Manufacturing Facility Validation Services
Validation for FDA-Regulated Manufacturing Facilities—An Overview
Clients who initiate a construction project want to be confident that the designs will meet their requirements. Unfortunately, many design requirements may be implied in a simple statement of FDA compliance, or meeting validation criteria. As design and construction is creative, sufficient latitude is given to the firm to propose a design that promotes good morale in a positive workplace, but often, the designers may not understand all the constraints, leading to lost contracts, unnecessary rework, and a frustrating relationship with the client.
A basic understanding of Validation, and the corresponding requirements should help circumvent such regrettable situations. The understanding of validation is also helpful to construction firms embarking on building their first FDA-regulated manufacturing facility, which is sure to result in higher-margin, more-profitable business, since such work entails a specialization unfamiliar to other construction firms.
Validation is different from commissioning in that it dives into the details of how exactly the facility is to be used, called “intended use.” For example, a cleanroom used for semiconductor manufacturing may differ significantly from a cleanroom for aseptically filling syringes of antibiotics, even though both rooms meet the definition of “cleanroom.” To build a facility that meets customer requirements therefore requires an understanding of the activities taking place within.
Because such an understanding is needed, it may be important to partner with another firm who understands the specific technical requirements so the validations of the space will pass on the first attempt, with little, if any need for rework. In fact, employing such an expert on the design team may avert considerable costs, especially for larger-scale plant expansions. To gain an understanding of what such a consultant would do, it helps to understand what validation is, so construction firms can see how this person’s focus can aid the design and construction project.
Validation can only be understood by breaking down its definition to carefully examine all the constituent components:
Validation: Confirmation, by examination and provision of objective evidence that the specified requirements have been fulfilled.
The first word of the definition is “confirmation.” The implication of this word is that the requirements are known to have already been fulfilled, only that proof of such fulfillment needs to be documented. In other words, validation is not exploratory. It is confirmation of previously established fact.
“Examination” implies that a skilled inspection needs to take place. A review of moisture-resistant finishes in a wet room, for example, may entail more detailed examination, such as the composition of the materials, and ratings of those materials regarding moisture resistance.
“Provision of objective evidence” is the most difficult to establish but can be done. Evidence can be established through spec sheets from the material manufacturers, but also measurements, using NIST-traceable calibrated equipment. In many instances, for instance in cleanrooms, measurements will include airflow testing, and leak testing of HEPA filters, but will also measure performance, such as viable and non-viable particulate counts for the air, surface microbial counts, employing a statistical sampling plan, and measurements of differential pressures between rooms, temperature mappings in summer and winter, under both static (unoccupied) and dynamic (occupied and in use at full capacity) conditions across multiple shifts. Any design that fails to support these implied needs of a cleanroom will entail considerable design rework. Harmonized standard documents should be consulted whenever possible, such as ISO 14644.
“Specified Requirements” can only be specified if the customer states what they are, but experienced construction firms understand that clients imply a great deal when they reference harmonized standards in their design requirements. In the same way that the definition of Validation needs close evaluation to understand its meaning, each of the harmonized standards have their own jargon and meanings that must be interpreted to determine the best design solution to meet client requirements.
Validation to specified requirements requires that the test plans and the criteria for meeting the requirements are written and approved before any testing commences. If testing fails, because the test was intended only to be a “confirmation,” an investigation into why the failure occurred, documented corrective actions, and repeat of the test or affected tests, must take place before a final test report is issued, and approved along with evidence of all the originally-completed test results (including failed testing.) Such stringent documentation requirements require someone with experience to document the information correctly the first time. If not documented correctly the first time, the entire process may need to be repeated, resulting in additional cost overruns.
Such level of detail, on its face, appears wasteful and disproportionate, but not only is this level of detail required by regulation, but is necessary, based on historical context of patient deaths resulting from flaws in facility or utility design. Before validation was mandated in the 1970’s, drug products purporting to be sterile were found to have microbial contamination, resulting in sepsis, and sometimes death of the end patients. Similarly, other end-use requirements could pose a public health threat if they are not carefully considered in the design and construction process.
This is not to say that all requirements need to be evaluated in close detail. An FDA compliance professional will understand how to appropriately assess risk, so the required validation elements are evaluated and inconsequential factors, are considered, but evaluated at a level proportionate to patient safety impacts.
A partner on your team during the bidding process will ensure that the solution is tailored to client needs, helping you to win the project, and complete it with an optimized cost profile, while minimizing the risk of unforeseen requirements and costs.
If a construction firm lacks expertise in these areas, it is a sound investment to partner with a firm experience in FDA-regulated facilities and utilities, as an insurance policy against unnecessary rework as well as an insurance policy against overengineered solutions, so that the cost of the project is a perfect fit for client needs.