Can an Appropriate Dissolution Method Transfer Protocol be Developed?

In simple terms, a dissolution method transfer protocol (“protocol”) is a description of a mutual understanding of two parties, developer or current user of an analytical method (“originator”) and the receiver (“recipient”) of the method as to how a dissolution test is to be conducted.

There are numerous situations where such protocols are needed, for example, transferring a method from R&D to the QC section, one plant to another plant, manufacturer to contract organization (CRO) or to sub contractor etc. The easiest and most practical approach for developing the protocol appears to be  that both parties work together to develop step by step instructions which are able to be followed by current or future analysts to conduct the test as expected to produce consistent results.

The understanding between the two parties reflects how a test is to be conducted and what kind of output should be expected. The protocol can be: (1) simple/verbal understanding between parties such as preparation of a 0.05M phosphate buffer having pH 5.8 as per USP or; (2) detailed and documented (written) step by step set of instructions for conducting the analytical test, e.g., dissolution. In both cases, the common aspect is that the method should be able to provide output which can be compared, for example; the final pH of the buffer solution, or dissolution results. For the comparison of results between two parties most often two sets of values are used which are the mean and standard deviation (STD) describing the characteristics of the test product.

Comparative testing is the most common form of method transfer approach in the pharmaceutical industry. It involves two or more laboratories executing a preapproved protocol resulting in data (means and STDs). The similarity or equivalency of these data is established based on statistical evaluation, often using Student t-test.

The most important and critical thing to consider here is that similarity or equivalency of results from the two parties or laboratories can only be established based on statistical evaluation using means and STDs. If the laboratories or parties cannot provide appropriate values for these two parameters then the comparison of the method cannot be established and there is no benefit of writing a protocol no matter how careful or elaborate practice of protocol writing may be.

In addition, a protocol requires a common product for testing with expected mean and STD values. This common product can be an in-house developed product or a reference product from an external source, such as a USP Reference Standard (RS).

In short, a method transfer protocol may be considered as a step-by-step cook-book type set of instructions (recipe) to follow for analyzing a (reference) product to obtain mean and STD values of parameter/characteristic, such as dissolution.

The question is, can such a protocol be written for a dissolution method transfer. The simple answer is, no. The dissolution tests as currently conducted would not meet the requirements for developing the protocol. Reason #1: A reference drug product with known dissolution characteristics, in particular, in humans is not available. Reason #2: Commonly, dissolution results are reported as individual values (e.g., Q-based), mostly without STD values. Therefore, appropriate (statistical) comparisons of results would not be possible.

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