Risk-based process validation requires method deployment on a new level

Risk-based process validation requires method deployment on a new level

Every day in the operational business, problems are dealt with which relate to process validation. For example: recurring high efforts dealing with deviations. Long release times affecting delays in delivery. Scrap rates from poor process performance leading to further costs.

This article

  • Looks at one of the main reasons why most pharmaceutical and medical devices companies are not reaching their potential when it comes to operational efficiency
  • Puts forward approaches for discussion which could provide remedies based on regulatory guidelines (see below)

In validation, there is still too little focus on the highly critical parameters of product quality, and process risks are being overlooked. At the same time many aspects are validated that are superfluous from a risk perspective. We observe that risk-based validation is carried out formally as required by the authorities, but at the same time validation is done the traditional way. The possibilities for economic benefits are falling short of their potential!

What do we mean by risk-based?

Classical process validation begins with determining process requirements. This is followed by proving that the process meets all aspects of the critical and non-critical requirements. In contrast, risk-based process validation means that all risks are systematically identified and then excluded, delivering a flawless product.

It is obvious that you can save a lot of effort if you only validate what really needs to be validated. It is also clear that processes run more safely if you focus on potential risks. By using analytical approaches risk-based validation attempts to effectively eliminate as many potential risks as possible from the outset. This leads to reliable quality with less effort.

Simple, right?

De facto, risk-based process validation requires a different working style!

In classic process validation, experts check every step of the process and validate primarily on the basis of their technical expertise. Specific Methods are used, but primarily to guide the process step-by-step. Deeper understanding of the method is hardly necessary, as the methods simply facilitate the work. A typical example is the Three Golden Batches approach.

In risk-based process validation, expertise must be supplemented by an overview of the entire process whether it’s from procurement to delivery or from dossier preparation to controlling samples. Process validation should build on the insights from process development. Goal-oriented teamwork is essential. No expert will be able to identify all relevant risks from a quiet room in an ivory tower.

Is insufficient staffing really the issue?

Staff capacity often seems insufficient to involve the required cross-functional team. Frequently, there is also a lack of methodical support and practice, which leads to inefficiency. Asking people to use methods without a background understanding leads to frustration.
People often do not feel comfortable using risk-based process validation because they do not know the approaches which make adoption simple. They would rather fall back and validate the way they always have. Too often, the result is greater expenditure of effort, with less to show for it. This is where we come in.

Economic benefits

There are two steps to risk-based validation working. First, organizations use cross-departmental collaboration to systematically identify risks. Second, risks are eliminated through smart preventative actions and data-based control plans. And this is the way to tap into considerable economic advantages.

Those who make use of the guidelines can gain a lot of additional benefits:

  • Well-understood processes lead to fewer deviations
  • Fewer deviations mean greater efficiency in all areas and fewer delays in product delivery
  • By understanding the process and the process risks we can systematically reduce controls, measurements, and samples which reduces the effort
  • Overall process validation is faster, because we only validate that which needs to be validated

And perhaps the greatest benefit: Companies that work together effectively during validation will work well together when problems arise. This is due to process oversight and collaboration becoming matters of course.

Systematically fast with understood methods

Tools and techniques make success repeatable and lead to systematic improvement. It’s key to understand the tools, and to adapt them where necessary. Cleverly adapted, well understood methods help to

  • Change long-standing habits
  • Reduce efforts in complex procedures
  • Move systematically and safely on the new terrain

Use of some simple techniques recommended by regulatory bodies

Simple tools for moderating and visualizing processes and risks can make a significant difference:

  • Process Maps: With cross-departmental staffing, procurement and production processes are mapped – including critical requirements and risks. Please note: 3 joint workshops of 30 minutes each are sufficient, everything else can be done by individual experts.
  • Fishbone diagrams / Ishikawa: For clear illustration of all potential root causes behind process deviation.
  • Check Sheets: Should follow each risk analysis. They translate risk protection into practice for the operational departments. Whoever sees such techniques in use in the company in the context of risk assessment and risk avoidance in process validation, has at least overcome the first initial difficulties of interdepartmental cooperation!

New methods of interdepartmental can seem daunting at first, but the above illustrates how they can be organized into logical steps.

Also of interest are various statistical methods, especially:

  • Determining CQAs (critical quality attributes): The critical limits within which the process is allowed to move should be driven by the risk or by customer requirements. It is often useful to work with regression analysis
  • Control Charts are the tool of choice for determining risk in different possible process conditions . Only on this basis can a concept for reasonable sample sizes be derived. This leads to the next point:
  • Sample Sizes, and Amount of Samples depends on how much a process varies, how close it comes to the allowable specifications, and the defined acceptable quality limits (AQLs). If you build on statistics, you can save a lot of sampling and analysis efforts and even reduce deviations in the running processes. In this way you can reduce effort compared to the traditional approach of three validation batches.

It’s necessary to be aware of the risks from the outset of process development.


In risk-based validation, the use of tools and techniques with understanding, a good eye, and a sense of appropriateness helps to keep costs low and to achieve reliable quality.

Relevant policies referred to here:

  • FDA and EMA: For more than 10 years, the FDA and EMA have been demanding that validation be carried out on the basis of risk, and no longer against requirements
  • EC, GMP, Annex 15: The risk assessment should determine the scope and depth of validation
  • ASTM Standard E2500 – based on ICH Q8, Q9 and Q10: enables a risk-based approach to qualification
  • ISO 13485 – Definition of the qualification phases
  • ICH Q9, Annex I: Methods for risk identification

Interesting topic?

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