Good manufacturing practice and FDA regulations require pharmaceutical companies to know their production processes. Understanding
the chemicals that potentially could migrate into final products is crucial, particularly for companies that incorporate single-use
equipment within their facilities. Manufacturers need to identify which chemicals could migrate and quantify the likelihood
of this migration. A forthcoming Parenteral Drug Association (PDA) technical report that recommends a risk-based approach,
and pending safety and analytical thresholds from the Product Quality Research Institute (PQRI), will help drugmakers develop
appropriate extractables-and-leachables strategies.
The PQRI document
In 2006, PQRI published recommendations to help drugmakers develop safety thresholds for extractables and leachables in orally
inhaled and nasal drug products (OINDP). The group is currently at work on a companion document that will address extractables
and leachables in parenteral and ophthalmic drug products (PODP). The new document will be submitted to the PQRI Steering
Committee in 2012, according to Diane Paskiet, chair of PQRI's leachables and extractables PODP working group.
IMAGE: ANDERSEN ROSS, LAWRENCE LAWRY, GETTY MAGES. COMPOSITE: DAN WARD
The PQRI working group writing the document includes industry experts and representatives of the US Pharmacopeia, FDA, and
HealthCanada. The group is divided into a chemistry team, which will discuss how to conduct extractables studies, and a toxicology
team, which will provide advice about evaluating chemicals' safety.
PQRI will submit the final recommendations document to FDA. The document is intended to demonstrate best practices for the
evaluation and qualification of leachables in parenteral and ophthalmic drug products. These practices have been extrapolated
from the OINDP recommendations, and future documents could potentially address other dosage forms or routes of administration,
The focus of the PODP document is to demonstrate how to conduct controlled extraction studies to understand the chemistry
of the materials and incorporate justifiable safety thresholds. "Our recommendations are to start the selection process during
development and begin to qualify components early, rather than in late phases of development, because if you have something
objectionable, you can understand the potential to cause patient harm and eliminate or mitigate the risk," says Paskiet.