MANUFACTURING AND MANUFACTURING AND PRODUCTION OF PRODUCTION OF

BIOLOGICAL PRODUCTSBIOLOGICAL PRODUCTS(ERT 455)(ERT 455)

GOOD MANUFACTURING PRACTICES (GMP) GOOD MANUFACTURING PRACTICES (GMP) FOR BIOLOGICAL PRODUCTSFOR BIOLOGICAL PRODUCTS

Munira Mohamed NazariSchool of Bioprocess Engineering

UniMAP

COURSE OUTCOME COURSE OUTCOME (CO3)(CO3)

Ability to FORMULATE and PROPOSE primary/secondary processing, and up-scaling facilities for bio products manufacturing in accordance with Good Manufacturing Practices (GMP)

TOPIC OUTLINETOPIC OUTLINEQuality Management

◦Quality assurance & Quality controlHeating Ventilation and air-

conditioning systemsValidation – biological productsApplication of hazard analysis

and critical control point (HACCP)

INTRODUCTIONINTRODUCTION

GoalGMP

QUALITY CONTROL

SAFETY

&

Pre-requisite program

AspectMS 1514

Certificate scheme

Required to be established before Hazard Analysis and Critical Control Points (HACCP) can be implemented, having GMP certification would definitely pave the way to an easier HACCP implementation and certification.

Assist manufacturers of food products and food related products to provide assurance to their customers that their products are manufactured in a hygienic manner and in accordance to best practices in manufacturing.

Design and facilities in the establishment, control of operations by equipment, temperature, time, pH or water activity control, maintenance and sanitation, personal hygiene, personnel training, transportation, conveyors, product information and consumer awareness

Standard for prescribing the requirements of pre-requisite programs which is required to be established before the implementation of HACCP. Applicable to all food manufacturers, primary and secondary processors, food catering and service operators, food retailers and food related industries

GMP is a sanitary and processing requirement applicable to all food processing establishments. Many food industry companies have implemented the GMP certification scheme for food processing as the foundation upon which they have developed and implemented other food quality assurance systems and food safety management systems, such as HACCP, SQF 2000, ISO 9001 and ISO 22000.

Certifying your food management system against the GMP standard will bring the following benefits:

Enhancement of your food safety management system; Demonstration of your commitment to producing and trading safe food; Prepare you for HACCP certification; Increase in consumer confidence in your products; and Prepare you for inspection by regulatory authorities and other stakeholders (food processing regulation compliant)

GMP Certification Scheme For Food Processing

GMP Basic RequirementGMP Basic RequirementWhat is GMP ?• Part of Quality Assurance (QA) which

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

GMP Basic RequirementGMP Basic Requirement◦Engineering for cGMP:

those activities performed throughout the project life-cycle, which ensures that it will be easy and natural to operate the completed facility in accordance with current Good Manufacturing Practice.

◦Project Life-Cycle means from project inception through feasibility

studies/ conceptual design, engineering, construction, installation, start-up, operation, maintenance to final plant decommissioning or modification.

1) Process issues- closed or open (piping and equipment, expose to environment- measure to prevent contamination)- level of batch to batch integrity required (simultaneous filling

self-emptying vessels, or cleaning, or drying, sterilization between batches?)

2) Layout issues - site location and layout – existing site, brown and green field, and overall site layout - facility layout – cored vs. linear layout, segregation of areas, environment, containment strategy, security etc.

GMP Design requirementsGMP Design requirements

3) Automation Strategy issues- level of technology, use of design tools and models

- availability / redundancy, modularization / expansion

- instrumentation / cabling / field devices

- paperless batch records, electronic signatures.

4) Flow issues- people (security, access, occupancy level)

- equipment (mobile or fixed, use of hard piping, cross-

contamination)

- components / materials (materials handling systems, cross-

contamination / mix-ups)

GMP Design requirementsGMP Design requirements

5) Regulatory issues- stage of development and production, category of the product (sterile medical, biological medical, herbal medicinal, medical gases, liquid, creams, tablets etc) and production process employed, facility location etc.

6) Validation Strategy issues- validation required, validation team(s), validation plan(s).

GMP Design requirementsGMP Design requirements

Categories suggested for guidanceCategories suggested for guidance1) Facilities and environment

2) Services and utilities

3) Personnel flows

4) Material flows

5) Equipment flows

6) Equipment design

7) Computerized systems

8) Maintenance and services

9) Waste management

10) Procedure and documentation

Wh

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QUALITY QUALITY MANAGEMENTMANAGEMENT

QUALITY MANAGEMENTQUALITY MANAGEMENTTo understand key issues in quality

assurance/ good manufacturing practices/quality control.

To understand specific requirements on quality management and quality assurance including:

Organization Procedures, processes and resources.

Ob

jecti

ves

QUALITY MANAGEMENTQUALITY MANAGEMENTDefining the overall policy of the organization towards quality, is over everything else.

Concept that ensures the policy is achieved.

Part of quality assurance. It deals with the risks that cannot be tested. It builds quality into the product.

It is that part of GMP that is focused on testing of the environment and facilities, as well as the testing of the materials, components and product in accordance with the standard.

QUALITY MANAGEMENTQUALITY MANAGEMENTWhat is Quality Management?

◦ Is defined as the aspect of management function that determines and implements the quality policy.

◦ The quality policy is a statement by the top management of the company of its overall intentions and direction relating to quality, formally expressed as a corporate policy. The top management of a company usually includes the board of directors or general manager of the company, the plant or factory managers together with the senior managers.P

hilo

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QUALITY MANAGEMENTQUALITY MANAGEMENTThe basic elements are:

◦An appropriate infrastructure or “quality system” encompassing the organization structure, procedures, processes and resources.

◦The systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for “Quality”

Ph

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The totality of these actions is termed “Quality Assurance”

QUALITY MANAGEMENTQUALITY MANAGEMENTQuality assurance is a management

tool.In contractual situations, it also

serves to generate confidence in a supplier.

QA, GMP and Quality Control are interrelated aspects of Quality Management.◦ They are described on the following slides in

order to emphasize their relationship and their fundamental importance to the production and control of pharmaceutical products.

Qu

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anag

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QUALITY MANAGEMENTQUALITY MANAGEMENTWide-ranging concept

◦covers all matters that individually or collectively influence the quality of a product.

Totality of the arrangements◦to ensure that the drug is of the right

quality for the intended use.Quality Assurance incorporates GMP

◦and also product design and development which is outside the scope of this moduleP

rin

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of

Qu

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ss

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nc

e (

QA

)

QUALITY MANAGEMENTQUALITY MANAGEMENTQA System should ensure:Products are designed and developed

correctly. Complying with, e.g. GMP, GCP, GLP

Production and control operations are defined.

Managerial responsibilities are defined In job descriptions

The manufacture, supply and use of correct starting and packaging materials.

GMP – Good Manufacturing PracticeGCP – Good Clinical Practice

GLP – Good Laboratory Practice

Qu

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QA

)

QUALITY MANAGEMENTQUALITY MANAGEMENTQA System should ensure (cont...):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 Qu

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QA

)

QUALITY MANAGEMENTQUALITY MANAGEMENTQA System should ensure (cont...):

Procedures for self-inspection and/or quality audits

Reporting, investigation and recording of deviations

System for change control/approvalRegular evaluation of product quality to

verify consistency and continued improvement Q

ual

ity

Ass

ura

nce

(Q

A)

QUALITY MANAGEMENTQUALITY MANAGEMENTManufacturer is responsible for the quality of

the product.Fit for intended useComply with marketing authorizationSafety, efficacy and quality

Senior management and commitment of all staff.

Requires a comprehensively designed and well implemented QA system.

Fully documented, and effectiveness monitored.

Competent personnel, sufficient premises, equipment and facilities.

Qu

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ssu

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ce (

QA

)

QUALITY MANAGEMENTQUALITY MANAGEMENTIs the part of QA that ensures that

products are consistently produced and controlled.

Quality standardsMarketing authorization

Aim: Diminishing risks that cannot be fully controlled by testing of the final product.

Cross-contamination

Go

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(G

MP

)

This risk can best be controlled by having a properly managed system of working that takes them into account. This means that there must be good design, and planned maintenance of facilities. The quality checking system also must be designed with this risk in mind and set out to find whether any errors have occurred. If we do not know what sort of cross contamination we have, then the work of the analyst is very difficult. The analyst should ideally know what to test for before commencing testing. In other words, if we do not know what the likely cross-contaminant is, then we cannot analyse for it.

EXAMPLE

QUALITY MANAGEMENTQUALITY MANAGEMENTBasic Requirements for GMP.

◦Clearly defined and systematically reviewed processes.

Batch documentationQuality specification Standard of Procedures (SOP)

◦Qualification and validation is performed.◦Appropriate resources are provided:Qualified and trained personnel Premises, space, equipment and services Materials, containers, labels Procedures, storage, transportLaboratories and in-process control

Go

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(G

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QUALITY MANAGEMENTQUALITY MANAGEMENTBasic Requirements for GMP. (cont..)

Clear, written instructions and proceduresTrained operators to carry out the

procedures correctly.Records of actions, deviations and

investigationsRecords for manufacture and distributionProper storage and distribution of the

products minimizes any risk to their quality.

Systems for complaints and recalls from sale or supply.

Go

od

Man

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(G

MP

)

QUALITY MANAGEMENTQUALITY MANAGEMENT

Focused on testing of the environment and facilities, as well as the testing of the materials, components and product in accordance with the standard.

Qu

alit

y C

on

tro

l (Q

C)

QUALITY MANAGEMENTQUALITY MANAGEMENT

QUALITY MANAGEMENTQUALITY MANAGEMENTWorld Health Organization, Basic

Principles of GMP, Module 2, January 2006

Quality Assurance of Pharmaceuticals, Volume 2, Good Manufacturing Practices and Inspection. World Health Organization. 2007R

efe

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HEATING VENTILATION HEATING VENTILATION AND AIR-CONDITIONING AND AIR-CONDITIONING

SYSTEMS SYSTEMS