Quality management is a crucial element in any operations. However, it is especially important for regulatory affairs professionals in regulated industries such as pharmaceuticals and medical devices, as well as in fast-moving consumer goods sectors (FMCGs) like food and cosmetics. Quality assurance provides the basis for market approval, helping prevent quality lapses that could trigger compliance actions or endanger public safety.
These lapses may lead to:
- Product withdrawal or recall
- Costly litigation
- Damage to brand and company reputation
- Personal consequences for an employee (civil or criminal) if due to negligence or misconduct
When we talk about quality management, there are three key elements:
- Quality Control Generally speaking, this is reactive and aims at identifying quality lapses in end products (or services) and their precursors. It answers the question: Are we meeting specifications?
- Quality Assurance This is a proactive, structured and methodological system encompassing the whole manufacturing or service processes. It is preventative in nature, and aims at incremental improvement of processes, leading to a higher quality product or service. It answers the question: Is everything we do right in preventing quality lapses? It takes in regulatory aspects, corporate policies and internal or external quality audits. [1]
- Risk Management This proactively identifies risk points, monitoring these and responding where change is required. Risk mitigation should be part of your overall quality assurance methodology and practice.
The bottom line is that you must have robust quality assurance in place that leads to improvement in safety and compliance, while maximising return on investment in the product.
Regulatory Compliance
Depending on the industry, product and market, your product and your processes must comply with specific regulations, including GMP and regulatory body-specific guidelines (e.g. FDA), and you would be well-advised to comply also with non-binding guidelines and voluntary regulations. Just some examples of regulations and guidelines are FDA 21 CFR Part 210 & 211 (cGMP for Pharmaceuticals), FDA 21 CFR Part 820 (medical devices), ISO 13485 (medical device management systems), FDA 21 CFR Part 11 (electronic records), and ICH (International Council for Harmonisation) Q8 (international best practices in pharma, and quality by design), Q9 (risk management) and Q10 (continuous improvement based on ISO 90001 and GMP. [2]
How QA Minimizes Regulatory Risks
Some examples of how QA minimizes regulatory risk and increases compliance are:
- Promotes proactive adherence to regulations and guidelines such as those outlined above, instead of capturing lapses after they occur.
- Integrates a risk-based approach in QA (e.g., IHC Q9, or ISO 14971 for medical devices).
- Promotes document integrity and compliance (ALCOA+; Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, and Available).
- Promotes root cause analysis (RCA) and robust Corrective and Preventive Actions (CAPA) to prevent quality deviations and lapses recurring, and to improve processes.
- Takes in third-party oversight (e.g., in the supply chain).
- Involves training and competency programs
- Through internal audits and self-inspection for risk mitigation
- By change control and validation oversight (prior to implementation)
- It helps ensure cross-functional regulatory alignment
- Reduces the risk of 483 observations from the FDA (regulatory violations and deficiencies) or critical findings following an inspection (EMA).
By understanding regulations and implementing risk reduction at every step of the process, you can avoid warning letters, batch recalls, non-compliance with specific market requirements (e.g., leading to recalls in that market) and delays in pharma clinical trials, submissions, approvals and product marketing.
Best practices for Quality Assurance to reduce errors and inconsistencies
This is obviously a very broad field as quality assurance must run through your entire processes. In the pharmaceutical industry, that ranges from drug discovery development, testing and clinical trials, submissions and approvals, through to labeling and packaging, as well as marketing. Here we will look at best QA practices for document verification, which includes labeling and packaging, but also other upstream and downstream documents.
- Knowledge Management
- Establish people and processes for understanding the relevant regulations, recommendations and guidelines. This provides the foundations for compliance.
- Monitor changing regulations in the specific markets. It’s a tall order in a global company, but essential.
- Put in place implementation plans for cascading and escalating regulation changes. Everyone must know their role and responsibility for achieving QA on an ongoing basis.
- QA is an integrated and holistic process. This applies to knowledge sharing too. There is no room for outliers.
- Understand methods and tools (see Risk Management below).
- Risk management
European Medicines Agency (EMA) is just one of the regulatory bodies with dedicated methods and tools for risk management. [3] These cover the whole spectrum, but it makes sense to carefully read all the methods and tools and ask yourself where you can apply them to your RA area. For example, a hazard operability analysis (HAZOP) may apply to production parameters and process safety, but it also suggests a useful brainstorming technique using guide words. Risk ranking and filtering is another useful tool. Make a list of the risks and give these a score (also give them, for example, a location in the workflow where they occur). For proofreading labeling and packaging, this might involve ranking and filtering possible errors, along with their severity. A proofreading mistake on a dosage or an illegible barcode would be very high.
Annex II of the EMA document gives potential applications for quality risk management. See here. [4]
Bringing together points 1 and 2, you need to foster a culture of regulatory learning and understand high-risk points.
- Leverage technology for best practices
It is important that you plan for the future. Your quality systems as well as technical systems must be scalable and able to cope with growth. That means having workflow systems that can be integrated into larger workflows, your SOPs, and are future-proof. Just one example is the rise of electronic labeling (e-labeling). This has placed a strong focus on barcode verification. Online and physical labeling must be consistent, and technology must be able to verify both types easily. It also means automating your proofreading processes, which provides greater accuracy and helps you avoid the pitfalls of manual proofreading.
- Maintain useful resources
In a global environment, that means maintaining style guides (visual and textual) for the different labeling and packaging language versions, style sheets, corporate nomenclature, and so forth. We cover this and other points for proofreading regulatory documents in more detail in an article here. [5]
- Evolve with the industry
Industry associations and industry events exist for good reason – companies, functions and RA professionals have common purposes and can learn from each other. Organizations such as the Regulatory Affairs Professionals Society (RAPS) have events and courses, which are perfect opportunities to learn from others and gain a perspective of your own practices.
- https://www.iso.org/quality-management/quality-assurance
- https://www.qualio.com/blog/quality-requirements-for-pharmaceutical-companies
- https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-guideline-q9-r1-quality-risk-management-step-5-revision-2_en.pdf
- https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-guideline-q9-r1-quality-risk-management-step-5-revision-2_en.pdf
- https://www.schlafenderhase.com/shblog/proofreading-regulated-documents-in-pharma
