Dec 31, 2013

An Argument for Effective Quality Management Systems

Kamaal Anas

by Kamaal Anas, Vice President Regulatory Affairs, Wright Medical Technology

All too often, quality management systems are seen as a cost of doing business – a requirement of regulators (e.g., 21 CFR 820), customers (e.g., ISO 9001:2008) or overbearing parent companies – rather than as a tool for management to effectively manage their organizations.  However, quality management systems that are effectively designed, implemented, utilized and continuously improved upon provide management with quality information, delivered in a timely fashion, which facilitate data-driven decision making.  Designing and implementing a quality management system that provides the appropriate information for management to make educated decisions requires careful thought and detailed planning.  Once accomplished, management will have the tools to effectively allocate resources to risk-prone areas and reduce the cost of poor quality.

Industry Backdrop

There are three proverbs/curses, attributed to the Chinese, that are applicable to many regulated companies, (1.) May You Live in Interesting Times, (2.) May You Find What You Are Looking For, and (3.) May You Come to the Attention of Those in Authority.

Dec 23, 2013

How to Confuse and Confound Your Trainees in 10 Easy Steps!

Jill Drummond

by Jill Drummond, Director Training  Education, Blood Systems

On-the-job training is usually conducted one-on-one or in small groups so it can be challenging to confuse trainees; but fear not — when employees start a new job, they are usually a little nervous or apprehensive.  They want to make a good impression and they want to be successful in learning their new tasks.  This is when they are most vulnerable and they are easy pickings for total confusion.  Follow these simple steps and you will have your new hires running for the hills and totally flabbergasted and ineffective in their jobs. 

Dec 18, 2013

10 Guidelines for Writing Superior SOPs

Robyn Barnes

by Robyn Barnes, Public Relations Specialist, MasterControl Inc.

Will you be prepared when tasked to write a standard operating procedure (SOP)? Writing SOPs--- shorthand for a written document that helps ensure accuracy and repeatability when executing a task---is an integral part of assembling a successful quality system. When poorly written, they are of limited value.  Using the following 10 guidelines, you can create a successful SOP document.

Dec 12, 2013

Biosimilars Establishing Themselves in Europe

Peter Calcott

by Peter Calcott, President, Calcott Consulting LLC.

From the introduction of the Guidelines for Biosimilars in the EU in 2004, Europe has been pressing hard for the introduction of these money-saving options into the marketplace.  The initial guidelines of 2004 were followed very rapidly with further guidances on comparability (2005), preclinical and clinical requirements (2005), recognition of the changing landscape (2010) and in 2011, further recommendations for studies and statement of the recognition of the issues surrounding licensure.  To aid developers they even issued product specific guidances, recognizing that each molecule would have specific challenges to overcome.  From the issuance of the first two in 2005 for granulocyte colony stimulating factor (GCSF) and human somatotropin, to interferon beta, follicle stimulating hormone and insulin in 2011, we have seen others in the intermediate period including epoietin, heparin, interferon alpha, and monoclonal antibodies (MoAbs).

The activity has not been simply issuance of guidances and guidelines, but actual approval of products, with them well-established in the market place. The first approval for human somatotropin was for Sandoz’s and BioPartners’ versions with the latter withdrawn by the manufacturer later.  We have seen various epoetins, filgrastims (GCSF) and follicle stimulating hormones with a total of 18 approvals with 2 withdrawals through 2012.

Dec 10, 2013

A Risk-Based Approach to Validation

Peter Knauer

by Peter Knauer, Partner Consultant, MasterControl Inc.

FDA classically has defined the requirements for validation under 21 CFR 820 and 210/211 regulations as a comprehensive testing process where all systems are given thorough examination and tested under equal weight, complete with an exhaustive evaluation process. Recent guidance and initiatives by FDA (Process Validation: General Principles and Practices) and ICH (Q11: DEVELOPMENT AND MANUFACTURE OF DRUG SUBSTANCES) have provided a streamlined risk based approach under an updated life cycle management methodology. Under this scenario, a new definition of validation has emerged, best described by FDA as “the collection and evaluation of data, from the process design stage through production, which establishes scientific evidence that a process is capable of consistently delivering quality products.” This is in contrast to the classical definition as perhaps best emphasized in the device regulations under 21 CFR 820.75:

“Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures.”

What this means is that a risk-based life cycle management approach with relevant scientific rationale and evidence can be used in lieu of a traditional top-down comprehensive approach. Many of us remember the golden rule of validation; triplicate test runs as an output of this classic approach. It didn’t matter the complexity or simplicity of the system, just always apply the test in triplicate. Essentially what FDA and ICH are now saying is that if you can justify a different test plan with a risk-based approach, it is fine with them. The end result is that many validation processes can be streamlined and production delays eliminated. Below is essentially a discussion on the ‘best practices” approach I have successfully used to meet these updated FDA and ICH guidances.

Dec 5, 2013

What If You Needed SOPs to Run Your Household?

Laurie Meehan

by Laurie Meehan, Internal Project Manager, Polaris Compliance Consultants, Inc.

In August, I traveled to Phoenix to videotape a presentation for Natural Products INSIDER’s Digital Summit.  The presentation, entitled “A Guide to SOPs and Compliance for Dietary Supplement Distributors,” goes into much more detail than our February blog post on the same subject (which you can read here: http://bit.ly/YGTQWd).

Rosanne Sylvia-Heeter, Director of cGMP Compliance at Polaris, is always chanting the
FDA compliance mantra, “If it’s not documented, it didn’t happen.”  As I worked on the blog post with her last winter, I was struck by the amount of documentation actually needed to comply with 21 CFR Part 111 distribution regulations.  As we worked on the Digital Summit presentation this summer, I was struck by something else.  In the course of simply maintaining a residence, members of my household actually perform a lot those Part 111 activities.  And so do yours.

The big difference is that we don’t have to write it all down.

Nov 14, 2013

6 Ways to Leverage Risk-Based Monitoring & Clinical CAPA

Cindy Fazzi

by Cindy Fazzi, Marketing Communications Specialist, MasterControl Inc. 

A big part of the cost of developing a new drug can be attributed to clinical research, which typically lasts at least eight-and-a-half years.  For this reason, regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are emphasizing the need to mitigate clinical-trial risks (1).

This is in addition to the requirement that sponsors and CROs integrate CAPA (corrective action and preventative action) as a tool for ensuring patient safety and data integrity throughout the clinical trial.

While most companies have risk management and clinical CAPA processes, they’re not leveraging CAPA to strengthen risk management and vice versa. If your company is a sponsor or a CRO, how effective are your risk management and clinical CAPA processes? Are you using them to supplement each other?

Nov 12, 2013

FDA Inspections: Be Prepared to Ensure Quality and Compliance

Michael R. Hamrell

by Michael R. Hamrell, Ph.D., RAC, FRAPs, CCRA, RQAP-GCP, MORIAH Consultants

You have just been informed by your boss that the FDA is coming to conduct an inspection of a clinical study recently completed at your facility.  Does this raise your anxiety level and that of your staff to near panic levels?  A FDA inspection can bring on images in your mind of a large room, bright lights and grueling questions.   Probably no other agency of our government can evoke a more frightening scenario, except for maybe an IRS audit.  However, with proper planning and preparation, a FDA inspection does not have to be a nightmare experience.

Regardless of your motivation or fears, proper preparation is the key to doing well in a FDA inspection.  The good news is that routine clinical inspections, unlike GMP inspections, are usually pre-announced and scheduled.  The bad news is that without good practices and proper procedures in place, no amount of advanced notice will give you enough time to build in compliance.  There is just no substitute for a prospective, quality approach to clinical research.

The Food and Drug Administration each year conducts approximately 900-1,100 worldwide inspections of clinical investigators involved in investigational studies for drugs, medical devices and biologic products. These inspections are carried out under the agency’s Bioresearch Monitoring Program (BIMO), which is designed to assess the quality and integrity of data that are submitted to the FDA to support product approval applications and to examine the human subject protection aspects of the study. The BIMO program comprises randomly selected, routine, on-site inspections and data audits to monitor all aspects of the conduct and reporting of FDA-regulated research. On occasion, the FDA will conduct a directed inspection of a specific site or study to look for problems that may have already been identified. The BIMO program is a global initiative and focuses on data collected at sites worldwide.  On the rare occasions that the inspection of a clinical study uncovers evidence of fraud or misconduct, the FDA must decide how to discipline the investigator and how to deal with the suspect data.

Grid Analysis for Simplified Supplier Selection

Jennifer Stepniowski

by Jennifer Stepniowski, Communications Director, Pro QC International

The selection of a new supplier can be an arduous process, and the importance of the decision is inarguable.  Changing suppliers when continuous improvement recommendations fail to succeed most surely will result in high switching costs.  Ultimately, the decision is worth careful evaluation, which makes a grid analysis a useful and easy tool to use.

In addition to objective evaluation, using a grid analysis is an excellent opportunity to incorporate brainstorming to consider the importance of various factors that have an effect on the decision.  This step is particularly important to the outcome of the process.

The grid analysis itself becomes less useful when factors are weighted incorrectly or excluded altogether. For the tool to work, the quality of what goes in (information) will directly affect the quality of what comes out (supplier selection).

Avoiding the Silo Effect: The Importance of Communication in Clinical Trials

Rebecca York

by Rebecca York, Senior Clinical Research Associate, PPD

As clinical research professionals, we rely on the adage, “If it wasn’t documented, it wasn’t done.” This simple concept guides our every effort in creating solid, reproducible scientific progress. However, without effective communication between stakeholders in clinical trials, research sites are doomed to repeat the same (well-documented) mistakes, and study progress can be hindered, shrouded in a fog of confusion and misunderstanding. With that in mind, perhaps the time has come for an addendum: “If it wasn’t documented, it wasn’t done – but if it wasn’t communicated, it can’t be corrected!” The flow of communication, from investigative sites through monitors to clients (study sponsors) and to regulatory authorities, must be clearly defined and maintained in order to assure the success of a trial.

Each trial stakeholder owns separate responsibilities, described in federal regulation and international guidance (Figure 1). Per 21CFR 312.50, clients are responsible to “provide investigators with the information needed to conduct an investigation properly,” and to ensure that regulatory authorities and investigators are “informed of significant new adverse effects or risks” with regard to the investigational product. Likewise, investigators are responsible for notifying the clients of “any adverse effect that may reasonably be regarded as caused by, or probably caused by, the drug.” Investigators also must communicate regular study progress to IRBs and clients to ensure that an investigation is “conducted according to the signed investigator statement, the investigational plan and applicable regulations.” Finally, the monitor is responsible to liaise between the client and investigator by facilitating the distribution of information from the client to investigational sites, as well as communicating site concerns to the client (ICH CGP E6 5.18.4).

Nov 4, 2013

MasterControl Electronic Quality Management Software Solutions Benefit a Wide Range of Industries

For more than two decades MasterControl software has made it possible for hundreds of companies in an extensive array of industries across the globe to improve quality processes and get products to market more quickly. Companies doing business in regulatory environments in particular use MasterControl solutions to ensure sustained compliance and stay ahead of competitors.

Is your organization’s primary goal to get products to market as quickly as possible without jeopardizing compliance or quality? Without a software solution that is specifically designed to enhance quality, ensure sustained compliance, and maximize efficiency through the automation of business processes (such as document management/control, employee training, audits, product lifecycle, etc.) that objective is unattainable.  By combining a customizable application with the best practices we have derived from all the industries in which our customers inhabit, MasterControl has developed the ultimate electronic quality management system that can fit the needs of organizations of all sizes and scopes.

Oct 24, 2013

Three Common Issues Involving Clinical Trials

by Cindy Fazzi, Marketing Communications Specialist, MasterControl Inc.

In clinical research, there are two major regulatory concerns: patient safety and data integrity. While there are many possible reasons for regulators to conduct an inspection during a clinical trial, most of the time, it’s to verify these two things and to ensure that the research is being conducted according to the study protocol and GCP regulations.

If your company is sponsoring a clinical trial or if it’s a CRO conducting research on behalf of a sponsor, are you ready for an inspection?

Common Clinical Trial Issues
The issues faced by sponsors and CROs during inspection vary from one clinical study to another, but here are three types of violations that have warranted FDA warning letters.

Oct 8, 2013

Developing a Winning FDA Strategy for Clinical Drug Development


by Robert L. Kunka, Ph.D., The Kunka Group, Inc.

The idea of interacting with the FDA is sometimes mysterious and unsettling for a pharmaceutical company.  The average person finds it difficult to work with a large organization that they don’t understand.  For example, large banks understand this and advertise themselves as the friendly bank that works to help “their neighbors” with buying a house.  The FDA’s clients are pharmaceutical companies.  Unlike banks, the FDA has significant leverage over the company because it is responsible for reviewing a company’s drug with the hope that FDA will approve it.  While many companies are also large, there is no real leverage that the company has over the FDA.  Thus, the company is at a distinct unsettling disadvantage.  However, both parties have the common desire to market safe and effective drug products.  Where the rubber hits the road is that the two parties need to agree on what is needed to demonstrate that the drug is safe and effective.

Innovation and the Quality Process


by Ken Peterson, Director of Quality and Consultation Services, MasterControl Inc.

Thinking of new ideas and putting those ideas to practical economic use can be more of an art than a science.  At times innovation sends a signal that is in opposition to quality.  If we are constantly trying to solve problems and find solutions through effective investigation of failures, do we ever consider that the best solution is to ignore the past and invent the future?  Those of us who have a wider view of what innovation should deliver seek entirely new approaches verses conventional problem-solving for cause.  It’s not that analytical thinking is unnecessary but on occasion, a new solution unrelated to cause removal is warranted.

What is Innovation and how is it Different from Creativity?

For most, creativity is coming up with a good idea.  Innovation is the process by which you conceive novel ideas and put them into practice.  Obviously creativity is of little value if you can’t put a new idea into practice.

Sep 17, 2013

SOP Training is Now “On-Line” But Are We Any More Compliant?


by Vivian Bringslimark, President, HPIS Consulting, Inc.

Well, I’m told we are now more compliant with ensuring that only the most current SOP version is used for training. And yes, our Learning Management System provides us with curricula updates and “percent complete” and “percent overdue” notifications. LMSes and eDoc systems have given us efficient mechanisms to document that employees have completed their training curricula. But do they understand their procedures enough to perform them correctly back on the job? Just look at our human error deviations and training-related CAPAs. Are the numbers declining? According to an excerpt from the PDA’s Pharmaceutical Sci-Tech Discussion Group, there is “almost a 100% correlation between the percentage of read and understood SOPs and the number of compliance issues the company has.” (1) Has efficiency become the new metric for training and compliance? Using technology to read SOPs doesn’t guarantee learning transfer.

It’s still “Read and Understand” SOPs!

Whether we access our SOPs through an eDoc system or the LMS portal, we are still only reading them. To call this eLearning is a bit of a stretch especially when compared to the design of today’s eLearning courses. Nonetheless, some new hires are still being provided with a long list of required SOPs and trained on where to find them in the LMS. “Oh,” I’m told, “but we’ve made it easier for them to manage their SOP list. They’re online now!”
My response: access is only one part of completing the requirements. A new hire needs to have optimal training experiences with a qualified trainer using a structured and deliberately planned approach to completing his/her assigned curricula. Yet, we ask our least experienced employees to “read and understand” a massive list of department SOPs with little to no prior experience and wonder why the learning curve is so lengthy! 

Sep 5, 2013



by Victor Gill, MasterControl Inc., Senior Product Manager of Cloud Solutions 

What exactly is Cloud? Or is it, The Cloud? Is it just me, or do no two people describe it the same way? As the product manager over the Cloud initiative at MasterControl, I hear these kinds of questions all of the time. With all of the advertising, mixed messaging, technical jargon, and promises of grandeur, it’s easy to see why so many consumers are confused. At its heart, the term Cloud has been a powerful marketing turn-of-phrase that has consolidated a large mix of technologies.

The general idea for the Cloud can be traced back to two simple business principles:

1. Focus on your core competencies. If you’re in the business of pharmaceuticals, medical devices, or manufacturing, you probably should avoid being in the business of creating software, managing servers, and the like.

2. Specialization improves performance and can generate economies of scale. If a company specializes in the production, maintenance, and operation of software and a sufficient number of customers chose that company’s services, the service level to the customer will be better than they could create themselves. In a nutshell the Cloud takes what software companies do best - create and maintain software - and gives access to what they have created via a wide area network, like the Internet.

    Aug 14, 2013

    Review of FDA Guidance "Codevelopment of Two or More New Investigational Drugs for Use in Combination"


    by Seth A. Mailhot, Special Counsel, Sheppard Mullin Richter & Hampton LLP

    On June 14, 2013, FDA issued the Guidance “Codevelopment of Two or More New Investigational Drugs for Use in Combination.”  The guidance discusses FDA’s recommendations for developing an entirely new combination therapy where none of the drugs to be used in combination have been previously developed.  FDA notes in the guidance that the recommendations do not apply to combination therapies involving previously developed drugs, or the combination of a new drug with a previously developed drug.  While codevelopment has generally been centered in oncology and infectious disease, FDA’s guidance is intended to address codevelopment from a high-level, making it applicable to other diseases.

    The complexity of certain diseases, such as cancer, cardiovascular disease, and infectious diseases, presents unique challenges to medicine.  As scientific understanding of pathophysiological processes has increased, development of combination therapies has become increasingly possible.  The potential benefits of combination therapies include improving treatment response by directing treatments at multiple therapeutic targets, minimizing development of drug resistance, and countering drug side effects and adverse events.

    Elements of Effective Quality Agreements


    by Steven Sharf, President and Principal Consultant, GMP Concepts

    Many GxP professionals are already familiar with the expectation of FDA and the requirement in the EU to have quality agreements with third parties and suppliers.  Throughout this article, I will define what a quality agreement is, when one is needed, the 24 basics that factor into this critical document, and some things to avoid when drafting one.  Finally, I will discuss alternate means of communicating quality expectations when a supplier will not agree to enter into a full quality agreement. 

    What is a quality agreement?
    A quality agreement is a contract between two parties that defines the role of each in the manufacture, packaging, testing, holding, and/or distribution of product to the marketplace.  It is through this document that both the sponsor (contract giver) and the contractor (contract receiver) know such things as who is responsible for investigating complaints; who is responsible for initiating a recall; what is the expectation for completing investigations; who is responsible for releasing material; and who are the key contacts within each organization when a quality issue arises.  While there are many elements to a robust quality agreement, I feel the most important is defining the role of each company in communicating change.  The quality agreement should be very clear as to the types of changes that require notification (this would apply to contractor-driven changes as well as those initiated by the sponsor), the timeframes for communicating and implementing changes, and the required approvals for change.  The amount of detail that goes into a quality agreement will be dependent on the companies involved (mainly on the sponsor’s requirements), the type of work being performed and the relationship between the sponsor and the contractor.

    Building a Quality Plan for Implementing EN ISO 14971:2012


    by Robert Packard, Regulatory Consultant, MedicalDeviceAcademy.com

    On May 16 of 2012, the European Committee for Standardization (CEN) approved a revised European National Standard for medical device risk management: EN ISO 14971:2012. There were no changes to the main body of the Standard (i.e. – Clauses 1 through 9). Instead, the revised European National (EN) version identifies seven deviations in Annex ZA, ZB, and ZC with respect to the intent of the MDD, the AIMD, and IVDD respectively. Those seven deviations are:

    1. Treatment of Negligible Risks
    2. Discretionary power of manufacturers as to the acceptability of risks
    3. Risk reduction “as far as possible” (AFAP) vs. “as low as reasonably practicable” (ALARP)
    4. Discretion as to whether a risk-benefit analysis needs to take place
    5. Discretion as to the risk control options/measures
    6. Deviation as to the first risk control option
    7. Information of the users influencing the residual risk

    The following sections of this article provide recommendations for how to update your existing risk management procedure and processes to ensure compliance for CE Marked medical devices.