Primary container considerations for prequalification · PDF fileCompliance with ISO 8362 (vials) –Other containers ... Primary container considerations for prequalification | 17

A Roundtable on Consideration for Primary Vaccine

Container Selection in Developing Countries :

Primary container considerations for prequalification

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1 |

Primary container

considerations for

prequalification




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2 |

Prequalification requirements

Compliance with ISO 8362 (vials)

– Other containers

• Prefilled syringes (PFS)

• Compact prefilled auto-disable device (CPAD)

• Ampoules

Consideration of Programmatic Suitability for

prequalification (PSPQ)




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3 |

PSPQ – Mandatory characteristics

Characteristic Applies to… Value Anti-microbial

preservative Only vaccines that:

are in ready to use (no

reconstitution) presentation.

and

are in multi-dose containers of more than 2 doses per vial

The vaccine presented for

prequalification should be adequately

preserved.

Thermostability

/ storage All vaccines The vaccine or any component

presented for prequalification should not require storage at less than -20°C .

Dose volume Only vaccines that are:

injectable;

and

indicated for infants and/or young children (<5 years old).

The vaccine presented for

prequalification should not be more than

1ml per dose for indicated use in

children aged 5 years or younger .




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4 |

PSPQ – Critical characteristics (1)

Characteristic Applies to …

Schedule All vaccines Not relevant to today's discussion

Process of

preparation for

administration

Oral vaccines The vaccine presented for prequalification should be packaged in a single

component/ready to use format.

Thermo-stability /

storage

All vaccines The vaccine presented for prequalification should not require storage below +2°C

for longer than 6 months.

Vaccine vial

monitor (VVM)

All vaccines Proof of feasibility and intent to apply a VVM to the proposed vaccine, as defined

below:

Materials, primary

and secondary

packaging, and

injection material

All vaccines The vaccine presented for prequalification should be packaged in materials

that can be disposed of appropriately in the field using standard procedures

(e.g., pit burning and burying, low temp incinerations, etc.).

Pre-filled injection

devices

Only vaccines that are

delivered in pre-filled

injection devices

The vaccine presented for prequalification in a prefilled injection device

should include an auto-disable (AD) feature (WHO/V&B/99.25).




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5 |

PSPQ – Critical characteristics (2)

Characteristic Applies to …

Dose volume Only injectable vaccines

The vaccine presented for prequalification

should be dosed in standardized volumes

(e.g., 0.5, 0.1, 0.05 ml) that can be easily

measured using available AD syringes .

Anti-microbial

preservative

Only vaccines that:

are in ready to use (no reconstitution) 2-dose vial

presentations or

are not live attenuated, in multi-dose

presentations and require reconstitution

The vaccine presented for prequalification

should be adequately preserved.

Antigenic stability

after reconstitution

Only vaccines that:

are in multidose presentations, and

require reconstitution of one or more components

And are adequately preserved

The components of the vaccine must show

antigenic stability for 28 days after

reconstitution. (Appropriate testing protocol

must be chosen by the manufacturer and

will be reviewed on a case by case basis)




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6 |

PSPQ – Preferred characteristics (1)

Characteristic Applies

to…

Value

Maximum packed

volume

All vaccines A smaller packed volume is preferred.

Where appropriate, components should be packed/shipped

together, e.g., for ready to use presentations: pre-filled AD syringe

with needle; etc.

Packaging devices should be considered to assure components are

shipped together, e.g., vial clip.

Dose volume

Oral

vaccines

Smaller volumes and standardized volumes are preferred.

Doses per

primary

container, non-

campaign setting

All vaccines Vials with ≤10 doses per vial are preferred

Doses per

primary

container,

campaign setting

All vaccines Vials with ≥ 10 doses per vial are preferred.

Doses per

secondary

container

All vaccines Should reflect logistics schedule and needs in order to minimize

stock accumulation at the peripheral level.




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7 |

PSPQ – Preferred characteristics (2)

Characteristic Applies to… Value

Process of

preparation for

administration

All vaccines Single component/ready to use (e.g., liquid) formats are

preferred.

For multi-component vaccines, vaccines with a short and simple

preparation process are preferred.

Thermo stability /

storage

All vaccines Vaccines and diluents that can be stored for extended periods at

temperatures above +8°C are preferred.

Freeze sensitivity All vaccines Vaccines that are not damaged by freezing temperatures (<0°C)

are preferred.

Materials,

primary and

secondary

packaging and

injection material

All vaccines Materials that minimize environmental impact are preferred.

Secondary

packaging,

diluents and

vaccines

Vaccines

requiring

reconstitution

Diluents and vaccines should have the same number of doses

per secondary container.




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8 |

Vaccine Presentation and Packaging Advisory Group

Generic Preferred Product Profile for Vaccines

Parameter Recommendations

Single vs multicomponent vaccines Provide Vaccines whenever possible, in “ready-to-use” presentations

that do not require the mixing of components.

Heat stability Vaccines should be stable at standard cold chain temperatures (2° to

8°C).

Maximise vaccine stability to improve effectiveness and enable higher

temperature storage

Freeze stability Formulate vaccines so that they will not be damaged by freezing,

where feasible

Presence of preservatives Include preservative in multi-dose vials of injectable vaccines, where

feasible, to allow safe use of opened containers in subsequent

sessions.

Product format Provide vaccines in formats to minimise (1) number of steps and (2)

potential for error during preparation and administration

Optimal number of doses per container

Prefilled injection devices Vaccine in prefilled injection devices syringes should have space

saving and auto-disabling features.

Multi-component vaccines

Maximum packed volume Minimise volume and weight of secondary and tertiary packaging, as

well as the need for repackaging for in-country supply chain

distribution

Materials, including the primary container and delivery device .Use materials for delivery devices, primary containers and secondary

and tertiary packaging that minimize the environmental impact of

waste disposal, for resource limited systems




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9 |

WHO maximum packaging volumes

From Vaccine Packaging Study

Feb 2012 (230-vaxpack-D4-

120212).docx




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10 |

Multidose vials

Multi-dose vials are commonly used in UNICEF procuring

countries and are likely to continue to be a vital part of

immunization programs – Trends in multi-dose vaccine vial use in UNICEF procuring countries, 2000-2011

MDVuse_UNICEFprocuringCountries_JLiu_v2_20110407.pdf




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11 |

Distribution of presentations by vaccine type – UNICEF procured

From Vaccine

Packaging Study Feb

2012 (230-vaxpack-D4-

120212).docx




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Thiomersal and multidose vials

Removal of thiomersal and switch to single-use vials affects

manufacturing capacity, health care workload, and has cold chain and

waste management implications, with very large increases in cost

There is a risk that some products (if alternative preservatives or no

preservatives are required to be introduced) may no longer be supported

by manufacturers

There is a high risk of serious disruption to routine immunization

programmes and mass immunization campaigns if thiomersal-preserved

vaccines are not available

– The consequences will be a predictable and sizable increase in

mortality, for very limited environmental impact




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13 |


Replacement of thiomersal with an alternative preservative

will require development of new products and their

registration in each jurisdiction of the world

New product development will be unpredictable since:

– there are no clear alternative candidate preservatives for the

near-or mid-term

– alternative preservatives may interact with the components of

the vaccine and removal of thiomersal may impact on vaccine

performance

– lack of incentive to reformulate current low cost vaccines (TT,

DTwP, hep B)




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In the long term, as an insurance policy to ensure availability of multidose vaccines, further work should be stimulated, recognizing

- there is, currently, little or no academic or regulatory research on alternative preservatives

- there is little or no operational research to evaluate the relationship between the criteria for antimicrobial tests for preservatives and the safety of multi-dose vaccines when used with current immunization practices

- that these efforts will be difficult and may not be successful

Investment and focused effort to identify (a) additional preservatives, and (b) preferred product presentations /delivery systems for multi-dose formulations with or without preservatives




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15 |

Synflorix 2-dose presentation

GSK proposed a 2-dose liquid unpreserved product for PQ

– a novel presentation for UN supported programmes

Submitted before formalised PSPQ evaluation process

established

Post introduction studies required

– No indication of increased AEFIs related to product misuse

– Some incorrect storage & waning of health worker knowledge

Synflorix 2-dose presentation remains PQed and now

available for use in other countries




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Countries need to be informed of the benefits and risks of

the presentation and have the responsibility for assuring

programmatic readiness to use such a presentation.

To be in place prior to introduction

– Enhanced training of HCWs

– Information stickers on storage fridges

Following introduction

– Monitoring of continued good practice

– On going training




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WHO and UNICEF consider the two dose preservative-

free presentation to introduce additional programmatic

risks for a product with a 1 dose alternative. Whilst the

benefit-risk will likely be favorable in the early post-

introduction period, this may change over time. For the

longer term, presentations that reduce programmatic risk

will likely be preferred.

– Single dose, unpreserved

– Multidose, preserved




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18 |

Summary

PQ : evaluation of technical requirements of containers

PQ : evaluation of programmatic requirements of

containers

Input to development of characteristics through VPPAG,

IPAC

Multidose vials

– A vital part of immunisation programmes

– Should contain preservative when feasible

– Supply at risk if thiomersal included in scope of mercury treaty

Documents

Primary container considerations for prequalification · PDF fileCompliance with ISO 8362 (vials) –Other containers ... Primary container considerations for prequalification | 17