Monitoring and Trending Data for Controlled Environments is Assisted by a Managing Microbes System - Part 1

A “cleanroom” by any other name…
Some medical manufacturers have taken a unique posture toward voluntary standards by describing certain manufacturing spaces as “controlled environments,” “whiterooms,” or “specified manufacturing areas” instead of “cleanrooms.” Perhaps this is done with the understanding that doing so relieves the potential requirementto comply with ISO 14644. [1, 2] The new versions of the standards and otherguidelines [3-5] list “controlled environments” as requiring certification,so the use of some other name for a cleanroom is not an escape. It is the intendedor required use of the environment that will be scrutinized by auditors, andnot the descriptive name.

More importantly however, monitoring and control of environments for manufacturing medical devices or other medical products is not necessarily a requirement. That is, it is not a requirement unless such controls are necessary to assure the “quality, dependability, reliability, safety, efficacy, performance, strength, purity or specificity” of the product. [6] There are many products that are not impacted by environmental par-ticulates or microbes. However, if a manufacturer cannot logically assert and support the contention that the environment could not have an impact on product quality attributes, then process specific, objective evidence would have to be generated to support such a contention. In this article, we will discuss the role of voluntary consensus standards in meeting non-voluntary regulatory requirements.

Regulations
FDA and ISO regulations [6, 7] cite the need for monitoring and control of the manufacturing environment. The FDA Quality System regulation addresses issues related to manufacturing environmental controls in sections 21 CFR 820.3, 820.70 and 820.75 discussing processes, process controls and validations. Sections 820.181 and 820.184 cover documentation requirements for processand device records.

Section 820.3 defines lots as components or finished devices that are manufactured under essentially the same conditions and quality. It further defines quality as the totality of the characteristics that bear on the devices fitness-for-use, including safety and performance. In addition, process validation requires objective evidence that a process consistently produces a product meeting its predetermined specifications.

820.70 states that each manufacturer “shall develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications… Where environmental conditions could reasonably be expected to have an adverse effect on product quality, the manufacturer shall establish and maintain procedures to adequately control these environmental conditions.” It also states that periodic inspections verifying the systems are functioning must be established, documented, and reviewed.

820.75 goes into further detail with the requirement that the processes discussed above must be validated when they cannot be fully verified, and that the processes be monitored so as to assure specified requirements continue to be met.

Rationale for Decisions
If a company chooses not to follow guidelines, then the supporting rationale for the decision should be documented and re-evaluated if product risk is altered. After all, one does not have to comply with any of these consensus standards, since they are all voluntary. A manufacturer can choose to comply with the standard or not, regardless of what terminology they use to define the manufacturing space. However, the non-voluntary FDA Quality System regulations dictate that if the environment could affect the product quality attributes then one must be able to justify the choice of the selected testing program and how one isassuring conformance to it.

Regulatory auditors have been delegated significant responsibility to assure safety of medical products, and directly or indirectly, the safety of the users. However, many such auditors cover a broad scope of technologies and may have limited education, experience, and understanding of particular topic like the rest of us. Therefore, these auditors will often rely on voluntary standards prepared by a consensus of knowledgeable professionals for guidance as to what factors may be important for controlling manufacturing environments. Auditors rely on voluntary standards for guidance on “good practice” in their efforts to make sound judgments regarding regulatory requirements. For manufacturers to fail to be knowledgeable about such voluntary standards would appear naïve, even if they choose not to comply.