Since the US BEBPA bioassay conference is nearly upon us (See latest brochure
HERE
)
w
e talked to Dr. Laureen Little, the president of BEBPA and Principal Consultant of Quality Services. Dr. Little has over 25 years working in the potency assay field. We specifically wanted to get her perspective on hot topics for biopharmaceuticals.
BEBPA
: Dr. Little, in your experience, as a consultant in the field and head of the BEBPA Bioassay Conference committee, what issue seems to be this year’s hot topic?
Dr. Little
: This year and last, I have personally worked on many projects about how to establish similarity criteria for the comparison of the reference vs. test sample dose-response curves. Most new assays are utilizing equivalence approaches for establishing the “goal-post” for equivalency as outlined in the USP <1032>. However, there have been many practical details which were not immediately obvious. The industry is struggling with determining what data is needed for setting these criteria, how the data should be handled and how/when to implement these criteria.
BEBPA
: You mention the USP, is there any plan to clarify the advice in these chapters?
Dr. Little
: That is a great question, and one which I can’t answer. However, Steven Walfish, the Principal Scientific Liaison from USP will be speaking at the upcoming BEBPA US Bioassay conference (His talk is titled:
USP Bioassay Chapter Revision Journey
). My bet is this will be one of the topics he will discuss with the audience.
BEBPA:
Can you tell us, in simple terms what the USP currently recommends for similarity criteria?
Dr. Little:
Well that is a bit more difficult than you might think. Currently there are three approaches outlined in the USP chapter for establishing similarity. They are:
- Utilize historical data of reference vs. reference to determine a “Zone of Indifference” for critical parts of the dose-response curve. (This is usually done early on in development prior to the availability of multiple lots.) This data is typically a point estimate.
- Utilize the historical data as in above, but instead of using simply a point estimate of the ratios of various curve parameters, utilizing a 95% confidence interval (or tolerance interval) for the non-parallelism estimate.
- Use product knowledge to link curve parameter changes structural changes of test samples. This approach requires structure/function knowledge and is typically not a useful approach until much later in development or for second generation products.
BEBPA:
In your consultancy, are these the approaches you see your clients using?
Dr. Little
: Yes and no. We use the historical data, but utilize the standard vs. standard and other acceptable GMP lots. I have found from a practical perspective that we use point estimates as described in approach
one
above, but supplement with goodness of fit requirements for each of the curves being compared. I don’t care for the use of the 95% confidence interval for non-parallelism as I find that any test sample at the end of the range of the assay (either hypo or hyper potent) will fail, even if the two curves are identical. This approach is explained in-depth in the pre-conference workshop about system similarity.
BEBPA
: Any other topics you would like to highlight?
Dr. Little
: There are so many interesting topics we are exploring with bioassays. Implementation of the acoustic drop technology and use of 384 well plates is all the new rage. I think thoughtful implementation of these technologies will make for robust, high throughput assays in the near future. Also the replacement of one potency with another is always an interesting problem. When and how do we replace assays? How do we confirm that our new proposed method is actually an improvement. One hint is to look at the stability indicating capability of any new method early on in development. If the new method is not stability indicating and the old one is – beware, you probably won’t be replacing the old method.
BEBPA
: Thank you for your time and insights. We look forward to seeing you at the upcoming US Bioassay conference.
Dr. Little
: Thank you. I look forward to seeing everyone at this great conference.
If you are interested in seeing other conference topics, you will find the full meeting brochure
HERE
.
