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Mark Copley graduated from the University of Bath, UK in 2000 with a Master’s Degree in Aerospace Engineering. For 8 years he was Technical Sales Manager and product specialist for Copley Scientific’s range of inhaler testing equipment, before becoming the Sales Director in 2009. He is now Chief Executive Officer for the company. Mark is considered a leading authority in testing methods and systems for metered-dose inhalers, dry powder inhalers, nebulisers and nasal sprays; authoring and contributing to more than 50 published articles.
Mark Copley -Chief Executive Officer at Copley Scientific
Here I am sharing an interview with Mark Copley -Chief Executive Officer at Copley Scientific Mr. Copley, what is the vision and focus at Copley Scientific? Copley is the world’s leading manufacturer of inhaler testing equipment and a global provider of test equipment for other pharmaceutical forms including tablets, capsules, powders, suppositories, semisolids, and transdermals. We also provide detergent testing equipment. Last year we established the Copley promise – Innovative, Compliant, Trusted – which summarizes our vision. Through innovation we deliver knowledge-based solutions that answer efficiently to the evolving needs of our customers. Most work in a highly regulated environment so products are certified to the standards defined in the global pharmacopoeias and by regulators. Trust comes from our longevity in the industry – we celebrate our 75th anniversary this year – and the day-to-day reliability and performance of our products. Copley is a stable, well-established company with an enviable track record of delivering smart, easy-to-use testing solutions.
Training at Copley Scientific Limited
Why is inhaled therapy so important? Across the globe respiratory diseases are a leading cause of death and disability, and rates are rising. For example, in India, cases of Chronic Obstructive Pulmonary Disease (COPD) increased from 28.1 million in 1990 to 55.3 million in 20161. Inhaled therapies such as long-acting bronchodilators and corticosteroids are a first line defense for these diseases delivering drug directly to the site of action to ease breathing. Developing effective, inexpensive inhalers is critical to lessen the impact of these illnesses on people’s lives, and on healthcare budgets. However, inhaled therapies also have potential for systemic drug delivery. Inhaled drug delivery avoids the risk of absorption in the gastrointestinal tract and can accelerate targeted onset in certain therapeutic areas. Inhaled sumatriptan is an established therapy for the treatment of migraine that overcomes issues of nausea and gastric statis, delivering fast pain relief with minimal side effects via drug absorption in the nasal cavity2. Vaccines for influenza are also delivered as a nasal spray and there is ongoing research into the viability and advantages of this route for a COVID-19 vaccine3.
What role does Copley Scientific play in the healthcare market?
We provide equipment that enables our customers to test products in line with strict pharmacopoeial specifications and regulatory requirements. For oral solid dosage forms we provide solutions for dissolution, disintegration, friability, and hardness testing. These parameters are critical quality attributes that quantify physical stability, how the product will break down once ingested, and the rate of release of the active drug. “Our inhaled product testing range is concentrated on the measurement of delivered dose uniformity and aerodynamic particle size distribution (APSD). These are critical quality attributes for all orally inhaled and nasal drug products (OINDPs) that quantify the consistency of the delivered dose and likely deposition behavior. Particles less than 10 microns are required for lung penetration with even finer particles associated with successful drug delivery to receptors in the deep lung.”
Copley Scientific Limited, Nottingham, NG4 2JY, United Kingdom
By providing robust analytical data we help customers to make sound decisions from R&D through to QC. An important focus for R&D is solutions that offer better in vitro-in vivo correlation, thereby improving the relevance of cost-effective lab studies, especially in the case of generic bioequivalence (BE). For QC, speed and sensitivity are critical and our equipment scores very highly in this regard with automated accessories reducing variability, notably with the test methods associated with OINDPs, which are manually intensive and prone to operator variability. With a recent drive towards Quality-by-Design (Qbd) in the product development lifecycle, a number of our products have been innovated to compliment this approach.
Why are the Inhalers, nebulisers and nasal sprays so important during this global pandemic to treat COPD and Respiratory issues?
COVID-19 is a respiratory illness so both new and existing OINDPs are a primary focus when it comes to identifying effective treatments. There is evidence that the prevalence of COVID-19 is relatively low in those with chronic respiratory disease suggesting that routine COPD/asthma treatments might offer some protection4. In the UK, trials are underway (Platform Randomised Trial of Interventions against COVID-19 in Older People (PRINCIPLE) trial) to investigate use of the inhaled corticosteroid (ICS) budesonide to aid recovery from the virus and reduce the risk of hospital admissions in the over-50s5. For sicker, hospitalized patients, SNG001, an inhaled (nebulized) interferon beta-1a from Synairgen, is showing promise, with Phase 3 trials now underway6. Trials of nasal vaccines for COVID 19 are in progress in the UK and in India following the recent granting of permission for Phase 1 trials of BBV154 from Bharat Biotech3.
What are the regulatory challenges with developing Inhaled therapy products? How different is it from other dosage forms?
A defining difference between inhaled drug products and other dosage forms is that complex interactions between the patient, the device, and the formulation influence the dose received. This gives rise to substantial variability, between different devices, formulations, and products, and in use. With an OINDP, poor technique or compromised lung function may mean that one patient inhales a much lower dose than another and APSD may also be affected.
Deposition behavior is dependent on APSD but difficult to assess and correlations with efficacy are elusive. We still have much to learn about inhaled drug delivery which is relatively new compared with drug delivery via oral solid dosage forms. The regulatory framework reflects this complexity and the associated risk. US FDA and EMA guidance is relevant across the world, for export reasons, but localized regulatory guidance is advancing rapidly; encouraging the development of generics is a shared goal. The Chinese FDA has recently issued new bioequivalence guidance for inhaled generics and Brazil is also well-established in this area with activities regulated by ANVISA (Agência Nacional de Vigilância Sanitária). Since 2013, the US FDA has released more than 42 product-specific guidance documents for inhaled drugs to support BE studies. That said OINDPs are ‘complex generics’ and achieving approval remains a lengthy and involved process.
How do you stay on top of changing regulations as well as changing techniques and technologies?
This is a major focus for us, and we invest considerable effort in this area.We attend all the regular inhalation conferences, across the globe, and they provide an excellent opportunity to learn about innovative research.
We are also active in key industry groups such as EPAG, the European Pharmaceutical Aerosol Group and IPAC-RS, the International Pharmaceutical Consortium on Regulation and Science. Both draw together experts from across the world to focus on consensus building and best practice in all aspects of OINDP science, development, and manufacture. The ongoing evolution of testing techniques and technology is an essential aspect of this work and the groups play an important role in shaping the methodologies adopted by the pharmacopoeias.
Finally, we learn a lot by listening to our customers. Longevity in the sector means that we have many established, fruitful relationships with scientists in academia and industry and their input on the difficulties and inefficiencies of routine testing is invaluable.
A great example of such collaboration is our work with Professor Finlay at the University of Alberta, Canada whose research underpinned our introduction of the Alberta Idealized Throats, both child and adult, for more clinically representative inhaler testing.
Given the aftereffects of the virus, do you think respiratory treatment through the lungs will need more focus in the healthcare industry?
There appears to be a risk of long-term lung damage from COVID-19 so it is reasonable to assume that respiratory therapies will attract greater attention going forward. Research into the virus will undoubtedly improve our understanding of the lung and this may prove helpful to those working in inhaled drug delivery. More generally, OINDPs are likely to play a crucial role in enabling us to live with the virus over the long-term. Greater emphasis on disease control for those suffering from respiratory illness, to mitigate the worst effects of the virus, may intensify requirements for inexpensive generic inhalers. And there is clearly potential to assess existing therapies for their wider protective potential. For the cohort of people for whom injectable vaccines are not suitable efforts to develop inhalable vaccines are particularly important. Focus on inhaled vaccines may therefore increase as higher proportions of our populations become vaccinated.
A lot of Pharmaceutical companies are involved in manufacturing different dosage forms but very few have products in inhaled therapy, why is this?
Complexity is a major barrier, as previously discussed, but so too is market size, and, for generics companies, the limited number of targets. The value of inhaled product markets tends to be smaller compared to other dosage forms, such as tablets, though Advair®/Seretide® is a notable exception. Delivering annualized revenues in excess of £5 billion up to 20137 Advair was a huge commercial success for GlaxoSmithKline and a key target for the generics sector for many years; approval of the first generic was granted as recently as 20198.
Inhaled products were pioneered by just a handful of large US and European pharmaceutical companies with the resources needed to overcome these barriers, focusing on topical therapies. The changing structure of the pharmaceutical industry has now dispersed this experience pool, across CROs, scientific consultancies and consortia, and into generic pharmaceutical companies. Increased demand, coupled with greater support for BE studies from the regulators, is helping to fuel development by an extended number of players.
What do you foresee for the Bio-pharmaceutical and healthcare Industry in the coming months?
COVID-19 has lifted the profile of the pharmaceutical industry, highlighting its critical value to society. Big pharmaceutical companies such as Pfizer and AstraZeneca have become household names and the collaborative nature of the industry has become evident from the role of BioNTec and Oxford University in developing successful vaccines. The expertise and manufacturing capabilities of countries such as India has also achieved greater global visibility.
It seems highly likely that as result investment in the pharmaceutical industry – both private and state funds – will continue to increase over the coming months and years. At the same time the economic damage done by the virus will intensify the need to control healthcare costs.
Trends towards greater efficiency, a more complete generic portfolio and secure pharmaceutical supply chains may well accelerate as countries shape their healthcare provision in the wake of the pandemic.
K. Paulson et al. “The burden of chronic respiratory diseases and their heterogeneity across the states of India: the Global Burden of Disease Study 1990–2016” The Lancet Global Health, September 2018 F. Granella ‘Inhaled migraine drug therapy: a state of the art therapeutic strategy or just another gimmick?’ https://www.tandfonline.com/doi/full/10.1080/14656566.2018.1524873 R. Kannan ‘The Hindu Explains: Is a nasal vaccine suitable for COVID 19’ The Hindu, Jan 24th 2021. Available to view at: https://www.thehindu.com/sci-tech/health/the-hindu-explains-is-a-nasal-vaccine-suitable-for-covid-19/article33646375.ece D.M.G Halpin et al. ‘Inhaled corticosteroids and COVID-19: a systemic review and clinical perspective’ European Respiratory Journal 2020. Available to view at: https://erj.ersjournals.com/content/early/2020/04/20/13993003.01009-2020 J. Robinson ‘Inhaled corticosteroid added to COVID-19 PRINCIPLE trial’ The Pharmaceutical Journal, 30th Nov 2020. Available to view at: https://www.pharmaceutical-journal.com/news-and-analysis/news/inhaled-corticosteroid-added-to-covid-19-principle-trial/20208609.article?firstPass=false News release ‘Synairgen announces commencement of dosing in its international Phase III study of inhaled interferon beta in hospitalised COVID-19 patients’ Available to view at: http://synairgen.web01.hosting.bdci.co.uk/umbraco/Surface/Download/GetFile?cid=d1270ada-6de4-4f3c-83b0-6ab415ab6985 Revenue of GlaxoSmithKline’s Seretide/Advair Worldwide from 2012 to 2019, by region. Available to view at: https://www.statista.com/statistics/312366/revenue-of-seretide-advair-worldwide-by-region/ FDA news release ‘FDA approves first generic Advair Diskus’. Available to view at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-advair-diskus