2.2.4 ICH Q6B Guideline

Добавил:

Sekretar kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Ростовский Государственный Медицинский Университет

Предмет:

Медицина общая

Файл:

Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5441_Библиотеки_им_академика_М_И_Перельмана.pdf

Скачиваний:

Добавлен:

10.10.2026

Размер:

9 Мб

Скачать

☆

<<< < Предыдущая 1 2 3 4 56 / 456 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

Table 2.5 Specic tests for new drug products (solid oral dosage forms)

Types of drug

products

Tests Description

References

Solid oral dosage

forms:

1. Tablets (coated/

uncoated)

2. Hard gelatine

capsules

3. Soft capsules or

granules

(a) Dissolution • It includes measurement of drug substance release from DP (immediate release and

extended-release DP)

• For immediate-release products, tests should be able to exclude products with altered

dissolution rates that can affect bioavailability

• IVIVC (in vitro/in vivo correlation), which is used to establish acceptability criteria

for bioavailability, is used for extended-release dosage forms

Bhavna and

Bhargava

(2022), ICH

Ofcial website

(2023a), Kestur

etal. (2023),

Nickerson etal.

(2018), Chen

etal. (2017a)

(b) Disintegration • Disintegration may be used instead of dissolution for products that dissolve quickly

(within 15min, and are pH dependent. At pH values of 1.2, 4 and 6.8, the dissolution

value is less than 80%) and involves products with high solubility across the

physiological region (>250mL of dose or solubility at pH ranges of 1.2–6.8)

ICH Ofcial

website (2023a),

Nickerson etal.

(2018)

friability

• Used for in-process testing

• In the case of chewable or dispersible tablets, a specic acceptable range should be

included

ICH Ofcial

website (2023a),

Pandit etal.

(2019)

(d) Uniformity of

dosage units

• This test takes into account both the weight of the dosage form and the quantity of the

active ingredient it contains; a pharmacopoeial protocol should be followed

ICH Ofcial

website (2023a),

Chen etal.

(2017b)

(e) Water content • The effect of moisture absorption on DP should be assessed

• The acceptable range can be decided by loss on drying, and moisture detection can be

done by Karl Fischer titration

ICH Ofcial

website (2023a),

Pandit etal.

(2019)

(f) Microbial limits • The overall number of aerobic microbes, the total number of moulds and yeasts and

the absence of any specic harmful bacteria (such as Staphylococcus aureus,

Pseudomonas aeruginosa, Salmonella and Escherichia coli) may need to be specied in

accordance with pharmacopoeial guidelines

ICH Ofcial

website (2023a),

Roesti (2019)

2 Design ofMaterials andProduct Specications forPharmaceutical Dosage Forms

Specic tests and acceptable ranges that must be applied to NDP have been

divided according to the dosage forms, i.e. (ICH Ofcial website 2023a):

1. Solid oral drug products/dosage forms (Table2.5)

2. Liquid oral drug products/dosage forms (Table2.6)

3. Small volume and large volume parenteral (Table2.7)

2.2.4 ICH Q6B Guideline

Test Procedures and Acceptance Criteria for Biotechnological/Biological

Products

According to the broad guidelines provided in this document, a unied set of world-

wide specications for biotechnological and biological products should be dened

and justied to a practical degree.

2.2.4.1 Scope

• The ideas described in this recommendation apply to proteins and protein chains

(polypeptides), as well as to the derivatives and end products (such as conju-

gates) made from them; this also covers proteins and polypeptides extracted

from body uids and tissues.

• This guideline does not include synthetic proteins and polypeptides, cell metabo-

lites, vitamins, heparins, allergenic extracts, DNA products, traditional vaccines,

whole blood, cells and cellular components of blood.

• This guideline is devoid of regulation of clinical/preclinical research material.

2.2.4.2 Specifications

Specic testing is chosen for each product and incorporated into the specications.

Explaining the reasoning behind the acceptable range of acceptance criteria is

essential. Data from lots used in preclinical and clinical investigations, data from

stability studies, data from lots used to demonstrate manufacturing consistency and

pertinent development data should be used to construct and justify acceptance crite-

ria (Pokar et al. 2020; ICH Harmonised Tripartite Guideline 2023; Pallagi

etal. 2018).

These specications have been described under two heads:

1. Specication for drug substances

2. Specications for drug products

2.2.4.2.1 Specifications forDrug Substance

All drug substances must pass the examinations and meet the acceptance standards

indicated in Table2.8. The drug substances should undergo pharmacopeial studies

(such as endotoxin detection) where required.

2.2.4.2.2 Specifications forDrug Products

All drug products must pass the following test tabulated in Table2.9.

A. Kishore et al.

Table 2.6 Specic tests for new drug products (liquid oral dosage forms)

Types of drug

products

Tests Description

References

1. Oral liquids

2. Powders

intended for

reconstitution as

oral liquids

(a) Dosage unit

uniformity

• This test refers to the dosage form’s weight and the amount of

the active ingredient it contains; a pharmacopeial protocol should

be followed

• Applicable on both single- and multi-dose packaging

ICH Ofcial website (2023a), Pandit etal.

(2019)

(b) pH • Strictly followed wherever needed, and the range should be

justied

ICH Ofcial website (2023a)

number of moulds and yeasts and the absence of any undesirable

bacteria (such as Pseudomonas aeruginosa, Escherichia coli,

Salmonella and Staphylococcus aureus) may need to be specied.

Following pharmacopeial guidelines, these should be determined

ICH Ofcial website (2023a), Roesti

(2019)

(d) Antimicrobial

preservative content

• An acceptable range should be set

• Generally, testing for antimicrobial preservative concentration

is done at the time of release

De Jong (2016), Ola etal. (2018)

(e) Content of

antioxidant

preservatives

• Antioxidant preservative quantity is tested at the time of release ICH Ofcial website (2023a), Knight

(2014), Pharmacopeial Forum 750 of the

USPC or the USP (2009)

(f) Extractables • Test for the content extracted and released in oral liquids from

containers and closures (e.g. cap liner, rubber stopper, plastic

bottles, etc.)

Pandit etal. (2019), Pharmaceutical

Technology Editorial Advisory Board

(2020)

(g) Alcohol content • Testing for alcohol content can be done by assay to match the

quantity labelled on the label

ICH Ofcial website (2023a), Knight

(2014)

(h) Dissolution • Dissolution testing is included in the case of suspensions and

powders for reconstituted in the form of suspension

• Pharmacopoeial tests are followed. Other tests have to be

justied

Knight (2014), Hiwale etal. (2008)

(Continued)

2 Design ofMaterials andProduct Specications forPharmaceutical Dosage Forms

Types of drug

products

Tests Description

References

(i) Particle size

distribution

• Applicable on oral suspensions

• Generally performed at the time of release or otherwise justied

• This test can also replace dissolution testing if justied

ICH Ofcial website (2023a), Pandit etal.

(2019), Ola etal. (2018)

(j) Re-dispersibility • Applicable to oral suspension to check re-dispersibility by

shaking method

Ola etal. (2018)

(k) Rheological

properties (viscosity/

specic gravity)

• Applicable to viscous solutions or suspensions

• The acceptance range and test method should be specied

Chan (2014)

(l) Reconstitution

time

• Reconstitution timing should be stated for dry powders

intended for reconstitution

• Diluent selection should be justied

ICH Ofcial website (2023a), Knight

(2014)

(m) Water content • When suitable, a water content test and acceptability criterion

for oral products that need reconstitution should be recommended

Pandit etal. (2019), Lin (2022)

Table 2.6 (continued)

A. Kishore et al.

Table 2.7 Specic tests for NDPs (parenteral dosage forms)

Types of

drug

products

Tests Remarks

References

Parenteral

dosage

forms

(a) Dosage unit

uniformity

• This test refers to both the dosage form’s weight and the amount of the

active ingredient it contains; a pharmacopeial protocol should be followed

• Applicable on powders for reconstitution

• Applicable on both single- and multi-dose packaging

ICH Ofcial website (2023a)

(b) pH • Whenever necessary, this rule must be followed appropriately, and the

range must be validated

ICH Ofcial website (2023a)

acceptable standard to determine its sterility. This approach may be

recommended for drug items that have undergone terminal sterilisation,

with data collected throughout development and validation supporting

parametric release

Nema and Ludwig (2016), Avis

(2018)

(d) Endotoxins/pyrogens • Specifying the acceptance range and test procedure for endotoxins, such

as the limulus amoebocyte lysate (LAL) test, is essential

• In some cases, it may be appropriate to check for the presence of

pyrogen instead of endotoxins

Akers (2016)

(e) Particulate matter • This test includes acceptable ranges for visible and sub-visible

particulates

Beg etal. (2020)

(f) Water content • Applicable to products intended to be reconstituted and to nonaqueous

parenteral

• Loss on drying test and Karl Fischer titration is used depending upon

set protocols

Radhakrishnan etal. (2019)

(g) Antimicrobial

preservative content

• An acceptable range should be set

• Generally, testing for antimicrobial preservative concentration is done at

the time of release

ICH (1999)

(h) Content of

antioxidant preservatives

• Antioxidant preservative quantity is tested at the time of release ICH (1999)

(Continued)

2 Design ofMaterials andProduct Specications forPharmaceutical Dosage Forms

Types of

drug

products

Tests Remarks

References

(i) Extractables • Test for the content extracted and released in oral liquids from

containers and closures (e.g. cap liner, rubber stopper, plastic bottles, etc.)

• More strictly followed as compared to oral liquids

Houston etal. (2022)

(j) Functionality testing

of delivery systems

• Delivery systems are those in which parenteral preparations are

generally packaged as auto- injector cartridges or prelled syringes;

functionality tests should be conducted according to established protocols

• Generally performed in-process

ICH (1999)

(k) Osmolarity • The product’s osmolarity should be maintained according to the set

tonicity of the product

Sangeetha etal. (2022)

(l) Particle size

distribution

• Applicable on injectable suspensions

• Generally performed at the time of release or otherwise justied

• This test can also replace dissolution testing if justied

Geigert (2019b)

(m) Re-dispersibility • Applicable to injectable suspensions to check re-dispersibility by

shaking method

Elder (2017)

(n) Reconstitution time • Reconstitution timing should be stated for all parenteral intended

reconstitution

• Diluent selection should be justied

Elder (2017)

Table 2.7 (continued)

A. Kishore et al.

Table 2.8 Specic tests for drug substances

S.No.

Test name Description

References

1 Appearance

and

description

• The physical appearance (solid/liquid) and colour

of drug substances should be specied

Knight

(2014),

Pokar etal.

(2020)

2 Identity • Tests for identity must be exact and based on the

chemical structure or other distinctive characteristics

• Several test methods (physicochemical,

immunochemical and biological) may be necessary to

prove identity

3 Purity and

impurities

• Results for purity and impurities are method-

dependent. A combination of methods is used to

determine purity. Analytical techniques can be

improved by separating the intended product from

impurities and related chemicals

• Impurities are categorised into two parts: (1)

process and (2) product related; separation techniques

should be optimised accordingly

4 Potency • Specications should include a pertinent, veried

potency assay

5 Quantity • An appropriate assay should be used to calculate

the drug substance’s quantity, which is often based on

protein content (mass)

• It might not be necessary to make a different

quantity determination in circumstances where

product manufacturing is based on potency

Table 2.9 Specic tests for drug products

S.No.

Test name Description

References

1 Appearance

and description

• The physical appearance (solid/liquid), colour and

transparency of the DP should be specied

Knight

(2014)

2 Identity • Tests for identity must be exact and based on the

chemical structure or other distinctive characteristics

• Several test methods (physicochemical,

immunochemical and biological) may be necessary to

prove identity

• Evaluation tests for a DP may also be

implemented for the rm establishment of identity

Knight

(2014)

3 Purity and

impurities

• During the DP’s production, storage or both,

impurities may be created or enhanced

• Impurities may be process related (if same as drug

substance, the examination is not mandatory) or

deterioration product while manufacturing or storage

(impurities should be quantied and acceptability

range should be decided)

• Separation techniques should be optimised

according to the desired product, deterioration

product from drug substance and excipients also

Pokar etal.

(2020)

(Continued)

2 Design ofMaterials andProduct Specications forPharmaceutical Dosage Forms

2.2.5 ICH Q8R2 Guidelines fortheProduct Specification

Pharmaceutical development aims to create high-quality products through manufac-

turing to deliver the products’ intended performance consistently. Quality should be

incorporated into products from the outset because they cannot be tested into them.

Data from pharmaceutical development studies can provide a foundation for quality

risk management. The development section aims to give reviewers and inspectors a

thorough grasp of the product and manufacturing procedure. The minimum approach

and enhanced knowledge approaches are the best keys in pharmaceutical develop-

ment studies. Critical formulation characteristics and process variables are typically

determined by evaluating the degree to which their change can affect the efcacy

of the DP.

The applicant also has the option of conducting pharmaceutical development

studies, which may result in a better understanding of how well a product performs

across a broader range of material characteristics, process parameters and process-

ing options; this information, in turn, can be converted into scientic understanding

that can further be used to establish more expanded design spaces. The design space

ensures the quality of the nished product, a multidimensional combination of the

properties of the raw material and process parameters. More adaptable regulatory

methods must be created to enable this. Regulatory decisions are predicated on risk

via review or inspections:

• Decrease in post-approval submissions

• Enhancement in the manufacturing process

• Real-time quality control

The foundation for science-based submissions and the regulatory assessment of

those submissions is the degree of knowledge attained, not the volume of data

(Narayan 2011; Mishra etal. 2018).

S.No.

Test name Description

References

4 Potency • Specications should include a pertinent, veried

potency assay

Pokar etal.

(2020)

5 Quantity • An appropriate assay should be used to calculate

the drug substance’s quantity, which is often based on

protein content (mass)

• It might not be necessary to make a different

quantity determination in circumstances where

product manufacturing is based on potency

Pokar etal.

(2020)

6 General tests • For the examination of the DP’s functions,

physical description and the evaluation of other

quality parameters are necessary. These tests may

include, for instance, pH and osmolarity testing

Davis (2013)

7 Additional

testing for

unique dosage

forms

• Some particular dosage forms may require testing

in addition to those listed above

Davis (2013)

Table 2.9 (continued)

A. Kishore et al.

2.2.5.1 Q8(R2): Structure—Parent Guideline (Knight 2014)

1. Pharmaceutical Development: Introduction

2. Components of the Drug Product

(a) Drug Substance

(b) Excipients

3. Drug Product

(a) Formulation Development

(b) Overages

4. Manufacturing Process Development

5. Container Closure System

6. Microbiological Attributes

7. Compatibility

2.2.5.1.1 Pharmaceutical Development: Introduction

Pharmaceutical development aims to create a high-quality product and its produc-

tion method to consistently achieve the product’s desired performance. Scientic

understanding assists in formulating the design space, specications and manufac-

turing controls based on information and expertise gathered through pharmaceutical

development research and manufacturing experience. Pharmaceutical development

study data can establish a foundation for effective risk management. It should be

noted that directly checking the quality of the nal product is impractical. However,

quality maintenance is crucial throughout each phase of product development.

This section should provide the concepts through which one can understand

whether the selected dosage form and proposed formulation are correct for the

intended dosage form or not. At the very least, it is necessary to identify and support

control techniques for those elements of drug ingredients, excipients, container

closing systems and manufacturing methods that are crucial to product quality.

Critical formulation characteristics and process variables are often determined by

evaluating the degree to which their modication can affect the efcacy of the

medicinal product (Maguire etal. 2017; Fahmy etal. 2013).

2.2.5.1.2 Components ofDrug Product

Drug Substances

Any DP comprises drug substances and excipients in the form of the formulation.

Drug substances are a vital part of DPs, highly affecting the product performance

due to their biological and physicochemical properties. Solubility, particle size,

water content, biological activity, crystal properties and permeability are some

examples of physicochemical and biological properties that may need investigation.

These qualities might be connected, so it may be necessary to consider them all.

ICH guidelines Q6A and Q6B provide detailed information about the NDS and

DP.The drug-excipient interaction study also plays an essential role in pharmaceuti-

cal development (PDA 2023).

2 Design ofMaterials andProduct Specications forPharmaceutical Dosage Forms

Excipients

An excipient is another prominent product ingredient that can alter bioavailability,

stability and manufacturability. When relevant, the compatibility of excipients with

each other should be assessed. Excipients must demonstrate the ability to function

throughout the designated DP shelf life and full their intended purpose. Examples

of such excipients include disintegrants, antioxidants, release-controlling agents

and penetration enhancers. The safety prole of each excipient should be examined

in accordance with regulatory guidelines (Maguire etal. 2017).

2.2.5.1.3 Drug Product

Formulation Development

A descriptive summary of the formulation’s development process should be pro-

vided, along with a list of essential qualities for the product’s quality. Consider the

intended use and route of administration. Information from formal experimental

designs can be used to identify critical or interacting variables and ensure the DP’s

quality. The formulation design, from the initial idea to the nal design, should be

highlighted in the summary. The same summary should justify the selection of

product components, manufacturing processes and excipient ranges based on expe-

rience gained. The information related to bioavailability and bioequivalence with

the in vitro dissolution prole should be presented. In vitro/in vivo correlation

should be established and justied with valid data wherever applicable

(Narayan 2011).

Overages

Generally, it is not recommended to use an excess of a drug substance to make up

for manufacturing defects, prolong a product’s shelf life or both. The batch formula

should include information related to the reason for overages, the amount of over-

ages and justication for the amount (D’Hondt etal. 2014).

Physicochemical andBiological Properties

Identifying and analysing the physicochemical and biological characteristics crucial

for the DP’s manufacturing, performance and safety is essential. This involves con-

sidering the physiological effects of the medication substance and formulation char-

acteristics (DeGrazio and Paskiet 2020).

2.2.5.1.4 Manufacturing Process Development

The selection of the manufacturing process for production should be mentioned in

the reports. The controls and improvements in the process should also reect the

proper description. The selection of particular equipment and implementation of the

process improvement programme should be part of the documentation. Any crucial

process parameters that need to be monitored or controlled for quality should be

identied by the manufacturing process development project or process improve-

ment scheme. The data should, for instance, include the following: (1) the manufac-

turing location, (2) the batch size, (3) the identity of the batches produced (e.g.

A. Kishore et al.

<<< < Предыдущая 1 2 3 4 56 / 456 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

Соседние файлы в папке Библиотека им академика М.И. Перельмана

#
10.10.202610 Мб0Книга_5434_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.202610 Мб0Книга_5435_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.20269 Мб0Книга_5436_Библиотеки_им_академика_М_И_Перельмана.pdf
#
29.08.202685 Мб0Книга_544_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.20269 Мб0Книга_5440_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.20269 Мб0Книга_5441_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.20269 Мб0Книга_5442_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.20269 Мб0Книга_5443_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.20269 Мб0Книга_5444_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.20268 Мб0Книга_5445_Библиотеки_им_академика_М_И_Перельмана.pdf
#
10.10.20268 Мб0Книга_5446_Библиотеки_им_академика_М_И_Перельмана.pdf