2 2 Excipients

Copenhagen Workshop May 2016
Excipients
L. Paleshnuik
Lead Quality
Assessor
PQTm
11 Lynda Paleshnuik | May 2016

Overview
Excipient assessment basics

In-house standard excipients
Problematic excipients
Paediatric products
Colourants
Preservatives
Capsule shells
Mixtures
Lynda Paleshnuik | May 2016 2
Excipient assessment basics

Excipients
In general, excipients can be considered a low

priority section.
Certain aspects are generally not considered during
assessment, for example excipient suppliers.
(exception: mixtures including capsule shells)

Excipients
An excellent resource for excipients:
This is available in pdf format.
It is an invaluable reference to have on your computer.

Excipient basics
First things first:
Understand the function of each excipient in
the formulation
Ensure the proposed (and primary batch)
formulations have not changed compared to
the biobatch/clinical batch formulation

Identifying function
Understand the function of each excipient in the
formulation
descriptions in the formulation tables are
usually incomplete; many excipients have
multiple functions. For multifunction
excipients, the main function is expected
to be listed.
an example follows
7
Lynda Paleshnuik | May 2016
Excipient basics
Ensure the proposed formulation has not
changed compared to the biobatch/clinical
batch formulation
Ensure the formulation of primary batches
are the same as biobatch/clinical batches
Small changes may be acceptable, e.g. as per
SUPAC IR/MR documents
8
SUPAC levels of change
Level 1 - unlikely to have a detectable impact

Level 2 - could have significant impact
Level 3 - likely to have significant impact
where Level 2 values: double level 1 values
and Level 3 values: > level 2 values

SUPAC levels of change
Note: adding or deleting an excipient is level 3

(except deleting a colour/flavour, or change in an
ink excipient).

Excipient basics
SUPAC acceptable changes:
http://www.fda.gov/downloads/Drugs/
GuidanceComplianceRegulatoryInformation/Guidances/
UCM070636.pdf
The level 1 allowances are also published in the

PQTm variation GL (TRS 981 An3) as
Appendix 2.
11
Excipient basics
Checking SUPAC acceptable changes
Now the first point is critical: know the real
function of excipients before checking
SUPAC allowances
12
Level 1 changes
Level 2
10.0%
Excipient % Excipient
L1 L2
Filler 5 10
1.0%
Disintegrant
Starch 3 6
Other 1 2
Binder 0.5 1 0.2%

Formulation changes
Two real examples:
#1: MCC called a diluent (filler), when its function
in the formulation is a binder. [2% change]
#2: silicon dioxide called a lubricant, but its a
glidant (2 separate cases) [0.5% change]
In all examples, a level 1 change was a level 3
change. In #2b, the level 3 change was not
declared at all.
Formulation
Function is critical changes
when considering change
Conclusion:
All changes should be discussed in the report and
may require consultations.
Level 3 changes usually require a supporting
biostudy.
The changes had serious implications in all
examples.
Excipient standards

Reviewing excipients - standards
When a compendial standard is claimed, for most

excipients, a very light review is required. A
statement that it meets the compendial standard can
suffice.
Exception: Some excipients of compendial
standard need additional tests/limits beyond the
monograph, for example modified release FPP
where PSD or viscosity of the excipient may affect
the release.
Novel excipients
Novel excipient: one that has not been used (at a

similar level and by the same route of administration)
in a product approved by an SRA or by WHO.
In PQ, novel excipients are not accepted.
A novel excipient would require full data equivalent to

the data required for an FPP, and including safety data.

Reviewing in-house standard excipients
We accept in-house standards for excipients, but most excipients
used should have a compendial monograph. (exceptions include
colourants, flavourants, flavours, inks)
The manufacturers/applicants specifications must be

reviewed (not the suppliers).
Check if there is a compendial monograph available.
If yes, compare the in-house specs to compendial

standards. The specs must meet at least one of the available
standards (BP/EP/USP/NF)
19\ Lynda Paleshnuik | May 2016

In-house standard excipients
Example issue: minor in-house components are not
reviewed e.g. Purified water is commonly IH standard.
If used in the manufacture, it must be identified in the

formulation and must have a specification. If in-
house standard, it must be assessed. (includes
manufacturing solvents, silicon for stoppers, nitrogen)
In-house specs need to be compared to compendial

standards and must meet at least one of the available
standards (BP/EP/USP/NF)

Excipients
Excipient review is normally low priority.

But there are exceptions.
In-house standards must be reviewed as stated.
In addition:

Problem excipient areas

Problem excipients
Areas that require more consideration:
Paediatric products
Colourants
Preservatives
Capsule shells
Mixtures

Paediatric products

Excipients in paediatrics
The following may not be appropriate for children,
especially infants and neonates:
benzyl alcohol
azo colouring agents - discussed in colourants
propylene glycol
ethanol
propyl paraben
Preservatives and colourants should be minimized.
Consult clinicians - reformulate? (e.g. tartrazine)

Resource for paediatric excipients
TRS 970 Annex 5: Development of paediatric medicines:
points to consider in formulation Sections include:
5.3: Excipients
5.4: Colouring agents
5.5: Antimicrobial preservatives
5.6: Sweetening agents
8.1: Parenterals - formulation considerations

Additional reference for further information:
WHO Food additives series (FAS):
http://www.who.int/foodsafety/publications/
monographs/en/
Different publications address different classes of
excipients, e.g. antimicrobials, antioxidants,
colours, emulsifiers, stabilizers, sweeteners, etc.
First resource for problematic
excipients in PQT
European Commission Guideline:
Excipients in the Label and Package Leaflet of
Medicinal Products for Human Use (http://
www.ema.europa.eu/docs/en_GB/document_library/
Scientific_guideline/2009/09/WC500003412.pdf) and
updates to this GL
Check excipients in the FPP against this GL and make

note of which are listed.
This GL is for all FPPs, not just paediatrics.

How it is used in PQTm
The Q assessor does the following and reports it in the
assessment report:
For excipient(s) listed in the EC GL:
label: ensure excipients are qualitatively declared on the
label as per EC GL, e.g. "contains lactose".
SmPC section 2: ensure excipients are quantitatively
listed, e.g. "Each tablet contains 70 mg of lactose.

How it is used in PQTm
PIL: Send the general comment for the excipients flagged
above:
"Due to the contents of <excipients listed in the GL> in the
formulation, a specific warning/precautionary statement
may have to be included in the product information. This
will be provided with the draft WHOPAR, including the
WHO recommended product information, at a later stage."

Colourants

Colourants (colouring agents)
Colourants are important for product identification.
Changes in colourants are considered low risk - (e.g.

deletion of a colour is SUPAC level 1)
BUT supportive data is required as per PQ Variation 23
The choice of colourants requires proper

assessment.

Dyes, pigments, lakes
Dyes - water soluble - must be used to have a clear

liquid
Pigments - water insoluble - provide better opacity
(help protect from light) - eg. TiO2, iron oxides
A pigment generally makes a better surface colourant

for tablets than a dye, due to less colour migration,
greater opacity and colour stability compared to dyes.

Lakes - insoluble forms of dyes - a Na or K salt of the dye

is adsorbed onto a very fine substrate of hydrated alumina,
followed by treatment with an Al salt.
A lake has the same benefits as a pigment for surface colour.
CAUTION
A dye and its lake are different products and may have
different acceptability, e.g. FD&C red #3 is acceptable, but
the lake is not permitted in medicinal products. It is
important to check each colourant used.

Lakes - insoluble forms of dyes - a Na or K salt of the dye

is adsorbed onto a very fine substrate of hydrated alumina,
followed by treatment with an Al salt.
A lake has the same benefits as a pigment for surface colour.
CAUTION
A dye and its lake are different products and may have
different acceptability, e.g. FD&C red #3 is acceptable, but
the lake is not permitted in medicinal products. It is
important to check each colourant used.

Dyes, pigments, lakes
Dyes lakes
pigments
Water soluble Opaque, water insoluble

Often applicants will use Colorcon colourant mixtures

for tablet coatings. These are generally acceptable if:
we have the Colorcon document showing the qualitative

formulation, and,
the manufacturers/applicants specifications for the

Opadry include an IR identification test.
All colourant excipients should be declared in SmPC/PIL.

Colourants
If the applicant manufactures their own coating, or otherwise uses

colourants (outside Colorcon products): (1)
The dyes, pigments and lakes must be verified to be permitted for

use either in Japanese pharmaceutical excipients, the European
Union (EU) List of permitted food colours, or the FDA Inactive
ingredient guide.
For proprietary mixtures, the suppliers product sheet with

the qualitative formulation should be submitted, along with the
FPP manufacturers specifications including identity testing.
(TRS970 An4)
More details under mixtures

It can get complicated
Colour index #47005 represents both:
a) D&C Yellow #10
and
b) Quinoline yellow (E104)
BUT: a) is accepted by FDA but not EU
b) is accepted by EU but not FDA
and a) is called quinoline yellow WS in HPE.

What to do?
For a given colourant:
Check the permitted lists:
Japanese pharmaceutical excipients,
European Union (EU) List of permitted food
colours,
FDA Inactive ingredient guide
If included in any list, it can be used.
Then check the EC GL for labeling requirements.
Colourants
Some colourants are listed as excipients with safety

concern in the EC GL above and must be treated
as discussed above. Partial list given:
E102, tartrazine
E110, sunset yellow FCF Good to know E#s
E122, azorubine, carmoisine
E123, amaranth
E124, ponceau 4R red, cochineal red A
E151 brilliant black BN, black PN

What about flavours?
Required to be submitted:
the qualitative composition, and,
a declaration that the excipients comply with

foodstuff regulations (e.g. USA or EU regulations).
(TRS970An4)

What about sweeteners?
Check if permitted for use, for example:

List of permitted sweeteners:
http://www.hc-sc.gc.ca/fn-an/securit/addit/list/9-
sweetener-edulcorant-eng.php
Gives a list of sweeteners, the foods they are
permitted in, and the maximum level of use/other
conditions.

Other additives
Note that the Canadian food and drug regulations
are available for download (1000 p) and include
other lists of permitted food additives, e.g:
pH Adjusting Agents, Acid-Reacting Materials and
Water Correcting Agents, Emulsifiers, Sequestering
Agents, Colourants
Preservatives (various classes), Solvents, etc.
[Often under max level of use it states only, GMP]

Preservatives

Preservatives
Antioxidants: Used to retard oxidation of APIs and
excipients.
Antimicrobials (AM): used to kill, prevent or reduce
microbial growth.
Q: What is a suitable amount?
A: The least necessary but still effective concentration.
All useful antimicrobial agents are toxic substances.
46
Preservatives
Q: AMs are toxic. Are there concerns with antioxidants?
A: Always consult the EC GL on excipients and labelling.
Some antioxidants are irritants in some formulations.
EMA GL states: Antioxidants should not be included in
a formulation unless it is demonstrated that they cannot
be avoided, even after optimization of the manufacturing
process (e.g. filling under inert headspace gas).
i.e. like AMs, the use of antioxidants should always be
justified.
47
Preservatives
Q: When should you expect to see preservatives?
A: In multiple-dose liquid and semi-solid FPPs - oral
and topical FPPs (unless inherent preservative efficacy
demonstrated). (Use in injections/ophthalmics now
discouraged, but still accepted)
Q: When should preservatives be justified in a
formulation?
A: Always. If the FPP is a paediatric product, this should
include the appropriateness for the target age group.
48
Preservatives
When should preservatives not be used?
To substitute for poor manufacturing practices.
Generally not necessary in solid orals (small
amounts are acceptable in capsule shells and in
film-coatings).
A single dose FPP generally does not need
preservatives.
49
Identifying preservatives
As noted previously:
Understand the role of each excipient in the
formulation
e.g. ethanol used as solvent and vehicle
(in a liquid product) may also function
as antimicrobial preservative
50
Antimicrobial (AM) preservatives
The HPE lists many antimicrobial preservatives including:
benzalkonium chloride, benzethonium chloride,
benzoic acid, benzyl alcohol, boric acid, bronopol,
butylene glycol, butylparaben, calcium chloride,
calcium lactate and many more.
If you are unfamiliar with any excipient, look it up
in the HPE. For example, benzyl alcohol is a common
AM preservative that has been fatal to newborns. (Also
listed in the EMA GL on excipients - not for babies<3y)
51
Common preservatives in oral FPPs
ReRemember
Remember that parabens are also named as hydroxybenzoates

Quality guidelines and
AM Preservatives

Quality guidelines and AM preservatives
For a solid oral, before going through the
requirements, make sure they have properly
justified the presence in the formulation
(exceptions are small amounts in the capsule
shell or coating solution).
Consult with senior assessors when AMs are
observed. Any need for reformulation
must be identified early.
54
If presence is justified - Q GL: Did they:
justify the proposed amount (should be lowest
effective concentration) with studies of FPP
formulated with different concentrations
demonstrate the effectiveness (1 batch), e.g.
AME USP <51> or EP 5.3.1.
demonstrate the effectiveness (1 batch) at the
lower limit if the lower assay limit is <90%
55
Q GL continued:
demonstrate effectiveness (1 batch) at the
end of the shelf-life. [note that a commitment
could also be accepted]
include assay of preservatives in
specifications (R and S)
56
ICH guidelines and preservatives
3.2.P.2.5 of ICH M4Q: include a discussion
of the selection and effectiveness of
preservative systems.
57
ICH guidelines and preservatives
Q6A: AM preservative assay should be conducted
at release plus AME throughout the shelf-life*.
Antioxidant assay should be conducted at release,
plus at shelf-life unless justified. If only release
testing is done, this must be reinvestigated for any
change in manufacture or packaging.
* Q GL is at end of shelf-life
See also decision tree #8. [AME = AM effectiveness]
58
Parabens

Parabens (hydroxybenzoates)
[AM preservatives]
e.g. propyl paraben
60
in solid oral products
Parabens have been allowed in some solid oral
products in PQTm, however only at a) low levels,
in b) non-paediatric products, and even in these
cases c) this should be questioned and
discouraged or asked to reformulate.
Use of parabens in solid orals is generally only done
by applicants with less high standards.
Do not allow parabens in a formulation without
consultation and adequate justification.
61
Justifications given (1):
The formulation contains aspartame,
therefore preservatives are required.
Many solid formulations with aspartame (up
to 8%!) are prequalified, but none require
preservatives.
Not adequate: why do they really need it?
62
Justifications given (2):
The binder requires preservatives.
Binders are regularly prepared with PW and no
preservatives. They should be used within a short
period of time (few hours, within a shift).
Not adequate: why do they really need it?
Check the master records, do they want a long hold
time for the binder solution?
63
Inadequate justification (3):
For one FPP, AMP in the binder was accepted
because it is considered an established product,
i.e. does not require pharmaceutical development
data. Luckily this dossier was cancelled prior to PQ.
An established product means we dont normally
have to review all the PD data, it doesn't mean we
dont question the formulation or process where
relevant.
64
Capsule shells
and other excipients with
TSE/BSE concern

Capsule shells
Capsule shells are sometimes overlooked or

treated in reports as outside normal requirements.
Gelatin shells are a critical part of assessment.
Two critical aspects:
potential BSE/TSE risk
potential contamination with chromium

BSE/TSE
Transmissible spongiform encephalopathies

(TSEs) are a family of diseases of humans and
animals characterized by spongy degeneration of
the brain with severe and fatal neurological signs
and symptoms.
BSE-contaminated food of bovine origin leads to
vCJD (fatal spongy degeneration of the brain).
200+ cases (12 countries) starting in 1996.

Capsule shells
Capsule shells have two sets of important

specifications:
shell specifications
shell excipient specifications or standards

Capsule shells
1. Supplier(s) of the capsule shells must be identified.

2. Capsule shell specifications (FPP manufacturers):
must be reviewed
should include microbial limits and chromium
tests
PF 2015 Jan-Feb has a draft monograph for empty
shells

Capsule shell excipients
Capsule shell excipients are a separate but

important aspect of the assessment.
We need the quantitative composition of the
shells, with the standard and/or specifications for
each excipient.

Shell excipients are sometimes accepted without looking at
their standards or specifications.
Excipients in shells (plus ink if used) should be treated like

other excipients in the following ways:
they must meet compendial standards when available,
in-house specifications must be reviewed.
Plus there are additional concerns.

Additional concerns for capsule shell excipients:

Gelatin is an excipient of concern
Note: there is no non-animal source of gelatin
First we need:
1. Information on the supplier(s) of gelatin
You are requested to identify the supplier(s) of
gelatin to the capsule shell manufacturer X.

2. Gelatin has potential for TSE/BSE

contamination. At minimum a valid EDQM
certificate of suitability (from each supplier) is
required.
You are requested to identify the supplier(s) of
gelatin to the capsule shell manufacturer X, and
submit copies of the EDQM certificate(s) of
suitability associated with these suppliers.

3. There are concerns regarding gelatin supplied

from China regarding chromium contamination.
You are requested to obtain confirmation from
your capsule shell supplier, X, that the gelatin used
conforms to USP, BP, Ph.Eur. or Ph.Int. standard
including a limit of NMT 10 ppm chromium.
Q: If there is a CEP, that makes it EP standard,
therefore chromium isnt an issue, right?
A: false, some CEPs are older than the EP limit
Capsule shells
Additional concerns for capsule shells:

Note that some shells are actually package units,
e.g. lopinavir/ritonavir sprinkles, and vitamin A,
and are intended to deliver the product but are not
intended to be consumed.
However, because they MAY be consumed, they
should be treated the same as other shells.

Other excipients with TSE/BSE concern
In some jurisdictions, only gelatin is identified as a

concern.
In PQT, the following are included (with gelatin):
Magnesium stearate
Stearic acid and other stearates (e.g. glyceryl
monostearate)
Phosphates (e.g. dibasic calcium phosphate)
Other excipients with TSE/BSE concern
What we need (for all but gelatin*):

Either a declaration that the excipient is from
plant origin, or
a CEP (preferably) or attestation confirming that
the excipient is without risk of transmitting agents
of animal SE (spongiform encephalopathies).
*For gelatin see requirements in previous slides.

Model Dossier Exercise

Model dossier exercise
Check the formulation in the QOS.

Could any of the excipients listed in 2.3.P.1 have
multiple functions?
What observed change(s) would make the
excipient functions critical?

The function depends on the formulation
and manufacturing process
As an assessor, good to know how
excipients function in the formulation
It is not generally necessary to question

the claimed function
It becomes important when

there is a formulation change
Check the formulation in the MD.

Identify any excipients of TSE/BSE concern
What data can be found to address concerns, and
where?
What is your concern level?
What is the fastest way to do this?


Mixtures

Example 1

Mixtures - example 1
Note that excipient suppliers are generally not

assessed. We have the applicant/FPP manufacturers
specifications for the excipient.
For a mixture, a 3rd party controls excipient quality
and performs some manufacturing steps.
For tablet coatings, Opadry products (Colorcon) are
well-established. However, a DMF may be
required to support a mixture from another
company.
85
Lynda Paleshnuik | March
2016
Note the change history in the first page of

the following master records:
86
2016
87
2016
The applicant did not:

declare the alternative coating mixture
elsewhere (although included in revised coating
records)
provide information on the mixture (excipients,
amounts, standards, proprietary information),
or,
include the information in the QIS (P.1, P.3.2, P.
3.3)
88
2016
The applicant was asked to provide:

the composition of the mixture
the standards of the excipients
a comparison to the Opadry that it is an
alternate for
if not Q&Q (to the Opadry), the alternate
should be removed or additional supportive
data is required
89
2016
Alternatives are not normally accepted for

excipients and should be discouraged. Treat them
cautiously.
In order for them to be accepted, full information is
needed on the products.
There should be no differences between alternatives.
Any alternatives should be fully declared in the QIS.
90
2016
Example 2

Tablet formulation: IH standard is declared for one
excipient, monoammonium glycyrrhizinate (MAG).
In the report: specs parameters/limits were listed,

and a request went out to include identity in the
specs. What was missing from review?
Is there a compendial monograph? (Yes) Therefore

a comparison must be made/discussed.
A comparison was made at the QA stage.
Outcome: Two available monographs (BP, NF), but

specs met neither monograph.
The QA comment went out: revise the specifications

to conform to BP or NF limits.

The applicant responded that the excipient is not
actually MAG.
It is a mixture of MAG, maltose and ethyl maltol.
And interestingly, MAG is not even the main

component, which is maltose (about 80%).

This raises three new concerns.
1. The applicant has not fully declared the

composition of the tablets. This could be deliberate
(to hide a problematic excipient) (to avoid issues
with a non-compendial excipient), or due to lack of
experience with stringent regulations.
2. Ethyl maltol is an uncommon excipient.

3. We need to look carefully at maltose, in case they
were trying to avoid declaring it. (This is a concern
because a mixture of mainly maltose was called
MAG, a minor component of the mixture)

We must learn more about ethyl maltol.
We check the recognized compendia: there is no

monograph in the recognized compendia.
We check the excipient handbook for uses and

concentrations and incompatibilities.
Nothing unusual comes up. (Flavourant used at the

proposed concentrations, no relevant incompatibilities)

We must look closely at maltose.
Maltose is a well-known excipient and they are declaring

NF standard.
There are no warnings regarding maltose in the EC

excipient GL.
The excipient handbook has no cautions for the amount

used, the use, or compatibility.

The API in this product (zinc) is also sensitive to
problems with excipients (absorption can be
affected).
A consultation/search had to be done for any record

of issues with the API and maltose or ethyl maltol.
No issues were identified.

Comment to applicant
It is noted that you did not previously disclose the
composition of the mixture <Tradename>. It is of critical
importance that the full quantitative formulation of each
product be declared in the dossier, QOS-PD and QIS. Note
that section P.1 b) ii) of the QIS and QOS-PD states,
Composition of all components purchased as mixtures
and should have included the composition of this mixture.
In addition, as monoammonium glycyrrhizinate is not the
main component of this mixture, it should preferably be
identified in the formulation as maltose mixture
([Tradename]), with all components and their relative
percentages listed below the formulation tables in the QIS.

The comment goes on to ask for revised blank
manufacturing records and product information
and QIS, that correctly identifies the product
composition.
These are where the full formulation must be

declared.

The applicant responds with the revised documents
that fully declare the composition.
We could find no indication that this was a

deliberate omission, and it is considered to be due to
inexperience (this is the applicants first dossier in
PQ).

Conclusion: what could have happened in such a situation, if the
IH standard had not been looked into prior to acceptance?
A company could be hiding the presence of excipients in a

product by declaring one excipient instead of a mixture. This
could lead to issues with the product after approval.
In such a case, it would be hard to defend how the regulators had

not observed this. The fact that the excipient did not meet
standards of a compendial monograph was the clue that it was
not really the excipient claimed.

Take-aways
Excipients are a low importance area, with

exceptions:
Paediatric products require special
considerations - check references
Ensure only acceptable colourants are used
Use of preservatives should always be
justified and adequately controlled
Gelatin capsules and mixtures require
special considerations
Thanks for your
attention!
105

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Copenhagen Workshop May 2016

11 Lynda Paleshnuik | May 2016

Excipient assessment basics

Lynda Paleshnuik | May 2016 3

In general, excipients can be considered a low

Lynda Paleshnuik | May 2016 4

This is available in pdf format.

It is an invaluable reference to have on your computer.

Lynda Paleshnuik | May 2016 5

Lynda Paleshnuik | May 2016 6

Level 1 - unlikely to have a detectable impact

Lynda Paleshnuik | May 2016 9

Note: adding or deleting an excipient is level 3

Lynda Paleshnuik | May 2016 10

The level 1 allowances are also published in the

Binder 0.5 1 0.2%

Lynda Paleshnuik | May 2016 16

When a compendial standard is claimed, for most

Novel excipient: one that has not been used (at a

A novel excipient would require full data equivalent to

18 Lynda Paleshnuik | May 2016

The manufacturers/applicants specifications must be

Check if there is a compendial monograph available.

If yes, compare the in-house specs to compendial

19\ Lynda Paleshnuik | May 2016

If used in the manufacture, it must be identified in the

In-house specs need to be compared to compendial

20 Lynda Paleshnuik | May 2016

Excipient review is normally low priority.

Lynda Paleshnuik | May 2016 21

Lynda Paleshnuik | May 2016 22

Areas that require more consideration:

Lynda Paleshnuik | May 2016 23

Lynda Paleshnuik | May 2016 24

Preservatives and colourants should be minimized.

Consult clinicians - reformulate? (e.g. tartrazine)

25 Lynda Paleshnuik | May 2016

26 Lynda Paleshnuik | May 2016

Check excipients in the FPP against this GL and make

28 Lynda Paleshnuik | May 2016

29 Lynda Paleshnuik | May 2016

30 Lynda Paleshnuik | May 2016

Lynda Paleshnuik | May 2016 31

Colourants are important for product identification.

Changes in colourants are considered low risk - (e.g.

BUT supportive data is required as per PQ Variation 23

The choice of colourants requires proper

32 Lynda Paleshnuik | May 2016

Dyes, pigments, lakes

Dyes - water soluble - must be used to have a clear

A pigment generally makes a better surface colourant

33 Lynda Paleshnuik | May 2016

Lakes - insoluble forms of dyes - a Na or K salt of the dye

A lake has the same benefits as a pigment for surface colour.

34 Lynda Paleshnuik | May 2016

Lakes - insoluble forms of dyes - a Na or K salt of the dye

A lake has the same benefits as a pigment for surface colour.

35 Lynda Paleshnuik | May 2016

Water soluble Opaque, water insoluble

Often applicants will use Colorcon colourant mixtures

we have the Colorcon document showing the qualitative

the manufacturers/applicants specifications for the

All colourant excipients should be declared in SmPC/PIL.

37 Lynda Paleshnuik | May 2016