There continues to be much interest within industry and FDA about the future of the GMPs. Discussion groups have been
spawned within professional organizations and at FDA to reevaluate the aging GMPs and associated guidance documents to ensure
that the government does not impede technological progress, focuses its resources effectively, and upholds its mandate to
protect the public. Although this trend is largely fueled by FDA's budgetary constraints, good things happen when we are reminded
to focus on the essentials.
The present struggle within industry and among regulators is to sort out how best to grasp the essentials. FDA must grasp
the essentials in order to translate them into regulations and guidance, and industry must grasp the essentials in order to
translate them into best practice and consistent behaviors. So far, there have emerged several key themes. We can expect this
lively dialog to lead to changes in how we answer the question: "Compliance with what?"
The following is a brief discussion of these key themes that are changing how we think about compliance and several practical
examples to elucidate the "mindful compliance" we seek to achieve. Beyond simple compliance with regulations, mindful compliance
entails aligning our operations to ensure a data-driven state of control.
Process knowledge is the collective awareness and experience of science and operations technology that ensure a product is
manufactured and delivered in a manner consistent with its intended design. The more knowledgeable we are about our processes,
the more we are able to control them and evaluate the impact of changes.
Consider the example of a medical device manufacturer that was proud of its progressive approach to managing its component
suppliers. Suppliers were certified by facility audits and inspections of incoming attributes on the first ten lots received.
Having cemented partnerships with its suppliers, the manufacturer accepted future shipments on the basis of the suppliers'
certificates of analysis. However, when an investigation into field complaints for failing devices implicated a certified
component, the supplier would not refund the manufacturer because the component met all of the agreed-upon inspection tests.
The manufacturer failed to recognize that qualification of the supplier was not based on anything related to the component's
performance in the final product. The manufacturer knew nothing about the supplier's process variability or statistical control.
The manufacturer had not communicated requirements in terms that related to the functionality for this critical component.
The qualifying audit was too general and largely relied on the fact that the supplier was ISO-certified. Additionally, the
incoming attribute inspection was an ineffective predictor of the component's actual performance in use.
The manufacturer had — and followed — a procedure for qualifying its suppliers. However, mindful compliance is based on process
knowledge that is data-driven and statistically treated. In this example, loss to the manufacturer in terms of revenue and
customer confidence could have been avoided by acquiring process knowledge and making a technical assessment of the supplier's
Risk knowledge is the collective awareness and experience of causes of unacceptable effects such as personal harm and financial
loss, controls that eliminate risk or reduce it to acceptable levels, and metrics that detect trends toward failure. The more
knowledgeable we are about risk, the more we can focus on the most critical aspects of the process and apply more rigorous
process development, technical transfer, monitoring, and control.