“Key Strategies for Enhancing GMP Compliance”- 12 Top Tips for Leaders and Qualified Persons

Article By Philip Rose, Independent Consultant for EPiC

Whether you work for a gold-standard site or one that needs to improve its GMP compliance, at some point, you will need to influence people to move compliance in the right direction. You may have joined a new company that is not where you would like it to be, identified risk areas with your site, or had adverse inspection findings.

I’ve been to several hundred sites around the World and have seen those QPs and leaders who stand out and inspire; they are commonly at sites that have good compliance or are moving in the right direction, which isn’t a coincidence. So, what makes those leaders so influential?

Here are my top tips for influencing compliance at your site:

1. Lead by example

This is by your actions, your behaviours and your attitude. Model the behaviour you want to see in others by doing it yourself. As a QP, don’t be the QP who approves everything because it’s easier. If you want to see good standards at your site, demonstrate them and maintain them personally.

When I’ve seen leaders I’ve looked up to and aspired to be like, this is the trait I’ve respected the most. It sets the standards but is also highly motivating for a workforce. Particularly for sites that have had issues. If they see a leader who is doing the right thing, upholding the standards of the site, and buying into the site, this will bring others with them.

With this trait, make sure the promises you make you follow through with, even the small ones. If you don’t, it is a lot quicker to lose respect than to get it back.

2. Be seen

You can’t hope to influence people and compliance if you aren’t there. Traditional QPs and leaders were chained to their desks and thought by the companies to be batch releasers. Modern QPs aren’t like this, and modern companies know how much more value a QP can bring if they aren’t just at their desks.

Leave your desk, or better still, move your desk to the factory. Be known in the factory, QC laboratories, warehouses and engineering departments.

This is visible leadership and demonstrates that you are present, engaged and actively involved with your teams and the site. It also shows you are interested and available.

If people know you, and that you are there, there’s a lot more chance that you can influence things which are going on.

With remote ways of working, this is more difficult, but it is critical if you want to be a great QP or leader.

3. Keep up to date

There have been more changes to legislation and guidance over the last few years than I can previously remember, particularly as we exited the EU with things like the Windsor Framework and with updates such as the revision to Eudralex, Volume 4, Annex 1. It makes sense that if you want to know your and your site’s responsibilities that you need to keep up to date with these updates. Use the resources available to you, such as conferences, forums and notifications services. Use your peers, network and join interest groups.

4. Know your processes

Make sure that you know your systems: your quality systems, production systems and your products. Know your dosage forms and your product portfolio. Importantly, know the risk points for these. Know where these risks exist for your products and processes.

Along with this, know your licenses and importantly that, what you are doing is operating within them.

Also, and importantly, know what is going on at your site and within your company. Know what is going well and what isn’t working so well. Know where you are understaffed or where there is inexperience in the team and link that back to the risk points.

With this knowledge you will be in a safer place. You will know your risks and be able to start tackling them. You will also be valued and be able to mentor your team and influence your company to where the risks exist.

5. Be curious

As QPs or leaders we often think we are meant to know everything. Don’t ever assume this is the case and keep that curiosity going. Those people that do think they know everything rarely do and are often quite dangerous as a result.

Ask lots of questions and keep learning. I know that I am constantly learning every time I go to a site. In order to influence compliance, we need to keep this curiosity and learning going, it’s how we find new ways of doing things. Those new ways may be different but also may be easier and potentially more compliant than the ways we may have today.

6. Listen

Listen to your team, your peers and your management team. You are doing this to understand their concerns and also their motivations. When doing this, put yourself in their shoes, even if what they are telling you doesn’t seem important to you, it is important to them, so make time to listen. By doing this, you will gain their respect, and that will allow you more opportunity to influence.

Importantly, it will also allow you to understand more and more of what is going on with the company. It allows you to understand more of the risks and challenges that you might not have identified otherwise.

Make sure you make time to listen to your team and that you do actually listen. Be present; leave your computer and phone behind.

7. Mentor, develop and encourage your team

As a QP or leader, you have a lot of knowledge and experience. If you can impart some of this to your team, they will grow and benefit. Not only will they grow and look up to you, but they will also be able to help you by taking some of the burden but also by influencing the wider company.

If the team and the company understand the “why” they will often be more compliant. This is always a much more effective approach than just telling them how to do something without any understanding behind it.

If you develop, mentor and build your team they will listen, respect you and help you with compliance along the way. You will almost certainly learn things from them along the way too.

8. Ensure your pharmaceutical quality system (PQS) is functional (and being used)

If the PQS isn’t being used then you can’t be compliant. As Michelle Yeomans has detailed in a previous “Top Tip” session, the MHRA commonly have given significant observations around failing quality systems and sometimes at the “critical” category.

So how can we do this?

Performing internal audits or self-inspections of the systems to review them and how compliant they are, is a good starting point. This is a regulatory requirement so should already be part of your processes.

Also, walk the areas (or better as mentioned above, you’ve already moved your desk to production). With these walks look at: are the systems being used and does this reflect what you are seeing? Are there deviations that aren’t being raised? Have changes occurred that you can see which haven’t gone through the change control system?

Another approach is to review the metrics you have. What do the figures look like and does it show that the systems are working, adequately resourced and when they aren’t, are they given the priority they need? With metrics it is often necessary to go one step further. How are the metrics designed and are they capable of showing us when things aren’t working, or are they themselves actually influencing the compliance – in the wrong way? This isn’t a new concept, the idea of metrics driving culture and compliance has been around since before I started in the industry, but at a lot of sites we haven’t moved very far with the concept. There are sites where they still have targets on the maximum number of deviations raised per month. What usually happens in this case is that, that number will be raised and no more. The other issues still may be happening but just aren’t put through the system. I much prefer trends being used as metrics rather than absolute figures. This way we can see which direction things are going in. Feel free to reach out to us if you would like a more in-depth review of your metrics.

Review your metrics and change them if you need to. You want a system which shows you how well your facility is operating in a useful way so that you can do something with it.

9. Get Involved

You are not going to be able to influence compliance unless you become part of the management team. Make sure you are part of the management review meetings and not just on a distribution list. Make sure that you have a voice in the forums within the company and that you are heard.

As an attendee at the meetings, you can make sure the meetings are useful and relevant. You can make sure that the focus is on those things which are important and where influence for compliance is needed.

10. Know when to ask for help

We all need help sometimes and knowing when you can’t do it on your own is vital. Sometimes the task is too big to do it on your own or you just need a second opinion. Sometimes you might even be completely stuck so rather than just leaving it, reach out and ask for help.

I have been contacted by people I’ve worked with at sites where they have significant issues, we can usually find a way to solve the problems or at least start to tackle them.

I often have to ask for help or second opinions on things. I will often reach out to other members of the EPiC team to ask for a second opinion or if I don’t know the answer to something. It goes back to the part about constantly learning. None of us knows everything and so knowing when we don’t know is very important.

Understand your strengths and weaknesses and don’t be worried about saying “I don’t know”.

Have a support network. This is very important and particularly when we are remote or travelling a lot. Have people both inside work and outside work who you can bounce things off. Nobody knows everything or can do all jobs on their own, and we all need support sometimes.

11. Be prepared to say “no”

 Although saying yes to everything is easy and largely stops conflict or challenge, it’s definitely not always in the interest of the patient – or the company. Sometimes as both QPs and leaders we need to be prepared to say no or stop.

To influence compliance sometimes we need to make those difficult decisions and saying no, can be part of that. However, it is often a last resort and shouldn’t be the only way we look to influence.

12. Finally – do the right thing

The final advice I would give to anyone in a leadership position is to do the right thing. Sometimes it can seem very lonely when we do this and I personally have had some sleepless nights as a result, questioning, “am I actually right?” and “why am I the only person thinking this?” Down the line though, you will remember why you did it and will know it was the right thing to do.

Additionally, you will also be influencing people, both those more senior and those more junior than yourself. People will look up to you and respect you when you show courage and make difficult decisions.

Remember, wrong is wrong, even if everyone else is doing it.

To summarise, being a QP or leader is a great role and a privilege to be given those opportunities in companies involved with pharmaceuticals. But both come with a lot of responsibility, both legally to the patients, as well as to the company and those people looking to you for leadership.

It can often be difficult and lonely, but if done correctly, with passion and the right attitude, it has a real opportunity to influence people and the company’s compliance.

Get in touch if you need further support with GMP compliance.

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

“Transform Your Training”-5 Top Tips for Implementing an Effective Training Program

Article By Vicki Pike, Operations Manager for EPiC Auditors

Training is essential in the pharmaceutical industry for several key reasons. Proper training helps maintain high standards of product quality and safety. Well-trained employees are better equipped to identify and prevent errors, ensuring that the products meet the required quality standards and are safe for patient use. Well-trained staff can perform their tasks more effectively, reducing waste and improving overall operational efficiency. Training also ensures that employees understand and adhere to GMP/GDP requirements, which is crucial for maintaining compliance.

The Eudralex GMP guide requires training for all personnel involved in production, storage, control labs, and other roles affecting product quality. This must include basic and role-specific training for new recruits, with ongoing training and periodic effectiveness assessments. Similarly, GDP mandates training for all personnel involved in wholesale distribution activities to ensure they are competent and experienced before starting their tasks. Training records must be kept, and effectiveness periodically assessed and documented.

Unfortunately, training deficiencies, such as overdue or incomplete training and failure to follow SOPs, have led to significant regulatory actions, including referrals to the MHRA Compliance Management Team (CMT) and Inspection Action Group (IAG). These issues are often part of broader systemic failures, which, although not cited directly as a training deficiency, inadequate training is a root cause or contributory factor.

During the EPiC Virtual Symposium on 28 November 2024, we held a round table discussion on GMDP training, including refresher training. Here are our top tips for implementing an Effective Training Program:

1. Tailor Training to Roles: Develop training plans specific to each job role, considering responsibilities and required experience. Use job descriptions and SOPs to identify relevant tasks and ensure everyone receives appropriate GMP/GDP training during induction and on an ongoing basis.
2. Effective Training Delivery: Choose the most effective training methods based on the role’s responsibilities. Options include:
   • reading SOPs, when awareness of the activity is only required
   • e-learning, can be used to pull out the key aspects of a procedure
   • instructor-led training (classroom or virtual), to be used when a role has direct responsibility for an activity
   • on-the-job training is best for practical demonstrations and coaching.
3. Understand the ‘Why’: Ensure training materials explain not just what to do, but why it is done that way. Understanding the reasons behind tasks helps employees remember and comply with procedures and understand the implications of errors.
4. Refresher training: Regular management reviews of the Quality System can identify adverse trends to plan topics for GMDP refresher training. Consider using real life examples of issues that have occurred at your own site for the basis of discussions and exercises, to make refresher training as relevant as possible to your teams.  Also consider changes to regulations and new legislation. Stay informed about industry trends and inspection findings from MHRA, EMA, and FDA, and use resources like blogs, newsletters, free webinars, symposia, and forums.
5. Interactive and Engaging Training: Make training interactive to promote engagement. For GMP/GDP refresher training, use a mix of shorter sessions throughout the year rather than one long annual session. Tailor training to the audience and include opportunities for questions and clarifications.

By following these top tips, companies can ensure their GMDP training is effective, relevant, and engaging, leading to better compliance and performance. 

To assess the effectiveness of training, please see our previous post EPiC Top Tips – Assessing the Effectiveness of Training

Get in touch if you want to know more about how EPiC can deliver targeted, engaging training on a variety of topics.

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

5 Top Tips for Implementing Effective Quality Risk Management

Article By Michelle Yeomans, Operations Manager for EPiC Auditors

Quality risk management (QRM) is an integral part of GMDP that strives to protect patients by applying a scientific and practical approach to decision-making for different aspects of pharmaceutical quality throughout the product lifecycle.

The ICH Q9 QRM Guideline is referenced in Chapter 1 of EU GMP and reproduced in Part III of the guide and is intended to provide guidance on the principles, and examples of tools for QRM that can be applied to different aspects of pharmaceutical quality.

Following the Revision 1 update of ICH Q9 which became effective in July 2023, EPiC have been providing bespoke training and supporting clients as they assess and update their own PQS procedures in line with the changes to make QRM activities more effective and value adding.

ICHQ9(R1) provides multiple examples of potential applications of QRM, and If you have not done so already, we recommend you review the training materials on the ICH Q9 webpage https://www.ich.org/page/quality-guidelines and follow our top tips for effective QRM:

1. QRM application – QRM can be applied anywhere there is potential risk across the business and across a product’s lifecycle. In applying QRM, it is important to ensure that patient safety and product quality considerations remain front and centre, as patients are putting trust in the decisions you make. QRM cannot be used to justify bad practice and non-compliance with GMP requirements.
2. Risk Review – Be proactive and develop mechanisms to prompt reviews of existing risk profiles and control measures as your knowledge and experience increases. For example, set aside time at Quality Management Review meetings to review risk registers, review risk assessments associated with specific manufacturing processes, perform a review of engineering activities to confirm that planned preventative maintenance is on track and equipment is performing as expected, periodically review supplier performance and changes to confirm existing risk ratings are appropriate.
3. Adopt a QA mindset – Design your processes to deliver a quality output rather than relying on problems/defects being detected at the end of the process. Provide training in the tools and techniques to the people involved in QRM activities and consider using experienced facilitators for more formal QRM processes.
4. Think about the people involved – subjectivity can directly impact the effectiveness of risk management activities and the decisions made, so it is important to be able to recognise and control subjectivity, bias, assumptions, and mental shortcuts. This can be achieved by ensuring that risk questions are clearly defined, appropriate QRM tools are applied, and by being objective and evidenced based when assessing data and proposed control measures.
5. Apply critical thinking – Critical thinking requires us to actively engage our brain to be able to work out complex problems. In working through the risk assessment, risk control and risk review phases of QRM, think clearly and rationally to understand the logical connection between ideas. Use the Q9 QRM toolkit to provide a systematic approach to identify, analyse, and solve problems rather than using intuition or instinct, but be prepared to question ideas and assumptions rather than accepting at face value e.g. is the tool fit for purpose, does the output seem right?

Effective and proactive QRM can enable better, more informed, and timely decisions throughout the product lifecycle, and we hope that our top tips will provide you with some useful ideas on how to further enhance your QRM processes.  

Get in touch if you want to know more about our bespoke QRM and critical thinking training.

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

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

“Keep Calm and Be Prepared” – 5 Top Tips for Inspection Readiness

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/