Global Pediatric Drug Development Collaboration

WHITE PAPER

Global Pediatric Drug Development Collaboration:

Part Two

Authors

Dr. Martine Dehlinger-Kremer Vice President of Scientific Affairs, Pediatric Subject Matter Expert Center for Pediatric Clinical DevelopmentPRA Health Sciences Jo Dewhurst, BSc (Hons), LLB DipPediatric Strategy Liaison, Center for Pediatric Clinical DevelopmentPRA Health Sciences Melissa Hansen, MSN, APRN, CNP-PediatricsPediatric Strategy Liaison, Center for Pediatric Clinical DevelopmentPRA Health Sciences Jacqui Whiteway, PhDSenior Pediatric Strategy Liaison, Center for Pediatric Clinical DevelopmentPRA Health Sciences

Pediatric Legislations in the US and the EU – Similarities and Differences The need for drug development programs specifically for

pediatric patients is an issue that authorities in the US have

been working on since the 1990s. In 2003, US authorities

made it mandatory for new products to have a pediatric

drug development plan. In the US, two laws govern pediatric

development: Best Pharmaceutical for Children Act (BPCA)1

and Pediatric Research Equity Act (PREA).2 PREA requires

companies to determine safety and efficacy of new drugs and

biological agents in pediatrics unless a waiver is granted or

the product is exempt from PREA. An initial Pediatric Study

Plan (iPSP) must be submitted to the FDA for medicines falling

under PREA. This means that, with exemption of waivers or

deferrals, marketing applications for new products need

to contain pediatric data as well. In 2006, the EU followed

suit, closely guided by the US model. In 2006, Regulation

1901/20063 as amended (Pediatric Regulation) was enacted

and came into force on January 26, 2007. The Pediatric

Regulation introduced a single system of pediatric obligations

and incentives to facilitate the evaluation of newly authorized

drugs protected by a Supplementary Protection Certificate.

For new products, the pediatric investigation plan (PIP)

applications are required to be submitted to the EMA no later

than upon completion of adult human pharmacokinetic studies.

An overview of pediatric legislations in the US and EU,

including similarities and differences, is depicted in Table 1.

White Paper | Global Pediatric Drug Development Collaboration: Part Two

IntroductionThe pediatric population who needs treatment represents a small population when compared to the adult population, hence the

importance of global drug developments. As pediatric legislations are not global, collaboration to achieve agency alignment is

a way to global drug development. Pediatric development is driven by US and EU legislations. These legislations have both similarities

and differences that must be overcome for global drug development. Several tools and processes have been implemented to

facilitate agencies collaboration in view of supporting global pediatric drug development.

In Part One of this white paper series, we outlined the unique challenges that face pediatric drug development and shared some

effective examples of industry collaboration. You can read Part One here. In Part Two, we discuss some of the different pediatric

legislations in place, as well as steps that global agencies are taking to better facilitate pediatric drug development. We share examples

of effective collaboration that have helped shape the current drug development paradigm, and call for continued harmonization

and innovation of pediatric science and research to ensure children get the medicines they need faster.

https://prahs.com/insights/global-pediatric-drug-development-collaboration-part-one

DescriptionEU US

PIP PUMA PREA BPCA

Applicable regulationRegulation (EC) No 1901/2006 and as amended 1902/2006

Regulation (EC) No 1901/2006 and as amended 1902/2006

PREA and FDASIA 2012 BPCA and FDASIA 2012

Scope Mandatory Optional Mandatory Optional

Applicable product classifications

Drugs, biologics (including orphan products): new products, new indications, or pharmaceutical forms that qualify for or are protected by a supplementary protection certificate (SPC)

• Already authorized• No longer covered by SPC

or patent that qualifies for a SPC

• Products indicated exclusively for use in the pediatric population

Drugs, biologics and biosimilars involving new active ingredient, indication, dosage form, dosing regimen, or route of administration

Drugs, biologics (including biosimilars, orphan products, and off-patent products)

Exemptions

• Genetics• Hybrids• Traditional herbal products• Biosimilars• Well-established use• “Class waiver” products

Not applicable, optional scope

• Orphan designated products*

• Generics• Dietary (including herbal)

supplements

Dietary (including herbal) supplements

Grounds for waiver (partial or full waivers)

• Likely to be ineffective or unsafe

• Condition only occurs in adults or a pediatric subset

• Does not represent significant therapeutic ben-efit over existing treatments for pediatrics

Not applicable

• Evidence strongly suggests product would be ineffective or unsafe

• Necessary studies impossible or highly impossible

• Does not represent significant therapeutic benefit over existing therapies for pediatrics and not likely to be used in a substantial number of pediatric patients

• Not possible to develop an age-appropriate pediatric formulation

Not applicable

Scope

• Derived from adult indication within the same condition

• One PIP may cover more than one condition/ indication

Condition/indication exclusive to pediatric use

• Only required for indication that will be under review

• One iPSP for each indication

Related to the entire moiety. The FDA may request studies for a different indication including an indication not approved in adults

Table 1: Regulatory requirements for PIP, PUMA, PREA, and BPCA

* The FDA Reauthorization Act of 2017 (PL-115-52 August 18, 2017) provides the FDA with new authority to require a pediatric investigation into an adult cancer drug if that drug is directed at a molecular target that is relevant to a pediatric cancer. Federal Food, Drug, and Cosmetic Act (as amended through P.L. 115-92, enacted 12 December 2017) Section 21 USC 321(g)(1). Office of the Legislative Counsel website (Available at: https://bit.ly/1k73myS)


DescriptionEU US

PIP PUMA PREA BPCA

TimingEnd of Phase 1 (adult pharmacokinetic data)

End of Phase 1 (adult pharmacokinetic data)

• Within 60 days of End of phase 2 (EOP2) meeting

• If no EOP2, at least 210 days prior to planned NDA/BLA filing

• Determination of exclusivity is based on completed reports for all studies listed in the written request (WRI)

• The FDA has up to six months to review reports to make a final determination

• The FDA’s decision on exclusivity determination should be made no later than nine months before the patient or exclusivity expiration or pediatric exclusivity will not be granted

Instrument PIP PIP iPSP

• Proposed pediatric study request (PPSR) issued by the sponsor to the FDA

• WR issued by the FDA

Key rewards and incentives

• Six month extension to supplementary protection certificate

• For orphan products an additional two years of market exclusivity

• Free pediatric scientific advice

• Automated access to centralized procedure

• Eight years data + two years of market protection

• Partial exemption from submission fees and post-authorization fees for one year

None

• Additional six months of exclusivity to an existing patent on the entire moiety

• Priority review status for pediatric applications/supplements

Table 1: Regulatory requirements for PIP, PUMA, PREA, and BPCA

The FDA’s two pediatric regulatory pillars, BPCA and PREA,

work together to accomplish the goal of obtaining adequate

efficacy and safety data for labeling. However, long periods

remain between adult approval and pediatric data and

labeling with nine years still being the norm.4 The needs of

pediatric-specific diseases are stark, especially in respect

of neonates and premature infants as well as for cancer and

genetic diseases.

Progress is being made gradually. We have seen the imple-

mentation of pediatric extrapolation, adoption of innovative

clinical trial designs, exploration and acceptance of Real

World Evidence, the set-up of clinical trial networks, and global

alignment activities led by regulators.


Global Agency Collaboration — Tools and Processes

FDA and EMA Parallel Scientific Advice

The parallel scientific advice program provides a mechanism

for FDA reviewers and EMA assessors to concurrently exchange

with sponsors their views on scientific issues during the

development phase of a new product. The interactions aim

to provide a deeper understanding of the bases of regulatory

decisions, optimize the development program, and avoid

unnecessary testing replication or unnecessary diverse

testing methodologies.

For pediatric developments, going through an EMA–FDA

parallel scientific advice procedure before finally drafting and

submitting the iPSP and PIP will facilitate global alignment of

the pediatric development program. This may be of particular

benefit to pediatric plans for medicines that are first in class or

present an innovative approach.

Pediatric scientific advice agreed upon by the Scientific Advice

Working Party (SAWP) and endorsed by the Committee for

Human Medicinal Products (CHMP), is considered as important

in the Pediatric Committee (PDCO) PIP assessment. There is

a close collaboration between the SAWP and the PDCO, the

latter being involved in pediatric scientific advice, including

the parallel scientific advice with the FDA.

Pediatric Cluster Meetings

The pediatric cluster meetings were established in 2007,

shortly after the first PDCO meeting took place. The cluster

meetings are monthly teleconferences held between the FDA

and EMA, together with Health Canada, Pharmaceutical and

Medical Device Agency (PMDA) (Japan), and Therapeutic

Goods Agency (TGA) (Australia). The objective of the cluster

is to support global development plans for pediatrics by

exchanging information on products and general issues. More

than one approach may be possible but unnecessary studies

are to be avoided. The aim is to seek a harmonized approach

to the fullest extent possible and, whenever possible, consensus

on their requirements for the individual pediatric plans.

Between August 2007 and March 2019, information has been

exchanged on 517 products, with 172 discussions on general

topics.5 Frequently discussed product issues include scope of

pediatric product development, waiver, quality, non-clinical,

adult and pediatric study results, indication, safety, trial design,

sample size, dose, endpoints, study population, extrapolation,

timelines, and long-term follow-up. General discussions

include endpoints, extrapolation, meetings/workshops, joint

publications, and regulatory action.

Between 2014 and 2017, convergence on approaches have

been achieved for 73% of the issues discussed. From 1997

to 2017, over 650 products in the US have been labeled with

additional information gathered from pediatric trials. Since

the implementation of the regulation in the EU, 238 new

medicines for use in children and 39 new pharmaceutical

forms appropriate for children were authorized between

2007 and 2015.6

The EMA and EU Commission also plan to enhance cluster

meetings on topics and therapeutic areas requiring greater

exchange of information.

In terms of product-specific discussions, between 2007 and

2016, 425 products were discussed. The majority of these

products were in oncology (see Figure 1), showing the

importance of oncology in the pediatric field and the need

for global development plans.


Oncology

Gastroenterology/Inborn Errors

Endocrine/Metabolic

Anti-Virals

Cardio/Renal

CBER

Neurology

Special pathogens/Transplant/Opthlamology

Anti-infectives

Pulmonary/Rheumatology

Anesthesia/Analgesia

Dermatology

Psychology

Hematology

Reproductive/Urology/Bone

0 10 20 30 40 50 60 70 80 90 100

92

55

50

46

36

28

20

18

17

16

14

12

9

8

4

Figure 1: Pediatric Cluster Product Discussions (2007-2016)7

Figure 2: Type of clinical trial issues discussed during the pediatric cluster meetings (2007-2016)

Pediatric Cluster Products Discussed by Division (2007–2016)

n=425

Number of Product Discussions

When reviewing the type of clinical trial issues discussed

during the cluster meetings for the period from 2007 to 2016,

the scope of pediatric development is the most important

subject followed by safety, trial design, and regulatory aspects.

Work

shop/M

eeting

Form

ulatio

n

Timing

Age Gro

up

Extrapolat

ion

Non-clinica

l

Dosing

Waive

rs (in

cludes F

ull

and Parti

al Waive

rs

Primary

Endpoint

Study P

opulatio

n

Types o

f Clin

ical T

rial

Regulatory

/

Regulatory

Acti

on

Trial D

esign

Safety

Scope o

f Pediat

ric

Develo

pment

Types of Clinical Trial Issues Discussed

Num

ber

of D

iscu

ssio

ns

250

200

150

100

50

0

27 29 3148

65 70 76 81 87 90 95 101 103

159

218


There are a few issues faced at the pediatric clusters. Individ-

ual divisions have varying levels of pediatric expertise and

international experience which have their importance as the

pediatric cluster aims to avoid the fragmentation of pediatric

development activities. The pediatric cluster is also responsible

for ensuring that the appropriate pediatric and other subject

matter experts are in attendance and providing additional

coordination with the Pediatric Review Committee (PeRC) and

other divisions.

These clusters are important because there are different laws

in different regions: PREA requires certain thing to be studied,

BPCA provides incentives for doing more, and the EU pediatric

legislation requires earlier commitment to pediatric plans.

Anticipating together, with the FDA and EMA, is essential to

avoid missed opportunities and learnings.

The pediatric cluster shows efficiency in resolving differences.

One example is in respect to the patient population for an

oncology product designed to treat a specific type of medullo-

blastoma. The sponsor proposed to the EMA newly diagnosed

and relapsed/refractory patients with medulloblastoma and

to the FDA relapsed/refractory patients with medulloblastoma

only. As an outcome of the common discussion, the FDA re-

quested the sponsor to study both patient populations.

The collaboration between the agencies is also successful in

resolving discrepancies in respect to timing of the pediatric

trials. For a drug to be used as add-on to insulin to treat Type

1 Diabetes Mellitus (T1DM), the initial position of the EMA was

that pediatric trials would start after efficacy and safety data

were available in adults with T1DM as the drug was an add-

on drug and the first in its class to be studied in children with

T1DM. The FDA position was that it would be sufficient to have

interim adult data in T1DM and pediatric PK/PD T2DM data

in patients who received this product. The FDA based their

position on the fact that there was a significant unmet need,

i.e., many children and adolescents with T1DM did not achieve

their glycemic targets on insulin alone. Following discussion in

the cluster meeting, the EMA understood the rationale of the

FDA and aligned with it on an earlier timing of the pediatric

program in order to address the significant unmet need.

These examples demonstrate how important a global pediatric

approach is to successfully develop much needed medicines

for children. Such a global approach can be realized through

ongoing harmonization of the science, which will make pediatric

product development easier and faster. Key contributors

to this are the pediatric cluster teleconferences, but also

initiatives such as joint working groups, workshops and expert

meetings for extended discussions, joint publications, and the

development of global pediatric trial networks and consortia.

The European Medicines Agency and European Commission

(DG Health and Food Safety) action plan on pediatrics published

in October 2018 includes a strengthening of cooperation of

decision makers. The plan foresees an enhanced integration

of EMA/FDA pediatric cluster activities to ensure knowledge

and information exchange between PDCO and the pediatric

regulatory cluster. This will also increase transparency with

regard to EMA/FDA pediatric cluster discussions to better

inform sponsors about pediatric cluster discussions and to

increase transparency for all relevant stakeholders regarding

outcomes of non-product related interactions. A deadline for

completion of the latter is June 2020. A progress report for

the action plan on pediatrics is to be published in July 2020.8

Common Commentary

A new tool, the “common commentary,” was launched in

2012 to inform sponsors of issues discussed for some

products at the pediatric cluster, showing a commitment to

a more collaborative approach with industry.

The common commentary serves to inform sponsors in writing

of products discussed where the FDA and EMA have come to

an agreement on the proposal at the pediatric cluster meeting.

The document is non-binding and is not regulatory advice.

The common commentaries pertain to pediatric development

plans that have been submitted to both the FDA and EMA, are

under review by both agencies, and have been discussed at

the cluster.

Between 2012 and 2015, 25 issues were considered. Oncology

(n=10) and gastroenterology (n=9) were the therapeutic areas

most often discussed, with the remaining therapeutic

areas being cardiology (n=2), and one each for neurology,

dermatology, inborn errors, and antimicrobial.

In addition, the two agencies have collaborated in publishing

manuscripts and editorials pertaining to development of

products for the treatment of pediatric ulcerative colitis,

Crohn’s disease, and type 2 diabetes mellitus.


Common Commentary – Impact on Pediatric Cancer Drug Development

With respect to oncology, joint efforts and common commen-

taries directly influenced the decisions on pediatric cancer

drug development plans. Between 2012 and 2016, 46

scientific discussions of 26 distinct oncology products were

held.9 Those discussions focused on toxicity, non-clinical data

versus adult patient experience and suggested monitoring

plans, eligible patient populations, planned indication,

and study design. Common commentaries were issued for

eight oncology products (see Table 2 below). All sponsors

expressed appreciation for the common commentaries.

Global collaborative studies were recommended in many cases.

All common commentaries directly influenced decisions PIPs,

PSPs, and Written Requests (WR). Initial common commentaries

resulted in parallel scientific advice in some cases. As of

today, two of the drugs have a pediatric labeling approved

and others have ongoing pediatric trials in view of approval

for the pediatric population.

Following the implementation of the Research to Accelerate

Cures and Equity (RACE) for Children Act, an increase in the

development of drugs for pediatric cancers is expected. For

those developments, collaboration for the investigation of new

agents will be key due to the small subpopulation of children

with low incidence cancers. Duplication and competing trials

must be avoided.

Product Sponsor Date Discussion Topics

Sonidegib Novartis 2012 Toxicity, eligibility, indication, in vitro diagnostic assay, unmet clinical need

Volasertib Boehringer Ingelheim 2013 Eligibility, indication, trial design, unmet clinical need

Nivolumab BMS 2013Toxicity, eligibility (age-related concerns), indication, dosing plans, combination therapy plans, trial design, potential for partial extrapolation

Blinatumomab Amgen 2013 Toxicity, eligibility, indication, trial design, dosing optimization

Evofosfamide Threshold 2013Relevance to pediatric cancer, clinical pharmacology, trial design, potential for partial extrapolation

Inotuzumab Pfizer Not sent Toxicity, eligibility, indication, trial design

Oncology Matrix Proposal Roche/Genentech 2015 Eligibility, indication, trial design

Dabrafenib Novartis 2016Toxicity, eligibility (age-related concerns), indication, dosing plans, combination therapy plans, trial design, in vitro diagnostic assay

Table 2: Examples of FDA EMA Common Commentaries 2012-201610


Common Commentary – Impact COVID-19 Pandemic

A unique and successful example of collaboration between

agencies is the global approach for the development of an

initial Pediatric Study Plan (iPSP) and Pediatric Investigation

Plan (PIP) for the prevention and treatment of COVID-19. Due

to the global public health crisis resulting from the coronavirus

disease 2019 (COVID-19) pandemic, the FDA and EMA are

providing procedural assistance to sponsors and applicants

who anticipate submission of pediatric product development

plans for new drugs and biological products for the treatment

or prevention of COVID-19.

On June 2, 2020, the FDA and EMA published a common

commentary to streamline administrative processes and

facilitate efficient submission of an iPSP and PIP. This common

commentary11 addresses only the submission of an iPSP

and PIP for a drug or biological product for treatment or

prevention of COVID-19. This is an excellent example of

how greater alignment can be achieved.

There are many similarities between FDA’s iPSP template and

EMA’s PIP template, as depicted in the diagram below. However,

due to the differences in legislations, a single template would

not serve the regulatory needs of both agencies.

Given the need to generate clinical trial data to inform safe

and effective use of products to treat and prevent COVID-19 in

pediatric patients, the FDA and EMA agree to and encourage

early submission of an iPSP and PIP (no difference in timelines).

Furthermore, the FDA and EMA would meet as needed to

exchange information to facilitate the product development

for the pediatric population. This is an encouraging example

that shows the flexibility of the agencies and what can be

achieved through close collaboration.


Table 3: Comparison of specific PSP and PIP template structures 12

PSP Template

Initial Pediatric Study Plan Template

1. Overview of the Disease in the Pediatric Population

2. Overview of the Drug or Biological Product

3. Overview of Planned Extrapolation of Effectiveness to Specific Pediatric Populations

4. Planned Request for Drug-Specific Waiver(s)

5. Plan to Request Deferral of Pediatric Studies

6. Tabular Summary of Planned Nonclinical and Clinical Studies

7. Age Appropriate Formulation Development

8. Nonclinical Studies

9. Clinical Data to Support Design and/or Initiation of Studies in Pediatric Patients

10. Planned Pediatric Clinical Studies10.1 A Brief Outline of Any Proposed Pharmacokinetic Studies10.2 A Brief Outline of Any Proposed Clinical Effectiveness and Safety Studies

11. Timeline of the Pediatric Development Plan

12. Agreements for Pediatric Studies with Other Regulatory Authorities

PIP Template

Part B Overall Development of the Medicinal ProductB.1.1 Similarities and differences of the disease/condition between populationsB.1.2 Pharmacological rationale and explanationB.2 Current methods of diagnosis, prevention, or treatment in pediatric populationB.3 Significant therapeutic benefit/fulfillment of therapeutic needs

Part C Applications for Product-specific WaiversC.1 Overview of waiver request(s)C.2 Justifications for a product-specific waiverC.2.1 Applications based on likely lack of efficacy or safetyC.2.2 Applications based on the disease or condition not occurring in the specified pediatric subset(s)C.2.3 Applications based on lack of significant therapeutic benefit

Part D Proposed Pediatric Investigation PlanD.1.1 Pediatric investigation plan indicationD.1.2 Selected pediatric subset(s)D.1.3 Information on the existing quality, non-clinical, and clinical dataD.2 Pediatric Formulation DevelopmentD.2.1 General strategyD.2.2 Summary of all planned and/or ongoing measures in the pharmaceutical developmentD.3 Non-clinical StudiesD.3.1 General StrategyD.3.2 Summary of all planned and/or ongoing non-clinical studiesD.4 Pediatric Clinical StudiesD.4.1 General StrategyD.4.2 Pediatric pharmacokinetic/pharmacodynamic studiesD.4.3 Clinical efficacy and safety studiesD.4.4 Summary of all planned and/or ongoing clinical studiesD.4.5 Details of the planned and/or ongoing pediatric clinical studiesD.5 Other Studies — Modeling and Simulation/ExtrapolationD.5.1 Modeling and simulation studiesD.5.2 Extrapolation studies

Part E Request for DeferralsE.1 Timelines


Ongoing Progress to Intensify Collaboration for Pediatric Drug Development

Relevant Molecular Targets in Pediatric Cancers

In March 2018, the EMA and European Commission held a

workshop with patients, academia, healthcare professionals,

industry, and FDA representatives to discuss how to better

apply the Pediatric Regulation to boost development of

medicines for children. One of the 21 actions following the

March 2018 meeting was to establish a framework for collabo-

ration with EMA/PDCO and the FDA’s Oncology Center of

Excellence to assess relevant molecular targets in pediatric

cancers by December 2019. The progress report of the pediatric

action plan will be published in July 2020. For the time being,

the EMA reviews pediatric oncology programs with the FDA

on a monthly basis via the pediatric cluster. Furthermore, both

the EMA and FDA have been represented in the ACCELERATE

steering committee since 2019 and are actively engaged in the

organization of pediatric strategy forums addressing needs in

children with malignancies.

The relevant molecular targets in pediatric cancers is not

envisioned to restrict authority or flexibility. The molecular

target list13 is a great example of international collaboration.

It was constructed by the Oncology Center of Excellence

(OCE) with the National Cancer Institute (NCI) and input from

international content experts in an open public meeting on

April 20, 2018 at the FDA. The target list is continuously

reviewed by means of semi-annual public workshops, with

the possibility of on-going recommendations for additions

and deletions through internal and external advice panels.

Enhance the Integration of EMA/FDA Pediatric Cluster Activities

Another of the 21 actions from the pediatric action items list

which resulted from the March 2018 stakeholder meeting

was to enhance the integration of EMA/FDA pediatric cluster

activities to ensure knowledge and information exchange

between PDCO/EMA and the pediatric regulatory cluster.

The deadline for final outcome is June 2020. A report is to

be published in July 2020.

Further Collaboration and Alignment NeededOne of the greatest challenges facing pediatric drug develop-

ment is the fact that children are generally healthy and therefore

pediatric patients are limited. Current pediatric legislations in

the US and EU do not present a possibility of prioritization of

disease based on unmet medical need or a data-driven process

that can equitably identify and prioritize drugs for clinical trials.

As a result, concerns regarding execution of the pediatric

trials that are part of agreed pediatric development plans have

been noted.14

In 2013, the EMA held a workshop in response to the pediatric

studies that were required under the Pediatric Regulation for

several new drugs for type 2 diabetes mellitus. At that time,16

PIPs (with a total of 31 studies) had been agreed upon across

the class of glucagon-like peptide-1 analogues, dipeptidyl

peptidase 4 inhibitors, and sodium-glucose co-transporter 2

inhibitors, of which none had been able to successfully progress.

ICH E11 (R1)

The FDA and EMA, along with other global regulatory authorities

and industry representatives, participated in the addendum

R1 of the International Council for Harmonization (ICH) E11

guideline, “Clinical Investigation of Medicinal Products in the

Pediatric Population.” The addendum aims to advance pediatric

research with clear, compatible guidance specific to global

product development of pediatric medicines. Addendum

R1 provides clarification and current regulatory perspectives in

pediatric drug development among others on commonality of

scientific approaches for pediatric drug development programs.

ICH E11A Pediatric Extrapolation

This new ICH Guideline is proposed for harmonization of

methodologies and strategies to incorporate pediatric

extrapolation into overall drug development plans. This will

improve the speed of access to new drugs for pediatric

patients while limiting the number of children required for

enrollment in clinical trials.


There is a need for a rational, collaborative, and data-driven

approach to identifying and prioritizing drugs for studies

that are within the scope of legislative requirements. Drug

development should be driven through science. There is also

a need for choosing and prioritizing the potentially best drugs

to move forward. Working together with regulators, sponsors,

patient advocates, and academic experts across company

portfolios will help better inform and facilitate prioritization

of developments.

EU and FDA regulators should continue to discuss coordinated

approaches to minimize unnecessary pediatric trials and to

optimize trial design, safety, and conduct so that the limited

pediatric populations available are enrolled only in ethically

implemented, scientifically important trials. Innovative

approaches to data generation, the creation of international

databases to facilitate data sharing, and the use of preexisting

data through innovative analytical strategies could be part of

the solution.

Conclusion Collaboration is essential for successful global pediatric drug

development. To ensure adequate availability of drugs for

children, the following aspects will be important:

• Regulatory collaboration to seek alignment

• Engagement with other stakeholders beside regulators

• Education on regulatory science and procedures

• Continued and collaborative discovery of efficient pathways

to ensure safe and effective medicines are developed

• Strategic and creative approach

• Emboldened approaches to public health

Discussions with the FDA and EMA could be facilitated to

shape pediatric development programs, resulting in optimal

development plans. One could envisage piloting an interaction

with the FDA and EMA on pediatric development programs to

further support global alignment, including:

• Use the pediatric cluster teleconferences as platform

• The output as non-binding common commentary provides

recommendations for streamlined PIP/PSP/PPSP addressing

children’s needs and regulatory requirements

• Option for trilateral discussions with the applicant and both

agencies at the same time

The agencies systematically collaborate using all of their

experience to support pediatric assessment. Discussion

of initial pediatric development plans and a coordinated

international scientific review is key for the efficient evaluation

of new agents and will be an essential success factor for

developing new agents to treat children with the drugs

they need.

Ongoing harmonization of pediatric science and research is

important to make pediatric product development easier and

faster in order for children to get the medicines they deserve.


1. US Congress. Best Pharmaceuticals for Children Act Amending Section 505A of the Federal Food, Drug & Cosmetic Act

(Public Law 107-109). 2002.

2. US Congress. Pediatric Research Equity Act amending Section 505B of the Federal Food, Drug & Cosmetic Act

(Public Law 108- 155). 2003.

3. European Parliament and the Council of the European Union. Regulation (EC) No. 1901/2006 on medicinal products

for pediatric use. 2006.

4. : Yao. L. (2017). Current state of pediatric drug development.

Available at https://www.fda.gov/media/107592/download.

5. US Food & Drug Administration. International Collaboration/Pediatric Cluster. 2020.

Available at https://www.fda.gov/science-research/pediatrics/international-collaboration-pediatric-cluster.

6. European Medicines Agency. 10-year Report to the European Commission. 15 August 2017. EMA/231225/2015.

Available at https://ec.europa.eu/health/sites/health/files/files/paediatrics/docs/paediatrics_10_years_ema_techni-

cal_report.pdf.

7. Kweder, S. (2017). Better together: Harmonizing pediatric drug development. Paediatric Conference, European

Commission and TOPRA Available at https://www.topra.org/topra/topra_member/pdfs/10_Sandra_Kweder.pdf.

8. Written communication from EMA dated 15 June 2020.

9. Reaman, G., Herold, R., Norga, K., et al. (2016). Impact of the Food and Drug Administration (FDA)-European

Medicines Agency (EMA) Common Commentary (CC) on Paediatric Cancer Drug Development. Ped.Blood Cancer,

63, S212.

10. Poster for the 48th Congress of the International Society of Paediatric Oncology, October 19-22, 2016 in Dublin,

Ireland, G. Reaman et al.

11. US Food & Drug Administration, European Medicines Agency. FDA/EMA Common Commentary on Submitting

an initial Pediatric Study Plan (iPSP) and Paediatric Investigation Plan (PIP) for the Prevention and Treatment of

COVID-19. 2 June 2020. Available at https://www.ema.europa.eu/en/documents/other/fda/ema-common-commen-

tary-submitting-initial-pediatric-study-plan-ipsp-paediatric-investigation-plan-pip_en.pdf.

12. The iPSP template is included in FDA’s draft guidance for industry, Pediatric Study Plans: Content of and Process

for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans, which when finalized will

represent FDA’s current thinking on the topic. Available at https://www.ema.europa.eu/en/documents/tem-

plate-form/template-scientific-document-part-b-f_en.doc.

13. Candidate Pediatric Molecular Target List. Available at https://www.fda.gov/media/120331/download.

14. Karres J., Pratt V., Guettier J.M., et al. (2014). Joining forces: a call for greater collaboration to study new medicines

in children and adolescents with type 2 diabetes. Diabetes Care, 37:2665–2667.

References


PRA Health Sciences conducts comprehensive Phase I-IV biopharmaceutical drug development. To learn more about our solutions, please visit us at prahs.com or email us at [email protected].

Contact Information

For further information, or to discuss any aspect of PRA’s services offered in the field of pediatric clinical development, please contact your Business Development Manager, or PRA’s Center for Pediatric Clinical Development below:

Center for Pediatric Clinical Development

[email protected]

https://prahs.com/centers/the-center-for-pediatric-clinical-development

World Headquarters

4130 ParkLake Avenue, Suite 400

Raleigh, North Carolina 27612 USA

Phone: +1 (919) 786 8200

Fax: +1 (919) 786 8201

www.prahs.com

JULY 2020


https://prahs.com/centers/the-center-for-pediatric-clinical-development

https://www.pm360online.com

Global Pediatric Drug Development Collaboration

Documents

Transcript of Global Pediatric Drug Development Collaboration