The use of contract manufacturers for the production of approved drug products has become more and more commonplace, particularly with the steady increase through the years of virtual pharmaceutical companies, a business model where the majority of the drug development and production work is outsourced to third parties as needed.  While the use of a contract manufacturing organization (CMO) may well be more cost efficient to a company, it also brings specific challenges for the regulatory department compiling and maintaining the drug product applications.

Documentation and application preparation time are topics that time and again arise with CMOs and regulatory affairs departments.  Each CMO has their own format and systems for meeting GMP documentation requirements (understandably so), which includes their own unique SOPs, work procedures, test methods, specifications and batch records.  What this means for a regulatory department is that, for every new CMO, they need re-educate themselves.

The impact of using of CMOs must be considered in post-approval regulatory tasks also, such as preparing annual reports or fulfilling annual obligations.  A successful CMO is an operating business with multiple products, multiple customers, and multiple similar requests.  They may well be the best and most responsive partner, but you still need to be prepared to get in line.  The delays related to this should be realistically factored in when attempting to meet regulatory deadlines; after all, there is no option to pop over to the manufacturing department to speed things up.  And, there are those routine but necessary annual requirements.  The annual facility fee is a big-ticket item and who pays it was likely settled in the initial contract.  But, has it been sorted out who will do their drug listings for your product?  Or the necessary blanket certifications at the end of the year?  If your product is a generic, who will be responsible to self-identify the site?  And will the other party get confirmation of it?  It’s these smaller but vital responsibilities that often get overlooked until the first time they come up after product approval, and then all you get is a blank stare when someone asks who is responsible.

So, what can be done to better assure smooth regulatory interactions with your selected CMO?  First, allow regulatory input into the original negotiations.  Quality and compliance input are a given when negotiating a Quality Agreement, but regulatory input can also be extremely beneficial.  This will go a long way to assure you and your CMO will work efficiently together for on time submissions.   Establish a regulatory contact at the CMO for your regulatory group to deal with.  All too often regulatory requests must go through quality, or project management, or sales to get to the CMO, at which point it becomes like a game of telephone, where much gets lost in the translation.  Foster transparency and cooperation with your CMO from the beginning.  Be clear about what you need, and why.  Share relevant Agency comments with the CMO, keep them advised on the progress of an application review.  If the CMO is treated like an active regulatory partner, they are more likely to be responsive to your regulatory needs.  Internally, assure sufficient regulatory preparation and review time is allotted – build in time to receive CMO documents, time to learn CMO documents, and time to ask and get answers on the CMO documents – then double it and you should be OK.

In conclusion. patience and collaboration are the answer.  If it is recognized by all vital departments, especially regulatory, quality, project planning and upper management, that it takes more time and more patience when dealing with an outside site on regulatory requirements, a pragmatic, peaceful and productive regulatory relationship is enjoyed by all.

If you have any questions or are need of services related to regulatory support, please reach out to Lachman Consultants at