Since the reference product would have been approved on the basis of clinical trials where the safety and efficacy of that product was established, the need to redo expensive and time consuming clinical trials to assess the safety and efficacy is considered unnecessary and instead, a surrogate measure whereby the concentration of drug in serum/plasma of human subjects is compared between the test and reference product is considered more appropriate. The assessment of the safety and efficacy of multisource (generic) products involves a comparative study between the generic (test) products to be registered versus the innovator (reference) where their respective bioavailabilities are compared. In this paper, a waiver of BA/BE studies is being proposed also for Class III. Highly permeable drug substances (Class I according to the BCS). The biopharmaceutics classification system (BCS): Class III drugs better candidates for BA/BE waiver Author links open overlay panel Henning H Blume Barbara S Schug.

Hussain's (USA Food and Drug Administration-FDA) presentation described the implications of gastrointestinal residence times on drugs with low permeability where incomplete absorption of such drugs may occur in spite of them having high solubility. Such dissolution tests will require specific dissolution media including perhaps surfactants, in order to reflect in vivo processes for low solubility drugs.Dr. He also discussed the possibility of extending the concept to Class 2 low solubility drugs with dissolution rate limited absorption provided theDissolution test reflects the in vivo solubilization and dissolution process.

Additional information includes chemical structural attributes, chirality, therapeutic indications, dose sizes, therapeutic window, polymorphism, pKa, partition coefficient, solubility, dissolution, permeability, absorption, distribution, metabolism and excretion information. He is in the process of establishing a database which will record various properties of drugs and drug products including their formulations and bioequivalence assessment. Dirk Barends of the National Institute of Public Health & The Environment, The Netherlands described his efforts of literature data mining, which can provide valuable evidence for waivers based upon the BCS. He reported that no application for waiving bioequivalence in the Mutual Recognition Procedure has been acceptable to date.The second session of the workshop involved presentations which described evidence for waivers based upon the BCS.Dr. Olling of the Medicines Evaluation Board of the Netherlands discussed the European guideline and acceptance of the BCS for waiving bioequivalence in the European Union.

He referred to a list of excipients and their effects on permeability from studies using CACO 2Cell lines. The main emphasis of this research is focused on drugs with high solubility but low permeability (class 3) which has resulted in 3 draft proposals which relate to the influence of common excipients on drug intestinal permeability, intestinal transit and absorption and criteria for dissolution profile similarity. James Polli of the University of Maryland's School of Pharmacy in Baltimore, USA described the efforts being made by the Product Quality Research Institute's (PQRI) BCS working Group. This is important information which could ultimately be used to obtain a biowaiver for class 3 drugs based uponDissolution rate coupled with solubility and permeability considerations.Dr.

Roman of GlaxoSmithKline, USA presented `in house' information where he showed that based upon the solubility, permeability and pharmacokinetics of a number of drugs under development, the criteria for receiving a BCS waiver as currently defined may be too restrictive. He emphasized the fact that acidic drugs can have high solubility above pH of 5, yet lower solubility below pH=5 and drugs that are weak bases can have low solubility above pH of 6 yet high solubility below pH=6.Dr. The contention is that many ionizable drugs may fail this definition due to insufficient drug solubility in only a portion of the pH range which is stipulated over 1 - 7.5. This information will be used to consider whether the current definition ofCan be broadened. The PQRI is currently collecting data on orally administered drugs which are ionizable. These excipients also affect intestinal transit times of some drugs.

Bcs Class 1 Drugs Example