In the pharmaceutical industry, automated control systems They constitute the basis for the safe, efficient and reproducible operation of production processes. From a SCADA system to a PLC or DCS, these equipment manage critical parameters that directly affect the product quality, patient safety and regulatory compliance.

Therefore, the Quality Risk Management (QRM) It is not just a regulatory requirement, but a strategic approach that guides the validation of these systems throughout their life cycle.

1. Efficient validation starts with understanding risk

The application of QRM principles (defined in the ICH Q9 guideline and reinforced in European GMP) allows validation efforts to be focused where the risk is highest. This means that qualification and testing activities are not carried out uniformly, but rather prioritizing those functions that directly impact the product quality, data integrity or patient safety.

During validation planning, tools such as Risk Analysis (RA), FMEA (Failure Mode and Effects Analysis) O Hazard Analysis They help identify the most critical failure modes, thus establishing controls proportional to the level of risk.

This approach not only optimizes resources, but also allows for documented justification of the decisions made, reinforcing traceability and transparency in the face of audits and inspections.

2. When the system changes, the risk changes: this is how it should be evaluated

Risk management is not an isolated exercise, but rather an integrated and continuous process that accompanies the automated control system from its conception to its retirement. This approach ensures that decisions related to validation and the level of control applied are always aligned with the actual system impact on product, process, and data integrity.

2.1. Design phase: definition of critical requirements

The life cycle begins with the preparation of the URS (User Requirement Specification).

Here, applying an early risk analysis allows:

• Identify critical functions (for example, regulation of temperature, pressure or filling rate).
• Differentiate essential requirements from accessory functionalities.
• Determine which parts of the system require enhanced validation.

Benefit: oversizing of validation is avoided and attention is prioritized on what has a real impact on the quality of the product.

2.2. Implementation and configuration: risk-based testing approach

Once the system is designed, the risk assessment guides the qualification activities:

• IQ (Installation Qualification): Ensures that the system has been installed as designed.
• OQ (Operational Qualification): Focuses on testing critical functions identified in the risk analysis.
• PQ (Performance Qualification): Verifies the operation of the system in real operating conditions.

Here the risk determines:

Risk level	Function example	Validation effort
Alto	Automatic process control (e.g. flow rate, pressure, dose).	Complete testing, detailed evidence, verified alarms.
Half	Recording of non-critical data.	Functional tests and audit trail verification.
Low	Auxiliary functions without direct impact.	Documentary evaluation or justified exclusion.

This approach is aligned with GAMP 5 and CSA: less redundant documentation, more meaningful testing.

23. Operation and maintenance: risk is dynamic

Once the system goes into operation, risks may change due to:

• Software or firmware updates.
• Replacing sensors or hardware.
• Changes in the process.
• Results of internal or external audits.
• Evolution of the level of cyber threats.

Therefore, they must be applied:

• Formal Change Control.
• Reassessment of risk after any modification.
• Partial or total revalidation when the risk demands it.

For example, if the PLC algorithm that regulates the flow of a sterile filler is modified, partial PQ and batch weight trend verification are required. If only a similar sensor is replaced, calibration and registration is sufficient.

2.4. Retirement and replacement: controlled closure of the life cycle

Risk management should also be applied at the end of the system's useful life:

• Preservation and secure migration of historical data.
• Controlled access deactivation.
• Documentary evidence of the withdrawal.
• Validation of the substitute system to ensure operational continuity.

The objective is to avoid loss of traceability or regulatory discontinuities.

3. Data integrity as a central element of risk in automated systems

In automated control systems used in the pharmaceutical industry, the data integrity It is an essential component of process control and decision making. The risk is not limited to the technical failure of the system, but also to the possibility of generating, modifying or interpreting data incorrectly, which could compromise the product or make traceability difficult in an audit. Therefore, risk mitigation requires applying complementary controls, both technological and procedural.

3.1. Technical controls (Technological controls)

These are implemented directly into the automated system or your digital infrastructure:

• Electronic signatures compliant with 21 CFR Part 11 / Annex 11. They ensure that every approval, adjustment or data release can be clearly attributed to an authorized person, without the possibility of repudiation.
• Audit Trail (audit traceability). Automatically logs any creation, modification or deletion of critical data.
  Its periodic review is key to detect improper access, trends or suspicious patterns.
• Role-based access management (RBAC). Ensures that each user has only the permissions necessary for their functions.
  This separation helps prevent operational errors and unauthorized acts.
• Version control and software configuration. It ensures that the system always operates with the validated and approved version of the program, avoiding deviations or undocumented configurations.
• Cybersecurity and protection against intrusions. The robustness of the system must extend to its connectivity: firewalls, strong authentication and network monitoring are essential to avoid external manipulations.

3.2. Organizational controls (Procedural controls)

These are measures linked to quality culture, documentary discipline and continuous training:

• Standard Work Procedures (SOP/SOP). They define step by step how systems should be configured, operated, reviewed and maintained.
  They constitute the framework that ensures uniformity and consistency.
• Training and qualification of personnel. Technology alone does not prevent risk. Staff must understand how to operate the system correctly, what actions can compromise traceability and how to identify and act on failure signals.
• System governance and clear ownership (System Ownership). The assignment of responsibilities between Engineering, Production, IT and Quality avoids ambiguities and accelerates decision making in audits and reviews.
• Periodic data review and internal audits. It allows confirming that the system operates in a controlled state and that the information generated remains reliable, consistent and complete.

4. Optimize validation effort based on impact on product and data

In the validation of automated control systems, one of the most common challenges is finding the balance between regulatory rigor and operational efficiency. Traditionally, many projects have applied a conservative approach in which “everything is validated” with the same level of detail, generating high document volume, long implementation periods and little relationship between the effort invested and the real risk.

The modern approach, driven by updating GAMP 5 (2nd edition) and for the guide Computer Software Assurance (CSA) of the FDA, proposes a significant change: validation should focus on those aspects that directly impact product quality, data integrity, and patient safety.

This means that not all system functions have the same criticality, and therefore should not receive the same level of proof.

So, What does proportional validation entail?

• Prioritize the critical functions of the system versus auxiliary functions.
• Reduce unnecessary testing on elements without direct impact on GxP.
• Strengthen the traceability between requirements, risks, tests and evidence.
• Optimize the use of resources (engineering times, QA, production).
• Maintain the regulatory defensibility, demonstrating logic in decisions.

In other words: validate with intent, not just with checklists.

4.1. The role of CSA (Computer Software Assurance)

The CSA philosophy promotes:

• Exploratory or challenge-based tests (challenge tests) for critical functions.
• Less purely documentary evidence and more significant evidence.
• Use of risk based testing rather than repeating standard tests already covered by the provider.
• Documentation clear, defensible and non-redundant.

This is especially useful in systems with proprietary firmware (for example, PLCs or I/O modules), where traditional validation often duplicated tests already performed by the manufacturer.

Tangible benefits of the proportional approach:

• Automation projects faster and more manageable.
• Reduction in document volume without compromising quality.
• Greater clarity in audits before agencies and clients.
• Better alignment between engineering, production and QA.
• Validations more robust, reproducible and sustainable in time.

In essence, proportional validation is not validating less, but validating better.
It is about applying resources where the risk is real and demonstrable, ensuring that automated systems operate in a controlled state in an efficient, defensible and lifecycle-aligned manner.

5. Practical application of risk analysis in the validation of control systems

During validation planning, the use of methodologies such as FMEA, Risk Analysis or Hazard Analysis It allows you to identify the system functions that directly impact the quality of the product and, therefore, require greater rigor in testing and controls.

Practical example: Validation of a PLC on an aseptic filling line

Process: Control of filling volume in sterile vials.

Associated risk: Overfilling, which leads to a loss of sterility and batch discard.

Potential bug identified in FMEA: Error in the level sensor or in the PLC control algorithm.

Evaluated element	Risk	Severity	Probability	Containment	Validation action
Level sensor reading	Incorrect filling volume	Alta	Media	Baja	Specific OQ tests to validate signals and calibration.
Automatic adjustment by PLC	Calculation error, which will lead to a systematic deviation	Alta	Baja	Baja	PQ testing with simulated batches and statistical verification.
Parameters modifiable by operator	Accidental or intentional tampering	Alta	Media	Media	Access management + Change audit (Audit Trail).

Result:

Validation activities focus on critical functions, rather than validating all software equally. This optimizes effort and demonstrates regulatory defensibility.

A risk-based approach to ensuring control status

The validation of automated control systems in the pharmaceutical industry should not be considered solely as a documentary activity or a specific requirement associated with the start-up of a facility. On the contrary, it constitutes a continuous process that accompanies the system throughout its life cycle and whose central purpose is to ensure that the process remains in place. controlled state, protecting product quality, data integrity and, ultimately, patient safety. The systematic application of Quality Risk Management, in accordance with ICH Q9, GAMP 5 (2nd Ed.) and CSA guidelines, allows efforts and resources to be prioritized in those functions that have the greatest impact, avoiding oversized, inconsistent or difficult validations to defend against audits.

The consideration of risk as a driving axis facilitates not only the definition and execution of proportionally relevant IQ/OQ/PQ activities, but also decision making in the face of changes, operational deviations and evolutionary maintenance of the system. Likewise, the incorporation of technological and organizational controls aimed at data integrity reinforces the reliability of electronic records and guarantees the traceability required by international health agencies. This integrated approach ensures that automated systems operate in a manner that is robust, reproducible and aligned with current regulatory standards.

In summary, validating based on risk is not validating less, but validating with criteria, evidence and purpose. The key is to demonstrate, in a clear and defensible manner, that the system always performs its intended function, is kept under control, and operates within limits that protect product quality and patient safety.