Extractables and leachables considerations for prefilled syringes.

INTRODUCTION: Use of pre-filled syringes as both a packaging and delivery system for pharmaceutical drug products is accelerating. Pre-filled syringes must meet the quality and suitability for use requirements for both systems, including compatibility with the drug product. Relevant incompatibilities between pre-filled syringes and drug products include the safety of syringe-based leachables that accumulate in drug products and the ability of leachables to interact with the drug product's ingredients as such interactions can affect safety, efficacy, stability and physical viability. AREAS COVERED: Relevant suitability considerations for pre-filled syringes are discussed herein and specific examples of suitability for use issues for pre-filled syringes are cited, focusing on extractables associated with pre-filled syringes and leachables derived from such syringes. Aspects considered include the toxicological impact of leachables, their ability to alter the efficacy of drug products and to produce other undesirable outcomes such as aggregation and immunogenic responses. EXPERT OPINION: Materials used in pre-filled syringes and the conditions of use minimize the traditional safety risk associated with leachables. However, drug products that use pre-filled syringes are prone to non-traditional interactions such as disruption of protein conformation, leading to potential efficacy, safety and quality issues. In order to qualify pre-filled syringes for use, the traditional approach of measuring extractables and leachables and inferring their effect must be augmented by rigorous compatibility testing. Research into the fundamental relationship between leachables and drug substances will be necessary so the more time- and cost-efficient 'measure and infer' approach can be widely implemented.