Paul Titley, Managing Director of R5 Pharmaceuticals, part of Aesica Pharmaceuticals, looks at the emerging trends in solid dosage forms and examines what contract manufacturers are doing to meet the changing and challenging demands.
As smaller and more specialty pharmaceutical and biotechnology companies, which comprise two-thirds of the development pipeline, are continuing to struggle in the wake of the recession and face significant capital constraints, many of the oral solids they had planned to research and develop remain on hold. As a result, many companies are focusing on the development of different dosage forms to bridge the gap.
So how are such trends affecting the industry as a whole and how are contract manufacturers adapting to meet these new demands?
As the recession took hold of the world’s economy in late 2008, early stage drug development froze. Companies cautiously restricted their plans for preclinical, phase 1 and phase 2 studies, concentrating their time and capital into ongoing projects and proven drugs that were guaranteed to deliver a return. Since the summer of 2009 the market has begun to recover and service companies are now receiving more enquiries than ever before, but those new enquiries are bringing with them new demands, which contract manufacturers have to adapt to in order to survive.
Pharmaceutical companies are now more cautious about investing in projects, forcing contract manufacturers to work harder and smarter, and prove that their service is attractive and can deliver on target. Clients are also becoming more savvy and demanding when it comes to service provision and contract manufacturing companies are required to show more definite end points, as well as more added value, so that clients know what to expect at every stage of the process.
As such, key players are being forced to restructure their organisation to ensure continuity and sustain profitability. For the contract manufacturer the need to constantly adapt and offer flexible solutions is a key driver in order to maintain a competitive advantage in the marketplace.
Playing it Safe
To ensure sustainability and minimise the risks associated with capital investment, pharmaceutical companies are turning to the development of existing drugs as a safer option in terms of diversifying their existing product range. Trends are emerging in the solid dosage market for different indications of existing drugs, which can offer for example an enhanced efficiency such as a change in dose or concentration, so that instead of taking a tablet three times a day patients can simply take one a day, or an entirely new indication (and possibly dose). Researching and developing new dosage forms is a much simpler process than developing an entirely new product, as companies already have a greater knowledge of the drug and its benefits and these have a proven safety profile, therefore reducing the level of risk on all levels.
Products that have been on the market for a considerable time, are now being viewed from a new perspective and pharmaceutical companies are evaluating their additional benefits and usage and how best to market the existing product in a new format to a new market. A simple example is Aspirin; originally developed and marketed as a treatment for pain, but now also widely used to reduce and treat heart related issues.
Some products are so often prescribed together that it might seem obvious to produce a combination product to enhance market share for both. However the regulatory challenges for these (so called) simple ideas are considerable and these Fixed-Dose Combinations (FDC’s) as they are known are still rare.
Developing different dosage forms of existing drugs such as topicals or injectables has therefore been another option for many companies, but in the long term oral solids will always remain the most popular as they remain the easiest for the patient to take. As such, clients seek out new forms such as extended release formulas or orally disintegrating tablets and are looking at targeted drug delivery systems and novel presentations such as wafers or oral films, alongside the development of conventional dosage forms.
Whether it’s for dementia, arthritis or heart disease that the medication is designed to treat, most patients will be taking oral forms at some stage of treatment. Pharmaceutical companies seeking an advantage may develop smaller tablets, change the shape to make them easier to swallow, dilute or mask the taste, or improve their onset of action. For example, when a patient requires instant relief from streaming eyes due to hay fever or pain from toothache, they want to take something that will work immediately and a fast dissolving tablet should be able to provide it. However they may be more expensive to produce (using new ingredients), require more stages in manufacture and often warrant a license from the inventor, so such forms require a significant period of sustained sales or even a prospective sales increase to be economic. Yet more are showing up in the consumer healthcare market, as these products are faster to gain market penetration and pharmaceutical companies are realising that such forms can often bring a greater and swifter return on investment.
Patents accounting for over 40 per cent of the highest revenue producing drugs in the industry are expected to expire by 2015, meaning that the pressure is increasingly on big pharmaceutical companies to continue to be innovative and create potential new blockbusters. With industry leaders suggesting that the value of these products will reach $130billion, many big pharmaceutical companies are bracing themselves for increased competition and decreased pricing. As drugs are coming off patent much quicker than new drugs are being patented, generic drug production is on the increase. Companies incur fewer costs in copying the generic product process and are therefore able to maintain profitability, but at a lower cost to consumers. Part of the lower cost model is the outsourcing of the manufacture of both the raw drug and the formulated product. It is not only the original patent holder that is looking for the new forms of the product, but also the legion of generic product marketing companies. They too must be cognisant of the competitive market in which they exist.
Meeting New Demands
As these new trends emerge, pharmaceutical companies are looking to contract manufacturing companies to provide them with specialist technologies and facilities to deliver their products. It is to their benefit that contractors can spread the overheads of managing specific suites over several projects, whether that is for steriles, controlled drugs or high containment. Pharmaceutical companies have an extensive portfolio of contract manufacturers to choose from and it is a competitive market. By using a contract manufacturer the pharmaceutical company, whether small, medium, or large, does not have to factor in time for that capital investment which can delay commercialisation and critically extend the time to market.
In response, contract manufacturers are also increasingly broadening their service offering to ensure that they are attractive to the market. In the past, separate companies offered development, drug substance manufacturing, drug product manufacturing or packaging. Some offered more services at the front end (clinical development), others at the back (sales support), so they could manage the whole product lifecycle, but more recently contract manufacturers are selecting new services to ensure they provide a coherent suite services for their clients. A full service offering can mean different things to different clients, as they will have individual views on where the start and end of their process is, but good contract manufacturers should offer a rational overarching service offering comprising a group of services that make sense to their clients.
The evolution of drug development and the use of more potent compounds has made high containment drug manufacturing a key focus for customers outsourcing their products and contract manufacturers need to be flexible enough to respond quickly to this demand. Other specialty services contract manufacturers are offering include new technologies such as GMP spray drying and specialized GMP milling equipment, which can provide unique reasons to choose a partner.
The benefits of developing products from the clinical stage through to final commercial supply with the same partner are likely to become increasingly attractive to pharmaceutical companies. Avoiding duplication and allowing the customer to remain with a partner throughout the process can only increase communication and develop a trusted relationship. A rare differentiator is a contractor that can offer API development and manufacture, alongside that of formulated products. The advantages of coordinated communication between API development and the resulting formulated product, should not be underestimated as the API scale up runs in parallel with that of the formulated product.
About Paul Titley
R5 is a subsidiary of Aesica Pharmaceuticals Ltd. Paul founded R5 Pharmaceuticals in 2006 to provide formulation development of all dosage forms, analytical chemistry, stability testing and GMP services to the global biotech and pharmaceutical industry. The company now has a staff of 50+ of highly experienced formulators and analysts and is widely acknowledged as one of the leading providers of pharmaceutical dosage form development across Europe.
Prior to forming R5, Paul qualified as a chemist during his twenty-five years’ service with Wellcome where he left in 1996 as Head of Worldwide Technical Support. He also worked in business development and senior management for Quintiles, before becoming an independent consultant in 2005 working with clients in India and the Czech Republic. He was then approached by BioCity to manage a new project, which led him to found R5.