20 June 2023
Any change from design or predefined processes requires risk assessment and potential impact evaluation for both the transport process and, consequently, the product. This article discusses the importance of having a structured, compliant Change Control (CC) process in place for medicinal product manufacturers as well as for their qualified logistics vendors.
Note: The following text is an abridged excerpt from the pre-reading material exclusively for participants of the ECA Live Online Training "GDP for Beginners" on 01/02 March 2023. The package was developed and written by Dr Zvonimir Majic from Teva Pharmaceutical Industries Ltd.
Regulatory guidance related to change control are set down to ensure that any change that could affect product or process quality is evaluated; risk assessed and pre-approved prior implementation. From extensive list of global provisions related to change control requirements, we are highlighting few.
Brazilian regulatory agency, ANVISA in their Guidelines on the qualification of transportation for biological products states requirements for having change control process in place for any change related to qualified shipping system: A requalification can be necessary when change of any item that impacts the qualified system is performed, such as for example, the type, quantity and position of the cooling elements, significant route change, modification of the minimum and maximum loads, transportation system change, in addition to other relevant modifications.
China Revised Good Supply Practice (GSP) Standards for Pharmaceutical Products states the following in Article 8: Distributors shall organize and carry out internal audits both periodically, as well as whenever there are significant changes made to key elements of the quality control system.
The Irish Guide to GDP states the following on change control process: The purpose of a change control system is to enable wholesalers to identify, document and assess changes that may affect compliance with GDP. Such changes may include, for example: a change in an insulated shipper used to transport cold chain medicinal products, a change in the settings of a heating system, or the relocation of a medicinal product storage area within a warehouse. Such changes may have a significant GDP impact and may have the potential to affect the quality of medicinal products wholesaled.
European commission in their 2013 GDP guidelines states specific change control requirements for distribution of medicinal products: A change control system should be in place. This system should incorporate quality risk management principles and be proportionate and effective. All critical steps of distribution processes and significant changes should be justified and where relevant validated. Equipment and processes should be respectively qualified and/or validated before commencing use and after any significant changes (e.g. repair or maintenance).
WHO Annex 5 also provides requirements for change control process: Procedures should be established and maintained for the preparation, review, approval, use of and control of changes to all documents relating to the distribution process.
Furthermore, the ICH Q10 document defines Change Management System as an important part of overall pharmaceutical Quality Management System requiring focus and continuous enhancement: In order to evaluate, approve and implement these changes properly, a company should have an effective change management system. The change management system ensures continual improvement is undertaken in a timely and effective manner. It should provide a high degree of assurance there are no unintended consequences of the change. The ICH Q9 document states that in respect of Risk Management any significant change should be risk assessed.
Revised General chapter of USP <1079> states that after validation, any modification to the system should be done according to change control procedures, and records of these changes should be kept.
To define which of the changes in global transport and distribution of medicinal products are significant and could have an adverse effect on process or product, a documented risk assessment on proposed change is required. Such process is designed to address any potential time or temperature abuse in process that could have an adverse effect on process and/or product integrity and cause deviations from predefined conditions.
The process can be summarized in following steps: