Take Responsibility - Quality of products is one of the most important parameters for global players, no matter in which branch, but when it comes to healthcare, it is definitely the most important of all. To ensure the highest standard in quality, it is inescapable to employ only the best experts on the market. Dr. Alen Guy is known as such an expert, working successfully in the excipients sector for several years. In May 2010 he joined IMCD Group one of the biggest distributors in the chemical industry, as technical director of pharmaceuticals. Brandi Schuster and Philipp Praet talked to him about responsibility in pharmaceutical affairs and new trends concerning the pharma industry.

CHEManager Europe: There is no universally accepted standard defining the GMP standards required in the manufacture of excipients. While most European manufacturers adhere to the Voluntary Guidelines, others do not, which puts Europeans at a cost disadvantage. What is your take on the situation?

A. Guy: My take on this situation is that excipient manufacturers should maintain their adherence to quality demands. The pharmaceutical industry will progressively be guided towards or be required to adhere to quality by design standards and principles. To do this they will need to work with excipient manufacturers that are prepared to provide them support that will not be possible or at least more difficult from lower cost environments. Quality costs money. At the moment low-cost suppliers of goods are adhering to minimums associated with monographs. Monographs do not deal with functionality and performance or, indeed, production stability.
Using lower cost excipients will likely force manufacturers to eventually suffer higher costs in managing their production. Operators will most likely see a greater incidence of variances in manufacturing.
By using higher quality materials it should be possible to quantify more important cost savings. These can be enshrined in such areas as operational excellence and go beyond simple bill of goods accounting.
The true cost of excipients in pharmaceutical and nutraceutical manufacturing is very often really quite small. The cost of using a minimal quality excipient at low-cost may eventually run into millions of dollars over the life of a pharmaceutical product.
Excipient manufacturers that operate in high quality management of processes will minimize this impact. It should not be a case of being able to afford high quality excipients as much as believing you cannot afford not to.

How much of the burden of responsibility do distributors shoulder when it comes to product quality?

A. Guy: Ultimately, the regulations in virtually every country state that finished product quality is the responsibility of the company making the finished product. However, distributors typically supply a very large number of companies; therefore their products touch an enormous number of finished products.
Some of these products will undoubtedly reach the shelves of friends and family. A distributor must always ensure its products are neither adulterated or at risk of adulteration. The distributor must believe in the quality and performance of the products it sells. To ignore this would just make it a trader of goods.

What can you tell us about new trends within solid dose formulations and the impact they are having on the industry?

A. Guy: Trends in formulation for solid doses can begin for a variety of straightforward commercial reasons, such as lifecycle management. However, their acceptance by health authorities and patients is created by therapeutic need and adherence improvement - the ease with which the patient can take the medicine.
The continuing trend toward orally dispersible tablets - also known as ODTs - granules or films has been pronounced. It is also true that controlled release doses are increasing in popularity but this area is tightly managed analytically. The orally dispersible trend has developed towards a variety of forms such as ODTs, thin-films, chewables and dispersible granules because of the ease in swallowing these compared with many tablets. I feel that it is orally dispersible forms that are the most challenging; have significant opportunity; and the formulation difficulties are less objective and more subjective than traditional solid dose formulations.

Can you explain why?

A. Guy: In its simplest form, a solid dose tablet is formulated to have minimal tableting quality issues; meet disintegration and dissolution properties that ensure the drug is delivered appropriately and quickly; and be economically viable. Such tablets are normally swallowed with a small amount of water. They are typically produced in high-speed tablet presses, often coated and are relatively simple to make. The performance is based upon strict analytical control with all tablet samples meeting criteria for dose loading, disintegration time and dissolution of the active. This is a very objective analysis, with little margin of error, when carried out in a well-controlled environment.
A solid dose orally dispersible tablet relies upon so much more than a simple tablet that is swallowed. All the necessary requirements for a drug product are still required - dose, disintegration, dissolution etc. - but now the human element appears. Therefore taste and mouth-feel become relevant. This is no longer objective. There comes a need for people that are expert in marketing and consumers to be present in the development process much earlier than otherwise expected. This can be unsettling for formulation and development groups.
The excipient choices for these forms are informed as much by how they taste and feel as to how they flow or compact. It is at this point that formulation gets tricky and formulators need more help. It is arguable that pharmacy is reverting to its roots and that the personal touch is becoming more apparent again.

What kinds of excipients lend themselves to such formulations?

A. Guy: These include polyols, sugar-based granulations, flavors, texture enhancers, disintegrants and coatings. The way these excipients interact is vital to understand, but once the product is working in production and the patients like them, they can become very difficult to dislodge from the segment. People become aware of how their medicine tastes and will notice even very subtle differences. Such differences may make the product less palatable, or even present the patient with some doubt as to its stability and performance.

Who stands to benefit from this?

A. Guy: I am excited by this trend as it could truly provide products that are easier to administer to difficult patient groups such as pediatric, long term care or the elderly. The number of people in these segments is growing and medicine needs to be more effective and adhered to in order to make our welfare system more cost-effective. Solid-dose formulation that includes orally dispersible forms to a much greater extent can have a profound effect on our healthcare provision.