Controlling the fabrication environment is not an end in itself. Manufacturers who process and assemble their product in controlled environments know that the clean-room or mini-environment must be appropriately designed and must also be maintained clean and contamination free. However, cleanliness of the product itself is the ultimate goal. This goal applies whether the application is from aerospace, military, medical device, pharmaceutical, or other disciplines.

Much can be modeled from those who process pharmaceuticals. High standards, many with the force of law, govern pharmaceutical and medical device production. The U.S. Food and Drug Administration (FDA) issues ever-increasing regulations to control the processes by which pharmaceuticals are manufactured and packaged. The regulations that appear in Title 21 of the Code of Federal Regulations, Section 210 (21CFR210) and in subsequent sections are referred to as Current Good Manufacturing Processes (cGMP). The word “current” emphasizes that knowledge of processes evolves and that a process that was “golden” 20 years ago may not be acceptable today. Similar medical device regulations are defined in other sections of 21CFR. Even those not governed by pharmaceutical or medical device requirements would profit by becoming familiar with the principles of cGMP practices.

CGMP HISTORY
The first GMP regulations from the FDA appeared back in 1963. A major revision in 1978 produced most of the regulatory language in use today. An axiom is that good manufacturing processes be documented and validated. Validationis defined as:

“Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.” ¹

In 2002, the FDA announced an initiative, Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century, to enhance and modernize the regulations. A key aspect of this initiative is to adopt risk management approaches in quality management systems. We have previously discussed the risk management approach for validating cleanliness of medical devices.²

Risk management inherently involves process understanding; so rather than being an expense, risk management can enhance productivity and profitability. In a report generated as a result of the initiative, the FDA states:

“Quality and productivity improvement share a common element — reduction in variability through process understanding (e.g., application of knowledge throughout the product lifecycle). Reducing variability provides a win-win opportunity from both public health and industry perspectives.” ³

CROSS CONTAMINATION
The recall of a pharmaceutical product due to cross-contamination led to increased FDA awareness of the importance of validation and control of cleaning procedures.⁴ Drums containing recycled solvent used for pharmaceutical production had previously been used for solvent recycled from pesticide manufacturing. As a result of inadequate cleaning procedures for the drums, pesticide residues were inadvertently transferred to the pharmaceutical product. The example also illustrates the need for well-documented acceptance and monitoring programsfor process chemicals and storage containers.