Coming to Terms with Compliance1

By: Fredrik Sundberg
Drug manufacturers are under increasing pressure to bring products to the market faster and more cost-effectively while simultaneously meeting stringent quality requirements. Changing regulatory environments make the task of monitoring and adhering to quality standards challenging -- but the costs of non-compliance are high. Failing to comply with and satisfy the demands of regulations can result in heavy fines, product recall and in some cases, plant closure.

VMP programme checklist

Before a drug can be marketed, it must gain approval from regulatory authorities such as the US Food and Drug Administration (FDA) and/or the European Agency for the Evaluation of Medicinal Products (EMEA). A company applying for marketing approval must demonstrate that the drug has been produced according to strictly controlled and validated procedures, so ensuring the safety and consistent quality of the product. According to FDA, process validation is defined as: "Establishing documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting the predetermined specifications and quality attributes." Regulatory compliance is necessary at all levels of the drug discovery and development chain, encompassing areas such as good laboratory practice (GLP), good manufacturing practice (GMP), and good clinical practice (GCP). GLP focusses on the in vitro and in vivo evaluation of toxicological safety, with an emphasis on anticipating safety issues for clinical evaluations. GCP requires the evaluation of both product efficacy and safety in a clinical context, whereas GMP focusses on the quality evaluation of the manufactured product.
The areas requiring regulatory compliance cover an extremely broad spectrum. Existing regulations are periodically updated and revised, and are stringently enforced. Drug manufacturers, therefore, must keep abreast of regulatory developments - even unintentional non-compliance can potentially cost millions in fines and disruption to operations. The costs of non-compliance A regulatory authority can impose routine inspections, mandatory alterations in procedures, forced closure and even criminal prosecution on companies failing to comply with regulations. During the past 5 years, there has been an increase in the number of consent decrees (legal agreements to settle disputes with FDA) in the US, which can incur costs of tens of millions of dollars.
A dispute in 1999 involving a high profile company resulted in a $100 million fine for failing to correct defects in its manufacturing processes despite 6 years of warnings (Washington Post 03/11/99).

Vendor qualification checklist

Warning letters from FDA to companies violating regulations, which are publicly displayed on FDA's website, are another cost that severely damages a company's reputation.The language is unequivocal and plainly states how a company has failed to meet regulatory requirements (www.fda.gov/foi/warning.htm). The ultimate cost, however, to those that fail to meet regulatory requirements is that potential revenue from a product will be lost, jeopardizing returns on investment.
Maintaining compliance Regulatory compliance is not a one-off procedure and should be an integral part of an organization; companies must take into account compliance. This may involve devising an ongoing management process that includes:

• company-specific interpretation of current regulations
• creation of a systems inventory
• identification of systems that do/do not comply
• a detailed assessment of any gaps in compliance
• development of an active implementation plan, describing the necessary corrective actions required to bring systems into compliance
• prioritization of systems that need to be upgraded
• ensuring compliance of systems according to a prioritized list
• ensuring documentation is in place, archived and properly maintained.

Validation master plan. To avoid unnecessary work and obtain a good overview of the entire project, the plan should not repeat any information that is available elsewhere, for example, in SOPs. Rather, it should refer to established documentation. Regularly updating and reviewing template documents is required to make sure that all the latest regulations are incorporated with newly introduced company policies.