Monday, 23 July, 10:15-12:15 - PowerPoint Presentation

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Monday, 23 July, 10:15-12:15Hall 11B, RAI Amsterdam

Uptake and Procurement of Optimal Formulations for Children

Nandita Sugandhi and Jennifer Cohn

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Disclosure

Reference:

https://www.cgr.nl/CGR.nl/media/CGR.nl/Gedragscode/Format-of-disclosure-slide-for-speakers-at-refresher-training-meetings.pdf

Relations that could be relevant for the meeting

Company

names

Sponsorship or refund funds

none

Payment or other financial remuneration

none

Shareholder rights

none

Other relations

none

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OVERVIEW

Selecting optimal formulations

Support for procurement of optimal formulations

Transitioning to new optimal ARVS

Program transitionHCW trainingCaregiver instructionsPharmacovigilance

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Uptake of preferred regimens historically has been slow: Evolution of NVP, EFV and LPV/r use in

Paeds 1st line (2009-2017)

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Uptake of preferred regimens historically has been slow: Evolution of NVP, EFV and LPV/r use in

Paeds 1st line (2009-2017)

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Approval and Introduction of the ABC/3TC 120mg/60mg scored

disp tab

Weight Band (Kg)

Pediatric

ABC/3TC (60/30 mg)

ABC/3TC (120/60 mg)

3-5.9

2

1

6-9.9

3

1.5

10-13.9

4

214-19.952.520-24.96325-34.91 adult tab (600/300mg)1 adult tab(600/300mg)

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120mg/60mg scored dispersible tablet developed and received approval in October, 2014Price parity to ABC/3TC 60mg/30mg scored tab (Equivalent PPY across weight bands)Projected lead time for commercialization: 16 weeksIncluded on the 2015 IATT Optimal FormularyAs of 2015 the ABC/3TC 60mg/30mg was ~20% APWG procurement

Oct 2014

Oct 2015

Mar

Mar

Mar

Oct 2016

1

st

order for 120mg/60mg placed 2 years later!

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ABC/3TC 120mg/60mg: What took so long?

Countries concerned about supply security

Programs not aware of availability

Product not included in procurement plans

Lack of orders = lack of commercialization

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How can we do better?

Challenges to rapid uptake of new

paediatric

ARV

formulations?Limited awarenessOf productsOf

necessity

Limited availability of new

products

Inadequate guidance for healthcare workers on transitioning to new products or

regimens

Complicated quantification for different age or weight groups

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Wide variety of

Paeds

ARV formulations 70+ Products and counting

9

NRTI

ABC

Tablet (

disp,scored

) as sulfate

60 mg

ABC

Tablet (scored) as sulfate

60 mg

ABC

Oral liquid as sulfate

100mg/5ml

AZT

Tablet (dispersible, scored)

60 mg

AZT

Oral liquid

50mg/5ml

AZT

Tablet (scored)

60mg

AZT

Capsule

100 mg

AZT

Tablet

100 mg

3TC

Oral liquid

50mg/5ml

3TC

Tablet (dispersible)

30mg

3TCTablets30mgD4TCapsule15mgD4TCapsule 20mgD4T Powder for Oral solution5mg/5mlDDICap, unbuffered, enteric coated125 mgDDICap, unbuffered, enteric coated200 mgDDITab (buffered, chewable, disp)25mgDDITablet (buffered, chewable, dispersible)50 mgDDITablet (buffered, chewable, dispersible)100 mgDDI powder for Oral liquid (Buffered)2g, 4g bottleFTCOral liquid10 mg/mlTDFOral powder40mg/scoopTDFTablet (unscored)150 mgTDFTablet (unscored)200mg

NNRTIEFVTablet (scored)200mgEFVTablet 50mg EFVTablet (unscored)200 mgEFVTablet (disp)100mgEFVCapsules50 mgEFVCapsules100 mgEFVCapsules200 mgEFVOral liquid150mg/5mlNVPTablet (dispersible, scored)50mgNVPTablet (non dispersible)50mgNVPTablet (non dispersible)100mgNVPOral liquid50mg/5mlNVPTablet (dispersible)100 mgNVPTablet (nondispersible)20mgETVTablet25mgETVTablet100mg

FDC’sAZT/3TCTablet (disp scored)60/30 mgAZT/3TCTablet (scored)60/30 mgAZT/3TC/NVPTablet (disp scored)60/30/50 mgD4T/3TC/NVPTablet (disp scored)6/30/50 mgD4T/3TC/NVPTablet (disp, scored)12/60/100 mgD4T/3TC Tablet (disp, scored)6/30 mgD4T/3TCTablet (dispersible, scored)12/30 mgABC/3TCTablet (disp, scored)120/60 mgABC/3TCTablet (scored)60/30 mgABC/3TC/AZTTablet (non disp, scored)60/30/60mgTDF/3TCTablet75mg/75mg

PILPV/rTablet (hs)100mg/25mgLPV/rOral liquid80/ 20 mg/mlLPV/rOral pellets40mg/10mg/capRTVOral liquid400mg/5mlRTVTablet25mg 50mgDRVTablets 75 mgDRVTablets 150 mgDRVOral liquid500mg/5mlATVcaps as sulfate100 mgATVcaps as sulfate150 mgATVPowder50mgATVcaps as sulfate200 mg

Integrase InhibitorsRALchewable Tabs (scored)100 mgRALchewable Tabs 25 mgRALPackets for oral susp100mgDTGFilm coated tablet25mgDTG Film coated tablet 10mg

PI

cont’d

TPV

Oral liquid

500mg/5mL

FPV

Oral

liquid

250mg/5mL

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IATT Optimal Paediatric

ARV Formulary

In mid-2011, the IATT began a selection process for optimal

paediatric

formulations given the following:

Market fragmentation from too many choices leading to instability in the

paediatric

marketplace

Normative guidance needed on the best options to deliver all required first- and second- line regimens for

paediatric

HIV patients

An optimal formulary was developed to serve as guidance for national programs

,

procurement agencies, manufacturers

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Normative Guidance

Revised in accordance with WHO GuidelinesInclusion of new optimal

paediatric

ARV

productsEndorsed by major global buyers of paeds ARVsGlobal Fund

PEPFAR

UNICEF

Optimal Formulary and Limited-use List are living products

2011

2013

2015

2016

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Starting with quality options: The optimal

paediatric ARV formulary

The Optimal Formulary and Limited-use list

have been

updated to

reflect

WHO 2018 guideline updates

The Optimal formulary provides normative guidance for national programs

,

procurement agencies, manufacturers on the best options to deliver all required first- and second- line regimens for

paediatric

HIV patients

The Limited-use List provides guidance on product selection for time limited circumstances or in special situations

ARV Formulations which are included in the WHO guidelines and are needed for a limited time or in low volumes

Optimal FormularyLimited-use ListMinimum number of ARV formulations needed to provide all currently recommended preferred and alternative first and second-line regimens for infants and children, and infant prophylaxis for PMTCT2018 Update

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What about AVAILABILITY?

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Availability is impacted by:

Supplier capacityIn-country registration

Licensing

Should products that are not widely available be included on the Optimal Formulary or Limited-use List?

LPV/r 40mg/10mg solid oral dosage formRAL granules, 25mg, 100mgDTG 10mg, 25mg

Availability of pediatric ARV dosage form is a prerequisite for actual implementation

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Who is responsible for ensuring optimal ARVs are available for children?

Country Programs?

Paradigm shift

Funding agencies

Suppliers

Procurement Entities

RegulatoryBodies

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Moving towards supply security:

the ARV Procurement Working Group

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The APWG was established to improve supply security for

paediatric

ARVs:

Ensure sustained supply through coordinated procurement mechanism

Strategically manage demand

Advocate

for and transition countries to use the IATT formulary list of optimal and limited-use

products to streamline product selection

With the recognition that coordination is also needed for some ARVs used in adolescent and adults, the scope was expanded to include all ARVs that may face procurement challenges (low volume and entry/exit ARVs)

Activities

Collating demand intelligence

Monitoring market challenges and developmentsSupporting the uptake of optimal products

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Successful uptake requires multiple stakeholders

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Tools and resources to support new product

introduction are available

CHAI toolkit

Lopinavir

/ritonavir pellet toolkitPAWG chapter Transition brief

https://

www.newhivdrugs.org

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Tools and resources to support new product

introduction are available

CHAI toolkit

Lopinavir

/ritonavir pellet toolkitPAWG chapter Transition brief

https://

aidsfree.usaid.gov/resources/toolkits/lpvr-pellet-toolkit

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Tools and resources to support new product

introduction are available

CHAI toolkit

Lopinavir

/ritonavir pellet toolkitPAWG chapter Transition brief

https://globalhealthtrainingcentre.tghn.org/research-toolkit-paediatric-antiretroviral-drug-and-formulation-development

/

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Tools and resources to support new product

introduction are available

CHAI toolkit

Lopinavir

/ritonavir pellet toolkitPAWG chapter Transition brief

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Transitioning to new paediatric ARVs

Adoption

Product Registra-tion

Procure-ment

KOL / Partner Engage-ment

Central-level Uptake Planning

Facility-Level Uptake Planning

Quantification

Uptake or transition scenario planning

Monitoring

PV

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Training components: More than just administration

Considerations:

Training rollout model

Product availability at time of training

Who to train: Train prescribers and dispensers

Include monitoring and reporting

Include pharmacovigilance

Training of PLHIV/ community

Ongoing supportive supervision and mentorship (adapt tools)

Prepare providers to manage ARV transition along other changes to service delivery models and standards of care

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Getting to the heart of the matter: Community engagement

Are these new drugs safe for my child?

When can my child get these better medicines?

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Pharmacovigilance

Taking off with a safety netActive pharmacovigilance: Formal observational cohort studies

Passive

pharmacovigalence

Support for stimulated pharmacovigilance and reportingRoutine toxicity monitoring critically important for new drugs

Keeping and eye on the long game

Infants and children

Exposed long term to ARVs

Exposed to maternal ARVs

in utero

and via breastmilk

Toxicity concerns

Potential impact on growth and development

Birth outcomes/defects with peri-conception exposure

FUNDINGAdvance planningLonger-Terminvestment

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Thank you