Ing. Helmut Schütz
Questions & Answers
EU – EMA
The EMA’s CHMP/EWP Pharmacokinetics Working Party (PKWP) published ‘Questions & Answers: Positions on specific questions addressed to the Pharmacokinetics Working Party’ EMEA/618604/2008 Rev. 13 (19 November 2015, published 03 March 2016; for previous versions see the end of the page).
Background
In the context of assessment procedures, the Pharmacokinetics Working Party (PKWP), or its predecessor the Therapeutic Subgroup on Pharmacokinetics of the Efficacy Working Party (EWP-PK subgroup), is occasionally consulted by the CHMP or, following CHMP’s agreement, by other Committees, Working parties or the CMD(h). The objective is to address specific questions in relation to pharmacokinetic evaluations and particularly the requirements and assessment of bioequivalence studies. The positions, which are being elaborated by the PKWP in response to such questions, are being forwarded to the enquiring party for consideration in their assessment.
It is understood that such position will be reflected in the procedure-related assessment reports if applicable. In some cases however, these position might also be of more general interest as they interpret a very specific aspect that would not necessarily be covered by guidelines. This paper summarises these positions which have been identified as being within this scope. In addition, general clarifications related to guidelines authored by the PKWP are subject to specific positions in this paper.
It should be noted that these positions are based on the current scientific knowledge as well as regulatory precedents. They should be read in conjunction with the applicable guidelines on bioequivalence in their current version. If the questions have initially been raised in the context of specific assessment procedures, details of these procedures have been redacted for reasons of confidentiality.
This compilation will be updated with new positions as soon as they become available. Likewise, if a position is being considered outdated, e.g. due to new evolutions in the scientific knowledge including revisions to the applicable guidelines, positions will be removed from this document. Positions previously prepared by the EWP-PK subgroup are endorsed by the current PKWP unless removed from this document.
The positions in this document are addressing very specific aspects. They should not be quoted as product-specific advice on a particular matter as this may require reflection of specific data available for this product. By no means should these positions be understood as being legally enforceable.
Topics covered are (or were):
Cocktail studies for investigating in vivo drug interaction potentialdeleted 09/2012 (covered in revised GL on the Investigation of Drug Interactions)Requirements for food-interaction studies for MR formulationsdeleted 07/2015 (covered in MR-GL)BE studies for paroxetine (SD versus MD studies)deleted 07/2010 (covered in BE-GL)Interpretation of BE data in relation to both parent and metabolite PK datadeleted 07/2010 (covered in BE-GL)- BE studies in children
BE of gastro-resistant preparations (e.g. omeprazole)deleted 07/2015 (covered in MR-GL)- BE studies for generic products containing clopidogrel updated 07/2010
- Acceptance criteria for BE studies for losartan new 07/2010
- BE assessment of generics for tacrolimus new 07/2010
- Requirements for demonstration of BE for ciclosporine generics new 07/2010
- Requirements for demonstration of BE for mycophenolate mofetil generics new 01/2011
- Recommendations on determination of absolute and relative BA new 01/2011
- Clarification on the recommended statistical method for the analysis of a BE study new 01/2011
Requirements for demonstration of BE for generics of biphasic MR formulations for oral usedeleted 07/2015 (covered in MR-GL)- Effect of sorbitol on the PK of highly permeable drug substances new 09/2012
- Requirement to perform ISR new 12/2012
- Number of subjects in a two-stage BE study design new 02/2013
- BE studies for generic application of omega 3 fatty acid ethylesters in a soft gelatine capsule new 10/2013
- Acceptability of an “additional strengths biowaiver” when BE to the reference product has been established with a BCS-based biowaiver new 10/2013
- Question on a generic application for Quetiapine Lambda 200, 300, 400 mg PR tablets new 10/2013
BCS classification of memantinedeleted 07/2015 (covered in memantine product-specific BE guidance)- Ebastine: use of metabolite data to demonstrate BE between inactive pro-drugs new 05/2014
- IQ Consortium Induction Working Group Questions new 10/2014
- Evaluation of orally inhaled medicinal products new 01/2015
- Clarifications on the “Evaluation of the pharmacokinetics of medicinal products in patients with impaired hepatic function” guideline new 01/2015
- Suitability of a 3-period replicate design scheme for the demonstration of within-subject variability for Cmax new 06/2015
Document’s changes and dates. Click the columns’ header to sort (JavaScript required):
| # | Edition/Revision | Date |
|---|---|---|
| 1 |  First version 87KB |
2009-01-22 |
| 2 | First version, update 94KB |
2009-06-22 |
| 3 | Revision 01 89KB |
2009-07-23 |
| 4 | Revision 02 182KB |
2010-07-22 |
| 5 | Revision 03 195KB |
2011-01-26 |
| 6 | Revision 04 282KB |
2012-02-16 |
| 7 | Revision 05 419KB |
2012-09-20 |
| 8 | Revision 06 300KB |
2012-12-10 |
| 9 | Revision 07 403KB |
2013-02-13 |
| 10 | Revision 08 452KB |
2013-10-10 |
| 11 | Revision 09 479KB |
2014-05-02 |
| 12 | Revision 10 494KB |
2014-10-07 |
| 13 | Revision 11 535KB |
2015-01-22 |
| 14 | Revision 12 507KB |
2015-06-25 |
| 15 |  Revision 13 473KB |
2015-11-19 |
document date 2009-03-06 | last update 2022-10-19