Impact of the revised USP Chapter <1058> [Analytical Instrument Qualification - AIQ] on the pharmacopeial drug dissolution testing – the beginning of the end of the use of current dissolution apparatuses including Basket/Paddle!

Recently USP revised the above mentioned chapter (https://tinyurl.com/y9wdfl58) to clarify AIQ terminologies including the definition of Design Qualification [DQ]. There is nothing new in the description that should not have been clearly understood by both – the users and manufacturers of the apparatuses including their service providers. However, confusion exists in the minds of analysts and manufacturers who consider that testing and re-testing of the fixed parameters are the qualification, calibration and/or performance verification steps. The chapter clearly describes that such fixed parameters never need to be retested or re-established. With regards to drug dissolution apparatuses, the so called mechanical calibration and/or meeting of the specifications as described in the USP dissolution chapters <711> and <724> would fall in the fixed parameters category, therefore, would never require testing or re-testing.

On the other hand, in the revised chapter a phrase “intended purpose” has repeatedly been used, which is important to note. For example, it is stated that “AIQ is the collection of documented evidence that an instrument performs suitably for its intended purpose (emphasis is mine).” The intended purpose of a dissolution apparatus is to provide dissolution characteristics of a product under standardized experimental conditions. For this purpose one requires a reference product with known dissolution characteristics established independently from a dissolution tester itself so that the tester could show its suitability of providing appropriate dissolution results. The reference product, with known dissolution characteristics, must be an approved product as the testers are used for testing products for human use. As there is no such reference product available at present, one cannot qualify a dissolution tester. If one cannot qualify a dissolution tester, then the USP General Chapters and the monographs, which referred to such testers, lose their validity and scientific credibility. Therefore, enforcement of pharmacopeial monographs for quality assessment of the products loses their purpose and usefulness.

Furthermore, as per the chapter, the requirement that “Users are ultimately responsible for specifying their needs and ensuring that a selected instrument meets them” appears confusing and contradictory to commonly understood roles of the pharmacopeias. In general, pharmacopeias set standards/specifications for instruments and provide guidance for their use so that users follow a common and standard protocol. However, this chapter appears to imply that pharmacopeias have no or limited role in this regard, but the users and manufacturers should decide between themselves as to what the intended use of the apparatuses is and what specifications are to be developed. This does not make sense that the pharmacopeia would not play any role in setting standards/specifications for instruments and for their operation. An indirect implication of this suggestion would be that as of now any tester with associated specifications of users’ choice could be used. This clearly opens up possibility of acceptance of non-compendial testers of users’ choice, at least for drug dissolution testing purposes.

Drug dissolution tests are included in the pharmacopeias to establish quality of the manufactured pharmaceutical products in particular tablet and capsule. Pharmacopeial standards/specifications play an important role in this regard by setting the standards/specifications. Therefore, there is an urgent need for an alternate qualified tester to fill this gap created by the revision of the USP Chapter. In this regard, three items which need to be addressed: (1) suggestion of a modified dissolution tester(s); (2) selection of a set of standardized experimental conditions; and (3) availability of a reference product, or its alternate, with known dissolution characteristics.

I have provided suggestions which would be helpful in fulfilling these requirements. These can be found at the links provided below. In addition, I provide detailed and thorough in-person seminars and customized on-site training to help in understanding the science of drug dissolution testing along with addressing its associated current problems for product evaluations. One may consider attending the seminars such as an upcoming one in Boston, MA (http://www.drug-dissolution-testing.com/?page_id=2101) or request for an on-site training at principal@pharmacomechanics.com.

Relevant links:

(1) Suggested tester and standard set of experimental conditions (link).

(2) Reference product or its alternate (link)

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