Actions for Noncompliance of cGMPs in the Quality Control Laboratory

Quality controls in laboratories are a major area for which the FDA issues 483’s. A laboratory is the venue for many activities, all of them of varying importance to the product. When controls in laboratories are not up to the standard, such a laboratory could produce products that do not meet quality and processes expectations, and hence invite 483’s.

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Issues with drug quality, drug integrity and data integrity, as well as data fabrication and human errors and even behavior towards the FDA inspectors during inspections are some of the reasons for which laboratories get hauled up by the FDA. The inappropriate or incomplete implementation of cGMPs in the Quality Control labs is a major area for which the FDA takes penal actions against them.

Most common areas of noncompliance

These are some of the most common areas in which the FDA is likely to find issues relating to cGMPs in Quality Control laboratories:

  • Out of Specification lab results
  • Laboratory error- improper analysis method, use of incorrect standards, and/or miscalculation of data
  • Operator error or non-process error
  • Fault in the manufacturing process
  • Product failures
  • Laboratory documentation and records
  • Validation of methods
  • Equipment errors
  • Problems with raw materials
  • Lack of in-process controls and specifications
  • Management of the laboratory
  • Unexplained anomalies

Ways of avoiding penal actions

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From about the 1980’s, the FDA has been targeting Quality Control laboratories ever more stringently. The way of avoiding receipt of 483’s, which could escalate into a Warning Letter if it not addressed properly, is to be aware of all the ways by which to meet the FDA’s requirements of cGMPs in Quality Control laboratories. Some of the steps a QC laboratory needs to take to avoid FDA actions include:

  • Carefully reviewing and analyzing the regulations, inspectional guidance, 483 observations and Warning Letter and internal audit observations and deviations
  • Thoroughly reviewing laboratory practice and procedures
  • Gaining knowledge of the areas the investigators review and the type of observations that are made in other organizations and using this information to ensure that their laboratory operations are improved

Implementing actions based on these is at the root of its strategy for avoiding future observations of non-compliance and the issuance of 483’s from the FDA.

A valuable learning session on implementing these

How do laboratories do all these? How do they implement the correct cGMPs in their Quality Control laboratories, so that they meet the FDA’s compliance requirements? A webinar on this highly relevant and meaningful topic from Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will show how.

John Lanese, an independent consultant with a focus on Quality Systems and the components of an effective Quality System and Founder of The Lanese Group, which consults with small and large medical device and pharmaceutical companies, including companies under FDA Consent Decree, API and excipient manufacturers, electronic firms and other manufacturing organizations; will be the speaker.

Please register for this highly valuable session by visiting and learn all that it takes to implement cGMPs in the Quality Control lab and avoid harsh penalties from the FDA, which could set your business back.

A thorough approach to imparting lessons on cGMPs

This is the approach that John will adapt for inculcating the lessons on cGMPs in the Quality Control laboratory:

He will apply one aspect of a proactive approach and review how this approach can be implemented for meeting regulatory requirements. He will then analyze 483 and Warning Letter observations to determine if similar observations that could serve as a benchmark to initiate further preventive actions could be made in the participants’ facility.

John will explain the non-conformances most often cited by the FDA, along with the relevant regulation. He will then show specific observations that relate to the laboratory cited in Warning Letters and FDA 483s. John will use these real life examples to show to participants the ways of analyzing what went wrong. He will explain the systems, procedures and records the laboratory should have in place that would prevent a similar observation. He will also familiarize the participants with several questions that a laboratory manager or an auditor might ask to assure that appropriate systems, procedures and records are in place and are being followed.

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Key personnel in laboratories, such as Quality Control Laboratory Managers, Quality Control Laboratory Supervisors, Quality Control Analysts, Quality Control Microbiologists, Quality Assurance Managers, and Quality Auditors will gain immense benefits by participating in this webinar. They will be able to critically evaluate key areas in the laboratory operations for compliance and identify areas for improvement after completion of this webinar.

John will cover the following areas at this webinar:

  • System Based Inspection Guidance
  • Laboratory Control System
  • Most common observations in the laboratory
  • 483 and Warning letter observations
  • Analysis of observations
  • Areas for preventive action.

The role of validation in HACCP

The Hazard Analysis and Critical Control Point (HACCP) is a process control system that is aimed at identifying the points or areas at which hazards (dangers) may arise in the food chain. It prescribes strict measures for manufacturers and transporters of food products to prevent contamination and the resultant hazards. Control of hazards in the food chain has always been a need, but HACCP assumes added significance in today’s world, where globalization has made it possible for food to travel to hitherto unexplored parts of the world.

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While this development has increased the choices before the consumers of food; it also brings challenges in the form of having to maintain hygiene and cleanliness standards throughout the often long food chains, usually over long periods of time. HACCP is considered a path breaking system in that it looks at food hazards very holistically and comprehensively. It seeks to control the onslaught of major microbiological contaminants in food such as E.coli, salmonella, listeria and many others that could cause diseases.

Tackling contamination from all sources

HACCP adapts a comprehensive view of all the sources of contamination, and seeks to prevent risks to food from all sources, such as:

  • Microbiological
  • Chemical
  • Physical

In addition, it also prescribes steps aimed at putting in place a hazard control system that consists of seven important steps:

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  1. Conducting a hazard analysis for identifying potential hazards that could enter the food production process
  2. Identifying the critical control points (CCPs), which are points in the process in which the potential hazards could occur and taking steps to prevent and control them
  3. Establishing critical limits for preventive measures associated with each CCP
  4. Establishing CCP monitoring requirements to ensure that each CCP stays within its limit
  5. Establishing corrective actions where monitoring shows that a CCP is not within the established limits. The aim of the corrective actions is to prevent public health hazards from occurring
  6. Establishing effective recordkeeping and documenting procedures to ensure that the HACCP system is working rightly. Documentation should show the ways in which CCPs are being monitored, as well as verification activities and deviation records
  7. Establishing procedures for verifying that the entire HACCP system is working and offering the desired outcomes.

Good intentions not backed by validation requirements  

The noble intentions behind the HACCP systems and the stringent and serious endeavors towards their implementation notwithstanding; one grouse that food experts have had of the HACCP till recently is that the validation aspect of these hazards has not been given the same importance as other factors. Validation has no doubt been a part of HACCP, but somehow, it has been sort of overshadowed by the emphasis on verification.

It is only of late that validation has been gaining in prominence as a control measure. Companies need to validate their products by properly designing and taking adequate control measures that are capable of controlling food hazards within the process.

Understanding the role of validation in HACCP

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A valuable learning session that will emphasize the importance of validation in the HACCP system is being organized by Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance.

Ruth Bell, a Food Safety/Quality and HACCP Management Consultant, Auditor and Trainer, who has worked on a number of projects helping organizations throughout the food chain to design, develop, implement and verify manageable food safety systems tailored to their needs, is the speaker at this webinar. Ruth is well known for her practical Quality and HACCP knowledge as an auditor, consultant and trainer. Please register for this webinar by visiting Food Safety Control Measures

Putting in place scientific validation measures

The aim of this session is to drive home the importance of validating food safety control measures to ensure food safety management system capability. Validation of food safety control measures is an essential measure in ensuring that a food safety management system will be capable of producing safe food and remains effective over a period of time.

Validating food safety control measures requires a theoretical examination of the scientific justifications for the control measures identified and practically challenging them to determine they will be suitable and capable of consistently achieving the required level of control to ensure safe food.  Ruth will dwell on these aspects in detail at this webinar.

This webinar is aimed at HACCP team members and leaders, technical/quality managers, food safety managers, as well as auditors of food safety and HACCP systems, and specifically for specialists in positions such as HACCP Team Members, Technical Managers, Production Managers, Engineering Managers, and Consultants.

The speaker will cover the following areas at this webinar:

  • Current Guidelines for Validation
  • Differences between Verification and Validation Activities
  • Components of Food Safety Management System Validation
  • Validation Techniques including SPC, Predictive Microbiological Methods, and Challenge Testing.

Ways of getting the PREDICT, ACE and the HTS right to smoothen shipping

In September 2014, the FDA deployed a new risk-based screening tool for imports called the Predictive Risk-based Evaluation for Dynamic Import Compliance Targeting (PREDICT). The main aim of PREDICT was bringing about improvement in screening and targeting of adulterated or misbranded goods or those that flout any of the FDA’s rules. The FDA seeks to bring this about by doing away with its legacy electronic system, OASIS’ admissibility screening function.

PREDICT is an important tool that helps entry reviewers target and inspect higher-risk shipments. In parallel, PREDICT also smoothens and accelerates the clearance of any cargo that carries lower risk, so long as accurate and complete data are provided by importers and entry filers.

The new import requirements have now become harsher and effective in unison with the U.S. Customs and Border Protection’s ACE software program. These programs together look for a lot more information from the foreign source of the goods than earlier. Not only are these requirements linked to the FDA’s product codes and U.S. Harmonized Tariff Schedule (HTS); there has to be a match between the information entered on the entry’s commercial or pro forma invoice with the one provided in and entered into PREDICT and ACE software.

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In the event of even a minor error or mismatch in the software coding information, importers and shippers can expect expensive delays and a possible refusal of the entry. Those who participate in a voluntary Affirmation of Compliance (AOC) are allowed some lenience by the FDA from the strict requirements. Yet, providing accurate information is imperative for aligning and reconciling the information contained in PREDICT, ACE, Invoice and AOC. Any lapse in adhering to any of these procedures or ensuring the accuracy of the data match has major consequences in the form of fines and delays.

It is critical to get all the procedures in the right order

In the nearly three years that the new import entry filing requirements have been in place, users have been facing problems. What happens when the importer is unable to meet the FDA’s and the Customs and Border Protection’s requirements? There are costly delays. When these delays happen, the importer has to turn to the FDA to resolve the problem. This can be tedious. The only really effective antidote to these issues is paying full and proper attention to how to use the two programs and getting their implementation right to a T.

And then, the importer has to also complete the task of linking the FDA’s and U.S. Custom’s software to an importer’s legal requirements by using the correct Harmonized Tariff Schedule (HTS) code. This is a major determinant of how the FDA will apply its requirements. Importing, however, becomes easier if the information on the manifest, invoice and affirmation of compliance are consistent with each other and correct. So, the crucial task for the importer is to get the harmonization of all these right, because apart from marking out a wrong entry as a problem that requires greater scrutiny for data verification; the FDA will also impose fines for filing incorrect entry data in ACE.

Proper guidance on the ways of meeting these requirements

Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will be organizing a webinar aimed at helping importers, shippers and others related to these activity get the alignment and matching of the PREDICT, ACE and the HTS right.

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Casper Uldriks, who owns the firm, Encore Insight LLC and has worked for over 32 years with the FDA or its divisions at various levels, will be the speaker at this webinar. His having developed enforcement actions and participated in the implementation of new statutory requirements over many years has given him sharp insights into the FDA’s way of thinking. If sharing the insights this expert brings into the FDA’s software programs is relevant to you and interests you, please register for this webinar by visiting Software Screening Program

The intention of this webinar is to explain the benefits from the new requirements of the software programs, which help importers to streamline the import documentation and let them check the status of their entry, as well as the communications between an importer or its broker and U.S. Customs.

Casper will cover the following areas at this webinar:

  • FDA’s required information for the PREDICT software screening prior to entry
  • FDA product codes
  • Custom’s required information for the ACE software system prior to entry
  • Custom’s Harmonized Tariff Schedule (HTS)
  • Affirmation of Compliance (AOC).

Understanding and applying ICH Q3A and Q3B

The ICH Q3A and Q3B are guidances on dealing with impurities in new drug products. These documents have been issued by the FDA and are updates of earlier versions on the same topic that were prepared by the ICH, which this FDA guideline complements. This is why the documents get their name. The FDA keeps revising these documents from time to time. After every revision, the latest version carries the added taxonomy of “R” to denote that the guidance is a revised one.

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The Q3A and the Q3B are two revised guidelines that relate to impurities in drugs. Impurities can happen due to a number of reasons. These are some of them:

  • Raw materials
  • Byproducts
  • Residual solvents
  • Reagents
  • Product reactions
  • Catalysts
  • Foreign impurities
  • Product degradation

The ICH guidelines Q3A and Q3B deal with the ways of addressing organic and anorganic substances, respectively.  They both follow the principles of reporting, identification and qualification of impurities at defined limits. They both exclude impurities arising out of the excipients of drug products.

Scope of Q3A

The scope of the Q3A guideline is limited to testing of impurities in new drug substances. It concerns itself with the content and qualification of chemical substances in new drugs. It is not meant for products derived from herbal, crude, animal or plant, or semi synthetic origin. It is also not for products in the clinical trial stage or for addressing extraneous contaminants, polymorphic forms or enantiomeric impurities.

Scope of Q3B

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The scope of the Q3B guideline differs in some ways from that of Q3A. It is meant for the content or qualification of degradation products. It excludes products of all the sources that Q3A does, and additionally also excludes impurities arising from excipients or extractables/leachables of the container closure system.

Thorough and full understanding of these guidelines

It is to offer a complete and thorough knowledge of how to apply the Q3A and Q3B guidelines that Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will be organizing a webinar. Greg Martin, who is the President of Complectors Consulting (www.complectors.com), which provides consulting and training in the area of Pharmaceutical Analytical Chemistry and served as Director of Pharmaceutical Analytical Chemistry (R&D) for a major Pharma company for a number of years during his over 25 years of experience in the pharmaceutical industry; will be the speaker at this webinar.

To gain clear insights into how these ICH/FDA guidelines apply to your laboratory or area of work, please register for this webinar by visiting Applying ICH Q3A and Q3B for Control

All about the guidelines and regulatory expectations

The objective of this webinar is to provide participants with an understanding of the regulatory expectations for controlling impurities and degradants, including DNA reactive/potential genotoxic impurities, in drug substances and drug products.

Participants who complete this course will be able to:

  • Understand regulatory expectations regarding impurities, degradants and potential genotoxic impurities in pharmaceuticals
  • Understand what specifications will conform to regulatory expectations
  • Develop a process for reporting impurities and addressing OOS situations

Greg will cover the following areas at this webinar:

  • Landscape of impurities requiring control in pharmaceutical products
    • General impurities: elemental impurities, residual solvents, microbiological
    • Drug-related impurities process impurities, degradants, potentially genotoxic impurities
  • Process Impurities
    • Understanding ICH Q3A
    • Where impurities originate
    • How impurities are characterized
    • How specifications are developed
    • How impurities should be reported
  • Degradants
    • Understanding ICH Q3B
    • Where degradants originate
    • How degradants are characterized
      • Potential genotoxic impurities
    • How specifications are developed
    • How degradants should be reported
  • Questions and discussion

Understanding GLP’s and their relationship with GMPs and SOP’s

Good Laboratory Practices (GLP’s) are a series of federal regulations passed in the US by the FDA under 21 CFR Part 58. In addition, Environmental Protection Agency (EPA) also has formed GLP’s both for Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) in 40 CFR Part 160 and for Toxic Substances Control Act (TSCA) in 40 CFR Part 792.

Biotechnology concept

GLP’s are Quality Systems that relate to the processes and conditions that organizations carrying out nonclinical studies concerning health and the environment have to comply with. The objective of creating these processes and conditions is to ensure proper planning, performance, monitoring, recording, archiving and reporting of these studies. GLP’s are not just guidelines; they have the effect of a law.

The intention of framing GLP’s is that a minimum standard has to be established for conducting nonclinical laboratory research. This acts as the basis for research or marketing of products that are regulated by the FDA or the EPA. Typically, products that come under GLP’s include:

  • Animal food additives
  • Medical devices that are meant for human use
  • Biological products
  • Pesticide products
  • Human and animal drugs
  • Electronic products

Cosmetic products do not come under GLP’s.

An understanding of GMPs

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Good Manufacturing Practices or GMPs are quality assurance standards which ensure that consistency and control go into the manufacture of products and that these products are in accordance with their quality standards that are required for their Intended Use and in conformity with the Market Authorization or the specifications that the product has to have.

What are SOP’s?

Standard Operating Procedures (SOP’s) are detailed written instructions that are aimed at bringing about maximization of safety and efficiency in the operations of select types of organizations such as:

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  • Pharmaceuticals
  • Clinical research
  • Emergency response
  • Government
  • Power

 

 

 

 

How are GLP’s related to GMPs and SOP’s?

Do GLP’s, GMPs and SOP’s have a close relationship with each other? How are they, all being vital elements of the industries to which they relate, connected with each other? GLP’s have nothing to do with GMPs, but what about SOP’s? What is the nature of the similarities between these and what are their differences?

This will be the important learning a webinar from Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will offer. At this webinar, the speaker is Joy McElroy. During the over 20 years of working in the pharmaceutical and biotech industries, Joy has gained extensive knowledge of Quality Assurance, Process and Cleaning Validation, and Equipment Qualification, which has enabled her to write and execute Equipment Qualification and Validation Protocols for several well-known companies.

To comprehend the nature of the relationship between GLP’s, GMPs and SOP’s, please register for which webinar by visiting Associated with GMPs and SOPs

Comparison and differences between GLP, GMP and SOP

Professionals such as Quality Assurance Personnel, Quality Control Personnel, Research and Development Personnel, Regulatory Affairs Personnel, Project Managers, Manufacturing Managers, Validation Engineers, Internal Auditing Personnel, Microbiology Personnel and Auditors will learn everything from:

  • What GLPs are
  • Why they were created
  • The objective of GLP’s
  • How they relate and are associated with GMPs.

Joy will explain what GLP’s are and help participants understand and compare the differences with GMPs.

 

Steps to IEC 60601-1 approval

The 60601-1 is a standard that relates to the safety of medical electrical equipment. This harmonized standard is recognized by most countries around the world. Existing and new medical devices have to comply with the requirements set out in IEC 60601-1.

The IEC 60601-1 is going through its latest revision, its 3rd edition, which came into effect in June 2012. The regulatory agencies of various countries that have adapted this standard are in various stages of implementation. Documentation and certification for IEC 60601-1 is to be done in stages at various dates, which will go up to 2018.

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Major product safety changes brought about by the 3rd edition

Through the publication of Amendment I, IEC 60601-1 brings in around 20 new requirements and some 60 modifications to the existing requirements. The major change IEC 60601-1’s latest version, 3.1 of the 3rd edition brings is that it makes a risk management file and process that aligns with ISO 14971 mandatory for manufacturers of medical electrical equipment. The ISO 14971 is the global standard that applies to risk management in medical devices.

The IEC 60601-1 3.1 Edition also requires design review and third party approval for medical devices. In addition, this version has also modified requirements in relation to these among many other areas:

  • Essential Performance
  • Documentation
  • Humidity
  • Marking and Labeling
  • Temperature Testing
  • Programmable Electrical Medical Systems (PEMS)
  • Mechanical Hazards
  • Electrical Hazards
  • Construction

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Stay clear of the complexity

Want to understand the ways by which the new IEC 60601-1 version works for your organization? Want to clear the confusions regarding implementation of the new IEC 60601-1 standard and gain acceptance by meeting compliance requirements set out by the various regulatory agencies? A webinar that is being organized by Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance will provide all the answers.

The guru of IEC 60601-1, Leonard Eisner, will be the speaker at this highly insightful session. The Founder and Principal Consultant at Eisner Safety Consultants, which specializes in helping medical device manufacturers through product safety, international regulatory (FDA 510(k), CE Mark, Canadian Medical Device Regulations (CMDR), etc.) and quality system processes; Leo, a licensed professional engineer in safety engineering, a Notified Body and Quality System auditor/technical reviewer, an expert in product safety for medical electrical devices (IEC 60601 series of standards) and an expert in CE marking for the medical device EU Directives, has helped countless clients through the Product Safety and Regulatory maze over his career.

To register for this highly interesting and relevant session, please visit 16 Steps to Get Approval to IEC 60601-1

Learning from others’ mistakes

Leo will help participants accelerate their time to market. He will show how to follow the steps and hasten the speed at which they can obtain their product certification to IEC 60601-1 series of standards. All the expectations for product testing set out by certification agencies to the IEC 60601-1 series of standards on medical electrical equipment and systems, such as UL, TUV, BSI, Intertek, etc., will be explained.

An important element of the learning at this webinar is the ways by which to learn from the mistakes Leo has seen others make that have gone on to slow their certification process. He will show the participants what proactive steps they can take to avoid these mistakes and ensure that their product doesn’t need to get redesigned after testing starts.

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Leo will cover the following areas at this webinar:

  • Learn about the scope of the IEC 60601-1 standard & if it applies to your product. Also, what are the Collateral Standards (IEC 60601-1-X) and Particular Standards are about
  • What you need to know to classify your products to the IEC 60601-1 series
  • What is an isolation diagram and how does that help me with my design?
  • Determine the applicable tests for your device
  • What are the marking and labeling requirements for the device?
  • Know your critical components
  • What pre-tests to run and what’s not worth pre-testing?

How to control those risks and monitor the effectiveness of the controls put in place

Overview of this session Product Risk Management is a critical aspect of ensuring medical devices are safe and effective for intended uses. This course will help you understand the regulatory requirements, including ISO14971, and how to create processes and procedures to implement them.

You’ll learn techniques that can help you identify hazards and potential harms. You’ll learn how to mitigate risk and effectively monitor risk to ensure your customers receive safe and effective products. A rigorous risk management process can prevent serious problems and costs for your company.

risk-management-definitionIn this webinar we’ll cover:

  • Overview and Definitions
  • FDA Expectations
  • ISO14971 Regulation
  • Linkages to Design Controls, Production Controls, Investigations, and CAPA
  • Risk Management throughout the product lifecycle
  • Common mistakes
  • Best Practices

Why should you have to Attend The cost of poor product risk management can be staggering. Complaints, Medical Device Reports, recalls, and serious adverse impact to your customers can all result from poor risk management. And these types of problems expose you to regulatory inspections and citations. Many companies have even experienced class action law suits because of product quality issues. An effective program of risk management can help you proactively identify and mitigate product risks. A good risk management process can help you methodically identify, mitigate, and monitor risk throughout the product life-cycle.

These are the areas covered by the speaker Susanne Manz

  • Overview of the ISO14971 standard as it applies to medical device companies
  • Integrating the new standard with ISO 13485 as part of your overall QMS
  • Conducting a review of the intended use of your device
  • Stages of Risk Management as well as Tools and Techniques
  • Identifying hazards in your product or production process, and estimating their severity
  • Judging the probability that harm may occur from those hazards
  • How to control those risks and monitor the effectiveness of the controls put in place

By login with this Risk Management Techniques for Medical Devices

Which are the experts benefited by this session are as shown in the below

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  • Design Engineer
  • Manufacturing Engineer
  • Quality Engineer
  • R&D Personnel
  • R&D Project Managers
  • Quality Managers
  • Auditors
  • Regulatory Affairs Specialist
  • R&D Manager

Susanne Manz is an accomplished leader in the medical device industry with emphasis on quality, compliance, and six sigma. She has an extensive background in quality and compliance for medical devices from new product development, to operations, to post-market activities. While at GE, J&J, and Medtronic, Susanne worked in various world-wide roles including Executive Business Consultant, WW Director of Quality Engineering and, Design Quality, and Director of Corporate Compliance. Susanne has a BS in Biomedical Engineering and an MBA from the University of NM.