The easier way to do it
Lean Validation – how to simplify validation without putting drug safety at risk

Should “lean” and “validation” be mentioned in the same breath? After all, “GMP“ is often interpreted to mean “great mountains of paper”, and suppliers often confront regulated producers with the question: “Would you like it right away or would you like it validated?” Is lean validation a contradiction in terms?

The lean approach to reducing resource wastage attempts to reduce drag in the process flow and identify the factors which are gumming up the works in the validation process. The argument that “the authorities want it done this way, and it is part of the validation process” has to an increasing extent allowed a bureaucratic mentality to creep in, which in fact does little to promote the overriding goal of cGxP, namely drug safety. Even inspectors now recognize that large volumes of paper do not automatically guarantee that a process or system is under control. On the contrary, too much documentation which is difficult to keep updated can actually be counterproductive. When you look for potential savings, the first step is to identify inefficiencies which can include such factors as overproduction of documents or tests, waiting loops, inadequate workflow organization, unnecessary movement and transport and finally errors.

The focus should initially be placed on optimization opportunities during the generation of documentation, because this activity accounts for the largest portion of the validation effort. SOPs, the use of templates and re-use of validation documentation should come under scrutiny. Risk analysis should be included in all of these activities to determine where attention should be focused. The following approach is not presented in any particular sequence. Instead, the items should be chosen to fit the actual situation at a company. The Chemgineering toolbox supports all of these methods.
Starting point: reorganizing SOPs
Streamlining the validation process should start with a review of SOPs, which can sometimes contain contradictory information. A topic can appear in more than one SOP, and the way in which it is presented may not be consistent with other SOPs. As organizations grow, business units or departments may not agree with the SOPs that apply to them, and they may want to generate their own SOPs. As a result, a number of SOPs are created which have a significant amount of overlap (60–90%). In many cases, it would actually be in the best interest of the company to have high-level SOPs for topics such as risk analysis.
The creation, administration and training effort involved means that there are no winners with the current solution. Over time, the Quality Assurance department often recognizes the excesses, but it is seldom able to implement effective countermeasures. Everyone is aware of how difficult it is to standardize or withdraw procedures once they exist, especially when other sites or functions have declared that SOPs, which have been declared as “obsolete” by company headquarters, are “valid” for them and they do not wish to change them. Quality departments are to some extent partially to blame for the excessive number of SOPs, because they have acquiesced in complaints from departments that there were no procedures to cover certain situations (such as Part 11 some years ago).
The employees in the departments were then given responsibility to create the SOP on their own to address the particular issue. These SOPs then did not fit into the normal structure, as we can see from the difficulty companies have in integrating departmental Part 11 SOPs into validation SOPs. This example shows very clearly that an analysis, and if necessary reorganization, of the procedures should be done prior to introducing lean validation. If small organizations or companies that supply products to the regulated industry have few SOPs or none at all, then the approach described in the section “Using templates” should be taken.
Recommendation for a lean SOP structure
Each topic should only be handled briefly in an SOP, and it should be universally valid. The SOP should also include templates as an addendum which have chapter headings and sample text to
provide a guideline for users who have less experience in validation. Detailed templates ensure that no item is omitted (e.g. access restrictions) and that documents have the same look and feel throughout the company even if they were written by different persons. The finishing touches are added during generation of department-specific templates for production, IT or the lab. Companies that have already used this approach are satisfied with the results.
Building on what others have done
SOPs must reflect the fact that supplier documents are being used to an increasing extent as validation documents during the validation process. It is not unusual to hear people say that the supplier’s test plan is not adequate for validation or that customers have to write the test plans because the supplier does not provide one. Suppliers will have to assume greater responsibility for generating proper documentation which can be used for validation. Documentation which a supplier should provide includes the functional design specification (FS), possibly an engineering risk analysis and test plans. If a supplier’s understanding of validation is really so low that it would not be reasonable to give it responsibility for generating the documentation, then maybe someone should question why the supplier was selected in the first place. This situation would give reason for concern that the supplier’s development activities may not comply with cGxP requirements.
Using templates during validation
If a regulated company or supplier does not have any validation SOPs yet, then it is advisable to use templates during validation of the first system. For every validation document in the V model, there is a template which contains pre-defined chapter headings and explanatory text outlining what should be included in each chapter. This enables users who have little or no validation experience to product high-quality documentation. This is the best approach when validation must be completed in a short period of time and persons involved want to (or have to) learn how validation is conducted using a practical example. Once validation documentation has been generated for the first system, it is much easier for these persons to write detailed procedures. This is a pragmatic way forward for a company which is faced with the decision to conduct validation at short notice, and a reasonable justification for this course of action can be presented to an inspecting body. These templates are part of the Chemgineering toolkit, and they are available for every document in the V model including lab equipment, production systems, process equipment, facilities engineering and IT systems. In addition to templates, there are off-the-shelf validation documents for widely used systems which can be modified to suit local circumstances. Re-usage levels can be as high as 80%. The toolkit includes validation documents for standard systems.
Risk analysis determines the scope of validation
Lastly and most importantly, risk analysis should be used to define the scope of validation. Not all systems, data, parameters and records are equally critical in the cGxP context. The closer we get to the pharmaceutical process, the more critical data and systems become from the cGxP point of view. The main risks related to a system or process should be identified when the user requirement specification (URS) is generated and documented. Risk analysis must become more detailed as the project progresses. To meet cGxP requirements, formal test plans must be written which demonstrate that the risks have been tested. However, you often find that the risk element has been given little consideration in the test plans, and all functions are tested with more or less equal rigor. Risk analysis must be used to provide focus for testing and subsequent monitoring. The risk-based approach, which the FDA has propagated for the past two years, shows that reduction is the right approach. This view is further supported by 21 CFR Part 11, which says that data should first be analyzed to identify critical items before the system which processes the data is evaluated.
Summary: lean validation offers several approaches
In summary, lean validation offers several approaches which are designed to do exactly what is necessary to take a company from where it is today to where it needs to go. In addition to the volume and content of documentation, lean validation also exploits significant optimization potential which exists in the management of flows, information paths and error reduction. This is however beyond the scope of this article, and experi
ence shows that organizational overhead is unfortunately far more difficult to reduce than the volume of documentation.