The ICH Q12 Guideline complements ICH Q8 to Q11 Guidelines and provides a framework to facilitate the management of post-approval Chemistry, Manufacturing and Controls (CMC) changes in a more predictable and efficient manner across the product lifecycle. The Q12 guideline highlights the need for an effective PQS as described in ICH Q10 and in compliance with regional GMP requirements. A key requirement for this effective PQS is appropriate change management, enabled by knowledge management, and management review. The guideline is clear: in order for a firm to avail themselves of the flexibilities specified in ICH Q12, the change control system must be robust and responsive!
Change Management and Culture
A change control system is used for the management of changes that are approved and implemented versus those that are refused. As an inspector, it is common to observe in the system of record only those changes that have been approved. Where is the institutional knowledge of the changes that have been refused and why kept? Does the change review board/ team even see these proposals that are refused? Is there (in fact) a primary Go/No-Go decision-making unit that decides based on financials prior to a change ever entering the Quality Management System? For example, consider this scenario: a firm’s water system is near the end of its life, and is no longer supported by the vendor / supplier. The firm has a stock of spare parts, but this stock is dwindling down and sourcing from online overseas 3rd party retailers is required in order to maintain the system. The procurement order has been submitted each year for the last three years and was refused for a combination of financial and supply reasoning. Is this captured in any way? There will be no record within the change management system for this request as it was refused for financial reasons and did not require entry into the PQS. Who is managing the change, the change review board/ team, or the financial/commercial team? On inspection, the water system has had multiple unplanned maintenances and out-of-specifications results. The inspector will conclude that maintenance is inappropriate, which is one deficiency, and the change control system is failing as this issue has not been documented by the site, within the PQS. The PIC/S document cited to in Part 1 of our blog (here) clearly requires the documentation of any decision in the following excerpt:
“The change management system ensures that changes are proposed in a timely manner, proposed changes are formally evaluated, and a decision to accept or reject the proposal is documented. For rejected/voided change proposals, particularly those that relate to mitigation of a quality/safety/efficacy/compliance hazard, the system ensures that the rationales for those decisions are documented and well justified, and that continued risks are adequately managed.”
Is your change control system simply a record of approvals? If so, the authors are of the opinion that your system is not managing the totality of changes on site and may be at risk of regulatory citation. If a change is refused, it still has impact; in the above scenario, the water system could impact product (and, by inference, patient health) but the continued refusal to upgrade needs to be evaluated in the formal change control system and risk managed if appropriate. This water system will continue to be an exception report generating machine and, if not tracked appropriately, the site runs the risk of being cited for repeat deviations/ineffective CAPAs as well as poor maintenance and change management.
What does this type of approach tell us about the culture within an organization? We know that changes can be refused at any phase during the decision-making regarding implementation, and, in many cases, there is ample justification for not implementing, but this rationale must be documented and if there is risk to product / patient as a result, there must be a discussion on how that risk is reduced/controlled. If it is not documented, then it is a poor reflection on the organizational culture and a signal for inspectors to look for corroborating data and information.
If we look at the following slide on Quality Management Maturity (QMM) from FDA, the criticality of a robust change management process is illustrated. A robust change management process is considered to be foundational to your firm’s culture and fundamental to a firm’s QMM approach.
Image from Harouaka, D. “Quality Management Maturity (QMM)”, presented at the FDA SBIA meeting, April 12, 2023, https://www.fda.gov/media/168940/download
Lachman Consultant Services has vast and varied global experience in evaluating change management across the pharmaceutical and medical device industries globally. We are available to help evolve change management systems within your organization to facilitate ICH Q12 compliance and Quality Management Maturity. If you have any questions related to ensuring that your firm has a robust change management system, Lachman can provide an unbiased assessment of your existing system. Please reach out to LCS@LachmanConsultants.com for a consultation.
