14 April 2020

EMA/PRAC/132684/2020
Human Division

Pharmacovigilance Risk Assessment Committee (PRAC)
Draft agenda for the meeting on 14-17 April 2020

Chair: Sabine Straus – Vice-Chair: Martin Huber
14 April 2020, 10:30 – 19:30, via teleconference
15 April 2020, 08:30 – 19:30, via teleconference
16 April 2020, 08:30 – 19:30, via teleconference
17 April 2020, 08:30 – 16:00, via teleconference
Organisational, regulatory and methodological matters (ORGAM)
30 April 2020, 09:00-12:00, via teleconference
Health and safety information
In accordance with the Agency’s health and safety policy, delegates are to be briefed on health, safety
and emergency information and procedures prior to the start of the meeting.
Disclaimers
Some of the information contained in this agenda is considered commercially confidential or sensitive
and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed
against products, it must be noted that these may not reflect the full wording proposed by applicants
and may also change during the course of the review. Additional details on some of these procedures
will be published in the PRAC meeting highlights once the procedures are finalised.
Of note, this agenda is a working document primarily designed for PRAC members and the work theCommittee undertakes.
Note on access to documents
Some documents mentioned in the agenda cannot be released at present following a request foraccess to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to ongoing procedures for which a final decision has not yet been adopted. They will become public when
adopted or considered public according to the principles stated in the Agency policy on access to
documents (EMA/127362/2006, Rev. 1).

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An agency of the European Union© European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged.

Table of contents
1.

Introduction

1.1.

Welcome and declarations of interest of members, alternates and experts .......... 12

1.2.

Agenda of the meeting on 14-17 April 2020 ......................................................... 12

1.3.

Minutes of the previous meeting on 09-12 March 2020 ........................................ 12

2.

EU referral procedures for safety reasons: urgent EU procedures 12

2.1.

Newly triggered procedures ................................................................................. 12

2.2.

Ongoing procedures ............................................................................................. 12

2.3.

Procedures for finalisation.................................................................................... 12

3.

EU referral procedures for safety reasons: other EU referral
procedures

3.1.

Newly triggered procedures ................................................................................. 12

3.2.

Ongoing procedures ............................................................................................. 12

3.3.

Procedures for finalisation.................................................................................... 13

3.3.1.

Ingenol mebutate - PICATO - EMEA/H/A-20/1489 ........................................................ 13

3.4.

Re-examination procedures .................................................................................. 13

3.5.

Others .................................................................................................................. 13

4.

Signals assessment and prioritisation

4.1.

New signals detected from EU spontaneous reporting systems ............................ 13

4.1.1.

Abiraterone – ZYTIGA (CAP) ..................................................................................... 13

4.1.2.

Bisoprolol (NAP) ...................................................................................................... 13

4.1.3.

Paclitaxel – ABRAXANE (CAP), APEALEA (CAP), PAZENIR (CAP); NAP ............................. 14

4.1.4.

Pomalidomide – IMNOVID (CAP) ................................................................................ 14

4.2.

New signals detected from other sources ............................................................. 14

4.2.1.

Vedolizumab – ENTYVIO (CAP) .................................................................................. 14

4.3.

Signals follow-up and prioritisation ...................................................................... 15

4.3.1.

Adalimumab – AMGEVITA (CAP), AMSPARITY (CAP), HALIMATOZ (CAP), HEFIYA (CAP), HULIO(CAP), HUMIRA (CAP) - EMEA/H/C/000481/SDA/116, HYRIMOZ (CAP), IDACIO (CAP), IMRALDI(CAP) ..................................................................................................................... 15

4.3.2.

5 alfa-reductase inhibitors (5ARIs): finasteride (NAP); dutasteride (NAP) ....................... 15

4.3.3.

Andexanet alfa – ONDEXXYA (CAP) - EMEA/H/C/004108/SDA/010................................. 15

4.3.4.

Ceftriaxone (NAP) .................................................................................................... 15

4.3.5.

Ibuprofen – PEDEA (CAP); NAP; ketoprofen (NAP) and fixed-dose combinations:chlorphenamine, ibuprofen, phenylephrine (NAP); dimenhydrinate, ibuprofen, caffeine (NAP);
ibuprofen, ascorbic acid (NAP); ibuprofen, caffeine (NAP); ibuprofen, codeine (NAP); ibuprofen,hydrocodone (NAP); ibuprofen, paracetamol (NAP); ibuprofen, phenylephrine (NAP);
ibuprofen, pseudoephedrine (NAP); ketoprofen, omeprazole (NAP), ketoprofen, sucralfate(NAP) ..................................................................................................................... 16

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4.3.6.

Idelalisib – ZYDELIG (CAP) - EMEA/H/C/003843/SDA/018 ............................................ 16

4.3.7.

Insulin: insulin aspart – FIASP (CAP) - EMEA/H/C/004046/SDA/004, NOVOMIX (CAP) EMEA/H/C/000308/SDA/055, NOVORAPID (CAP) - EMEA/H/C/000258/SDA/050; insulin aspart,
insulin degludec – RYZODEG (CAP) - EMEA/H/C/002499/SDA/007; insulin bovine (NAP);
insulin degludec – TRESIBA (CAP) - EMEA/H/C/002498/SDA/014; insulin degludec, liraglutide– XULTOPHY (CAP) - EMEA/H/C/002647/SDA/004; insulin determir – LEVEMIR (CAP) EMEA/H/C/000528/SDA/053; insulin glargine, lixisenatide - SULIQUA (CAP) EMEA/H/C/004243/SDA/007; insulin glulisine – APIDRA (CAP) - EMEA/H/C/000557/SDA/042;
insulin human – ACTRAPHANE (CAP) - EMEA/H/C/000427/SDA/025, ACTRAPID (CAP) EMEA/H/C/000424/SDA/026, INSULATARD (CAP) - EMEA/H/C/000441/SDA/029, INSUMAN(CAP) - EMEA/H/C/000201/SDA/050, MIXTARD (CAP) - EMEA/H/C/000428/SDA/027,
PROTAPHANE (CAP) - EMEA/H/C/000442/SDA/029, NAP; insulin lispro – HUMALOG (CAP) EMEA/H/C/000088/SDA/033, INSULIN LISPRO SANOFI (CAP) - EMEA/H/C/004303/SDA/002,
LIPROLOG (CAP) - EMEA/H/C/000393/SDA/026; insulin porcine (NAP) ........................... 16

4.3.8.

Tumour necrosis factor (TNF) inhibitors: adalimumab - AMGEVITA (CAP), AMSPARITY (CAP),
HALIMATOZ (CAP), HEFIYA (CAP), HULIO (CAP), HUMIRA (CAP), HYRIMOZ (CAP), IDACIO(CAP), IMRALDI (CAP); certolizumab pegol - CIMZIA (CAP); etanercept - BENEPALI (CAP),ENBREL (CAP), ERELZI (CAP); golimumab - SIMPONI (CAP); infliximab - FLIXABI (CAP),
INFLECTRA (CAP), REMICADE (CAP), REMSIMA (CAP), ZESSLY (CAP) ............................ 17

5.

Risk management plans (RMPs)

5.1.

Medicines in the pre-authorisation phase ............................................................. 17

5.1.1.

Amikacin - EMEA/H/C/005264, Orphan ....................................................................... 17

5.1.2.

Avapritinib - EMEA/H/C/005208, Orphan .................................................................... 17

5.1.3.

Belantamab mafodotin - EMEA/H/C/004935, Orphan .................................................... 17

5.1.4.

Cabazitaxel - EMEA/H/C/005178 ............................................................................... 18

5.1.5.

Crizanlizumab - EMEA/H/C/004874, Orphan ................................................................ 18

5.1.6.

Fostemsavir - EMEA/H/C/005011 ............................................................................... 18

5.1.7.

Idebenone - EMEA/H/C/005123, Orphan .................................................................... 18

5.1.8.

Luspatercept - EMEA/H/C/004444, Orphan ................................................................. 18

5.1.9.

Paliperidone - EMEA/H/C/005486 .............................................................................. 18

5.1.10.

Sodium oxybate – HOPVEUS (CAP MAA) - EMEA/H/C/004962........................................ 18

5.1.11.

Teriparatide - EMEA/H/C/005233 ............................................................................... 19

5.1.12.

Valoctocogene roxaparvovec - EMEA/H/C/004749, Orphan, ATMP ................................. 19

5.2.

Medicines in the post-authorisation phase – PRAC-led procedures ....................... 19

5.2.1.

Alemtuzumab - LEMTRADA (CAP) - EMEA/H/C/003718/II/0031 ..................................... 19

5.2.2.

Asparaginase - SPECTRILA (CAP) - EMEA/H/C/002661/II/0017 ..................................... 19

5.2.3.

Dexamethasone - OZURDEX (CAP) - EMEA/H/C/001140/II/0037 ................................... 20

5.2.4.

Docetaxel - DOCETAXEL ZENTIVA (CAP) - EMEA/H/C/000808/II/0061 ........................... 20

5.2.5.

Docetaxel - TAXOTERE (CAP) - EMEA/H/C/000073/II/0134 ........................................... 20

5.2.6.

Histamine dihydrochloride - CEPLENE (CAP) - EMEA/H/C/000796/II/0040 ...................... 20

5.2.7.

Nonacog alfa - BENEFIX (CAP) - EMEA/H/C/000139/II/0163 ......................................... 21

5.2.8.

Rivastigmine - EXELON (CAP) - EMEA/H/C/000169/WS1773/0128; PROMETAX (CAP) EMEA/H/C/000255/WS1773/0128 ............................................................................. 21

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5.2.9.

Sevelamer - RENAGEL (CAP) - EMEA/H/C/000254/WS1775/0114; Sevelamer carbonate RENVELA (CAP) - EMEA/H/C/000993/WS1775/0051;SEVELAMER CARBONATE WINTHROP(CAP) - EMEA/H/C/003971/WS1775/0024 .................................................................. 21

5.2.10.

Tegafur, gimeracil, oteracil - TEYSUNO (CAP) - EMEA/H/C/001242/II/0042 .................... 21

5.3.

Medicines in the post-authorisation phase – CHMP-led procedures ...................... 22

5.3.1.

Andexanet alfa - ONDEXXYA (CAP) - EMEA/H/C/004108/II/0009/G ............................... 22

5.3.2.

Anidulafungin - ECALTA (CAP) - EMEA/H/C/000788/II/0040.......................................... 22

5.3.3.

Avelumab - BAVENCIO (CAP) - EMEA/H/C/004338/II/0015 ........................................... 22

5.3.4.

Bedaquiline - SIRTURO (CAP) - EMEA/H/C/002614/X/0036/G, Orphan ........................... 23

5.3.5.

Encorafenib - BRAFTOVI (CAP) - EMEA/H/C/004580/WS1695/0008; Binimetinib - MEKTOVI(CAP) - EMEA/H/C/004579/WS1695/0007 .................................................................. 23

5.3.6.

Brodalumab - KYNTHEUM (CAP) - EMEA/H/C/003959/II/0014 ....................................... 23

5.3.7.

Buprenorphine, naloxone - SUBOXONE (CAP) - EMEA/H/C/000697/X/0042 ..................... 24

5.3.8.

Canagliflozin - INVOKANA (CAP) - EMEA/H/C/002649/II/0046....................................... 24

5.3.9.

Canagliflozin, metformin - VOKANAMET (CAP) - EMEA/H/C/002656/II/0051.................... 24

5.3.10.

Carfilzomib - KYPROLIS (CAP) - EMEA/H/C/003790/II/0043, Orphan ............................. 25

5.3.11.

Catridecacog - NOVOTHIRTEEN (CAP) - EMEA/H/C/002284/II/0026/G ........................... 25

5.3.12.

Certolizumab pegol - CIMZIA (CAP) - EMEA/H/C/001037/II/0084/G............................... 25

5.3.13.

Certolizumab pegol - CIMZIA (CAP) - EMEA/H/C/001037/II/0087 .................................. 26

5.3.14.

Clopidogrel - ISCOVER (CAP) - EMEA/H/C/000175/WS1769/0140; PLAVIX (CAP) EMEA/H/C/000174/WS1769/0138 ............................................................................. 26

5.3.15.

Delamanid - DELTYBA (CAP) - EMEA/H/C/002552/II/0040, Orphan................................ 26

5.3.16.

Dupilumab - DUPIXENT (CAP) - EMEA/H/C/004390/II/0027 .......................................... 27

5.3.17.

Esketamine - SPRAVATO (CAP) - EMEA/H/C/004535/II/0001/G ..................................... 27

5.3.18.

Granisetron - SANCUSO (CAP) - EMEA/H/C/002296/II/0056/G ...................................... 27

5.3.19.

Herpes zoster vaccine (recombinant, adjuvanted) - SHINGRIX (CAP) EMEA/H/C/004336/II/0022 ....................................................................................... 28

5.3.20.

Ibrutinib - IMBRUVICA (CAP) - EMEA/H/C/003791/II/0059, Orphan ............................... 28

5.3.21.

Infliximab - REMSIMA (CAP) - EMEA/H/C/002576/II/0082 ............................................ 29

5.3.22.

Insulin glargine - ABASAGLAR (CAP) - EMEA/H/C/002835/WS1587/0028/G; insulin lispro HUMALOG (CAP) - EMEA/H/C/000088/WS1587/0178/G................................................ 29

5.3.23.

Ivacaftor - KALYDECO (CAP) - EMEA/H/C/002494/II/0082, Orphan ............................... 29

5.3.24.

Ixekizumab - TALTZ (CAP) - EMEA/H/C/003943/II/0031 .............................................. 29

5.3.25.

Lacosamide - LACOSAMIDE UCB (CAP) - EMEA/H/C/005243/WS1782/0006; VIMPAT (CAP) EMEA/H/C/000863/WS1782/0088 ............................................................................. 30

5.3.26.

Lenalidomide - REVLIMID (CAP) - EMEA/H/C/000717/II/0112/G .................................... 30

5.3.27.

Levetiracetam - KEPPRA (CAP) - EMEA/H/C/000277/WS1664/0187 ............................... 30

5.3.28.

Lumacaftor, ivacaftor - ORKAMBI (CAP) - EMEA/H/C/003954/II/0055 ............................ 31

5.3.29.

Methotrexate - NORDIMET (CAP) - EMEA/H/C/003983/II/0016...................................... 31

5.3.30.

Nivolumab - OPDIVO (CAP) - EMEA/H/C/003985/II/0080 ............................................. 31

5.3.31.

Obinutuzumab - GAZYVARO (CAP) - EMEA/H/C/002799/II/0038, Orphan ....................... 32

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5.3.32.

Ocrelizumab - OCREVUS (CAP) - EMEA/H/C/004043/II/0017 ........................................ 32

5.3.33.

Olaparib - LYNPARZA (CAP) - EMEA/H/C/003726/II/0033 ............................................. 32

5.3.34.

Pegvaliase - PALYNZIQ (CAP) - EMEA/H/C/004744/II/0007/G, Orphan ........................... 33

5.3.35.

Perampanel - FYCOMPA (CAP) - EMEA/H/C/002434/II/0047.......................................... 33

5.3.36.

Pomalidomide - IMNOVID (CAP) - EMEA/H/C/002682/II/0036/G, Orphan ....................... 33

5.3.37.

Ravulizumab - ULTOMIRIS (CAP) - EMEA/H/C/004954/II/0002...................................... 33

5.3.38.

Rivaroxaban - XARELTO (CAP) - EMEA/H/C/000944/X/0074/G ...................................... 34

5.3.39.

Thalidomide - THALIDOMIDE CELGENE (CAP) - EMEA/H/C/000823/II/0061/G ................. 34

5.3.40.

Zoledronic acid - ZOMETA (CAP) - EMEA/H/C/000336/II/0091 ...................................... 34

6.

Periodic safety update reports (PSURs)

6.1.

PSUR single assessment (PSUSA) procedures including centrally authorised products(CAPs) only .......................................................................................................... 35

6.1.1.

Abemaciclib - VERZENIOS (CAP) - PSUSA/00010724/201909 ........................................ 35

6.1.2.

Alemtuzumab - LEMTRADA (CAP) - PSUSA/00010055/201909 ...................................... 35

6.1.3.

Avelumab - BAVENCIO (CAP) - PSUSA/00010635/201909 ............................................ 35

6.1.4.

Bedaquiline - SIRTURO (CAP) - PSUSA/00010074/201909 ............................................ 35

6.1.5.

Cariprazine - REAGILA (CAP) - PSUSA/00010623/201910 ............................................. 36

6.1.6.

Cemiplimab - LIBTAYO (CAP) - PSUSA/00010780/201909 ............................................ 36

6.1.7.

Chenodeoxycholic acid - CHENODEOXYCHOLIC ACID LEADIANT (CAP) PSUSA/00010590/201910 ........................................................................................ 36

6.1.8.

Cholic acid - ORPHACOL (CAP) - PSUSA/00010208/201909 .......................................... 36

6.1.9.

Choriogonadotropin alfa - OVITRELLE (CAP) - PSUSA/00000736/201909 ........................ 36

6.1.10.

Ciclosporin - IKERVIS (CAP); VERKAZIA (CAP) - PSUSA/00010362/201909 .................... 37

6.1.11.

Crizotinib - XALKORI (CAP) - PSUSA/00010042/201908 ............................................... 37

6.1.12.

Dacomitinib - VIZIMPRO (CAP) - PSUSA/00010757/201909 .......................................... 37

6.1.13.

Dapagliflozin - EDISTRIDE (CAP); FORXIGA (CAP) - PSUSA/00010029/201910 ............... 37

6.1.14.

Darunavir, cobicistat, emtricitabine, tenofovir alafenamide - SYMTUZA (CAP) PSUSA/00010646/201909 ........................................................................................ 37

6.1.15.

Darvadstrocel - ALOFISEL (CAP) - PSUSA/00010676/201909 ........................................ 37

6.1.16.

Denosumab - PROLIA (CAP) - PSUSA/00000954/201909 .............................................. 38

6.1.17.

Dexamethasone - NEOFORDEX (CAP) - PSUSA/00010480/201909 ................................. 38

6.1.18.

Dulaglutide - TRULICITY (CAP) - PSUSA/00010311/201909 .......................................... 38

6.1.19.

Dupilumab - DUPIXENT (CAP) - PSUSA/00010645/201909 ........................................... 38

6.1.20.

Eluxadoline - TRUBERZI (CAP) - PSUSA/00010528/201909........................................... 38

6.1.21.

Etravirine - INTELENCE (CAP) - PSUSA/00001335/201909............................................ 39

6.1.22.

Fremanezumab - AJOVY (CAP) - PSUSA/00010758/201909 .......................................... 39

6.1.23.

Galcanezumab - EMGALITY (CAP) - PSUSA/00010733/201909 ...................................... 39

6.1.24.

Glycopyrronium - SIALANAR (CAP) - PSUSA/00010529/201909 .................................... 39

6.1.25.

Idebenone - RAXONE (CAP) - PSUSA/00010412/201909 .............................................. 39

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6.1.26.

Infliximab - FLIXABI (CAP); INFLECTRA (CAP); REMICADE (CAP); REMSIMA (CAP); ZESSLY(CAP) - PSUSA/00010759/201908 ............................................................................. 39

6.1.27.

Insulin aspart - FIASP (CAP); NOVOMIX (CAP); NOVORAPID (CAP) - PSUSA/00001749/201909............................................................................................................................. 40

6.1.28.

Insulin degludec, liraglutide - XULTOPHY (CAP) - PSUSA/00010272/201909 ................... 40

6.1.29.

Isavuconazole - CRESEMBA (CAP) - PSUSA/00010426/201909...................................... 40

6.1.30.

Lorlatinib - LORVIQUA (CAP) - PSUSA/00010760/201909 ............................................. 40

6.1.31.

Lusutrombopag - MULPLEO (CAP) - PSUSA/00010755/201909 ...................................... 40

6.1.32.

Mepolizumab - NUCALA (CAP) - PSUSA/00010456/201909 ........................................... 41

6.1.33.

Mogamulizumab - POTELIGEO (CAP) - PSUSA/00010741/201909 .................................. 41

6.1.34.

Naldemedine - RIZMOIC (CAP) - PSUSA/00010753/201909 .......................................... 41

6.1.35.

Naloxegol - MOVENTIG (CAP) - PSUSA/00010317/201909 ............................................ 41

6.1.36.

Naltrexone, bupropion - MYSIMBA (CAP) - PSUSA/00010366/201909 ............................ 41

6.1.37.

Netupitant, palonosetron - AKYNZEO (CAP) - PSUSA/00010393/201910......................... 41

6.1.38.

Niraparib - ZEJULA (CAP) - PSUSA/00010655/201909 .................................................. 42

6.1.39.

Ocrelizumab - OCREVUS (CAP) - PSUSA/00010662/201909 .......................................... 42

6.1.40.

Panitumumab - VECTIBIX (CAP) - PSUSA/00002283/201909 ........................................ 42

6.1.41.

Pitolisant - WAKIX (CAP) - PSUSA/00010490/201909 .................................................. 42

6.1.42.

Raltegravir - ISENTRESS (CAP) - PSUSA/00010373/201909 ......................................... 42

6.1.43.

Ribociclib - KISQALI (CAP) - PSUSA/00010633/201909 ................................................ 42

6.1.44.

Risankizumab - SKYRIZI (CAP) - PSUSA/00010765/201909 .......................................... 43

6.1.45.

Ritonavir - NORVIR (CAP) - PSUSA/00002651/201908 ................................................. 43

6.1.46.

Rivaroxaban - XARELTO (CAP) - PSUSA/00002653/201909........................................... 43

6.1.47.

Sodium zirconium cyclosilicate - LOKELMA (CAP) - PSUSA/00010675/201909 ................. 43

6.1.48.

Sofosbuvir, ledipasvir - HARVONI (CAP) - PSUSA/00010306/201910 ............................. 43

6.1.49.

Telbivudine - SEBIVO (CAP) - PSUSA/00002880/201908 .............................................. 43

6.1.50.

Tenecteplase - METALYSE (CAP) - PSUSA/00002888/201908 ........................................ 44

6.1.51.

Tildrakizumab - ILUMETRI (CAP) - PSUSA/00010720/201909........................................ 44

6.1.52.

Tobramycin - VANTOBRA (CAP) - PSUSA/00010370/201909 ......................................... 44

6.1.53.

Trabectedin - YONDELIS (CAP) - PSUSA/00003001/201909 .......................................... 44

6.1.54.

Velmanase alfa - LAMZEDE (CAP) - PSUSA/00010677/201909 ...................................... 44

6.1.55.

Vernakalant hydrochloride - BRINAVESS (CAP) - PSUSA/00003109/201908 .................... 45

6.1.56.

Vortioxetine - BRINTELLIX (CAP) - PSUSA/00010052/201909 ....................................... 45

6.2.

PSUR single assessment (PSUSA) procedures including centrally authorised products(CAPs) and nationally authorised products (NAPs) .............................................. 45

6.2.1.

Anagrelide - ANAGRELIDE MYLAN (CAP); XAGRID (CAP); NAP - PSUSA/00000208/20190945

6.2.2.

Budesonide, formoterol - BIRESP SPIROMAX (CAP); DUORESP SPIROMAX (CAP); NAP PSUSA/00010585/201908 ........................................................................................ 45

6.2.3.

Octocog alfa - ADVATE (CAP); HELIXATE NEXGEN; KOGENATE BAYER (CAP); KOVALTRY(CAP); NAP - PSUSA/00002200/201908 ..................................................................... 45

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6.2.4.

Thalidomide - THALIDOMIDE CELGENE (CAP); NAP - PSUSA/00002919/201910 .............. 46

6.2.5.

Trientine - CUFENCE (CAP); CUPRIOR (CAP); NAP - PSUSA/00010637/201909 ............... 46

6.2.6.

Zoledronic acid - ZOLEDRONIC ACID HOSPIRA (CAP); ZOLEDRONIC ACID MEDAC (CAP);ZOMETA (CAP); NAP - PSUSA/00003149/201908 ........................................................ 46

6.3.

PSUR single assessment (PSUSA) procedures including nationally authorised
products (NAPs) only ........................................................................................... 46

6.3.1.

Biperiden (NAP) – PSUSA/00000415/201908 .............................................................. 46

6.3.2.

Conjugated estrogens (CE), medroxyprogesterone acetate (MPA) (NAP) –PSUSA/00000582/201908 ........................................................................................ 46

6.3.3.

Dermatophagoides pteronyssinus, dermatophagoides farina (NAP) –PSUSA/00010582/201909 ........................................................................................ 47

6.3.4.

Dexamfetamine (NAP) – PSUSA/00000986/201909 ..................................................... 47

6.3.5.

Finasteride (NAP) – PSUSA/00001392/201908 ............................................................ 47

6.3.6.

Fluocinolone acetonide (NAP) – PSUSA/00010224/201908............................................ 47

6.3.7.

Human plasma protease C1 inhibitor (NAP) – PSUSA/00010163/201908 ........................ 47

6.3.8.

Hydrocortisone (NAP) – PSUSA/00010328/201908 ...................................................... 48

6.3.9.

Lercanidipine (NAP) – PSUSA/00001841/201908 ......................................................... 48

6.3.10.

Modafinil (NAP) – PSUSA/00010242/201908 ............................................................... 48

6.3.11.

Nifuroxazide (NAP) – PSUSA/00002160/201908 .......................................................... 48

6.3.12.

Oxcarbazepine (NAP) – PSUSA/00002235/201908 ....................................................... 48

6.3.13.

Paricalcitol (NAP) – PSUSA/00002316/201908 ............................................................ 49

6.3.14.

Sotalol (NAP) – PSUSA/00002774/201908 .................................................................. 49

6.4.

Follow-up to PSUR/PSUSA procedures ................................................................. 49

6.4.1.

Apixaban - ELIQUIS (CAP) - EMEA/H/C/002148/LEG 036 .............................................. 49

6.4.2.

Brodalumab - KYNTHEUM (CAP) - EMEA/H/C/003959/LEG 005.1 ................................... 49

6.4.3.

Ixekizumab - TALTZ (CAP) - EMEA/H/C/003943/LEG 004.1........................................... 49

6.4.4.

Natalizumab - TYSABRI (CAP) - EMEA/H/C/000603/LEG 070 ......................................... 50

6.4.5.

Secukinumab - COSENTYX (CAP) - EMEA/H/C/003729/LEG 007.1.................................. 50

6.5.

Variation procedure(s) resulting from PSUSA evaluation ..................................... 50

6.5.1.

Docetaxel - TAXOTERE (CAP) - EMEA/H/C/000073/II/0136/G ....................................... 50

7.

Post-authorisation safety studies (PASS)

7.1.

Protocols of PASS imposed in the marketing authorisation(s) .............................. 51

7.1.1.

Asfotase alfa – STRENSIQ (CAP) – EMEA/H/C/PSA/S/0050 ........................................... 51

7.1.2.

Rurioctocog alfa pegol – ADYNOVI (CAP) - EMEA/H/C/PSA/S/0045.1 .............................. 51

7.1.3.

Turoctocog alfa pegol – ESPEROCT (CAP) - EMEA/H/C/PSP/S/0085.1 ............................. 51

7.1.4.

Volanesorsen – WAYLIVRA (CAP) - EMEA/H/C/PSP/S/0080.2 ........................................ 52

7.2.

Protocols of PASS non-imposed in the marketing authorisation(s) ...................... 52

7.2.1.

Cangrelor - KENGREXAL (CAP) - EMEA/H/C/003773/MEA 002.2..................................... 52

7.2.2.

Dibotermin alfa - INDUCTOS (CAP) - EMEA/H/C/000408/LEG 074.2 ............................... 52

7.2.3.

Emtricitabine, tenofovir disoproxil - TRUVADA (CAP) - EMEA/H/C/000594/MEA 047.4 ...... 52

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7.2.4.

Flutemetamol (18F) - VIZAMYL (CAP) - EMEA/H/C/002557/MEA 002.3 ............................ 53

7.2.5.

Hydrocortisone - PLENADREN (CAP) - EMEA/H/C/002185/MEA 009.2 ............................. 53

7.2.6.

Inotersen - TEGSEDI (CAP) - EMEA/H/C/004782/MEA 001.3 ......................................... 53

7.2.7.

Inotersen - TEGSEDI (CAP) - EMEA/H/C/004782/MEA 002.3 ......................................... 53

7.2.8.

Interferon beta-1a - AVONEX (CAP) - EMEA/H/C/000102/MEA 088 ................................ 54

7.2.9.

Interferon beta-1a - REBIF (CAP) - EMEA/H/C/000136/MEA 045 ................................... 54

7.2.10.

Interferon beta-1b - BETAFERON (CAP) - EMEA/H/C/000081/MEA 025 ........................... 54

7.2.11.

Interferon beta-1b - EXTAVIA (CAP) - EMEA/H/C/000933/MEA 023................................ 54

7.2.12.

Patisiran - ONPATTRO (CAP) - EMEA/H/C/004699/MEA 002.3 ........................................ 55

7.2.13.

Peginterferon beta-1a - PLEGRIDY (CAP) - EMEA/H/C/002827/MEA 010 ......................... 55

7.2.14.

Romosozumab - EVENITY (CAP) - EMEA/H/C/004465/MEA 001 ..................................... 55

7.2.15.

Romosozumab - EVENITY (CAP) - EMEA/H/C/004465/MEA 002 ..................................... 55

7.2.16.

Romosozumab - EVENITY (CAP) - EMEA/H/C/004465/MEA 003 ..................................... 56

7.2.17.

Ropeginterferon alfa-2b - BESREMI (CAP) - EMEA/H/C/004128/MEA 001.2 ..................... 56

7.2.18.

Sotagliflozin - ZYNQUISTA (CAP) - EMEA/H/C/004889/MEA 004.1 ................................. 56

7.3.

Results of PASS imposed in the marketing authorisation(s) ................................. 56

7.4.

Results of PASS non-imposed in the marketing authorisation(s).......................... 57

7.4.1.

Agalsidase beta - FABRAZYME (CAP) - EMEA/H/C/000370/II/0113................................. 57

7.4.2.

Blinatumomab - BLINCYTO (CAP) - EMEA/H/C/003731/II/0034/G, Orphan ..................... 57

7.4.3.

Deferasirox - EXJADE (CAP) - EMEA/H/C/000670/II/0068 ............................................. 57

7.4.4.

Etanercept - ENBREL (CAP) - EMEA/H/C/000262/WS1653/0230; LIFMIOR (CAP) EMEA/H/C/004167/WS1653/0024 ............................................................................. 57

7.4.5.

Hydroxycarbamide - SIKLOS (CAP) - EMEA/H/C/000689/II/0045................................... 58

7.4.6.

Infliximab - INFLECTRA (CAP) - EMEA/H/C/002778/II/0079 .......................................... 58

7.4.7.

Infliximab - INFLECTRA (CAP) - EMEA/H/C/002778/II/0080 .......................................... 58

7.4.8.

Infliximab - REMSIMA (CAP) - EMEA/H/C/002576/II/0073 ............................................ 59

7.4.9.

Infliximab - REMSIMA (CAP) - EMEA/H/C/002576/II/0074 ............................................ 59

7.5.

Interim results of imposed and non-imposed PASS submitted before the entry into
force of the revised variation regulation ............................................................... 59

7.5.1.

Alemtuzumab - LEMTRADA (CAP) - EMEA/H/C/003718/MEA 007.9 ................................. 59

7.5.2.

Etanercept - BENEPALI (CAP) - EMEA/H/C/004007/MEA 002.3 ...................................... 59

7.5.3.

Etanercept - BENEPALI (CAP) - EMEA/H/C/004007/MEA 003.3 ...................................... 60

7.5.4.

Etanercept - BENEPALI (CAP) - EMEA/H/C/004007/MEA 004.3 ...................................... 60

7.5.5.

Etanercept - BENEPALI (CAP) - EMEA/H/C/004007/MEA 005.3 ...................................... 60

7.5.6.

Golimumab - SIMPONI (CAP) - EMEA/H/C/000992/MEA 033.3....................................... 60

7.5.7.

Lonoctocog alfa - AFSTYLA (CAP) - EMEA/H/C/004075/MEA 002.1 ................................. 61

7.5.8.

Nivolumab - OPDIVO (CAP) - EMEA/H/C/003985/MEA 008.7 ......................................... 61

7.5.9.

Rivastigmine - EXELON (CAP) - EMEA/H/C/000169/MEA 036.5 ...................................... 61

7.5.10.

Rivastigmine - PROMETAX (CAP) - EMEA/H/C/000255/MEA 037.5 .................................. 61

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7.5.11.

Sirolimus - RAPAMUNE (CAP) - EMEA/H/C/000273/MEA 054.2 ...................................... 62

7.5.12.

Ustekinumab - STELARA (CAP) - EMEA/H/C/000958/MEA 022.19 .................................. 62

7.6.

Others .................................................................................................................. 62

7.6.1.

Deferasirox - EXJADE (CAP) - EMEA/H/C/000670/MEA 075.1 ........................................ 62

7.6.2.

Emicizumab - HEMLIBRA (CAP) - EMEA/H/C/004406/MEA 005 ...................................... 62

7.7.

New Scientific Advice ........................................................................................... 63

7.8.

Ongoing Scientific Advice ..................................................................................... 63

7.9.

Final Scientific Advice (Reports and Scientific Advice letters) .............................. 63

8.

Renewals of the marketing authorisation, conditional renewal andannual reassessments
63

8.1.

Annual reassessments of the marketing authorisation ......................................... 63

8.1.1.

Afamelanotide - SCENESSE (CAP) - EMEA/H/C/002548/S/0032 (without RMP) ................ 63

8.1.2.

Cholic acid - ORPHACOL (CAP) - EMEA/H/C/001250/S/0033 (without RMP)..................... 63

8.1.3.

Susoctocog alfa - OBIZUR (CAP) - EMEA/H/C/002792/S/0028 (without RMP) .................. 63

8.1.4.

Tafamidis - VYNDAQEL (CAP) - EMEA/H/C/002294/S/0055 (without RMP) ...................... 64

8.2.

Conditional renewals of the marketing authorisation ........................................... 64

8.2.1.

Ataluren - TRANSLARNA (CAP) - EMEA/H/C/002720/R/0057 (without RMP) .................... 64

8.3.

Renewals of the marketing authorisation ............................................................. 64

8.3.1.

Aripiprazole - ARIPIPRAZOLE SANDOZ (CAP) - EMEA/H/C/004008/R/0014 (without RMP) . 64

8.3.2.

Carfilzomib - KYPROLIS (CAP) - EMEA/H/C/003790/R/0044 (without RMP) ..................... 64

8.3.3.

Cobimetinib - COTELLIC (CAP) - EMEA/H/C/003960/R/0019 (without RMP)..................... 64

8.3.4.

Everolimus - VOTUBIA (CAP) - EMEA/H/C/002311/R/0065 (without RMP) ....................... 65

8.3.5.

Glycerol phenylbutyrate - RAVICTI (CAP) - EMEA/H/C/003822/R/0034 (without RMP) ...... 65

8.3.6.

Mepolizumab - NUCALA (CAP) - EMEA/H/C/003860/R/0031 (with RMP) .......................... 65

8.3.7.

Pemetrexed - PEMETREXED MEDAC (CAP) - EMEA/H/C/003905/R/0008 (with RMP) ......... 65

8.3.8.

Pemetrexed - PEMETREXED SANDOZ (CAP) - EMEA/H/C/004011/R/0008 (without RMP) .. 65

8.3.9.

Phenylephrine, ketorolac - OMIDRIA (CAP) - EMEA/H/C/003702/R/0015 (with RMP) ........ 65

8.3.10.

Pregabalin - PREGABALIN ACCORD (CAP) - EMEA/H/C/004024/R/0015 (with RMP) .......... 66

8.3.11.

Pregabalin - PREGABALIN SANDOZ (CAP) - EMEA/H/C/004010/R/0012 (with RMP) .......... 66

8.3.12.

Pregabalin - PREGABALIN SANDOZ GMBH (CAP) - EMEA/H/C/004070/R/0013 (with RMP) 66

8.3.13.

Sacubitril, valsartan - ENTRESTO (CAP) - EMEA/H/C/004062/R/0031 (without RMP) ........ 66

8.3.14.

Tasimelteon - HETLIOZ (CAP) - EMEA/H/C/003870/R/0018 (without RMP) ...................... 66

9.

Product related pharmacovigilance inspections

9.1.

List of planned pharmacovigilance inspections ..................................................... 67

9.2.

Ongoing or concluded pharmacovigilance inspections .......................................... 67

9.3.

Others .................................................................................................................. 67

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10.

Other safety issues for discussion requested by the CHMP or the EMA
67

10.1.

Safety related variations of the marketing authorisation...................................... 67

10.2.

Timing and message content in relation to Member States’ safety announcements67

10.3.

Other requests ...................................................................................................... 67

10.4.

Scientific Advice ................................................................................................... 67

11.

Other safety issues for discussion requested by the Member States68

11.1.

Safety related variations of the marketing authorisation...................................... 68

11.2.

Other requests ...................................................................................................... 68

12.

Organisational, regulatory and methodological matters

12.1.

Mandate and organisation of the PRAC ................................................................. 68

12.1.1.

PRAC Rules of Procedure - revision ............................................................................ 68

12.2.

Coordination with EMA Scientific Committees or CMDh-v ..................................... 68

12.3.

Coordination with EMA Working Parties/Working Groups/Drafting Groups ......... 68

12.4.

Cooperation within the EU regulatory network ..................................................... 68

12.4.1.

Coronavirus (COVID-19) pandemic - update ............................................................... 68

12.4.2.

Heads of Medicines Agencies (HMA)-EMA joint big data taskforce – call for nomination to thesteering group......................................................................................................... 68

12.5.

Cooperation with International Regulators........................................................... 68

12.6.

Contacts of the PRAC with external parties and interaction with the Interested
Parties to the Committee ...................................................................................... 69

12.7.

PRAC work plan .................................................................................................... 69

12.8.

Planning and reporting ......................................................................................... 69

12.8.1.

Marketing authorisation applications (MAA) forecast for 2020 – planning update dated Q1 2020............................................................................................................................. 69

12.9.

Pharmacovigilance audits and inspections ........................................................... 69

12.9.1.

Pharmacovigilance systems and their quality systems .................................................. 69

12.9.2.

Pharmacovigilance inspections .................................................................................. 69

12.9.3.

Pharmacovigilance audits.......................................................................................... 69

12.10.

Periodic safety update reports (PSURs) & Union reference date (EURD) list ........ 69

12.10.1.

Periodic safety update reports ................................................................................... 69

12.10.2.

Granularity and Periodicity Advisory Group (GPAG) ...................................................... 69

12.10.3.

PSURs repository ..................................................................................................... 69

12.10.4.

Union reference date list – consultation on the draft list ............................................... 70

12.11.

Signal management .............................................................................................. 70

12.11.1.

Signal management – feedback from Signal Management Review Technical (SMART) Working
Group .................................................................................................................... 70

12.12.

Adverse drug reactions reporting and additional reporting .................................. 70

12.12.1.

Management and reporting of adverse reactions to medicinal products........................... 70

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12.12.2.

Additional monitoring ............................................................................................... 70

12.12.3.

List of products under additional monitoring – consultation on the draft list .................... 70

12.13.

EudraVigilance database ...................................................................................... 70

12.13.1.

Activities related to the confirmation of full functionality ............................................... 70

12.14.

Risk management plans and effectiveness of risk minimisations.......................... 70

12.14.1.

Risk management systems ....................................................................................... 70

12.14.2.

Tools, educational materials and effectiveness measurement of risk minimisations .......... 70

12.15.

Post-authorisation safety studies (PASS) ............................................................. 71

12.15.1.

Post-authorisation Safety Studies – imposed PASS ...................................................... 71

12.15.2.

Post-authorisation Safety Studies – non-imposed PASS ................................................ 71

12.16.

Community procedures ......................................................................................... 71

12.16.1.

Referral procedures for safety reasons ....................................................................... 71

12.17.

Renewals, conditional renewals, annual reassessments ....................................... 71

12.18.

Risk communication and transparency ................................................................. 71

12.18.1.

Public participation in pharmacovigilance .................................................................... 71

12.18.2.

Safety communication .............................................................................................. 71

12.19.

Continuous pharmacovigilance ............................................................................. 71

12.19.1.

Incident management .............................................................................................. 71

12.20.

Others .................................................................................................................. 71

12.20.1.

Strategy on measuring the impact of pharmacovigilance - PRAC interest group (IG) Impact –results and recommendations from case study on stakeholder engagement for valproate . 71

12.20.2.

Summary of product characteristics (SmPC) Advisory Group (AG) – call for nomination.... 72

12.20.3.

Workshop on the role of registries in the monitoring of cancer therapies based on tumours’
genetic and molecular features, 29 November 2019, Amsterdam, the Netherlands – final
report: main observation and follow-up actions ........................................................... 72

13.

Any other business

72

14.

Explanatory notes

73

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1.

Introduction

1.1.

Welcome and declarations of interest of members, alternates andexperts
Pre-meeting list of participants and restrictions in relation to declarations of interests
applicable to the items of the agenda for the PRAC plenary session to be held 14-17 April
2020. See April 2020 PRAC minutes (to be published post May 2020 PRAC meeting).

1.2.

Agenda of the meeting on 14-17 April 2020
Action: For adoption

1.3.

Minutes of the previous meeting on 09-12 March 2020
Action: For adoption

2.

EU referral procedures for safety reasons: urgent EU
procedures

2.1.

Newly triggered procedures
None

2.2.

Ongoing procedures
None

2.3.

Procedures for finalisation
None

3.

EU referral procedures for safety reasons: other EU referral
procedures

3.1.

Newly triggered procedures
None

3.2.

Ongoing procedures
None

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3.3.

Procedures for finalisation

3.3.1.

Ingenol mebutate - PICATO 1 - EMEA/H/A-20/1489
Applicant: LEO Laboratories Ltd
PRAC Rapporteur: Adam Przybylkowski; PRAC Co-rapporteur: Adrien Inoubli
Scope: Review of the benefit-risk balance following notification by the European
Commission (EC) of a referral under Article 20 of Regulation (EC) No 726/2004, based on
pharmacovigilance data
Action: For adoption of a recommendation to CHMP

3.4.

Re-examination procedures 2
None

3.5.

OthersNone

4.

Signals assessment and prioritisation 3

4.1.

New signals detected from EU spontaneous reporting systems

4.1.1.

Abiraterone – ZYTIGA (CAP)
Applicant(s): Janssen-Cilag International NV
PRAC Rapporteur: Eva Segovia
Scope: Signal of anaphylactic reaction
Action: For adoption of PRAC recommendation
EPITT 19535 – New signal
Lead Member State(s): ES

4.1.2.

Bisoprolol (NAP)
Applicant(s): various
PRAC Rapporteur: To be appointed

1
European Commission (EC) decision on marketing authorisation (MA) withdrawal dated 11 February 2020, at the request of
the MAH
2
Re-examination of PRAC recommendation under Article 32 of Directive 2001/83/EC
3Each signal refers to a substance or therapeutic class. The route of marketing authorisation is indicated in brackets (CAP forCentrally Authorised Products; NAP for Nationally Authorised Products including products authorised via Mutual Recognition
Procedures and Decentralised Procedure). Product names are listed for reference Centrally Authorised Products (CAP) only.
PRAC recommendations will specify the products concerned in case of any regulatory action required

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Scope: Signal of angioedema
Action: For adoption of PRAC recommendation
EPITT 19542 – New signal
Lead Member State(s): FI

4.1.3.

Paclitaxel – ABRAXANE (CAP), APEALEA (CAP), PAZENIR (CAP); NAP
Applicant(s): Celgene Europe BV (Abraxane), Oasmia Pharmaceutical AB (Apealea),
ratiopharm GmbH (Pazenir), various
PRAC Rapporteur: Menno van der Elst
Scope: Signal of progressive multifocal leukoencephalopathy (PML)
Action: For adoption of PRAC recommendation
EPITT 19553 – New signal
Lead Member State(s): NL, PT

4.1.4.

Pomalidomide – IMNOVID (CAP)
Applicant(s): Celgene Europe BV
PRAC Rapporteur: Eva Segovia
Scope: Signal of progressive multifocal leukoencephalopathy (PML)
Action: For adoption of PRAC recommendation
EPITT 19546 – New signal
Lead Member State(s): ES

4.2.

New signals detected from other sources

4.2.1.

Vedolizumab – ENTYVIO (CAP)
Applicant(s): Takeda Pharma A/S
PRAC Rapporteur: Adam Przybylkowski
Scope: Signal of Evans’ syndrome, autoimmune haemolytic anaemia, immune
thrombocytopenic purpura
Action: For adoption of PRAC recommendation
EPITT 19547 – New signal
Lead Member State(s): PL

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4.3.

Signals follow-up and prioritisation

4.3.1.

Adalimumab – AMGEVITA (CAP), AMSPARITY (CAP), HALIMATOZ (CAP), HEFIYA(CAP), HULIO (CAP), HUMIRA (CAP) - EMEA/H/C/000481/SDA/116, HYRIMOZ(CAP), IDACIO (CAP), IMRALDI (CAP)
Applicant(s): AbbVie Deutschland GmbH & Co. KG (Humira), Amgen Europe B.V.
(Amgevita), Fresenius Kabi Deutschland GmbH (Idacio), Mylan S.A.S (Hulio), Pfizer Europe
MA EEIG (Amsparity), Samsung Bioepis NL B.V. (Imraldi), Sandoz GmbH (Halimatoz,
Hefiya, Hyrimoz)
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Signal of autoimmune encephalitis
Action: For adoption of PRAC recommendation
EPITT 19483 – Follow-up to November 2019

4.3.2.

5 alfa-reductase inhibitors (5ARIs): finasteride (NAP); dutasteride (NAP)
Applicant(s): various
PRAC Rapporteur: Annika Folin
Scope: Signal of type 2 diabetes mellitus (T2DM)
Action: For adoption of PRAC recommendation
EPITT 19424 – Follow-up to November 2019

4.3.3.

Andexanet alfa – ONDEXXYA (CAP) - EMEA/H/C/004108/SDA/010
Applicant(s): Portola Netherlands B.V.
PRAC Rapporteur: Menno van der Elst
Scope: Signal of erroneous assay results for levels of anti-factor Xa activity with use of
andexanet alfa
Action: For adoption of PRAC recommendation
EPITT 19493 – Follow-up to December 2019

4.3.4.

Ceftriaxone (NAP)
Applicant(s): various
PRAC Rapporteur: Zane Neikena
Scope: Signal of encephalopathy
Action: For adoption of PRAC recommendation
EPITT 19492 – Follow-up to November 2019Pharmacovigilance Risk Assessment Committee (PRAC)
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4.3.5.

Ibuprofen – PEDEA (CAP); NAP; ketoprofen (NAP) and fixed-dose combinations:chlorphenamine, ibuprofen, phenylephrine (NAP); dimenhydrinate, ibuprofen,
caffeine (NAP); ibuprofen, ascorbic acid (NAP); ibuprofen, caffeine (NAP);
ibuprofen, codeine (NAP); ibuprofen, hydrocodone (NAP); ibuprofen,
paracetamol (NAP); ibuprofen, phenylephrine (NAP); ibuprofen, pseudoephedrine(NAP); ketoprofen, omeprazole (NAP), ketoprofen, sucralfate (NAP)
Applicant(s): Recordati Rare Diseases (Pedea), various
PRAC Rapporteur: Anette Kirstine Stark
Scope: Signal of serious exacerbation of infections
Action: For adoption of PRAC recommendation
EPITT 19415 – Follow-up to November 2019

4.3.6.

Idelalisib – ZYDELIG (CAP) - EMEA/H/C/003843/SDA/018
Applicant: Gilead Sciences Ireland UC
PRAC Rapporteur: Martin Huber
Scope: Signal of drug reaction with eosinophilia and systemic symptoms (DRESS)
Action: For adoption of PRAC recommendation
EPITT 19500 – Follow-up to December 2019

4.3.7.

Insulin:insulin aspart – FIASP (CAP) - EMEA/H/C/004046/SDA/004, NOVOMIX (CAP) EMEA/H/C/000308/SDA/055, NOVORAPID (CAP) - EMEA/H/C/000258/SDA/050;
insulin aspart, insulin degludec – RYZODEG (CAP) - EMEA/H/C/002499/SDA/007;
insulin bovine (NAP); insulin degludec – TRESIBA (CAP) EMEA/H/C/002498/SDA/014; insulin degludec, liraglutide – XULTOPHY (CAP) EMEA/H/C/002647/SDA/004; insulin determir – LEVEMIR (CAP) EMEA/H/C/000528/SDA/053; insulin glargine, lixisenatide - SULIQUA (CAP) EMEA/H/C/004243/SDA/007; insulin glulisine – APIDRA (CAP) EMEA/H/C/000557/SDA/042; insulin human – ACTRAPHANE (CAP) EMEA/H/C/000427/SDA/025, ACTRAPID (CAP) - EMEA/H/C/000424/SDA/026,
INSULATARD (CAP) - EMEA/H/C/000441/SDA/029, INSUMAN (CAP) EMEA/H/C/000201/SDA/050, MIXTARD (CAP) - EMEA/H/C/000428/SDA/027,
PROTAPHANE (CAP) - EMEA/H/C/000442/SDA/029, NAP; insulin lispro – HUMALOG(CAP) - EMEA/H/C/000088/SDA/033, INSULIN LISPRO SANOFI (CAP) EMEA/H/C/004303/SDA/002, LIPROLOG (CAP) - EMEA/H/C/000393/SDA/026;
insulin porcine (NAP)
Applicant(s): Eli Lilly Nederland B.V. (Humalog, Liprolog), Novo Nordisk A/S (Actraphane,
Actrapid, Fiasp, Insulatard, Levemir, Mixtard, NovoMix, NovoRapid, Protaphane, Ryzodeg,
Tresiba, Xultophy), Sanofi-Aventis Deutschland GmbH (Apidra, Insuman), Sanofi-aventis
groupe (Insulin Lispro Sanofi, Suliqua), various
PRAC Rapporteur: Hans Christian Siersted
Scope: Signal of cutaneous amyloidosis
Action: For adoption of PRAC recommendation
EPITT 19499 – Follow-up to December 2019Pharmacovigilance Risk Assessment Committee (PRAC)
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4.3.8.

Tumour necrosis factor (TNF) inhibitors:
adalimumab - AMGEVITA (CAP), AMSPARITY (CAP), HALIMATOZ (CAP), HEFIYA(CAP), HULIO (CAP), HUMIRA (CAP), HYRIMOZ (CAP), IDACIO (CAP), IMRALDI(CAP); certolizumab pegol - CIMZIA (CAP); etanercept - BENEPALI (CAP), ENBREL(CAP), ERELZI (CAP); golimumab - SIMPONI (CAP); infliximab - FLIXABI (CAP),
INFLECTRA (CAP), REMICADE (CAP), REMSIMA (CAP), ZESSLY (CAP)
Applicant(s): AbbVie Deutschland GmbH Co. KG (Humira), Amgen Europe B.V. (Amgevita),
Celltrion Healthcare Hungary Kft. (Remsima), Fresenius Kabi Deutschland GmbH (Idacio),
Mylan S.A.S. (Hulio), Janssen Biologics B.V. (Simponi, Remicade), Pfizer Europe MA EEIG
(Amsparity, Enbrel, Inflectra), Samsung Bioepis NL B.V. (Benepali, Flixabi, Imraldi), SandozGmbH (Erelzi, Halimatoz, Hefiya, Hyrimoz, Zessly), UCB Pharma S.A. (Cimzia)
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Signal of Kaposi’s sarcoma
Action: For adoption of PRAC recommendation
EPITT 19480 – Follow-up to November 20195.

Risk management plans (RMPs)

5.1.

Medicines in the pre-authorisation phase

5.1.1.

Amikacin - EMEA/H/C/005264, Orphan
Applicant: Insmed Netherlands B.V.
Scope: Treatment of lung infection as part of combination antibacterial drug regiment in
adultsAction: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.2.

Avapritinib - EMEA/H/C/005208, Orphan
Applicant: Blueprint Medicines (Netherlands) B.V.
Scope: Treatment of gastrointestinal stromal tumours
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.3.

Belantamab mafodotin - EMEA/H/C/004935, Orphan
Applicant: GlaxoSmithKline (Ireland) Limited
Scope (accelerated assessment): Treatment of patients with relapsed or refractory multiple
myeloma
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

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5.1.4.

Cabazitaxel - EMEA/H/C/005178
Scope: Treatment of adult patients with metastatic castration resistant prostate cancer
previously treated with a docetaxel-containing regimen
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.5.

Crizanlizumab - EMEA/H/C/004874, Orphan
Applicant: Novartis Europharm Limited
Scope: Treatment of sickle cell disease
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.6.

Fostemsavir - EMEA/H/C/005011
Scope (accelerated assessment): Treatment in combination with other antiretrovirals ofadults with multidrug resistant human immunodeficiency virus-1 (HIV-1) infection for whom
it is otherwise not possible to construct a suppressive anti-viral regimen due to resistance,
intolerance or safety considerations
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.7.

Idebenone - EMEA/H/C/005123, Orphan
Applicant: Santhera Pharmaceuticals (Deutschland) GmbH
Scope: Treatment of respiratory dysfunction in patients with Duchenne muscular dystrophy(DMD) not using glucocorticoids
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.8.

Luspatercept - EMEA/H/C/004444, Orphan
Applicant: Celgene Europe BV
Scope: Treatment of adult patients with very low- to intermediate-risk myelodysplastic
syndromes (MDS)-associated anaemia and treatment of adult patients with betathalassaemia (β-thalassaemia)-associated anaemia who require red blood cell (RBC)
transfusions
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.9.

Paliperidone - EMEA/H/C/005486
Scope: Treatment of schizophrenia
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.10.

Sodium oxybate – HOPVEUS (CAP MAA) - EMEA/H/C/004962
Applicant: D&A Pharma

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Scope (re-examination): Medium to long-term maintenance of alcohol abstinence andtreatment of mild to moderate alcohol withdrawal syndrome
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.11.

Teriparatide - EMEA/H/C/005233
Scope: Treatment of osteoporosis
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.1.12.

Valoctocogene roxaparvovec - EMEA/H/C/004749, Orphan, ATMP
Applicant: BioMarin International Limited, ATMP 4
Scope (accelerated assessment): Treatment of haemophilia A
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CAT
and CHMP

5.2.

Medicines in the post-authorisation phase – PRAC-led procedures

5.2.1.

Alemtuzumab - LEMTRADA (CAP) - EMEA/H/C/003718/II/0031
Applicant: Sanofi Belgium
PRAC Rapporteur: Anette Kirstine Stark
Scope: Submission of an updated RMP (version 7.0) in order to reflect all amendments andadditional activities as per the outcome of the referral procedure under Article 20 ofRegulation (EC) No 726/2004 completed in November 2019 (EMEA/H/A-20/1483)
Action: For adoption of PRAC Assessment Report

5.2.2.

Asparaginase - SPECTRILA (CAP) - EMEA/H/C/002661/II/0017
Applicant: medac Gesellschaft fur klinische Spezialpraparate mbH
PRAC Rapporteur: Jan Neuhauser
Scope: Submission of an updated RMP (version 12) in line with revision 2 of GVP module Von ‘Risk management systems’ and in line with revision 2.0.1 of the guidance on the format
of RMP in the EU (template). The milestones and timelines for study MC-Spectrila.1/ALL: aclinical phase 2 trial to describe pharmacokinetics, pharmacodynamics, safety andimmunogenicity of Spectrila (asparaginase) with the pharmaceutical active ingredient
recombinant L asparaginase in adult subjects with newly diagnosed acute B-Celllymphoblastic leukaemia are updated in accordance with the newly applied data lock point(DLP) for the RMP
Action: For adoption of PRAC Assessment Report

4

Advanced therapy medicinal product
Pharmacovigilance Risk Assessment Committee (PRAC)
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5.2.3.

Dexamethasone - OZURDEX (CAP) - EMEA/H/C/001140/II/0037
Applicant: Allergan Pharmaceuticals Ireland
PRAC Rapporteur: Eva Segovia
Scope: Submission of an updated RMP (version 9.0) in order to reflect increased knowledgeof the medicinal product and bring it in line with revision 2 of the guidance on the format of
RMP in the EU (template)
Action: For adoption of PRAC Assessment Report

5.2.4.

Docetaxel - DOCETAXEL ZENTIVA (CAP) - EMEA/H/C/000808/II/0061
Applicant: Zentiva, k.s.
PRAC Rapporteur: Ghania Chamouni
Scope: Submission of an updated RMP (version 1.1) in order to revise the list of safetyconcerns in line with revision 2 of GVP module V on ‘Risk management systems’ and tocomplete Part II modules
Action: For adoption of PRAC Assessment Report

5.2.5.

Docetaxel - TAXOTERE (CAP) - EMEA/H/C/000073/II/0134
Applicant: Sanofi Mature IP
PRAC Rapporteur: Ghania Chamouni
Scope: Submission of an updated RMP (version 1.1) in order to revise the list of safetyconcerns in line with revision 2 of GVP module V on ‘Risk management systems’ and tocomplete Part II modules
Action: For adoption of PRAC Assessment Report

5.2.6.

Histamine dihydrochloride - CEPLENE (CAP) - EMEA/H/C/000796/II/0040
Applicant: Noventia Pharma Srl
PRAC Rapporteur: Rhea Fitzgerald
Scope: Submission of an updated RMP (version 8.1) in order to include information about
the termination/finalisation of: 1) non-interventional study Ceplene-3290 (listed as acategory 3 study in the RMP): an open study designed to gain further knowledge on Ceplene(histamine dihydrochloride) under day to day conditions with special emphasis on
tolerability, practicability, usage, and measurable minimal residual disease and course of
blast cells and; 2) post-authorisation efficacy study (PAES) Ceplene cohort study 3306: an
international, multicentre, observational, non-interventional, registry-based cohort study
aiming to describe and evaluate minimal residual disease (MRD) at baseline and follow-up
for the assessment of the anti-leukaemic activity of Ceplene (histamine
dihydrochloride)/interleukin-2 (IL-2) as remission maintenance therapy in adult patientswith acute myeloid leukaemia (AML) in first complete remission (CR1) compared to matched
control patients who did not receive Ceplene (histamine dihydrochloride)/IL-2. In addition,
the RMP is brought in line with revision 2.0.1 of the guidance on the format of RMP in the

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EU (template). As a consequence, the list of safety concerns is amended in particular ‘drug
effect decreased as a consequence of drug interaction’ is added as a new important
potential risk
Action: For adoption of PRAC Assessment Report

5.2.7.

Nonacog alfa - BENEFIX (CAP) - EMEA/H/C/000139/II/0163
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: Submission of an updated RMP (version 10.0) to remove ‘less than therapeutic
effect (LETE)’ as an important identified risk. In addition, specific patient populations
previously identified as missing information are removed from the RMP in line with revision
2 of GVP module V on ‘Risk management systems’
Action: For adoption of PRAC Assessment Report

5.2.8.

Rivastigmine - EXELON (CAP) - EMEA/H/C/000169/WS1773/0128; PROMETAX(CAP) - EMEA/H/C/000255/WS1773/0128
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Ghania Chamouni
Scope: Submission of an updated RMP (version 10.0) to reflect the results of study
CENA713D2409: a drug utilisation study (DUS) aimed to assess the extent of inappropriate
use of Exelon/Prometax (rivastigmine) as per the conclusions of variation WS1557 adopted
in July 2019. In addition, the list of safety concerns of the RMP is updated in line withrevision 2 of GVP module V on ‘Risk management systems’ and in line with the conclusionsof the PSUR single assessment (PSUSA) procedure (PSUSA/00002654/201901) finalised in
September 2019
Action: For adoption of PRAC Assessment Report

5.2.9.

Sevelamer - RENAGEL (CAP) - EMEA/H/C/000254/WS1775/0114;
Sevelamer carbonate - RENVELA (CAP) EMEA/H/C/000993/WS1775/0051;SEVELAMER CARBONATE WINTHROP (CAP) EMEA/H/C/003971/WS1775/0024
Applicant: Genzyme Europe BV
PRAC Rapporteur: Laurence de Fays
Scope: Submission of an updated RMP (version 10) in order to remove from the list ofsafety concerns ‘sevelamer crystals associated with serious gastrointestinal disorders’ as animportant potential risk as per the conclusions of the renewal procedure for Sevelamer
Carbonate Winthrop (R/0022) finalised in September 2019
Action: For adoption of PRAC Assessment Report

5.2.10.

Tegafur, gimeracil, oteracil - TEYSUNO (CAP) - EMEA/H/C/001242/II/0042
Applicant: Nordic Group B.V.

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PRAC Rapporteur: Menno van der Elst
Scope: Submission of an updated RMP (version 9.0) in order to revise the list of safetyconcerns in line with revision 2 of GVP module V on ‘Risk management systems’ asrequested in the conclusions of the periodic safety update report single assessment (PSUSA)
procedure PSUSA/00002875/201801 adopted in September 2018
Action: For adoption of PRAC Assessment Report

5.3.

Medicines in the post-authorisation phase – CHMP-led procedures

5.3.1.

Andexanet alfa - ONDEXXYA (CAP) - EMEA/H/C/004108/II/0009/G
Applicant: Portola Netherlands B.V.
PRAC Rapporteur: Menno van der Elst
Scope: Grouped variations consisting of an update of section 5.2 of the SmPC in order toupdate pharmacokinetic (PK) information based on the clinical study results (CSR) from: 1)
study 19-514 evaluating the PK comparability of generation 1 process 3 andexanet andgeneration 2 andexanet (PK comparability); 2): study 16-508: a phase 2 randomised,double-blind, placebo-controlled study to evaluate the efficacy, safety, tolerability andPK/pharmacodynamics (PD) of andexanet alfa administered to healthy Japanese andCaucasian subjects (Japanese ethnicity study). Annex II-D on ‘Specific obligation tocomplete post-authorisation measures for the conditional marketing authorisation’ isupdated accordingly. The RMP (version 2.1) is updated in accordanceAction: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.2.

Anidulafungin - ECALTA (CAP) - EMEA/H/C/000788/II/0040
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Liana Gross-Martirosyan
Scope: Extension of the approved indication ‘treatment of invasive candidiasis (ICC)’ to
include paediatric patients aged from 1 month to less than 18 years of age. As aconsequence, sections 4.1, 4.2, 4.4, 4.8, 4.9, 5.1, 5.2, 5.3 and 6.6 of the SmPC are
updated. The package leaflet and the RMP (version 13.0) are updated accordingly. The RMP
is also updated in line with revision 2 of GVP module V on ‘Risk management systems’. In
addition, the MAH took the opportunity to update the information in the product information
on fructose in line with the European Commission (EC) guideline on ‘excipients in thelabelling and package leaflet of medicinal products for human use’
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.3.

Avelumab - BAVENCIO (CAP) - EMEA/H/C/004338/II/0015
Applicant: Merck Europe B.V.
PRAC Rapporteur: Hans Christian Siersted
Scope: Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to change posology
recommendations, to amend an existing warning and to add myasthenia gravis andPharmacovigilance Risk Assessment Committee (PRAC)
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myasthenic syndrome as new adverse drug reactions (ADRs) with a frequency uncommon.
The update results from an update of the company core data sheet (CCDS) based on thereview of cases of myasthenia gravis/myasthenic syndrome. The package leaflet is updated
accordingly. The RMP (version 2.2) is updated with a proposal to reclassify ‘other immunerelated events (myasthenic syndrome)’ from an important potential risk to an important
identified risk of ‘other immune-related events (myasthenia gravis/myasthenic syndrome)’
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.4.

Bedaquiline - SIRTURO (CAP) - EMEA/H/C/002614/X/0036/G, Orphan
Applicant: Janssen-Cilag International NV
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Grouped application consisting of: 1) extension application to add a new strength(20 mg tablets); 2) extension of the existing indication on pulmonary multidrug-resistanttuberculosis (MDR-TB) to include paediatric patients aged from 5 years to less than 18
years of age and weighing more than 15 kg based on the results of the week 24 analysis ofcohort 2 (paediatric subjects aged ≥5 to <12 years) of study TMC207-C211: a phase 2,
open-label, multicentre, single-arm study to evaluate the pharmacokinetics, safety,
tolerability and antimycobacterial activity of TMC207 (bedaquiline) in combination with abackground regimen (BR) of MDR-TB Medications for the treatment of children andadolescents 0 months to <18 years of age who have confirmed or probable pulmonary
MDR-TB. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 are updated. The
package leaflet and the RMP (version 4.4) are updated in accordanceAction: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.5.

Encorafenib - BRAFTOVI (CAP) - EMEA/H/C/004580/WS1695/0008;
Binimetinib - MEKTOVI (CAP) - EMEA/H/C/004579/WS1695/0007
Applicant: Pierre Fabre Medicament
PRAC Rapporteur: Marcia Sofia Sanches de Castro Lopes Silva
Scope: Extension of indication to include encorafenib in combination with binimetinib andcetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) witha BRAF V600E mutation, who have received prior systemic therapy. As a consequence,
sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2, 5.3 of the SmPC are updated. The package leaflet
and the RMP (version 1.1) are updated accordingly. Furthermore, the product information isbrought in line with the latest quality review of documents (QRD) template (version 10.1)
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.6.

Brodalumab - KYNTHEUM (CAP) - EMEA/H/C/003959/II/0014
Applicant: LEO Pharma A/S
PRAC Rapporteur: Eva Segovia
Scope: Update of sections 4.4 and 4.8 of the SmPC to reflect a signal of anaphylactic
reaction detected in post marketing setting. The package leaflet and the RMP (version 1.2)
are updated accordingly. The MAH took the opportunity to introduce minor updates

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throughout the product information
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.7.

Buprenorphine, naloxone - SUBOXONE (CAP) - EMEA/H/C/000697/X/0042
Applicant: Indivior Europe Limited
PRAC Rapporteur: Martin Huber
Scope: Extension application to introduce a new pharmaceutical form (sublingual film)
associated with four new strengths (2/0.5 mg, 4/1 mg, 8/2 mg and 16/4 mg) and a newroute of administration (either sublingual or buccal administration). The RMP (version 14.0)
is updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.8.

Canagliflozin - INVOKANA (CAP) - EMEA/H/C/002649/II/0046
Applicant: Janssen-Cilag International NV
PRAC Rapporteur: Martin Huber
Scope: Extension of indication to add the treatment of stage 2 or 3 chronic kidney disease(CKD) and albuminuria, as an adjunct to standard of care, in adults with type 2 diabetes
mellitus (T2DM), based on new clinical efficacy and safety data from study DNE3001(CREDENCE): a randomised, double-blind, event-driven, placebo-controlled, multicentre
phase 3 study of the effects of canagliflozin on renal and cardiovascular outcomes insubjects with T2DM and diabetic nephropathy. As a consequence, sections 4.1, 4.2, 4.8 and5.1 of the SmPC are updated. The package leaflet and the RMP (version 8.1) are updated
accordingly. In addition, the MAH took the opportunity to update the list of local
representatives in the package leaflet
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.9.

Canagliflozin, metformin - VOKANAMET (CAP) - EMEA/H/C/002656/II/0051
Applicant: Janssen-Cilag International NV
PRAC Rapporteur: Menno van der Elst
Scope: Extension of indication to add the treatment of stage 2 or 3 chronic kidney disease(CKD) and albuminuria, as an adjunct to standard of care, in adults with type 2 diabetes
mellitus (T2DM), based on new clinical efficacy and safety data from study DNE3001(CREDENCE): a randomised, double-blind, event-driven, placebo-controlled, multicentre
phase 3 study of the effects of canagliflozin on renal and cardiovascular outcomes insubjects with T2DM and diabetic nephropathy. As a consequence, sections 4.1, 4.2, 4.8 and5.1 of the SmPC are updated. The package leaflet and the RMP (version 8.1) are updated
accordingly. In addition, the MAH took the opportunity to update the list of local
representatives in the package leaflet
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

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5.3.10.

Carfilzomib - KYPROLIS (CAP) - EMEA/H/C/003790/II/0043, Orphan
Applicant: Amgen Europe B.V.
PRAC Rapporteur: Nikica Mirošević Skvrce
Scope: Update of section 4.8 of the SmPC in order to include cardiomyopathy as a new
adverse drug reaction (ADR) with a frequency uncommon. The RMP (version 11.0) is
updated accordingly. In addition, the MAH took the opportunity to introduce minor editorialchanges to the product information
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.11.

Catridecacog - NOVOTHIRTEEN (CAP) - EMEA/H/C/002284/II/0026/G
Applicant: Novo Nordisk A/S
PRAC Rapporteur: Ghania Chamouni
Scope: Grouped variations consisting of an extension of indication to include treatment of
bleeding episodes in patients with congenital factor XIII A-subunit deficiency as well as
minor surgery based on the results of: 1) study NN1841-3868: Use of recombinant factor
XIII (rFXIII) in treatment of congenital FXIII deficiency, a prospective multi-centre
observational study; 2) registry PRO-RBDD: a prospective rare bleeding disorders databaseregistry. As a consequence, sections 4.1, 4.2, 4.4, 4.6, 5.1 and 5.2 of the SmPC are
updated. The package leaflet, Annex II-D on ‘Conditions or restrictions with regard to thesafe and effective use of the medicinal product’ and the RMP (version 15) are updated
accordingly. Furthermore, the product information is brought in line with the latest quality
review of documents (QRD) template (version 10.1). Finally, the MAH took the opportunity
to introduce minor editorial changes to the product information
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.12.

Certolizumab pegol - CIMZIA (CAP) - EMEA/H/C/001037/II/0084/G
Applicant: UCB Pharma S.A.
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Update of sections 4.8 and 5.1 of the SmPC in order to update the safety andefficacy information following the final results from three studies (listed as category 3
studies in the RMP) namely: 1) study PS0002 (CIMPASI-2): a phase 3, multicentre,
randomized, double-blind, parallel-group, study followed by a dose-blind period and openlabel follow-up to evaluate the efficacy and safety of certolizumab pegol in subjects withmoderate to severe chronic plaque psoriasis; 2) study PS0003 (CIMPACT): a phase 3,
multicentre, randomized, double-blind, parallel-group, placebo- and active-controlled study
followed by a placebo-controlled maintenance period and open-label follow-up to evaluate
the efficacy and safety of certolizumab pegol in subjects with moderate to severe chronicplaque psoriasis; 3) study PS0005 (CIMPASI-1): a phase 3, multicentre, randomized,
double-blind, parallel-group, study followed by a dose-blind period and open-label follow-up
to evaluate the efficacy and safety of certolizumab pegol in subjects with moderate tosevere chronic plaque psoriasis. The RMP (version 16.0) is updated accordingly. In addition,
the MAH took the opportunity to bring the product information in line with the latest quality
review of documents (QRD) template (version 10.1)

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Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.13.

Certolizumab pegol - CIMZIA (CAP) - EMEA/H/C/001037/II/0087
Applicant: UCB Pharma S.A.
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Update of sections 4.2, 4.8 and 5.1 of the SmPC in order to introduce a change inposology for axial spondyloarthritis (aSpA) and to update the safety and efficacy information
based on the results of study AS0005 (C-OPTIMISE) (listed as a category 3 study in theRMP): a multicentre, open-label (part A) followed by a randomised, double-blind, parallelgroup, placebo-controlled study (part B) to evaluate maintenance of remission in subjects
with active axSpA receiving either certolizumab pegol 200mg once every 2 weeks (q2w) or
200mg once every 4 weeks (q4w) as compared to placebo. The package leaflet and the RMP(version 17.0) are updated accordingly. In addition, the interim study reports for studies
AS0006 and AS0007 are submitted to include additional pooled safety data in the SmPC.
Study AS0006 is a phase 3, multicentre, randomised, placebo-controlled, double-blind study
to evaluate efficacy and safety of certolizumab pegol in subjects with active aSpA without xray evidence of ankylosing spondylitis and objective signs of inflammation. Study AS0007 isa multicentre, open-label study to assess the effects of certolizumab pegol on the reductionof anterior uveitis flares in aSpA subjects with a history of anterior uveitis (C-VIEW)
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.14.

Clopidogrel - ISCOVER (CAP) - EMEA/H/C/000175/WS1769/0140; PLAVIX (CAP) EMEA/H/C/000174/WS1769/0138
Applicant: Sanofi-aventis groupe
PRAC Rapporteur: Marcia Sofia Sanches de Castro Lopes Silva
Scope: Extension of indication to include adult patients with high risk transient ischemic
attack (TIA) (ABCD2 score ≥4) or minor ischemic stroke (IS) (National Institutes of Health
Stroke Scale (NIHSS) ≤3) within 24 hours of either the TIA or IS event. The new indication
is based on the results of 1) study POINT: a double-blind, randomised, placebo-controlled
phase 3 study on platelet-oriented inhibition in new TIA and minor IS; 2) study CHANCE: adouble-blind, randomised, placebo-controlled phase 3 study comparing the effects of a 3month clopidogrel regimen, combined with acetylsalicylic acid (ASA) during the first 21days,
versus ASA alone for the acute treatment of TIA or minor stroke. As a consequence,
sections 4.1, 4.2, 4.4 and 5.1 of the SmPC are updated. The package leaflet and the RMP(version 1.0) are updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.15.

Delamanid - DELTYBA (CAP) - EMEA/H/C/002552/II/0040, Orphan
Applicant: Otsuka Novel Products GmbH
PRAC Rapporteur: Laurence de Fays
Scope: Extension of indication to include adolescents and children above 6 years with abody weight of at least 30 kg. As a consequence, sections 4.1, 4.2, 5.1 and 5.2 of the SmPC

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are updated. The package leaflet and the RMP (version 3.2) are updated accordingly.
Furthermore, the product information is brought in line with the latest quality review of
documents (QRD) template (version 10.1)
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.16.

Dupilumab - DUPIXENT (CAP) - EMEA/H/C/004390/II/0027
Applicant: Sanofi-aventis groupe
PRAC Rapporteur: Kimmo Jaakkola
Scope: Extension of indication to include atopic dermatitis patients from 6 years to 11
years. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The
package leaflet and the RMP (version 5.0) are updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.17.

Esketamine - SPRAVATO (CAP) - EMEA/H/C/004535/II/0001/G
Applicant: Janssen-Cilag International N.V.
PRAC Rapporteur: Kirsti Villikka
Scope: Grouped variations consisting of: 1) extension of indication to include a new
indication for the rapid reduction of depressive symptoms in adult patients with a moderate
to severe depressive episode of major depressive disorder (MMD) who have current suicidal
ideation with intent. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 the SmPC are
updated. The package leaflet and the RMP (version 2.1) are updated accordingly; 2)
addition of a new pack size (multipack) of 24 nasal spray devices (multipack of 8 packs of 3
nasal spray devices) corresponding to 4 weeks of treatment in the new indication. The
package leaflet and labelling are updated in accordance. In addition, the MAH took theopportunity to clarify the wording in Annex II-D on ‘Conditions or restrictions with regard to
the safe and effective use of the medicinal product’Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.18.

Granisetron - SANCUSO (CAP) - EMEA/H/C/002296/II/0056/G
Applicant: Kyowa Kirin Holdings B.V.
PRAC Rapporteur: Rugile Pilviniene
Scope: Grouped variations consisting of: 1) update of section 5.2 of the SmPC to add
pharmacokinetic (PK) information following the completion of paediatric PK study
392MD/44/C: an open-label, cross-over, pharmacokinetic study to assess the safety andpharmacokinetics of transdermal granisetron (Sancuso patch) and intravenous (IV)granisetron in a paediatric oncology population (aged 13 to 17 years). The RMP (version4.0) is updated accordingly; 2) update of the RMP in line with revision 2 of the guidance on
the format of RMP in the EU (template). The MAH took the opportunity to update thepregnancy information in section 4.6 to align with the quality review document (QRD)
template
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

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5.3.19.

Herpes zoster vaccine (recombinant, adjuvanted) - SHINGRIX (CAP) EMEA/H/C/004336/II/0022
Applicant: GlaxoSmithkline Biologicals SA
PRAC Rapporteur: Sonja Hrabcik
Scope: Extension of indication to include adults of 18 years of age or older at increased riskof herpes zoster, supported by clinical studies: 1) study ZOSTER-002: a phase 3,
randomised, observer-blind, placebo-controlled, multicentre, clinical trial to assess theprophylactic efficacy, safety, and immunogenicity of Shingrix (herpes zoster vaccine) whenadministered intramuscularly on a two-dose schedule to adult autologous haematopoietic
stem cell transplant (HCT) recipients (MEA 001); 2) study ZOSTER-039: a phase 3,
randomised, observer-blind, placebo-controlled, multicentre study to assess the safety andimmunogenicity of Shingrix (herpes zoster vaccine) when administered intramuscularly on a
two-dose schedule to adults aged 18 years and older with haematologic malignancies (MEA002); 3) study ZOSTER-041: a phase 3, randomised, observer-blind, placebo-controlled,
multicentre clinical study to assess the immunogenicity and safety of Shingrix (herpes
zoster vaccine) when administered intramuscularly on a 0- and 1- to 2-months schedule toadults ≥ 18 years of age with renal transplant (MEA 003); 4) study ZOSTER-028: a phase
2/3, randomised, observer-blind, placebo-controlled, multicentre, clinical trial to assess theimmunogenicity and safety of Shingrix (herpes zoster vaccine) when administeredintramuscularly on a 0 and 1 to 2 months schedule to adults of 18 years of age with solid
tumours receiving chemotherapy (MEA 004); 5) study ZOSTER-001: a phase 1/2a,
randomised, observer-blind, placebo-controlled, multicentre study to evaluate the safety
and immunogenicity of Shingrix (herpes zoster vaccine) and to saline (placebo) whenadministered as 2 doses or 3 doses to autologous HCT recipients ; 6) study ZOSTER-015: aphase 1/2a, randomised, observer-blind, placebo-controlled, multicentre study to evaluate
the safety and immunogenicity of Shingrix (herpes zoster vaccine) in comparison to placebo
when administered as 3 doses to adult human immunodeficiency virus (HIV)-infectedsubjects.. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated inorder to add the indication, delete a warning and add new safety and efficacy information.
The package leaflet and the RMP (version 2.1) are updated in accordanceAction: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.20.

Ibrutinib - IMBRUVICA (CAP) - EMEA/H/C/003791/II/0059, Orphan
Applicant: Janssen-Cilag International NV
PRAC Rapporteur: Nikica Mirošević Skvrce
Scope: Extension of indication to add the combination with rituximab or obinutuzumab forthe treatment of adult patients with previously untreated chronic lymphocytic leukaemia(CLL), based on results from study E1912 (PCYC-1126e-CA): a randomized phase 3 study ofibrutinib-based therapy vs standard fludarabine, cyclophosphamide, and rituximab (FCR)
chemoimmunotherapy in untreated younger patients with CLL. As a consequence, sections
4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated to include information related to the
new indication. The package leaflet and the RMP (version 16.1) are updated accordingly.
The MAH took the opportunity to introduce minor editorial changes in Annex II and thelabelling (Annex III-A)
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

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5.3.21.

Infliximab - REMSIMA (CAP) - EMEA/H/C/002576/II/0082
Applicant: Celltrion Healthcare Hungary Kft.
PRAC Rapporteur: Kimmo Jaakkola
Scope: Extension of indication to add Crohn's disease, ulcerative colitis, ankylosing
spondylitis, psoriatic arthritis and psoriasis to subcutaneous (SC) route of administration
presentations in order to bring them in line with the intravenous (IV) route of administration
presentations. The RMP (version 12.1) is updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.22.

Insulin glargine - ABASAGLAR (CAP) - EMEA/H/C/002835/WS1587/0028/G; insulin
lispro - HUMALOG (CAP) - EMEA/H/C/000088/WS1587/0178/G
Applicant: Eli Lilly Nederland B.V.
PRAC Rapporteur: Annika Folin
Scope: Grouped variations consisting of: 1) introduction of an additional prefilled pen
presentation for Abasaglar (insulin glargine), solution for injection, Humalog (insulin lispro)
solution for injection, Humalog (insulin lispro) Kwikpen solution for injection and Humalog(insulin lispro) Junior Kwikpen solution for injection. Each pack contains 5 pre-filled pens.;2) extension to two x5 multipacks. As a consequence, sections 1, 4.2, 4.4, 6.2, 6.4, 6.5, 6.6
and 8 of the SmPC are updated. The package leaflet and labelling are updated accordingly.
In addition, the MAH took the opportunity to introduce an editorial change in the Slovakian
address of the package leaflet
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.23.

Ivacaftor - KALYDECO (CAP) - EMEA/H/C/002494/II/0082, Orphan
Applicant: Vertex Pharmaceuticals (Ireland) Limited
PRAC Rapporteur: Maria del Pilar Rayon
Scope: Extension of indication to include a new population for Kalydeco (ivacaftor) 150 mg
tablets to extend the use to patients with cystic fibrosis (CF) aged 6 years and older andweighing 25 kg or more who have an R117H mutation in the cystic fibrosis transmembrane
conductance regulator (CFTR) gene and for Kalydeco (ivacaftor) granules 75 mg and 50 mg,
to add patients with CF aged 12 months and older and weighing 7 kg to less than 25 kg who
have an R117H mutation in the CFTR gene. This is based on a clinical trial and literature
data, and post-marketing experience with Kalydeco (ivacaftor). As a consequence, sections
4.1, 4.2, 4.4 and 5.1 of the SmPC are updated. The package leaflet and the RMP (version
8.5) are updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.24.

Ixekizumab - TALTZ (CAP) - EMEA/H/C/003943/II/0031
Applicant: Eli Lilly Nederland B.V.
PRAC Rapporteur: Brigitte Keller-Stanislawski

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Scope: Extension of indication to include the treatment of moderate to severe plaquepsoriasis in children from the age of 6 years and adolescents who are candidates for
systemic therapy for Taltz (ixekizumab). As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1
and 5.2 of the SmPC are updated with new safety and efficacy information. The package
leaflet and the RMP (version 7.1) are updated accordingly. In addition, the MAH took theopportunity to update the list of local representatives in the package leaflet
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.25.

Lacosamide - LACOSAMIDE UCB (CAP) - EMEA/H/C/005243/WS1782/0006; VIMPAT(CAP) - EMEA/H/C/000863/WS1782/0088
Applicant: UCB Pharma S.A.
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Extension of indication to include the treatment as adjunctive therapy of primary
generalised tonic-clonic seizures in adults, adolescents and children from 4 years of age
with idiopathic generalised epilepsy. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the
SmPC are updated. The package leaflet and the RMP (version 15.0) are updated inaccordance. Furthermore, the MAH took the opportunity to bring the product information inline with the latest quality review of documents (QRD) template (version 10.1), to align the
product information of Lacosamide UCB (lacosamide) with the product information of Vimpat(lacosamide) and to implement some minor corrections in the Bulgarian, Czech, Danish,French, German, Hungarian, Polish and Spanish versions of the product information
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.26.

Lenalidomide - REVLIMID (CAP) - EMEA/H/C/000717/II/0112/G
Applicant: Celgene Europe BV
PRAC Rapporteur: Ghania Chamouni
Scope: Grouped variations consisting of: 1) update of sections 4.2, 4.4 and 4.8 of the SmPC
with anaphylaxis following a safety review. The package leaflet is updated accordingly; 2)update of section 6.6 of the SmPC in order to include recommendations to minimise the riskof unintended occupational exposures in healthcare professionals. The MAH took theopportunity to include minor updates to section 4.4 of the SmPC and to introduce moreclarity in Annex II-D on ‘Specific obligation to complete post-authorisation measures for theconditional marketing authorisation’ regarding the educational materials, prescribing anddispensing restrictions. Finally, the MAH introduced some editorial changes throughout the
product information
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.27.

Levetiracetam - KEPPRA (CAP) - EMEA/H/C/000277/WS1664/0187
Applicant: UCB Pharma S.A.
PRAC Rapporteur: Laurence de Fays
Scope: Update of section 4.2 of the SmPC to recommend the same dosing for monotherapy
and adjunctive therapy based on data from modelling and simulation project. The package

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leaflet and the RMP (version 9.0) are updated accordingly. The MAH took the opportunity
the opportunity to move Braille to another box section and to review and adapt the German
product information in line with the latest quality review of documents (QRD) template(version 10.1)
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.28.

Lumacaftor, ivacaftor - ORKAMBI (CAP) - EMEA/H/C/003954/II/0055
Applicant: Vertex Pharmaceuticals (Ireland) Limited
PRAC Rapporteur: Rhea Fitzgerald
Scope: Update of section 4.8 of the SmPC following results from study VX16-809-116(study 106, safety study in children): a phase 3, open-label, rollover extension study
evaluating the long-term safety of lumacaftor/ivacaftor in patients with cystic fibrosis aged
2 and older, homozygous for the deletion of phenylalanine in position 508 of the cystic
fibrosis transmembrane conductance regulator (F508del-CFTR) mutation, who initiatedtreatment in parent study 115. The package leaflet and the RMP (version 7.1) are updated
accordingly. The MAH took the opportunity to bring the product information in line with thelatest quality review of documents (QRD) template (version 10.1)
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.29.

Methotrexate - NORDIMET (CAP) - EMEA/H/C/003983/II/0016
Applicant: Nordic Group B.V.
PRAC Rapporteur: Martin Huber
Scope: Extension of indication to include the treatment of mild to moderate Crohn's disease
either alone or in combination with corticosteroids in patients refractory or intolerant tothiopurines. As a consequence, sections 4.1, 4.2 and 5.1 of the SmPC are updated. The
package leaflet and the RMP (version 5.0) are updated in accordance. Furthermore, theMAH took the opportunity to update the RMP in line with revision 2.0.1 of the guidance on
the format of RMP in the EU (template) and the outcome of the referral procedure formethotrexate-containing products under Article 31 of Directive 2001/83/EC (EMEA/H/A31/1463) finalised in July 2019
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.30.

Nivolumab - OPDIVO (CAP) - EMEA/H/C/003985/II/0080
Applicant: Bristol-Myers Squibb Pharma EEIGPRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: Extension of indication to include treatment of adult patients with unresectableadvanced, recurrent or metastatic oesophageal squamous cell carcinoma (OSCC) after priorfluoropyrimidine- and platinum-based chemotherapy. As a consequence, sections 4.1, 4.2,
4.4, 4.8 and 5.1 of the SmPC are updated. The package leaflet and the RMP (version 16.0)
are updated in accordanceAction: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

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5.3.31.

Obinutuzumab - GAZYVARO (CAP) - EMEA/H/C/002799/II/0038, Orphan
Applicant: Roche Registration GmbH
PRAC Rapporteur: Annika Folin
Scope: Submission of final clinical study report (CSR) for study MO28543/GREEN: amulticentre, open-label, single-arm, phase 3b, international study evaluating the safety ofobinutuzumab alone or in combination with chemotherapy in patients with previously
untreated or relapsed/refractory chronic lymphocytic leukaemia (in fulfilment of the post
authorisation commitment MEA 005). The RMP (version 6.1) is updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.32.

Ocrelizumab - OCREVUS (CAP) - EMEA/H/C/004043/II/0017
Applicant: Roche Registration GmbH
PRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: Update of sections 4.2, 4.8 and 5.1 of the SmPC in order to add the option of ashorter infusion for second and subsequent doses of Ocrevus (ocrelizumab): from theapproved 3.5 hours infusion to 2 hours, based on the primary analysis of a therapeutic use
substudy MA30143 (shorter infusion substudy (Ensemble Plus)): an open-label, single-arm
study to evaluate the effectiveness and safety of ocrelizumab in patients with early stage
relapsing remitting multiple sclerosis. The Package Leaflet is updated accordingly. The RMP(version 4.0) is updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.33.

Olaparib - LYNPARZA (CAP) - EMEA/H/C/003726/II/0033
Applicant: AstraZeneca AB
PRAC Rapporteur: Amelia Cupelli
Scope: Extension of indication to support the use of Lynparza (olaparib) tablets (100 mg
and 150 mg) for the maintenance treatment of germline breast cancer gene (BRCA)
mutation (gBRCAm) metastatic pancreatic cancer based on the results from the pivotal
phase 3 study POLO: a phase 3, randomised, double blind, placebo controlled, multicentre
study of maintenance olaparib monotherapy in patients with gBRCA mutated metastatic
pancreatic cancer whose disease has not progressed on first line platinum based
chemotherapy. As a consequence, sections 4.1, 4.2, 4.8, 5.1 of the SmPC are updated. The
package leaflet and the RMP (version 18) are updated in accordance. In addition, the MAH
took the opportunity to update section 4.8 for Lynparza (olaparib) hard capsules (50 mg) torevise the list of adverse drug reactions (ADR) based on a pooled safety data analysis.
Furthermore, the product information is brought in line with the latest Annex to theEuropean Commission (EC) guideline on ‘excipients in the labelling and package leaflet of
medicinal products for human use’ on sodium content. The MAH also took the opportunity toinclude some minor editorial changes in the product information
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

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5.3.34.

Pegvaliase - PALYNZIQ (CAP) - EMEA/H/C/004744/II/0007/G, Orphan
Applicant: BioMarin International Limited
PRAC Rapporteur: Rhea Fitzgerald
Scope: Grouped variations consisting of an update of sections 4.4, 4.8 and 5.1 of the SmPC
based on final results from: 1) study 1655-003 (listed as a category 3 study in the RMP): along-term extension of a phase 2, open-label, dose-finding study; 2) study 165-302 (listed
as a category 3 study in the RMP): a phase 3, randomised, double-blind, placebo-controlled,
four-arm, discontinuation study to evaluate executive function in adults withphenylketonuria. The RMP (version 2.0) is updated accordingly. In addition, the MAH took
the opportunity to introduce minor editorial changes in the product information
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.35.

Perampanel - FYCOMPA (CAP) - EMEA/H/C/002434/II/0047
Applicant: Eisai GmbH
PRAC Rapporteur: Ghania Chamouni
Scope: Extension of indication to include adjunctive treatment in paediatric patients from 2
to 11 years of age in partial-onset (focal) seizures with or without secondary generalisationand primary generalised tonic-clonic seizures with idiopathic generalised epilepsy. As aconsequence, sections 4.1, 4.2, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The
package leaflet and the RMP (version 4.3) are updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.36.

Pomalidomide - IMNOVID (CAP) - EMEA/H/C/002682/II/0036/G, Orphan
Applicant: Celgene Europe BV
PRAC Rapporteur: Eva Segovia
Scope: Grouped variations consisting of: 1) update of sections 4.2, 4.4 and 4.8 of the SmPC
with information on anaphylaxis and section 4.8 of SmPC with hypothyroidism as anadverse drug reaction (ADR) following a safety review. The package leaflet is updated
accordingly; 2) update of section 6.6 of the SmPC in order to include recommendations tominimise the risk of unintended occupational exposures in healthcare professionals. The
MAH took the opportunity to include minor updates to section 4.4 of the SmPC and to
introduce more clarity in Annex II-D on ‘Specific obligation to complete post-authorisation
measures for the conditional marketing authorisation’ regarding the educational materials,prescribing and dispensing restrictions
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.37.

Ravulizumab - ULTOMIRIS (CAP) - EMEA/H/C/004954/II/0002
Applicant: Alexion Europe SAS
PRAC Rapporteur: Kimmo Jaakkola
Scope: Extension of indication to include the treatment of patients with atypical haemolytic

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uremic syndrome (aHUS). As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 6.6 of
the SmPC are updated. The package leaflet and the RMP (version 1.6) are updated
accordingly. In addition, Annex II-D on ‘Conditions or restrictions with regard to the safeand effective use of the medicinal product’ is updated to include in the educational materials
the risk of thrombotic microangiopathy (TMA) with the new indication
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.38.

Rivaroxaban - XARELTO (CAP) - EMEA/H/C/000944/X/0074/G
Applicant: Bayer AG
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Grouped applications consisting of: 1) extension application to introduce a newpharmaceutical form, granules for oral suspension, 1 mg/mL; 2) extension of indication to
include treatment of venous thromboembolism (VTE) and prevention of VTE recurrence interm neonates, infants and toddlers, children and adolescents aged less than 18 years
following initiation of standard anticoagulation treatment for Xarelto (rivaroxaban) 15 mg
and 20 mg tablets. As a consequence, sections 4.2, 4.4, 4.5, 4.8, 4.9, 5.1 and 5.2 of the
SmPC are updated. The package leaflet and the RMP (version 12.1) are updated
accordingly. In addition, sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated for allother dose strengths (2.5/10 mg and 15/20 mg initiation packs). Furthermore, the MAH
took the opportunity to update the product information with regards to sodium content inline with the Annex to the European Commission (EC) guideline on ‘excipients in thelabelling and package leaflet of medicinal products for human use’
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.39.

Thalidomide - THALIDOMIDE CELGENE (CAP) - EMEA/H/C/000823/II/0061/G
Applicant: Celgene Europe BV
PRAC Rapporteur: Ghania Chamouni
Scope: Grouped variations consisting of: 1) update of sections 4.2, 4.4 and 4.8 of the SmPC
with information on anaphylaxis following a safety review. The package leaflet is updated
accordingly; 2) update of section 6.6 of the SmPC in order to include recommendations tominimise the risk of unintended occupational exposures in healthcare professionals. The
MAH took the opportunity to include minor updates to section 4.4 of the SmPC and to
introduce more clarity in Annex II-D on ‘Specific obligation to complete post-authorisation
measures for the conditional marketing authorisation’ regarding the educational materials,prescribing and dispensing restrictions
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

5.3.40.

Zoledronic acid - ZOMETA (CAP) - EMEA/H/C/000336/II/0091
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Anette Kirstine Stark
Scope: Update of sections 4.4 and 5.1 of the SmPC in order to update the safety
information on osteonecrosis of the jaw (ONJ) based on final results from study

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CZOL446EUS122 (listed as a category 3 study in the RMP): a non-interventional,
prospective, observational, multicentre cohort study to assess the incidence of ONJ incancer patients with bone metastases starting zoledronic acid treatment. The RMP (version12) is updated accordingly
Action: For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP

6.

Periodic safety update reports (PSURs)

6.1.

PSUR single assessment (PSUSA) procedures including centrally
authorised products (CAPs) only

6.1.1.

Abemaciclib - VERZENIOS (CAP) - PSUSA/00010724/201909
Applicant: Eli Lilly Nederland B.V.
PRAC Rapporteur: Marcia Sofia Sanches de Castro Lopes Silva
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.2.

Alemtuzumab - LEMTRADA (CAP) - PSUSA/00010055/201909
Applicant: Sanofi Belgium
PRAC Rapporteur: Anette Kirstine Stark
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.3.

Avelumab - BAVENCIO (CAP) - PSUSA/00010635/201909
Applicant: Merck Europe B.V.
PRAC Rapporteur: Hans Christian Siersted
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.4.

Bedaquiline - SIRTURO (CAP) - PSUSA/00010074/201909
Applicant: Janssen-Cilag International NV
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

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6.1.5.

Cariprazine - REAGILA (CAP) - PSUSA/00010623/201910
Applicant: Gedeon Richter Plc.
PRAC Rapporteur: Ana Sofia Diniz Martins
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.6.

Cemiplimab - LIBTAYO (CAP) - PSUSA/00010780/201909
Applicant: Regeneron Ireland Designated Activity Company (DAC)
PRAC Rapporteur: Menno van der Elst
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.7.

Chenodeoxycholic acid 5 - CHENODEOXYCHOLIC ACID LEADIANT (CAP) PSUSA/00010590/201910
Applicant: Leadiant GmbH
PRAC Rapporteur: Adam Przybylkowski
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.8.

Cholic acid 6 - ORPHACOL (CAP) - PSUSA/00010208/201909
Applicant: Laboratoires CTRSPRAC Rapporteur: Sofia Trantza
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.9.

Choriogonadotropin alfa - OVITRELLE (CAP) - PSUSA/00000736/201909
Applicant: Merck Europe B.V.
PRAC Rapporteur: Menno van der Elst
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

5

Indicated for the treatment of inborn errors of primary bile acid synthesis due to sterol 27 hydroxylase deficiency (presenting
as cerebrotendinous xanthomatosis (CTX)) in infants, children and adolescents aged 1 month to 18 years and adults –centrally authorised product(s) only
6
Treatment of inborn errors in primary bile acid synthesis due to 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency or Δ43-oxosteroid-5β-reductase indication(s) only
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6.1.10.

Ciclosporin 7 - IKERVIS (CAP); VERKAZIA (CAP) - PSUSA/00010362/201909
Applicant: Santen Oy
PRAC Rapporteur: Jan Neuhauser
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.11.

Crizotinib - XALKORI (CAP) - PSUSA/00010042/201908
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Ghania Chamouni
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.12.

Dacomitinib - VIZIMPRO (CAP) - PSUSA/00010757/201909
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Menno van der Elst
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.13.

Dapagliflozin - EDISTRIDE (CAP); FORXIGA (CAP) - PSUSA/00010029/201910
Applicant: AstraZeneca AB
PRAC Rapporteur: Annika Folin
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.14.

Darunavir, cobicistat, emtricitabine, tenofovir alafenamide - SYMTUZA (CAP) PSUSA/00010646/201909
Applicant: Janssen-Cilag International N.V.
PRAC Rapporteur: Ana Sofia Diniz Martins
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.15.

Darvadstrocel - ALOFISEL (CAP) - PSUSA/00010676/201909
Applicant: Takeda Pharma A/S, ATMP 8

7
8

Topical use only
Advanced therapy medicinal product
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PRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CAT and CHMP

6.1.16.

Denosumab 9 - PROLIA (CAP) - PSUSA/00000954/201909
Applicant: Amgen Europe B.V.
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.17.

Dexamethasone 10 - NEOFORDEX (CAP) - PSUSA/00010480/201909
Applicant: Laboratoires CTRSPRAC Rapporteur: Ghania Chamouni
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.18.

Dulaglutide - TRULICITY (CAP) - PSUSA/00010311/201909
Applicant: Eli Lilly Nederland B.V.
PRAC Rapporteur: Ilaria Baldelli
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.19.

Dupilumab - DUPIXENT (CAP) - PSUSA/00010645/201909
Applicant: Sanofi-aventis groupe
PRAC Rapporteur: Kimmo Jaakkola
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.20.

Eluxadoline - TRUBERZI (CAP) - PSUSA/00010528/201909
Applicant: Allergan Pharmaceuticals International Limited
PRAC Rapporteur: Adam Przybylkowski
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

9

Indicated for osteoporosis and for bone loss associated with hormone ablation in prostate cancer only
Indicated in symptomatic multiple myeloma only, centrally authorised product(s) only

10

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6.1.21.

Etravirine - INTELENCE (CAP) - PSUSA/00001335/201909
Applicant: Janssen-Cilag International NV
PRAC Rapporteur: Adrien Inoubli
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.22.

Fremanezumab - AJOVY (CAP) - PSUSA/00010758/201909
Applicant: Teva GmbH
PRAC Rapporteur: Kirsti Villikka
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.23.

Galcanezumab - EMGALITY (CAP) - PSUSA/00010733/201909
Applicant: Eli Lilly Nederland B.V.
PRAC Rapporteur: Kirsti Villikka
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.24.

Glycopyrronium 11 - SIALANAR (CAP) - PSUSA/00010529/201909
Applicant: Proveca Pharma Limited
PRAC Rapporteur: Zane Neikena
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.25.

Idebenone 12 - RAXONE (CAP) - PSUSA/00010412/201909
Applicant: Santhera Pharmaceuticals (Deutschland) GmbH
PRAC Rapporteur: Amelia Cupelli
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.26.

Infliximab - FLIXABI (CAP); INFLECTRA (CAP); REMICADE (CAP); REMSIMA (CAP);ZESSLY (CAP) - PSUSA/00010759/201908
Applicant(s): Celltrion Healthcare Hungary Kft. (Remsima), Janssen Biologics B.V.
(Remicade), Pfizer Europe MA EEIG (Inflectra), Sandoz GmbH (Zessly), Samsung Bioepis NL

11
12

Indicated for the treatment of severe sialorrhea (chronic pathological drooling), centrally authorised product(s) only
Centrally authorised product(s) only

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B.V. (Flixabi)
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.27.

Insulin aspart - FIASP (CAP); NOVOMIX (CAP); NOVORAPID (CAP) PSUSA/00001749/201909
Applicant: Novo Nordisk A/S
PRAC Rapporteur: Annika Folin
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.28.

Insulin degludec, liraglutide - XULTOPHY (CAP) - PSUSA/00010272/201909
Applicant: Novo Nordisk A/S
PRAC Rapporteur: Menno van der Elst
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.29.

Isavuconazole - CRESEMBA (CAP) - PSUSA/00010426/201909
Applicant: Basilea Pharmaceutica Deutschland GmbH
PRAC Rapporteur: Adam Przybylkowski
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.30.

Lorlatinib - LORVIQUA (CAP) - PSUSA/00010760/201909
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Nikica Mirošević Skvrce
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.31.

Lusutrombopag - MULPLEO (CAP) - PSUSA/00010755/201909
Applicant: Shionogi B.V.
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

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6.1.32.

Mepolizumab - NUCALA (CAP) - PSUSA/00010456/201909
Applicant: GlaxoSmithKline Trading Services Limited
PRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.33.

Mogamulizumab - POTELIGEO (CAP) - PSUSA/00010741/201909
Applicant: Kyowa Kirin Holdings B.V.
PRAC Rapporteur: Hans Christian Siersted
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.34.

Naldemedine - RIZMOIC (CAP) - PSUSA/00010753/201909
Applicant: Shionogi B.V.
PRAC Rapporteur: Rhea Fitzgerald
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.35.

Naloxegol - MOVENTIG (CAP) - PSUSA/00010317/201909
Applicant: Kyowa Kirin Holdings B.V.
PRAC Rapporteur: Ronan Grimes
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.36.

Naltrexone, bupropion - MYSIMBA (CAP) - PSUSA/00010366/201909
Applicant: Orexigen Therapeutics Ireland Limited
PRAC Rapporteur: Martin Huber
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.37.

Netupitant, palonosetron - AKYNZEO (CAP) - PSUSA/00010393/201910
Applicant: Helsinn Birex Pharmaceuticals Limited
PRAC Rapporteur: Ilaria Baldelli
Scope: Evaluation of a PSUSA procedure

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Action: For adoption of recommendation to CHMP

6.1.38.

Niraparib - ZEJULA (CAP) - PSUSA/00010655/201909
Applicant: GlaxoSmithKline (Ireland) Limited
PRAC Rapporteur: Jan Neuhauser
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.39.

Ocrelizumab - OCREVUS (CAP) - PSUSA/00010662/201909
Applicant: Roche Registration GmbH
PRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.40.

Panitumumab - VECTIBIX (CAP) - PSUSA/00002283/201909
Applicant: Amgen Europe B.V.
PRAC Rapporteur: David Olsen
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.41.

Pitolisant - WAKIX (CAP) - PSUSA/00010490/201909
Applicant: Bioprojet Pharma
PRAC Rapporteur: Kirsti Villikka
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.42.

Raltegravir - ISENTRESS (CAP) - PSUSA/00010373/201909
Applicant: Merck Sharp & Dohme B.V.
PRAC Rapporteur: Adrien Inoubli
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.43.

Ribociclib - KISQALI (CAP) - PSUSA/00010633/201909
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Hans Christian Siersted

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Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.44.

Risankizumab - SKYRIZI (CAP) - PSUSA/00010765/201909
Applicant: AbbVie Deutschland GmbH & Co. KG
PRAC Rapporteur: Liana Gross-Martirosyan
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.45.

Ritonavir - NORVIR (CAP) - PSUSA/00002651/201908
Applicant: AbbVie Deutschland GmbH & Co. KG
PRAC Rapporteur: Liana Gross-Martirosyan
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.46.

Rivaroxaban - XARELTO (CAP) - PSUSA/00002653/201909
Applicant: Bayer AG
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.47.

Sodium zirconium cyclosilicate - LOKELMA (CAP) - PSUSA/00010675/201909
Applicant: AstraZeneca AB
PRAC Rapporteur: Kirsti Villikka
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.48.

Sofosbuvir, ledipasvir - HARVONI (CAP) - PSUSA/00010306/201910
Applicant: Gilead Sciences Ireland UC
PRAC Rapporteur: Ana Sofia Diniz Martins
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.49.

Telbivudine - SEBIVO (CAP) - PSUSA/00002880/201908
Applicant: Novartis Europharm Limited

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PRAC Rapporteur: Adrien Inoubli
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.50.

Tenecteplase - METALYSE (CAP) - PSUSA/00002888/201908
Applicant: Boehringer Ingelheim International GmbH
PRAC Rapporteur: Martin Huber
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.51.

Tildrakizumab - ILUMETRI (CAP) - PSUSA/00010720/201909
Applicant: Almirall S.A
PRAC Rapporteur: Adam Przybylkowski
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.52.

Tobramycin 13 - VANTOBRA (CAP) - PSUSA/00010370/201909
Applicant: PARI Pharma GmbH
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.53.

Trabectedin - YONDELIS (CAP) - PSUSA/00003001/201909
Applicant: Pharma Mar, S.A.
PRAC Rapporteur: Hans Christian Siersted
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.54.

Velmanase alfa - LAMZEDE (CAP) - PSUSA/00010677/201909
Applicant: Chiesi Farmaceutici S.p.A.
PRAC Rapporteur: Jan Neuhauser
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

13

Nebuliser solution, centrally authorised product(s) only

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6.1.55.

Vernakalant hydrochloride - BRINAVESS (CAP) - PSUSA/00003109/201908
Applicant: Correvio
PRAC Rapporteur: Menno van der Elst
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.1.56.

Vortioxetine - BRINTELLIX (CAP) - PSUSA/00010052/201909
Applicant: H. Lundbeck A/S
PRAC Rapporteur: Laurence de Fays
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.2.

PSUR single assessment (PSUSA) procedures including centrally
authorised products (CAPs) and nationally authorised products(NAPs)

6.2.1.

Anagrelide - ANAGRELIDE MYLAN (CAP); XAGRID (CAP); NAP PSUSA/00000208/201909
Applicants: Mylan S.A.S (Anagrelide Mylan), Shire Pharmaceuticals Ireland Limited (Xagrid),
various
PRAC Rapporteur: Ghania Chamouni
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.2.2.

Budesonide, formoterol - BIRESP SPIROMAX (CAP); DUORESP SPIROMAX (CAP);
NAP - PSUSA/00010585/201908
Applicants: Teva Pharma B.V. (BiResp Spiromax, DuoResp Spiromax), various
PRAC Rapporteur: Hans Christian Siersted
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.2.3.

Octocog alfa - ADVATE (CAP); HELIXATE NEXGEN 14; KOGENATE BAYER (CAP);KOVALTRY (CAP); NAP - PSUSA/00002200/201908
Applicants: Baxter AG (Advate), Bayer AG (Helixate NexGen, Kogenate Bayer, Kovaltry),
various
PRAC Rapporteur: Brigitte Keller-Stanislawski

14

European Commission (EC) decision on the marketing authorisation withdrawal granted on 19 December 2019Pharmacovigilance Risk Assessment Committee (PRAC)
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Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.2.4.

Thalidomide - THALIDOMIDE CELGENE (CAP); NAP - PSUSA/00002919/201910
Applicants: Celgene Europe BV (Thalidomide Celgene), various
PRAC Rapporteur: Ghania Chamouni
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.2.5.

Trientine - CUFENCE (CAP); CUPRIOR (CAP); NAP - PSUSA/00010637/201909
Applicants: GMP-Orphan SA (Cuprior), Univar Solutions BV (Cufence), various
PRAC Rapporteur: Ana Sofia Diniz Martins
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.2.6.

Zoledronic acid 15 - ZOLEDRONIC ACID HOSPIRA (CAP); ZOLEDRONIC ACID MEDAC(CAP); ZOMETA (CAP); NAP - PSUSA/00003149/201908
Applicants: Medac Gesellschaft fur klinische Spezialpraparate mbH (Zoledronic acid medac),
Novartis Europharm Limited (Zometa), Pfizer Europe MA EEIG (Zoledronic acid Hospira),
various
PRAC Rapporteur: Anette Kirstine Stark
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CHMP

6.3.

PSUR single assessment (PSUSA) procedures including nationallyauthorised products (NAPs) only

6.3.1.

Biperiden (NAP) – PSUSA/00000415/201908
Applicant(s): various
PRAC Lead: Jan Neuhauser
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.2.

Conjugated estrogens (CE), medroxyprogesterone acetate (MPA) (NAP) –PSUSA/00000582/201908
Applicant(s): various

15

Indicated for the treatment of cancer and fractures only

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PRAC Lead: Martin Huber
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.3.

Dermatophagoides pteronyssinus, dermatophagoides farina 16 17 18 (NAP) –PSUSA/00010582/201909
Applicant(s): various
PRAC Lead: Brigitte Keller-Stanislawski
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.4.

Dexamfetamine (NAP) – PSUSA/00000986/201909
Applicant(s): various
PRAC Lead: Ana Sofia Diniz Martins
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.5.

Finasteride (NAP) – PSUSA/00001392/201908
Applicant(s): various
PRAC Lead: Annika Folin
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.6.

Fluocinolone acetonide 19 (NAP) – PSUSA/00010224/201908
Applicant(s): various
PRAC Lead: Marcia Sofia Sanches de Castro Lopes Silva
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.7.

Human plasma protease C1 inhibitor 20 (NAP) – PSUSA/00010163/201908
Applicant(s): various
PRAC Lead: Brigitte Keller-Stanislawski

16

Allergen for therapy
For oromucosal use only
Medicinal product(s) authorised via mutually recognition procedure and decentralised procedure only
19
Intravitreal implant(s) in applicator only
20
Nationally authorised product(s) only
17
18

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Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.8.

Hydrocortisone 21 (NAP) – PSUSA/00010328/201908
Applicant(s): various
PRAC Lead: Željana Margan Koletić
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.9.

Lercanidipine (NAP) – PSUSA/00001841/201908
Applicant(s): various
PRAC Lead: Kimmo Jaakkola
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.10.

Modafinil (NAP) – PSUSA/00010242/201908
Applicant(s): various
PRAC Lead: Martin Huber
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.11.

Nifuroxazide (NAP) – PSUSA/00002160/201908
Applicant(s): various
PRAC Lead: Jana Lukačišinová
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.12.

Oxcarbazepine (NAP) – PSUSA/00002235/201908
Applicant(s): various
PRAC Lead: Anette Kirstine Stark
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

21

Except medicinal product(s) indicated in adrenal insufficiency in a modified release tablet formulation

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6.3.13.

Paricalcitol (NAP) – PSUSA/00002316/201908
Applicant(s): various
PRAC Lead: Eva Segovia
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.3.14.

Sotalol (NAP) – PSUSA/00002774/201908
Applicant(s): various
PRAC Lead: Anette Kirstine Stark
Scope: Evaluation of a PSUSA procedure
Action: For adoption of recommendation to CMDh

6.4.

Follow-up to PSUR/PSUSA procedures

6.4.1.

Apixaban - ELIQUIS (CAP) - EMEA/H/C/002148/LEG 036
Applicant: Bristol-Myers Squibb / Pfizer EEIGPRAC Rapporteur: Menno van der Elst
Scope: Cumulative review of cases of angioedema as requested in the conclusions of the
PSUR single assessment (PSUSA) procedure (PSUSA/00000226/201905) adopted in
December 2019
Action: For adoption of advice to CHMP

6.4.2.

Brodalumab - KYNTHEUM (CAP) - EMEA/H/C/003959/LEG 005.1
Applicant: LEO Pharma A/S
PRAC Rapporteur: Eva Segovia
Scope: MAH’s response to LEG 005 [review of all available data from clinical trials,
spontaneous reports and published literature relating to the risk of inflammatory bowel
disease (IBD) and potential mechanism/biological plausibility of the occurrence of IBD asrequested in the conclusions of the PSUR single assessment (PSUSA) procedure(PSUSA/00010341/201812) for secukinumab adopted in July 2019] as per the request for
supplementary information (RSI) adopted in December 2019
Action: For adoption of advice to CHMP

6.4.3.

Ixekizumab - TALTZ (CAP) - EMEA/H/C/003943/LEG 004.1
Applicant: Eli Lilly Nederland B.V.
PRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: MAH’s response to LEG 004 [review of all available data from clinical trials,

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spontaneous reports and published literature relating to the risk of inflammatory bowel
disease (IBD) and potential mechanism/biological plausibility of the occurrence of IBD asrequested in the conclusions of the PSUR single assessment (PSUSA) procedure(PSUSA/00010341/201812) for secukinumab adopted in July 2019] as per the request for
supplementary information (RSI) adopted in December 2019
Action: For adoption of advice to CHMP

6.4.4.

Natalizumab - TYSABRI (CAP) - EMEA/H/C/000603/LEG 070
Applicant: Biogen Netherlands B.V.
PRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: Analyses of cumulative data on pregnancy including foetal outcomes as requested in
the conclusions of the PSUR single assessment (PSUSA) procedure(PSUSA/00002127/201908) adopted in February 2020
Action: For adoption of advice to CHMP

6.4.5.

Secukinumab - COSENTYX (CAP) - EMEA/H/C/003729/LEG 007.1
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Eva Segovia
Scope: MAH’s response to LEG 007 [review of all available data from clinical trials,
spontaneous reports and published literature relating to the risk of inflammatory bowel
disease (IBD) and potential mechanism/biological plausibility of the occurrence of IBD asrequested in the conclusions of the PSUR single assessment (PSUSA) procedure(PSUSA/00010341/201812) adopted in July 2019] as per the request for supplementary
information (RSI) adopted in December 2019
Action: For adoption of advice to CHMP

6.5.

Variation procedure(s) resulting from PSUSA evaluation

6.5.1.

Docetaxel - TAXOTERE (CAP) - EMEA/H/C/000073/II/0136/G
Applicant: Sanofi Mature IP
PRAC Rapporteur: Ghania Chamouni
Scope: Grouped variations consisting of: 1) update of sections 4.4 and 4.8 of the SmPC to
add a warning and safety information about tumour lysis syndrome (TLS) based on a
cumulative safety review requested in the conclusions of the latest periodic safety update
report single assessment (PSUSA) procedure (PSUSA/00001152/201611) concluded in
September 2017. The package leaflet is updated accordingly. In addition, the MAH took theopportunity to make minor corrections to the SmPC and update the list of local
representatives in the package leaflet; 2) update of section 4.8 of the SmPC to add safety
information about myositis based on cumulative safety review requested in the conclusionsof the latest PSUSA procedure (PSUSA/00001152/201611) concluded in September 2017.
The package leaflet is updated accordingly

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Action: For adoption of PRAC Assessment Report

7.

Post-authorisation safety studies (PASS)

7.1.

Protocols of PASS imposed in the marketing authorisation(s) 22

7.1.1.

Asfotase alfa – STRENSIQ (CAP) – EMEA/H/C/PSA/S/0050
Applicant: Alexion Europe SAS
PRAC Rapporteur: Rhea Fitzgerald
Scope: Substantial amendment to a protocol previously agreed in May 2016 (PSP/0032.1)
for study ALX-HPP-501: an observational, longitudinal, prospective, long-term registry ofpatients with hypophosphatasia to collect information on the epidemiology of the disease,including clinical outcomes and quality of life, and to evaluate safety and effectiveness datain patients treated with Strensiq (asfotase alfa)
Action: For adoption of PRAC Assessment Report, PRAC outcome letter

7.1.2.

Rurioctocog alfa pegol – ADYNOVI (CAP) - EMEA/H/C/PSA/S/0045.1
Applicant: Baxalta Innovations GmbH
PRAC Rapporteur: Menno van der Elst
Scope: MAH’s response to PSA/S/0045.1 [substantial amendment to a protocol previously
agreed in July 2019 (PSP/S/0077.1) for a study evaluating the long-term safety of
Adynovi/Adynovate (rurioctocog alfa pegol) in adults and adolescents ≥12 years of age withhaemophilia A] as per the request for supplementary information (RSI) adopted in
December 2019
Action: For adoption of PRAC Assessment Report, PRAC outcome letter

7.1.3.

Turoctocog alfa pegol – ESPEROCT (CAP) - EMEA/H/C/PSP/S/0085.1
Applicant: Novo Nordisk A/S
PRAC Rapporteur: Brigitte Keller Stanislawski
Scope: MAH’s response to PSP/S/0085 [protocol for a multinational, prospective, open
labelled, non-controlled, non-interventional post-authorisation study of turoctocog alfa pegol(N8-GP) including the polyethylene glycol (PEG) moiety during long-term routine
prophylaxis and treatment of bleeding episodes in patients with haemophilia A] as per therequest for supplementary information (RSI) adopted in January 2020
Action: For adoption of PRAC Assessment Report, PRAC outcome letter

22

In accordance with Article 107n of Directive 2001/83/EC

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7.1.4.

Volanesorsen – WAYLIVRA (CAP) - EMEA/H/C/PSP/S/0080.2
Applicant: Akcea Therapeutics Ireland Limited
PRAC Rapporteur: Martin Huber
Scope: MAH’s response to PSP/S/0080.1 [protocol for a multinational observational registry(WAY4001) of patients treated with volanesorsen to evaluate the safety on severe
thrombocytopenia and bleeding in patients with familial chylomicronemia syndrome (FCS)]
as per the request for supplementary information (RSI) adopted in January 2020
Action: For adoption of PRAC Assessment Report, PRAC outcome letter

7.2.

Protocols of PASS non-imposed in the marketing authorisation(s) 23

7.2.1.

Cangrelor - KENGREXAL (CAP) - EMEA/H/C/003773/MEA 002.2
Applicant: Chiesi Farmaceutici S.p.A.
PRAC Rapporteur: Ilaria Baldelli
Scope: MAH’s response to MEA 002.1 [protocol for study DFIDM-1801 (ARCANGELO (itAlianpRospective study on CANGrELOr)): a multicentre prospective observational study of acutecoronary syndrome patients undergoing percutaneous coronary intervention (PCI) who
receive cangrelor and transition to either clopidogrel, prasugrel or ticagrelor] as per therequest for supplementary information (RSI) adopted in December 2019
Action: For adoption of advice to CHMP

7.2.2.

Dibotermin alfa - INDUCTOS (CAP) - EMEA/H/C/000408/LEG 074.2
Applicant: Medtronic BioPharma B.V.
PRAC Rapporteur: Menno van der Elst
Scope: MAH’s response to LEG 074.1 [MAH’s response to LEG 074.1 [detailed evaluation of
the effectiveness of the current educational materials as requested in the conclusions of theconclusions of the PSUR single assessment (PSUSA) procedure (PSUSA/00001034/201709)
adopted in April 2018, including the submission of a protocol for a survey amongst
physicians to assess their knowledge and understanding of selected risks of Inductos(dibotermin alfa) in Europe] as per the request for supplementary information (RSI)
adopted in November 2019
Action: For adoption of advice to CHMP

7.2.3.

Emtricitabine, tenofovir disoproxil - TRUVADA (CAP) - EMEA/H/C/000594/MEA
047.4
Applicant: Gilead Sciences Ireland UC
PRAC Rapporteur: Ana Sofia Diniz Martins23

In accordance with Article 107m of Directive 2001/83/EC, supervised by PRAC in accordance with Article 61a (6) ofRegulation (EC) No 726/2004
Pharmacovigilance Risk Assessment Committee (PRAC)
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Scope: MAH’s response to MEA 047.3 [protocol for study No GS EU 276 4487: aprospective, longitudinal, observational registry of emtricitabine/tenofovir disoproxil
fumarate for human immunodeficiency virus 1 (HIV-1) pre-exposure prophylaxis (PrEP) of
adults and adolescents in Europe] as per the request for supplementary information (RSI)
adopted in December 2019
Action: For adoption of advice to CHMP

7.2.4.

Flutemetamol (18F) - VIZAMYL (CAP) - EMEA/H/C/002557/MEA 002.3
Applicant: GE Healthcare AS
PRAC Rapporteur: Martin Huber
Scope: Amendment to a previously agreed protocol in December 2015 for study GE067-027
CPR in order to evaluate the effectiveness of Vizamyl (flutemetamol (18F)) reader training inEurope and to assess the frequency of image classification errors in clinical practice
Action: For adoption of advice to CHMP

7.2.5.

Hydrocortisone - PLENADREN (CAP) - EMEA/H/C/002185/MEA 009.2
Applicant: Shire Services BVBAPRAC Rapporteur: Annika Folin
Scope: MAH’s response to MEA 009.1 [amended protocol for study SHP617-400 (EU AIR)
(0918-400): a non-interventional (PASS) registry study: A European multicentre, multicountry, post-authorisation observational study (registry) to monitor the safety of long-term
treatment with Plenadren (hydrocortisone) and other glucocorticoid replacement therapies
in patients with chronic adrenal insufficiency with a focus on intercurrent illness, adrenal
crisis and serious adverse events] as per the request for supplementary information (RSI)
adopted in November 2019
Action: For adoption of advice to CHMP

7.2.6.

Inotersen - TEGSEDI (CAP) - EMEA/H/C/004782/MEA 001.3
Applicant: Akcea Therapeutics Ireland Limited
PRAC Rapporteur: Rhea Fitzgerald
Scope: MAH’s response to MEA 001.2 [protocol for a long-term observational study toevaluate and further characterize the events of thrombocytopenia, glomerulonephritis andretinal toxicity/eye disease related to vitamin A deficiency when Tegsedi (inotersen) isprescribed in normal clinical practice, consisting of a protocol for a cohort of inotersenexposed patients (TEG4001) and a protocol for an external comparator cohort (TEG4003)]
as per the request for supplementary information (RSI) adopted in November 2019
Action: For adoption of advice to CHMP

7.2.7.

Inotersen - TEGSEDI (CAP) - EMEA/H/C/004782/MEA 002.3
Applicant: Akcea Therapeutics Ireland Limited

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PRAC Rapporteur: Rhea Fitzgerald
Scope: MAH’s response to MEA 002.2 [protocol for study TEG4002: a retrospective chart
review for evaluating adherence to and effectiveness of the proposed platelet monitoringschedule, proposed cut-off points, dose adaptation, and initiation of corticosteroids onthrombocyte recovery] as per the request for supplementary information (RSI) adopted in
November 2019
Action: For adoption of advice to CHMP

7.2.8.

Interferon beta-1a - AVONEX (CAP) - EMEA/H/C/000102/MEA 088
Applicant: Biogen Netherlands B.V.
PRAC Rapporteur: Maria del Pilar Rayon
Scope: Protocol for a joint PASS for study 2600153 (INFORM): an observational study
regarding interferon beta exposure in the second and third trimesters of pregnancy - aregister-based drug utilisation study (DUS) in Finland and Sweden
Action: For adoption of advice to CHMP

7.2.9.

Interferon beta-1a - REBIF (CAP) - EMEA/H/C/000136/MEA 045
Applicant: Merck Europe B.V.
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Protocol for a joint PASS for study 2600153 (INFORM): an observational study
regarding interferon beta exposure in the second and third trimesters of pregnancy - aregister-based drug utilisation study (DUS) in Finland and Sweden
Action: For adoption of advice to CHMP

7.2.10.

Interferon beta-1b - BETAFERON (CAP) - EMEA/H/C/000081/MEA 025
Applicant: Bayer AG
PRAC Rapporteur: Martin Huber
Scope: Protocol for a joint PASS for study 2600153 (INFORM): an observational study
regarding interferon beta exposure in the second and third trimesters of pregnancy - aregister-based drug utilisation study (DUS) in Finland and Sweden
Action: For adoption of advice to CHMP

7.2.11.

Interferon beta-1b - EXTAVIA (CAP) - EMEA/H/C/000933/MEA 023
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Martin Huber
Scope: Protocol for a joint PASS for study 2600153 (INFORM): an observational study
regarding interferon beta exposure in the second and third trimesters of pregnancy - aregister-based drug utilisation study (DUS) in Finland and Sweden

Pharmacovigilance Risk Assessment Committee (PRAC)
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Action: For adoption of advice to CHMP

7.2.12.

Patisiran - ONPATTRO (CAP) - EMEA/H/C/004699/MEA 002.3
Applicant: Alnylam Netherlands B.V.
PRAC Rapporteur: Rhea Fitzgerald
Scope: MAH’s response to MEA 002.2 [protocol for study ALN-TTR02-0009: a prospective
observational study to monitor and assess the safety of Onpattro (patisiran) in a real-worldcohort of hereditary transthyretin amyloidosis (hATTR) patients] as per the request for
supplementary information (RSI) adopted in December 2019
Action: For adoption of advice to CHMP

7.2.13.

Peginterferon beta-1a - PLEGRIDY (CAP) - EMEA/H/C/002827/MEA 010
Applicant: Biogen Netherlands B.V.
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Protocol for a joint PASS for study 2600153 (INFORM): an observational study
regarding interferon beta exposure in the second and third trimesters of pregnancy - aregister-based drug utilisation study (DUS) in Finland and Sweden
Action: For adoption of advice to CHMP

7.2.14.

Romosozumab - EVENITY (CAP) - EMEA/H/C/004465/MEA 001
Applicant: UCB Pharma S.A.
PRAC Rapporteur: Adrien Inoubli
Scope: Protocol for study OP0005: a European non-interventional PASS to study theadherence to the risk minimisation measures (RMMs) in the product information by
estimating the compliance with contraindications and target indication(s) amongst incident
romosozumab users, and analysing the utilisation pattern using the EU-adverse drug
reactions (EU-ADR) Alliance [final study results expected in March 2026] (from initial
opinion/marketing authorisation)
Action: For adoption of advice to CHMP

7.2.15.

Romosozumab - EVENITY (CAP) - EMEA/H/C/004465/MEA 002
Applicant: UCB Pharma S.A.
PRAC Rapporteur: Adrien Inoubli
Scope: Protocol for study OP0004: a European non-interventional PASS to evaluate
potential differences in terms of serious cardiovascular adverse events between
romosozumab and currently available therapies used in comparable patients in real-world
conditions using the EU-adverse drug reactions (EU-ADR) Alliance [final study results
expected in December 2026] (from initial opinion/marketing authorisation)
Action: For adoption of advice to CHMP

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7.2.16.

Romosozumab - EVENITY (CAP) - EMEA/H/C/004465/MEA 003
Applicant: UCB Pharma S.A.
PRAC Rapporteur: Adrien Inoubli
Scope: Protocol for study OP0006: a European non-interventional PASS to evaluate
potential differences in terms of serious infection between romosozumab and currently
available therapies used in comparable patients in real-world conditions using the EUadverse drug reactions (EU-ADR) Alliance [final study results expected in December 2024](from initial opinion/marketing authorisation)
Action: For adoption of advice to CHMP

7.2.17.

Ropeginterferon alfa-2b - BESREMI (CAP) - EMEA/H/C/004128/MEA 001.2
Applicant: AOP Orphan Pharmaceuticals AG
PRAC Rapporteur: Ana Sofia Diniz Martins
Scope: MAH’s response to MEA 001.1 [protocol for EUPAS29462 study: a prospective,
multicentre, non-interventional observational PASS to further investigate the safety andtolerability of ropeginterferon alfa-2b in polycythaemia vera patients with a special focus on
hepatotoxicity to evaluate the effectiveness of risk minimisation measures and to evaluate
cardiovascular safety during titration phase [final study report expected in Q3 2023]] as per
the request for supplementary information (RSI) adopted December 2019
Action: For adoption of advice to CHMP

7.2.18.

Sotagliflozin - ZYNQUISTA (CAP) - EMEA/H/C/004889/MEA 004.1
Applicant: Navigant Germany GmbH
PRAC Rapporteur: Martin Huber
Scope: MAH’s response to MEA 004 [protocol for a nested, case-control study to evaluate
the risk of malignancies (bladder, renal, breast, Leydig cell, pancreatic, thyroid and prostatecancers) in adult patients with type 1 diabetes mellitus (T1DM) using sotagliflozin in existing
healthcare databases in Europe and in the United States [final clinical study report (CSR)
expected in April 2030]] as per the request for supplementary information (RSI) adopted in
November 2019
Action: For adoption of advice to CHMP

7.3.

Results of PASS imposed in the marketing authorisation(s) 24
None

24

In accordance with Article 107p-q of Directive 2001/83/EC

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7.4.

Results of PASS non-imposed in the marketing authorisation(s) 25

7.4.1.

Agalsidase beta - FABRAZYME (CAP) - EMEA/H/C/000370/II/0113
Applicant: Genzyme Europe BV
PRAC Rapporteur: Liana Gross-Martirosyan
Scope: Submission of the final report from study AGALSC08994 (listed as a category 3
study in the RMP): a post-authorisation study on Fabrazyme (agalsidase beta) home
infusion educational materials effectiveness evaluation: a survey of healthcare providers
and patients/caregivers. The RMP (version 2.0) is updated accordingly. The RMP is also
updated in line with revision 2 of the guidance on the format of RMP in the EU (template)
and with information on study AGAL02603: a multicentre, multinational study of the effectsof Fabrazyme (agalsidase beta) treatment on lactation and infants and study AGAL19211:
the Fabry registry/pregnancy sub-registry
Action: For adoption of PRAC Assessment Report

7.4.2.

Blinatumomab - BLINCYTO (CAP) - EMEA/H/C/003731/II/0034/G, Orphan
Applicant: Amgen Europe B.V.
PRAC Rapporteur: Eva Jirsová
Scope: Submission of the final reports from studies 20150163 and 20150228 (listed as
category 3 studies in the RMP) assessing the effectiveness of the additional risk
minimisation measures (aRMM) for healthcare professionals (study 20150163) andpatients/caregivers (study 20150228)
Action: For adoption of PRAC Assessment Report

7.4.3.

Deferasirox - EXJADE (CAP) - EMEA/H/C/000670/II/0068
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Ghania Chamouni
Scope: Submission of the final report related to the physician survey (NO6987) conducted
for Exjade (deferasirox) to assess the impact of educational materials on the prescribers'
awareness of doses and biological monitoring recommendations and to assess theawareness and appropriate use of both formulations (dispersible tablets and film-coatedtablets). The RMP (version 17.1) is updated accordingly
Action: For adoption of PRAC Assessment Report

7.4.4.

Etanercept - ENBREL (CAP) - EMEA/H/C/000262/WS1653/0230; LIFMIOR (CAP) EMEA/H/C/004167/WS1653/0024
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Eva Segovia

25

In accordance with Article 61a (6) of Regulation (EC) No 726/2004, in line with the revised variations regulation for any
submission as of 4 August 2013
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Scope: Submission of the second 5-year report from the British Society for Rheumatology
Biologics Register (BSRBR) also referred as study B1801309 (listed as a category 3 study in
the RMP). This is a prospective observational cohort study which investigates the long-term
outcomes of patients with rheumatoid arthritis treated with etanercept with particularreference to safety
Action: For adoption of PRAC Assessment Report

7.4.5.

Hydroxycarbamide - SIKLOS (CAP) - EMEA/H/C/000689/II/0045
Applicant: Addmedica S.A.S.
PRAC Rapporteur: Laurence de Fays
Scope: Update of sections 4.2, 4.3, 4.4, 4.5, 4.6, 4.8 and 4.9 of the SmPC in order toreflect the final study results of non-interventional cohort study ESCORT-HU (European
Sickle Cell Disease Cohort-Hydroxyurea): an observational prospective cohort study tomeasure the occurrence of adverse events and serious adverse events and to harmonise theproduct information with other hydroxyurea (HU)-containing products. In addition, Annex
II-D on ‘Conditions or restrictions with regard to the safe and effective use of the medicinal
product’ is amended to delete the reference to the treatment guide for physicians. The
package leaflet and the RMP (version 20) are updated accordingly
Action: For adoption of PRAC Assessment Report

7.4.6.

Infliximab - INFLECTRA (CAP) - EMEA/H/C/002778/II/0079
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Kimmo Jaakkola
Scope: Submission of the final clinical study report (CSR) for study C1231002 (PERSIST):an observational cohort study designed to evaluate real life drug persistence in biologic
naive rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis patients receiving
CT-P13 (infliximab biosimilar) or those switched to CT-P13 from stable treatment with thereference medicinal product containing infliximab
Action: For adoption of PRAC Assessment Report

7.4.7.

Infliximab - INFLECTRA (CAP) - EMEA/H/C/002778/II/0080
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Kimmo Jaakkola
Scope: Submission of the final clinical study report (CSR) for study C1231001 (CONNECTIBD): a non-interventional study designated as a PASS conducted voluntarily to capture
data from real-world clinical practice to characterise the population and document drug
utilisation patterns. In addition, available safety data and data on the effectiveness of CTP13 (infliximab biosimilar) was collected in patients with Crohn's disease or ulcerative colitis
in the context of standard of care utilisation of the reference medicinal product containing
infliximab
Action: For adoption of PRAC Assessment Report

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7.4.8.

Infliximab - REMSIMA (CAP) - EMEA/H/C/002576/II/0073
Applicant: Celltrion Healthcare Hungary Kft.
PRAC Rapporteur: Kimmo Jaakkola
Scope: Submission of the final clinical study report (CSR) for study C1231001 (CONNECTIBD): a non-interventional study designated as a PASS conducted voluntarily to capture
data from real-world clinical practice to characterise the population and document drug
utilisation patterns. In addition, available safety data and data on the effectiveness of CTP13 (infliximab biosimilar) was collected in patients with Crohn's disease or ulcerative colitis
in the context of standard of care utilisation of the reference medicinal product containing
infliximab
Action: For adoption of PRAC Assessment Report

7.4.9.

Infliximab - REMSIMA (CAP) - EMEA/H/C/002576/II/0074
Applicant: Celltrion Healthcare Hungary Kft.
PRAC Rapporteur: Kimmo Jaakkola
Scope: Submission of the final clinical study report (CSR) for study C1231002 (PERSIST):an observational cohort study designed to evaluate real life drug persistence in biologic
naive rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis patients receiving
CT-P13 (infliximab biosimilar) or those switched to CT-P13 from stable treatment with thereference medicinal product containing infliximab
Action: For adoption of PRAC Assessment Report

7.5.

Interim results of imposed and non-imposed PASS submitted before
the entry into force of the revised variation regulation

7.5.1.

Alemtuzumab - LEMTRADA (CAP) - EMEA/H/C/003718/MEA 007.9
Applicant: Sanofi Belgium
PRAC Rapporteur: Anette Kirstine Stark
Scope: Fifth annual report for study OBS13434: a prospective, multicentre, observational
PASS to evaluate the long term safety profile of Lemtrada (alemtuzumab) treatment inpatients with relapsing forms of multiple sclerosis (MS) and to determine the incidence ofadverse events of special interest (AESIs)
Action: For adoption of advice to CHMP

7.5.2.

Etanercept - BENEPALI (CAP) - EMEA/H/C/004007/MEA 002.3
Applicant: Samsung Bioepis NL B.V.
PRAC Rapporteur: Eva Segovia
Scope: Fourth annual interim report from an established nationwide register (British Society
for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA)) for patients with

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rheumatological disorders treated with biologic agents, designed as a national prospective
study whose primary purpose is to assess long-term toxicity from the use of these agents inroutine practice [final report expected in 2027]
Action: For adoption of advice to CHMP

7.5.3.

Etanercept - BENEPALI (CAP) - EMEA/H/C/004007/MEA 003.3
Applicant: Samsung Bioepis NL B.V.
PRAC Rapporteur: Eva Segovia
Scope: Fourth annual interim report from an established nationwide register (Rheumatoide
Arthritis: Beobachtung der Biologika-Therapie (RABBIT)) for patients with rheumatologicaldisorders treated with biologic agents, designed as a national prospective study whose
primary purpose is to assess long-term toxicity from the use of these agents in routine
practice [final report expected in 2027]
Action: For adoption of advice to CHMP

7.5.4.

Etanercept - BENEPALI (CAP) - EMEA/H/C/004007/MEA 004.3
Applicant: Samsung Bioepis NL B.V.
PRAC Rapporteur: Eva Segovia
Scope: Fourth annual interim report for study from ARTIS (Anti-Rheumatic Treatment in
Sweden) register: a national prospective, observational, uncontrolled cohort study
evaluating the risk of selected adverse events (AEs) in rheumatoid arthritis (RA), juvenile
idiopathic arthritis, and other rheumatic disease patients treated with etanercept [final
report expected in 2027]
Action: For adoption of advice to CHMP

7.5.5.

Etanercept - BENEPALI (CAP) - EMEA/H/C/004007/MEA 005.3
Applicant: Samsung Bioepis NL B.V.
PRAC Rapporteur: Eva Segovia
Scope: Fourth annual interim report for study from BADBIR (British Association of
Dermatologists Biologic Interventions Register) register: a national prospective,
observational, uncontrolled cohort study evaluating the risk of selected adverse events(AEs) in rheumatoid arthritis (RA), juvenile idiopathic arthritis, and other rheumatic disease
patients treated with etanercept [final report expected in 2027]
Action: For adoption of advice to CHMP

7.5.6.

Golimumab - SIMPONI (CAP) - EMEA/H/C/000992/MEA 033.3
Applicant: Janssen Biologics B.V.
PRAC Rapporteur: Ulla Wändel Liminga
Scope: Second annual interim report for study MK-8259-050 (listed as a category 3 study in

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the RMP): an observational PASS for golimumab in treatment of poly-articular juvenile
idiopathic arthritis (pJIA) using the German Biologics JIA registry (BiKeR)
Action: For adoption of advice to CHMP

7.5.7.

Lonoctocog alfa - AFSTYLA (CAP) - EMEA/H/C/004075/MEA 002.1
Applicant: CSL Behring GmbH
PRAC Rapporteur: Sonja Hrabcik
Scope: Progress report for study CSL627_3001: a multicentre, open-label, phase 3
extension study which will investigate the safety and efficacy of recombinant factor VIII
(rVIII)-single chain (CSL627) for prophylaxis and on-demand treatment of bleeding
episodes in a total of at least 250 previously treated patients (PTP) with severe congenital
haemophilia A
Action: For adoption of advice to CHMP

7.5.8.

Nivolumab - OPDIVO (CAP) - EMEA/H/C/003985/MEA 008.7
Applicant: Bristol-Myers Squibb Pharma EEIGPRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: MAH’s response to MEA 008.6 [third annual interim report for study CA209234(listed as a category 3 study in the RMP): a PASS exploring the pattern of use, safety, andeffectiveness of nivolumab in routine oncology practice [final clinical study report (CSR)
expected in December 2024] as per the request for supplementary information (RSI)
adopted in December 2019
Action: For adoption of advice to CHMP

7.5.9.

Rivastigmine - EXELON (CAP) - EMEA/H/C/000169/MEA 036.5
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Ghania Chamouni
Scope: Annual report (covering the period from 01 February 2018 to 31 January 2019) of
the drug utilisation study (DUS) on the effectiveness of risk minimisation measures (RMM)
for multiple patch use
Action: For adoption of advice to CHMP

7.5.10.

Rivastigmine - PROMETAX (CAP) - EMEA/H/C/000255/MEA 037.5
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Ghania Chamouni
Scope: Annual report (covering the period from 01 February 2018 to 31 January 2019) of
the drug utilisation study (DUS) on the effectiveness of risk minimisation measures (RMM)
for multiple patch use
Action: For adoption of advice to CHMP

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7.5.11.

Sirolimus - RAPAMUNE (CAP) - EMEA/H/C/000273/MEA 054.2
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Ulla Wändel Liminga
Scope: Interim analysis study report for study B1741224: a non-interventional
observational population-based cohort study to monitor the safety and effectiveness ofsirolimus in patients with sporadic lymphangioleiomyomatosis (S-LAM)
Action: For adoption of advice to CHMP

7.5.12.

Ustekinumab - STELARA (CAP) - EMEA/H/C/000958/MEA 022.19
Applicant: Janssen-Cilag International NV
PRAC Rapporteur: Rhea Fitzgerald
Scope: Ninth annual report for study C0168Z03 (PSOLAR: PSOriasis Longitudinal
Assessment and Registry): an international prospective cohort study/registry programme
designed to collect data on psoriasis (PSO) patients that are eligible to receive systemic
therapies, including generalised phototherapy and biologics, together with MAH’s response
to MEA 022.18 [eighth annual report for study C0168Z03] as per the request for
supplementary information (RSI) adopted in January 2020
Action: For adoption of advice to CHMP

7.6.

Others

7.6.1.

Deferasirox - EXJADE (CAP) - EMEA/H/C/000670/MEA 075.1
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Ghania Chamouni
Scope: MAH’s response to MEA 075 [interim study results for study CICL670F2202(CALYPSO): a randomized, open-label, multicentre, two arm, phase 2 study allowing toevaluate the safety of deferasirox granules in paediatric patients with iron overload [final
clinical study report (CSR) expected in June 2021] (from X/54)] as per the request for
supplementary information (RSI) adopted in November 2019
Action: For adoption of advice to CHMP

7.6.2.

Emicizumab - HEMLIBRA (CAP) - EMEA/H/C/004406/MEA 005
Applicant: Roche Registration GmbH
PRAC Rapporteur: Amelia Cupelli
Scope: Evaluation of the MAH’s assessment of a letter to the editor in the New England
Journal of Medicine (NEJM) entitled ‘deaths associated with emicizumab in patients withhemophilia A’ 26 published in November 201926

N Engl J Med 2019; 381: 1878-1879: DOI 10.1056/nejmC1909742

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Action: For adoption of advice to CHMP

7.7.

New Scientific Advice
None

7.8.

Ongoing Scientific Advice
Information related to this section cannot be released at the present time as it is deemed tocontain commercially confidential information.

7.9.

Final Scientific Advice (Reports and Scientific Advice letters)
None

8.

Renewals of the marketing authorisation, conditional renewal
and annual reassessments

8.1.

Annual reassessments of the marketing authorisation

8.1.1.

Afamelanotide - SCENESSE (CAP) - EMEA/H/C/002548/S/0032 (without RMP)
Applicant: Clinuvel Europe Limited
PRAC Rapporteur: Martin Huber
Scope: Annual reassessment of the marketing authorisation
Action: For adoption of advice to CHMP

8.1.2.

Cholic acid - ORPHACOL (CAP) - EMEA/H/C/001250/S/0033 (without RMP)
Applicant: Laboratoires CTRSPRAC Rapporteur: Sofia Trantza
Scope: Annual reassessment of the marketing authorisation
Action: For adoption of advice to CHMP

8.1.3.

Susoctocog alfa - OBIZUR (CAP) - EMEA/H/C/002792/S/0028 (without RMP)
Applicant: Baxalta Innovations GmbH
PRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: Annual reassessment of the marketing authorisation
Action: For adoption of advice to CHMP

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8.1.4.

Tafamidis - VYNDAQEL (CAP) - EMEA/H/C/002294/S/0055 (without RMP)
Applicant: Pfizer Europe MA EEIGPRAC Rapporteur: Ghania Chamouni
Scope: Annual reassessment of the marketing authorisation
Action: For adoption of advice to CHMP

8.2.

Conditional renewals of the marketing authorisation

8.2.1.

Ataluren - TRANSLARNA (CAP) - EMEA/H/C/002720/R/0057 (without RMP)
Applicant: PTC Therapeutics International Limited
PRAC Rapporteur: Liana Gross-Martirosyan
Scope: Annual reassessment of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.

Renewals of the marketing authorisation

8.3.1.

Aripiprazole - ARIPIPRAZOLE SANDOZ (CAP) - EMEA/H/C/004008/R/0014 (without
RMP)
Applicant: Sandoz GmbH
PRAC Rapporteur: Ana Sofia Diniz Martins
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.2.

Carfilzomib - KYPROLIS (CAP) - EMEA/H/C/003790/R/0044 (without RMP)
Applicant: Amgen Europe B.V.
PRAC Rapporteur: Nikica Mirošević Skvrce
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.3.

Cobimetinib - COTELLIC (CAP) - EMEA/H/C/003960/R/0019 (without RMP)
Applicant: Roche Registration GmbH
PRAC Rapporteur: Menno van der Elst
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

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8.3.4.

Everolimus - VOTUBIA (CAP) - EMEA/H/C/002311/R/0065 (without RMP)
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Martin Huber
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.5.

Glycerol phenylbutyrate - RAVICTI (CAP) - EMEA/H/C/003822/R/0034 (without
RMP)
Applicant: lmmedica Pharma AB
PRAC Rapporteur: Ilaria Baldelli
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.6.

Mepolizumab - NUCALA (CAP) - EMEA/H/C/003860/R/0031 (with RMP)
Applicant: GlaxoSmithKline Trading Services Limited
PRAC Rapporteur: Brigitte Keller-Stanislawski
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.7.

Pemetrexed - PEMETREXED MEDAC (CAP) - EMEA/H/C/003905/R/0008 (with RMP)
Applicant: medac Gesellschaft fur klinische Spezialpraparate mbH
PRAC Rapporteur: Ghania Chamouni
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.8.

Pemetrexed - PEMETREXED SANDOZ (CAP) - EMEA/H/C/004011/R/0008 (without
RMP)
Applicant: Sandoz GmbH
PRAC Rapporteur: Ghania Chamouni
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.9.

Phenylephrine, ketorolac - OMIDRIA (CAP) - EMEA/H/C/003702/R/0015 (with RMP)
Applicant: Omeros Ireland Limited
PRAC Rapporteur: Jan Neuhauser

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Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.10.

Pregabalin - PREGABALIN ACCORD (CAP) - EMEA/H/C/004024/R/0015 (with RMP)
Applicant: Accord Healthcare S.L.U.
PRAC Rapporteur: Liana Gross-Martirosyan
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.11.

Pregabalin - PREGABALIN SANDOZ (CAP) - EMEA/H/C/004010/R/0012 (with RMP)
Applicant: Sandoz GmbH
PRAC Rapporteur: Liana Gross-Martirosyan
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.12.

Pregabalin - PREGABALIN SANDOZ GMBH (CAP) - EMEA/H/C/004070/R/0013 (withRMP)
Applicant: Sandoz GmbH
PRAC Rapporteur: Liana Gross-Martirosyan
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.13.

Sacubitril, valsartan - ENTRESTO (CAP) - EMEA/H/C/004062/R/0031 (without RMP)
Applicant: Novartis Europharm Limited
PRAC Rapporteur: Anette Kirstine Stark
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

8.3.14.

Tasimelteon - HETLIOZ (CAP) - EMEA/H/C/003870/R/0018 (without RMP)
Applicant: Vanda Pharmaceuticals Germany GmbH
PRAC Rapporteur: Adam Przybylkowski
Scope: 5-year renewal of the marketing authorisation
Action: For adoption of advice to CHMP

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9.

Product related pharmacovigilance inspections

9.1.

List of planned pharmacovigilance inspections
Disclosure of information on pharmacovigilance inspections could undermine the protectionof the purpose of these inspections, investigations and audits. Therefore such information is
not reported in the agenda.

9.2.

Ongoing or concluded pharmacovigilance inspections
Disclosure of information on results of pharmacovigilance inspections could undermine theprotection of the purpose of these inspections, investigations and audits. Therefore suchinformation is not reported in the agenda.

9.3.

OthersNone

10.

Other safety issues for discussion requested by the CHMP or
the EMA

10.1.

Safety related variations of the marketing authorisation
None

10.2.

Timing and message content in relation to Member States’ safety
announcements
None

10.3.

Other requests
None

10.4.

Scientific Advice
Information related to this section cannot be released at the present time as it is deemed tocontain commercially confidential information.

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11.

Other safety issues for discussion requested by the Member
States

11.1.

Safety related variations of the marketing authorisation
None

11.2.

Other requests
None

12.

Organisational, regulatory and methodological matters

12.1.

Mandate and organisation of the PRAC

12.1.1.

PRAC Rules of Procedure - revision
Action: For adoption

12.2.

Coordination with EMA Scientific Committees or CMDh-v
None

12.3.

Coordination with EMA Working Parties/Working Groups/DraftingGroupsNone

12.4.

Cooperation within the EU regulatory network

12.4.1.

Coronavirus (COVID-19) pandemic - update
Action: For discussion

12.4.2.

Heads of Medicines Agencies (HMA)-EMA joint big data taskforce – call for
nomination to the steering group
Action: For adoption

12.5.

Cooperation with International Regulators
None

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12.6.

Contacts of the PRAC with external parties and interaction with theInterested Parties to the Committee
None

12.7.

PRAC work plan
None

12.8.

Planning and reporting

12.8.1.

Marketing authorisation applications (MAA) forecast for 2020 – planning update
dated Q1 2020
Action: For information

12.9.

Pharmacovigilance audits and inspections

12.9.1.

Pharmacovigilance systems and their quality systems
None

12.9.2.

Pharmacovigilance inspections
None

12.9.3.

Pharmacovigilance auditsNone

12.10.

Periodic safety update reports (PSURs) & Union reference date
(EURD) list

12.10.1.

Periodic safety update reports
None

12.10.2.

Granularity and Periodicity Advisory Group (GPAG)
PRAC lead: Menno van der Elst, Maia Uusküla
Action: For discussion

12.10.3.

PSURs repository
None

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12.10.4.

Union reference date list – consultation on the draft list
Action: For adoption

12.11.

Signal management

12.11.1.

Signal management – feedback from Signal Management Review Technical(SMART) Working Group
PRAC lead: Menno van der Elst
Action: For discussion

12.12.

Adverse drug reactions reporting and additional reporting

12.12.1.

Management and reporting of adverse reactions to medicinal products
None

12.12.2.

Additional monitoring
None

12.12.3.

List of products under additional monitoring – consultation on the draft list
Action: For adoption

12.13.

EudraVigilance database

12.13.1.

Activities related to the confirmation of full functionality
None

12.14.

Risk management plans and effectiveness of risk minimisations

12.14.1.

Risk management systems
None

12.14.2.

Tools, educational materials and effectiveness measurement of risk minimisations
None

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12.15.

Post-authorisation safety studies (PASS)

12.15.1.

Post-authorisation Safety Studies – imposed PASS
None

12.15.2.

Post-authorisation Safety Studies – non-imposed PASS
None

12.16.

Community procedures

12.16.1.

Referral procedures for safety reasonsNone

12.17.

Renewals, conditional renewals, annual reassessments
None

12.18.

Risk communication and transparency

12.18.1.

Public participation in pharmacovigilanceNone

12.18.2.

Safety communication
None

12.19.

Continuous pharmacovigilance

12.19.1.

Incident management
None

12.20.

Others12.20.1.

Strategy on measuring the impact of pharmacovigilance - PRAC interest group (IG)Impact – results and recommendations from case study on stakeholder engagement
for valproate
PRAC lead: Antoine Pariente, Daniel Morales
Action: For discussion

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12.20.2.

Summary of product characteristics (SmPC) Advisory Group (AG) – call for
nomination
Action: For adoption

12.20.3.

Workshop on the role of registries in the monitoring of cancer therapies based on
tumours’ genetic and molecular features, 29 November 2019, Amsterdam, theNetherlands – final report: main observation and follow-up actions
Action: For discussion

13.

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14.

Explanatory notes

The Notes give a brief explanation of relevant agenda items and should be read in conjunction with theagenda.
EU Referral procedures for safety reasons: Urgent EU procedures and Other EU referral
procedures(Items 2 and 3 of the PRAC agenda)
A referral is a procedure used to resolve issues such as concerns over the safety or benefit-risk balance of a
medicine or a class of medicines. In a referral, the EMA is requested to conduct a scientific assessment of aparticular medicine or class of medicines on behalf of the European Union (EU). For further detailed
information on safety related referrals please see:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000150.jsp&mid=WC0b01ac05800240d0
Signals assessment and prioritisation(Item 4 of the PRAC agenda)
A safety signal is information on a new or incompletely documented adverse event that is potentially caused
by a medicine and that warrants further investigation. Signals are generated from several sources such as
spontaneous reports, clinical studies and the scientific literature. The evaluation of safety signals is a routine
part of pharmacovigilance and is essential to ensuring that regulatory authorities have a comprehensive
knowledge of a medicine’s benefits and risks.
The presence of a safety signal does not mean that a medicine has caused the reported adverse event. The
adverse event could be a symptom of another illness or caused by another medicine taken by the patient.
The evaluation of safety signals is required to establish whether or not there is a causal relationship between
the medicine and the reported adverse event.
The evaluation of safety signals may not necessarily conclude that the medicine caused the adverse event inquestion. In cases where a causal relationship is confirmed or considered likely, regulatory action may benecessary and this usually takes the form of an update of the summary of product characteristics and the
package leaflet.
Risk Management Plans (RMPs)(Item 5 of the PRAC agenda)
The RMP describes what is known and not known about the side effects of a medicine and states how theserisks will be prevented or minimised in patients. It also includes plans for studies and other activities to gain
more knowledge about the safety of the medicine and risk factors for developing side effects.
RMPs are continually modified and updated throughout the lifetime of the medicine as new information
becomes available.
Assessment of Periodic Safety Update Reports (PSURs)(Item 6 of the PRAC agenda)
A PSUR is a report providing an evaluation of the benefit-risk balance of a medicine, which is submitted bymarketing authorisation holders at defined time points following a medicine’s authorisation.
PSURs summarises data on the benefits and risks of a medicine and includes the results of all studies carriedout with this medicine (in the authorised and unauthorised indications).
Post-authorisation Safety Studies (PASS)(Item 7 of the PRAC agenda)
A PASS is a study of an authorised medicinal product carried out to obtain further information on its safety,
or to measure the effectiveness of risk management measures. The results of a PASS help regulatory
agencies to evaluate the safety and benefit-risk profile of a medicine.
Product related pharmacovigilance inspections(Item 9 of the PRAC agenda)
Inspections carried out by regulatory agencies to ensure that marketing authorisation holders comply with
their pharmacovigilance obligations.
More detailed information on the above terms can be found on the EMA website: www.ema.europa.eu/

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