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.

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).

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.

Understanding the way the FDA works in handling food imports

The FDA’s task is cut out when it comes to one of its core functions –that of regulating imports. With the US economy absorbing food imports to the tune of $ 49 billion every year and with its allied regulatory agencies overseeing an astronomical number of nearly half a million facilities in the US and abroad; the FDA is certainly in a most unenviable position.

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In view of the fact that these foods are imported from almost all over the world to be sold into the US market; the FDA has strict regulations for ensuring the quality of the food items that enter the US market. Its primary task is to ensure that the foods and food products that enter the US market met the rigorous standards it sets in relation to safety, sanitation, wholesomeness and labeling.

Coordination with agencies across the country

Considering this fact, plus the fact that over two thirds of seafood and more than a third of all the food items consumed in the US are imported; it is no surprise that the FDA has a varied number of agencies with which it coordinates and whose help it takes to carry out its functions. These are some of them:

  • Homeland Security                              12662901_f520
  • Customs and Border Protection
  • The FDA and the USDA
  • Center for Disease Control
  • Food Safety Inspection Service
  • Agricultural and Marketing Services
  • Food and Nutrition Services
  • The U.S. Department of Commerce
  • Department of Defense, and
  • The Federal Trade Commission (FTC).

In-depth understanding of the FDA’s work on food imports

Want to explore how to understand these agencies work in tandem with the FDA and want to ensure that your products reach US shores without hassles and get regulatory approval from the FDA? Then, you need to attend a webinar that is being organized by Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance.

The speaker at this webinar is John Ryan, who began Ryan Systems a decade ago and who has been involved in the manufacturing, food, transportation and Internet industries over the past 30 years. To enroll for this webinar and gain the immensely sharp insights John brings into the FDA’s thinking on food imports, please visit

http://www.compliance4all.com/control/w_product/~product_id=501359LIVE?Wordpress-SEO

Complete understanding of the FDA’s work on food imports

John will offer understanding of the ways in which the various agencies work with the FDA in respect to food imports. A deep understanding in this area is necessary for those who want to import food to the US and gain regulatory approval for their products, since they all work with the FDA at various levels.

He will cover the following areas at this session:

  • Global Food Markets drive new import food safety requirements
  • Review how the FDA’s Food Safety and Modernization Act (FSMA) are changing things
  • Understand “Prior Notice” requirements
  • Foreign Supplier Verification Program (FSVP)
  • Prepare for the Foreign Facility Inspection Program
  • Learn what is in the “Investigations Operation Manual” (IOM)
  • What can happen to your product when seized
  • Learn what other countries require for food import
  • Review the proposed rules for food safety and quality during transportation processes
  • Learn how much food and what food is imported from different countries
  • Understand what the Imported Seafood Safety Program includes
  • PREDICT & OASIS Systems
  • Other resources available to help you.

About 7 decades since the FDA was first formulated in its earliest avatar

Considering the slew of regulations that exist for medical devices today –to the extent that this is among the areas of the highest regulation from the FDA –it is rather ironical that the US Congress had not empowered the FDA to regulate medical devices till as recently as mid-1976. This is when the Medical Device Amendments were added to the Federal Food, Drug, and Cosmetic Act (FDCA). This was about seven decades since the FDA was first formulated in its earliest avatar.

The reason for which medical device software started getting regulated during this time is that it was in the mid-1970’s that computer software started to grow and evolve into a field of its own. Being in a state of infancy for most of that decade; it was only towards the end of the next decade that software began to get used in medical devices, albeit in a manner that appears rather crude by today’s standards. Because of this, the FDA did not have the need to create a software regulatory policy.

Separate regulations based on the nature of devices and software

Since then, however, software has made giant strides in its uses in medical devices. The growth has been so fast and wide-ranging that today, there are regulations for:

o  Software that can be a device by itself (i.e., stand-alone, or what the FDA calls Software as a Medical Device or SaMD)

o  Software that is incorporated into another device as a component, part or accessory.

Other factors to be taken into consideration

So, the FDA’s regulations on medical device software are based on its thinking that there is a distinction between stand-alone software and software that is a component, part or accessory to a device. Also, software validation is a major theme for most manufacturers of medical devices. Software validation of medical devices has to be not just satisfied; it has to be evidenced from a number of stringent perspectives. There is a clear distinction between medical device software and medical device hardware. Additionally, there are design user requirements to be met, and off-the-shelf software and automated equipment have to be validated.

In the realm of clinical valuation of an SaMD; the FDA requires medical device manufacturers to meet and demonstrate reasonable assurance of safety, performance and effectiveness since these devices have a very major impact on the health and safety of its users. This clinical evaluation has to thus be thorough and systematic, and should be well planned. The FDA’s clinical valuation of an SaMD should meet the following:

o  Clinical validity

o  Scientific validity

o  Clinical performance

o  Analytical validity

Deep and clear understanding

Professionals who work in the field of medical devices and whose work is related in some or another way to medical devices need to be aware of the FDA’s regulation of medical devices. This requires detailed understanding of the regulations as they exist, as well as the knowledge needed to interpret and apply them into medical devices or software, whatever the case may be.

This is the understanding a webinar from Compliance4All, a leading provider of professional trainings for the areas of regulatory compliance, will be offering. Thomas E. Colonna, who provides consulting services in the scientific and regulatory aspects of a wide range of medical devices and biologics with particular expertise in the areas of in vitro diagnostics, medical device software and biotechnology-based products, and holds academic appointments at Johns Hopkins University and the University of Sciences in Philadelphia, will be the speaker at this webinar.

To gain complete understanding of the FDA’s thinking on medical device regulation and to get a grasp of how to apply it for practical use, please register for this webinar by logging on to FDA’s Regulation of Medical Device Software

At this webinar, Dr. Thomas E. Colonna will offer fundamental understanding of FDA regulation of medical device software. Expectedly, this session will be of immense benefit to professionals at various levels in the field of medical devices and medical device software, such as Compliance Managers, Validation Managers, Regulatory Managers, QC Managers and QA Managers.

At this session, Dr. Colonna will cover the following areas:

o  Definition of medical device software

o  FDA’s medical device software regulatory scheme

o  Software validation

o  Level of concern.

Healthcare services that drives up the cost of the health benefit plan

Employers who sponsor self-funded health benefit plan programs have a difficulty in finding methods that are acceptable and compliant from the regulatory perspective. Covered individuals have to show high levels of cooperation if they have to adapt these benefit plan programs, because if cooperation is lacking among covered individuals; it leads to less than desirable and ineffective use of healthcare services.

This in turn raises the cost of the health benefit plan, making it burdensome for employers and failing to meet employee expectations. Many of the programs and incentives that employers have adopted have aimed at controlling health benefit plan use, so that the overall cost of offering health benefits can be reduced. However, many of these incentives have violated the privacy of covered individuals because they track health related activities and outcomes. This is viewed seriously by regulators.

This leaves employers confused about the kind of benefit plan programs that are compliant, because compliant programs are the only means to ensuring that the benefit plan programs serve their purpose and are also valid from the legal and regulatory perspectives.

Clearing the confusion

How do employers adapt such benefit plan programs? How do they wade through the muddle to clear the air about regulatory requirements for benefit plan programs? This is the teaching a webinar from Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will be offering.

The speaker of this valuable session is Jed Constantz, who is a healthcare professional from upstate New York with over 30 years of experience in the healthcare industry. He has served in a number of administrative and management positions for two upstate New York hospitals, a home health agency, several physician organizations, and a physician/hospital organization. To gain insights into how to adapt benefit plan programs that are useful and compliant from the regulatory perspective; please log on to Employees Health Benefit Plan to register.

At this session, which will be highly useful to professionals who deal with benefit plan programs, such as CEO’s, CFO’s, COO’s, VP HR/Benefits and Benefit Plan Brokers/Consultants; Jed will offer useful insights into regulatory compliant models and strategies that employers can leverage to elicit increased cooperation among covered individuals. He will also guide them on the appropriate incentive models that protect the privacy of those who choose to participate in these programs.

Helping employers get employee cooperation

Employers, naturally, look for strategies and concepts that drive high levels of cooperation among health plan covered individuals and are compliant with federal regulations concerning non-discrimination. They are often apprehensive about violating Protected Health Information (PHI) privacy rules and are uncertain about best practices for high level health plan participant cooperation. The speaker at this webinar will seek to clear their doubts about existing models and programs and help create high level health plan participant cooperation.

Jed will cover the following areas at this webinar:

o  Regulatory Compliant models for gaining and increasing covered individual cooperation with health benefit plan cost control initiatives

o  Aligning the interests of covered individuals with those of the employer sponsor of a self-funded benefit plan

o  Development of incentives for covered individuals that reward behaviors and completed activities that are compliant with Federal requirements and regulations.

Paper records to electronic for pharmaceutical companies

Following the rapid advances being made in the field of information management in the past quarter of a century or so, computers have increasingly come to replace paper as the source in which important documents are created and stored. Till the last decade of the previous century, organizations used paper to record and document information relating to their research, development and business. From around the start of the 1990’s; the shift towards computerization of paper records has been noticeable.

Many differences between paper and electronic records

One of the defining differences between this electronic standard and traditional paper records is that while the latter used to be stored in a central, protected environment and managed by a designated managers; electronic records are spread over many locations.

Although some are managed by a central authority; most are under the control of individuals. Individuals in charge of this work have a wide range of computer based devices such as phones, laptops, tablets and USB storage devices at their disposal, which can be used for functions such as authoring, storing, and copying and transmitting relevant information.

Also, the information available on these systems can be stored and shared within several locations on the web, with the option of protecting some better than others. What has also changed substantially is the process of verifying the authenticity of a record. Earlier, the method used to authenticate paper records was via inked signatures of the author and witness. Encrypted e-signatures are replacing this practice.

Submissions to the regulatory authorities

In line with this development, the FDA and other global regulatory agencies started accepting electronic files, or at least parts of submissions, for testing and marketing drugs. This movement, which started in the early 1990’s, led to the creation of the Common Technical Document (eCTD) standard. This standard is now required in the US and most countries around the world.

If pharmaceutical and life sciences companies have to submit documents such as the NDA, ANDA, IND, BLA, DMF and the BMF to the FDA electronically, the eCTD has been the pan-industry, widely accepted standard since 2008. Submissions are, in fact, no longer done via paper records. If companies have to incorporate legacy paper records into an eCTD; they have to scan those and put them into a text readable format.

A source of important information

Despite the existence of this method; many companies continue to possess huge troves of paper based information, which are yet to enter the cyber realm. These records contain important information relating to the pre-clinical, clinical and drug safety paper records of drugs that did not make it to the marketing stage for a variety of reasons, because of which these companies have archived this information.

This archived data, if harnessed effectively, could be a rich source for offering knowledge that will go on to enhance inputs for submissions for other new or emerging indications for the drug or support efficacy or safety for related drugs. Many organizations have a large collection of paper records with retention times of 50 years or more. There is a dilemma of how to best preserve and utilize these records.

What is the way of going about for transiting?

Many companies are in a quandary about what to do in a situation in which the majority of records are electronic, but a substantial number remain as aging paper records. If the wealth of information available in paper format is to be exploited meaningfully, should they convert all the paper records to an electronic format, convert some of them, or just leave them in their current form? Given that complete conversion and subsequent integration is a very expensive and laborious exercise; a better option will be to convert on an as-needed basis.

The ways of how to do this effectively will be the topic of a highly educative webinar from Compliance4All, a provider of professional trainings for all the areas of regulatory compliance. At this webinar, Dr. Charlie Sodano, an experienced, globally recognized information management professional who launched eOrganizedWorld a consulting firm specializing in the planning and implementation of records and information management systems, will be the speaker.

To understand and have these issues resolved from the expert, please register for this webinar by logging on to Records policy and procedures

Dr. Sodano will take up and explain the issues relating to conversion of paper records into electronic, and the ways in which the submissions need to be made. This training is of importance to professionals in Research & Development, Regulatory, Clinical, Legal, Information Technology and Validation.

During the course of this session, Dr. Sodano will cover the following areas:

o  Records policy and procedures

o  Records data map

o  Incorporating paper records into a eCTD

o  Converting paper documents into a useful electronic format

o  Scanning costs and resources

o  Indexing and organizing scanned records and integrating them

o  Long term record storage and retrieval.