In the practice of computerized system validation (CSV), a basic but crucial question often arises: Is the first step in the whole validation life cycle to write a detailed user requirements statement (URS) or to conduct an initial risk analysis?

For organizations pursuing compliance and efficiency, this sequence is not an optional process dispute, but a cornerstone of whether the whole verification work has the rationality of regulations. Starting from international drug regulatory regulations (e.g. FDA 21 CFR Part 211, Part 11, EU GMP Annex 11) and industry standards (e.g. ICH Q9), the answer is very clear: the first step must be an initial risk analysis.

一、Mandatory Requirements of Regulations: Risk-driven Approach

The core requirement of the world's major drug regulators is that all validation activities must be based on quality risk management principles.

· EU GMP Annex 11, Computerized Systems, States at the outset: "Risk management should be applied throughout the life cycle of a computerized system …"

· As the cornerstone of the industry, ICH Q9 Quality Risk Management establishes that the risk management process begins with "risk identification" and then "risk analysis and evaluation".

The initial risk analysis is the specific implementation of ICH Q9 principles in the project initiation phase. Its core purpose is to answer a fundamental regulatory question before committing any substantial validation resources: "Why are we validating this system?"

Specifically, the initial risk analysis sets the tone for all subsequent activities by assessing the GxP criticality of the system (i.e., whether it impacts patient safety, product quality, or data integrity) and the software category:

· If not GxP critical: the system may not need to be formally validated, saving significant resources.

· If GxP is critical, the scope and extent of its validation (i.e., how broad and deep the validation effort is) will be directly determined by the level of risk identified in this analysis.

URS is a document that defines what the system "must do" on this basis. It is the legal basis for subsequent design, test and acceptance.

二、Logical discrimination: Why can't URS be the first step?

A common misconception is that "we should first know what we want (URS) and then analyze the risks". This line of thinking puts the cart before the horse in CSV.

Placing URS before the initial risk analysis results in:

1. URS lacks regulatory focus: a URS written without risk analysis guidance can easily become a "big and comprehensive" list of features that may contain a large number of non-critical requirements, but weaken or omit core requirements that are critical to regulatory compliance. For example, the user interface may be described in detail without sufficient emphasis on the mandatory requirements for data integrity (e.g., audit trails, access controls).

2. The verification strategy loses its basis: the essence of verification is to "provide a high degree of assurance" that the system can continue to meet its intended use and control risks. If the first step is URS, then "why should a requirement be validated" and "how rigorously should it be validated" will lose the basis for the decision. The whole verification strategy has become a passive water.

On the contrary, the correct sequence of "risk analysis → URS" constructs a rigorous legal logic chain:

· Step 1: Initial Risk Analysis

"Lack of controlled electronic signature capability" was identified as a high data integrity risk.

· Step 2: Write URS

Accordingly, it is proposed that "the system must meet the requirements of 21 CFR Part 11 and realize the electronic signature function with audit trail correlation and security."

· Step 3: Develop a validation strategy

Rigorous and sufficient test cases are designed for this requirement to demonstrate that they effectively mitigate the identified risks.

三、Conclusion: Construction of traceable compliance evidence chain

To sum up, the initial risk analysis is undoubtedly the first step in the GAMP5 framework and modern CSV practices. This sequence is not only a best practice in the process, but also a necessary requirement for building a strong chain of evidence for compliance.

It ensures that:

· Each critical requirement in the URS is directly derived from the identification and mitigation intent of a specific quality risk.

· Each of the key tests in the validation plan can be traced back to the specific requirements in the URS and ultimately to the risks assessed in the initial risk analysis.

Therefore, putting the initial risk analysis first means that the entire CSV lifecycle is built from the ground up on a solid, defensible regulatory foundation. It makes it clear to regulators that our validation work is risk-driven, critical-focused, and fully compliant with ICH Q9 and GMP core principles from start to finish. For any organization that pursues excellence and compliance, this first step is the right direction to take.