Lean compliance and adopting a true risk-based approach to validation

By Mark Stevens, GxPi

Word count: 1974

Overview

With the increasing need for businesses to reduce cost and demonstrate value, there is a requirement

to look at all aspects of the pharmaceutical and biopharmaceutical industry to achieve improvements

in efficiency, including how quality and compliance is managed. This article will investigate how GXP

best practice should be implemented and how lean methodologies, originally developed for

manufacturing operations, can be utilised to achieve improvements in efficiency and compliance.

Introducing Risk Assessment

Risk assessment is a frequently used term and today almost every industry sector has adopted this

as a standard working practice in some form. The healthcare industry is required to manage the

balance between increased regulation with the need to be more efficient and effective at each stage

of the drug development and manufacturing process. Both sides of this are driven by the need to

achieve continuous improvement. If done correctly and consistently, these business, regulatory and

legislative requirements can be aligned. 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).

The process of identifying and quantifying a GXP risk within any component of the drug development

and manufacturing process is often done inefficiently, most often due to the focus of the exercise not

being correct or as well defined as it could be. In many cases, this can be due to the process being

used to conduct the risk assessment being inappropriate and / or over-complicated. The purpose of

the process is not to generate comprehensive reports, it is to identify where there is potential risk to

the patient and 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 order to maximise this, it is necessary to conduct an objective

assessment of each system and each 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 this may

not always be the most appropriate solution.

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 the drug

manufacturing process can have an impact on product safety. By challenging the classification

necessary in order to conduct Good Manufacturing Practice (GMP) / Good Laboratory Practice (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 the drug

development and manufacturing process, including quality and must not be restricted to new facilities,

as the robust review of existing facilities is often beneficial.

Introducing Lean Compliance

Lean compliance involves the process of clearly identifying what an organisation does to achieve

GXP compliance. This includes factors such as how the organisation measures success, what can be

measured in order to quantify success and improvement and identifying tools to seek better and more

efficient ways of either improving performance or maintaining performance with less resource. In

terms of quality and compliance, this means driving a bigger margin between the resource 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 as not every

company is a multi-national, multi-product organisation able to achieve 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 resource 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 below.

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, that the applicable regulations are fulfilled and can be

demonstrated, that regulations are generally fulfilled to provide a feeling of security and that

corporate policy is adhered to.

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 sub-section of a process as shown in

Table 1:

Value-adding Activity that transforms or adds value to the quality / compliance operation

Make as effective as possible

Business Value Activity that does not add value but is necessary to the business

Reduce and Minimise

Waste Activity that uses resources but creates no value

Eliminate and Prevent

Table 1: Summary of function value categorisation

In order to maximise the value of this overall process, it is essential that the focus is on the

identification and elimination of waste. As demonstrated in Figure 1, 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, one must

consider which components of this actually have any GXP impact and require validation. It is

important to determine how many of the „Business Value‟ elements are truly necessary and if 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. It is therefore

important that a risk assessment process not only looks to identify what is required to ensure

compliance but also enables clear identification of what is not required.

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

As with any quality system, the route to success involves setting out the „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 the buy-in from the organisation and readiness to change. This is a change

management project and must be managed appropriately – a brilliant idea will remain just that 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 upon 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.

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 require a smart adaptation of those tools that actually work for a „project-based‟ approach, as

there will be a level of uniqueness in each study, project and activity performed.

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 the overall success. Depending upon 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 which 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 below in Figure 2.

PhilosophiesWhat drives me at work?

- Customer First

- Elimination of Waste

- Respect for the individual

PrinciplesWhat approach should we apply?

- Standardised way of working

- Continuous improvements

- Focus on the process flow

- Visual Management

MethodsWhat tools do we need?

- DMAIC, PDCA

- 5S

- Value Stream Mapping

- Visible Planning

ResultHow do we measure success?

- Clear KPI

- e.g. Cost / time benefit analysis

- e.g. Delivery performance

Figure 2: Lean Compliance process overview

Lean Compliance case study:

Lean compliance is a methodology that GxPi uses within the provision of its solutions and services. It

is built upon those same principles and processes that have been used to great effect within

traditional manufacturing industries. 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 Contract Manufacturing

Organisation (CMO) in order to reduce the time and cost needed to review and release CTM. In order

to be successful, the lean compliance 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 QC / QA cycle time was reduced from 200+ days to 56 days, a reduction of 72%

of the original time taken. These process improvements were incorporated into standard operating

procedure (SOP) for release of CTM and have enabled knowledge sharing between different sites of

the CMO, significantly enhancing business processes.

Recent debate: eCTD demonstrating lean compliance?

Regulatory submissions using the Electronic Common Technical Document (eCTD) guidelines are

becoming increasingly common in the pharmaceutical industry and a greater number of national

agencies have begun to insist upon this method. Whether eCTD demonstrates lean compliance,

saving time and costs during product registration, has become a matter of debate. In a recent survey,

Pharma IQ 1 asked members of the pharmaceutical industry if electronic submissions saved time in

the laboratory. The majority of respondents said yes (62.1%) but some either did not notice a change

in time or said that time spent on submissions had increased. One respondent highlighted the need

for processes and training, saying that while managing applications electronically has given their

organisation the potential to be more efficient, it is up to the business to create, train and support

processes that can leverage the strengths the technology has to offer. Like any new method, it is

expected that the benefits of eCTD will become clearer once people are fully trained in using the

system.

Conclusion

Using a true risk-based approach to quality and compliance is an essential component of ensuring an

organisation not only fulfils its regulatory requirements but also does so with a clear understanding of

the priority and relative resource that should be given to each element. It also enables the

identification of those areas that do not have any notable impact upon patient safety or GXP data

integrity, giving 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 value-adding 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 value-adding

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 if 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 and compliance.

The key to success with any lean compliance project is the same as any good business or project

management practice – establishing the key objectives, clear communication throughout the group,

maintaining the focus and support needed to drive success and measuring that success. Companies

such as GxPi provide access to skills and experience that can help enable lean compliance projects

but it is the energy and ideas within the organisation that are the key to delivering success.

Reference

1. http://www.pharma-iq.com/article.cfm?externalID=2928

For more information on GxPi, please call +44 (0) 115 924 8475 or email info@gxpi.com. Alternatively

please visit www.gxpi.com for further information.

About GxPi

GxPi makes regulatory compliance leaner, by providing products and services to the biotechnology,

pharmaceutical, consumer healthcare, medical devices and veterinary industries, that are “simply

compliant”. GxPi‟s services arm delivers High Value, High Impact consulting services which cover all

aspects of regulatory compliance (GMP, GAMP, GLP, GEP, GCP, GDP), qualified person (QP),

quality assurance (QA), validation services (process engineering, computer systems, laboratory

equipment), clinical technology, training and project management. GxPi‟s solutions arm, provides

electronic Document Management solutions (eDMS) to the life sciences sector via the x-docs™

platform. x-docs™ is a new class of document management software which is powerful and practical

in enabling organisations to comply with increasing regulatory requirements. x-docs™ is easy to

configure, requires little IT support, is cost-effective for organisations of all sizes and are entirely

intuitive to use with minimal training.

For further press information please contact: Fiona Robinson, The Scott Partnership, 1 Whiteside,

Station Road, Holmes Chapel, Cheshire CW4 8AA, United Kingdom Tel: + 44 1477 539 539 Fax: +44

1477 539 540 E-mail: gxpi@scottpr.com