Quality Oversight Brings Quality By Design To R&D

In the pharmaceutical industry, quality by design (QbD) has long been applied to manufacturing. Incorporating good manufacturing practices (GMP) into the production process is expected and required by the Food and Drug Administration (FDA). Yet, rarely are QbD practices adopted before the drug enters commercial production.

The problem with not following QbD prior to commercial production is that it is extremely difficult to insert or force quality into a suboptimal process.  Doing so leads to awkward and inefficient practices, duplicative efforts and “Band-Aid” approaches to quality. Building a quality pharmaceutical begins with building quality into the research and development phase.

One may argue that QbD is already built into R&D through clinical quality assurance (QA). While QA certainly is an important part of clinical research, it does not build quality into the process. Because it is traditionally conducted as an assessment at one point in time, it does not provide a continuous assessment over the course of the trial and therefore cannot be considered as part of the process.

What can pharmaceutical companies do to build quality into research and development? They can implement a third-party quality oversight program. Quality oversight upholds the principles of QbD, because it is performed over the course of the trial and it represents a simultaneous exchange of information that allows for real-time corrective and preventive action (CAPA).

What is quality oversight?
Third-party quality oversight provides an unbiased and objective assessment of the vendor contract research organization (CRO) work effort. Sponsors utilize many processes to evaluate the quality of their clinical trial data; however, the bias that may exist in a long-term relationship between a sponsor and its clinical trial CRO makes it more difficult for the sponsor to adequately assess the vendor CRO’s performance. Third-party quality oversight eliminates this bias and provides reliable information in real time.

An optimally structured quality oversight program should not result in any duplication of effort on the part of the sponsor. Quality oversight is all about processes and adherence to contractual and regulatory requirements. It is not about co-monitoring or re-auditing the study.

Quality oversight builds quality into a clinical trial by ensuring that CRO performance meets FDA and other regulatory body requirements and that the work also meets FDA expectations.

Let’s take a closer look.

Ensure that CRO performance meets FDA requirements
While sponsors always have been responsible for the quality of their vendors’ work, it is now clear that sponsors also are being held directly accountable for that quality. Nowhere is this more evident than in the case of recent FDA warning letters issued to top-quality pharmaceutical firms for failure to oversee the activities of their vendors.

Problems don’t have to reach warning letter status to attract the attention of regulatory authorities. Several sponsors have reported that FDA investigators are specifically asking how the sponsor oversees the activities and assures the quality of its clinical vendors. This is a legitimate question and one that industry sources expect will gain more currency as part of the inspectional process. Third-party quality oversight answers this question.

Ensure that the work meets FDA expectations
FDA’s good clinical practice (GCP) requirements are quite thin—most are expectations of ethical and scientific quality standards rather than codified regulations. So how can a sponsor successfully navigate what could become a mine field of expectations? By retaining an expert with significant experience in FDA submissions.

The quality oversight provider should have extensive experience in GMP as well as GCP in order to bring GMP-quality methodology to the clinical process. The quality oversight team should be comprised of senior clinical research associates with significant experience in this type of activity. Through accrued experience, the quality oversight provider should thoroughly examine the CRO work effort and authoritatively weigh its adherence to FDA expectations.

Incorporating QbD into research and development through third-party quality oversight of clinical trials helps pharmaceutical companies ensure that FDA requirements and expectations have been met long before a drug enters commercial production. Entering production without this assurance can mean costly delays and unnecessary re-work.

This article appeared in Pharmaceutical Compliance Monitor on January 16, 2012.

Date posted: January 30, 2012

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