The term harmonization has become a buzzword in the life science sector and doesn't just refer to the harmonization of international standards created by various regulatory (or voluntary) bodies but can also refer to the harmonization of company-wide cultural and political differences as well as the harmonization of varying policies and procedures introduced by company mergers and acquisitions.
These internal needs for harmonization often result in the centralization of operations with the objective of promoting efficiencies, quality control and regulatory compliance. This paper explores some of the steps toward harmonization implementation and the urgency of doing so. It also recommends various desirable features in an automated quality audit system that will assist in the unification of quality processes in a single system and provide a healthy ROI.
Step #1: Benefit – Cost Analysis
Before initiating any harmonization project, companies of necessity, should consider the benefits of the project versus the cost. In the life science industry, evaluating the possible costs associated with non-compliance is useful particularly if a statement for the justification of change is needed.
Worst case scenario: non-compliance could lead to a product recall or even serious harm to a patient or trial subject. From this perspective, it is easy to see how the cost of non-compliance can negatively impact a company, particularly if it involves human tragedy. Getting things back to a compliant state after such an event is going to cost a great deal more than getting things right initially.
This is the idea behind the prevention, appraisal, failure (PAF) model, which evaluates the activities that constitute prevention, appraisal and failure.
Step #2: Understanding the Effects of Not Implementing a Quality System - Use of the PAF Model
A product recall is an example of an external failure. The worst example would be the death or serious injury of a person or persons using a product that has undergone flawed safety testing. Internal failures are the costs that would disappear if no defects / errors existed in the product prior to receipt by the customer. Examples include scrap, re-work, re-testing, downtime and disposition.
Appraisal costs are the costs incurred in discovering the condition of the product, mainly during ‘first off’ inspection. Appraisal costs include: goods in inspection, inspection and testing of materials, calibration, checking documentation, materials and services consumed and evaluation of stocks. Other appraisal costs might include the measurement of process performance, delivery performance and customer satisfaction.
Prevention costs are the costs incurred to keep failure and appraisal costs to a minimum. Prevention costs include: quality planning, new product review, training, process control, collecting and evaluating data, quality reporting and quality improvement initiatives. Prevention costs and issues are not usually directly associated with the GxPs but are more common under the ISO 9000:2000 system.
The PAF model is usually applied to organizations looking to decrease costs, using established accountancy figures. The example given below is based on a traditional manufacturing company. However, the model can be readily applied to any product (or service) by identifying the prevention, appraisal and failure activities.
In the traditional PAF model appraisal costs and prevention costs are zero, the product is 100% defective. To improve conformance, these costs are increased until perfection is approached. Here the prevention costs rise exponentially, becoming infinite at 100% conformance. Conversely, failure costs at 100% non-conformance (100% defective) become infinite (Fig 1a), however in a more modern view the total costs reach a finite level (Fig 1b).
The following graphs shows the principal quality costs involved in achieving fitness for purpose using the traditional and modern PAF models.
Step #3: Getting Employees on Board
When employees hear that a company’s operations are going to be harmonized, they often react with considerable apprehension. This is a natural reaction but is often a reaction that results in challenges to the overall harmonization effort. This "natural reaction" therefore leads to the logical conclusion that an important first step in internal company harmonization is to enroll employees in the benefits of such a program, both to the company and in particular to its employees.
Step #4: Consider the Implementation of Additional Standards
Those employed in the life science sector are well familiar with current GMP, GLP, and GCP quality standards. Each standard has a distinct primary focus.
Effects of Technological Change on Harmonization
The rapidity with which the electronic age is advancing greatly affects any harmonization effort. We are currently in a position where what is considered to be a fairly basic calculator has far more computing power than the tools that helped NASA put the first man on the moon— and the speed of advancement does not appear for a moment to be slowing down.
While, on the one hand, technology has given us electronic data capture systems and the Internet/Intranet, which allow us to share information across multiple locations (even across entire countries or continents) thereby facilitating harmonization efforts, technology can also hamper harmonization. This is especially true when automation solutions are purchased and cannot be easily upgraded/validated. However those software providers that can easily upgrade and validate their solutions are likely to provide the solutions that greatly enhance harmonization processes.
Considerations When Searching for Automated Quality Audit Systems An integrated quality audit system provides the ability to audit/inspect companies across various regulatory disciplines e.g GCP, GLP and GMP. It allows management to plan better when there is a need to cover short-term illness, unexpected absence from the workplace or a change in anticipated workload. It is also more efficient when an inspector or auditor is providing a service to a particular area that has a significant number GxPs in operation.
When moving towards a single quality system covering more than one quality standard, it is important to consider:
Managing the Workload Assuming that the inspector is not an expert in every field, his or her ability to answer the vast majority of queries without having to resort to the expertise of colleagues provides the advantage of prompter service. Furthermore, for businesses situated in a specific locality, the ability to inspect, audit and offer advice across a number of good practice disciplines increases the number of potential opportunities for the auditor / inspector.
Training cross-functional auditors can also reduce the number of auditors needed within a business, and—as a result of the advice and input from auditors—encourage the sharing of best practices across disciplines. This is because problems recognized and resolved in one area tend to make it easier to anticipate and therefore quickly respond to (or prevent) problems in other areas.
A Case Study
One company that underwent significant change to harmonize numerous non-GxP quality systems into a single, integrated GxP system realized many benefits as a result, including:
As a result of these benefits, the company strongly felt that it had saved money and secured more lucrative business opportunities.
In light of the heparin debacle and the GAO reports it is interesting to note that the Supreme Court recognized the "rigorous" process that Class II devices undergo.
The decision now makes regulatory compliance an affirmative defense for Class III medical devices that receive pre-market approval from the FDA, except in the rare circumstance where a device maker knowingly commits fraud on the FDA. Potential plaintiffs faced with such design defects would be required to prove that the device manufacturer failed to comply with FDA regulations, or that doctors or other medical personnel misused the device, placing an even greater strain on the medical profession.
Benefits and Risks of Adopting a Single Quality Management System
The benefits versus risks of adopting a single quality management system are summarized below.
Another primary benefit to a company starting off with a fully encompassing quality system is that the system should not need any significant modification or re-evaluation for many years to come.
Because so many life science companies have segmented into parts that each operates more or less independently, the need for harmonization is very great in the life science industry.
We examined this need and several important reasons for not “putting off” harmonizing a regulated company’s quality processes. One reason is because the rapidity of technological change tends to magnify existing divergence.
We looked at a case study of a company that harmonized numerous non-GxP quality systems into a single, integrated GxP system and realized many benefits as a result—including financial savings and more lucrative business opportunities.
We also looked at some important considerations when implementing an integrated quality management system, and we saw that the benefits far outweigh the risks of adopting such a system.
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