The FDA expects drugmakers to have quality agreements with their suppliers, but how those agreements are crafted says a lot about a company’s internal auditing program.
Quality agreements are a major component of success for all drug manufacturers and necessary for all third parties, including contract manufacturers, packagers, labs and API manufacturers.
Steven Scharf, senior consultant at Validant and president of GMP Concepts, highlighted the 24 elements every drugmaker should include in its quality agreements during a recent FDAnews webinar.
Scharf said he prefers drafting quality agreements that use a “responsibility matrix” approach, in which roles and responsibility are clearly defined. “It’s more clear cut” than narrative quality agreements, he said.
Following are some of the two dozen major elements of a world-class quality agreement:
Batch records: Make sure your suppliers furnish a Certificate of Analysis or Conformance with each shipment. “You want to review batch documentation almost as a final release.” And you should sign off on the master batch documents to make sure the suppliers are using the latest documents.
Change control: Specify who’s in charge throughout the production process, and who signs off on changes. “Don’t let a supplier or a third party present you with a change and [have it get] lost in a black hole somewhere.”
Out-of-specification deviations in the laboratory: “You may want to require notification of critical deviations that arrive during production or during packaging.”
Field alerts and recalls: Manufacturers should include a section in the agreement that details who is responsible for filing field alerts and for initiating recalls.
Materials and package components: Manufacturers need to demonstrate that their laboratory can successfully execute GMP methods, but they don’t need to validate them as they would for in-house methods. If the contractor is performing inspections, manufacturers should generally have a set of specific requirements.
Retesting and resampling: These responsibilities need to be spelled out in detail in the agreement.
Artwork: Always specify who’s responsible for release of the label.
Complaint investigations and interim investigation reports: It’s important to establish deadlines and timeframes and who has the responsibility for maintaining complaint files and reporting adverse events.
Audits and inspections: “You need to make sure that your quality agreement includes a caveat that allows you or a representative of your organization to go in and do an audit with adequate advance notice, typically during business hours, of the third party.”
FDA 483s: Consider putting in a requirement that says if you’re given a 483, or a regulatory action, you will be notified.
Subcontracting: “Do not allow subcontracting of any part of what you’re contracting out without your prior written approval.”
Dispute resolution: Third parties will inevitably do things that they think are right, which you may disagree with. For these situations, you need a dispute resolution provision in the quality agreement and a determination of who needs to be part of the resolution.
Tech transfers: Determine who’s responsible for maintaining the original data, and for how long that results from a transfer.
Stability: The agreement should spell out the answers to these questions. Who is performing stability? How many samples are pulled? Who is responsible for protocol and approval of the protocol? How are samples selected? Who does the testing of the stability samples?
In addition, Scharf said, it’s important to have established procedures for process validation, documentation, records retention, sample retention, and warehousing.
Finally, Scharf said, even the best quality agreement may need changes. However, change agreements “should be reserved for less critical suppliers that won’t sign your full-blown, 15, 20-page document. And in your change agreement, you should list specifically what types of changes require notification and what type of changes do not.”
Order our webinar The 24 Elements You Need For a World-Class Quality Agreement to learn more about the elements that must be included in your quality agreement.