Mark Stevens is Operations Director at GxPi.

Mark Stevens 

Risk assessment is a frequently used term and today almost every industry sector has adopted this in some form as a standard working practice. The bio/pharma industry must manage the balance between increased regulation and the need to be more efficient and effective at each stage of drug development and manufacturing, with both factors being driven by the need for continuous improvement. In particular, it is important to understand what truly represents a risk to a patient or critical information that is ultimately associated with the care of a patient. If done correctly and consistently, however, business, regulatory and legislative requirements can be aligned. 

The process of identifying and quantifying a GXP risk within any component of drug development and manufacturing is often done inefficiently, most often due to the focus of the exercise not being correct or as welldefined as it could be. In many cases, this can be attributed to the risk assessment process being inappropriate and/or over-complicated. The purpose of the process is not to generate comprehensive reports, but to identify where there is potential risk to the patient and then to eliminate or minimise this risk.  

The International Society for Pharmaceutical Engineering (ISPE) Baseline Guide and Good Automated Manufacturing Practices (GAMP) documentation provides an excellent foundation upon which to base risk assessment. In accordance with these guidelines, it is necessary to conduct an objective assessment of each system and activity. It is important to challenge the way things have been done historically, as well as the way things are done in different parts of the organisation, as these may not always be the most appropriate solutions.  

For instance, the classification of environmental conditions for a work area can have a significant cost impact in terms of design, installation, validation and ongoing monitoring. For pharmaceutical companies, it is important to consider whether reducing the classification across elements of drug manufacturing can have an impact on product safety. By challenging the classification necessary to conduct GMP/GLP operations within an environment that is adequate for the operation, companies may be able to achieve significant savings. A value engineering study must challenge all areas of drug development and manufacturing, including quality, and must not be restricted to new facilities, as the robust review of existing facilities is also often beneficial. 

Lean compliance involves clearly identifying what an organisation does to achieve GXP compliance. This includes factors such as how the organisation measures success; what can be measured to quantify success and improvement; and identifying tools to seek better and more efficient ways of either improving performance or maintaining performance with less resources. In terms of quality and compliance, this means driving a bigger margin between the resources needed to achieve and demonstrate the appropriate and applicable level of compliance. Using the manufacturing analogy, improvements in efficiency can be driven through economies of scale; for example, having more products in the development pipeline or marketed products that are managed by the quality and compliance functions. However, this presents a number of challenges because not every company is a multinational, multiproduct organisation capable of achieving savings in this way. Secondly, larger organisations with manufacturing capabilities have already seen the benefits of applying lean thinking to their production operations, so it is important to examine how this can be applied to other parts of the business. In other words, how can the same level of resources be used to support an increasing pipeline or increasing regulatory requirement? Or, how can a reduced level of resource support the current level of regulatory requirement? This is represented in 

Figure 1: Lean compliance resource savings identification and cost benefit diagram. 			

Lean compliance is a means by which all parts of an organisation are aligned to contribute to achieving optimal performance. Each component of the business process is also made truly accountable. Lean compliance addresses the costs and return of QA compliance and how this improves the quality or confidence in a product or process. It also questions how much effort is given to ensuring the ultimate safety of the patient, and whether the applicable regulations and corporate policy are fulfilled and can be demonstrated. It should also identify and challenge those non valueadding components where regulations and policy are generally fulfilled to provide a feeling of security rather than being driven simply by necessity. 

The focus of such a process is to conduct an objective assessment of the quality, compliance and validation functions in order to categorise each process and subsection of a process, as shown in 

Table 1: Summary of function value categorisation.			

To maximise the value of this overall process, it is essential that the focus be on the identification and elimination of waste. As demonstrated in 

, the savings of waste prevention will typically far exceed the savings from efficiency improvements. To achieve this, it is necessary to challenge the quality and compliance activities that the business is performing. For example, if a new enterprise resource planning (ERP) system is to be deployed within an organisation, it must be considered which components will have any impact on GXP and require validation. It is also important to determine how many 'Business Value' elements are truly necessary and whether any can be downgraded to waste. This approach can quickly facilitate real savings in cost and time, both in terms of implementation and ongoing use of systems within the GXP environment. Therefore, it is important for the risk assessment to look not only at what is required to ensure compliance, but also to enable clear identification of what is not required. 

As with any quality system, the route to success involves setting out 'policies' to communicate what the organisation wishes to achieve, the 'guides' for how this should be done (principles), the details of how this must be completed (methods) and the measurement system and expected results by which success and adoption will be measured. Fundamental to the success of any lean compliance programme is buyin from the organisation and readiness to change. This is a change management project and must be managed appropriately — a brilliant idea will remain just an idea if it is not clearly communicated and adopted with the necessary understanding of its purpose and benefit.  

The objective of lean compliance is to enable organisations to focus on those elements that truly impact patient safety and eliminate those that do not. If an organisation successfully adopts a leaner approach to compliance then they will have a significant commercial advantage over competitors. 

Figure 2: Lean Compliance process overview.			

Whilst traditional lean methodologies can be easily transposed to a manufacturing operation for a marketed product, this is not always the case with clinical manufacture or GLP and GCP operations. These processes require smart adaptation of tools that can be customised, as there will be a level of uniqueness in each study, project and activity performed. 

Recent debate: eCTD demonstrating lean compliance 			

In order for the lean compliance process to be successful, it is essential to have the correct blend of internal knowledge and ownership of the operations, combined with the right amount of sympathetic expertise to drive overall success. Depending on the size and internal capabilities of an organisation, this may require secondment of personnel from a different business unit, or the use of third party GXP consultants. This is a people process that requires expert guidance to ensure communication, coaching, cooperation, consistency and a collective and clear understanding of the results and success. The roadmap to success is shown in 

The following real life example demonstrates how lean compliance can result in significant cost and time savings for the release of Clinical Trial Material (CTM).

A lean compliance initiative has been implemented within a leading CMO to reduce the time and cost needed to review and release CTM. To be successful, the quality approval process was mapped, documented and explained to all key stakeholders to create a collective understanding of the operation. Through the use of lean methodologies, the quality control/quality assurance cycle time was reduced from more than 200 days to 56 days — a reduction of 72% of the original time taken. These recommended process improvements — based around changes to the quality function within the business, e.g., review, approval and communication of quality records and data — were incorporated into standard operating procedures (SOPs) for release of CTM and have enabled knowledge sharing between different sites of the CMO, significantly enhancing business processes, knowledge sharing and profitability. 

Using a true riskbased approach to quality and compliance is an essential component of ensuring that an organisation not only fulfils its regulatory requirements, but also does so with a clear understanding of the priority and relative resources that should be given to each element. It also enables identification of those areas that do not have any notable impact on patient safety or GXP data integrity, providing justification for eliminating or ignoring these. 

Lean compliance is a business process efficiency concept used to ensure that GXP best practice is achieved as efficiently and effectively as possible. By carefully using proven and established lean methodologies and tools, the quality and compliance functions of an organisation can be challenged. Lean compliance establishes the true valueadding operations within a business and looks at how these can be maximised. It decides which business value operations are necessary to ensure compliance, and how these can be simplified and reduced. It also highlights the non valueadding operations that can be eliminated and prevented to save time and cost. The objective is to truly challenge each component of a process and determine whether it is really essential. The main question is whether something is being validated because it has always been done that way or because it really has an impact on quality, compliance and, most importantly, patient safety. 

The key to success with any lean compliance project is the same as any good business or project management practice — establishing key objectives, clear communication throughout the group, and maintaining the focus and support needed to drive and measure success. 

1. Pharma iQ, "Do Electronic Submissions Save Pharmaceutical Companies Time? 62% says Yes!" (2010). 

Articles

With the increasing need for businesses to reduce costs and demonstrate value, there is a requirement to look at all aspects of bio/pharma drug development and manufacturing to achieve efficiency improvements.