Computer program facilitates comparison of drug liberation profiles: faster bioequivalence testing now possible

The rate of drug liberation is only one of the many parameters measured during bioequivalence testing. Drug liberation or dissolution from solids is caused by a series of both simultaneous and successive processes including wetting, capillary penetration, swelling, disintegration and diffusion. The shape of the drug liberation-time curve for each dosage level of a particular drug, which is packaged in a particular medium, is unique. The mathematical equations for describing these curves are very complex.

A freely available computer program called DDSolver simplifies the mathematical calculations used to compare the drug liberation profiles of drugs undergoing bioequivalence testing according to Yong Zhang, et al. in AAPS Journal.  These researchers report that DDSolver can perform "most existing techniques for comparing drug release data" and that "Sample runs of the program demonstrated that the results were satisfactory."

Best-in-Class Bioequivalence Test Providers:

• Ensure that the route of administration and intended use simulate actual conditions
• Test for strength, quality and performance characteristics
• Make sure drugs are comparable in dosage form

Top Considerations Before Selecting Bioequivalence Test Provider:

Data from bioequivalence studies may not be enough to gain regulatory approval. In the past, the U.S. Food and Drug Administration (FDA) has held up marketing of bioequivalent drugs until further analyses were performed like analytical method validation and in vitro-in vivo correlation studies. Your bioequivalence test provider should be able to give some guidance on the possibility of whether that may happen with your product.

Key Producers:

1. Rules-Based Medicine, Inc. (RBM) is the world's leading biomarker testing laboratory. RBM’s CustomMAP service can help researchers engaged in bioequivalence testing. This service involves the use of a larger more comprehensive MAP to cast a wide net in the search for novel biomarker patterns and then a smaller more focused MAP of just the biomarker assays of interest. Founded in 1998, RBM has corporate headquarters and CLIA-certified biomarker testing laboratory in Austin, TX; multiplex assay development and manufacturing in Lake Placid, NY and a wholly owned subsidiary EDI GmbH in Reutlingen, Germany. Through EDI GmbH, RBM provides Human Organo-Typic (HOT) cell culture systems which serve as a platform for ex vivo drug safety and efficacy studies.

2. Cetero Research has expertise in the following types of studies: Bioavailability; Absolute Bioavailability; Bioequivalence; First-in-Human; Single and multiple ascending dose in healthy participants or patients; Proof-of-Concept; Interaction; and Drug-drug, drug-food, and alcohol interaction. Cetero has more than 20 years experience in bioanalytical research, which includes providing a quantitative measure of the active drug and its metabolites for bioequivalence studies. This company reports that “Our 50 instruments offer substantial capacity to analyze your samples…in a high-throughput environment to meet the most demanding schedules.” Cetero Research has two state-of-the-art facilities in Houston, TX and Toronto, Canada. This company was formed in 2006 and 2007 by the merger of five research companies that had all been in business since the 1980s.

3. The Jackson Laboratory supports bioequivalence testing by providing scientific resources, techniques, software, data and mice colonies for test animals to scientists in research institutions and laboratories around the world. Services include testing numerous medicinal entities, including small molecules, antibodies, siRNAs and ES cell-derived therapies, as well as customizable compound evaluation, phenotyping and pathology services. It fulfills its mission statement of “discover(ing) the genetic basis for preventing, treating and curing human disease, and…enable(ing) research and education for the global biomedical community" by offering academic programs for teachers, and high school through predoctoral students, as well as offering student internships and hosting events on campuses. A third laboratory in Florida will be added to its two existing facilities in Maine and California.

4. Atlantic Life Sciences Inc. offers Bioequivalence, Bioavailability, Nutraceuticals and Biosimilars clinical trial services for Phase 0 and Phase 1. Clients have the company’s undivided attention because it only conducts one study at a time. It takes 2 to 3 weeks for ALS to put a bioequivalence study in place and 3 to 4 weeks after collection of the last sample for the final report to be sent to the customer. ALS reports that "We gained the reputation of accomplishing complex studies on time and get them done right from the first time. Our studies pass the regulatory review and inspections successfully."

Bioequivalence Test
Definition: Test which is performed to see if bioequivalence (BE) is achieved. BE occurs when there is no statistical difference between the rate and extent of absorption of the active ingredient from those of a reference product which has been administered at the same molar dose under the same conditions as the active ingredient. BE involves the comparison of the bioavailability (BA) of one product with the BA of another product.