Contamination Control Strategies for Innovation and Regulatory Compliance
Introduction
A Contamination Control Strategy (CCS) outlines a method to identify and analyze risk, review the mitigating opportunities and innovations, and ultimately define corrective and preventive action plans. Implementation of a CCS attempts to address the varied causes of contamination and compromised sterility.
Execution of a robust Contamination Control Strategy needs the support of subject matter experts in Manufacturing, Regulatory, Quality Control, Quality Assurance, and supporting departments.
This is a CCS as defined in Annex 1:
“Contamination Control Strategy (CCS) – A planned set of controls for microorganisms, pyrogens and particulates, derived from current product and process understanding that assures process performance and product quality. The controls can include parameters and attributes related to active substance, excipient and drug product materials and components, facility and equipment operating conditions, inprocess controls, finished product specifications, and the associated methods and frequency of monitoring and control.”
Annex 1 (2022)
Background
The development of a comprehensive Contamination Control Strategy addresses environmental control and detection optimization. To maintain reliability and inform the construction of the CCS, manufacturers should implement Quality Risk Management (QRM) and Quality by Design into their production facility, equipment, personnel flows, and supportive processes. It is also critical to review historical data and trend analysis in order to appropriately measure and identify gaps, risk potentiality, and opportunities for mitigation; all of these play a part in making a CCS. The design, procedures, organization, and technology controls are most effective when they complement each other in a holistic manner.
Development of a Contamination Control Strategy
The proposed elements to be considered for the CCS are listed in Annex 1:
“2.5 The development of the CCS requires detailed technical and process knowledge. Potential sources of contamination are attributable to microbial and cellular debris (e.g. pyrogen, endotoxin) as well as particulate (e.g. glass and other visible and sub-visible particles).
Elements to be considered within a CCS should include (but are not limited to):
i. Design of both the plant and processes including the associated documentation.
ii. Premises and equipment.
iii. Personnel.
iv. Utilities.
v. Raw material controls – including in-process controls.
vi. Product containers and closures.
vii. Vendor approval – such as key component suppliers, sterilization of components and single use systems (SUS), and critical service providers.
viii. Management of outsourced activities and availability/transfer of critical information between parties, e.g. contract sterilization services.
ix. Process risk management.
x. Process validation.
xi. Validation of sterilization processes.
xii. Preventative maintenance – maintaining equipment, utilities and premises (planned and unplanned maintenance) to a standard that will ensure there is no additional risk of contamination.
xiii. Cleaning and disinfection.
xiv. Monitoring systems – including an assessment of the feasibility of the introduction of scientifically sound, alternative methods that optimize the detection of environmental contamination.
xv. Prevention mechanisms – trend analysis, detailed investigation, root cause determination, corrective and preventive actions (CAPA) and the need for comprehensive investigational tools.
xvi. Continuous improvement based on information derived from the above.”
Annex 1 (2022)
