Q. What specific systems are considered critical utilities in the pharma environment?
A. The answer to this question will vary somewhat from one organization to the next. However, most will agree that critical utilities minimally include direct impact systems used for product formulation and compounding or for cleaning and sanitizing product contact surfaces. Examples include compendial water (WFI, PW & HPW), Pure Steam, Clean-in-Place (CIP) systems and systems used for the generation and distribution of Process Gasses.

Q. What are the various elements that need to be addressed when designing critical utilities in pharma?
A. Unlike most plant utilities, these systems need to meet the same rigorous criteria as the process systems they support. Those criteria extend directly from 21CFR Part 211 Subpart D, which states “Equipment used in the manufacture, processing, packing, or holding of a drug product shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance”. While ambiguous, this statement casts a wide net and outlines the fundamental requirements for all of the equipment used in the facility. As direct impact systems, they are validated in the same manner as any product contact system. 

Q. Do you examine and validate each part of the critical utility systems separately along the way, handle that as part of the integrated project, or both?
A. Traditionally every part of a critical system is “Validated.” Precisely what “validation” means can vary somewhat for different organizations and different market segments. Many will argue that beginning in the 1980’s and moving into the new century, the Validation pendulum swung pretty far to the conservative side of the spectrum, often adding costs that were not offset by corresponding improvements to the integrity of the products being produced. For the last decade, the zeitgeist has been more centrist with the pharmaceutical industry leaning toward a risk-based approach to validation. That said, it is important to ensure that every critical quality attribute (CQA) is identified, quantified and verified in the context of the intended use. CQA’s associated with the manufacture of injectable solutions may not be the same as those associated with the production of small molecule API’s (active pharmaceutical ingredients). 

Q. What steps are taken to monitor the environment to be certain that product quality is not adversely affected by a malfunction, even a minor one? 
A. For some critical utilities, the CQA’s are defined by the underlying regulatory basis. For example, the requirements associated with Purified Water are partly defined by the compendial monograph (i.e. USP, EP, JP, etc.), which outline Conductivity Limits, TOC Limits and so forth. Other CQA’s associated with that type of system will be specific to the intended use and could include attributes like Pressure, Temperature or Microbial limits. So measures such the steps taken to monitor the environment will be specific to the intended use.

Q. Once critical utilities are properly functioning and validated, how closely must they be monitored during actual product production?
A. As with all other aspects of an owner’s validation program, the intensity of the Monitoring program should correspond to the anticipated level of risk. Many critical attributes, like conductivity and total organic carbon (TOC), will be continuously monitored online. Other attributes, like microbial or non-viable particulates, may be sampled periodically based upon the practical limits of the corresponding test methods, risks associated with the intended use and an assessment of the impact of non-compliance.

Q. Can legacy systems be successfully incorporated into an overall critical utilitydesign?
A. Absolutely! Legacy systems are a fact of life throughout the industry. The tried and true systems of yesteryear often have the advantage of a demonstrated history of compliance. As long as those systems remain reliable and the associated equipment remains serviceable and supportable, there is no overarching reason to invest in replacements. However, when valves, instruments or other critical parts are no longer supported by the original equipment manufacturers, they can represent a meaningful threat to business continuity and should be considered for retirement.

Q. Once critical utilities are properly functioning and validated, how closely must they be monitored during actual product production?
A – As with all other aspects of an owner’s validation program, the intensity of the Monitoring program should correspond to the anticipated level of risk. Many critical attributes, like conductivity and total organic carbon (TOC), will be continuously monitored online. Other attributes, like microbial or non-viable particulates, may be sampled periodically based upon the practical limits of the corresponding test methods, risks associated with the intended use and an assessment of the impact of non-compliance.

Q. Can legacy systems be successfully incorporated into an overall critical utility design?
A – Absolutely! Legacy systems are a fact of life throughout the industry. The tried and true systems of yesteryear often have the advantage of a demonstrated history of compliance. As long as those systems remain reliable and the associated equipment remains serviceable and supportable, there is no overarching reason to invest in replacements. However, when valves, instruments or other critical parts are no longer supported by the original equipment manufacturers, they can represent a meaningful threat to business continuity and should be considered for retirement.