agency inspections in Europe hit their high point in 2009, then began to level out somewhat. We believe this leveling is due to the major, worldwide regulatory agencies reaching their inspectional resources limits.  The FDA is still conducting the most inspections in Europe followed by the EU, then Brazil, South Korea, Japan and Mexico.  Of concern to us is the ever-growing number of inspectorates conducting “foreign” inspections.  And while China is not represented in the 2010 data, they are anticipated to become a major inspectorate in coming years.


As more and more countries begin implementing GMPs as a requirement for import, inspections of facilities in the US may continue to increase. However, Regulatory Agencies are also realizing that the number of manufacturing sites is growing faster, worldwide, than their resources available to perform inspections. We hope the number of inspections being performed will remain close to current levels.

Several factors make us think this will be true. For example, having the US FDA and other global inspectorates gain entrance to PIC/S will hopefully allow for better information-sharing between agencies, including inspection reports and resource sharing by inspectorates through joint inspections, one example being the recent EMA and FDA joint inspections which should reduce the number of on-site visits by Health Authorities.


At Enterey, in partnership with Mark Tucker, LLC, we can help you meet all your inspection management systems needs. This includes a system to help you self-identify and fully understand your compliance gaps; prioritize work and allocate resources to close those gaps; track gaps, actions taken and assess residual risk; fulfill the compliance requirements of ICH Q10; maintain an inspection-ready posture at all times; and respond to Agency findings systemically and quickly.


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Published by Mark Tucker | Partner of Enterey

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5 Qualities of a Great Project Manager

Tags: Enterey, FDA, Inspection Management, Mark Tucker, ICH Q10, Drug Manufacturers, EU

Behind the Scenes of a Facility Maintenance Shutdown

Posted by Tita Tavares on Tue, Jan 10, 2012 @ 10:11 AM

Take a look at what happens behind the scenes of a facility maintenance shutdown. Facilities that go without a maintenance shutdown could suffer system breakdowns at the most inconvenient time – like while processing a batch worth millions of dollars.  If your facility’s heating, ventilation and air conditioning (HVAC) system breaks down during processing, your manufacturing environment can be compromised, which could then compromise your product.

Facility Shutdown Behind the Scences 

From an equipment standpoint, if a fan should stop working or if belts are not properly aligned, it could damage your system -- at a significant cost – as well as impact the cleanliness of your facility.

Typically, during a facility shutdown, maintenance should be performed on the following systems: HVAC; water systems: reverse osmosis deionized water (RODI) and/or water for injection (WFI), compressed air/gas systems, steam systems and other utilities.  This is a good time to test your backup generators and uninterruptable power supply (UPS) systems as well.

There are some other basic facility maintenance steps that should be planned during this downtime as manufacturing facilities all sustain a certain amount of wear and tear that may need repairs.  Take a look at the walls and floors for any significant damage and schedule any needed repairs. 

Use this opportunity to take a look at your process systems as well.  They could require minor or major annual, semi-annual or bi-annual maintenance during this maintenance shutdown.  With Biologics facilities, take a look at bioreactors, filtration systems, and chromatography skids, while at pharmaceutical facilities, it might be synthesizers and separation systems.  In addition to required maintenance, you can also use this facility downtime to make any desired modifications or upgrades to systems.

Maintenance shutdowns are typically scheduled for two to four weeks’ time, although this will vary depending on the size of the facility and the demands of the manufacturing schedule.  It is important that the maintenance activities are planned to ensure that the events go as smoothly as possible.  To ensure all repairs are made during this important time, it is best to contact your service vendors in advance so they can schedule time to be available onsite during your shutdown. 

Schedule your planning and coordination meetings as it is important to involve the different facility stakeholders.  Arrange for planning meetings with the stakeholders to discuss any proposed projects and their impact to the shutdown.  Develop a schedule of activities and ensure that it is communicated throughout the organization.  Schedule daily coordination meetings to track activities as they occur and make updates to the shutdown schedule.

Allow time for a restart of your facility and process systems and be on alert for issues.  Schedule the cleaning and environmental monitoring for the manufacturing areas as this will likely be required before the facility is released for manufacturing. 

By planning your facility shutdown in advance, you can look forward to a smooth shutdown, longevity of your systems, smooth uninterrupted operations, maximum efficiency, and cost savings to your systems by preventing expensive repairs and facility downtime.

Industry example:
Read about Ben Venue's extension of their manufacturing maintenance process.


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Published by Murtaza Kapadia | Senior Manager, Enterey

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Agency Inspections Are On the Rise


Tags: Enterey, Facility Maintenance Shutdowns, Facility Maintenance, Manufacturing Process

Why Inspection Management Systems Matter

Posted by Tita Tavares on Wed, Dec 28, 2011 @ 12:01 PM

There are many reasons why it is important for companies to develop and implement an effective inspection management system. In this blog, we’ll outline some of the reasons and how having an effective inspection system can benefit your bottom line.

Since FDA Commissioner Margaret A. Hamburg’s arrival in 2009, the FDA and other regulatory agencies have noticeably raised the bar on measures they are willing to take to protect patients’ safety. In her well-publicized speech of 2009 to the Food and Drug Law Institute entitled, "Effective Enforcement and Benefits to Public Health," Hamburg outlined measures being implemented to make the FDA stronger, more credible to the public, and more vigilant in their role of inspecting companies to ensure compliance. Her remarks included her desire for the Agency to take fast, effective actions when a company was non-compliant with the regulations.  As a result, the following actions have occurred at FDA:

  1. More Inspections: In 2011, more FDA inspectors were sent out in the field performing more inspections (particularly overseas).
  2. More/ Quicker Warning Letters: Companies no longer receive multiple warning letters like they did under previous administrations.  FDA is much more willing to take significant action after just one “poor” inspection.
  3. Elimination of Mandatory Legal Reviews: In doing so, the FDA has increased the speed of issuing warning letters while giving Districts more control over the tone and language of the letters.
  4. Post-Inspection Deadlines: Companies have 15 working days to respond to any problems that have been identified on the FDA 483 if they want to mitigate a possible Warning Letter.

 Why Inspection Management Gold

Increase in Consent Decrees: The FDA appears to be much more willing to use this Agency’s resource-intensive legal tool to get a company’s attention.  These actions are very expensive for both the Company and FDA; the willingness of the Agency to use this tool demonstrates their commitment to increase enforcement.


Willingness to Entertain Misdemeanor Prosecutions: At the 2010 FDLI Annual Conference, Eric Blumberg, FDA deputy chief for litigation in the Office of the Chief Counsel, heralded the reemergence of the Park Doctrine as part of FDA's new enforcement efforts. The Park doctrine allows the government to seek misdemeanor convictions against company officials for alleged violations of the FDCA – even if the officials were unaware of the violations – if they were in positions of authority to prevent or correct violations and did not.


A Good IMS Equals Good Business:

Implementing an inspection management system on an ongoing basis, 24/7, 365 days a year is just good business.  A well-functioning inspection management system is really a “work prioritization and resource allocation” tool designed to allow you to remain current in your compliance with appropriate laws and regulations.  With the multitude of areas that require maintenance, an effective system will help you rank your risks by criticality so that you can address your most urgent weaknesses and continually eliminate problems and issues.


A good IMS System:

  1. Allows you to self-identify and fully understand your compliance gaps.
  2. Allows you to prioritize work and allocate resources to close those gaps.
  3. Allows you to track gaps, actions taken, and assess residual risk.
  4. Helps fulfill the compliance requirements of ICH Q10 by helping to keep senior management informed about your state of compliance.
  5. Maintains an inspection-ready posture at all times so when the FDA inspector arrives unannounced, you are ready.
  6. Allows you to respond to Agency findings systemically and quickly.


Enterey, in partnership with Mark Tucker, LLC, offers a customized approach to help companies develop and implement an inspection management system that will help you meet these criteria. We will talk to you about what you have and need. Then, depending on your needs, we will help you develop an appropriate system and train your staff on implementation. Our training will allow you the ability to implement your new system, so that you can seamlessly interact with the Agency during and after an inspection.


What if a “Bad” Inspection Takes Place?

In the event of a bad inspection, we can help you prepare your response; including helping you understand if and where your inspection system failed.  Ultimately, your goal is to eliminate all gaps. If you invest upfront in preventative maintenance of your Quality system, you may avoid large expenditures on emergencies or reacting to regulatory agencies as you eliminate sources of error.   And when a significant issue does arise, you will be knowledgeable about the issue and able to present it to the FDA knowing you have done a good, documented investigation.  


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Published by Mark Tucker | Partner of Enterey


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Agency Inspections are on the Rise.

Tags: Enterey, FDA, 483 FDA Warning Letter, Inspection Management, Inspection Readiness, Inspection Management Systems, IMS, Mark Tucker

4 Rules to Facility Start-up. Looking Deeper Into Rule #3

Posted by Tita Tavares on Wed, Aug 10, 2011 @ 12:25 PM

Rule #3: A deeper look into facility start-up.


Remember Humpty Dumpty”

Now I’m sure you’re wondering what this rule has to do with facility start-ups, but before we go down that path let’s start with a simple exercise: draw Humpty Dumpty.  Go ahead, get out a sheet of paper and draw Humpty Dumpty.  It doesn’t need to be a masterpiece, just draw what you think of when you hear Humpty Dumpty…I’ll wait.   How many of you drew something that resembles an egg?  Before we go further, go ahead and read the typical version of the nursery rhyme “Humpty Dumpty”


Humpty Dumpty sat on a wall,
Humpty Dumpty had a great fall.
All the king's horses and all the king's men
Couldn't put Humpty together again

Facility Start-up

After reading the rhyme, I’ll ask a simple question, where does it say that Humpty Dumpty is an egg?  Obviously it doesn’t but we’ve been trained to think of Humpty Dumpty as an egg because someone drew him/her/it (I’ll use him for ease) that way many moons ago.  If you didn’t draw him as an egg; bravo!  I know I would have drawn him as an egg.  The point I’m trying to make is that it is important not to set artificial boundaries, particularly when trying to solve a problem.



During facility start-up the only thing you can count on is that things will change.  Issues will arise that are unexpected and that will require creative solutions.  When trying to come up with a solution just remember; Humpty Dumpty does not have to be an egg.  In other words, question everything and don’t set artificial boundaries for yourself.  Life sciences is already a regulated industry and you certainly don’t need to add more “artificial” regulations.

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Published by Carlo Odicino | Former Director, Client Services


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4th Rule of Facility Start-up

Tags: Enterey, Enterey News, Life Sciences Industry News, Facility Start-up, Life Sciences Industry News Life Sciences News & H

Where Do We Go From Here With Our Process Validation?

Posted by Tita Tavares on Fri, Apr 22, 2011 @ 01:00 PM

What are the next steps?

Having read our first 3 blogs to become familiar with the FDA’s recent Guidance for Industry Process Validation: General Principles and Practices (January 2011), you now need to start thinking about where you and your company go from here to align your organization and process validation activities with the new guidance.

Process Validation Success

NEXT STEPS to help you: 

1. Build your knowledge base early. A successful validation program relies on information and knowledge obtained early from product and process development. This knowledge and understanding is the basis for establishing your approach to controlling the manufacturing process through continued process verification to produce products with desired quality attributes.

2. Understand the sources of your variation and the impact this variation has on your process and product. Detect the presence and degree of variation in your process. Control your variation proportionate to the risk it poses to your process and product.

3. Develop and implement a Risk Management program. Establish procedures, train personnel, and document and manage your risks in a risk management plan to reduce, eliminate, or accept process risks.

4. Use a Lifecycle Approach. Process validation activities occur over the lifecycle of the product and process from Process Design (Stage 1) to Process Qualification (Stage 2) to Continued Process Verification (Stage 3).  Science and process understanding will increase through the lifecycle.

5. Perform process monitoring to continually analyze your product and process data to ensure a state of control. This will eliminate the need for revalidation. Opportunities for process improvements can be identified, evaluated and implemented.

6. Use an integrated team approach to Process Validation. Include subject matter experts from various disciplines including process engineering, industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing, and quality assurance. Project plans with full support of senior leadership are important to success.

7. Plan and conduct all studies using sound science, appropriately documented, and approved per established procedures throughout the product and process lifecycle.

8. Develop an ongoing program to collect and analyze product and process data as required per 211.180(e). The data should include process trends and quality of incoming materials, in-process materials, and finished products, and be statistically trended and reviewed by trained personnel. A statistician or person trained in statistical process control is recommended.

9. Identify gaps in your existing process validation procedures and implement a plan to revise them appropriately to meet the expectations in the new guidance.

10. Prepare to address questions and show documented evidence to demonstrate that your manufacturing processes have been validated and are in a state of control though continued process monitoring.

Published by: Jim Anthony, Enterey| Director

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Trends Update! Social Media in Life Sciences

Tags: Enterey, FDA New Guidance for Industry, Process Validation, Quality Assurance, Risk Management, Variation, Lifecycle Approach, Process Monitoring, State of Control, Process Improvements, Manufacturing Process, Industrial Pharmacy, Program Development, Identify Gaps, Life Sciences Industry News Life Sciences News & H

What Are the Differences in the New Process Validation Guidances?

Posted by Tita Tavares on Thu, Apr 14, 2011 @ 04:40 PM

  Enterey Process Validation Differences

What should you be doing differently?

There has been an FDA industry paradigm shift, with which you will need to align. Provided below is an easy reference table pointing out key elements of FDA’s Guidance for Industry Process Validation: General Principles and Practices (January 2011), some of the differences in the new guidance, and the areas of focus for FDA during their next inspection of your facility as it pertains to process validation.

Take a look at how these modifications could influence today’s current practices.

FDA Guidance for Industry
Process Validation: General Principles and Practices (2011)

Scope includes entire Product and Process Lifecycle

Decisions are based on Sound Science and Risk Management

3-Staged Approach to Process Validation:

1)       Process Design

2)       Process Qualification (PQ)

3)       Continued Process Verification

Emphasis on Process Design – Process design is dependent on process knowledge and understanding obtained; testing to failure is not required or expected; studies are conducted with sound scientific methods and principles, including good documentation practices

Process Qualification (PQ) differs from 1987 guidance - Process Performance Qualification (PPQ) is milestone in product lifecycle prior to commercial distribution; PPQ  is based on sound science, product and process understanding, and demonstrable control

Emphasis on Continued Process Verification and Process Control – Process knowledge and understanding is basis for approach to process control; ongoing program must be established to collect and analyze product and process data, trends, quality of incoming materials, in-process material, and finished products

Statistics – Statistician or person with adequate training in statistical process control to develop data collection plan for Continued Process Verification, statistical methods and procedures to measure and evaluate process capability, intra-batch and inter-batch variation is recommended

Revalidation and Retrospective Process Validation has been eliminated with Continued Process Verification

There is no magic number of required lots or runs in PPQ;  a documented justification and rationale that assurance is achieved and the process is in a state of control is stated in the PPQ Protocol Execution and Report

Level of PQ effort, documentation, testing, degree of control over attributes or parameters during Continued Process Verification, etc. are all commensurate to the level of risk to the process or product

Publishe by: Jim Anthony, Enterey | Director

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Tags: Enterey, Enterey News, FDA New Guidance for Industry, Process Validation, Process Verification, Process Qualification, Reference Guide, Process Design, Statistics, PPQ, PQ, Product Lifecycle, Process Lifecycle, Differences in Process Validation Principals and P