BEBAC   Ing. Helmut Schütz

EU – EMA

EMA promotes consistent development of bio­equi­va­lence studies through product-specific guidance

On 15 Nov 2013 EMA released its first product-specific guidance on the demonstration of bioequivalence for 16 active substances (dated 24 October 2013) for a three-month public consultation period (i.e., until 15 February 2014).

This is the first wave of product-specific bioequivalence guidance, and the Agency intends to continue developing this type of guidance, which is based on the general principles set out in the Agency’s overarching Guideline on the investigation of bioequivalence, with another wave planned in 2014.*
The aim is to enable a consistent approach to the assessment of applications supported by bioequivalence data, particularly generic applications, across all authorisation routes i.e. centralised, decentralised, mutual-recognition and national authorisation procedures.
The guidance is intended to help companies design study programmes that meet the expectations of European Union regulators, allowing for better transparency and predict­ability of the scientific assessment during the authorisation process.

For each medicine, the document provides guidance in the form of a table on:

Guidances by active substance(s), date of publication of the draft, end of consultation, and dates of adoption and coming into effect. Click the columns’ header to sort (JavaScript required):

# active substance(s) published consultation adopted effective
1Capecitabine (draft, adopted, comments) 2013-11-152014-02-152015-05-212015-12-01
2Carglumic acid (draft, adopted, comments) 2013-11-152014-02-152015-04-082015-10-01
3Dasatinib (draft, adopted) 2013-11-152014-02-152014-11-202015-06-01
4Emtricitabine/Tenofovir Disproxil (draft, adopted) 2013-11-152014-02-152014-11-202015-06-01
5Erlotinib (draft, adopted) 2013-11-152014-02-152014-11-202015-06-01
6Imatinib (draft, adopted, comments) 2013-11-152014-02-152015-04-082015-10-01
7Memantine (draft, adopted, comments) 2013-11-152014-02-152015-04-082015-10-01
8Miglustat (draft, adopted) 2013-11-152014-02-152014-11-202015-06-01
9Oseltamivir (draft, adopted, comments) 2013-11-152014-02-152015-04-082015-10-01
10Posaconazole (draft, adopted, comments) 2013-11-152014-02-152015-04-082015-10-01
11Repaglinide (draft, adopted) 2013-11-152014-02-152014-11-202015-06-01
12Sirolimus (draft, adopted, comments) 2013-11-152014-02-152015-05-212015-12-01
13Sorafenib draft, adopted, comments) 2013-11-152014-02-152015-05-212015-12-01
14Tadalafil (draft, adopted, comments) 2013-11-152014-02-152015-05-212015-12-01
15Telithromycin (draft, adopted, comments) 2013-11-152014-02-152015-05-212015-12-01
16Voriconazole (draft, adopted, comments) 2013-11-152014-02-152015-05-212015-12-01
17Sunitinib (draft, adopted, comments) 2013-12-042014-03-032015-05-212015-12-01
18Asenapine (draft, adopted) 2015-07-152015-11-012016-04-012016-11-01
19Prasugrel (draft, adopted) 2015-07-152015-11-012016-04-012016-11-01
20Sitagliptin (draft, adopted) 2015-07-152015-11-012016-04-012016-11-01
21Zonisamide (draft, adopted) 2015-07-152015-11-012016-04-012016-11-01
22Entecavir (draft, adopted) 2015-10-062016-01-012016-04-012016-11-01
23Rivaroxaban (draft, adopted) 2015-10-062016-01-012016-04-012016-11-01
24Lenalidomide (draft, adopted) 2015-10-062016-01-012016-04-012016-11-01
25Tacrolimus (draft, adopted) 2015-10-062016-01-012016-04-012016-11-01
26Ticagrelor (draft, adopted) 2015-10-062016-01-012016-04-012016-11-01
27Everolimus (draft, adopted) 2016-05-022016-07-312016-12-152017-07-01
28Fingolimod (draft, adopted) 2016-05-022016-07-312016-12-152017-07-01
31Levodopa/Carbidopa/Entacapone (draft, adopted) 2016-05-022016-07-312016-12-152017-07-01
29Paliperidone (draft, adopted) 2016-05-022016-07-312016-12-152017-07-01
30Pazopanib (draft, adopted) 2016-05-022016-07-312016-12-152017-07-01
31Crizotinib (draft) 2016-12-222017-03-31  
32Dabigatran (draft) 2016-12-222017-03-31  
33Elvitegravir / cobicistat / emtricitabine / te­no­fovir disoproxil (draft) 2016-12-222017-03-31  
34Elvitegravir (draft) 2016-12-222017-03-31  
35Emtricitabine, rilpivirine, tenofovir, disopro­xil (draft) 2016-12-222017-03-31  
36Vortioxetine (draft) 2016-12-222017-03-31  

Comments should be provided using this template and sent no later than the respective end of consultation to PKWPsecretariat@ema.europa.eu.


Update 1

APIs requested by the PKWP for review in 2014 so far: asenapine, prasugel, sitagliptin, tacrolimus, and zonisamide (thanks to Jan Welink/MEB for sharing this information).

Update 2

The “Compilation of individual product-specific guidance on demonstration of bioequivalence” (EMA/CHMP/736403/2014) dated 17 Dec was published by the EMA on 19 Dec 2014.

This guideline provides a compilation of product-specific guidance on the demonstration of bioequivalence for individual products authorised within the EU. The procedure for publication is as follows:

Update 3

This […] batch of individual guidance (EMA/CHMP/736403/2014 Rev 1) dated 8 April 2015 replaces the “Compilation of individual product-specific guidance on demonstration of bioequivalence” EMA/CHMP/736403/2014.
New Annex B: Carglumic acid, imatinib, memantine, oseltamivir, and posaconazole. Date for coming into effect: 1 October 2015.

Update 4

EMA/CHMP/736403/2014 Rev 2 dated 21 May 2015 (published on 7 July 2015) replaces EMA/CHMP/736403/2014 Rev 1.

Guidance for capecitabine, sirolimus, sorafenib, sunitinib, tadalafil, telithromycin, and voriconazole were adopted by the CHMP on 21 May 2015.
New Annex C: For products mentioned above. Date for coming into effect: 1 November 2015.

Update 5

New draft guidance for asenapine, prasugrel, sitagliptin, and zonisamide (dated 25 June 2015, published on 15 July 2015).

Update 6

New draft guidance for entecavir, lenalidomide, rivaroxaban, tacrolimus, and ticagrelor (dated 24 September 2015, published on 6 October 2015).

Update 7

EMA/CHMP/736403/2014 Rev 3 dated 1 April 2016 (published on 7 April 2016) replaces EMA/CHMP/736403/2014 Rev 2.

Guidance for asenapine, entecavir, lenalidomide, prasugrel, rivaroxaban, sitagliptin, tacrolimus, ticagrelor, and zonisamide were adopted by the CHMP in April 2016.
New Annex D: For products mentioned above. Date for coming into effect: 1 November 2016.

New draft guidance for everolimus, fingolimod, levodopa / carbidopa / entacapone, paliperidone, and pazopanib (dated 1 April 2016, published on 7 April 2016).

Update 8

Guidance for everolimus, fingolimod, levodopa / carbidopa / entacapone, paliperidone, and pazopanib were adopted by the CHMP in December 2016. Date for coming into effect: 1 July 2017.

New draft guidance for crizotinib, dabigatran, elvitegravir / cobicistat / emtricitabine / tenofovir disoproxil, elvitegravir, and vortioxetine (dated 15 December 2016, published on 22 December 2016).

BEBAC