The Enterey Blog

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.  

Inspection 

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

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

Key Points & Concepts: FDA’s New Guidance Docs for Process Validation

Posted by Tita Tavares on Mon, Apr 11, 2011 @ 11:00 AM

FDA: NEW Guidance for Industry Process Validation: General Principles and Practices - Issued January 2011

FDA’s new guidance aligns process validation with the product lifecycle concept and ICH Guidelines Q8 (R2) Pharmaceutical Development, Q9 (Quality Risk Management), and Q10 (Pharmaceutical Quality System).

The guidance encourages the implementation of modern development concepts of Quality by Design (QbD), such as design space, Quality Risk Management (QRM) and control strategy, throughout the product lifecycle.

The lifecycle concept links product and process development, qualification of commercial manufacturing process, and maintenance of the process in the state of control during commercial production.

Process Validation Key Points and Concepts

The guidance supports process improvement and innovation through sound science and knowledge management.

Effective process validation contributes significantly to assurance of drug quality and that the drug produced is fit for its intended use.

The guidance defines process validation as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product.

 

Process validation activities occur over the product and process lifecycle in 3 stages:

1 | Process Design: The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities. The goal of this stage is to design a process suitable for routine commercial manufacturing that can consistently deliver a product that meets its quality attributes.

Process knowledge and understanding are obtained and captured during this stage. Studies should be conducted with sound scientific methods and principles and documented. Design of Experiment (DOE) studies help develop process knowledge. Risk analysis can be used to screen variables to minimize number of experiments while maximizing knowledge gained. Process information from product development can be leveraged in the process design stage and used in process qualification and continued process verification stages when the process design is revised or the control strategy changed.

The process knowledge and understanding gained at this stage form the basis for establishing a process control strategy.

 

2 | Process Qualification: During the process qualification (PQ) stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.

PQ consists of 2 elements:
1) Facility design and qualification of equipment and utilities
2) Process performance qualification (PPQ).

Facility design and commissioning precede PPQ. CGMP procedures must be followed.

Completion of this stage is necessary prior to commercial distribution. If acceptable, products can be released for distribution.

The PPQ combines the actual facility, utilities, qualified equipment, and trained personnel with the commercial process under normal operating conditions.

A successful PPQ confirms process design and demonstrates commercial manufacturing process performs as expected. PPQ is based on sound science and manufacturer’s overall level of product and process understanding and demonstrable control. Higher level of sampling, additional testing, and greater scrutiny of process performance usually occurs during PPQ. The PPQ protocol is reviewed and approved by quality unit. The PPQ protocol execution and report, also reviewed and approved by all appropriate departments and quality unit, state a clear conclusion that the process is in a state of control.

 

3 | Continued Process Verification: During this stage, there is continual assurance that the process remains in a state of control (validated state) during commercial manufacture.

An on-going program to collect and analyze product and process data must be established. Data collected includes process trends and quality of incoming materials or components, in process materials, and finished products. Data should be statistically trended by trained personnel Production data is collected to evaluate process capability and stability. Continued process monitoring and sampling occurs at the level established during process qualification until sufficient data are available to generate significant variability estimates. Monitoring can then be adjusted to statistically appropriate and representative levels.

Knowledge and understanding gained is the basis for establishing an approach to control the process.

Manufactures should understand the sources of variation, be able to detect the variation, understand the impact of variation on the process and product, and control the variation commensurate with the level of risk to the process and product.

Controls can consist of material analysis and equipment monitoring at significant processing points.

Manufacturers of legacy products can benefit from knowledge gained from the original process development, qualification and experience. Legacy products and processes would likely begin with Stage 3 activities for continued process verification.

Homogeneity within a batch and consistency between batches are goals of process validation activities. 

 

Recommendations:

FDA recommends an integrated team approach to process validation with subject matter experts from process engineering, industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing, and quality assurance. Project plans and full support of senior management are necessary for success.

Published by: Jim Anthony, Enterey | Director

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Up Next: What is different about the new process validation guidance? What should we be doing differently?

 

Tags: Life Sciences Industry News, Life Sciences News & Hot Topics, FDA New Guidance for Industry, Process Validation, ICH Q8, ICH Q9, ICH Q10, QRM, Quality Risk Managment, Process Verification, Process Qualification, Facility Design, CGMP, DOE, Quality Assurance, Drug Manufacturers