Page 123 - Assurance of Sterility for Sensitive Combination Products and Materials

Package/container closures 107

Under 3.2.2.2. “Pharmaceutical development” directive 2001/83/EC states.
(g) The suitability of the container and closure system used for the storage, ship-
ping and use of the finished product shall be documented. A possible interaction
between medicinal product and container may need to be considered.
The International Council for Harmonization of Technical Requirements
for Pharmaceuticals for Human Use (ICH) issued a series stability study
guidelines. These documents have been adopted by the United States,
Europe and Japan, and other regulatory agencies. The documents can be
downloaded on the ICH website under quality guidelines [83] and are
also available through the FDA in the United States, EMA in Europe, and
PMDA in Japan.
SBSs and product stability studies are typically conducted together.
When the drug or device stability is explored concurrently with packaging,
interactions will also be captured (see FDA guidance: Early Development
Considerations for Innovative Combination Products [32]). As per ICH
Q1A (R2) [84] Guideline for “Stability Testing of New Drug Substances and
Products” “The stability studies should be conducted on the drug substance packaged
in a container closure system that is the same as or simulates the packaging proposed
for storage and distribution.”

5.3.5 Forming, sealing (closure) and assembly process
validation
Validation of processes is a key quality management system requirement (ISO
13845 [35]) when “the resulting output cannot be verified by subsequent monitoring
or measurement. “A number of guidance documents referred to by the Center
for Devices and Radiological Health (CDRH) of the United States Food
and Drug Administration (US FDA) and other national authorities for med-
ical devices help define the process: the Global Harmonization Task Force
(GHTF) document GHTF/SG3/N99-10:2004 [85] or Guidance for Industry
Process Validation by the US FDA [86]. The US FDA guidance applies a life
cycle approach to process validation linking processes development, qualifica-
tion, and routine monitoring to ensure the process is maintained in a state of
control. The GHTF document [85] includes a list of elements to be included
for the development of a validation protocol and provides a detailed annex
on statistical methods and tools to help designing capability/studies, control
plans, designed experiments, gauge R&R studies and data analysis as well as
approaches for determining sample sizes. It also advocates for a risk based and
a quality-by-design approach. It defines process validation as “the collection and
evaluation of data, from the process design stage through commercial production, which