Poliovirus Potentially Infectious Materials:

Risk Classification and Risk Mitigation

Biosafety Branch, Ministry of Health

7 & 15 January 2019

Contents

• Definitions & background

• WHO Guidance document for non-poliovirus facilities• Risk Classification

• Risk Mitigation Measures

Differentiating Poliovirus IM and PIM

Infectious Materials (IM)

PotentiallyInfectious

Materials (PIM)

Definitions

Poliovirus Infectious Material (IM)

Any sample that has been tested or is known to contain poliovirus e.g.

Wild-type poliovirus (WPV)

Vaccine derived poliovirus (VDPV)

Oral poliovirus vaccine/Sabin (OPV/Sabin)

For definition of the different types of poliovirus infectious materials, please refer to WHO Global Action Plan III (http://polioeradication.org/polio-today/preparing-for-a-polio-free-world/containment/containment-resources/)

Definitions

Poliovirus Potentially Infectious Material (PIM)

Faecal, respiratory, concentrated sewage samples or derivatives of such samples, collected at a time of poliovirus circulation in the community, or when live, attenuated poliovirus vaccine is used; regardless of the purpose of sample collection

WPV PIM Any of the above sample types or derivatives of such samples, collected at a time of wild-type poliovirus circulation in the community

VDPV PIM Any of the above sample types or derivatives of such samples, collected at a time of vaccine derived poliovirus outbreak in the community

OPV/Sabin PIM Any of the above sample types or derivatives of such samples, collected at a time when live, attenuated poliovirus vaccine is used in the community

Modified from WHO Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses (http://polioeradication.org/polio-today/preparing-for-a-polio-free-world/containment/containment-resources/)

WHO Poliovirus Eradication and Endgame Strategic Plan

Outside the Laboratory/Facility Laboratory/Facility

• Interruption of WPV and VDPVtransmission

• Containment of poliovirus IM & PIM;poliovirus type 2 followed by type 1 and 3

• Strengthen immunization programme and withdraw oral poliovirus vaccine

• Poliovirus essential facility (PEF):Undergo certification for containment of WPV IM & PIM, VDPV IM & PIM, OPV/Sabin IM

• Non-poliovirus essential facility: Risk elimination or risk mitigation for containment of OPV/Sabin PIM

Long term goal: minimize risk of reintroducing PV into the population

Modified based on WHO Polio Eradication & Endgame Strategic Plan 2013-2018 and WHO Global Action Plan III

WHO Poliovirus Containment Timeline

Phase 1

Preparation for containment of poliovirus type 2

Identification of poliovirus-essential facility (PEF)

Phase 2

Poliovirus type 2 containment period

Containment of WPV2, VDPV2 IM & PIM, OPV/Sabin2 IM

Switch from tOPV to bOPV

Certification of PEF

Safe-handling of OPV/Sabin PIM in non-PEF

Phase 3

Final containment of all WPV, VDPV IM & PIM

Final containment of all OPV/Sabin IM

Cessation of bOPV use

Certification of PEF

Safe-handling of OPV/Sabin PIM in non-PEF

Certification of PEF

Safe-handling of OPV/Sabin PIM in non-PEF

Modified based on the containment timeline in WHO Global Polio Action Plan III

Singapore: PV IM and PIM

WPV2 IM & PIM

OPV3 IM & PIM

Prior to 31 Dec 1972

OPV2 IM & PIM

1 Jan 1979 to 31 Jul 2016 1 Aug 2016 onwards

OPV1 IM & PIM

WPV3 IM & PIM

WPV1 IM & PIM

1 Jan 1973 to 31 Dec 1978

Cessation of bOPV

Overseas Samples: PV IM and PIM

• Determine whether samples are WPV2/VDPV2 or OPV/Sabin2 IM or PIM based on collection period and country of origin; also sample type for PIM

• Country and territory-specific poliovirus data is available in Annex 2 of WHO guidance document

Extracted from Annex 2 of WHO Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses (http://polioeradication.org/polio-today/preparing-for-a-polio-free-world/containment/containment-resources/)

Containment in Non-Poliovirus Essential Facility

• WPV2/VDPV2 IM and PIM, OPV/Sabin2 IM: Destroy or transfer to a poliovirus essential facility

• OPV/Sabin 2 PIM: Destroy or implement risk mitigation based on risk classification

Material identification

• Determined based on sample type and associated work activitiesRisk

Classification

• Determined based on risk classificationRisk Mitigation

Risk Classification of OPV/Sabin PIM

Type of PV PIM* Procedure used with PIM Risk Level

Faecal samples or concentrated sewage

Inoculation into PV-permissive cells Moderate

Other laboratory procedures** Low

Extracted nucleic acid from faecalsamples or concentrated sewage

Transfection into PV-permissive cells Moderate

Other laboratory procedures** Lowest

Respiratory tract samples Inoculation into PV-permissive cells Low

Other laboratory procedures** Lowest

Extracted nucleic acid from respiratory tract samples

Transfection into PV-permissive cells Low

Other laboratory procedures** Lowest

* Cerebrospinal fluid (CSF), serum/blood, and other clinical materials not listed in Table 1 are not considered PV PIM** Other laboratory procedures may include, but are not limited to, inoculation into PV non-permissive cells, bacterial culture, PCR (DNA or RNA), mass spectrometry, or ELISA.

PV PIM that have been inactivated using a validated method are no longer considered PIM

Source: WHO Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses (http://polioeradication.org/polio-today/preparing-for-a-polio-free-world/containment/containment-resources/)

Some examples of PV-permissive cell linesCell lines Origin

CaCo-2 Human

HeLa Human

HEp-2 Human

HEK Human

MRC-5 Human

Various neuroblastoma (e.g. IMR-32, SK-N- MC) Human

BGMK (sometimes referred to as BGM or GMK) Non-Human Primate

LLC-MK2 Non-Human Primate

MA-104 (Vero derivative) Non-Human Primate

Primary monkey kidney cells Non-Human Primate

Vero Non-Human Primate

L20B Mouse

Source: WHO Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses (http://polioeradication.org/polio-today/preparing-for-a-polio-free-world/containment/containment-resources/)

Risk Mitigation Strategies for Handling PV PIMRisk level

Risk mitigation strategy Moderate Low Lowest Storage only2

Declare PV PIM in National PV Survey and maintain accurate inventory

Biosecurity (including, for example, locked freezers, limited access, staff training)

Biosafety (including, for example, good laboratory/microbiological practices, and documentation and validation of methods/ standard operating procedures, as described in GAPIII, Annex 6)

n/a

Risk assessment for specific procedures being used

Required polio immunization of staff n/a3 n/a

Certification to a national or international standard that includes biosafety and biosecurity components

n/a n/a n/a

Source: WHO Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses (http://polioeradication.org/polio-today/preparing-for-a-polio-free-world/containment/containment-resources/)

: must comply with the risk mitigation strategy; n/a: not applicable 2 For short-term retention while the final disposition of the collection is being considered. If “stored” samples are to be handled, the risk mitigation strategies for moderate, low, and lowest risk groups must be applied as appropriate for the sample type and procedure (Table 1). 3 recommended

What do I need to do?

• Each facility to complete and submit “Facility Reporting Form 1” by 18 February 2019• Facility information

• Types of samples that are destroyed or being retained

• Risk classification of work activities and rationale for sample retention

• Each facility retaining OPV/Sabin type 2 PIM, to submit Risk Mitigation Plan in place by 18 March 2019

Reference Materials from WHO

WHO Containment Resources• WHO Guidance to Minimize Risk for Facilities Collecting, Handling or Storing

Materials Potentially Infectious for Polioviruses

• Annex 2 of WHO Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses

• WHO Global Action Plan III