Essar ● 2006-08-22 11:07 (6449 d 18:12 ago) Posting: # 235 Views: 5,418 |
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Dear All, Greetings! Just as we receive recommendations from Office of Generic Drugs (OGD) of US-FDA regarding which BE study design to be followed and what in-vitro dissolution criteria to be adopted, does any regulatory authority in EU provides similar recommendations? Request you to please provide your inputs. Regards, Essar |
Helmut ★★★ Vienna, Austria, 2006-08-22 17:45 (6449 d 11:34 ago) @ Essar Posting: # 236 Views: 4,792 |
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Hello Essar! ❝ Just as we receive recommendations from Office of Generic Drugs (OGD) of US-FDA regarding which BE study design to be followed and what in-vitro dissolution criteria to be adopted, does any regulatory authority in EU provides similar recommendations? Let's start with the easy one: BCS is part of the European Note for Guidance (NfG) on BA/BE (Appendix II), which is - with minor differences - the same as the US-regulation. Some conditions of US-FDA's regulations (e.g., the pH range) are expected to be relaxed in the near future. pH-range US: 1.0-7.5EU: 1.0-6.8Sampling points US: <4EU: <3Coefficient of variation US: <20% at earlier time pointsEU: no restrictionsUS: <10% at other time pointsEU: <10% at other time pointsConcerning BE designs, recommendations are less specific in the European guideline than US-FDA's are; at '3.1 Design' the EU-NfG states: The study should be designed in such a way that the formulation effect can be distinguished from other effects. If the number of formulations to be compared is two, a two-period, twosequence crossover design is often considered to be the design of choice.
EMEA published a document concerning multiplicity in 2002 (in the example given above you should calculate a 95% confidence interval instead of the common 90% CI). Another point are acceptance ranges other than 80%-125% (standard for all drugs in the US): an extended acceptance range of e.g., 75%-133% was possible (if based on sound clinical justification) in the EU for many years, but according to a recently published document European authorities are expected to be more restrictive in their practice (see also this post). A concept paper for Highly Variable Drugs / Drug Products is currently in preparation: replicate designs and reference scaled average BE are on their way (= current practice in the US). Population and Individual Bioequivalence is not covered in any European Guideline; if you want to perform such a study, a scientific advisory meeting is almost inevitable.
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