Commissioning Verification and Validation
Its value in the pursuit of regulatory compliance
One of the most critical challenges facing today’s research facilities is the acquisition of regulatory compliance—that stamp of approval that defines an institution as highly qualified, safe and desirable for the demands and challenges of complex and highly technical research. The inability to acquire regulatory compliance can affect a lab’s capacity to procure needed funding, conduct regulated work and attract top tier researchers. Lack of licensure can also push a research lab to the back burner of the industry, thus impacting its future viability as a recognised scientific research entity.
It’s anticipated the licensure process will become more complex as well. Demand for qualified, high containment research facilities is increasing as human, plant and animal populations are impacted with expanding and changing disease forms. It’s one of the many challenges being faced in the industry today.
To acquire licensure in this ever-changing environment, institutions are devoting valuable time and resources to the regulatory process with solutions to improve that process being sought from many directions and sources. One approach quickly gaining acceptance is the use of a highly purposeful and rigorous, two-tiered commissioning (Cx) verification and validation (CVV) program. This process (CVV) provides a second tier of monitoring, assessment, evaluation and recommendations above and beyond the traditional Cx process.
WHAT IS CVV?
CVV is the combined activities of two independent steps.
- Verifying that the Cx process has been completed to the best practice performance standards in the industry, and
- Validating the planning, design and operations of the facility to ensure it was designed and built as planned and is fit for intended use.
The activities of the traditional Cx process have been in use for a considerable time and in some instances is delivered by the contractor. However, CVV is bringing a new paradigm to the industry. CVV combines the protocol of verifying the Cx of a qualified system with the more robust approach of validation (qualification). It provides a second set of eyes on the project and a viewpoint independent of the Cx/contractor role; a viewpoint that is committed to and usually contracted directly by the client.
In addition, CVV can go well beyond the Cx model traditionally used in Food and Drug Administration-approved facilities and the pharma industries. The CVV approach is moving the needle in the direction of ASTM E2500, which relies more on subject matter expertise in commissioning laboratory settings and focuses on product (laboratory output) quality and user/environmental safety.
WHAT ROLE CAN ASTM E2500 PLAY IN CVV?
ASTM E2500 can play a major role in CVV. Per Pharmaceutical Engineering Magazine, for many years, a Qualified system meant that there existed a QA pre-approved, executed and QA post-approved set of documents consisting of an IQ and OQ (and in many cases a PQ) protocol. What mattered was whether the local procedure was followed to develop, execute and approve each protocol.
ASTM E2500 goes beyond that by stating that verification is “a systematic approach to prove that Critical Elements, acting singly or in combination, are fit for intended use, have been properly installed, and operating correctly”. It extends beyond traditional Cx and the V model by stating that “the extent of verification and the level of detail of documentation should be based on risk to product quality and user/environmental safety”.
Thus, CVV and ASTM E2500 require the higher levels of expertise found with Subject Matter Experts (SMEs) as well as the professional and technical background of engineers who are well-versed in the type of facility and systems being designed, verified and validated. In reality, it moves the process from checking boxes on a pre-established list of review items to a more dynamic environment where adjustments can be made and experts can view the entire project from risk management, functionality, operability, safety and efficiency in the facility’s ability to achieve its mission.
The ISPE new Baseline® Guide 12: Science and Risk Based Approach for the Delivery of Facilities, Systems, and Equipment provides the “how to” for implementation of the verification approach described in the ASTM E2500-07 Standard.
HOW CAN CVV ASSIST IN THE LICENSURE PROCESS?
One of the key values of CVV is the support it provides to an organisation in advancing the pursuit of licensure. With the expert oversight of SMEs, the involvement of qualified engineers, and the independent viewpoints of the CVV consultant, it can shorten the timeframe to and increase the probability of achieving licensure. This is accomplished with:
- involving SMEs who are vigilant in observing potential failure points and other areas of concern. These professionals are typically expert in programming, planning, designing, commissioning, Standard Operating Procedures, certification and other aspects of biocontainment labs.
- integrating Cx and CVV from the project’s beginning thus ensuring the added value of multiple sets of eyes during planning and design to monitor and flag crucial issues throughout the entire process.
KEYS TO SUCCESS IN CVV
A prime key to success in CVV is the involvement of the Cx agent and the CVV consultant early in the planning and design process, preferably prior to the start of programming and design. With CVV consultants as experts in the type of facility being designed, their insights can assist clients and the design team in avoiding pitfalls that may not typically show up until construction is underway. Adjustments can be made in the design program thus circumventing additional costs and extended construction times.
Other keys to success in CVV include:
Develop a Verification/Validation Strategy
CVV is more successful with a Verification and Validation strategy. This strategy provides the guidelines for the entire team to adhere to and milestone checkpoints to ensure the team is on track with specific tasks. The Verification and Validation strategy should include, in general:
- Employer Requirements: Contractually supported Employer Requirements (ERs) to define what specific tasks need to be completed that are not already included in the general contractor’s or engineer/architect’s scope of work.
- Validation Master Plan: The framework within which the validation of the facility, environment, services, equipment, systems and processes will be organised, completed and documented in accordance with the requirements of the licensing organisation’s regulations and guidelines.
- Risk Assessments (Biosecurity, HAZOPS, SWIFTS): Identification of systems critical to bio-containment and ensuring appropriate risk assessment techniques are employed, e.g. Hazard and Operability studies (HAZOP), Structured What-if Technique (SWIFT) sessions to ensure compliance with the bio-containment design philosophy.
- Design Review, Design Qualification: Design review by SMEs to ensure the design complies with both ERs and regulatory requirements.
- Factory Acceptance Tests (FAT): FAT testing, with witnessing by CVV consultant, to ensure systems have been tested and documentation provided (at the manufacturer’s location) to verify the supplier has fulfilled contractual responsibilities related to the engineering design prior to delivery and installation of systems.
- Site Acceptance Tests (SAT): SAT testing, with witnessing by CVV consultant, to ensure systems have been tested and documentation provided (at the client’s location) to verify the supplier has fulfilled contractual responsibilities with regard to the delivery and installation.
- Commissioning Calibration: Calibration to ensure all bench calibrations and device operational checks are performed in accordance with any contractual agreements, design documents and project requirements.
- Handover Package (HOP) Verification: HOP information and data to be provided by the Cx contractor to the CVV consultant prior to verification and validation activities. This package would include such items as FAT and SAT results; equipment schedules; room data sheets and floor plans (showing containment zones); design substantiation reports for validation of critical systems; instrument data sheets; control panel drawings; instrument installation details; alarm set point and interlock schedules; valve list; manuals (installation, operation, maintenance, lubrication, operator interface, operator/user); instrument calibration sheets; calibration procedures; warranty information.
- Verification/Validation; Standard Operating Procedures (SOP): SOP drafts provided prior to commencement of verification and validation activities.
- Re-Verification (Sustainability): Cyclical testing to be determined by the client in conjunction with the SMEs and compliance with regulatory requirements.
Validation Master Plan
Develop a Validation Master Plan (VMP) that clearly defines all CVV activities to take place during planning, design, construction and facility turnover. The VMP should be developed, reviewed and finalised prior to the design being finalised and definitely before construction begins. Sample contents would include:
- Objectives and Regulatory Requirements Overview
- Facility Description
- Scope of Validation
- Verification and Validation Strategy
- Key Validation Activities
- Licensing Acceptance Criteria
- Validation Team
- CVV Program
- Document Format and Control
- References and Associated Documents
Guidelines and Regulations
Understand the guidelines and regulations, completely, of the regulating agencies who will be reviewing and approving your facility’s licensure. This is where the value of a CVV consultant can come into play. As SMEs in the industry, CVV professionals can review the guidelines and regulations from a more experienced viewpoint and identify any crucial points of concern.
Engage with the Regulator early in the process. This engagement allows your team to share all aspects of the process and facility as well as pointing out the challenges to the project and how the team is resolving those. When the facility is under review for licensure, the Regulator will have a better understanding of the process and end result.
Think of the Future
Understand the programs that will potentially be conducted in the facility. SOPs and codes of practice are especially valuable as the design team and SMEs consider what types of activities will or may be conducted in the facility. Also, understand transitions that may occur, i.e. moving current programs into a new facility or re-directing research focus in a facility. This understanding allows the team to “design-in” flexibility for future uses.
Consider the long-term operational aspects of the facility and the continuing pursuit of license compliance. Regulations are changing and are, typically, becoming more stringent. The design team, the CxA and the CVV consultant should design toward creating a baseline operational footing that will ensure the facility’s continuing operations and ability to acquire licensure.
Engage in a collaborative team approach during planning and design with the Cx agent and the CVV consultant already in place and participating throughout the planning and design phases. This allows the CVV SMEs to identify areas of potential failure early in the process and make changes in the plans at a time when the changes are less costly and less time-consuming to make. In addition, the collaborative team approach is valuable to all team members. The designbuild team is taking on the risk of the project and they benefit from having the CVV consultant advising, early in the process, to de-risk some elements. The CVV consultant is in an especially valuable position due to their independence from the design and construction team.
The results of not acquiring regulatory compliance run deep and last long. In keeping with the adage, “begin with the end in mind,” the acquisition of regulatory compliance should be a common and highlighted theme throughout planning and design. With a collaborative team in place from project start, SMEs providing facility-specific expertise, objective oversight of the Cx process and facility validation by the CVV consultant, and the engagement of the regulating agency in the process, regulatory compliance should be within easier reach and within a shorter timeframe for those pursuing licensure effectively.
Gilles Tremblay, CET, is Director of Commissioning Services for Merrick & Company where he focuses on commissioning, verification, and validation of laboratories and high containment facilities. His background includes work for the US Centers for Disease Control, the US National Institutes of Health, the US Department of Agriculture, the Canadian Science Center for Human and Animal Health, the US Defense Threat Reduction Agency, the US Department of Homeland Security, The Pirbright Institute (UK) and other international clients/agencies.
Spencer Andrews, BEng, CEng, of Merrick, serves as the firm’s Design and Safety Case Project Manager in Europe. He specialises in the defence and nuclear sectors with expertise in design development, optioneering, commissioning, construction, safety case development, and independent safety advice/peer review support.