News for the Metro Chapter

Defining a Strategy for the Validation and Qualification of Sterile Filtration Processes of Investigational Medicinal Compounds

Presented by Ross Acucena, Regulatory Consultant, Provantage Services EMD Millipore

March 4, 2014, Somerset, NJ
Sterile filtration process validation is clearly necessary to confirm that patients are provided with sterile drug products. But the question arises, at what phase of drug development should filtration validation or qualification start? Ross Acucena has been asked this question many times, and as a Regulatory Consultant for Millipore he is well positioned to answer it.
Ross walked our group through the regulations governing sterile filtration validation in the US and EU revealing a lack of consistency in validation initiation. From a practical point of view, early phase filter validation will minimize the risk for patients and give reliable results from clinical trials, but at this point the drug developer may have limited knowledge of product formulation, may only have small amounts of product available for testing, and the process itself may not yet be well defined.
Facing these challenges, Ross recommended a strategy that focused on three elements of filtration validation: 1.) compatibility, 2.) extractables testing, and 3.) retention testing. If the formulation is incompatible with the filter or housing, there is no point in proceeding with process development with this filtration product. Similarly, if the filter or housing leaches harmful components into the drug formula, than clearly the process is inadequate and an alternative process should be sourced. And finally, if the filter does not adequately retain microbes suspended in the drug product, then it is not meeting its primary function. The attached presentation details these elements of filtration validation and offers some real world solutions to the aforementioned challenges encountered during early phase validation. The presentation was well received and sparked questions from the audience about filter validation considerations for the development of biosimilar products and extractable testing.
Special thanks to Millipore, Pall, and 3M for supporting this meeting.

Strategies for Developing Biosimilars and Biobetters

Presented by Dr. Michiel Ultee, Chief Scientific Office Gallus Biopharmaceuticals

January 30, 2014, Somerset, NJ
As the pipeline for block buster small molecules began to dwindle, innovator pharmaceutical companies were restructuring to commercialize therapeutic large molecule drugs. This biologics market is now quite large, but is facing the same patent cliff that has altered the landscape of therapeutic chemical entities. In the next 5 years alone, $70 billion in biologics revenue will be open to competitive manufacturing as innovator patents expire. This presents a great opportunity for drug makers -- but what exactly is a “generic” biologic?
Dr. Mike Ultee helped our group understand the unique challenges of developing and receiving regulatory approval for biosimilar drugs. As Chief Scientific Officer at Gallus Biopharmaceuticals, Dr. Ultee brought useful perspective in his presentation of the challenges and potential rewards of developing and manufacturing these complex molecules. Gallus is a well established CMO with decades of experience in biologic manufacturing.
The complexity of biological molecules results in a very different regulatory approval strategy than generic small molecule drugs. Not only are the protein sequences very large, but the secondary, tertiary and quartenary folding sequences can be quite complex. Add to this the difficult to control post translational modifications and you have a highly variable process.
Hence the term “biosimilar”, as the name implies these are recombinant protein therapeutics that resemble, but are not identical to the original or reference product. They closely resemble reference product in safety, purity, and potency and show no meaningful clinical differences. Dr. Ultee described the road map to a biosimilar approval, including regulatory, analytical, safety, purity and scale up concerns.
He also outlined a strategy for developing “biobetters”. A biobetter molecule is actually an enhanced version of the reference product. Since the molecule claims enhanced efficacy, clinically meaningful differences must be demonstrated through clinical trials. Dr. Ultee outlined the rationale for a biobetter strategy, versus biosimilar, as well as potential drawbacks. All of this information is in his attached presentation.
The presentation was well received and sparked lively discussion with the audience about the benefits of pursuing a biobetter pathway and why is there a different regulatory culture in Europe from America. Europe has already approved several biosimilar drugs, the US has yet to do so.
Special thanks to Ed Trappler of Lyophilization Technology, Inc. (www. for supporting this meeting as a vendor. Lyophilization is a critical component of biologic manufacturing and LTI is a CDMO that focuses on all aspects of lyophilization. Ed heads the Lyophilization Interest Group for PDA.