European Association of Hospital Pharmacists Guidance on the Pharmacy Handling of Licensed Gene Medicines

1
European Association of Hospital Pharmacists
Guidance on the Pharmacy Handling of Licensed
Gene Medicines

• Dr. Nicola Stoner Consultant Pharmacist, Cancer
  Services Cancer Research UKOxford Radcliffe
  Hospitals NHS Trust.Principal Visiting Fellow,
  The University of Reading.BOPA October 14th,
  2007

2
The History

• May 2006 Ark Therapeutics approached the EAHP
  President
• Suggestion to collaborate with the EAHP to
  develop guidance on the handling of gene
  medicines
• EAHP President recommended consultation with EAHP
  board member Professor Arnold Vulto
• August 2006 First meeting between Professor
  Arnold Vulto and Ark Therapeutics approval of
  the plan by the EAHP board
• Ark Therapeutics provided unrestricted funding
  for the establishment of a working group and the
  development of the guidance

3
The History (continued)

• September 2006 National delegations at the EAHP
  General Assembly were approached to nominate gene
  medicines-experienced hospital pharmacists to
  take part in the working group to develop the
  guidance
• Ten expert gene medicines hospital pharmacists
  across 8 EU countries were selected and invited
  to participate in the development of the EAHP
  guidance
• All were locally recognised as gene medicine
  specialist pharmacists

4
The Experts

• Austria Andrea Wolfsberger
• Czech Republic Hana Balásová
• Finland Kirsi Kontra
• Germany Torsten Hoppe Tichy
• The Netherlands Arnold G Vulto, András Vermes
• Spain Juan L Vinent Genestar, Ana-Cristina
  Cercos
• Sweden Per Nydert
• United Kingdom Nicola Stoner

5
The Philosophy

• Guidance for licensed gene medicine, not research
  setting
• Limit to class I or II biosafety level
• As such, similar procedures to cytotoxic
  preparations and handling
• Recommendations should be practical, and feasible
  to implement in hospital pharmacies providing
  standard of oncology pharmacy support
• Risk level and procedures not exceeding an
  existing routine comparator product like BCG
  bladder instillation

6
The Process

• Review of existing literature, guidance and local
  practices
• Existing guidelines were collated and sent to all
  members prior to first meeting to gain insight
  into current standards
• All members completed a pre-meeting survey on
  handling of gene medicines in their
  country/facility
• First working group meeting (November 2006)
• 8 members attended the 1-day workshop in Schiphol
  Airport, Amsterdam, for in depth discussions
• Professor Vulto chaired the workshop
• Consensus on major points of the guidance reached

7
The Process (continued)

• Standard operating procedure (SOP) charts and
  tables drafted and reviewed by the working group
• Based on input prior to and during November
  meeting
• Editorial support was provided by Michelle
  ODonovan, PhD, Ogilvy Healthworld Medical
  Education
• Text to accompany SoPs drafted and reviewed by
  the working group
• Extensive review and consultation by all members
  in advance of second meeting in April 2007

8
The Process (continued)

• Second working group meeting (April 2007)
• Outstanding issues discussed in great detail and
  consensus reached
• Full text, including discussion section, drafted
  and reviewed by the working group
• External validation of the guidelines by three
  external experts

9
External Validation

• Prof Gavin Brooks, School of Pharmacy,
  University of Reading, UK
• Dr Marion Watson, Biological Safety Officer,
  Oxford Radcliffe Hospitals NHS Trust, UK
• V'lain Fenton-May, Hospital Pharmacist and QA
  Officer, Pharmacy Department, University Hospital
  of Wales, Cardiff, UK

10
The Process (continued)

1. Draft sent to EAHP board
2. June 2007 presentation of the results of the EAHP
   Working Group to the EAHP General Assembly

11
Final Outputs of this Working Group

• Submission as publication in European Journal of
  Hospital Pharmacy-Practice edition
• Available on EAHP website downloadable versions
  of SOPs and charts easy to update

12
Gene Therapy - Definition

• The introduction of genetic material into an
  individual, or the modification of the
  individuals genetic material, to achieve a
  therapeutic objective.
• The World Health Organization (WHO)

13
Genetically Modified Organism (GMO)

• An organism in which the genetic material has
  been altered in a way that does not occur
  naturally using recombinant nucleic acid
  techniques involving the formation of new
  combinations of genetic material by the insertion
  of nucleic acid molecules, into any virus,
  bacterial plasmid or other vector system and
  their incorporation into a host organism in which
  they do not naturally occur but in which they are
  capable of continued propagation.
• The Health and Safety Executive (HSE), UK

14
Need for Guidance on Handling Gene Medicines

• Viral vectors used in gene medicines include
  adeno-, retro-, adeno-associated, pox viral
  vectors
• Handling as biological agents
• Procedures similar to handling cytotoxics or
  Bacillus Calmette-Guérin (BCG)
• Hazards of gene medicines less than other
  infectious organisms in hospitals.

15
Existing Guidance

• Gene Therapy Advisory Committee (GTAC) UK
• Medicines for Human Use (Clinical Trials)
  Regulations 2004
• EU Council Directive 98/81/EC
• Health and Safety Executive (HSE) UK

16
Aims, scope and target of the guidance

• Centers that already have a dedicated gene
  medicine suite are in the best position to safely
  prepare and administer gene medicines.
• The guidance aims to provide broad, practical
  recommendations for the handling of licensed gene
  medicines in clinical practice within Europe.
• It encompasses recommendations for storage,
  transportation, preparation, dispensing,
  administration, waste disposal, decontamination
  and accidental exposure.

17
The Guidance

• Gene Medicines at biosafety level 1 or 2 in
  Europe
• Licensed medicine
• All staff involved at any stage of handling
• Presented as tables and flowcharts
• To be used in conjunction with Summary of Product
  Characteristics (SPC)
• Practice must comply with national legislation

18
Patient Care Handling Gene Medicines and
Patient Specimens

• Appropriate protective clothing for task
• Universal precautions
• Biological safety device for preparation
• No specific precautions for patient specimens
• Handling as for infectious diseases

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Chart 1. Storage of gene medicine
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Gene Medicine Storage

• Disposable protective clothing
• Package opening - biosafety cabinet
• Fridge, freezer (20o or 70ºC)
• Separate shelves for each gene medicine
• Secure, restricted access
• Temperature monitoring

23
Chart 2. Preparation of gene medicine and
decontamination of biological safety device used
for gene medicine procedures
24
Preparation (1)

• Biological safety device
• Pharmaceutical grade isolator
• Class II biological safety cabinet
• Exhaust to the outside, no recirculation
• Negative pressure (risk assessment)
• Prevention of cross contamination
• Use of biohazard sign outside the room
• Use of appropriate disinfectant (e.g. 12
  Virkon or 6 hydrogen peroxide)

25
Preparation (2)

• Co-ordination of preparation with administration
• Aseptic procedures
• Disinfectant in biosafety device
• Records of decontamination
• Eradication of aerosols

26
Transportation

• Seal in plastic bag/secondary container
• Leak-proof, labelled, biohazard container
• Temperature control
• Spill kit to be available
• Use immediately

27
Chart 3. Dispensing procedure for gene medicine
28
Dispensing

• Prescriptions checked - normal procedure
• Appropriate protective clothing
• Disposable absorbent in safety cabinet
• Transfer gene medicine
• Defrost if required and dispense
• Place in plastic bag
• Staff exposure log

29
Chart 4. Administration procedure for gene
medicine Guidance for clinical staff to develop
SoPs
30
Administration

• Co-ordination between pharmacy and administration
• Administer within recommended timelines
• Appropriate protective clothing
• Inpatient/outpatient/containment depends on risk
  assessment for each product

31
Chart 5. Gene medicine waste disposal
32
Waste Disposal

• Limit contact with the environment and people
• Non-disposable items must be cleaned with
  appropriate disinfectant
• Autoclaving
• Incineration
• Label appropriately
• Local regulations/legislation

33
Chart 6. Decontamination of gene medicine product
spills
34
Spillage Kit

• 2 disposable gowns or arm covers
• 4 gloves
• 2 aprons
• 2 pairs of goggles
• 4 disposable shoe covers
• 2 disinfectant sachets
• Absorbent paper towels
• 2 disposable forceps
• 2 biohazard disposal bags
• Emergency contact number
• Spillage procedure

35
Spill Decontamination

• Spillage kit available at all times
• Procedures for within and outside a biological
  safety device
• Person spilling the agent responsible for
  initiating decontamination procedure

36
Chart 7. Accidental exposure to a gene medicine
37
Accidental Exposure

• Manufacturers guidance
• Normal hospital procedure
• Occupational health
• Biological Safety Officer
• Incident reporting

38
Roles and Responsibilities

• Physician
• Chief Pharmacist
• Pharmacists
• Pharmacy Technicians
• Nursing staff
• Biological Safety Officer
• Infection Control
• Occupational Health
• Waste disposal services
• Hospital Management

39
Future Congress Activity

• Seminar at 13th EAHP Congress 2008 (2729
  February 2008, Maastricht, The Netherlands)
• Other presentations/posters at professional
  meetings
• ESGT 2007 15th Annual Congress of the European
  Society of Gene and Cell Therapy (2730 Oct 2007,
  Rotterdam, The Netherlands)
• BSGT 2008 5th British Society for Gene Therapy
  Annual Conference (79 April 2008, Edinburgh, UK)
• ESOP 2008 European Society of Oncology Pharmacy
  (Hamburg 2008 meeting)
• BOPA 2007 British Oncology Pharmacy Association
  (1214 October, Glasgow, UK)
• ASHP 2007 American Society of Health-System
  Pharmacists (26 December, Las Vegas, USA)

40
Timeline Overview
2006 2006 2006 2006 2007 2007 2007 2007 2007 2007 2007 2007 2007 2007 2007 2007 2008 2008 2008 2008 2008 2008
9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 2 4 6 8 10 12
Advisory board group
Mtg 1
Mtg 2
Publication of guidance
EJHP-P Print
EAHP website
Guidance drafting
and submission
External validation
EAHP endorsement
Advisory group reviews
Other activities
ASHP 2007
BOPA 2007
EAHP 2008
BSGT 2008
ESOP 2007
ESGT 2007
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The Result

• EAHP is taking the lead in providing guidance on
  a new form of therapy to be introduced in medical
  practice
• The process guarantees broad acceptance of the
  guidance, compliant with current regulations
• European hospital pharmacists can support medical
  practice with confidence when this new form of
  therapy is being introduced

42
The Result (continued)

• EAHP has been instrumental in providing this
  unique first in the world service to it
  membership
• This project shows the synergistic power of EAHP,
  integrating scientific knowledge, professional
  standards and a unique way of communicating with
  all the members (ie the official journal EJHP and
  open-platform publication on the EAHP website,
  keeping the guidance up to date and available to
  all interested parties)

43
References (1)

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References (2)

• 9. Armistead J, Zillich A, Williams K, Sitzlar S,
  Wermeling D. Hospital and Pharmacy Departmental
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  amending Directive 90/219/EEC on the contained
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Contact Details

• Dr Nicola Stoner
• Consultant Pharmacist, Cancer Services Cancer
  Research UK
• Oxford Radcliffe Hospitals NHS Trust.
• Principal Visiting Fellow, The University of
  Reading
• Cancer Research UK Medical Oncology Unit
• The Churchill
• Oxford Radcliffe Hospitals NHS Trust
• Headington
• Oxford OX3 7LJ
• Tel. [phone]
• Fax. [phone]
• Email nicola.stoner_at_orh.nhs.uk