prequalification of medicines
DESCRIPTION
Prequalification of Medicines. Dr Lembit Rägo, Coordinator Quality Assurance and Safety: Medicines (QSM) Department of Essential Medicines and Pharmaceutical Policies (EMP) Geneva, Switzerland. Web site updated constantly – www.who.int/prequal. Prequalification of Medicines Programme. - PowerPoint PPT PresentationTRANSCRIPT
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Prequalification of Medicines
Dr Lembit Rägo, CoordinatorQuality Assurance and Safety: Medicines (QSM) Department of Essential Medicines and Pharmaceutical Policies (EMP)Geneva, Switzerland
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Web site updated constantly – www.who.int/prequal
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Prequalification of Medicines ProgrammePrequalification of Medicines Programme
The UN Prequalification Programme is ensuring that medicines procured with international funds are of assessed and inspected quality, efficacy and safety.
The Prequalification Programme is an action plan for expanding access to priority essential medicines in the following four areas:
- HIV/AIDS - Tuberculosis- Malaria- Reproductive Health- Selected individual products for other diseases such as oseltamivir and Zinc sulphate
A UN Prequalification Program of Quality Control Laboratories exists to facilitate the quality control of the prequalified products.
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Prequalification of Medicinal Products: ObjectivesPrequalification of Medicinal Products: Objectives
- Propose a list of prequalified products and manufacturers meeting international norms and standards of which the quality, efficacy and safety has been assessed, inspected and controlled
- Ensure that international norms and standards are applied at all the steps of the Prequalification Programme.
- Make sure re-evaluation and maintenance of the list are performed and that variations and changes are correctly controlled.
- Help the national drug regulatory authorities to build up capacity in assessment, inspection and control meeting
international norms and standards.
- Develop the local possibilities of production and clinical studies by offering customized technical assistance.
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Expression of Interest
Compliance
Additional informationand data
Corrective actions
Compliance
Assessment Inspections
Medicines Prequalification ProcessMedicines Prequalification Process
Prequalification
Monitoring
Product dossierSMF
Dossier maintenance(variations)
Handling of complaints
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Assessment of the product dossier i.e. quality specifications, pharmaceutical development, stability, bioequivalence…
Copenhagen assessment week- 15 to 20 assessors during one week at least every two months - Every dossier part (mostly Q and BE) is assessed by at least 2 assessors including one senior assessor for the second assessment
- An assessment report is issued- Letter summarizing the findings and asking for clarification and additional data if necessary; sent first by e-mail to the applicant followed by surface mail
Handling of variations of already prequalified products- Done in house and during Copenhagen-week
Prequalification of Priority Essential Medicines Organisation (1) Prequalification of Priority Essential Medicines Organisation (1)
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Variations – 2009 (as of 30 October)Variations – 2009 (as of 30 October)
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Inspections of manufacturers of 1. - Finished Products (FPP) - Selected Active Pharmaceutical Ingredient (API) and also - Selected Contract Research Organizations (CRO, which
carry out clinical/bioequivalence studies)Team of inspectors - - WHO representative (qualified GMP inspector)- - Inspector from well-established inspectorate- - National inspectors invited to be part of the team as
observers but have no decision making power (different GMP standards, potential conflict of interest)
- -Inspector of potential target countries (and other countries in need for capacity building) as observers, for capacity building purpose.
Prequalification of Priority Essential Medicines Organisation (2)Prequalification of Priority Essential Medicines Organisation (2)
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Assessment & Inspections
Key numbers for 2008• 40 products prequalified (21 in 2007), • 92 dossiers submitted (90 in 2007)• 732 assessment reports (463 in 2007)• 52 inspections (45 in 2007)
For each prequalified product there were: 5-15 assessment reports In most cases, at least 1 inspection (may be more e.g. API,
FPP, CRO) 2 years total time on average to get prequalified (the clock
stops for PQ when request for additional information/corrective actions is sent to the applicant)
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
2005 2006 2007 2008HIV 67 42 25 42TB 17 9 17 12 Malaria 3 5 7 9Repr Health - - 10 4
Product dossiers accepted for evaluation
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
As of 31 January 2009 :
68 products for treatment of HIV/AIDS and related diseases
41 products for treatment of tuberculosis
17 products for treatment of malaria
11 reproductive health products
Total 137
Currently under evaluation in WHO Prequalification Programme
Currently under evaluation in WHO Prequalification Programme
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Transparency – dossier status information on the web
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Inspections - statistics in 2008 vs 2007
A total of 62 (2007 – 46) inspections were carried out in 2008:
• 27 (26) inspections of the manufacturing sites of finished product manufacturers
• 11 (6) inspections of the manufacturing sites of active pharmaceutical ingredients (APIs)
• 14 (13) inspections of contract research organizations (CROs)
• 10 (1) Quality control laboratories
In 2008 four/three inspectors in-house
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Prequalification Programme:Transparency - WHOPIRs and NOCsPrequalification Programme:Transparency - WHOPIRs and NOCs
These are published in response to the WHA Resolution WHA57.14 of 22 May 2004, which requested WHO, among other actions:• "3. (4) to ensure that the prequalification review
process and the results of inspection and assessment reports of the listed products, aside from proprietary and confidential information, are made publicly available;"
A WHO Public Inspection Report (WHOPIR) provides a summary of the inspection (where found to be GMP complaint)
A Notice of Concern (NOC) is a letter reflecting areas of concern where the non-compliances require urgent attention and corrective action by the manufacturer or research organization.
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Transparency – Inspection outcomes on the web
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Suspension of some TB medicines in 2009
APRIL 28, 2009, 12:32 P.M. ET WHO To Avoid Tuberculosis Drugs Made By Wyeth In Pakistan By Jared A. Favole Of DOW JONES NEWSWIRES WASHINGTON (Dow Jones)--The World Health Organization,
saying it can't assure the quality of several tuberculosis products made at a Wyeth (WYE) plant in Pakistan, will suspend recommending purchases of the drugs.
Wyeth Pakistan Ltd., a unit of Wyeth, introduced new active ingredients into the medications and changed the storage conditions without getting approval of the WHO, according to a letter the agency sent the company on Monday. The letter was posted online Tuesday.
The suspension affects four drugs manufactured at the plant that are used to treat tuberculosis, a deadly infectious disease that commonly affects the lungs.
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Products included in the WHO List of Prequalified MedicinesProducts included in the WHO List of Prequalified Medicines
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Products included in the WHO List of Prequalified Medicines by Therapeutic Area (cumulative numbers)Products included in the WHO List of Prequalified Medicines by Therapeutic Area (cumulative numbers)
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Capacity building: whom it affects?Capacity building: whom it affects?
WHO support to the generation of expertise for development, manufacture, control and regulation of medicines
Manufacturers
National Regulatory Authorities (NRAs)
Quality control laboratories (QCLs)
Clinical Research Organizations (CROs)
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Since November 2006 – present
8 fellows – from Zimbabwe, Uganda, Tanzania, Ethiopia and Ukraine• More fellows to join in 2009 including GMP
inspectors 3-months hands-on experience in everyday work
of the PQ Program team Optional participation as observer in inspections Follow-up plan for implementation at home
NMRA upon return
Rotational Position at WHO HQ
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
4
9
4
11
4
6
1
0
2
4
6
8
10
12
14
16
2006 2007 2008 2009 )I-IX(
Trainings organized or supported by PQP
PQP supported
PQP organized
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Trainings organized or supported byQSM in 2009 (I-IX) (1)
Trainings organized or supported byQSM in 2009 (I-IX) (1)
Assessment of pharmaceutical quality in PQP• Copenhagen, Denmark, January 14-16, 2009
WHO Prequalification programme and requirements• Damascus, Syria, February 8-9, 2009
WHO Prequalification programme and requirements• Cairo, Egypt, February 11-12, 2009
Training workshop on ACTs• Kampala, Uganda, February 23-27, 2009
Training workshop on the Assessment of Multisource Interchangeable Medicines• Mombasa, Kenya, July 10-14, 2009
Interregional seminar for Quality Control Laboratories• Nairobi, Kenya, September 23-25, 2009
Quality of Active Pharmaceutical Ingredients (APIs)• Hyderabad, India, September 5-7, 2009
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
165
198
103
57
263
301
568
195
122
5219
0
100
200
300
400
500
600
700
2007 2008 2009 )I-IX(
Participants in trainings organized or co-organized/supported by PQP
Others
QCL staff
Regulators
Manufacturers
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Countries hosting workshops organized or supported by Prequalification Programme
)2006-2009/I-IX(
0
1
2
3
4
Viet
nam
Ukr
aine
Uga
nda
Tanz
ania
Switz
erla
nd
Sout
h
Sene
gal
Paki
stan
Nic
arag
ua
Mor
occo
Mal
aysi
a
Ken
ya
Jord
an Iran
Indo
nesi
a
Indi
a
Gha
na
Fran
ce
Esto
nia
Egyp
t
Den
mar
k
Chi
na
Bra
zil
Bel
gium
Aus
tria
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Stimulates harmonization among• NMRAs
group assessments pass on skills readily available, user friendly guidelines - easy to
adopt/adapt Building trust among regulatory staff from same
region e.g. EAC• Manufacturers
Gives access to certain market free of charge Improve dossiers by use of WHO guidelines for
markets that do not have own guidelines yet Experience in submitting PQ dossiers improves
appreciation of regulatory requirements in other regions
Reduced cost – same dossiers to PQP and to NMRAs
Other Benefits
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
QCLs Prequalification ProcedureQCLs Prequalification Procedure (1)(1)September 2009QCLs Prequalification ProcedureQCLs Prequalification Procedure (1)(1)September 2009
83
10
3
16
3
22
8
24
11
24
0
5
10
15
20
25
30
35
2004 2005 2006 2007 2008 Sep-09
QCLs Prequalified QCLs Interested
Prequalified QCLs:
South Africa, RIIP+CENQAM (2005)
Algeria, LNCPP (2005)
South Africa, Adcock Ingram (2007)
Morocco, LNCM (2008)
Kenya, NQCL (2008)
India, Vimta Labs (2008)
France, CHMP (2008)
Vietnam, NIDQC (2008)
Kenya, MEDS (2009)
Singapore, HSA (2009)
Singapore, TÜV (2009)
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Capacity buildingCapacity building
Technical assistance provided to 8 national medicines QC laboratories • Focus on implementation of quality system and microbiological testing, inventory audits
Trainings in Quality Assurance, Quality Control and Ph.Int. under preparation (2007)• Morocco, 44 participants from 16 Francophone countries (AFRO, EMRO), cooperation with
EDQM and AFSSAPS• Tanzania, 46 participants from 23 Anglophone countries (AFRO, EMRO, PAHO/AMRO)
Seminar on rational sampling and testing in quality control of medicines (2009)• Kenya, 45 participants from 21 countries (AFRO, EMRO, WPRO)
Participation in EDQM Quality Assurance training for OMCLs• 2005, 5 participants from AFRO and EMRO• 2007, 12 participants from AFRO, EMRO and EURO
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Sampling and testing projects in 2008Sampling and testing projects in 2008Sampling and testing projects in 2008Sampling and testing projects in 2008
Quality survey of antimalarials (ACTs and sulfadoxine-pyrimethamine)• Cooperation with NDRAs in Cameroon, Ethiopia, Ghana, Kenya,
Madagascar, Nigeria, Senegal, Tanzania, Uganda• 936 samples collected and screened by Minilab, 299 selected for full
testing in laboratory (testing ongoing)• Assessment of quality of product information (Labelling and PIL)
Quality monitoring of products funded by UNITAID • Pilot phase (paediatric and second-line antiretrovirals) in cooperation
with NDRAs in Kenya, Tanzania, Uganda, Zambia• 378 samples collected and tested in laboratory (testing ongoing)• Assessment of quality of product information (Labelling and PIL)
Quality survey of anti-TB medicines in Eastern Europe• Cooperation with NDRAs in Armenia, Azerbaijan, Belarus, Kazakhstan,
Ukraine, Uzbekistan; Focused on Rifampicin, Isoniazid, Rifampicin/Isoniazid, Ofloxacin, Kanamycin (360 samples planned)
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Technical Assistance - Policy
Criteria for the products in relation to which technical assistance is considered:
Inclusion in the list of expression of interest High value for Public Health purposes Poor representation on the Prequalification list Manufacture has applied for PQ (exemptions can be made
upon justified requests for technical assistance from regional offices) danger
Criteria for the experts: Excellent qualifications and long standing experience in the
area where expertise is required Absence of conflict of interest Total intellectual independence from the prequalification
programme, no participation in inspections or assessments.
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Experts participating in TAs
2
6 10
5
11
12
0
5
10
15
20
25
2006 2007 2008
Involvement ofother experts inmissions
Involvement ofOTECI experts
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Revision of PQ procedure in 2008
Reasons for revision• 5 years experience from implementation• Differences between procedure and actual activities
practices• unclear responsibilities of parties
Aims of revision• increase transparency of PQ activities• publish more details of prequalified products• harmonize terminology and clarify procedures• better define responsibilities• confidentiality agreement with applicants
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Problems
Antimalarials and antituberculosis products – old problems but few new solutions• Immature submissions – takes time to get to the maturity needed• Relative lack of motivation from applicants• Relative lack of new innovator products • Generic products with no innovator• …or problem "new" products• GMP non compliance (both for finished dosage form and API)• Quality part of the dossier – specifications, stability data etc
incomplete• Bioequivalence – failures in studies (from design to GCP
compliance) Safety and efficacy – poor clinical and safety data, poor quality
information, poor information for users
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Summary remarks
International buyers – increasing quality requirements, new QA policies (e.g. GFTAM)
The purpose of the prequalification programme is to list good quality, safe and effective medicinal products in the interest of public health in resource-limited countries.
The products should be submitted with technical data proving the quality of API and finished product together with necessary data on safety and efficacy (quality submissions in demand)
Manufacturing sites of API s and finished products should operate according to GMP principles in order to deliver consistent quality products
CROs should conduct studies in compliance with GCP / GLP as appropriate
Second African Medicines Regulators Conference^, 24 ‐ 26 November 2009, Maputo, Mozambique,
Summary remarks (2)
Technical assistance for promising manufacturers/products can be made available to achieve the goal and speed up the prequalification process.
Close cooperation with international procurement and financial institutions• quality as prerequisite for procurement decision• instruments to support quality production
Encourage manufacturers to invest into quality, and to apply for independent evaluation
Main aim of PQ – to increase choice and access to quality products without compromising requirements for quality, safety and efficacy should remain unchanged