Biotechnology took over the development of new drugs and personalized medicine is about to deliver first success stories. Presentations at the PDA Annual Meeting 2012 reported of first successes in cell based therapies.
This year Phoenix/Arizona was the host of the PDA Annual Meeting 2012 (Parenteral Drug Association). As in previous meetings it was challenging to choose between many outstanding presentations.
The trends are obvious. This year a session on „personalized medicine“ including ATMPs (Advanced Therapy Medicinal Products) was offered the first time. While this topic is still in its infancy the presentations demonstrated that the field has moved from research to first successes are in application. Tom Finn, Ph.D., FDA (Office of Cellular, Tissue, and Gene Therapies, CBER) gave an outstanding presentation on: „FDA Perspective: Challenges in Manufacturing of Cell Therapies for Personalised Medicines“.
Cell based therapies as targeted therapies can range from a single product aiming at subpopulations of patients through companion diagnostics to highly customized products manipulated and designed for a single patient.
The advantages of cell & gene therapy are:
After the advantages Tom Finn highlighted the challenges of manufacturing, quality systems and validation.
The challenges for the manufacturing and quality systems are:
A key focus for patient-specific products has to be a rigorous tracking from source material through product administration. Also the qualification of reagents needs to be considered at the earliest stages of development.
Validation of individualized drugs
Tom Finn addressed critical validation topics of such products. Process validation can help identify false assumptions, inconsistencies, variations and contradictions in the manufacturing process that are difficult to address by other means. And control of manufacturing rather than complexity is the important issue in this area.
Challenges in manufacturing consistency are:
As in other fields of application, final product testing by itself may not adequately capture all relevant information and in-process testing can help to gain important information about the process and the cell production and the cell itself.
In order to get a full picture, process validation studies should be conducted, as they would be for producing the intended product. Representative starting material should be used and ideally worst-case scenarios have to be included, where possible.
Acceptance criteria for release specifications should be based on scientific principles and product characterizations. Assays and methods must support those criteria.
The importance of the assay validation was emphasized. ICH recommendations should be applied, although not all elements are directly applicable. A simple assay does not necessarily equal easy validation. It was recommended that even assays meant „for informational purposes only“ should be validated as the data might become useful at a later time.
At the end of the presentation it became clear that the current regulations do not justify all the requirement of the cell and gene therapy manufacturing. Some examples show that personal medicines clash with existing regulations. And the FDA recommended to contact them if there are potential conflicts.
Regulation: Retain samples for a period of at least 6 months after expiration.
Practice: Some products expire within hours.
Regulation: Each active ingredient shall be retained.
Practice: It is not always clear what the „active ingredient“ is for a cell therapy with a fixed population of cells.
Manufacturing and testing should be aligned so that they are consistent with one another and suitable for the intended purpose.
Cell and gene therapies present special challenges that may need novel approaches to achieve the intended goals:
The FDA is open to meet the challenges of personalized medicine by cell and gene therapy. The further developments in this sector will be interesting. We will see what will happen in the future.
Maas & Peither AG, Germany
Halfmann Goetsch Peither AG, Switzerland, Germany, Singapore