The ISPE Baseline Guide Volume 5: Commissioning and Qualification is now in its second edition providing guidance on the Commissioning and Qualification (C&Q) of Pharma / Biotech / CTG manufacturing facilities.
The first edition of the Baseline guide was a good start to help the industry standardize an approach to Commissioning and Qualification projects. Nothing like it had ever existed before and was fully endorsed by the FDA. The guide was fairly well written but was also confusing to many.
Besides a few topics such as the System Impact Assessment and Critical Component Assessment, there were few other examples of how to handle C&Q projects.
Another concern was the title. The title, “Commissioning AND Qualification,” implied that both phases were required. This was not the case or the intent. It was up to companies to interpret the intent. If work was done in the commissioning phase and met the acceptance criteria, then how was qualification to be handled? The Quality Unit (QU) struggled with the concept as well.
The second edition of the ISPE Baseline Guide is an improvement, as it combines three separate guides into one. The guide also incorporates ASTM E2500, the Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment.
Why was this important? ASTM covers risk to the patient and ISPE previously did not. Now they both discuss “risk to the patient” when making decisions.
Full List of Major Changes to ISPE Baseline Guide
We compiled a comprehensive list of the changes that were incorporated in the second edition of the ISPE Baseline Guide for C&Q.
1. The guide introduces new definitions, Critical Aspects, and Critical Design Elements.
2. The URS (User Requirement Specification) has been clarified as to its importance, but the examples given in the new guide could use further clarification.
One example is that clean gasses used in production (that come in contact with the “product to be”) can now be considered Direct, but only AFTER the final filter that is typically inside the cleanroom, production area, or part of the boundary of the tank used to manufacture the product. This may lead to variable interpretation since the production and distribution of the clean gas only requires commissioning, but sampling is required after the final filter (part of the boundary of the “user”), so, therefore, it is “Direct.”
The only requirement for testing past commissioning is sampling after the final filter. This is normally done by the company’s internal resources. To develop the URS according to the new guide, the CQAs and CPPs must be well understood.
For most companies today, URSs are poorly understood, developed, and executed. “URSs” are mostly a combination of design wishes and do not address the Users’ needs. Quite often, there is no User identified or “consulted,” and the URSs are developed by a separate engineering group.
3. The System Impact Assessment has been changed to System Classification. Why? The System Impact Assessment was not written clearly enough and created confusion.
As an early reviewer of this document, we understood the actual intent that did not come through into the final document. The questions were to be answered in the order written, and once you answered “yes” to any of the questions, you could stop.
Question 1 was confusing enough, as the meaning was for the equipment/system to actually “touch” by coming in contact with the “product.” The “product” was not defined well, as some interpreted that to mean raw material, ingredients, or incipient. They are very different.
Indirect impact systems were not understood well by the industry and no formal training was provided. There were no good examples provided to give guidance. Companies just defaulted on an answer and decided to qualify them “just in case,” which was not the intent.
4. ISPE added System Risk Assessment and recommends that it be done on Direct Impact Systems only. The guide discusses the critical design controls (CAs/CDEs) required to mitigate system risks.
5. The guide clarifies Design review and Design qualification. We don’t think it’s a good idea to differentiate the reviews, as a review should be done for all utilities and production equipment/systems. Lab equipment is typically ordered from a Catalog and does not usually need a “design review.” The “design” can be verified by reviewing the specifications or data sheets.
6. The guide attempts to clarify the role of QAs in the C&Q program that has been misunderstood for a long time. QA was not supposed to approve every qualification document but have oversight over the validation life cycle (PQ and onwards), including qualification for Direct Impact systems.
It is very clear that commissioning thru OQ is an engineering exercise, while QA was to consult and help ensure the equipment is “fit for its intended use.” QA is not expected to have the expertise in engineering, for instance, but should rely on SMEs (engineering, C&Q, etc.) to perform the work and QA “review.”
If the URSs are written well, then a clear path can be taken to the final handover of any system, with minimal oversight and traceability to clear acceptance criteria.
What’s Next for Pharma/Biotech/CGT Commissioning and Qualification
AM Technical Solutions (AMTS) has been on top of the changes to the ISPE Baseline Guide Volume 5 for Commissioning and Qualification. We work directly with clients to capture exactly what is needed to make the right decisions and change. By focusing on the critical requirements for pharma facility C&Q, we can make your project easier to plan and execute.
“We have the personnel and templates to execute commissioning and qualification adaptations for pharmaceutical facilities without needing to invest in expensive software solutions,” says Stig Bockman-Pedersen, AMTS Sr. Manager CQ. “We can also work with current programs to simplify templates that are easy to develop and work with.”
- We invite you to contact us for more information on utilizing our cleanroom commissioning and qualification capabilities for pharmaceutical, as well as other critical industries.