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Life Sciences White Paper

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Life Sciences

Connecting the dots across the labeling life cycle

White Paper


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The labeling text in the regulatory space, also referred to as the prescribing information or package insert (PI), includes the approved uses of the product as well as instructions for use, along with warning details that coincide with information necessary to ensure the drug is used safely and effectively. This extends to all the data and statistics on adverse events, findings from clinical trials, and manufacturing specifications. Labeling text should be derived from the company core data sheet (CCDS), the approved internal source document that is the basis for product, labeling, artwork, packaging and promotional materials.

There are significant business complexities with regard to managing labeling text. One of the most critical aspects is creating and managing the CCDS, which must account for all product information of commercial relevance to the company in addition to all Health Authority (HA) labeling requirements across regions. Organizations also often experience significant difficulty in tracking and capturing the reasons for any deviations that may exist between the content in local submission documents (e.g., Summary of Product Characteristics [SmPC]) and the content in the CCDS. Given the global nature of pharmaceutical products, companies must be able to respond quickly and accurately to regional mandates and changes.

In this multifaceted, highly regulated and global environment, life sciences companies need to adopt processes and solutions that will enable them to respond rapidly to change and achieve actionable insights across the entire labeling life cycle. This will result in improved regulatory operations as well as enhanced collaboration with all relevant stakeholders — regulatory, manufacturing, marketing and legal.

A strategic, enterprise-wide approach to labeling — where content, including the CCDS, can be easily shared and updated — will help deliver multiple benefits to companies and drive value across the following five business scenarios.

Faced with a rigorous regulatory environment and heightened business demands, life sciences companies are under continual pressure to better manage their labeling to reduce errors, avoid misbranding, improve consistency and gain efficiencies. Labeling content is subject to constant change, whether because of product development, mergers and acquisitions (M&A), regulations, regional differences, product updates or safety findings. Failure to act quickly and accurately puts companies at risk of noncompliance, which can result in fines and damage to the brand as well as to the organization.

How a Strategic Approach Enables Cross-Functional Visibility in Labeling



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Scenario 1: Adopting a global perspective

Between the time a product is approved in its first market and its approval in other markets, more often than not, the labeling text is adjusted to some degree to meet local legislative requirements. This will have an impact on the core documentation, so it’s important that those adjustments, however small, are accurately captured, updated and reflected in the CCDS — this being a single-source-of-truth document to be used and modified by all data owners — capturing all affected labeling text(s). Often this is an area where complexities and inconsistencies arise due to fragmented systems and processes.

Companies must also ensure adherence to specific regional requirements. In the United States, the U.S. Food and Drug Administration (FDA) amended its prescription drug and biological product labeling regulations in December 2014 to require electronic distribution of PIs. However, other markets, including Europe, still require traditional paper-based PIs.

In Europe, companies are required to have their labeling and artwork approved and translated into each country’s language — or, as is the case in some markets such as Belgium, multiple languages. Companies must not only manage those translations but must verify that the translated text conforms to the source documentation — the labeling text, typically the English source derived from the CCDS. Compounding the difficulty with translation is capturing the approved translation and versioning it against the original English-language version, identifying the right terminology and updating accordingly. New information might identify potential new market opportunities — such as allowing a product to be administered in a wider setting — but the challenge can lie in maintaining consistency across the labeling text for all countries through hundreds or even thousands of revisions over the course of a product’s life on the market.

Historically, this has been a manual approach. Having a piecemeal method for managing global labeling can create significant complications with regard to version control. Moreover, failure to maintain a CCDS — with all relevant product and regional labeling information — will make global labeling activities unnecessarily burdensome. For example, if there is no formal CCDS and some regions use file-sharing and/or email to submit labeling updates, it can be difficult for headquarters to determine whether what has been sent is from core documentation. If affiliates are redeveloping content from scratch, the likelihood of inaccuracy increases, leading to noncompliance.

In conjunction with a robust CCDS, an electronic, cloud-based approach that ensures version control reduces the risk of downstream errors and delivers greater global harmonization.


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Scenario 2: Managing deviations

Life sciences companies have struggled with labeling-text consistency for several reasons. The first obstacle is the limited corporate compliance oversight of labeling text outside of major markets, as explored in Scenario 1. Companies must be able to quickly identify and control the version being used, especially by third-party vendors and local regional representatives.

Second, problems arise because of uncontrolled and unstructured labeling content when it moves from regulatory affairs to artwork teams. The difficulty is that once the text goes from the regulatory affairs team to the labeling one, to manufacturing to disseminate the product, and to marketing to create promotional material, it’s hard to have proper oversight into what’s happening while also maintaining consistency and version control.

A third issue relates to fragmented primary and secondary labeling processes compared with factory processes, since each market — and often each function — has its own practices. Having a system that provides all stakeholders with visibility into any changes and deviations, and keeps track of alignment and variations from the CCDS, helps companies achieve a true interoperability strategy across all regions and functions.

As already mentioned, updating information and terminology in the CCDS and ultimately the labeling text — not only in a primary language but also across any regional variants — has historically been a laborious manual activity. Teams of people are tasked with finding and updating phrases and/or artifacts across all labeling documents. For example, a product initially launched in a single country will need to satisfy the labeling and regulatory content requirements specified by each local and/or regional HA responsible for granting market authorization, potentially resulting in multiple variants of a common set of statements and claims. Adopting a solution capable of tracking deviations, where labeling content for both HA submissions and artwork creation is derived from — and traceable back to — a single master source of content both reduces the risk of uncontrolled deviations and also simplifies updates.

One example of how this approach can be beneficial is when the labeling text for the product needs to be searched and updated, allowing for greater control and traceability. An automated, content-focused approach also enables a very quick search and replacement of any affected labeling text — typically starting with the primary-language version — after which the system can identify all localized translations that need updating.


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Scenario 3: Gaining efficiencies and realizing cost benefits

Typically, regulatory-driven changes can take months to determine and implement due to a lack of clear oversight of what labeling text has been used where. Multiple stakeholders across different departments and regions must coordinate to implement changes affecting numerous interrelated parts: the labeling text, a carton, a bottle, the label for the bottle, right down to the factory-printed labels for bulk shipper cases. Marketing products in regions with multilanguage requirements further complicates things, since all of those components must be translated into each language, and all of the translations must be consistent across languages. Managing the sheer volume of labeling activities is a resource and time challenge for companies.

When inaccurate or noncompliant labeling occurs — including misbranding or mislabeling — the outcome can range from a delayed product launch to a full-blown recall. Indeed, labeling errors or mix-ups are oft-cited reasons for product recalls, which always come with severe financial ramifications. In the case of a recall, companies are required to identify the affected products and make necessary labeling corrections before the product can be returned to the market. Not only is misbranding or mislabeling a threat to public health and safety, but the resulting delays in returning a product to market are clearly detrimental to a company’s bottom line. In fact, it has been estimated that a delay in launch can cost companies an average of $15 million per drug, per day.1 There is also the significant cost of waste to factor in. In an industry making increased use of distributed supply chains, downstream relabeling is often not an economic option.

A centralized, automated approach to labeling — incorporating phrasing, imagery, logos, etc. — reduces the risk of noncompliance and, where problems do occur, being able to readily tailor the search for affected phrases makes it easier to find and recall those products.

The situation for medical devices companies is somewhat more complicated, since they are obliged to develop a significant amount of labeling content before starting clinical trials. They will, therefore, need to find ways to gain efficiencies with their processes early on.

Preparing artwork and labeling from structured content drives both quality and productivity by allowing all stakeholders to leverage standardized business assets, such as reusable imagery and phrases. Recent advances in technology and tools for labeling activities can improve processes involving the collation and storage of labeling content; the labeling and artwork-creation process; approval and version control; the transfer and archiving of artwork-related files; alignment of print functions; and signature and audit trails. As a result, these activities, which typically can take weeks to manage, are completed within minutes.

Scenario 4: Breaking down silos and enabling collaboration

As companies partner more, or undergo mergers and acquisitions, it’s vital that all parties share information that is pertinent to labeling. For example, when one partner manufactures the product while another is responsible for product licensing and

1 T. Noffke, No Time to Delay, PharmExec.com, March 1, 2007, http://www.pharmexec.com/no-time-delay


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promotion, it’s imperative that labeling information is relayed from the manufacturer to the partner’s regulatory function as well as to marketing, to facilitate adaptation of labeling text into promotional materials.

Despite recent delays to implementation, the looming identification of medicinal products (IDMP) standards also place increased focus on improved collaboration and visibility between functions. Historically, dedicated labeling groups — which may include global labeling content management, global labeling operations and global labeling compliance — have been responsible for handling updates to the label and packaging artwork and submitting them to the health authorities. The department responsible for labeling simply provided its update to the HA annually or as required.

IDMP requires timely and accurate submission data that will include packaging and labeling elements so organizations can gain approval to market their products. This will involve more frequent reporting, driving greater collaboration between labeling, supply chain, manufacturing, regulatory and other functions, including clinical, pharmacovigilance and Pharmaceutical Quality/CMC — some elements of which are outside the scope of the CCDS.

Capturing each of these elements as structured content will be essential in simplifying the submission and management of all product-related content (including labeling). Organizations will need to move away from the constraints imposed by managing content as unstructured data in fragmented silos to achieve greater collaboration and more robust compliance.

Scenario 5: Improving transparency and visibility

Traceability regulations such as Unique Device Identification (UDI), plus serialization in the form of the Falsified Medicines Directive (FMD) in Europe, and the U.S. Drug Supply Chain Security Act (DSCSA) require greater alignment across increasingly granular global labeling and artwork content. The difficulty has been the fact that content at the manufacturing/supply chain and third-party printing level is not always electronic or unified. Ensuring transparency in labeling and preventing inaccurate or misleading content should be made a priority. If companies are to remain compliant, they must adopt a solution that easily integrates with a number of controlled/managed data sources to transform content into compliant labeling components — labeling combined with harmonized processes to tackle the problems created by silos — and thereby achieve data consistency.

The increased focus on safety has also added to the need for greater visibility across the entire supply chain. For example, in 2013, the European Medicines Agency intro-duced a requirement that the label of certain medicines that are being monitored carry a black inverted triangle. The purpose is to denote products that have been found to have serious adverse effects that could have an impact on patients. Similarly, the U.S. FDA requires boxed warnings about serious risks, such as for opioid analgesics and immediate-release opioid pain medications. The difficulty is that without clear visibility into which products are affected by these labeling requirements, it is difficult for companies to comply quickly. The ability to generate detailed audit trails capturing changes that have both local and global impact has become increasingly important in demonstrating compliance.


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The full labeling picture

The life sciences industry must adopt a joined-up approach to managing labeling text, artwork, packaging and promotional materials to ensure country-specific rules are obeyed and labeling changes can be made quickly and accurately. If processes lack visibility, or there is a breakdown in collaboration between functions and regions, or there are systemic inefficiencies or new corporate merger-and-acquisition activity, companies will struggle to achieve cost reductions and productivity gains that could otherwise have a positive impact on both time to market and faster integration of newly acquired businesses. The potential ramifications include fines, products held at customs, having products pulled from the market, delays in bringing products to market or, perhaps, having the brand name tarnished.

When all the cogs in the wheel work together, improved management of labeling content ensures better insight of compliance as well as greater synergy across reporting, artwork, packaging and promotional materials. While promotional materials are currently managed by regulators under separate guidelines, it’s only a matter of time before HAs make the correlation between the labeling text and promotional materials. In June 2017, the FDA’s electronic Common Technical Documents (e-CTD) Module 1 guidance for advertising and promotional materials — currently voluntary — will become mandatory, and it won’t be a huge leap for authorities to identify disconnects between content in labeling text and content in promotional materials.

Companies need to ensure that they have the tools and processes to manage their labeling content more holistically to avoid risk of noncompliance. Leveraging a centralized, automated approach makes good regulatory and business sense.

Figure 1. Structured Content Underpins Robust Compliance

Mock-upGeneration

PackagingComponents

PatientInformation

ClinicalTrials

OnlineContent

Marketing Collateral Regional

VariationsCoreStructured

Content

CoreDataSheet


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White Paper

From discovery to post-marketing: labeling across the spectrum

Life sciences companies often think of labeling and artwork as documentation and activities related to the marketed product. But the regulatory text that must appear on the labeling and packaging content is developed much earlier and exists in multiple places — the supply chain system, clinical documentation and regulatory submission information.

Primary Approach — Labeling Post-Market

Regulated documents (labeling, package inserts, etc.) approved

Subject to ongoing updates

Potential maintenance, including translations

Changes affect multiple functional groups

Growth in promotional materials management (such as TV ad spend)

Methodology Change — Labeling from Phase 3

Time is key — agility, visibility, quick responses

Master labeling content and processes early to improve capture of all key information

Support activities vs. manage documents to enable a seamless move from premarketed activities to Phase 4 or approval

New Approach for Drug, Required for Devices — Labeling from Phases 1 and 2

Invest time and resources in clear update to product company core data sheet (CDS); CDS becomes foundation for product labeling and supports company core safety information

Support clinical trials, since labeling details are needed in the investigator brochure and to administer product, especially for devices

Support from the Ground Up — Labeling from Discovery

Labeling details emerge, plus support for supply chain activities

Manufacturing and controls are key to product and substance specifications and generate data for labeling and packaging

Gain transparency from developmental process and engage functions in use of platform approach

Figure 2. Labeling Throughout the Life Cycle: The Benefits of Starting Early

Learn more at www.dxc.technology/ life_sciences

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