Ramprasad Kaparaboyena, regulatory affairs manager/QP for pharmacovigilance, Gaelic Laboratories discusses how to expand market reach.
Gaelic Laboratories
Have you been thinking about expanding your market? If the answer is yes, you’re not alone – geographic expansion is an important strategy for any pharma company, and it’s something most companies are continuously striving to achieve. Access to new markets allows you to tap into new customer bases and increase market shares, while helping to spread your revenue sources and reduce the impact of individual market fluctuations. Establishing a strong presence in more than one region can also enhance your company’s reputation as a reliable global partner, helping to improve your competitive edge and achieve sustainable growth.
However, as pharma companies expand their reach globally, numerous challenges – especially those pertaining to regulatory approvals – need to be addressed. Ramprasad Kaparaboyena, Regulatory Affairs Manager at Gaelic Laboratories, has recently managed the expansion of several product lines, with the objective of launching them in new global regions. Here, he shares some of the challenges that his team faced, and offers guidance on how to best overcome them, to help other companies interested in expanding their markets to new parts of the world.
What is the strategic rationale for you to expand your market now?
Our vision has always been to be a significant player in the generic pharmaceutical industry through the manufacture and commercialisation of our own Beta-Lactam products, as well as the provision of contract manufacturing services. Since our inauguration four years ago, we have focussed on the UK and EU, and we recently established an infrastructure in the United Arab Emirates (UAE) that gave us access to the emerging Middle East market. More recently, our acquisition of Athlone Laboratories means that, across the two companies, we now provide antibiotics to customers in the EU, UK, Middle East, North Africa, Canada, Australia and Russia.
The acquisition of Athlone Laboratories effectively doubled our global footprint overnight, but it did more than that – it gave us the opportunity to expand the markets of the legacy products of both companies. This is why it is strategic for us to expand our market now – we have the means, and we have the opportunity. However, to properly leverage those channels for both companies, we need to make sure that our products are registered and approved for the regions in which we want to market them. For example, most recently, we have been focussing on expanding a range of antibiotics for new generic launches in the EU.
Which generic products are these?
We have developed a new portfolio of beta-lactam antibiotic combination products and prepared the associated regulatory dossiers for submission in a number of regions, including the EU, UK, Middle East and North Africa. As antimicrobial resistance (AMR) continues to be recognised as a significant global health challenge, maintaining the availability of established combination antibiotic medicines remains an important priority for healthcare systems worldwide.
Meanwhile, we also had several very old dossiers, dating back to the 1980s, that we acquired when we bought the Gaelic Laboratories site in Clonmel from its previous owners four years ago. These old dossiers are related to long-established beta-lactam medicines that had previously been authorised in the UK. However, due to the ages of the dossiers, they had limited information – certainly not enough to support a new filing in regions like the EU – so when we decided to launch these products in countries other than the UK, we had to upgrade them to make them fit for purpose. The old 1980s dossiers were missing a lot of the standard data required for an EU filing, so we needed to perform tests to generate the missing data; the new EU dossiers were then compiled as brand-new documents.
Overall, it took us about 9 months to complete all the tests and compile the new dossiers. We have now submitted them to the authorities, with a view to first registering them in Ireland and Malta, and we have responded to their initial queries, so we are hoping for approvals within the next 12 to 18 months.
What were your biggest challenges, and how did you address them?
The main challenge stemmed from the fact that the original dossiers had been prepared over 40 years ago under regulatory guidelines that have since evolved. They simply did not meet the standards required for a regulatory submission in the EU today.
We were in the situation of needing to conduct a comprehensive gap analysis to determine what needed to be done to meet guidelines for an EU submission. We were then able to selectively regenerate and rewrite sections to ensure full compliance – particularly within Module 3, which demonstrates the quality of the medicinal product. In summary, we uncovered issues with the API supplier and supporting documentation, process validation requirements, stability data, and minor formulation and excipient-related changes.
We addressed these challenges in five main steps:
Step 1: We worked with the API manufacturer to obtain current documentation, reassess impurity profiles according to ICH Q3 guidelines, and ensure regulatory alignment with present-day expectations. This gave us updated Active Substance Master File (ASMF)/Drug Master File (DMF) information, impurity profiling and GMP status.
Step 2: Manufacturing processes and control strategies described in the 1980s dossiers did not reflect current process validation requirements. Process validation is actually one of the core offerings of our contract analysis services, so we were fortunate to have a high level of expertise in house to help with updating process descriptions, identifying critical process parameters, and generating additional validation data where necessary to demonstrate consistent and robust manufacturing performance.
Step 3: Stability data in the 1980s dossiers had been generated using older protocols –often under conditions no longer acceptable to regulators – so we initiated new stability studies that were ICH compliant, ensured adequate batch representation, and implemented an ongoing stability commitment to support the proposed shelf life.
Step 4: We needed to strengthen the submission with new bioequivalence and bioanalytical studies, to test the bioavailability of our generic products and to demonstrate that they are therapeutically equivalent to branded counterparts. This was supported by contemporary dissolution data, and by making sure that all assumptions were clearly justified and aligned with current regulatory requirements.
Step 5: Since the 1980s, minor formulation and excipient-related changes had occurred, including differences in excipient grades and suppliers. These changes needed to be reflected in the new dossiers, so we reassessed excipient functionality, updated compatibility data where needed, and provided clear justification to demonstrate that these changes did not impact product quality, safety or performance.
How can these experiences be applied to companies looking to expand their own portfolios?
I think that you could generalise our experience by saying that companies need to start by identifying the most suitable region(s) for expansion, and establishing the regulatory requirements for those regions. The next core activity is the gap analysis – recognising any data or information that the new region’s regulatory body requires, but is missing from your current approved dossiers. The importance of this gap analysis really cannot be overestimated, because it forms the foundation for the rest of the process, and outlines the steps you need to take to complete any tests and gather new information for the new dossiers. Getting this part wrong could be an expensive mistake, with significant time and cost penalties, so I would stress the importance of making sure you get your gap analysis right.
Then, you need to either perform those tests yourself, or outsource them to a contract partner, and you need to gather all the missing information before compiling your new dossier according to the new region’s regulatory guidelines. Local regional knowledge can be highly beneficial at this stage, especially in parts of the world with rapidly evolving regulations.
The obvious obstacle to entering any new regional market is regulatory approval, and getting that wrong can be extremely expensive. If you don’t have the relevant regional regulatory expertise in-house, then partnering with another company that understands local requirements, and can offer that support, is a good strategy.