“Remember that failure is an event, not a person."—Zig Ziglar
FDA dietary supplement cGMPs (current good manufacturing practices) are a set of best practices for manufacturing dietary supplements, providing a system of processes, procedures and documentation to ensure a finished product has the identity, strength, composition, quality and purity it claims.
GMPs are codified in 21 CFR Part 111 Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements. The final GMP rule has been mandatory for all supplement manufacturing companies since 2010. Although audits are not specifically defined in 21 CFR Part 111, they have become a critical part to ensure that companies are complying with GMP regulations.
FDA holds marketers or own-label distributors of dietary supplements responsible for following cGMPs. These sellers are ultimately responsible for the finished product, and need to establish their own quality systems. They need to put a quality agreement in place and set product specifications with their contract manufacturer, as well as perform facility audits and test their products independently.
GMP compliance audits are performed by FDA, third-party certifiers (e.g., Natural Products Association [NPA], NSF International, etc.), and by companies performing their own vendor audits. The audit will typically cover several areas, including:
• Personnel (organization, training records and hygiene)
• Physical plant (layout, cleanliness and sanitation)
• Equipment and utensils
• Production and process control systems
o Manufacturing operations
o Master manufacturing records (MMRs)
o Master batch records (MBRs)
o Standard operating procedures (SOPs)
• Packaging and labeling operations
o Requirements for components, packaging and labels
o Label SOPs, label storage, label review, etc.
• Quality systems
o Quality control (QC)
o Supplier and/or component qualifications
o Laboratory operations
o Material and finished good specifications
o Analytical testing
o Vendor qualification
o Records and record keeping (document control)
o Change control
o Mock recalls
o Product complaints, adverse event reports (AERs), corrective action preventive action (CAPA), out of specification (OOS), etc.
• Holding and distribution
o Warehouse physical conditions
o Allergens and hazard analysis critical control point (HACCP)
o Returned/rejected dietary supplements or raw materials
Tips for Auditing a Vendor
Because FDA doesn’t specifically define the scope of GMP audits, it’s up to the auditor to decide the relevant areas to focus on. Although audits are time-consuming and can be expensive (with travel, lodging, etc.), they can also be conducted in an efficient and effective manner with the proper planning and communication.
Audit Notification: The first step is to schedule a mutually workable date for the audit with the vendor. Unlike regulatory audits that are oftentimes unannounced, customer/vendor audits are typically scheduled, as audits require a significant amount of time and human resources for the vendor. A planning window of up to three months is not unusual; however a vendor continuously extending an audit date might be a red flag.
Audit Agenda: The next step is to send the vendor the audit agenda. This will help both sides be more organized and efficient. It’s normal for the scope of the audit to go beyond the agenda, and companies shouldn’t be surprised if asked about a topic not on the original agenda.
During the Audit: Be mindful that the vendor is an ongoing business and needs to able to function as usual. An auditor’s primary focus shouldn’t be to try to catch the vendor doing something wrong, but to understand the way the vendor works. Does it have the proper procedures in place? Are the employees trained in the procedures and following them? Is the documentation correct? If there is a discrepancy, how is that handled or communicated?
Exit Interview: Have an exit interview or close-out meeting to go over the audit and set expectations for the next steps. The close-out meeting might be a place to have a more detailed discussion about certain observations or discrepancies. Often, the auditor will get a better sense of the vendor’s open-mindedness to suggestions or to putting an improvement process in place.
Tips for Vendors Preparing for an Audit
The best defense is a good offense. Being prepared for an audit can minimize troubles and contribute to a successful positive audit outcome.
Documentation: Any auditor knows, “If it’s not written down, it doesn’t exist." Keep documents and records accurate, current and complete. This includes: company policies, SOPs, raw material and finished good specifications, MMRs and MBRs, change control, logbooks, testing, complaints, AERs, CAPAs, personnel training records, etc. These should be able to be retrieved quickly.
Internal Audit: Performing a self-audit on a regular basis can help prepare the organization for outside audits. Audit each area separately: facility, warehouse, production, quality, laboratory and documentation. Update SOPs regularly. Make sure training records are up-to-date. These self-audits can show where gaps are, so they can be corrected.
Audit Notification: If you receive a request for an audit, ask for an agenda. Make sure the date agreed upon is workable with your staff, so no surprise visits occur.
Exit Interview: Always request to have an exit interview with the auditor. Sometimes any misunderstandings can be cleared up before being formalized. And the feedback can be beneficial.
Report: When you receive the audit report, follow up and respond in a timely manner to any corrections requested.
Being compliant with GMPs, along with having strong, quality systems in place, helps to control and ensure that dietary supplement products consistently meet specifications; this creates successful audit outcomes. The vendor/customer relationship is becoming more intimate and dynamic, and having a good relationship with open communication is a key for success. Audits are an important check and balance, and provide a structured conduit for continual improvement for both parties. A good audit system can strengthen the customer/vendor relationship, which will improve quality and overall satisfaction.
Robin Koon is executive vice president at Best Formulations (bestformulations.com), and has more than 35 years of pharmaceutical experience in clinical pharmacy, as a retail drug chain executive, in managed care and in manufacturing.