Stephanie Harden is senior manager, Product Marketing, at Waters.

Stephanie Harden

Change can be intimidating, and for most an aversion to change is understandable. However, in the heavily regulated pharmaceutical quality control (QC) environment, change can be much more daunting—and the associated risks far greater. For the quality assurance (QA) unit and related staff, the first risk that comes to mind tends to be regulatory risk, but in reality patient safety is by far the most important factor.

With patient safety in mind, hesitancy regarding changes in the lab is common, but labs nonetheless continue to evolve and improve. Increased digitization, the adoption of automation, and modern, intelligent technologies are common themes in routine testing laboratories today. The many benefits of modernization are driving change, including reduced compliance risks, improved quality, higher throughput, and fewer instances of human error.

That said, it’s essential that the change process is well managed, and members of the pharmaceutical industry must ensure that change is handled properly and in a way that protects patients. This article will explore how to satisfy these responsibilities, document reasons for unease in the face of change, and provide points on best practices to consider when making the changes that matter most.

The pharmaceutical industry is fueled by technological innovation. Advances in technology have improved analytical processes and enhanced the provision of consistent product to patients, while the introduction of progressive regulation has enabled these technologies to be used in the labs that need them. This trend is clearly at odds with the overarching hesitation regarding change in the laboratory setting, which stems from corresponding requisite procedures. This includes the need to update standard operating procedures when introducing new equipment, as well as all changes needing to be approved by the relevant regulatory bodies.

This latter point on regulatory involvement is particularly pertinent to those working in regulated laboratories. Proposed changes must first be evaluated against the marketing authorization and the possible impact to patient safety. Pharmaceutical companies must also balance the need for continual innovation with the requirement to comply with the good manufacturing process (GMP) standards specified by regulatory authorities.

For the European Union, the rules and regulations governing medicinal products are summarized in the EudraLex volumes. One volume, for the specific classification of advanced therapy medicinal products (Volume 4 Part IV: GMP requirements), speaks to the fact that new and alternative approaches and technologies can be implemented as long as appropriate regulatory and quality management requirements are complied with. “These Guidelines do not intend to place any restrain on the development of new concepts of new technologies. While this document describes the standard expectations, alternative approaches may be implemented by manufacturers if it is demonstrated that the alternative approach is capable of meeting the same objective. Any adaptation applied must be compatible with the need to ensure the quality, safety, efficacy and traceability of the product” (1).

Such guidance is representative of a shift in attitude across regulatory bodies in recent years towards enabling greater post-approval flexibility. In the past, QA was more reluctant to initiate changes to validated procedures, regardless of inefficiencies in the testing process. Even as regulators have become more open to the needs of organizations to modernize, some companies have remained reluctant to adopt new products, processes, or facilities without the regulators’ “blessing” in the form of specific rules or guidance. The slow progress of official regulatory modernization is exemplified by the time taken for the regulatory adoption process for continuous manufacturing, which took a decade or more for official guidance—International Council for Harmonisation (ICH) Q13—to be written, agreed on, and then fully adopted into regional regulations (2). Today, however, FDA has publicly stated that new drug product submissions that leverage such modern innovations will be reviewed and approved favorably (3).

The real-time release testing (RTRT) system adopted by AstraZeneca is another example of increasing autonomy in the pharma industry (4). This type of system provides assurance that a product is of its intended quality based on information gathered throughout its manufacturing, rather than testing quality only once the product is completed (2). AstraZeneca did not wait for regulatory guidance when launching their RTRT system, but instead engaged directly with FDA and American Medical Association before introducing the scheme at a manufacturing plant in Germany. The project was a success and regulators subsequently provided feedback to help further improve the process (5). This example highlights a positive shift in the pharma industry towards change and modernization, but any changes made to established ways of working must be managed appropriately. 

Companies must deploy and maintain a pharmaceutical quality system (PQS) to meet the needs of key stakeholders, including patients and regulators. Effective change management is integral to a successful PQS; in fact, change management (CM) is so central to the success of pharmaceutical labs that it often constitutes a focus of regulatory inspections and is frequently cited on warning letters from FDA. For example, one warning letter sent in December 2022 noted that an inadequate CM process resulted in “damaged and inappropriately designed” equipment to remain in use. The warning letter goes on to instruct the recipient to undertake “a comprehensive, independent assessment of [its] change management system” (6). Consequently, poor change management can directly result in both reputational and financial consequences.

On the other hand, innovation and continual improvement is essential to a lab’s effectiveness and efficiency. However, innovation relies heavily on the support of exemplary change management practices. This fact is typified by guidance provided by ICH in guideline Q10: “Innovation, continual improvement, the outputs of process performance and product quality monitoring and CAPA [corrective action and preventive action] drive change. In order to evaluate, approve and implement these changes properly, a company should have an effective change management system” (7).

It’s also important to note that change management takes different forms at different sites, depending on the activities and products involved as well as the intended market. A site that produces medical devices for the United States will be regulated in a different way than a site that only makes drug products for Japan, which must be accounted for in the change management strategy used at each site. However, for quality management, the move to standardize and adopt ICH guidelines is paving the way for global harmonization of change management expectations. 

Strategic considerations for effective change management

Many factors must be considered in the strategic management of change, including:

Identifying the processes that will most benefit

A key factor to consider is prioritization: which changes should be enacted before others? The answer to this question will differ between different sites with different objectives. Prioritization represents a core consideration in the strategic management of change, but it is far from the only one.

As an example, a common goal for lab innovation or improvement that initiates (or requires the initiation of) change management is the need and demand for simplification.Simple processes in the lab can support employees by reducing the likelihood of human error as well as the training burden, while also improving the usability of equipment and overall productivity and throughput.

Consequently, measures such as result invalidation rates, right-first time results, or orphan data review time should all be impacted by simplification changes.

Risk management tools can be used to evaluate the risks associated with proposed changes and guide decision making. Levels of risk are evaluated from multiple perspectives, including GMP and general regulator requirements, but these tools should always be focused on delivering quality product for patients. This process represents a key element of prioritization, as discounting high-risk changes allows companies to direct their resources to plans that demonstrate promise but are not associated with prohibitive levels of risk. Once deemed that the risk is minimized to an acceptable level, proposed changes can then proceed to the appropriate internal and external approvals.

Reflecting on the success (or lack thereof) represents another crucial element of strategic change management; it should occur not just when the change is “implemented” or finished, but also during the iterative steps along the journey. From a business perspective, success is ideally quantified as a return on investment. On the other hand, impacted employees are likely more interested in outcomes that make their tasks quantifiably easier or simpler.

If a quantified metric of improvement can be presented to senior management, as well as employees involved in the change process, then similar changes may be prioritized elsewhere in the future. Or, a company wanting to try a similar change in the future can use the historical numbers to modify the change and improve the associated benefits.

Feedback from colleagues can also be valuable in the retrospective evaluation of changes. People will inevitably have their own opinions on how the processes or software associated with a particular change might be improved after “living with it” for a given period. This feedback should be gathered and used to maximize the value of that change. In parallel, this feedback could also be used to troubleshoot future proposed changes: how can they be delivered in a way that is aligned with preferred ways of working in the lab? After all, the changes are meant to make colleagues’ lives easier, not harder.

An effective PQS is one thing, but what does it mean without a satisfied and invested workforce? The best organizations recognize that quality extends beyond a great PQS. With this in mind, companies should aim to create a culture of excellence that encourages discourse. The requirements of the PQS are more likely to be met in this work environment when employees feel involved in the strategic management of change. Additionally, demoralization associated with lacking visible benefits in the wake of large-scale change may be avoided.

Perhaps the greatest advantage inferred by a culture of excellence is the development of an environment in which employees are comfortable approaching senior management with their own suggestions to drive innovation. People must be able to talk about change in order to take ownership of change. Open communication of this kind also instils colleagues with a natural desire to enact meaningful change in the lab, creating a cycle in which employees continue to submit ideas to senior management after seeing their previous ideas realized. Innovation schemes can open these channels of communication in some labs by inviting employees to submit their ideas for change and forwarding them to a risk assessor for evaluation.

Creating a culture that celebrates change is not always easy, though. Encouraging people to embrace certain changes can be a challenge—for example, consider technology-averse employees faced with new equipment. This is especially the case in situations where one larger change constitutes many smaller changes. However, a positive experience with one change can improve outlooks regarding future change. Celebrating these small victories can make a tangible difference and helps people feel at ease with the fact that changes are beneficial, rather than happening simply for the sake of change.

Implementing new systems in the QC lab doesn’t need to be a stressful experience, but change must be managed in a way that allows crucial therapies to continue reaching patients while the residual risks associated with them are minimized. It is only by considering key factors, such as the potential risks of their use and the logistical factors associated with integrating new systems into existing workflows, that allows the possibility for capitalizing on the opportunities for change that they afford.

For regulated laboratories continually challenged with tight deadlines, evolving regulatory guidelines, and staff retention, continual improvement can be seen as an additional burden. However, with a strong company vision and highly motivated staff, it is possible to begin to forge a path towards improved quality and patient safety while reducing regulatory and business risks. The future is bright—see you there.

Volume 4, Good Manufacturing Practice (GMP) guidelines, Part IV – GMP requirements for Advanced Therapy Medicinal Products,

ontinuous Manufacturing of Drug Substances and Drug Products 

Ramanadham, M. An FDA Self-Audit of Continuous Manufacturing for Drug Products. 

Hughes, R. Perspectives on Pharma: The Role of Change Management in Supporting Innovation in Regulated Pharma. 

Markl, D.; et al. Review of Real-Time Release Testing of Pharmaceutical 1 Tablets: State-of-the Art, Challenges and Future Perspective. 

European Medicines Agency. ICH Guideline Q10 on Pharmaceutical Quality System. 

Stephanie Harden is senior manager, Product Marketing, at Waters. Heather Longden is an independent regulatory compliance consultant.

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