Module 9 2024

03/09/2024

Example Drug Substance FIH Specification

Quality Attribute

Test Method

Acceptance Criteria

Appearance (Colour)

Ph. Eur. 2.2.1

Not more intensely coloured than Y3

Appearance (Clarity)

Ph. Eur. 2.2.2

Less than reference standard 4 (30NTU)

Appearance Visible Particles

Ph. Eur. 2.9.20

Report result

pH

Ph. Eur. 2.2.3, USP<791>

x.x ± 0.5 pH units

Protein content

In house

x.x ± 10% mg/ml

Identity

Method choice (PMAP, IEX, ELISA)

Comparable to reference standard

Monomer Purity Total Aggregates

In house – SEC HPLC

% Monomer ≥90.0 % % Aggregate ≤5.0 %

Purity (Reduced)

In house – Reduced CE-SDS

≥90.0 % as heavy and light chains

Purity (Non-reduced)

In house – Non-Reduced

≥85.0 % as Intact IgG

Charge Heterogeneity

In house – (e.g IEX, icIEF)

Profile comparable to reference Report % acidic, basic, main isoforms

Potency (Binding ELISA)

In house

50 – 150 % relative to reference

NP-HPLC (glycosylation)

In house

Report rel. % of major glycans

rDNA

In house

Not more than xx ppb Complies with WHO limit 10ng/dose

rPrA

In house

< x ppm

rHCP

In house

< x ppm

Bacterial endotoxins

Ph. Eur. 2.6.14, USP<85>

Not more than x.x EU/mg Refer to Ph. Eur for calculation

Bioburden

Ph. Eur. 2.6.12, USP<61>

Not more than x CFU/x ml (1 CFU / 10ml or 10 CFU/100 ml)

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Example Drug Substance Specification

Quality Attribute

Test Method

Acceptance Criteria

Appearance (Colour)

Ph. Eur. 2.2.1

Not more intensely coloured than Y3

Appearance (Clarity)

Ph. Eur. 2.2.2

Less than reference standard 4 (30NTU)

Appearance Visible Particles

Ph. Eur. 2.9.20

Practically free from visible particles

Sub-visible particles

Ph. Eur. 2.9.19, USP<788>

≥10 µm: ≤6000 particles/vial ≥25 µm: ≤600 particles/vial

pH

Ph. Eur. 2.2.3, USP<791>

x.x ± 0.5 pH units

Quantity - Protein content

In house – UV, gravimetric

x.x ± 10%

Identity

In house - PMAP, IEX, ELISA

Comparable to reference standard

Extractable volume

Ph. Eur. 2.9.17 and USP<1>

≥ X.X mL

Uniformity of Dosage Units

Ph. Eur. 2.9.40 and USP<40>

Conforms

Monomer Purity Total Aggregates

In house – SEC HPLC

% Monomer ≥90.0 % % Aggregate ≤5.0 %

Purity (Reduced)

In house – Reduced CE-SDS

≥90.0 % as heavy and light chains

Purity (Non-reduced)

In house – Non-Reduced

≥85.0 % as Intact IgG

Charge Heterogeneity

In house – (e.g IEX, icIEF)

Profile comparable to reference Report % acidic, basic, main isoforms

Potency (e.g Binding ELISA)

In house

50 – 150 % relative to reference

Bacterial endotoxins

Ph. Eur. 2.6.14, USP<85>

Not more than x.x EU/mg Refer to Ph. Eur for calculation

Sterility

Ph. Eur. 2.6.1, 71

Sterile

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