The European Medicines Agency published a draft list of questions and answers on postapproval change-management protocols last week. Postapproval change-management protocols were introduced in the 2008 European Union legislation EC (1234/2008). The Q&A is meant to outline general principles for using and implementing the protocols.
The document defines a postapproval change-management protocol as “specific changes that a company would like to implement during the lifecycle of the product and how these would be prepared and verified.” The protocol is meant to take a “stepwise approach” including early and later evaluation of key data about the postapproval product change.
According to the document, drug manufacturers should submit to EMA as part of a marketing authorization application (or as a stand-alone variation) the relevant data needed to demonstrate that they have "acquired adequate knowledge to prepare and manage the impact of the change." For example, the protocol may include a risk assessment of the effect of the change on product quality and a description of the studies to be performed to assess the effect of the proposed change on product quality. Other examples are included in the draft Q&A.
The Q&A also discusses how and when the change should be implemented after EMA approves the protocol, and what types of changes apply. The document notes that the types of changes to include in this submission would “depend on the complexity of the product and its manufacturing process, as well as the understanding that the company has gained about them.” The Q&A goes on to say that “it is strongly recommended that companies submit postapproval change-management protocols only for those changes that they are highly likely to implement and whose feasibility has already been investigated and is supported by relevant data.”
Finally, the draft document addresses how to handle multiple changes and the logistics of submitting information to EMA. Comments on the draft are due on Feb. 28, 2011.
The US Food and Drug Administration issued a draft guidance for industry on chemistry, manufacturing, and controls (CMC) postapproval manufacturing changes this past June. The US draft guidance focuses on changes that are considered to have minimal effect on product quality and therefore can be reported to the agency through annual reports. More significant changes to approved new drug or abbreviated new drug applications (NDAs or ANDAs) follow reporting lines under the agency’s 2004 guidance on Changes to an Approved NDA or ANDA and section 506A of the Federal Food, Drug, and Cosmetic Act.