Understanding the Requirements for Ready-to-Sterilize Stoppers
While all major regulatory agencies have expectations regarding the ability of a pharmaceutical wash process to provide a suitable level of pre-sterilization depyrogenation, the United States (U.S.) Food and Drug Administration’s (FDA) requirements appear to be particularly stringent.
Current FDA thinking is outlined in the “Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – current Good Manufacturing Practice (September 2004).” This guidance includes the requirement that container closure depyrogenation processes must demonstrate validation of a minimum 3-log reduction in endotoxin levels. The Westar® RS (Ready-to-Sterilize) pharmaceutical wash process developed by West is supported by an ongoing validation program that meets the demanding expectations of the FDA for a broad range of elastomeric products. This information is contained in our portfolio of Type V Drug Master Files (DMFs) with the FDA and Type II DMFs with Health Canada.
In addition, the Westar RS process produces elastomeric components that meet defined specification limits for particulates and bioburden. Process capabilities exist globally at West’s facilities in Eschweiler, Germany; Jersey Shore, Pa.; Jurong, Singapore; and LeNouvion, France. To help support a successful review by the FDA, drug manufactures contemplating a pharmaceutical regulatory submission in the U.S. should consider elastomeric components washed by West.
The transition to the Westar RS process isn’t as difficult as you might think. In June 2010, FDA issued the “Draft Guidance for Industry: CMC Postapproval Manufacturing Changes Reportable in Annual Reports,” which was intended as an adjunct to the existing “Guidance for Industry: Changes to an Approved NDA or ANDA (2004).” The draft guidance identified a new group of changes that are considered to be Annual Reportable including the following:
Use of a contract manufacturing organization (CMO) for the washing of a drug product stopper, provided the applicant certifies that the CMO’s washing process has been validated and the CMO’s site has been audited by the applicant (or by another party sponsored by the applicant) and found cGMP compliant.
West’s recent experience has been that this type of transition can be covered by a Changes Being Effected (CBE-30) submission, however the guidance indicates that the FDA views this kind of change as having minimal potential to impact drug product quality adversely.
Westar® is a registered trademark of West Pharmaceutical Services, Inc., in the United States and other jurisdictions.