Enterprise Quality Management: Key to Quality Clinical Outsourcing

Pharmaceutical companies are paying more attention to value than ever before. With budgeting pressures and mergers and acquisitions, companies are forced to restructure resources and invest in the intangibles such as quality, responsiveness, flexibility and real-time reporting. At the same time, there is a push to develop innovative, quality medicines to support accelerated drug development programs. To meet this demand of doing more with less, many pharmaceutical companies are shifting towards outsourcing as part of their business model.

Specifically, outsourcing clinical work is a growing trend in the pharmaceutical industry, no matter the size of the company. The high costs of conducting clinical trials in the U.S., the difficulty in recruiting patients and bureaucratic delays are causing small biotechnology and large pharmaceutical companies to seek clinical trials partnerships outside the U.S (Nicholas 2012, 1045) As a result, Clinical Research Organizations (CROs) are quickly growing, which makes it even harder for pharmaceutical companies to track and manage work outsourced across multiple organizations.

Clinical testing was once conducted within the same four walls of the company marketing the product. Now it is more often outsourced to contracted researchers all over the world and conducted in different ways. Today, when a pharmaceutical company decides to outsource clinical trials, the company limits its control over how the clinical testing is being conducted and the chosen method to record the results. The collected data could be stored in an Excel document, or just written in a notebook, for example.

North American pharmaceutical companies historically have had an advantage when it came to outsourcing clinical work because of relative economic stability, scientific experience and proximity to the majority of the pharmaceutical industry. That advantage gave pharmaceutical companies a sense of reassurance knowing these organizations are familiar with regulations and quality practices. With CROs expanding in regions all over the world, more and more pharmaceutical companies are drawn to the upfront cost savings from having clinical trials performed overseas.

However, the travel required overseas to audit and qualify CROs is time consuming. Pharmaceutical companies outsourcing work must take the appropriate steps when evaluating and selecting qualified outsourced partnerships because in the end their product label is the ultimate affirmation to customers. Once a lab is qualified, the company outsourcing the work may have to leverage significant resources to ensure the proper procedures are being followed throughout the testing process.

The company outsourcing work must then ensure that the contracted company’s data is dependable by confirming that uniformed processes are used to administer, document and manage change throughout all phases of testing per FDA regulations and the company’s own requirements. Poor clinical practices or inexperience in meeting required regulations are often the cause of data being rejected. If not done correctly, the company outsourcing the work can be held accountable for any potential issues.

For example, in October 2012, the New England Compounding Center (NECC) made headlines when some of the products distributed by the compounding pharmacy contained fungal meningitis. This resulted in serious injuries, including five deaths. Historically, pharmacists have been compounders of active and inert ingredients under the direction of physicians to assist individual patients. Investigation into the exact source of the outbreak is still ongoing, but the outbreak is associated with a potentially contaminated medication.

While this is a unique example of alternative pharmaceutical manufacturing, the NECC seemingly took advantage of the lack of regulatory oversight and mass-produced and sold compounded copies of existing licensed drugs across state lines at a discounted price over the approved branded pharmaceutical products. This same limited regulatory oversight exists for many offshore CRO locations, and the quality and accuracy of the data is the ultimate responsibility of the pharmaceutical company contracting the trials.

Whether it is small batch processing, correspondence or audits, it is critical that quality processes are managed throughout research and development in order to optimize time to market of a safe and effective drug. 

The need for clinical quality management technologies to help manage compliance and quality processes using a single, centralized system is imperative whether or not clinical development is outsourced. To accommodate this shift, organizations are removing the walls that isolate quality as a function and taking back-to-basics approaches to embedding it as an end-to-end organizational competency (Jacobson 2011, 1).

Today’s leading pharmaceutical companies rely on enterprise quality management systems (EQMS) to manage the myriad of standard quality processes - whether or not they outsource clinical work - such as audits, corrective and preventive actions (CAPA), deviation, and out of specification/out of trend (OOS/OOT). The technology is in place to streamline the oftentimes siloed quality processes followed when bringing a final product to market as well as to create a holistic and transparent view of a company’s quality data.

With an enterprise quality management system, pharmaceutical companies can plan and execute audits to identify operational and compliance risks, such as a trial not being administered the same way throughout the testing period, and help to ensure that findings are resolved in a timely and effective manner.

By taking a holistic approach to quality, pharmaceutical companies can automate CAPAs precipitated by deviations, complaints, audit findings and laboratory findings and manage the process of carrying out CAPA plans and verification of the plans’ effectiveness on a global scale.

Outsourced organizations have their own processes, procedures and systems that may not translate into complete transparency that the hiring company would require should an issue arise. This could result in falsified documentation and lack of trust in believing these organizations are doing what they say they are doing. The company outsourcing the work must examine how product specifications are defined across multiple CROs. Avoiding common definitions for units of measure, specifications and recipes, item classification, product serialization, complaint classification, risk matrices and metrics will only exacerbate any existing inconsistencies (Jacobson 2011, 6). Automating clinical quality processes from A to Z can help pharmaceutical companies define the universal criteria needed to ensure testing procedures are conducted in a uniformed matter and trust the people they work with by providing evidence those proper procedures are being followed.

As outsourced contractors are held to the same FDA guidelines and requirements as pharmaceutical companies, having an enterprise quality management system can ensure specifications are understood and issues, such as deviations and complaints, are properly and efficiently investigated and brought to resolution through the tracking and managing of the initial report, phased investigation, root cause analysis and any resulting CAPAs and controlled changes, fully closing the quality loop.

Many CAPA processes end with requiring changes to trial criteria, documentation, or additional critical areas of the trial or product manufacturing.  Most of these changes require a formal change control process.  Some work could be spread out among several organizations, making it harder to confirm the trials and subsequent CAPAs and changes are conducted in uniformity from the products being used to how the trial is being conducted. Managing these changes is critical, because any change can impact the results of the trial or consistency of the product being tested resulting in a deferred time to market.  Having change control as part of an enterprise quality system closes the loop from event discovery, through the investigation to any CAPAs and changes made.

Pharmaceutical companies marketing a product are ultimately responsible for ensuring all regulations are followed and its brand and label are a clear representation of what that product intends to treat. When a pharmaceutical company gives up any control to outsourced researchers and organizations, they may gain increased flexibility and capital, but if not done correctly, it could become very costly. An enterprise quality management system helps ensure quality processes are systematically managed throughout drug research and development in order to optimize time to market as well as comply with regulatory requirements.

Sources:

Jacobson, Simon F. 2011. “Best Practices for Taking Quality Beyond Manufacturing and Into a Business Capability Supporting the Value Chain.” Gartner: 4-10.

Nicholas, Joanne, “Outsourcing Clinical Trials,” Journal of the National Cancer Institute 1043 (2012): 1043-1045, accessed June 7, 2013, http://jnci.oxfordjournals.org/content/104/14/1043.full.pdf+html

FDA “New England Compounding Center (NECC) Potentially Contaminated Medication: Fungal Meningitis Outbreak,” accessed June 12, 2012, http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm322849.htm