Every year, the US Food and Drug Administration issues scores of Warning Letters to pharmaceutical, medical device, and biologics
companies. Although Warning Letters can be triggered by situations such as customer complaints and whistleblower statements,
the majority follow an inadequate company response to a Form 483 issued by FDA after an on-site inspection has identified
potential violations of regulatory requirements.
Surprisingly, many companies' violations center on failure to have, or to properly use, Standard Operating Procedures (SOPs),
the most fundamental component of current Good Manufacturing Practices (cGMPs). Although different regulations apply to each
of the life sciences sectors, SOP compliance is required for all companies within those business arenas.
SOPs and Quality
The purpose of an SOP is straightforward: to ensure that essential job tasks are performed correctly, consistently, and in
conformance with internally approved procedures. Clearly, employees' correct, consistent performance of essential job tasks
is as much a business and quality issue as it is a regulatory requirement.
By its nature, poor employee performance has a negative impact on overall operational performance. That impact may be even
greater than recognized by many organizations, with some studies suggesting that up to 40% of operational inefficiencies can
be attributed to employees' failure to fulfill their job responsibilities. Even companies that have implemented costly process
improvement systems continue to feel the operational impacts of "human error" on their efficiencies and quality control.
Few industries are more vulnerable to risk than the life sciences sector. Although all industries share a financial vulnerability
resulting from operational inefficiency, the liability associated with compromised product quality can hit a life sciences
company particularly hard. Compromised product quality can easily result in product recalls, regulatory enforcement, and governmental
litigation, but even the suspicion of quality problems can send patient, healthcare professional, and stakeholder confidence
plunging. With highly publicized product recalls still fresh in the minds of the public and regulators, life sciences companies
and their products are coming under greater scrutiny than ever before. And, because FDA's Warning Letters are public information,
public scrutiny is quickly fueled by news reports via the media or the Internet.
Although FDA has long emphasized the importance of SOP compliance, the Agency's evolving focus on quality as the driver of
compliance adds weight to the importance of a comprehensive corporate approach to development and use of SOPs. Warning Letters
routinely conclude with a sober reminder that "... violations may result in FDA taking regulatory action without further notice
to you." FDA has an arsenal of actions it can impose, from confiscating product inventory to initiating product recalls, assessing
civil penalties and fines, or pursuing criminal prosecution.
FDA's definition of an SOP is deceptively simple. SOPs are, according to a variety of FDA regulations, written procedures
that accurately describe and detail essential job tasks. For example, in 21 CFR 211.100, the regulation states: "There shall be written procedures for production and process control designed to assure
that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Such procedures
shall include all requirements in this subpart. These written procedures, including any changes, shall be drafted, reviewed,
and approved by the appropriate organizational units and reviewed and approved by the quality control unit."
Beyond the written procedure, SOP compliance includes a requirement to train employees on essential job tasks, something expressed
in 21 CFR 211.25, which applies directly to the pharmaceutical industry, but is applicable to all life sciences industries. "Each person
engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, experience,
or any combination thereof to enable that person to perform the assigned function." It is this combination of written procedure
and employee training that assures the quality of a drug product or medical device being tested or manufactured and its compliance
with applicable FDA regulations.