Switch to xmLabeling Leads to Big Rewards

A U.S.-based pharmaceutical company with 25,000 employees worldwide and approximately $20 billion in revenue was looking to create a central repository for its labeling content. The goal was to have one, authoritative source for its worldwide labeling—a system capable of tracking changes from the Core Data Sheet to local labeling documents, and of generating Structured Product Labeling (SPL) files directly from the labeling content without having to go through manual conversion. After looking at software from various vendors and going through an extensive search process, the company chose Glemser’s xmLabeling solutions.

Challenges

Pharmaceutical companies spend a significant amount of time and energy organizing product-labeling documents such as U.S. Package Inserts, Summaries of Product Characteristics and Core Data Sheets. The information is published to product websites and included in final product packages. It’s an enormous task to manage and coordinate this body of information across all markets. At the same time, pharmaceutical companies must support multiple labeling business processes and regulatory requirements. These processes and their submission parameters can vary widely, depending upon where in the world a company is doing business. For example, in the United States the Food and Drug Administration (FDA) requires that companies submit labeling content annually. In addition, if content is updated during the year, and depending on the change’s impact, requirements could warrant submission in advance of the label content changes or at the time of the changes. In either case, the FDA mandates that companies submit labeling content electronically in a specific way—in an XML format called Structured Product Labeling (SPL). Meanwhile, the European Medicines Agency (EMA) allows companies to submit labeling content via centralized, decentralized, mutual recognition, or national submission procedures. Whichever path is chosen, however, companies must submit European labeling content in Microsoft Word in accordance with Quality Review of Documents (QRD) guidelines. As a result of these constraints, information is often repeated over and over again for various documents for different formulations, strengths and presentations. If efforts are not effectively coordinated, the result is the creation of multiple, nearly identical master versions that become unwieldy to update and track. Worse still, it can create inaccurate labeling documents potentially resulting in the recall of batches of pharmaceutical products. The pharmaceutical company in question was dealing with such document generation and tracking issues on a daily basis. Its labeling content was kept in multiple repositories worldwide. With 25,000 employees and distribution in more than 170 countries, duplication was rampant and tracking documents for accuracy and compliance was difficult to manage effectively. Labeling content was created and updated in a Microsoft Word document that was that was then cut and pasted into an SPL document—creating two documents. To satisfy the different formulations, strengths, presentations and any additional tweaks needed for each market, nearly identical documents were created.

The company could end up with 50 or more labels for one drug. While it was laborious to create the first time, it became a nightmare whenever updates were needed. Ensuring all labels had the correct changes meant hours of tedious, painstaking proofreading. Adding to the duplication and tracking conundrum was the fact that individuals at the company kept labels on their personal computers and laptops. Although new versions of labels were tracked in an Excel Spreadsheet, it was difficult for the Labeling Author to know for certain what information was the most recent or the most accurate. Was it the original word document with its edits, or the SPL file? Tracking and duplication also created disconnects between the company’s Core Data Sheets and local labels. Local country labels were housed in each individual country of ce, and not always uploaded to headquarters in a timely manner. There was no guarantee that what was being housed at headquarters was the most up-to-date version.

“The technology and Glemser staff bridge Regulatory and IT professionals, so that we can quickly adapt to changes in international regulations.”

– Manager, R&D IT Risk and Compliance

Solution

To make its labeling processes more manageable, ensure accuracy and employ tighter control, the company decided to implement xmLabeling through Glemser Technologies. xmLabeling is a proven, comprehensive application for effectively managing global labeling content and related processes. It handles (among other requirements) SPL, content fragment linking and re-use, translation management, automatic generation of submissible content that complies with the latest SPL standard and QRD guidelines, regulatory compliance and tracking, and Word-like editing with revision tracking. Glemser, with more than 27 years of practical business knowledge, drew on its extensive, in-depth experience implementing large-scale, IT solutions for global companies to successfully execute the implementation of the new xmLabeling system.

Today, the company in question has a single repository for its labeling content, and a single authoritative source for each label. Everything is in one place. A Master XML File is rendered in MS Word, which is automatically sent to the website and into an SPL file. Versions of each label are now controlled—employees check out labeling content from the single repository, and check it back in when they are nished. Duplication is eliminated, and changes are only made to this single, authoritative source. In addition, the company is also able to track changes to its Core Data Sheets all the way through to local labels, ensuring all individual country offices have the same information.

Results

The switch to xmLabeling has improved compliance and reduced risk while also improving efficiency and reducing costs. “The xmLabeling and xmRender products have helped us achieve uniform and compliant processes for our complex global pharmaceutical labeling operations,” said the company’s manager for R&D IT Risk and Compliance.

For the company’s Regulatory Operations division, compliance is easier to manage. All regulatory assets are in a central place—easily controlled while also allowing for seamless integration with other regulatory requirements. For example, in the past when an auditor requested documentation, it could take up to a month to supply the necessary materials. Now, it takes a few hours. Plus, Regulatory Operations is able to supply comprehensive tracking documentation proving the company met all requirements and followed all procedures properly.

For the company’s Labeling Strategists and Labeling Authors, there is reduced complexity and increased efficiency in coordinating the Core Data Sheets. Because the company manages a single set of labeling content, the Labeling Strategist or Author no longer needs to manually cut and paste information, but can easily re-use core components, saving time and effort and reducing costs. The Labeling Author can easily track changes to Core Data Sheets. For example, local country offices are notified of changes to the data sheet, and changes to local labels are tracked against updated data sheets. Labeling content is no longer kept on individual computers or laptops, but checked in and out from the central server.

Finally, the centralized, controlled system powered by xmLabeling has increased accuracy and asset management across the board. This in turn has given the company the ability to make better, more accurate, business decisions because it is working with up-to-date information. The company can better predict, for example, the number of labels it will need, and can forecast future needs more easily. “The technology and Glemser staff bridge Regulatory and IT professionals, so that we can quickly adapt to changes in international regulations,” the company’s manager said.


Quality Implementations for Life Science Client under a Consent Decree

The Client

The client is a diversified, multinational, life sciences company. The consumer division of this company manufactures and sells health care products worldwide.

The Situation

In one of the company’s divisions, the US Food and Drug Administration (FDA) found several violations during routine inspections. These included a variety of problems such as the performance of operations outside of approved standard operating procedures, outdated procedures, mislabels and more. As a result, the FDA issued warning letters.

Unfortunately, the company could not consistently demonstrate sufficient control of its quality systems to the FDA in compliance with current good manufacturing practices. After the company recalled several products, and received inspectional observation reports, called 483s, and a warning letter from the FDA, the FDA placed this company under a consent decree.

A consent decree is a legal agreement between a company and the FDA under which the company agrees to address specific violations and implement oversight processes. Consent decrees include heavy fines, reimbursement to the government for applicable inspection oversight costs, commitments to due dates for specific actions and penalties for non-compliance. Entering a consent decree can have a major impact on the affected manufacturing sites, and obtaining a release from a consent decree typically takes many years. As a result, a consent decree could cost a life sciences company millions of dollars in regulatory fines, additional expenses, and lost revenue.

The Solution

While implementing quality system changes may seem straightforward on the surface, changing a corporate culture along with its legacy quality management systems is a large and complex task, involving people, processes and technologies. The client chose to secure release from the consent decree by embarking on an eight-year program.

During the first three years under its consent decree, the company:

  • Remediated known issues
  • Improved its quality systems
  • Defined new quality processes
  • Implemented external oversight
  • Ensured internal governance oversight
  • Implemented quality reporting metrics

Over the remaining five years, the company will:

  • Sustain new quality processes
  • Continue external oversight
  • Monitor and measure performance
  • Implement additional quality system improvements
  • Participate in routine regulatory audits

The company started consent decree remediation by defining the quality standards for applicable business functions, implementing interim controls and organizing the overall quality system into distinct quality system elements, such as quality assurance, documentation control, new product development, technology transfer, manufacturing operations, etc. Each quality system element was broken down into multiple process steps, each of which was addressed in the following approach:

  1. Process – The implementation of new procedures to address critical business functions.
  2. Remediation – The execution of specific activities to address known product- and process-related gaps. Remediation steps included updating legacy documents, such as finished product specifications, to comply with new procedures provided by related process steps.
  3. Information Technology (IT) – The updates to legacy IT systems to address known issues and the implementation of new IT systems to ensure compliance with new procedures.

Although the approach to executing process, remediation and IT can vary significantly, each of these steps were remediated through the following four phases.

  1. Plan and Design

The intent of the plan and design phase is to define the process for effective and compliant quality procedures. During this phase, teams organized by quality system elements:

  • Reviewed applicable quality standards and known gaps and issues
  • Assessed “as is” processes and developed “to be” processes with detailed process maps
  • Developed a detailed project plan and metrics for measuring compliance
  • Signed a deliverables concurrence document to align participant expectations with respect to deliverables
  1. Implementation

The intent of the implementation phase is to make the quality system effective by training employees to run quality operations according to approved procedures supported with validated quality IT systems. During this phase, teams organized by quality system elements:

  • Developed and approved new standard operating procedures
  • Implemented and updated IT systems required to support new procedures
  • Implemented metrics reporting
  • Trained users on the new processes
  • Developed trace matrices to ensure that all quality standard elements and gaps were addressed
  • Conducted an independent assessment to confirm that new processes were adequate and in place
  1. In Use

The intent of the “in use” phase is to have employees run the business according to the new quality procedures while assembling compliance documentation in an evidence binder for inspection by the FDA. During this phase, teams organized by quality system elements:

  • Conducted routine business using newly effective procedures
  • Gathered “in use” evidence to support subsequent verification
  • Captured and reported applicable metrics
  • Received “hypercare” support for six months by core team members to feel comfortable with the new quality standards and procedures
  1. Verification

The intent of the verification phase is to have internal and third-party auditors review the evidence binders and resolve and remediate any findings through the non-conformance quality process. During this phase, auditors organized by quality system elements:

  • Assessed evidence to ensure that “in use” business activities were compliant with applicable quality procedures
  • Appraised points for future evaluation to ensure that deferred “in place” confirmation observations were addressed and closed

 

Results to Date

The company has met all of its commitments to the FDA so far. The development of the company’s quality system elements and procedures have followed the process described above and have been confirmed and verified when required. Since this is the first time that the company entered a consent decree, this process had to be modified along the way to address issues and implement improvements based on lessons learned and evolving best practices. 

 

Future Outlook

The company is on track to re-establish its quality system with strong standards and processes within the first three years of its consent decree. The company has demonstrated its ability to successfully execute every aspect of its consent decree work plan. The next milestone is to obtain certification for each affected site to manufacture quality products for US consumers. After certification, the FDA will perform two audits in the fourth year and then one annual audit in the subsequent three years. The company will demonstrate the sustainability of its quality system by successfully completing FDA audits over a five-year period, with the goal of emerging from its consent decree over a total of eight years.

 

Glemser’s Involvement

Glemser consultants combined deep domain knowledge, a practical understanding of regulatory requirements and a proven track record of successfully implementing enterprise compliance software to help the client with several critical quality system element work streams.

Specifically, Glemser consultants:

  • Performed project management activities including:
    • Program management of project consultants
    • Project planning and coordination of activities and deliverables
    • Definition of risks and management of mitigation strategies
    • Facilitation of project meetings
    • Submission of status reports
    • Issue escalation and management of resolution
  • Gathered and assessed IT requirements in support of new processes
  • Performed process analysis and modeling
  • Maintained budgets and resource requirements
  • Facilitated various process excellence activities
  • Coordinated and managed training activities
  • Managed interdependencies between different quality system elements
  • Facilitated workshops to analyze processes and develop process maps

Glemser helped the client meet critical project needs by providing consultants that have deep life sciences domain experience, knowledge of regulations, expertise in applying information technology, an ability to drive client behaviors, and the strong desire to make clients successful.


Process Management Case Study (Changing Medical Device Labels)

Executive Summary

In this case study, Glemser Technologies worked with a client to smooth the integration of a new acquisition. The client purchased a competitor in order to create a more well-rounded medical device group. Once purchased, the new group had to be integrated through a potentially complicated, laborious process of rebranding and relabeling the products to comply with the new parent companies’ requirements and new European Union requirements. Glemser worked with the client to create a new, smoother process to be deployed in the coming years.

Case Study

Challenges

A life sciences client purchased a competitor’s surgical vision organization to combine with its own consumer vision group in order to broaden its range of optical solutions and create synergy in an integrated vision medical device group. A complicated process for changing labels evolved from a series of observations in quality audits that resulted in Corrective and Preventive Actions (CAPAs) in the acquired company. Programs to rebrand medical device labels and ensure compliance with the emerging European Medical Device Regulation (EU MDR) highlighted the need for a streamlining of the cumbersome quality process to change product labels.

Solutions

Glemser analyzed the labeling change procedure and developed the following recommendations to improve the process:

• A comparative labeling change benchmark with a similar medical device group
• An optimized set of process steps built through workshops with the labeling team
• An intake form to improve initial planning of labeling changes
• A workflow diagram to establish an accurate initial scope of a labeling change
• Proposed regulatory guidance documentation, including examples, for the labeling change team to correctly interpret North American and European labeling requirements

Results

Glemser presented its recommendations to Supply Chain, Regulatory, and Quality leaders in a program that included approaches to challenges in process, organization, information, and technology. This allowed the labeling team to take steps to improve the change process. Glemser also collaborated with leaders in Supply Chain and Finance to develop a rough-cut business case to seek funding for full deployment of labeling change optimization over the next couple of years.