Q&A: Stepwise Implementation of a Clinical Quality Management System

Advarra expert Steffen Engel answers questions from the recent webinar, Stepwise Implementation of a Clinical Quality Management System.

Q: How do you promote a quality culture when senior management has a lack of knowledge of quality management systems (QMS) and is more interested in deliverables rather than quality? 

A: That is a tough one. First, congratulations on realizing such a mindset may exist. Acknowledging and identifying QMS resistance and its root causes is an important step when addressing it. Management surely has an interest in successful, prioritized “deliverables”. Teaching them to understand doing things right and on time with desired, well-controlled results is the definition of quality. Again, quality is the successful outcome of the fulfillment of customer requirements – so if management (business or project) is focused on fulfilling customer requirements, then they should be highly interested in quality.

The process descriptions (procedures or standard operating procedures [SOPs]) should reflect the way things are done or are supposed to be done, promoting efficiency and effectiveness. This ensures quality results are delivered.

Organizations can promote a quality culture through seeking agreement and gaining enterprise alignment of harmonized processes. This enables them to perform actions and initiatives in a reproducible and effective way.

Q: What are the key factors to consider when merging two contract research organizations (CROs) from two different countries? (Harmonization of the QMS and all SOPs, etc.) 

• Conduct a thorough assessment of each site’s QMS
• Align and compare each QMS to the parent company
• Evaluate the organizational setup as well as the cross-functional disciplines

If both CROs are doing similar tasks, they can develop and roll out a more common QMS across both sites. If they are different in their functions, organizations can conduct strengths, weaknesses, opportunities, and threats (SWOT) and task analyses to help drive the QMS selection as they harmonize and align both processes into one.

Q: What are some of the quality processes for the transition from paper to electronic? 

A: To create a smooth and seamless transition, this process must be carefully designed in a project. There are several factors to consider – most importantly are the many principles of data integrity to apply when, for example, migrating records and data into an electronic system (as well as data originality, true copy validation, etc.).

An evaluation regarding changes in the existing process should be conducted. Based on the nature of the electronic system, processes may change and/or adjusted to account for new requirements.

Consider all relevant equipment and computerized systems and potentially a stepwise inclusion in the electronic QMS developed. Doing it all simultaneously may overwhelm some organizations and quality systems (processes). Overwhelming the system could lead to increased numbers of deviations, which should be avoided at all costs.

Q: I am being tasked to build a “roadmap” of GCLP. What does GCLP entail? 

A: If the GCLP term referenced is interpreted as a combination of good laboratory practice (GLP) and good clinical practice (GCP), then the roadmap needs to include processes covering pre-clinical and clinical development stages. Covering the pre-clinical and clinical stages in development, this also means early inclusion of current good manufacturing practice (cGMP) requirements for any clinical trial material produced. Even at the contract development manufacturing organization (CDMO), the clinical study sponsor must assure oversight.
Creating a compliant QMS and an effective roadmap requires a comprehensive, customized evaluation to ensure fit-for-purpose quality systems at every phase.

Q: Currently in the final stages before organizational implementation, what is your best tip to prepare before launch? 

A: From a quality and QMS perspective, all the processes are already built at this stage. Receiving market launch approval requires completing the preparation for a pre-approval inspection (PAI) and transferring the production process into the area which will produce for market supply. This area needs to operate under full cGMP (manufacturing, quality control [QC], packaging, quality assurance [QA], and logistics).

If product supply is done externally, the product sponsor must assure appropriate CMO/CDMO quality oversight.

Q: What are some important issues that you recommend keeping an eye on during implementation? 

A: After completing the assessment and developing the QMS implementation roadmap, it is especially important to carefully follow the project plan. Many processes may be defined through SOPs. When a detailed process evaluation is done, the organization can then evaluate any changes and proactively address identified issues.

There may be cases when the existing process needs adjustments based on regulatory requirements, and/or compliance issues. In such cases, existing habits or behaviors require change accompanied by the requisite organizational training and communication.

In a good, and effective implementation, there should be flexibility and repeated consideration for adjusting the path, so the new quality systems (procedures) are fit-for-purpose and support the ongoing activities, and not complicate or overly formalize them.

Q: What have been the biggest challenges in implementing QMS? 

A: When a company is already further along in its growth and product development, it becomes more challenging to educate and build the understanding that quality is not a superimposed formalistic bureaucratic system. It’s merely the reflection of the ongoing process descriptions which help propel a company’s success. Additionally, companies at a later stage of development need to “catch up” with building their QMS from the foundation to their current stage of development. In these cases, companies may need multiple quality systems to also fulfill the regulatory requirements.

Q: How often should management reviews occur for startup biotech organizations? 

A: There are probably already organizational or management meetings with development staff (project management meetings) continually evaluating ongoing activities and initiatives. These meetings can easily integrate quality aspects and review ongoing processes for performance. The organization may already track some key performance indicators (KPIs) regarding performance in product development and projects. Those would be the quality systems for review at this early stage.
With more quality processes added, the meeting may vary in terms of meeting time, content, and scope.

If kept separate, a management review can occur on a quarterly basis in earlier stages, moving to monthly while advancing through phases and including more quality systems.

Q: Startups may not have the budget for early implementation of QMS systems, e.g., “well-defined archives” or validated clinical safety databases. Please comment on options for use of “lite” versions of such archives/databases that can be scalable as the company grows. 

A: The first option is to avoid costly, electronic QMS systems at the early stages. A company may implement a paper-based QMS with policies and procedures. These may be archived in folder structures using available file management systems. This may be scaled for company growth, and at a suitable time, could be converted into electronic systems. However, this is not a requirement, and it may not deliver an enhanced level of compliance.

Q: How do you effectively create a quality culture in a fully remote organization? 

A: Working in a remote environment may pose additional organizational challenges. It is important to enhance communication and establish open dialogue and transparent processes. In all communication, the organization needs to demonstrate loyalty to its statements, processes, and procedures. A quality culture relies on trust and understanding, which is achieved through open communication and clear commitment to quality in all aspects (e.g., managing projects, business, and compliance).

Q: Please expand on successful working practices to implement a QMS by academics who are initiating a “startup” company, often with very few people and dominated by academic work standards for organizations and protocols that do not include similar QMS “culture”. 

A: This may be a special situation, yet it may follow a similar pattern as described in the presentation.
Start with an assessment and evaluate the situation of the team and startup. For both academic and early-stage companies, scientific development activities should have a minimum number of procedures to establish. Companies can adapt procedure content to the academic environment and simply reflect the processes as they are supposed to be executed. Such a description may help to align the way things are done and how to conduct research. Future data and record review is better supported – e.g., tasks like writing scientific papers may be more efficient.

Q: When should you start to establish quality metrics? 

A: As soon as quality processes are established, monitor them for performance. Early processes perceived as project management and scientific product development may receive performance tracking. If so, quality aspects may grow organically for the organization and a quality culture is built along with it.

Q: What do you mean by “validation due diligence”?  

A: This is meant for processes when an identified target is confirmed and validated.
The due diligence process may occur when an asset (target, application programming interface [API], or similar) is acquired for further product development. In the process, there is a due diligence evaluation to support the decision.

Q: When do you implement your QMS? If your organization begins at the development stage (virology), then progresses through pre-clinical immunology), to Phases I, II, III clinical, where should you enforce the rules/guidelines of a QMS? 

• You expect processes to be established and followed
• Data is created and may impact decision making in the development process or referenced at a later stage

Whenever defined, adhere to each process, and expect repeated execution for certain tasks. Then, develop and implement your QMS. It should allow for clear process definition, documented description of how to conduct tasks, and archives developed in a manner where data and records are easily organized.

In the case of the example given, the recommendation would be to already have a QMS as any new development process begins.

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