Page 126 - Assurance of Sterility for Sensitive Combination Products and Materials

110 Assurance of sterility for sensitive combination products and materials

from previous IQ and OQ. If a machine is used for several SBSs, it is good
practice to perform a machine focused IQ and OQ to set the basis for a
reliable and properly validated equipment. Care should be taken to ensure
that the machine IQ/OQ limits cover the extremes of all the SBS seal-
ing process windows. It is recommended that product-specific OQ and
PQ elements are covered in a separate study. This is also important in case
of changes to or repairs of the packaging machine. In this case, only the
machine-specific aspects have to be repeated.

5.3.7 Managing changes and revalidation
Control of design and development changes is a key quality system require-
ment [7, 35] which obviously also applies to packaging. ISO 13485:2016
[35] further clarified under 7.5.7: “Processes for sterilization and sterile barrier
systems shall be validated prior to implementation and following product or process
changes, as appropriate.” In addition to reviews after changes, periodic reviews
should be conducted to detect any changes that went unnoticed or com-
binations of minor subtle changes that together can compromise the state
of validation. The Notified Body Operations Group (NBOG) in Europe
issued in 2014 new guidance on Reporting of Design Changes and Changes of
the Quality System [87], explicitly labeling changes to the packaging process
as “substantial.” It further states: “Changes in packaging characteristics of a sterile
medical device, configuration or density could affect the absorption or penetration of
the sterilant, the residue levels (where applicable) and the effectiveness of the steril-
ization process in addition to the safety of the sterile device. Issues of compatibility
between the packaging material and the sterilization process must also be taken
into consideration to ensure that seal integrity is not affected and that the packaging
preserves the functionality and safety of the device throughout its declared shelf-life.”
Wagner and Scholla published an article in 2013 [88] summarizing the
regulatory requirements for revalidation of sterile packaging. They recom-
mended a structured risk-based approach for the validation steps that allows
the revalidation effort to be limited to those areas that are affected. This can
have a significant effect on time and cost. There is a growing expectation
by regulators to improve products based on market feedback and docu-
mented CAPA. With this background, ISO Technical Committee TC84 has
created a new working group (WG 15) in 2014 to address Device Change
Management for pharmaceutical products. The committee draft document
has been published in 2016 and recommends a risk-based approach to es-
tablish a level of verification and to take a “step-wise approach to testing… until
such time that the data is sufficient to support a scientifically valid conclusion that