Pharma Change Control: Strategies for Successful Company-Wide Implementation
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Change control programs are considered essential elements of pharmaceutical quality assurance sys-
tems. The glossary to Annex 15 of the EU GMP Guidelines denes “change control” as:
“A formal system by which qualied representatives of appropriate disciplines review
proposed or actual changes that might affect the validated status of facilities, systems,
equipment or processes. The intent is to determine the need for action that would ensure
and document that the system is maintained in a validated state.”
Chapter 5.23 of the EU GMP Guidelines says this about the handling of changes:
“Signicant amendments to the manufacturing process, including any change in
equipment or materials, which may affect product quality and/or the reproducibility of
the process should be validated.”
There are also two brief notes in the Code of Federal Regulations (CFR) on the topic of “change
control” (21 CFR, 211.100 and 21 CFR, 211.160):
§ 211.100 Written procedures; deviations.
(a) “There shall be written procedures for production and process control designed
to assure that the drug products have the identity, strength, quality, and purity they pur-
port or are represented to possess. Such procedures shall include all requirements in this
subpart. These written procedures, including any changes, shall be drafted, reviewed,
and approved by the appropriate organizational units and reviewed and approved by the
quality control unit.”
§ 211.160 General requirements.
(a) “The establishment of any specications, standards, sampling plans, test proce-
dures, or other laboratory control mechanisms required by this subpart, including any
change in such specications, standards, sampling plans, test procedures, or other labo-
ratory control mechanisms, shall be drafted by the appropriate organizational unit and
reviewed and approved by the quality control unit. The requirements in this subpart shall
be followed and shall be documented at the time of performance. Any deviation from the
written specications, standards, sampling plans, test procedures, or other laboratory
control mechanisms shall be recorded and justied.”
In the US the quality control unit is responsible for the verication and authorization of changes.
The responsibility is not assigned in the relevant EU regulations. However, as change control is consid-
ered an essential element of the pharmaceutical quality assurance system, it makes sense to transfer the
responsibility for the function of the change control program to the person responsible for quality assur-
ance (QA representative, QA head).
Change control is not department-specic, rather the task of the whole company. This is due to the
wide area of application of change control, as described in both Annex 15 and in The Pharmaceutical
Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) document PI 006-2.
“Written procedures should be in place to describe the actions to be taken if a change
is proposed to a starting material, product component, process equipment, process en-
vironment (or site), method of production or testing or any other change that may affect