TOPIC 2 Standards and Quality Variation Flashcards by ceej rogan

are defined as documents that provide
requirements, specifications, guidelines, or characteristics
that can be used consistently to ensure that materials,
products, processes, and services are fit for their purpose

Quality standards

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defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. ____ are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities as conditions of approval

Specification

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defined
as documents that provide
requirements, specifications,
guidelines, or characteristics that
can be used consistently to
ensure that materials, products,
processes, and services are fit for
their purpose. ___

Standards
(ASQ)

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is a list of detailed
requirements (acceptance
criteria for the prescribed test
procedures) with which the
substance or pharmaceutical
product has to conform to
ensure suitable quality.

Specification

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To avoid producing a defective
product, 1.__& 2. ___ are developed to
serve as basis for accepting or
rejecting a product.
Example of this is 3.___

Standards and Specifications

1-2. standards and
specifications
3. Drug Reference Standard
(RS)

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is a standardized substance which is
used as a measurement base for similar
substances. Where the exact active
substances of a new drug are not known, a
reference standard provides a calibrated
level of biological effects against which new
preparations of the drug can be compared.

Drug Reference Standard
(RS)

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This is concise and precise statement of the
ingredients that comprise the product, together with the
percentage and/or weight of each.

Formula

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This should enumerate
the characteristics of all the materials that go into the
product and the permissible range of purity of each
ingredient. Standard compendia like the USP, NF, BP,
BPC, Merck Index, etc., provide this valuable
information.

Raw Material Specification

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This is a
step by step method on how to go about a
job. It must spell out all information and
instructions that assure that variations in
production from day to day and week to
week will be held to within acceptable
established ranges.

Standard Operating Procedure.

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This should
be set for everything that goes around the
product, i.e., bottles, cans, aluminum foil,
cellophane, jars, caps, cap liners, labels,
printed inserts, cartons, wrapping papers,
and shipping cases.

Packaging Material Standard

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This
should cover all characteristics that affect
the proper performance, purity, safety and
stability of the product.

Finished Product Specification

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These are indispensable
in assuring conformity to standards. Since
they play such a vital role, testing
procedures must be standardized so that
they yield results of comparable precision
and accuracy in the hands of different
operators and laboratories. The tests must
be validated to ensure precision and
accuracy on application.

Testing Methods

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What are the Official References: (primary)

v United States Pharmacopoeia and National Formulary
v Japan Pharmacopeia
v British Pharmacopeia
v European Pharmacopeia
v International Pharmacopeia

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is a legally
binding collection, prepared by a
national or regional authority of
standards and quality
specifications for medicines used
in that country or region

Pharmacopoeia

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a is used to furnish quality
specifications for active pharmaceutical
ingredients (APIs), FPPs and general
requirements.

Pharmacopoeia

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presents the basic assumptions,
definitions, and default conditions for the
interpretation and application of the USPNF

General Notices Section

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Requirements stated apply to all
articles recognized in the USP and NF
and to all general chapters unless
specifically stated otherwise.

General Notices Section

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General Chapters 1 to 999

Example is 1.__

Physical tests and determinations,
microbiological tests, Chemical tests and
assays, Biological tests and assays

ENFORCEABLE

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General Chapters 1000 to 1999

General Information (no
mandatory requirement)

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General Chapter Above 2000

apply to articles classified as
Dietary ingredient or supplements

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<1>

Injections

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<2>

Oral Drug Products—Product Quality Tests

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<231>

Heavy Metals

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<621>

Chromatography

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<671>

Containers

<761>

Nuclear Magnetic Resonance

<851>

Spectrophotometry

<781>

Optical Rotation

<1160>

Pharmaceutical Calculations in Prescription Compounding

<1176>

Prescription Balances and Volumetric Apparatus Used in Compounding:

<2232>

Elemental Contaminants in Dietary Supplements

<2750>

Manufacturing Practices for Dietary Supplements

is a combination of two official compendia:

The USP–NF 1-2. United States Pharmacopeia (USP) and the National Formulary (NF).

Monographs for drug substances and preparations are featured in the 1.__

1. USP

Monographs for 1-2. __ appear in a separate section of the USP.

1. dietary supplements and ingredients

Excipient monographs are found in the 1.___

NF.

Year of creation to signing of the first Philippine Pharmacopeia in cooperation with the Japanese Government through the initiatives of 2-3.___

1. 1996 2-3. Dr. Conrado S. Dayrit and Prof Akira Hamada.

1. When was the creation of Pharmacopeia Organization for the preparation and publication of the Phil Pharmacopeia thru _2_ 3. Declaring and adopting the Phil Pharmacopeia as the Official book of Standards nd Reference for Pharmaceutical Products and Crude plant drugs in the Philippines

1. May 26, 1999 2. Department Order no. 216-F 3. Exec. Order 302 (2004)

approved Standard Setting Organization or its foreign equivalent

1. ANSI Standards Setting Organization (SSO)

a government sponsored organization (where sponsorship is not based solely on financial contributions by the government), a multimember consortia or industry recognized organization Standards Setting Organization (SSO)

Standards Setting Organization (SSO)

(Guidelines: Norms and Standards for Pharmaceuticals)

WHO

Current Good Manufacturing Practice (CGMP) Regulations

FDA

Adoption and Implementation of the Pharmaceutical Inspection and Scheme )PIC/S) Guides for the Good manufacturing practice for medicinal products

AO 2012 – 0008

Guidelines for The Classification of Deficiencies Observed During Inspection of Drug Manufacturers

Circular No.2019-003

is the leading the international development, implementation and maintenance of harmonized GMP standards and quality systems of Inspectorates in the field of medicinal products

PIC/S - Pharmaceutical Inspection Cooperation Scheme Guides ◎ICH - International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use:

Establish a uniform set of standards for drug registration non-profit Association under Swiss law on 2.___

1. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 2. October 23, 2015

Brings the regulatory authorities and pharmaceutical industry to discuss about scientific and technical aspects about drug registration.

International Council for Harmonisation

Reduction of unnecessary animal testing without compromising safety and effectiveness accomplished through 1.__ that are implemented by the regulatory authorities.

Technical Guidelines

Main goal of International Council for Harmonisation is to

achieve greater harmonization worldwide.

ICH - Purpose Promotion of public health through international harmonisation that contributes to: 1-4.

* Prevention of unnecessary duplication of clinical trials and post market clinical evaluations * Development and manufacturing of new medicines * Registration and supervision of new medicines * Reduction of unnecessary animal testing without compromising safety and effectiveness accomplished through Technical Guidelines that are implemented by the regulatory authorities

ICH – Founding members 1-5.

1. Europe 2. European Commission 3. Japan 4. Ministry of Health, Labor and Welfare (MHLW) 5. or Pharmaceuticals and Medical Devices Agency (PMDA) US

ICH – Standing Observers

1. WHO 2. International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Observers Regulatory authorities Regional Harmonisation Initiatives international industry pharmaceutical organisations international organisations regulated or affected by ICH Guidelines

Clinical trials conducted in one ICH region can be used in other ICH regions by setting the common standards on science and ethics.

GCP (Good Clinical Practice)

brings together all Quality, Safety and Efficacy information in a common, harmonised format, accepted by regulators in all ICH regions. It has revolutionised regulatory review processes for regulators and industry.

CTD/eCTD (Common Technical Document)

Highly specific, standardised medical terminology developed by ICH to facilitate sharing of regulatory information

MedDRA (Medical Dictionary for Regulatory Activities)

It is used for registration, documentation and safety monitoring of medical products both before and after marketing authorisation

MedDRA (Medical Dictionary for Regulatory Activities)

ICH Guidelines

Quality – 14 Guidelines Safety - 23 Guidelines Efficacy – 21 Guidelines Multidisciplinary - 6 Guidelines

14 Guidelines

Quality

Safety - 23 Guidelines

Safety

21 Guidelines

Efficacy

6 Guidelines

Multidisciplinary

stability studies, defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality

Quality

potential risks like carcinogenicity, genotoxicity and reprotoxicity

Safety

conduct, safety and reporting of clinical trials

Efficacy

ICH medical terminology (MedDRA), the Common Technical Document (CTD) and the development of Electronic Standards for the Transfer of Regulatory Information (ESTRI).

Multidisciplinary

Q S E M

QUALITY SAFETY EFFICACY MULTIDISCIPLINARY

Q4B-Annex 7

Dissolution Test General Chapter

ICH QUALITY GUIDELINES

1. Finished Product Control Compendial Requirements for Liquid and Solid Dosage Forms (ICH Q6) 2. Statistical Quality Control (ICH Q9, Annex I.9- Supporting Statistical Tools) 3. Stability Studies (ICH Q1) 4. Validation (ICH Q2)

(ICH Q6)

Finished Product Control Compendial Requirements for Liquid and Solid Dosage Form

(ICH Q9, Annex I.9- Supporting Statistical Tools)

Statistical Quality Control

(ICH Q1)

Stability Studies

is an undesirable characteristic of a product.

defect

(ICH Q2)

Validation

It is defined as a failure to conform to specifications.

defect

A unit of a product which contains one or more defects is called a ___.

defective

Any unwanted event that represents a departure from approved processes or procedures or instruction or specification or established standard or from what is required. Deviations can occur during manufacturing, packing, sampling and testing of drug products.

Deviation

change in data, expected outcomes, or slight changes in production quality

VARITION

Examples of Defects: 1-13

Mottling Chipping Lamination Telescoping Caking Coalescence Creaming Off-color Capping - wrong volume - missing label - misplaced dropper - sub potent

– a defect which can be measured directly by instruments. Examples are: 1-8

Variable defect Ex. length, weight, height, thickness, concentration, volume, viscosity, pH or size particles.

– a defect which cannot be measured directly by instruments. It shows mainly the conformance or nonconformance. Examples are: 1-6

Attribute defect Ex. Functional, Texture, presence of dents, cracks, missing buttons, cracks

Attribute defect can be ___

Counted

a defect which may endanger life or property and may render the product non – functional. Examples are: 1.

Critical defect Ex: Absence of a warning in a label for a potent drug or disintegration time of one hour for an analgesic.

a defect which may affect the function of the object and therefore, may render the product useless or aesthetically objectionable

Major defect Ex: Presence of a crack in a bottle.

Stains that may appear

Major defect

a defect which does not endanger life or property nor will it affect the function but nevertheless remains a defect since it is outside the prescribed limits. Examples are: 1

Minor defect Ex: slight deviation of the color of the label from the color standards.

Scratches or dents

Minor defect

What are defect According to measurability: 1-2

Variable defect Attribute defect

According to seriousness or gravity:

Critical defect Major defect Minor defect

According to nature:

Ocular defect Internal defect Performance defect

a defect that is visible.

Ocular defect e.g., foreign particulate contamination.

a defect which is not seen although present.

Internal defect e.g., a sub – potent drug product.

a defect in function.

Performance defect e.g., suppository that does not melt at body temperature.

is the method of withdrawing or correcting unsafe or hazardous health products from the distribution chain that may present a health hazard to the consumer or user.

Recall

a situation in which there is a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death.

Class I recall

a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.

Class II recall

a situation in which use of or exposure to a violative product is not likely to cause adverse health consequences

Class III recall

Class I Pathogens:

I- Salmonella, Listeria monocytegenes, E. coli, Clostridium

Class II Pathogens:

II – Shigella, Cyclospora, Cryptosporidium, hepatitis A

Class III Pathogens:

III – Low levels of pesticide residue

Type of Defects Adverse reactions related to a product defect.

}Packaging, bottling/filling and labelling. }Deviations from specifications }Contamination }Packaging defects

Other deviations: Other deviations typically concern reports of non-compliance with GMP, counterfeit medicines, authorized variation applications and the suspension of marketing authorizations leading to withdrawals, as well as defects related to the product itself, e.g. precipitation,

Product Recall Examples:

wrong (potent) product (label and contents are different products) with serious medical consequences chemical or microbial contamination with serious medical consequences or in sterile preparations wrong active ingredient in a multi-component product with serious medical consequences. Defective pacemaker, defibrillator Hot/cold packs containing toxic substances Software and hardwares (used for critical conditions) defects

Product Recall Examples:

mislabeling (for example, incorrect or missing text or figures) non-compliance with specification, such as in an assay, stability, fill or weight resulting in medical consequences insecure or incorrect closures for medicines such as cytotoxics, potent products and medicines requiring child-resistant packaging resulting in medical consequences. faulty packaging, such as wrong or missing batch number or expiry date faulty closure not resulting in any medical consequences contamination with no medical consequences

Sources and Control of Quality Variation manufacturing processes become more complex -->

The risk of errors increases

material control, GMP, packaging control, automation and statistical sampling plans are employed -->

To minimize and eliminate the sources of errors which can cause product quality variation

Sources of Variation:

materials machines methods men

Variation between suppliers of same substance.

materials

Variation of equipment for the same process.

machines

Inexact procedures.

methods

Variation between batches from same supplier.

materials

Aging and improper care.

machines

Negligence by chance.

methods

Inadequate procedures.

methods

Difference in adjustment of equipment.

machines

Variation within a batch.

materials

Improper working conditions.

men

Inadequate training, and understanding.

men

Dishonesty, fatigue and carelessness.

men

a visualization tool for categorizing the potential causes of a problem in order to identify its root causes.

A fishbone diagram,____ diagram or Ishikawa diagram

“cause and effect”

Dr. Kaoru Ishikawa, a Japanese quality control expert: 1-2

Quality improvement is a continuous process Customer continued service

4P's

(Policies, Procedures, People and Plant

TOPIC 2 Standards and Quality Variation Flashcards

WEEK 2