Old news I know, and you probably always have done it this way, but did you know with the January 2018 adoption of PIC/S PE009-13 by the TGA, a User Requirement Specification (URS) is now mandatory?
Annex 15, §3.1 and 3.2 state that a User Requirement Specification should be a point of reference in the validation life cycle of equipment, facilities, utilities or systems and be available through the system lifecycle. While new regulations do not usually trigger re-execution of legacy work, the suitability and availability of existing work to integrate into the validation lifecycle should be considered
This new approach signals a need to have an ongoing, live document from initial scoping of a GMP system or equipment through to decommissioning. Companies should be aware that they need to maintain these documents for a minimum of 5 years, §4.11.
Clause 3.2 in Annex 15 also includes an option for a functional specification to compliment or even replace URS. There is no guidance on what constitutes functional specification, and this could be one, two or more documents and the approach explained by the regulated company. For simple systems or equipment, it is reasonable to assume that a single URS is sufficient to contain the required information. More complex computerised or compartmentalised systems may need multiple functional specifications to supplement the main URS for the system. The level of documentation required should not be presumed, and each situation needs to be considered individually as suggested by PIC/S 13 paragraph 3.1.
Clause 3.2 also indicates the expectation for formal quality risk assessment at this stage (specification). By now, formal risk assessment should be ingrained in our processes as we move toward a consistent QbD approach in all aspects of product and process lifecycle. Annex 15 now makes such thinking mandatory for our validation effort too.
Quality Risk Management
At the specification stage, the assessment should be focused on GMP risks specific to the equipment or system undergoing specification. The level of residual risk identified after assessment and mitigation should inform the decisions around the scope of qualification and validation work required. Logically, the higher the residual risk, the more effort is required to demonstrate process control and product quality.
The list of risks due to the system or equipment is drawn up and assessed to the level of risk to the safety, quality and efficacy firstly to the consumer and then to any commercial and EHS considerations. Assessment teams should be broad-based and include system owner(s) and/or user(s), quality, engineering and validation representatives.
During such an assessment, it is important to consider as many simple and complex scenarios as can be identified (which is why the team approach is critical). Examples of the sort of questions that may be asked include:
- What can go wrong (what happens if something fails, or does not perform as expected)
- Compatibility questions (e.g. does the system/equipment have product contact lubricants or materials of construction and are they compatible with the product/process)
- Criticality questions (which functions and components are critical to product quality or GMP regulations)
- Functionality questions (does the system have the range or capability extents or limitations which may impact product quality)
As written and presented by Ashley Isbel, Australia’s leading validation expert in many PharmOut GMP training events and Forums since 2011, and more recently since the update to PIC/S Annex 15 in 2015, a User Requirement Specification (URS) can be designed in a traditional V Model format or can incorporate other elements such as traceability matrix. See figure 1 below.
Figure 1: Slide extract from “Writing an effective URS for Facilities, Services & Equipment”
The User Requirement Specification (URS) is a document that can be and should be used to its’ full potential by procurement, engineering, quality, operations (i.e. lean improvements) and validation departments instead of “just another document to complete and file away”.
Figure 2: Where URS can be used.
Of course, in line with the Stage 1, 2 and 3 thinking embedded in the US FDA Process Validation Lifecycle; process and product knowledge learnt at this early stage of Product Development should be captured in quality/technical assessments and formally transferred to the process design teams.
PharmOut engineers often struggle with this aspect when designing manufacturing plants. In our experience, the Critical Quality Attributes (CQA) and more importantly the Critical Process Parameters (CCP) are rarely pre-defined and available when commencing design. The URS is an essential document to capture this information.
It is worthwhile noting, however, that most legacy processes follow the lifecycle on a 3-1-2 basis. Let me explain; often we don’t have the full QbD information or a documented Control Strategy for legacy products. Instead, we need to use the output from our continued/ongoing verification (Stage 3) to assess process capability. if the verification activity suggests that our process is demonstrating reduced capability, it may be a trigger to move from Stage 3 back to stage 1 or 2. We do this to close gaps in our understanding of the product or process and may even revert to product development to perform Design of Experiments (DoE). This is why we say legacy products tend to adopt a 3-1-2 stage approach.
Why is this important to note when discussing URS documentation? Obviously, any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, should be formally documented, in a change control and new or revised User Requirements Specification (URS), and the impact on the validated status or control strategy must be assessed.
5.24 The method by which the process will be verified should be defined. There should be a science based control strategy for the required attributes for incoming materials, critical quality attributes and critical process parameters to confirm product realisation. This should also include regular evaluation of the control strategy. Process Analytical Technology and multivariate statistical process control may be used as tools. Each manufacturer must determine and justify the number of batches necessary to demonstrate a high level of assurance that the process is capable of consistently delivering quality product.
Want to learn more?
Why not attend one on the many training sessions offered by PharmOut on PIC/S version 13 and Annex 11 and Annex 15, the last led by Australia’s validation expert Ashley Isbel on say Process Validation.
Our full GMP training calendar.
Presentation on 10 things every (CSV) URS should consider
Read about the PIC/S GMP version 14 major changes here.