Consequences of violations of the Food, Drug, and Cosmetic Act

Violations of the Food, Drug, and Cosmetic Act are not only expensive but may lead to extensive civil as well as criminal liability against the products, the companies, and individuals deemed responsible (10). While a product recall is generally a voluntary action by the distributor, the Act provides the authority for a seizure action against the product. This would occur if, for any reason, there were a refusal to recall or a recall was ineffective. In addition, the Act authorizes actions to enjoin the parties involved in the violations of the Act. Such injunctive actions by the courts includes court ordered plant closures and enjoining individual defendants for violations of the Act or even operating a pharmaceutical company in violation of the statues. The Act also authorizes the criminal prosecution for violations of the Act. A person may be prosecuted and serve a term in prison even if they can demonstrate they had no intention to violate the Act. While such strict liability may be quite onerous, the legislation deemed this necessary to protect the public health.

Finally, perhaps one of the strongest and most widely used action in the FDA arsenal is to issue (or share its intention to issue) a press release to alert the public of regulatory violations by a company. Press releases lead hesitant distributors to decide on recalling a nonconforming product (and therefore, avoid a seizure action against the product) and even to close plants for taking corrective and preventive measures to bring the manufacturing facilities into compliance.

Often, the financial cost of a failure in quality is measured by lost sales and increased costs of material. While these may represent direct cost, the indirect loss may be devastating for some companies and damaging to a lesser extent for others with a large cash-balance. Understanding the major sources of variation is essential to the design and control of robust processes in the manufacture of pharmaceuticals. Failure to adequately detect emerging problems, control processes, and prevent defects can pose risk to consumers, affect product availability, and yield undesirable regulatory and business outcomes. Sources of variability may include inadequate training, poorly understood standard operating procedures, processing parameters that are not well understood, lack of skill sets, lack of procedural control, and inadequate resources. A key source is possible human error and inadequate change control management and risk management. Unsuitable equipment, deficient preventive maintenance, and inadequate equipment calibration also lead to process variability. Inadequate understanding of the inherent variability and inappropriate characterization of excipients, APIs, and components can lead to an unacceptable process variation, and can be one of the most complex areas to track during the lifecycle of a pharmaceutical product.

If not controlled, these factors may lead to poor quality, product failure, regulatory enforcement actions, and ultimately have significant impact on profitability and potentially on the viability of the manufacturer. Notwithstanding the financial impact, for recurring and serious regulatory violations resulting in harm, the manufacturers and their senior executives are liable for civil as well as monetary penalties to consumers, to regulators, and to their shareholders.

Acknowledgments

The authors would like to thank Rick Friedman (US FDA), Rajendra Uppoor (US FDA), Margaret Szymczak, and Vinod Shah (USP) for their invaluable input, comments, and suggestions for this paper. Friedman, Uppoor, and Szymczak participated with Avraham Yacobi on the first PQRI–FDA workshop on Process Drift.

Satish Asotra is an independent consultant and founder of Pharmaceuticals Development, Regulatory and Process Management Consulting Group. Alexander Cossin is an independent consultant. Avraham Yacobi* is an independent consultant and a member of the Board of Directors, Product Quality Research Institute, and founder of Pharmaceuticals Development, Regulatory and Process Management Consulting Group, avi.yacobi@gmail.com
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*To whom all correspondence should be addressed.