0

MHRA annual statistics 2011/12

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Contents Inspection and Standards Good Manufacturing Practice (GMP) 2 Defective Medicines Report Centre (DMRC) 2 Good Distribution Practice (GDP) 2 Good Clinical Practice (GCP) 2 Good Pharmacovigilance Practice (GPvP) 2 Good Laboratory Practice Monitoring Authority (GLPMA) 2 Manufacturers’ and wholesale dealers’ licences plus export certificates 2 Import Notification Section 3 Medicines Testing Scheme 3 Pharmacovigilance Reporting source of ADRs in the UK 4 Spontaneous UK ADR reports 5 Non-UK reports of suspected ADRs 5 Devices Adverse incident reports, numbers received, sources and outcomes 6 Safety warning notices issued 6 Enforcement Medicines 7 Referrals 7 Investigation outcomes 7 Intelligence Unit outcomes 7 Enforcement Policy Unit outcomes 7 Devices 8 Compliance investigations: Reactive 8 Compliance investigations: Proactive 8 Notified body audits 9 Clinical investigations undertaken 9 Clinical trial authorisations (CTA) 10 New active substances (NAS) assessed 10 Marketing authorisation (MA) applications determined 11 Parallel imports 11 CHMP scientific advice 12 MHRA Scientific Advice 12 Centralised rapporteur and co-rapporteurships 13 Renewals 13 Advertising 14 Borderline medicines considered 14 Sales of British Pharmacopoeia (BP)/BP Chemical Reference Substances 15 MHRA Customer Services enquiries 15 Medicines Information enquiries 16 Press Office 16

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Inspection and Standards 2011/12 Good Manufacturing Practice (GMP) In summary, GMP performed a total of 550 inspections, of which 149 were overseas, of which 37 were EMA inspections. Defective Medicines Reporting Centre Reports received: 902 Drug alerts issued: 35 Good Distribution Practice (GDP) GDP performed 703 inspections. Good Clinical Practice (GCP) Organisations inspected: 101 Investigator sites done: 28 Good Pharmacovigilance Practice (GPvP) 81 inspections performed. Of these,10 were performed to fulfil the EMA Routine Pharmacovigilance Inspection Programme. Total number of inspections conducted by GLPMA team (GLP, GMP and GCP) = 111 Good Laboratory Practice (GLP) breakdown: 65 routine biennial 6 for cause Total GLP Inspections = 71 Total GMP QC Lab inspections = 23 Total GCP Lab inspections = 13 Manufacturers and wholesale dealer’s licences plus export certificates Licences issued Manufacturer’s licences 27 Wholesale Dealer’s licences 289 Manufacturer’s licence variations 723 Wholesale dealer’s licence variations

994

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Export certificates Certificates issued: 6582 Unlicensed import notifications Total number of notifications 109402 Objections to importation 1259 Clinical emergencies 4607 The number of Clinical Emergencies processed was greater than in previous years as a result of an increased number of critical product shortages Medicines Testing Scheme Reports Received

Source of Samples 2008/09 2009/10 2010/11 2011/12 Defect Samples DMRC Inc Comparators 48 56 40 42

Medicines Inspectorate 16 64 88 49 Enforcement/Borderline 341 446 578 505 Pre-Approval (internal MHRA) inc Comparators 229 326 327 249

Market Surveillance Studies 1448 1159 754 237 EMEA (Centrally Authorised Products) 6 10 9 6 Counterfeit surveillance samples; authentication

Not recorded 608 493 567

Other (Includes Public, NHS, Contract Analysis and European Collaboration 374 186 152 98

Commentary Surveillance sampling this year has continued to be more focussed on “high risk” products and sites. In particular a large amount of work has been done providing analytical support to the cross-Agency Levothyroxine working party. MHRA laboratory staff assisted MHRA Enforcement and UK Border Agency staff during Operation Pangea IV. Two analysts took our portable spectroscopy equipment to the Coventry mail hub, where it was used to identify counterfeit products entering the country through the postal service. The instruments even made an appearance on the BBC programme “Fake Britain”. Proactive continuous surveillance of selected high risk products has continued throughout the year. Samples are collected on behalf of MTS by the General Pharmaceutical Council inspectors and from wholesalers collected by the GDP Inspectorate. This programme provides reassurance that products reaching patients are genuine. MTS collaborated with EDQM in the sampling of 3 Centrally Authorised Products (CAP) (Angiox, Atripla and Revalimid) and analysis of 3 CAP products (Myocet, Retacript and

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Silapo). We also analysis Clopidogrel products (Plavix and generic equivalents) as part of a European market surveillance study. MTS has continued to provide “Contract Analysis” support to other European Agencies lacking laboratory facilities (Malta and Ireland) and has worked with colleagues in the Official Medicines Control Laboratory network such as Infarmed and Swissmedic. Pharmacovigilance 2011/12 Reporting source of suspected ADRs in the UK received

Reporter qualification for direct UK spontaneous ADR reports received in 2011-2012

0

5

10

15

20

25

30

GPNurs

e

Hospital D

octor

Patien

t

Other Hea

lthca

re Pro

fessio

nal*

Hospital P

harmacis

t

Hospital N

urse

Community Pharm

acist

Other Pharm

acist

Physici

an

Reporter group

% o

f AD

R re

ports

rece

ived

Reporter Group Percentage Community Pharmacist 5% GP 25% Hospital Doctor 14% Hospital Nurse 5% Hospital Pharmacist 8% Nurse 15% Other HCP* 10% Other Pharmacist 3% Patient 13% Physician 2%

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* Other Healthcare Professionals (HCPs) include: chiropodist, coroner, dentist, healthcare assistant, medical student, midwife, optometrist, paramedic, radiographer, unspecified healthcare professionals. UK spontaneous suspected ADR reports Total Reports Fatal (%) Serious (%) 2011-2012 25846 7 87 2010-2011 23411 7 87 2009-2010 26173 4 81 2008-2009 24369 5 84 2007-2008 22201 5 86 Non-UK spontaneous suspected ADR reports

Non-UK reports of suspected ADRs

123755

151844

210835

84938106247

0

50000

100000

150000

200000

250000

2007-2008 2008-2009 2009-2010 2010-2011 2011-2012

Financial year

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Devices Adverse incident reports, numbers received, sources and outcomes Incidents reported 2011/12 11970 Investigated by MHRA 2459

Source Number Percentage Manufacturer 5959 49.8 NHS 3158 26.4 Non-govt organisation 127 1.1 Other govt. dept. 1064 8.9 Overseas reporting organisation 586 4.9 Private healthcare 740 6.2 Patient / MOP 336 2.8

Total 11970 100.0

Outcome Number Percentage No further action yet - trend only 8872 71.6 Single faulty device 976 7.9 Design change of device, label or packaging 895 7.2 Manufacturer changed /Improved QA 754 6.1 Device recall / Field Correction 1719 13.9 Improved maintenance 100 0.8 Revised/additional user training/publicity 238 1.9 MHRA safety warning / Manufacturer notice or letter 343 2.8 Production ceased 61 0.5 Safety warning notices issued Medical Device Alerts - Immediate Action - 2 Medical Device Alerts - Immediate Update - 1 Medical Device Alerts - Action - 101 Total MDAs issued: 104

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Enforcement Medicines Referrals New investigations 253 New intelligence files 335 Referral dealt with by CRC 2408 TOTAL 3000 Number of these referrals relating to counterfeit allegations Received through dedicated hotline 131 Received through other channels 135 TOTAL 266 Investigation outcomes Visits conducted 199 Value of medicines seized £8,230,830 Compliance advice given 139 Formal cautions 32 Prosecutions completed 16 Prosecutions pending 27 Confiscation orders £111,088 Conviction rate 82% Intelligence Unit outcomes Covert test purchases 109 Intelligence shared with UK agencies 163 Intelligence shared overseas 110 Enforcement Policy Unit outcomes Parliamentary Questions answered (includes POs, TOs and DEs)

16 (+7 contributions)

FOI requests answered 16 (+3 contributions) Ministerial briefings provided 9 (+3 contributions) Other government briefings provided 17 Devices The agency changed its focus in relation to proactive investigations where they now focus on a risk based proactive investigations regime, where they select devices, manufacturers and specific areas identified through complaints, incidents and completed reactive cases meeting a specific criteria . As a result of this the agency started 22 proactive cases and completed 27. It opened 269 reactive cases and completed 317. There are currently 93 under investigation. There were 23 inspections where the agency obtained search warrants to gain entry to premises. The Agency issued 4 compliance notices and in addition 6 devices were removed from the market as a result of compliance action and another 14 cases referred to

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other Member States for Investigation. All other cases were resolved satisfactory by working co-operatively with the manufacturers concerned. Compliance Investigations: Reactive Compliance Investigations: Proactive

Compliance Investigation: Reactive

174 189

254 263 255 269248

151

207 217 217

317

70108

155

201229

93

0

50

100

150

200

250

300

350

2006/07 2007/08 2008/09 2009/10 2010/11 2011/12

Opened Closed Carried forw ard

Compliance Investigation: Proactive

198 188201

169

60

22

209188

207

147

68

27

94 93 8770

57 52

0

50

100

150

200

250

2006/07 2007/08 2008/09 2009/10 2010/11 2011/12

Opened Closed Carried Forw ard

9

Notified Body Audits

Clinical Investigations Undertaken

We have also reviewed 11 Supplementary Evaluation Reports prepared by Notified Bodies in respect of devices utilising tissues of animal origin

Notified Body Audits

13

12

13

11 11

13

10

10.5

11

11.5

12

12.5

13

13.5

2006/07 2007/08 2008/09 2009/10 2010/11 2011/12

Clinical Investigations Undertaken

57 5954

64

45

74

0

10

20

30

40

50

60

70

80

2006/07 2007/08 2008/09 2009/10 2010/11 2011/12

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Clinical trial authorisations (CTA) Number of Phase 1 applications received 220 Average assessment time for Phase 1 (target 14.0) 12.4 Percentage Phase 1 assessed in 30 days (target 98%) 100% Number of other CTA applications 700 Percentage approved in 30 days (target 98%) 100% All performance metrics for CTA applications are now published on the MHRA website and updated monthly. New active substances (NAS) assessed

0

20

40

60

80

100

120

1989-90

1990-91

1991-92

1992-93

1993-94

1995-96

1996-97

1997-98

1998-99

1999-00

2000-01

2001-02

2002-03

2003-04

2004-05

2005-06

2006-07

2007-08

2008-09

2009-10

2010-11

2011-12

Assessment time (days)

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Marketing authorisation applications determined Marketing authorisation applications determined

1380 1456 1517 1575

157 118 69

566 569551

522

836

672

510

777

550

0

500

1000

1500

2000

2500

2005/06 2006/07 2007/08 2008/09 2009/10 2010/11 2011/20

Prod

uct L

icen

ses

and

Reg

ista

rtio

ns

UK only inc THRDCP RMSDCP CMSMRPALL

Parallel imports

3329

2009

1029 1123 1036 954

3380

1603

2308

3429

2379

15921164 954

8848

7146

5770

7003

78978332

8597

15564

6783

4499

7474

9741

8582

9682

14499

22892867

8846

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

2004/05 2005/06 2006/07 2007/08 2008/09 2009/10 2010/11 2011/12

Applications received Applications determined Variations received Variations determined

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CHMP scientific advice

CHMP scientific advice

2228

39 4248

7063

117 116

129

0

20

40

60

80

100

120

140

2002/03 2003/04 2004/05 2005/06 2006/07 2007/08 2008/09 2009/10 2010/11 2011/12

MHRA scientific advice

0

50

100

150

200

250

300

2008-2009 2009-2010 2010-2011 2011-2012

13

Centralised rapporteur and co-rapporteurships

Rap & Co-Rapporteurships appointments2000/01-2011/12

0

5

10

15

20

25

30

35

40

45

Denmark Spain Netherlands France Germany Sw eden United Kingdom

2000-01

2001-02

2002-03

2003-04

2004-05

2005-06

2006-07

2007-08

2008-09

2009-10

2010-11

2011-12

Generics included since 2008-9

Renewals The Agency received an average of 25 national renewal applications per month in 2011/2012 which is in line with the figures for 2010/201. The UK acted as reference member State in 242 MR procedures which is significantly higher than in the previous year. The UK was Rapporteur or Co-Rapporteur for 15 centralised procedures which is a slight increase on the previous year.

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Advertising 2008/2009 2009/2010 2010/2011 2011/2012 Number of complaints received

199

371

358

325

Number of advertisements withdrawn or amended as a result of action on complaints

107

273

293

238

Number of advertisements withdrawn or amended as a result of Agency scrutiny

6

6

6

2

Number of Corrective statements published

1

4

3

2

Products for which advertising was reviewed prior to issue

55

50

50

46

Additional information can be found in the Agency’s sixth annual report on the regulation of medicines advertising, Delivering high standards in medicines advertising regulation. This covers the period from January 2011 to December 2011 and can be found on the MHRA website, www.mhra.gov.uk. The 2012 annual report will be published in early 2013. Borderline medicines Complaints of breaches of legislation: received 276, cleared 226 Advice requests: received 508, cleared 537 Statutory determinations issued: provisional 13, Final 14

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Sales of British Pharmacopoeia (BP)/BP Chemical Reference Substances British Pharmacopoeia 2011 3073 copies; 161 active online subscribers British Pharmacopoeia 2012 (to end June 2012) 2565 copies; 175 active online subscribers Sales of BP Chemical Reference 2008/09 2009/10 2010/11 2011/12 Substances (No of vials sold) 11,645 12,461 13,375 15,697 Number of Invented Names assessed Year: 2008/9 2010/11 2011/2012 Number of EMA Names 549 698 963 Number of National Names 461 516 574 Total Number of Names: 1010 1214 1537 MHRA Customer Services enquiries

Customer Services Financial Year statistics

21,3

61

26,7

08 34,7

14

30,6

29

33,7

38

37,5

38

32,1

79

29,6

29

8,10

5 10,5

32

13,9

60

13,6

26

14,9

10 16,4

34 17,6

48

16,8

79

15,0

73

31,7

97

0

10,000

20,000

30,000

40,000

50,000

60,000

2003/04 2004/05 2005/06 2006/07 2007/08 2008/09 2009/10 2010/11 2011/12

Year

Num

ber C

EP e

nqui

ries

hand

led

Calls answered Emails answered

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Medicines Information enquiries Medicines Information received 3,351 enquiries in 2011/12. Press Office enquiries

Number of enquiries Number of proactive enquiries Percentage

Apr-11 225 146 64%May-11 139 67 48%Jun-11 165 74 45%Jul-11 159 73 46%

Aug-11 280 199 71%Sep-11 353 205 58%Oct-11 165 98 58%Nov-11 162 87 50%Dec-11 232 118 51%Jan-12 257 126 49%Feb-12 356 171 48%Mar-12 176 55 3%Apr-12 163 65 40%