During the past two decades, regulations have evolved in both Europe and the US to accommodate the technological developments in the pharmaceutical, biotechnology and medical device industries. However, these changing regulations are often increasingly stringent and complex.

In the US, the regulatory landscape has altered significantly. By the mid-1980s, biotechnology was a rapidly growing industry and there was an urgent need to address how biological drugs differed from traditional pharmaceutical products. In 1987, the FDA Center for Drugs and Biologics was divided into two entities: the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER). The division was necessary to cope with the huge number of new drug applications (NDAs), and to address issues in drugs and biologic evaluation.

The European regulatory landscape has also altered during the last two decades; for example, through the introduction, expansion and refinement of EudraLex: The Rules Governing Medicinal Products in the European Union.¹ EudraLex is a group of European directives and regulations that are constantly reviewed and updated to reflect Europe's changing technologies and environment. It also standardizes regulations with FDA through ICH.

FDA Title 21 CFR Part 11 was introduced in 1997 to govern the growing use of electronic records and signatures, and sets out acceptable criteria for the trustworthiness of this format. This new regulation sought to educate the industry on best practice logical and procedural controls, audit trail requirements and validation for the use of such records. Unfortunately, the legislation caused significant upheaval and change at a time when computing and software programming were redefining manufacturing and operations. This led to the unusual step of FDA clarifying within their Scope and Applications guidance document a much narrower interpretation of the ruling,² together with a statement of intention to use enforcement discretion with respect to certain Part 11 requirements. Additional guidance was drafted by FDA regarding this area, but much of it has been subsequently withdrawn as it was too restrictive for evolving technologies.

On the go...

Regulatory changes provide a foundation for the pharmaceutical industry to keep pace with progress by facilitating and clarifying acceptable processes within the industry. Standardization is also improved as the minimum requirements are set by the regulatory agency rather than being at the discretion of each individual regulatory inspector. However, in some cases numerous legislative alterations can lead to a greater focus on ensuring compliance rather than achieving quality. It is, therefore, possible that regulatory agencies enforcing legislation through frequent inspections cause quality assurance resources to be diverted to activities such as audit preparation, inspection hosting, responding to audit observations and implementing multiple corrective action and preventative actions in response to observations. Regulators' activities could risk being seen as obstacles to, rather than guardians of, quality.

The reach of regulations is moving further up the drug development chain, affecting many more areas than the traditional manufacturing process. The medical devices industry has, in recent years, adopted and validated product life cycle management applications to electronically manage the device master record and the device history record, including the handling and storage of early stage design data and drawings. The adoption of similar applications across the biotechnology and pharmaceutical industries is only a matter of time, particularly in view of FDA's 21st Century Risk-Based Approach goal to harmonize quality systems across all its activities.³

The regulatory and validation service and support market has grown significantly during the past 20 years, reflecting the high activity of regulatory compliance and quality assurance within the industry. The trend looks set to continue, but in a much more technologically focussed way because the regulatory authorities are demanding electronic means of submission, further communications and additions, and integrity of data storage.