The European Medicines Agency (EMA) issued draft guidance documents focused on the quality of oral modified release products and transdermal delivery patches last week and called on interested parties to provide feedback by March next year.
The guidelines for patches set out what developers must do to ensure drugs can pass through the skin without causing irritation – from the physical characteristics of the systems themselves to the excipients and solvents used to enhance delivery.
The EMA also outlined how manufacturers should try to prevent active pharmaceutical ingredients (API) crystallising as a result of the higher concentrations used in such delivery systems.
“Transdermal patches usually contain an excess of drug substance than that delivered to the patient during use. This excess is necessary to maintain a clinically effective rate of delivery over time and allow the minimum patch surface area.
“Because the concentration of the drug substance can be near to its saturation limit, there is a risk of crystallisation on storage with potential adverse effects on the quality and efficacy of the product.”
In contrast the new draft guidelines on oral dosage forms are less broad, touching only on prolonged and delayed release products.
Dissolution testing is the core focus of the section on prolonged-release drugs, with the EMA stressing the importance of monitoring this characteristic throughout the formulation development process.
“The quality of a prolonged release dosage form is continuously improved during the development of a new drug product…As soon as the constituents are chosen, gradual scaling up of the manufacturing process will start. During this period it is reasonable to expect that adjustments will be necessary to reach full-scale production.
“In some cases these adjustments may have an effect on the properties of the drug product. It is therefore recommended that an in vitro dissolution test is developed which is able to detect changes which may have an effect on the efficacy or safety of the product.”
The agency goes on to set out the dissolution data that developers will be required to provide under the proposed guidelines.
The section on delayed release forms focuses solely on gastro-resistant dosage forms, setting out the information the EMA requires from firms developing such products for the European market.