Presented by:

Mahesh D. Patil(M.Pharm-2nd Sem)

DEPARTMENT OF BIOPHARMACEUTICS.

H. R. PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION & RESEARCH, SHIRPUR

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Content

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E = Empowering the subject for the consent.

T = Transparent processes to follow.

H = Humane thinking in the clinical trial.

I = Internationally accepted data by following ethics.

C = Consult the guidance regularly.

A = Authenticity of trial objectives.

L = Legal representation .

Defination Ethics are the study of values and customs of a person or group. Local may conflict with universal.

WHO GuidelinesQuality assuranceQuality controlGMPSanitation and hygieneQualification and validationComplaintsProduct recallsContract production and analysisSelf-inspection and quality auditsPersonnelPremisesEquipment and materialsDocumentation

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Quality assurance“Quality assurance” is a wide-ranging concept covering all

matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use.

QA System should ensure:Products are designed and developed correctly

Complying with, e.g. GMP, GLPProduction and control operations are definedManagerial responsibilities are defined

In job descriptions

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Quality assurance Controls are performed, including intermediates, bulk, calibration and validation Correct processing and checking of the finished product Products are sold/supplied only after review by the authorized person

Complying with marketing authorization, production and QC requirements

Proper storage, distribution and handling Reporting, investigation and recording of deviations Regular evaluation of product quality to verify consistency and continued improvement

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Quality Control

QC is part of GMP - refer to the handout

SamplingTestingrelease proceduresrecalls and complaintsSpecifications

Authorizationlaboratory operationsrelease decisionsinvestigation and reporting

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Good Manufacturing PracticesGood manufacturing practice is that part of quality assurance which

ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.

Aim: to diminish the risks inherent in any pharmaceutical production.

Under GMP:Clearly defined and systematically reviewed processes Qualification and validation is performedAppropriate resources are provided:

Qualified and trained personnel Premises, space, equipment and Laboratories Materials, containers, labels Procedures, storage, transport

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Good Manufacturing Practices Clear, written instructions and procedures Trained operators Records for manufacture and distribution Systems for complaints and recalls

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Sanitation and hygieneThe scope of sanitation and hygiene covers personnel,

premises, equipment and apparatus, production materials and containers, products for cleaning and disinfection, and anything that could become a source of contamination to the product.

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Qualification and validationValidationAction of proving, in accordance with the principles of GMP, that

any procedure, process, equipment, material, activity or system actually leads to the expected results

QualificationAction of proving that any premises, systems and items of equipment

work correctly and actually lead to the expected results

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Qualification and validationQualification and validation should establish and provide documentary

evidence that: (a) the premises, supporting utilities, equipment and processes have been

designed in accordance with the requirements for GMP (design qualification, or DQ);

(b) the premises, supporting utilities and equipment have been built and installed in compliance with their design specifications (installation qualification, or IQ);

(c) the premises, supporting utilities and equipment operate in accordance with their design specifications (operational qualification, or OQ);

(d) a specific process will consistently produce a product meeting its predetermined specifications and quality attributes (process validation, or PV, also called performance qualification, or PQ).

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Areas of Validation

Validation of Buildings and FacilitiesValidation of EquipmentProcess Validation Cleaning ValidationValidation of Analytical MethodsValidation of Computer SystemsValidation of Specific Dosage Forms

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ComplaintsAll complaints and other information concerning potentially

defective products should be carefully reviewed according to written procedures and the corrective action should be taken.

Designated responsible person:To handle complaintDecide on measure to be taken Sufficient support staffAccess to records

Written procedure (SOP):Describes action to be taken Includes need to consider a recall (e.g. possible product

defect)

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Complaints Due to product defect (discovered or suspected):

Consider checking other batches Investigation and evaluation should result in appropriate follow-

up actionsMay include a "recall"

All decisions and measures taken should be recorded Inform competent authorities in case of serious quality problems

such as: Faulty manufacture Product deteriorationCounterfeiting

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Product recallsThere should be a system to recall from the market, promptly and

effectively, products known or suspected to be defective.The authorized person should be responsible for:

-To execute and coordinate recalls

-Decide on measure to be taken Sufficient support staff

-To handle all aspects and urgency of recall• SOP for Recall

Established written proceduresDetailed actions to be takenStore recalled products in a secure, segregated area

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Product recallsAll competent authorities of all countries to which a given product

has been distributed should be promptly informed.Distribution records available to authorized person and contain

sufficient information on Wholesalers, Direct customers, Export locations, Batch numbers and quantities, Including for clinical tests and medical samples to permit effective recall.

The progress during the recall and disposition of the product should be recorded.

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Contract production and analysisContract production and analysis must be correctly defined, agreed

and controlled in order to avoid misunderstandings that could result in a product or work or analysis of unsatisfactory quality.

The contract giver:Must assess competence and compliance of contract accepter with

GMPAll necessary information must be provided to the contract accepter

in order to:have the operations carried out correctly in accordance with the

manufacturing authorisation and other legal requirements

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Contract production and analysisbe fully aware of any problems with the product, work, tests that

might pose a hazard to premises, equipment, personnel, other materials or other products.

The contract accepter-must have the necessary facilities, premises and equipment, both in

type and in quantity, to undertake the work.must have a manufacturing authorization to do this type of work.its staff must have the necessary qualifications, training and

experience to be able to do the workshould not pass to a third party any of the work entrusted to him or

her under the contract without the contract giver’s prior evaluation and approval of the arrangements.

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Contract production and analysisThe contract-Each party’s responsibilities definedMaterials purchasing, testing and releasingRecords:

manufacturinganalysisdistribution

should be kept by or made available to the contract giver

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Self-inspection and quality auditsPurpose: to evaluate whether a company’s operations remain

compliant with GMPperformed routinely, and may be, in addition, performed on special

occasions, e.g. in the case of product recalls or repeated rejections, or when an inspection by the health authorities is announced.

Self-inspection team with authority sufficient experiencemay be from inside or outside the company experts in their own field familiar with GMP

• Frequency of self-inspection: at least once a year

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Self-inspection and quality auditsSelf-inspection report includes:

evaluation conclusions recommended corrective measures

Quality auditA quality audit is an examination of all or part of quality system with

specific aim of improving itUsually conducted by outside experts or team appointed by

managementMay be extended to suppliers and contractors

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PersonnelEstablishment and maintenance of satisfactory system of QA,

manufacture and control of products and actives rely on people.Individual responsibilities must be clearly defined and understood by

individuals concernedAll personnel should be aware of the principles of GMP that affect

them

Personnel requirements:Adequate number of personsWith necessary qualificationsWith practical experience

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PersonnelHave adequate authority to carry out responsibilitiesMotivated to

support the establishmentmaintain high-quality standards

Prevent unauthorized people accessTo production areas Storage areasQuality control

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PremisesImportant aspects to be kept in mind to ensure the suitability of the

operations to be carried out for different dosage forms and product range:

Location

Design

Construction

Adaptation

Maintenance• The layout and design should aim to:

Minimize risks of errors

Permit effective cleaning

Permit effective maintenance25

Premises Avoid cross-contamination, build-up of dirt and dust

Avoid any adverse effect on the quality of products Ancillary Areas Rest and refreshment rooms separate from manufacturing and

quality control areas Animal houses well isolated – separate air handling and entrance Storage Areas Separate and segregated areas: starting materials, packaging

materials, intermediates, bulk, finished products, quarantined, released, rejected, returned and recalled products and materials

Appropriate temperature and relative humidity conditions within defined limits Provided, controlled, monitored and recorded

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PremisesWeighing areasWeighing operations – in separated areasCleaning procedures and recordsDocumentation, e.g. SOPs, logs and records

Production areasLayout in accordance with sequence of productionIncluding filtration of air to a sufficient level to prevent

contamination and cross-contaminationControl of temperature and relative humidity where necessaryMinimize risk of cross-contamination

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PremisesQuality Control areasQC laboratories should be separate from production areasSeparate areas for biological, microbiological and radioisotope

methodsSuitable space for storage samples, reference standards, solvents,

reagents and recordsSeparate rooms for some instruments to protect them from

interference (e.g. electrical, vibration, moisture, etc.)

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EquipmentEquipment must be located, designed,

constructed, adapted, and maintained to suit the operations to be carried out.

The layout and design of equipment must aim to minimize the risk of errors and permit effective cleaning and maintenance in order to avoid cross-contamination, build-up of dust or dirt, and, in general, any adverse effect on the quality of products.

Balances and other measuring equipment of an appropriate range and precision should be available and calibrated on a scheduled basis.

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EquipmentProduction equipmentAppropriate design

easily and thoroughly cleaned on a scheduled basis

No hazard to the products contact parts of suitable non-reactive materials non additive and not absorptive

Defective equipment removed, or labelled to prevent use

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MaterialsPrinciple:Objective of the pharmaceutical manufacturer

produce finished products for patient's use from a combination of materials

Materials combinedActive pharmaceutical ingredients andExcipients Packaging materials

Materials include alsoGases, solvents, reagents etc. Special attention

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MaterialsGeneral requirements for materialsMaterials for cleaning, lubrication, and pest control

Not in direct contact with product

All incoming materials and finished products quarantined after receipt or processing

– until released for use or distribution stored

– under appropriate conditions– orderly fashion– stock rotation

Water – suitable for intended use

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Documentation Good documentation is an essential part of the QA system Should exist for all aspects of GMP Purpose of documentation

Defines specifications and procedures for all materials and methods of manufacture and control

Ensures all personnel know what to do and when to do itEnsure that authorized persons have all information

necessary for release of productEnsures documented evidence, traceability, provide

records and audit trail for investigationEnsures availability of data for validation, review and

statistical analysis

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DocumentationTypes of Documentation

Labels

Specifications and testing procedures

Master formulae and instructions

Batch processing and batch packaging records

Standard Operating Procedures (SOPs)

Records

Stock control and distribution records

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ReferencesForensic Pharmacy by Dr. Kuchekar, Khadatare, Itkar, Nirali

Prakashan, 7th Edition, page no. 17.25Pharmaceutical Quality Assurance, by manohar potdar, Nirali

Prakashan, 1st editionwww.who.int

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