Identification of acceptable comparators and comparator ... · Manufacturers meeting, Geneva, April 2011 2 | Introduction Multi-source (generic) drug products must satisfy the same

Manufacturers meeting, Geneva, April 2011

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Identification of acceptable comparators

and comparator issues.

Dr. Jan Welink


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IntroductionIntroduction

Multi-source (generic) drug products must satisfy the same standards as those applicable to the originator’s product.

In addition, assurance must be provided that they are, as intended, clinically interchangeable with nominally equivalent market products.


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BioequivalenceBioequivalence

Reference Test

Pharmaceutical Equivalent

Products

Possible Differences

Drug particle size, ..

Excipients

Manufacturing process

Equipment

Site of manufacture

Batch size ….

Documented Bioequivalence

= Therapeutic Equivalence


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ComparatorComparator

Introducing the comparator:

* a pharmaceutical product with which the multi-

source product is intended to be interchangeable in clinical practice.

* the selection of the comparator product is usually made at the national level by the drug regulatory authority.


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Choice of the comparator:


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ComparatorComparator

Example of how a national DRA can select a comparator:

� choose national granted innovator for which quality, safety and efficacy has been established (nationally authorised innovator)

� choose WHO comparator product from the comparator list (WHO comparator product)

� choose innovator product from well-regulated country (ICH et al. innovator)

� if no innovator comparator is available, a generic market leader can be chosen


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Comparator

Selection of a comparator for a single

national market:

cannot be translated in case other countries are at stake

national comparator may be the national market leader

no problem in that market but others!?


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EMA (Europe)EMA (Europe)

Differentiate between use for single market or many countries!

A u s tria

F ran c e

L a tv ia

P o lan d

B e lg iu m

G erm a n y

L ie c hten s te in

P o rtu g a l

C yp ru s

G ree ce

L ith u a n ia

S lo vak R e pu b lic

C zec h R ep u b lic

H u n g ary

L u x em b u rg

S lo ven ia

D e n m ark

Ic e la n d

M a lta

S p a in

E sto n ia

Ire lan d

T h e N e th e rlan d s

S w ed en

F in la n d

Ita ly

N o rw ay

U n ited K in g d o m

EMA:

For an abridged application claiming essential similarity to a reference product, application to reference product from one Member numerous Member States based on bioequivalence with a

can be made.State


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Prequalification program


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EOI

To manufacturers of medicinal products:

HIV/AIDS - 10th Invitation for EOI

Malaria - 8th Invitation for EOI

Tuberculosis - 10th Invitation for EOI

Reproductive Health - 5th Invitation for EOI

Influenza - 2nd Invitation for EOI

Zinc - 1st Invitation for EOI


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Comparator lists

List of acceptable reference products for the

prequalification project for reproductive health


prequalification project for reproductive health


prequalification project for Zinc


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Identifying comparators


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Guidance documentsGuidance documents

Comparator products:

Comparator products should be obtained from a well regulated market with stringent regulatory authority i.e., from countries participating in

the International Conference on Harmonization (ICH)

Countries officially participating in ICH are the ICH members European Union, Japan and USA; and the ICH observers Canada and Switzerland.

Note: some are not available in ICH


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Guidance documentsGuidance documents

Information Requirements

Within the submitted dossier, the country of origin of the comparator product should be reported

together with lot number and expiry date, as well as results of pharmaceutical analysis to prove

pharmaceutical equivalence. Further, in order to prove the origin of the comparator product the

applicant must present all of the following documents:

1. Copy of the comparator product labelling. The name of the product, name and address of the

manufacturer, batch number, and expiry date should be clearly visible on the labelling.

2. Copy of the invoice from the distributor or company from which the comparator product was

purchased. The address of the distributor must be clearly visible on the invoice.

3. Documentation verifying the method of shipment and storage conditions of the comparator

product from the time of purchase to the time of study initiation.

4. A signed statement certifying the authenticity of the above documents and that the comparator

product was purchased from the specified national market. The certification should be signed by th

company executive or equivalent responsible for the application to the Prequalification Programme


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An example of selectionAn example of selection

Terizidone: - first selection Terizidex

Questions from CROs regarding availability!

meanwhile, Terivalidin was included in South Africa’s National Tuberculosis Control Program!


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comparator issuescomparator issues

comparator from non-ICH countries


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wrong comparator from ICH countries

Choice justification:

- national market leader


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unclear from which country

Statement:

- The comparator product was bought in an US pharmacy by a relative and carried in his luggage to India!


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unclear from which country

Protocol:

Study report:


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ConclusionConclusion

For the Prequalification Program:

* the comparator should be selected from the comparator list (http://apps.who.int/prequal/info_applicants/info_for_applicants_BE_comparator.htm)

* guidance on selection and the to be provided documents should be followed.

* if comparator is not available, information can be obtained at: [email protected]


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End

Thank you for your attention

Documents

Identification of acceptable comparators and comparator ... · Manufacturers meeting, Geneva, April 2011 2 | Introduction Multi-source (generic) drug products must satisfy the same