While pharmaceutical innovators streamline operations in the developed regions, significant investment is being poured into emerging markets to fuel growth, specifically by manufacturers of generics, as more pharma products go off patent. It is estimated that generic competition eroded $67 billion from top drug companies’ annual sales in the U.S. between 2007 and 2012, with more than three dozen drugs losing patent protection during this period (DeRuiter and Holston, 2012). EvaluatePharma’s (2012) analysis shows that more than $290 billion of prescription drug sales are at risk from patent expirations between 2011 and 2018.

In response to these pressures, the global pharma industry is exploring new growth opportunities in emerging markets, strengthening R&D by collaborating with industry and academic partners, moving towards a mixed portfolio of innovative and generic products and focusing on operational efficiency. As a result, even the marketing of these products is being driven more by partnerships between multiple companies. There has been a substantial increase in the number of licensing and supply partnerships between generics manufacturers based in emerging markets and large or mid-sized global pharmaceutical companies. Indeed, it is predicted that “Pharmerging” will be responsible for more than 50% of the growth in the global pharma markets (Management Centre Europe, 2012). Apart from the sharing of risk, collaborations with manufacturers of generics allow innovators to increase their product portfolio and ensure their economic viability.

This global expansion across different geographies has led to decentralization that can, in many cases, slow down complex processes and reduce operational efficiency and profitability, while delaying time-to-market. Furthermore, the need for greater quality checks to ensure brand integrity is paramount in the global marketplace in order to comply with local regulatory mandates and to manage the resources that are spread across multiple geographies.

Product labeling is one such process affected in maintaining a company-wide quality system within a global business model. Product labels are an essential part of the marketed product as they provide comprehensive information about the drug, and also represent a significant percentage of the manufacturing cost and commercialization risk in terms of ensuring patient safety. With innovators undertaking manufacturing in emerging countries, conducting quality checks in another country and marketing the product in a third country, the business model has grown to such dimensions that it has become extremely complex to maintain a company-wide quality system that standardizes product labeling processes globally.

Regulatory Challenges
Pharmaceutical product labeling is a highly regulated and complex process that is an integral part of a company’s overall quality system. It includes vital information related to the product: the drug’s name, the manufacturer’s name and address, an identification code, lot number, active and inactive ingredients, quantity of product in the container, indications, safety information, usage instructions, storage conditions, and an expiration date. A product with a wide geographical footprint requires labels in each country/region to comply with the requirements of local regulatory agencies. This increases the risk of having inconsistent information across labels of the same product.

Ensuring that labeling processes are standardized and updated in accordance with regulatory updates is a challenge for both pharma innovators and manufacturers of generics. This has been highlighted in the recent plans announced by the U.S. FDA to establish similar labeling guidelines for generics and branded drug manufacturers, which will further increase the regulatory challenge for generics companies (Reuters, 2013) (Reginfo, 2013). As it stands, manufacturers of generics are prevented from updating their labels for potential safety issues without special FDA approval, although branded drug manufacturers can. After the law comes into practice, generics manufacturers will be allowed to update labels based on new safety information.

Manufacturers of generics run the same risks as the innovators and therefore face unlimited liability if the labels on their products fail to include vital information or if their products cause any injury to a consumer (Forbes 2013). Ensuring label accuracy and the implementation of associated quality controls with suppliers and distributors, together with regulatory compliance across regions that have varying regulatory requirements, are therefore among the prime concerns for any pharma company.

The Labeling Process
Product labeling is a collaborative process, from initiation of a clinical trial to commercialization, with multiple sources of inputs and hand-offs that ultimately result in an internal reference document known as the Company Core Data Sheet (CCDS). The CCDS includes all the relevant information on the product to be labeled, and is used to map labeling information for different regions. Every CCDS may require multiple changes depending on the markets where the drug is approved and sold. Complexities increase while managing regional documents because the approach needs to accommodate local regulatory requirements, languages, writing styles, and conventions. The issue is further compounded when these regional adaptations need to be updated whenever there is a change in the master CCDS; frequent changes in regulatory requirements and the number of hand-offs make the process even more complex.

For most organizations, the primary processes involved in developing a product label are manual, labor intensive, and prone to costly mistakes. Moreover, the processes are time consuming, as multiple stakeholders such as medical, regulatory, legal, manufacturing, and quality specialists need to be involved in each label update. For example, updates to the prescribing information of a product, changes to the manufacturing processes and new side effects, need to be included in the label. The process of creating the updates to the prescribing information is labor intensive, as the changes must be reviewed and transcribed into different formats (e.g. leaflets and artwork). Each version of the product label requires its own artwork, and significant resources are required for proofreading and validating artwork files to ensure that the printed label is error-free. Having a portfolio of products distributed across multiple regions with the associated requirement to comply with the regulations of multiple agencies increases this complexity and therefore also increases the cost exponentially.

Drivers for Labeling Automation
Currently, organizations develop standard operating procedures (SOPs) to streamline operations and minimize errors; however they often lack the automation required to build a robust and error-free process. While the use of an automated process can reduce cycle time and costs, the primary drivers for its use are label accuracy and quality. Error-free data submitted to regulatory agencies during the approval process prior to a product’s release to market is critical for its success. There is also significant motivation to shave time-to-market — while holding the integrity of the product — and the associated process costs.

Failure to ensure these key requisites of label accuracy and quality can lead to labeling errors that are highly visible and can seriously damage the reputation of a pharma company. Labeling errors, mix-ups and misbranding are among the most prevalent labeling errors that can lead to product recalls. The results can be crippling to an organization in terms of loss of revenue and market share, as well as negative publicity that can severely tarnish a company’s image. Research has highlighted that a company’s stock price declines up to 22% within two weeks after a recall is announced (Rapid Recall Exchange, 2010).

Recent product recalls by major pharmaceutical companies have highlighted this threat. In 2013, Vita Health Products Inc. voluntarily recalled a variety of health products from the Canadian market because of labeling issues (Health Canada, 2013). The recalled products pose a risk to health because the labels contain errors such as suggesting packages are child resistant when they are not, or are missing warning statements for consumers with allergies or existing medical conditions.

Given these labeling risks, pharma companies are continuously looking at making fundamental changes to their operations to adapt to the growing complexity, minimise risk and improve efficiency of the labeling process. However, managing the end-to-end process, such as multi-language translation of labels, may not be a core competency for many companies, nor do the majority have the expertise to handle the issues in-house. In order to focus on their core expertise of delivering new products to market, innovators and generic manufacturers can look to outsource the activity of updating labels to a partner with the required expertise, processes, and tools to improve the accuracy and quality of labels.

Meeting the Challenges with Labeling Automation
By outsourcing global labeling operations to specialized vendors, innovators and generic manufacturers are able to access managed services spanning Commercialization to Adverse Event Labeling processes (CAEL). Vendors that implement innovative tools and LEAN processes address the aforementioned labeling challenges by providing automated text comparison, content management, and workflow management. Automation reduces human intervention and ensures the development of high quality deliverables that significantly reduce overall operational costs and improve the time-to-market across organizational product lines.

An example of automation is updating the regional labeling documents from the master CCDS. In order to find and implement updates in different formats and languages, organizations utilize key resources to first make a side-by-side comparison of the two documents, and then update the local label. This is both labor-intensive and error-prone. By implementing automation tools, differences are automatically highlighted between the documents, significantly reducing operational costs, and improving quality and time-to-market due to the steep reduction of human intervention. In the case of generic products, where the update of generic labels based on the Reference Listed Drug (RLD) might require the comparison of a number of pages and multiple voluminous tables, significant time and labor investments are needed. Manual intervention contributes to quality issues. Auto-generation of a comparison table using various source documents (generic label, RLD label and generic proposed label) is extremely helpful in saving significant amounts of time and developing error-free updated labels and change logs. Implementing a streamlined workflow management process, along with a document management system that standardizes label and artwork content and allows for version control, increases accuracy as it synchronizes content and versions across global geographies.

Due to the high demands of regulatory compliance, accurate labeling of pharmaceutical products has become a critical safety matter. Lack of effective control measures and processes to eliminate labeling errors could result in serious health hazards, regulatory actions, and a tarnished reputation for a pharma company.

In conjunction with compliance to the requirements of multiple regulatory agencies, there is a pressing need to address the challenge of ensuring content consistency across a broad portfolio of products across multiple regions. The issue of managing large labeling documents, multi-lingual information and effective translation management has forced both pharma innovators and generic manufacturers to view the labeling process from a different perspective. With such activities not at their core, these companies are now turning to external partners equipped with the latest LEAN and automation services to address the challenges associated with the growing complexity of the labeling process.

Based on our experiences, pharmaceutical innovators and manufacturers of generics can benefit through the attainment of a reduction in approval cycle times of 50%+, error reduction by 95%+, and an overall cost reduction of 45%+ – figures that represent clear financial benefits. The automated processes produce consistent and quality documentation that promotes the accuracy required to maintain patient safety as well as brand integrity. With a reduction in manual interventions of 60%+, changes can be managed much more quickly, saving significant amounts of time for pharma companies.

With the pharma industry addressing the challenge of diverse languages in emerging markets while reducing costs and complying with multiple regulatory agencies, there is a compelling need for automating labeling processes to reduce risk by ensuring greater content consistency across a broad range of products. 

References

• DeRuiter, J. and Holston, P. L. (2012). ‘Drug patent expirations and the ‘patent cliff.’ U.S. Pharm 37 (6) (Generic suppl): pp.12-20.
• Evaluate Pharma (2012). ‘Patent expirations put more than $290 billion in prescription drug sales at risk through 2018.’ Available at http://www.evaluategroup.com/public/PressReleases/Patent-Expirations-Put-More-Than-$290-Billion-in-Prescription-Drug-Sales-at-Risk-Through-2018.aspx Accessed 5/20/13
• Forbes (2013). ‘Generic Drug Makers Will Soon Face The Regulatory Music.’ Available at http://www.forbes.com/sites/richardlevick/2013/07/15/generic-drug-makers-will-soon-face-the-regulatory-music/ Accessed 10/2/13
• Health Canada (2013): Vita Health recalls numerous Over-the-counter products because of labelling errors. Available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2013/35525a-eng.php Accessed 10/20/13
• Management Centre Europe (2012). ‘New Opportunities & Strategies in the Pharmaceutical Industry.’ Available at http:// www.mce-ama.com/executive-issue-38-pharma-industry-2012/ Accessed 10/3/13
• Rapid Recall Exchange (2010). ‘Patent expirations put more than $290 billion in prescription drug sales at risk through 2018.’ Available at http://www.rapidrecallexchange.org/LinkClick.aspx?fileticket=6o5DhktwSe8%3D&tabid=37  Accessed 9/30/13
• Reuters (2013). ‘U.S. FDA to propose allowing generic drugmakers to update drug labels.’ Available at http://www.reuters.com/article/2013/07/03/fda-generics-idUSL2N0F92B320130703 Accessed 10/20/13
• Reginfo (2013). ‘View rule – Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products.’ Available at http://www.reginfo.gov/public/do/eAgendaViewRule?pubId=201304&RIN=0910-AG94 Accessed 10/20/13

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Chitra Lele, Ph.D. is chief scientific officer, Sciformix Corporation. Bindu Narang is director regulatory affairs and scientific writing, Sciformix Corporation. Copies of the pharmaceutical product labeling whitepaper from Sciformix are available by emailing ask@sciformix.com. For further press information, please contact David Bertram at sciformix@scottpr.com or Susan Najjar, director of marketing, Sciformix Corp., at susan.najjar@sciformix.com.