GXP Compliance Challenges

The constantly evolving landscape within the pharmaceutical industry presents a myriad of challenges, especially when it comes to compliance. Across the GXP’s the range of compliance areas is vast and varied.

Your experiences and insights are invaluable to us, as they help us customise our services to better address the real-world challenges you face. Your feedback will shape our future symposia, articles and top tips, ensuring we focus on the areas that will most benefit your operation.

Please let us know which aspects of regulatory compliance you find most challenging and why and share your thoughts and ideas about the compliance hurdles that have the greatest impact on your business.

Getting to the Root of the Problem – 5 Top Tips for Root Cause Analysis & Investigations

Article By Michelle Yeomans, Operations Manager for EPiC Auditors

During my time as MHRA GMDP Inspectorate Operation Manager part of my role involved taking overall responsibility for planning and delivery of the annual MHRA GMP Symposium.

Year on year delegates would request an update on deficiency data and examples of the most cited deficiency topic areas. And year on year the most common deficiency references related to Pharmaceutical Quality System (PQS) and Documentation requirements.

This may not be surprising given that regardless of the size, complexity, and licence type of the site being inspected, all are expected to have a PQS and associated documentation, and at least some of the elements of the PQS will always be inspected.

Is it therefore, inevitable that all GMP inspections are destined to receive a PQS-related deficiency, or is it possible to buck the trend by getting to the root of the problem?

A closer look at the latest MHRA deficiency data from 2019 Good Manufacturing Practice Inspection Deficiencies – GOV.UK (www.gov.uk), and from EPiC’s own experiences of providing pre-inspection and remediation support, shows EU GMP Chapter 1 reference C1.4(xiv) relating to poor root cause investigations and ineffective CAPA as the most frequent recurring PQS deficiency.

Here are our top tips for improving root cause investigations to help you get to the root of the problem:

1. Understanding the meaning of Root Cause Analysis (RCA) – RCA is an activity intended to identify the origin or root cause of the problem. The root cause is the leading cause of the problem and may be made up of several factors. It’s essential to the identify root cause rather than just causal factors. Causal factors are contributing actions that affect an incident/event’s outcome. Removing a causal factor will be beneficial but on it’s own, won’t prevent the problem from recurring.
2. Use an appropriate level of RCA – The level of RCA undertaken should be commensurate with risk and be based on Quality Risk Management (QRM) principles. For a simple problem that presents no risk to product quality or patient safety for which there is an obvious root cause, then a simple correction to fix and document the issue can be justified without the need for RCA and additional CAPA. However more complex or recurring problems that present a potential risk to patient safety and have no obvious root cause will require in depth investigation using RCA tools and may generate multiple CAPAs.
3. Thorough documentation – RCA investigations should be thoroughly documented to demonstrate the risk-based rationale, tools, and critical evaluation of potential root causes and causal factors used to identify the root cause. The information could provide learnings for future investigations or for education and training such as examples for inclusion in GMP refresher training. Having the complete picture to hand will also help you explain in a clear and succinct way what the issues were and what is being done to improve the situation should you need to present RCA investigation data during an inspection.
4. It’s a team effort – RCA investigations should involve as many people as is reasonably practicable. Multidisciplinary teams contribute different knowledge, experience and points of view that are valuable to the investigation as they help to generate a wider range of potential root causes and causal factors and can enhance the application of critical thinking to form a judgement on the likely root cause. Sharing the issues and output from the investigation through team meetings, Quality forums, newsletters etc. can help others learn from the issue which may prevent similar issues elsewhere.      
5. PQS metric targets – Beware of setting targets e.g. 30 days to complete RCA investigations as this may drive the wrong behaviours. Although it makes sense to have a target to complete investigations as soon as possible, speed is not as important as identifying the true root cause. Meeting the target should not prevent a thorough investigation and investigations should not be stopped at an inappropriate level just to meet a target. The PQS should therefore acknowledge that complex investigations may take longer than the target and have a mechanism to document and maintain oversight.

By following these tips, you can turn the inevitable into avoidable by enhancing your RCA knowledge and investigation process, and reduce the likelihood of receiving a PQS deficiency for poor RCA investigations.

Get in touch if you want to know more about our bespoke root cause analysis and effective CAPA training.

Telephone: +44 (0)1244 980544 or email us at enquiries@epic-auditors.com

Pharma Discovery to Distribution

The EPiC team were pleased to be able to attend the UK’s Making Pharmaceuticals Conference 2024 in Coventry from 23rd to 24th April 2024.

The two-day conference covered topics spanning the entire product lifecycle, from discovery to distribution, and it was a fantastic opportunity to explain and promote our services to the conference attendees as well as meet with many of our current and past clients

“Keep Calm and Be Prepared” – Inspection Readiness Top Tips

Article By Michelle Yeomans, Operations Manager for EPiC Auditors

Judging by the number of enquiries we are receiving to provide ex MHRA Inspectors to assist with inspection readiness preparations or remediation activities; it certainly looks like the number of regulatory inspections and supplier due diligence audits are returning to pre-pandemic levels.

Inspections are an opportunity to demonstrate compliance, so when you receive notification of a regulatory inspection (or external audit), keep calm, and use our top tips to help be prepared:

1. Inspection Scope  – Make sure that the purpose and scope of the inspection are clearly understood to help identify the relevant people, products, premises, systems, processes, and procedures that are likely to be involved so that these can all be factored into an inspection readiness plan. As part of the plan, consider the need for inspection awareness training for staff likely to be directly involved, especially if they have not previously experienced a regulatory inspection. Do not forget to check any contractual agreements, as contract acceptors may be required to notify the contract giver of any regulatory inspections.  

2. Compliance Status – Leverage output from the pharmaceutical quality system by referring to performance and trend data from self-inspections, deviations and CAPA, risk assessments, management review, etc. to understand how the quality system and operational processes are performing. This will either give you assurance that you are inspection ready or help identify specific compliance concerns or weakness to enable you to focus on implementing mitigating actions.  

3. Front and Back Room Organisation – Based on the scope and purpose of the inspection, identify and assign appropriate numbers of personnel (including deputies) to act as hosts, tour guides, scribes, runners, back-room staff handling document requests, and subject matter expects (SMEs). Provide some basic inspection preparation awareness training to give an overview of the inspection process and ensure everyone involved has a clearly defined role and purpose. 

4. Turning Negatives into Positives – In completing your inspection readiness plan you may have identified potential deficiencies or there may be questions you would not want an inspector to ask. Encourage the SME’s who know the areas of weakness to practice explaining in a clear and succinct way what the issues are and what is being done to improve the situation. Being able to clearly explain the issues, mitigating actions and CAPA already in place can help to reassure the inspector that a situation is under control and may avoid or reduce the severity of a deficiency.    

5. First Impressions Count – Get the inspection off to a positive start by anticipating likely questions and areas of interest and have documentation and premises ready for inspection.  Prepare a brief presentation covering site activities and confirm any significant changes since the previous inspection (if it is not the first inspection). Check that previous inspection actions have been closed and have evidence of closure to hand. Identify and walk the physical inspection routes and tidy the areas focusing on housekeeping and first impressions. Plan to walk the expected route each day to check on housekeeping, as new deliveries may have arrived, new production batches set up, new teams on shift, etc.   

By following these tips, you can prepare for an inspection by using practice runs and role-play scenarios to practice hosting, tracking, and responding to questions (including the difficult ones!) and help build confidence in being able to demonstrate compliance. 

Get in touch if you want to know more about our mock inspections or bespoke inspection readiness training.  

Telephone: +44 (0)1244 980544 or email us at enquiries@epic-auditors.com

 You may also like to read our Case Study 1: Inspection Readiness: https://epic-auditors.com/case-study-inspection-readiness/

Measuring Success – Top Tips for Assessing the Effectiveness of Training

Article By Michelle Yeomans, Operations Manager for EPiC Auditors

The Covid-19 pandemic led to changes in the amount and delivery method used by Pharmaceutical companies to conduct training. Some companies cut back on training to conserve resources for core functions, whilst others invested in virtual training and e-learning to provide continued development opportunities for their employees. The situation was no different for regulators.

During the pandemic, I was the Unit Manager of the GMP and GDP Inspectorate at the MHRA, and as well as developing remote inspection approaches to ensure a continued level of regulatory oversight, MHRA used the opportunity to dedicate Inspectorate resource to enhance the range of training materials available within the ‘Inspector Academy’ knowledge hub and developed virtual training modules and competency frameworks. At the time, it was a case of adapting to the situation and being innovative in exploring available tools and techniques to identify the “least worst” available option.

Post pandemic, several conferences and training events have now returned to being run as face-to-face events, while others are continuing to offer virtual or hybrid options to maximise accessibility and minimise costs. EU GMP Chapter 2, 2.11 refers to the need for “continuing training” to be given and for its “practical effectiveness” to be periodically assessed. Continuing training is an ongoing process of learning and acquiring new skills and knowledge to help individuals stay updated with the latest developments and changes relevant to their role and industry sector. Continuing training can include self-learning so is not just limited to attending workshops, seminars, conferences, or specialist courses. The key point is finding a way to stay current with industry trends, which will help increase expertise and proficiency and support compliance with GMP requirements. Another key consideration is the need to keep a record to document the training, as training records are routinely reviewed during a regulatory inspection and provide evidence of continuing professional development.

With different training opportunities and formats on offer, it is important to have clearly defined learning objectives and ways of collecting information to determine whether the training provided has produced the desired effect and contributed to the development of the trainee.

Here are our top tips for assessing the practical effectiveness of training:

1. Pre and post-assessments: Conducting assessments, questionnaires, or quizzes before and after the training can help measure the knowledge, skills, or behaviour changes that have occurred as a result of the training. Comparing the scores or performance levels before and after the training provides an indication of the impact of the training.
2. Observations and simulations: Observing participants during or after the training session can help assess their application of the newly acquired knowledge and skills. This can be done through simulations or real-world scenarios to evaluate their ability to transfer the learning into practical situations.
3. Follow-up assessments: Conducting assessments weeks or months after the training has taken place can help evaluate the long-term impact and effectiveness of the training. This can provide insights into whether the learning has been retained, and if it has influenced the individual’s work performance over time.
4. Feedback: Soliciting feedback from trainees and supervisors or managers who work closely with the individuals can provide an additional perspective on the effectiveness of the training. They can assess whether the training has positively impacted the individuals’ job performance, productivity, or overall contribution to the organisation.
5. Performance metrics: Comparing PQS performance, KPIs or Quality metrics before and after the training can yield insights into any improvements or changes in the workplace performance of individuals or teams who participated in the training. An overview of GMP related training completed, and a review of PQS performance to identify compliance improvement topics for inclusion in further GMP refresher training should be included as agenda items at periodic Management Review meetings.

By using a combination of these assessment methods, organisations can gain a comprehensive understanding of the effectiveness of their training efforts and identify areas for improvement.

Please get in touch if you want to know more about our virtual symposia and bespoke in-house training courses.

Telephone: +44 (0)1244 980544 or email us at enquiries@epic-auditors.com