As demand for generic medicines and biologics grows alongside an increasingly complex regulatory environment, firms large and small are contracting with outsourced manufacturers at a rapid pace. A 2018 study estimates global biopharma contract manufacturing (combined small and large molecule) will grow globally at an annualized 4.8% rate over the next ten years.
With this wave of regulated contracted manufacturing comes a growing need for organizations to maintain quality and compliance standards and practices, especially as regulators signal more stringent expectations for quality across the world.
Auditing, in its many forms and functions, will only become more critical in maintaining quality and compliance as production becomes a networked effort between sponsors and partnering firms. That’s why we’ve taken a moment to explore routine current Good Manufacturing Practice (CGMP) auditing through the lens of this growing trend.
CGMP audits between a sponsor and a CMO should have a precise goal: verifying quality and compliance systems.
More specifically, however, auditors must determine if the contractor’s systems are supported with full documentation and are being maintained while ensuring that any changes have been adequately controlled to avoid introducing new problems.
Let’s explore a few expert tips for ensuring these audits are the effective assessments they need to be to ensure a safe, effective product and a strong relationship between sponsors and CMOs.
Preparing for the Audit
To make audits both effective assessments of a contract manufacturer’s systems while making the most efficient use of an auditor’s time-on-site, make sure the project kicks off with a healthy dose of planning already in place.
Consider the following tips as a starting point in the lead-up to a contractor audit:
- Make the necessary arrangements to review any documents that don’t require auditors to be on-site. This can save precious time later.
- Gather a summary of any and all issues identified during and since the previous audit. This should include previous audit reports and responses, all lab OOS notices related to facilities, processes, and testing, change control summaries, adverse event reports, any FDA 483s or Warning Letters, a list of rejected lots and associated investigations, stability reports, and any other specific information critical to your assessment.
- Schedule the audit with operations in mind. While audits should always be planned to be as efficient as possible, scheduling should leave enough time for assessment without becoming a disruption to the contractor. Typically, a one-month notice strikes a reasonable balance between giving the contractor the time they need to plan for availability throughout the audit and avoiding too long of a preparation window.
Improving CGMP Assessment: 10 Questions
Regular quality system auditing is critical for all regulated manufacturers. But making the routine genuinely effective and valuable between sponsors and their contractors requires both parties to collaborate on corrective and preventive action plans from previous audits with measurable progress made between each assessment.
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More than this, routine CGMP auditing shouldn’t just be treated merely as a recurring “exercise.” Contractors can’t simply present the same material to their sponsor time and time again without, again, any measurable progress in quality measures.
To elevate routine contract manufacturing audits into the valuable assessments they ought to be, consider the following questions:
- Has the CMO carried out all the corrective actions included in the previous audit? If not, why not, and what needs to be done?
- How many deviations and/or investigations have occurred or been conducted since corrective actions were taken?
- Review the rejections. How many have occurred, what is the scrap rate, and how is it trending?
- If change controls have been implemented, how many human or process-related errors have been detected since? Have they been adequately investigated?
- Do changes in personnel suggest organizational issues of any kind? How have staffing changes resulted in shifts in talent, experience, and skillsets?
- Has the CMO experienced notable increases in workload? If so, has its capacity for production or testing-related activities been affected?
- How are quality/compliance initiatives being addressed within the organization? Are activities, goals, projects, and programs receiving the support they need?
- Have regulators taken any actions against the company? If so, what kind of actions were taken and how has it been addressed?
- How significant is your business to the contractor and how does that affect the relationship
- Has there been any change in the ownership of the company? If so, will that translate to significant changes in operations?
During an audit, be sure each observation is tactfully verified through evidence, such as documentation or processes and reserve detailed discussions for the final audit report. Following the assessment, the audit report should contain substantiated findings with all observations classified under the systems they’re a part of.
Tips for Audit Follow-Up & Remediation Planning
Following a sponsor-led audit, contracting organizations should provide a prompt response following up on all corrective and preventive action items. If suggested actions are deemed inadequate, schedule a meeting of senior management to discuss issues and present an alternative plan of action with any necessary follow-up meetings to confirm implementation.
Any corrective and preventive actions should be formalized and documented in a remediation plan. Some corrective actions may be obvious. Others may be more complex and take some planning to formulate.
After the analysis is complete and the subsequent report has been sent to management, the next steps should typically look something like this:
- Follow-up with the management team to ensure they fully understand the findings.
- Make sure the project lead prepares a timely, complete remediation plan to address the gaps you’ve uncovered.
- Determine the feasibility of your existing resources to implement the approved plan and identify the people who will initiate and implement it and/or secure the external resources needed to do so.
- Implement the plan. (Read our free white paper for a step-by-step guide to resourcing and implementation.)
- Verify success, determine the need for follow-up assessments.
Grab our free white paper to learn how to transform a quality assessment into a practical project plan. Inside, you’ll find a strategy for planning the resources necessary for quality system remediation and tips for implementing your plan efficiently from start to finish.
Need auditing assistance now? Our certified, experienced auditors plan, schedule, and execute vendor/supplier quality management audits to identify areas of conformance and nonconformance with applicable global regulations. Learn more.
Gap Analysis Remediation: A Guide to Resourcing & Implementation