Orion GxP consuting

Women in Industry – Inspire Inclusion

Lee — Thu, 07 Mar 2024 09:13:02 +0000

International Women’s Day is about empowering women and the work they do. To strive for a world free from bias, stereotypes, and discrimination. This year, in 2024, the theme for International Women’s Day is “Inspire Inclusion”. It is about the importance of creating an inclusive society where women are valued, respected and empowered to participate fully in all aspects of life.

As a woman, I am very interested in seeing how this is accomplished in the world of business. My name is Lee Maxwell, and I am the Business Manager at Orion GXP Consulting. By day, I manage the business and admin in Orion GXP Consulting, and by night, I am currently studying to be a Criminal Psychologist. I find it very hard sometimes to participate in all aspects of life. Sometimes, when work is busy, I find it hard to have time for family and study; likewise, when assignments are due, family and the house are put on hold for a day or two to complete everything until I can get up to speed and get things back to normal. I consider myself extremely lucky in the work I do in that I have a very supportive family and a very understanding company that helps me juggle everything I have to do each day to make sure it gets completed. Because of this, I always feel valued and respected in all aspects of my work and study.
Here at Orion GXP Consulting, we are very proud to have a predominantly female team, and we asked a couple of members of our team to tell us about what it was like working in the industry as a woman and what their day looked like.

A day in the life of – Kay Flahive

No two days are the same when working as a contract QP/QA consultant with Orion GXP. One day, you could be working on Clinical Trial releases into Europe for an Investigational Medicinal Product. This involves preparing the product specification files, review of the batch records, shipping data, deviations, change controls, etc and liaising with the project manager/sponsor on various quality/regulatory queries. The next, you could be delivering quality-related training, auditing a client site, working on a QMS improvement project, or providing general QA/Reg support on various topics (e.g. technical agreements, submitting a variation to MIA licence), or a mix of the above.

The work I am doing in Orion GXP has allowed me to take the knowledge and skills I have amassed with my industrial experience to date and further build on this as each new situation, project, query, etc arises. As well as the work being very interesting and varied, it is also very rewarding knowing that you are part of the process of assessing new and cutting-edge treatments.

I also love the flexibility and improved work-life balance it provides. I moved from a 5-day week fully on-site role (that involved a 5:30 am rise to avoid traffic in the Jack Lynch tunnel ) to a 4-day week remote role, which allows me to drop/collect kids from school, walk dogs at lunchtime, while still delivering on the client’s needs.

Now, over to one of our UK team members, Nim Tarry!

A day in the life of – Nim Tarry

As an Associate Director and consultant RP/ RPi (in the UK) who works full time, 5 days a week, my clients are at different stages of the processes of WDA(h) licenses in full swing or applications that need submitting. Their needs are different, some may need QMS support, while others need a QM writing from scratch, I may be needed to provide training and auditing support, so no day is the same and it can feel quite crazy.

My role requires me to be flexible and adaptable, and being flexible is great for me, as I can carry out my work so that it fits around my home life too and vice versa, which creates a fantastic work-life balance for me and my family. I am able to take the time when I need it, take a breath and walk my crazy cockapoo puppy. This, for me, is great with the stresses and demands of the role to balance out.

Being a part of the Orion GXP consulting team allows me to feel empowered; things many women would have had to fight for in the past are now just a part of everyday living and working. Being in a world where there is no prejudice for being a woman and a woman at work is a long way away from where women in the past would have been, and the support received at Orion GXP consulting for its workforce of women just re-enforces this.

Thanks so much to Kay and Nim for sharing your thoughts and for being part of our fantastic and growing team!

The role of the Responsible Person for Import (RPi) – Nirmal Kaur Tarry (Q&A)

Charley — Tue, 09 Jan 2024 09:14:18 +0000

Here at Orion GXP Consulting, we can assist our pharmaceutical clients when they need an extra pair of hands, tapping into our network of industry subject matter experts, including statutory roles such as the Responsible Person and Responsible Person for Import.
Rather than having to repeat the checks carried out by the EU QP, which would be bureaucratic and unnecessary, the MHRA created the role of Responsible Person (import) RPi, which enables UK companies to accept EU/EEA QP certification and to import and release under a Wholesale Distribution Authorisation (WDA).

We decided to kick off the New Year by talking to Nim Tarry our Associate Director, Consultant Responsible Person/Responsible Person for Import and our latest hire about the role of RPi and what it entails!

Hi Nim, so how did we end up in a situation where the UK has this different system? Why are there now two paths to approve using either a QP or an RPi?

Hi Charley, essentially due to Brexit (the UK chose to exit the European Union (EU) by vote) when the UK became a third country, the need for the RPi arose in the UK and this was defined by the MHRA via guidelines including The Human Medicines Act 2012. The QP is still very much needed to release batches that have not been manufactured or tested in the UK/ EU. However the RPi will release batches received from a country on the approved countries list which have EU QP certification providing all RPI checks are complete.

What exactly is the point of the separate RPi role and how does this differ from the Responsible Person?

The RPi performs a release of product that is imported in to the UK, under a companies WDA(h) from countries on the approved list. The RPi ensures that QP certification is complete and in order, alongside ensuring all temperature data is available and within specification The RP cannot legally do this.
The RP is however needed for products sourced from NI for wholesale purposes. Products manufactured and released in the UK that are supplied under the WDA(h).

How did you end up becoming an RPi and what should the readers of this article know before considering training for this role?

Having worked in industry and being on a WDA(h) licence for some years, I felt that this was an area I would like to develop in to and work in. There are pre-requirements that an individual must fulfil prior to being added to the WDA(h) as an RPi, these are defined in a guidance document as follows https://www.gov.uk/guidance/acting-as-a-responsible-person-import. This document goes in to detail regarding experience needed, qualifications, professional bodies and eligibility and suitability.

What does a typical day look like for an RPi?

No day is the same, there are times when I will perform RP duties, as you mentioned Charley I am an RP and RPi and other times when a delivery requires RPi release all the required checks are completed. Some days there are a number of deliveries other there aren’t so many. But in between the deliveries there is the management of the QMS, ensuring training is up to date. All individuals working on GDP matters are adequately GDP trained. The management of any outsourced providers such as 3PLs, this all lies with the RPi also. Ensuring regular quality meetings are held to discuss new suppliers and customers. Occasionally there may be issues which require non-conformances, or complaints, or returns all of which need input from the RP/RPi.

When you first started as a consultant RP/RPi, what surprised you about consulting and how this differed from working in a full-time industry role?

I think the biggest thing was the flexibility it gives the client and also myself, and it was so interesting to see the various stages that each client was at in the process. There are clients that are at the initials stages of needing to submit an application and then there are clients that are fully established needing on-going support.
Also, when you are working full time with one company you don’t see all the other ways of working and the stages that companies may be at. As you are only on that companies journey.
I now have clients at all stages of the process and it makes it very interesting no client is the same. Each requires my support in different ways.

What do you think the pros and cons are for hiring a fulltime RP/RPi vs engaging a consultant and what circumstances works best for each?

Depending on the business model and the expected volume of deliveries it may be necessary to have an individual full time. However if this isn’t the case the company will be paying for an RP/RPi that is not fully utilised and it may be more cost effective to use a consultant.
A consultant will also have the experience having worked with a number of companies, I feel this gives the consultant RPi/RP a wider breadth of knowledge that can be applied.
The downside is there will be days the consultant may not be available when the client may wish, however depending on the nature of the issue this could be worked around.

Thank you so much, Nim, for giving us your insights and for all the hard work you do for our clients!
If you wish to avail of our services and are interested in the leanest path to getting pharma products into and onto the UK market, please email us at charley@oriongxp.com or call the office at +44 (0)203 4750375.

Why hire a consultant to solve a business-critical quality compliance issue?

Charley — Tue, 17 Oct 2023 16:50:42 +0000

If you’re facing a quality or regulatory compliance issue that’s critical to your business and needs to be resolved quickly and effectively, you may be wondering whether to hire a consultant or handle it yourself. While both options have advantages and disadvantages, hiring a consultant can provide many benefits that can help you overcome your challenges and achieve your goals. In this article, I’ll discuss some of the key benefits of using consultants and how they can add value to your organisation.

What is a Consultant and What Do They Do?

Quality and Regulatory Consultants are experienced professionals who provide specialised guidance, advice, and assistance to clients regarding assuring the quality safety and efficacy of the medicinal product or medical device. They are typically renowned for their extensive expertise and experience in their field, which allows them to competently analyse, diagnose, and solve complex problems using their many years or decades of experience. Typically, consultants offer recommendations, propose solutions, and help businesses implement necessary changes. In a regulatory compliance scenario, this may be in areas such as strengthening the QMS, training staff, managing risk, and making complex decisions on release of material or equipment.

Hiring a consultant can provide your business with several advantages, helping you resolve critical issues more effectively and efficiently. Often, it is more cost-effective to hire a consultant instead of using internal resources or hiring additional permanent employees.
Some of the main benefits of hiring a consultant include:

Unique Solutions

Consultants can offer you various benefits, including unique solutions that are customized to achieve compliance with minimal impact to cost or labour. They can fine-tune their approach and methodology to suit your needs, budget, and timeline. Additionally, consultants can bring fresh perspectives and insights that your organisation may not have considered to help you view your problem from a different angle and discover new opportunities to achieve the same quality and compliance goals.

Speed

One of the advantages of working with consultants is their ability to deliver quick results within a reasonable timeframe. Unlike internal resources that may be distracted by their everyday work or have additional duties, consultants can remain laser-focused on the task at hand. This ultimately ensures that the project is completed on time and to a high standard. The consultant will be solely dedicated to the project at hand, with the motivation to complete it quickly and effectively. Consultants are already equipped with the necessary skills and knowledge, eliminating the need for training or background reading to address your issue.

Knowledge of Best Practices

Consultants also offer their expertise in best practices and effective solutions within the industry. Because consultants often work with multiple clients across different product types and different regions, they will have knowledge of dealing with different competent authorities and regional and global approaches, which they can bring to your unique problem or project. This can help you to stay compliant and achieve your goals of continuous improvement of your quality system. They can use their experience and expertise to help you identify gaps, level up your performance, and implement the right solutions.

Specific Skills

The next benefit of using consultants is that they can add specific skills to your organization that you may not have internally. For example, if you have never had to deal with a recall or defect notification or you have a warning letter or non-compliance statement due to non-compliance with a new regulation, you can hire a consultant who has the relevant skill set and experience to assist you. This allows you to access talent without hiring, training, or retaining staff and the longer your team works with the consultant the more they too will learn about the issue or regulations.

Creating Change

One of the most important benefits is their ability to help drive positive change within the organisation. Change can be a daunting task, requiring the implementation of new processes, technologies, and cultural shifts. Consultants can assist with this process by bringing in fresh perspectives, innovative ideas, and proven methodologies. Consultants can ensure smooth day-to-day operations by providing ongoing support throughout the stages of the consulting process. This includes monitoring progress, identifying any issues or roadblocks, and adjusting as necessary to stay on track. By doing so, consultants can help organisations achieve their objectives and successfully navigate the challenges that come with bringing about the various changes that the consultant recommends for remaining in or regaining compliance.

As you can see, hiring a consultant can offer you many benefits that can help you solve your business-critical quality compliance issue more efficiently and effectively. Consultants can provide you with unique solutions, speed, knowledge of best practices, specific skills, and creating change.
If you need help with maintaining compliance and ensuring your products adhere to the highest quality, safety and efficacy standards, Orion GXP Consulting has a network of highly professional consultants who can jump straight into your issue and provide immediate and cost-effective solutions.
Please feel free to reach out to us if this is a service you need – info@oriongxp.com or call +353(0)71 98 10101

How to Prepare for a Pharmaceutical Customer Audit

Charley — Sun, 01 Oct 2023 21:39:17 +0000

So, you have received a request for a supplier qualification audit; great! This has probably been the culmination of months of discussions and negotiations by your business development teams to get to a proposed contract stage and ready for qualification.

The process of evaluating the quality and compliance of your company as a supplier or subcontractor that provides products or services to the new pharmaceutical customer is a pharmaceutical customer audit. Typically, the quality assurance unit of the new pharmaceutical customer or an external auditor hired by them conducts these audits. Depending on the contract and the risk level of the supplier or subcontractor, customer audits can be very in-depth multi-day team audits through to single-day and even partial days with some level of remote assessment for lower-risk activities.

Completing a customer audit is vital for the customer to ensure that your company, as the supplier or subcontractor, meets the pharmaceutical company’s specifications, requirements, and relevant regulations and standards. These audits can also highlight potential risks, best practices, and areas that need improvement.

Getting ready for a customer audit can be difficult, particularly when it’s unexpected or with little notice. Nonetheless, by organising and getting ready appropriately, you can effectively pass a customer audit and display your dedication to quality and compliance. In this article, I explore some of the steps to follow for getting ready for a customer audit.

It is common enough for the audit host team to feel some anxiety during the auditing process. However, it’s essential to take a moment to breathe, ground everyone and remember that auditors usually aren’t trying to catch you out. Their goal is to ensure that you have what it takes to make their products and adhere to regulations to complete the subcontracted work.

Step 1: Understand the scope and who is auditing you.

The first step in preparing for a customer audit is to understand the scope and purpose of the audit. The audit scope defines what aspects of the supplier’s or subcontractor’s operations and processes will be audited.

It’s essential for the customer to clearly communicate the scope and purpose of the audit to their supplier or subcontractor beforehand, ideally in writing. You should then thoroughly review and understand the scope and purpose of the audit and ask the customer any questions or seek clarification if needed before the audit. Find out the auditor’s name and reach out within the organisation to determine if anyone has been audited by them before. It’s a good idea to find out if the auditor has any specific areas of expertise as it can help to know what areas will need to be well prepared and if there might be any weaknesses going into the audit.

Step 2: Plan for the audit

Next, you should assign roles and responsibilities for the customer audit, including designating a person or team to coordinate and manage audit activities. It is important to ensure that everyone participating in the audit is fully informed of their duties and obligations, as well as the objectives and parameters of the audit. Additionally, it is best practice to offer appropriate education and guidance to staff on communicating professionally and efficiently with the auditor.

Step 3: Collect and review the documents requested.

The third step to prepare for a customer audit is to carefully review all requested documents and records to ensure they are ready for auditing. It’s essential to ensure that all relevant documents and records are accurate, complete, up-to-date, consistent, easily accessible, and compliant with regulations and standards. The auditor may request documents and records, including the Quality Manual, Site Master File, Procedures, validation reports, non-conformances, CAPA records, risk assessments, and batch records.

Before handing over any documents or records to the auditor, it is essential to review them thoroughly and ensure they are approved by authorised personnel. Any changes made should be documented with justification, and all deviations must be investigated with a robust root cause analysis. Corrections should be implemented with proper verification, and corrective actions must be completed with an evaluation of their effectiveness. If suppliers or subcontractors play a crucial role for the potential customer, it will be necessary to ensure all suppliers have been adequately qualified and that appropriate agreements are in place.

Step 4: Create an atmosphere of integrity and Professionalism on the day.

It’s crucial to make an excellent first impression, and it’s equally important to have senior management present during the opening and closing meetings to reinforce your company’s dedication to the end product’s quality, safety and efficacy. Additionally, don’t forget to prepare anyone interacting with the auditor to prepare them for any questions that the auditor may ask.

When the auditors visit your facility, they will almost certainly want to meet the team responsible for the work. They will also review the training files and may wish to speak with the trainee. If your team can confidently and comfortably communicate with the auditor, it will reflect positively on the company.

During the audit, it is best to be honest if you or another team member are unsure of an answer. It is easy to detect when someone is trying to conceal their lack of knowledge. Inform the auditor that you are unsure and require advice from the Subject Matter Experts (SMEs) before responding. In most cases, they are understanding and will provide sufficient time for you to give a response.

Step 5: Be ready at the close-out meeting.

When undergoing an audit, you will likely receive findings from the auditor. It is a rare occurrence to have no findings at all. It is important to note that each auditor may have their own interpretation of the same regulations, which could result in varying recommendations from audit to audit. If you feel that a finding is not in line with the regulations and you are compliant, it is appropriate to voice your interpretation and push back. However, you MUST remain professional and courteous and be prepared to see both sides if the auditor goes on to explain their interpretation of the regulations. Remember, this is a customer you are trying to build a long-term relationship with, and you may need to assess whether it is worth getting into an argument if the potential CAPA will not place an undue burden. Likewise, the customer will respect your knowledge and competence if your pushback is justified, and it isn’t unheard of for auditors to see the auditee’s point of view (where justified).

Step 6: Promptly follow up with Robust CAPAs where required.

If you receive major findings, it may not be the end of the world. Treat it proactively as an opportunity for improvement, and be prepared to discuss how to resolve the problem. Follow up with any immediate CAPA plans and leave the auditor with an understanding that you will rectify the issue.

A CAPA plan is a concise document describing how you will address and resolve any nonconformities or deficiencies identified during the customer audit. A corrective action plan should include the following elements:

- The description of the non-conformity or deficiency;
- The determined root cause of the non-conformity or deficiency;
- The corrective action to be taken to eliminate the non-conformity or deficiency;
- The preventive action to be taken to prevent the recurrence of the nonconformity or deficiency;
- The responsible person or team for implementing the corrective action and preventive action;
- The target date for completing the corrective action and preventive action.

You should prepare the corrective action plan as soon as possible after receiving the customer audit report, preferably within a week or two at the most. You should also present the corrective action plan to the customer and the auditor for review and approval and follow up with them until all nonconformities or deficiencies are closed.

Maintaining clear communication and adhering to action plans demonstrates your proactive approach and proficiency in resolving issues promptly and competently. This, in turn, instils confidence in the auditor and assures your client that their decision to approve your facility is well-founded.

Preparing for a pharmaceutical customer audit is crucial for ensuring quality and compliance in the industry. By following these steps, you can effectively and efficiently demonstrate your capability and reliability to the customer and improve their satisfaction. A successful audit can also increase business opportunities and enhance your reputation.

At Orion Consulting, we can assist with preparing for that critical customer audit. We have a team of GXP audit professionals with experience managing bespoke audit requirements to assess technology transfer capabilities and manufacturing technologies or to conduct an initial assessment or mock inspection of sites to GMP, GLP, GCP and GDP regulations.

We have assisted many clients in getting ready for qualification audits, and we can review the company readiness and assist during and after the audit with document preparation and CAPA planning.

If you need immediate assistance or have a critical or urgent audit that you need to prepare for then, please get in touch with us at: info@oriongxp.com or phone +353 (0)7198 10101

The Importance of a Well-Designed and Fit-for-Purpose Pharmaceutical Quality Management System

Charley — Sun, 17 Sep 2023 16:27:37 +0000

The pharmaceutical industry is responsible for developing, manufacturing, and distributing life-saving medicines, making it one of the most complex and highly regulated sectors. However, the industry constantly faces challenges, including product quality, regulatory compliance, and customer satisfaction concerns. To overcome these challenges and ensure the safety and efficacy of their products, pharmaceutical companies need to implement a well-designed and fit-for-purpose quality management system (QMS).

We sometimes get approached by new clients looking for licence authorisations to allow them to enter new markets or change their business model and expand into new types of pharmaceutical operations. There are usually different authorisations required, and before any application can be made, the QMS and organisational structures need to be put in place for each one, as well as an inspection completed by the competent authority in the country of operation.

A Quality Management System (QMS) is the first step, which comprises all of the policies, processes, and procedures (SOPs) to guarantee consistent and high-quality production of pharmaceuticals. A Quality Management System (QMS) should be tailored to the unique requirements of the pharmaceutical company and regulatory standards. It must encompass all product lifecycle stages, including research, development, manufacturing, distribution, and post-marketing surveillance.

A good QMS will help achieve the following important objectives:

Ensure that products manufactured or distributed according to the QMS meets all identity, strength, purity, and stability requirements.
To comply with the relevant laws and regulations that govern the pharmaceutical industry, such as FDA 21 CFR Part 210 in the US and Eudralex Volume 4 in the EU.
To continuously monitor, evaluate, and improve the performance and effectiveness of the QMS.

There are some dos and don’ts when writing a pharmaceutical QMS that will ensure the organisation’s success once licencing is obtained and the QMS is used.

The first and most important thing is to clearly define the scope and objectives of the QMS and align them with the organisation’s business goals and regulatory requirements. The easiest way to do this is to meet with everyone likely involved in each new process and thoroughly map out the desired method, including responsibilities, objectives and critical tasks or steps. This will then ensure that the SOP will broadly match the expectations of the most critical stakeholders.

It’s essential to create document templates for each document type and utilise built-in styles and formats to ensure consistency and readability. It’s also recommended to use clear and accurate language, avoiding jargon, abbreviations, or acronyms that may not be familiar to all readers.

It is also essential to avoid using redundant or unnecessary language in the written procedures. Additionally, it is essential to avoid using vague or ambiguous terms such as “as appropriate”, “as needed”, or “where possible”, which may lead to confusion or inconsistency in implementing the QMS. Better to use “shall”, “will”, or “must”.

The next step is to implement the QMS processes and then monitor and measure the QMS performance to verify the effectiveness and efficiency of the QMS processes. Typically, this will be through ongoing management review and metrics evaluation, as well as internal audits to verify the conformity and compliance of the QMS processes. The organisation must compare the actual performance of the QMS processes with the expected performance based on established quality objectives or an annual quality plan. They also need to identify gaps, weaknesses, or opportunities for improvement in the QMS processes.

Finally, there should be mechanisms for continuous improvement; typically, this will require implementing robust corrective actions or preventive actions (CAPA) to address any gaps or potential nonconformities in the QMS processes. The pharmaceutical organisation must implement improvement actions to enhance the QMS processes based on feedback, suggestions, and best practices.

A well-designed and fit-for-purpose QMS is essential for the pharmaceutical industry to ensure the quality of its products and the safety of its customers. A well-designed Quality Management System (QMS) should encompass all business processes, personnel duties, and standards, including manuals, policies, and procedures. This system guarantees that regulated operations are conducted in a controlled manner, resulting in the production of safe, effective, and high-quality products. At Orion GXP Consulting, we collaborate with clients to create customised QMS documentation that caters to their proposed facilities, products, and business processes. Afterwards, we follow up to ensure that the written procedures are properly trained and implemented at their manufacturing and distribution facilities for optimal performance.

Orion GXP Consulting has developed pharmaceutical Quality Management Systems for our many satisfied clients, from small virtual wholesalers to large pharma multinationals. If you would like to chat about your QMS or licensing requirements, please reach out.

email: info@oriongxp.com or call +353 (0)7198 10101

Preparing for a Pharmaceutical Regulatory Inspection: The Benefits of a Mock Inspection

Charley — Sun, 03 Sep 2023 21:58:02 +0000

A regulatory inspection by the local competent health authority is a critical event that can have a significant impact on ongoing operations and is designed to indicate the level of quality, safety, and efficacy of the products manufactured by a pharmaceutical company. The inspections are each government’s way of ensuring that the medicines produced, imported, or distributed by that company are safe, effective, and of high quality for the patients who use them. Regulatory inspections will be conducted at regular intervals by health authorities, such as the US Food and Drug Administration (FDA), here in Ireland by the HPRA, or in the UK by the MHRA. They aim to determine if the company complies with the applicable laws, regulations, and guidelines.

A health authority inspection can be routine or can be triggered by an event, such as a complaint, a recall, or a serious adverse event. In any case, the inspection itself can be stressful and challenging for the company being inspected. This is particularly true if major deficiencies or non-compliance are revealed, which can lead to warning letters, fines, sanctions, or even product withdrawals.
It is crucial therefore for pharmaceutical companies to be fully prepared for regulatory inspections and to be able to demonstrate processes that are in control, methods and procedures that are compliant and products that are safe. To achieve this, conducting a thorough mock inspection beforehand is one of the most effective methods.

A mock inspection is a practice run of a regulatory inspection, which imitates the process, scope, and objectives of a real inspection. It is most usually conducted by senior quality staff or external consultants who possess experience and expertise in regulatory affairs and quality assurance.

A mock inspection can help the company to:

Identify and correct gaps or weaknesses in the pharmaceutical quality system, processes, procedures, documentation, and records.
Evaluate and improve readiness and performance in responding to inspectors’ questions, requests, and observations.
Train and coach, its staff on how to interact with inspectors in a professional and confident manner.
Evaluate and improve the organisation’s commitment to quality and compliance.
Minimize the possibility of unfavourable results and conclusions during the inspection process.

A mock inspection can be conducted at any time, but it is especially recommended in the months leading up to the actual or anticipated regulatory inspection.

When conducting a mock inspection, it is important to thoroughly assess all relevant aspects of the company’s operations. This includes examining the quality management system, organization and personnel, facilities and equipment, materials management, production and process control, packaging and labelling, laboratory control, validation, change control, deviation management, complaint handling, recall management, adverse event reporting, product stability, and data integrity.

So what are the differences between a mock inspection and a regular audit?

A mock inspection and a supplier or quality systems audit are both methods of evaluating the compliance and quality of the company in question, but they have some differences.

A mock inspection will attempt to simulate a real competent health authority inspection (e.g., FDA/HPRA) and is more often conducted by specialists with the aim of preparing the company for the upcoming inspection. They will assess the company against the specific directives or federal codes within the scope of the company’s licenced operations. Whereas a supplier or quality systems audit will be a systematic and independent examination of the company’s quality system by a member of the audit team of a prospective customer or their appointed consultants to determine whether the company conforms to pre-defined criteria and will instead tend to focus on specific products and services that are to be provided by the company rather than directives or federal codes.

In order to be ready for a real inspection, it’s important to conduct a fair, unbiased, and constructive mock inspection. During the mock inspection, it’s crucial for the inspectors to provide honest feedback and recommendations for the company to improve. The company should take the mock inspection seriously and be ready to take prompt corrective actions.

Although a mock inspection does not guarantee success in the actual inspection, it is an excellent chance to learn from errors, enhance performance, and boost confidence. A pharmaceutical company can achieve its quality objectives and enhance product safety and efficacy for patients and public health by conducting a mock inspection. By using a consultancy company to help them prepare for a regulatory inspection, a pharma company can benefit from the expertise, experience, and perspective of the consultants, and increase their chances of passing the inspection with minimal or no findings. This can save time, money, and reputation for the pharma company, and ensure that their product or process meets the regulatory standards and expectations.

Sometimes lean organisations just do not have the capacity to handle all their audit or mock inspection requirements and will leverage outside organisations and contractors to help facilitate some or most of their audit and assessment programs. Selecting the right partners is critical, and we can help you with this.

Here at Orion Consulting we have built a team of GXP audit professionals with a vast breadth of experience in GMP inspections and audits of global active pharmaceutical ingredients and finished dose manufacturing sites across the world. We also have experience in managing bespoke audit requirements to assess technology transfer capabilities, manufacturing technologies, or to carry out an initial assessment or mock inspection of sites to GMP, GLP, GCP and GDP regulations.

For each assessment, we work with our clients to discuss their individual needs, review the company or site to be assessed and determine the capabilities to be assessed and regulatory standards to be applied. We then work with our client to ensure the audit is booked and to identify the best auditor for the type of assessment.

We can work closely to identify the right expert for your audit requirements, whether supplier assessments, storage sites, testing laboratories or internal or external manufacturing sites.

If you need an immediate assessment of your audit program or have a critical or urgent audit that you need to address then, please contact us at: info@oriongxp.com or phone +353 07198 10101

How the Windsor Framework will affect the supply of medicines in the UK and Ireland

Charley — Thu, 31 Aug 2023 11:23:23 +0000

The MHRA has published new guidance over the past few months on labelling and packaging following the agreement on the Windsor Framework. For those who are not aware, the Windsor Framework is the latest agreement between the UK and the EU which aimed among other things to finally address all the challenges posed by the Northern Ireland Protocol on the supply of medicines into Northern Ireland.
The Northern Ireland Protocol as it stood had meant that medicines entering Northern Ireland from Great Britain needed to comply with all EU regulations, which was leading to both regulatory and supply chain roadblocks with the potential to impact patients.

So, what does the new Windsor Framework mean for Medicines supply?

The Windsor Framework, which was announced on 9 June 2023, sets out a long-term solution that will allow medicines to be approved and licensed on a UK-wide basis by the Medicines and Healthcare products Regulatory Agency (MHRA), without requiring separate authorisations from the European Medicines Agency (EMA). This will enable medicines to use the same packaging and labelling across the UK, with a clearly legible ‘UK only’ label to indicate that they are not for sale in the EU. These measures will come into effect on 01 January 2025, subject to written guarantees from the UK to protect the integrity of the EU internal market.

The measures described will commence from 1^st January 2025 as follows:

- All medicines in Northern Ireland currently under scope of the EU Centralised Procedure will be authorised by MHRA for the UK market, and current GB-only licences will be converted to UK-wide.
- These products will only be sold in the UK and will not be available in Ireland or elsewhere in the EU.
- Packaging for all UK-wide products must have a “UK Only” label.
- These UK-Wide packs will not include the 2D barcode safety feature required under the EU Falsified Medicines Directive (FMD).
- Joint EU/UK packs will no longer be allowed to enter the supply chain.

The Windsor Framework is expected to have significant implications for the supply of medicines in the UK and Ireland, especially for those products that are currently shared between the UK and the Republic of Ireland. The loss of safety features for medicines in Northern Ireland will mean a common pack across the UK and will reduce costs and complexity for manufacturers. However, it also means that medicines in Northern Ireland will not benefit from the enhanced protection against counterfeit and falsified products that the FMD provides. More significantly however, it will prevent joint packs between the UK and the Republic of Ireland. The Windsor Framework also stipulates that new novel medicines authorised by the EU (centralised medicines) will not be permitted on the Northern Ireland market, and only those authorised by the UK authorities will be allowed.

This means that patients in Northern Ireland will not have access to some innovative medicines that are available in other parts of the UK and in the EU, unless they are also approved by the MHRA.

The Windsor Framework requires that all medicines on the Northern Ireland market must have a ‘UK only’ label on their packaging, to indicate that they are not for sale in the EU. This will mean that some manufacturers with PLGB products will need to switch to a UK-wide product with the ‘UK only’ label on all UK packs. This would require some reorganisation for manufacturers and would affect parallel trade of medicines between different markets, as products with a ‘UK only’ label would not be allowed to enter or exit the EU.

So what exactly are the new ‘UK only’ Label requirements?

- The label may be presented anywhere on the outer packaging.
- The text must be conspicuous/clear and must be at least size 7-point font.

- The “UK Only” statement can be applied via a sticker for a limited time of 6 months until 30 June 2025. After this date “UK Only” must be printed directly on to the packaging.

- The application of a ‘UK Only’ sticker will need to be completed prior to certification by a Qualified Person (QP). The stickering must be completed by the site named on the Marketing Authorisation (MA) prior to QP Certification.
- Packs released prior to 1^st January 2025 can remain without the need to use a sticker or over label.
- MHRA will need to be provided with an updated mock-up of the outer packaging. This can be done as part of any variation (except Type IA variations) or through the usual self-certification route applicable for artwork updates.

FMD/Serialisation features:
From the 1^st January 2025 the EU Falsified Medicines Directive (FMD) will no longer apply to Northern Ireland, and features on packs may be removed. Existing 2D barcodes, serial numbers etc. on already release packs can remain in the market. Anti-tampering features are however encouraged to remain on UK packs.

Early Implementation:
The “UK Only” label can be applied to the outer packaging before the 1st January 2025, but on packs with serialisation features.
PLGB licence packs with “UK Only” cannot be made available to the market until the 1^st January 2025.
PLGB Licences will become a UK-wide licence, further MHRA guidance will follow on the necessary steps to implement this.

The Windsor Framework is intended to provide a long-term solution for the supply of medicines into Northern Ireland, while respecting both UK sovereignty and EU single market rules. However, it also poses significant challenges and changes for manufacturers, distributors, regulators, healthcare providers, and patients in both the UK and Ireland. Stakeholders should prepare for these changes well in advance of their implementation date and seek further guidance from relevant authorities (i.e. the MHRA) as it becomes available.

Orion GXP Consulting’s team of GXP experts is ready to help you review your licencing and distribution needs. If you need support, please get in touch with us today to ensure your products are safe and all regulatory requirements are in place.

Get in touch today by emailing info@oriongxp.com or by calling us IRL – 07198 10101 or UK – 0203 475 0375

What are the requirements for setting up a GMP warehouse in the EU?

Charley — Sun, 27 Aug 2023 21:36:22 +0000

Over the past couple of years, we have been asked on a few occasions to assist clients with new green-field pharmaceutical import and distribution operations in the EU. Ireland is often the location of choice due to being in the EU, the business-friendly environment, low tax, English language, and a strong pharmaceutical sector presence. Where the client wants a high level of control, they may decide to set up the Site of Physical Import (SOPI) themselves. Setting up and qualifying a GMP warehouse is usually the first step before licencing, as it will need to be listed on the authorisations at the later stages before launching in Europe. The warehouse needs to be ready to store and distribute the client’s medicinal products in compliance with good manufacturing practice (GMP) standards, and this will require several commissioning and qualification activities to ensure the quality, safety, and efficacy of medicines when they arrive and are stored at the facility.

Setting up a GMP warehouse in the EU requires the following:

An up-front assessment to identify the critical aspects of the warehouse design, operation, and maintenance that may affect the quality, safety, and efficacy of the medicinal products stored there. This includes ensuring adequate storage space, security measures, temperature and humidity control, lighting, ventilation, and sanitation.
Set up all required equipment designed, constructed, maintained, and cleaned to protect the products from contamination, deterioration, or damage.
Installation of air handling units and building management systems to designate, manage and control the GMP areas as controlled ambient, i.e., maintained at 15-25°C and below 65% relative humidity and maintained at 2-8°C for refrigerated storage. This will be connected to a system to control this and alert if the temperature is not maintained.
A validation showing that the warehouse consistently performs according to the required specifications under normal operating conditions. This would require testing and commissioning of air handling and temperature mapping of the facility under normal operating conditions.
Then, the warehouse is included in an application for an MIA to the local EU competent authority, i.e., the HPRA in Ireland. The authorisation specifies the activities and types of products that the warehouse is authorised to handle.
Finally, the warehouse will have to undergo an inspection by the competent authority to verify its compliance with GMP standards. This will then be recorded in the EudraGMDP database and used by customers to confirm the authorisation and compliance with GMP.

Thermal mapping is often one of the main exercises; this is a process of taking measurements across a standard period (usually a typical working week) and recording regular temperature and humidity data points within the storage area under differing conditions to identify any hot or cold spots that may affect the product quality. Thermal mapping must be carried out by experienced personnel using calibrated equipment, and they should follow a predefined validation protocol that sets out the scope, acceptance criteria and responsibilities for the thermal mapping.

Typically, there will be three different temperature mapping exercises in the first year of operation of the controlled warehouse locations. The first will be once the warehouse is ready for use before any product is introduced, and this will then be followed by Summer or Winter mapping once the warehouse is in use and the product has been introduced. This will allow the authorisation holder to verify worst-case conditions at extremes of hot and cold outdoor conditions. A risk assessment will determine the number of mapping sensors to use and their locations. It must include any areas where products are stored, pallet racking, packaging areas and temporary storage locations such as hold and reject locations. The conditions during the thermal mapping should encompass all normal operations, such as loading and unloading, short power outages, and door opening (loading bay roller doors).

The output of the temperature mapping should be a report that should include:

An executive summary covering the findings,
Details of the temperature data,
Identification of any hot or cold spots,
Recommendations for corrective actions or improvements,
A conclusion on whether the warehouse meets the predefined acceptance criteria.

Before applying for the MIA authorisation, at least the empty mapping should be complete, and all other aspects of the requirements for the MIA should be inspection-ready. This includes the Pharmaceutical Quality System or PQS. The PQS should cover all aspects of the site operations, such as organisation, personnel, premises, equipment, documentation, production, quality control, outsourcing, complaints, recalls, self-inspection and risk management. The quality system must be based on the principles of quality assurance and continuous improvement and must ensure that the warehouse complies with the relevant legislation and guidelines. As a GMP company, you need qualified and competent personnel responsible for implementing and maintaining the quality system and performing the activities detailed in the PQS.

Setting up a GMP warehouse in the EU is not easy, but it is essential if you want to import, release and distribute medicines safely and legally. By following the GMP guidelines and obtaining an MIA, you will ensure that the products imported and stored meet the quality and safety standards expected by customers and regulators. Having your own compliant warehouse rather than outsourcing will also give you a competitive edge and enhance your reputation in the pharmaceutical market.

Orion GXP Consulting’s team of GMDP experts is ready to help you review your warehousing, licencing and EU launch strategy. If you need support, please get in touch with us today to ensure your products are safe and all required authorisations are ready for a trouble-free EU launch.

Get in touch today by emailing info@oriongxp.com or by calling us IRL – 07198 10101 or UK – 0203 475 0375

ICH Q3D, what is it, and how is it used in the Pharmaceutical Industry?

Charley — Fri, 21 Apr 2023 11:02:43 +0000

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has in place a guideline, ICH Q3D, to assess the risk of excessive exposure to elemental impurities in pharmaceuticals. ICH Q3D covers 24 elements, including arsenic, cadmium, lead, and mercury, which are known to be toxic and can have adverse effects on human health. The guideline itself provides all the background safety information as well as a series of tables and calculation methods which can be used to determine if there is an excessive risk of overexposure to these toxic elements as a result of patients taking daily doses of our medicinal products.
This guideline is based on the principles of quality risk management, and it takes into account the potential exposure to elemental impurities, the toxicity of the impurity, and the sensitivity of the patient population.

By reviewing potential exposure, ICHQ3D assessments look at the likelihood that humans or animals may come into contact with these elements in drug products entering the body through injection, ingestion, inhalation or absorption through skin contact. In simplest terms, we determine this by assessing all potential exposure risks in the formulation and manufacturing process. We calculate the maximum potential exposure using control measures and limit specifications from all process water, equipment, constituent excipients and Active pharmaceutical ingredients to determine a calculated maximum potential daily intake. Where control limits may not be in place, there would be a requirement to test representative samples using an appropriate method such as ICP-MS to determine the actual levels present in either a constituent or in the final drug product. The result would be a calculated or measured maximum potential daily intake.

A review of the toxicity determines the ability of these elements where present to then cause harm when they enter the subject and this will consider factors such as genotoxicity, carcinogenicity, neurotoxicity and teratogenicity. ICH Q3D also considers the sensitivity of the patient population, and factors such as age and pre-existing conditions may be taken into account and lead to safety limiting factors used in the subsequent calculations. From this, we determine a maximum Permitted Daily Exposure (PDE) limit for each of the elements required using the tables in the guideline and based on the route of administration of the drug. We then compare the calculated or measured maximum potential daily intake of each element and determine if it exceeds the Permitted Daily Exposure limit.

ICH Q3D uses a control threshold which is defined as a level that is 30% of the established PDE in the drug product. This control threshold is typically used to determine whether additional risk mitigation controls may be required. If the calculated or measured maximum potential daily intake for a particular element is less than the 30% control threshold, we may conclude that no further control measures or mitigation is required. Where the calculated or measured maximum potential daily intake is less than the permitted daily exposure, but still greater than the control threshold, then we may need to consider additional controls. This may be in the form of periodic testing or a change of raw material to a grade or source with a lower risk of exposure to the element in question.

Where the calculated or measured maximum potential daily intake is in excess of the permitted daily exposure limit for an element, then we must consider steps to reduce this, such as multiple changes to the grades or sources of raw materials or even reformulation of the drug product.

The ICH Q3D guideline has become an essential part of regulatory compliance in the pharmaceutical industry and it provides a standardised approach for evaluating the presence of toxic elemental impurities in drug products, drug substances and excipients.

Pharmaceutical companies must comply with ICHQ3D during the drug development process and throughout the product lifecycle. This requires an investment in analytical testing, quality control and risk analysis measures to ensure that the product meets the standards set out in the guideline. Also, changes to manufacturing processes and alternate suppliers require continual reassessment of product ICH Q3D assessments to ensure that the levels of elemental impurities in the product remain safe for patients. From a patient perspective, ICHQ3D is a positive development, as it ensures that pharmaceutical products are safe and free from harmful impurities.

Orion GXP Consulting has a team of Risk Management and ICH Q3D subject matter experts ready to help you review your elemental impurity program and assist you in ensuring it is on track. If you are in any doubts, please contact us today to ensure your products are safe and that the risk of exposing patients to potentially harmful impurities are appropriately assessed and controlled.

Get in touch today by emailing info@oriongxp.com; or by calling us IRL – 07198 10101 or UK – 0203 475 0375

Focus on: Pharmaceutical Supplier or Contractor Qualification Audits

Charley — Wed, 29 Mar 2023 15:39:08 +0000

As we progress into spring 2023 and the audit season gets into full swing and following our successful Qualistery webinar on the topic, we wanted to highlight and talk about auditing and supplier qualification in some more detail, as this is one of the core services that we offer.

There are many different types of Audits for different situations, and each has its own approach and requirements, which we will delve into in more detail below. There are also overall program requirements, such as having a mechanism for feeding new qualification audits into the program and a periodic risk assessment of all suppliers to ensure we are selecting the correct qualification or audit process.

So… First things first, what is an audit?

An audit in the pharmaceutical industry is where we complete an independent and systematic examination of the company we wish to qualify and where we establish if the activities performed by that supplier or contractor are in alignment with all current industry standard regulations.

There are many different types of audits. Our industry usually employs a combined approach to look at the Quality Management System and the product and processes to ensure our material or product is manufactured according to set requirements. For a new supplier or contractor, an initial risk assessment should be completed to determine the appropriate level of qualification and mitigation actions required. This should be governed by the change control and NPI processes within your organisation. This will ensure that the supplier/contractor is onboarded and qualified using a systematic approach while at the same time protecting the product and, ultimately, the patient.

What type of audit should we complete?

For the initial qualification of new API suppliers or new contract manufacturing sites, the criticality will usually necessitate an in-person audit of the site to properly assess the facilities, organisation structure and processes at the site being evaluated.

For the lowest risk suppliers – A desktop audit where a data pack is reviewed with a short follow-up meeting might be appropriate, for example, for a manufacturing aid or simple excipient like talc. A remote audit might be suitable for a chemical excipient or unprinted packaging supplier, and this could be necessitated if the supplier does not allow in-person full-day audits. Then a single-person in-person audit would be appropriate for higher-risk suppliers like API, printed packaging, functional excipients, or outsourced services (so examples here might be. capsule shells, sterilisation, micronisation, etc.). Finally, for critical risk suppliers like entirely outsourced end-to-end manufacturing processes or upstream/downstream biologic processes, then a multi-day team audit would be appropriate in this situation, and this will need to include the QP (or person responsible for release if outside the EU) and possibly the RP if holding and distribution are being completed.

Who should complete the audit?

Your organisation must ensure that any auditor you use is qualified to assess the potential supplier. Also, they should have experience in the manufacturing process and regulatory standards that the supplier or service provider will be evaluated against. For example, a junior QA team member would only audit an aseptic process if they have a sterile manufacturing background. There should be appropriate experience, a lead auditor qualification or robust internal training, and one or more accompanied audits with a previously qualified individual or team. Finally, most of the regulatory standards require that the assessment of the auditor and their CV is retained on file, either with the audit report or the change control used to introduce the supplier. This is particularly important if an outsourced contractor or sister company auditor is used where it may be difficult later or in a regulatory inspection to justify why that person was acceptable to use.

What about Virtual Audits and when are these appropriate?

These are sometimes referred to as remote or distance audits, and they came to the fore during the Pandemic in 2020. While they can be appropriate in many situations where risk is deemed low such as for routine surveillance of established suppliers, they may not suit all situations. For example, if you are contracting out a critical process or setting up a new warehouse that will be acting as the main site of physical import and storage for GMP importation then certainly for a first audit, it would be expected that this would be multi-day and onsite.
If you do consider that the risk level allows for a remote audit, then you should ensure that you set this up for success. You need to ensure that a remote data room is set up to allow you to see all the documentation as and when you are ready to view it while at the same time protecting the auditee company’s intellectual property rights and confidentiality.

Technology will be the key to successful remote audits; you will need to have the filesharing capabilities set up well in advance and tested, and the auditee site should reassure you that they will have the camera and internet bandwidth to allow for virtual tours of the facility. Do not be afraid to insist on this as these companies would have had to have this in place for their health authority inspections during the pandemic years so there is no reason why they cannot accommodate this now.

Sometimes lean organisations just do not have the capacity to handle all their audit requirements and will leverage outside organisations and contractors to help facilitate some or most of their audit programs. Selecting the right partners is critical, and we can help you with this. Orion GXP Consulting has a panel of highly competent GMP, GDP and GCP lead auditors including QPs and RPs with decades of experience in this field.

We would be happy to review your program and either assist you in streamlining or help with audits to keep your qualification program on track.
Get in touch today by emailing info@oriongxp.com; or by calling us IRL – 07198 10101 or UK 0203 475 0375.