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GOOD MANUFACTURING PRACTICE

ASPECTS OF GMP

PUTRI HASANAH RAHMIN

0811012051

FACULTY OF PHARMACY

ANDALAS UNIVERSITY

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GMPs are part of the qualityassurance activities that ensure thatproducts are consistently produced

and controlled to the qualitystandards appropriate to theirintended use and required by the

drug regulatory authorities.

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Aspects of GMP

GMP guidelines in

accordance with the POMcovers 12 aspects:

1. quality management

2. personnel

3. premises and facilities

4. equipment

5. sanitation and hygiene

6. production

7) quality control

8) self-inspections andquality audits

9) handling of productcomplaints and productrecalls and productreturns,

10) documentation

11) making and analysisbased on contract

12) qualification andvalidation

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1. QUALITY MANAGEMENT

The pharmaceutical industry must be able to make

drugs to suit the intended use, meets therequirements specified in the authorizationdocument and does not pose risks that endangerusers. There is a need for quality management to

achieve consistent quality thoroughly designed andimplemented correctly.

Basic elements of quality management are: Anappropriate quality system includes organizational

structure, procedures, processes and resources.

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Systematic actions necessary toobtain assurance with a high levelof confidence, so that products (orservices) generated always meet

predefined requirements. Theentire action is called the Qualityassurance.

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In the aspect of quality management areimportant matters, namely:

Quality assurance (QA)

Quality assurance is the totality of all

measurements are made with a view to ensuringthat the drug is produced with quality inaccordance with the purpose of use.

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GoodManufacturing Practice (GMP)

Part of quality assurance which ensures that thedrug created and consistently to achieve thedesired quality standards appropriate to the

intended use and as required in the marketingauthorization and product specifications. GMPcovers all production and quality control.

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Continue Quality control (QC)

Part of the GMP are associated withsampling, specifications and the necessaryand relevant tests have been performed andthe materials that have not been released isnot used as well as products not yet releasedcan not be sold or supplied before theirquality assessed and found to qualify.Function / agency should be independent ofother parts.

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Assessment of product quality

Assessment of quality of productsmade periodically to all registered drug,including export products to prove theconsistency of the process, the suitability ofthe specifications for starting materials,packaging materials and finished drug, to see

trends and identify where improvement isusually done every year and documented,taking into account previous review .

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2. PERSONNEL

The number of employees in all parts should havesufficient knowledge, skills and abilities in

accordance with their fields, have mental andphysical health is good so that they can do their

job professionally and properly, and to have theattitude and awareness to carry out the

appropriate high-GMP.

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Things that need to be considered in thisaspect are:

Organization, qualification andresponsibility

The production and quality control within theorganizational structure of the pharmaceuticalcompany led by a different pharmacist responsibilityand authority to both sections is clear. Each part wasgiven full authority and adequate facilities to carry outtheir duties effectively and efficiently. Both parts maynot have other interests outside the factory

organization, so as to inhibit, limit the liability sectionand cause personal or financial conflict of interestInaddition, a production manager and quality controlshould be a pharmacist skilled,

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Training

Training given to all employees, whether relateddirectly to the process of drug production or not.Employees are trained on an activity in

accordance with their duties and the principlesofGMP. The training given by experts.Particular attention in the training given to those

who work in the room sterile and for those whowork using materials that have a high risk ofdangerous, toxic, sensitizing.

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Exercise of the GMP must be done

continuously and with sufficientfrequency to ensure that employeesunderstand and fully understand the

requirements ofGMP-related dutiesTraining on GMP implementedaccording to a written program that

has been approved by the productionmanager and manager oversight.

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3. BUILDINGS AND FACILITIES Building for the manufacture of the drug has the

size, design, construction and location sufficient

to facilitate the implementation of the work,cleaning and maintenance is good. Means ofadequate work is necessary to minimize the riskof error, cross contamination and various other

errors that can degrade the quality of the drugcan be avoided and controlled.

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Terms of buildings and facilities accordingto GMP are as follows:

-- Location of buildings designed to preventpollution of the surrounding environment,such as pollution of air, soil and water.

-- The building is designed and maintainedto protect them from the influence ofweather, flood, seepage through the soil aswell as incoming and animal breeding.

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Necessary considerations in determining thedesign and building layout is as follows:

1) Compliance with other activities, which maybe done in the same facility or in an adjoiningfacility.

2) The layout of the space in such a way as toallow production activities can be conductedeffectively and efficiently.

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The division of the class room made for separateroom inside the production buildings, such as

locker rooms, indoor raw material productionand processing room.

Availability of storage facilities with specialconditions, for example: temperature, humidityand certain security.

Making sewerage should be large enough andhave good control boxes.

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4. EQUIPMENT

Equipment used in the manufacture of

drugs has design and proper construction,of adequate size and appropriately placed,so the quality is designed for each drugproduct occurred uniformly from batch tobatch as well as to facilitate cleaning andequipment.

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Terms ofGMP equipment specified are as follows:D

esign and

co

nstructio

n1) The equipment used should not react or causedue to the material processed.

2) Equipment can be cleaned easily both insideand outside as well as the equipment may not causean adverse effect on the product.

3) All equipment used in processing chemicalsare flammable, or placed in areas where flammablematerials are used, should fitted with explosive-

proof electrical equipment and properly grounded.4) Equipment used for weighing, measuring,

testing and record should be calibrated according toa program and the proper procedures.

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Installation and placement

1) Installation and equipment placementarranged so that production processes canbe run effectively and efficiently.

2) Channels of water, steam, compressed airor vacuum should be installed such that iteasily reached during the activity takes

place.3) Each major equipment should be given aclear identification number.

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4) All pipe, tanks, steam pipe or pipe casingcooling should be good insulation to prevent anypossible defects and minimize energy loss.

5) The system-support systems such asheating systems, ventilation, air conditioning,drinking water, water purity, water distillationand other facilities should be validated to ensure

that the systems always function in accordancewith the objectives.

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Maintenance

1) Equipment maintained according toappropriate schedule to keep it functioningproperly and prevent pollution that can changethe identity, quality or purity of the product.

2) written procedures for maintenance ofequipment made and adhered to.

3) Notes on the implementation ofmaintenance and use of major equipment are

recorded in a logbookNote to equipment usedexclusively for one product can be put into batchproduction record of a particular product.

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5. SANITATION AND HIGIENI

Sanitation and hygiene levels are high is applied

to every aspect of drug manufacturing. Thescope of sanitation and hygiene coverspersonnel, premises, equipment and supplies, as

well as container production, and every thing

can be a source of productcontaminationSources of pollution should beeliminated through a program of sanitation andhygiene comprehensive and integrated.

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a. Personnel

1) All employees undergo health checks before andduring work, and regular eye examinations.

2) All employees applying good personal hygiene.

3) Each employee who suffered from a disease that

can harm the quality of products prohibited fromdealing with the materials to recover.

4) All employees are to report things that can harmthe product.

5) Use gloves to avoid direct contact between thehand with the materials and products.

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6) Employees use protective clothing for its ownsecurity.

7) Only authorized personnel are allowed to enterrestricted areas of buildings and facilities.

8) Employees are instructed to wash their handsbefore entering production areas.

9) Smoking, eating, and drinking are prohibited inproduction areas, laboratories, and other areasthat can harm the product.

10) The procedure is applied to everyoneindividually.

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b. Buildings and facilities

1) The building was designed and constructed appropriatelyto facilitate the implementation of improved sanitation.

2) Toilet with good ventilation is provided with enough.3) adequate storage for clothes.

4) The washing is placed outside the sterile area. Wheneverpossible should be equipped with a good system.

5) Storage, preparation and consumption of food isrestricted in specific areas and meet hygiene standards.

6) Waste must not be allowed to accumulate and collected in

appropriate containers.7) Rodenticides, insecticides, fumigation materials, and

cleaning materials must not contaminate equipment andmaterials.

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c. Cleaning and Equipment

1) Equipment is cleaned, maintained and stored in aclean condition and checked for cleanliness beforeuse.

2) Cleaning is done by vacuum or wet, and wherepossible avoid product contamination.

3) Cleaning and storage of tools and cleaningmaterials performed in a room separate from theprocessing.

4) written procedures for cleaning and sanitationmade complied with and implemented.

5) Note the cleaning, sanitation, sterilization, and theinspection itself is stored.

Validation of cleaning and sanitation procedures

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6. PRODUCTION

Production carried out with establishedprocedures which always can assure drugproducts that meet defined specifications.

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The starting material

1. All income, expenses, and the rest of the recordedmaterial, including a description of the inventory.

2. Each of the starting materials meet specificationsand should be labeled with the name stated in thespecifications.

3. For each batch of shipment and given a referencenumber that shows a clear identity.

4. At the time of receipt of goods carried out a visualinspection, and samples taken from the officer,

were tested against the specifications of thematerial in question.

5. Post a starting material is quarantined untilapproved and released for use.

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6. The label placed by officers appointed by the party

responsible for quality control.7. Beginning inventory is checked once in a while.8. Starting materials that are unstable by the influence

of temperature, stored in a temperature regulated.

9. The starting materials which tend to be damaged instorage potential stated age limit.10. Expenditure early material performed by authorized

personnel.11. Availability of delivery of the remaining areas to

prevent cross-contamination.12. All starting materials that do not qualify are marked

cross, stored separately and immediately destroyedor returned to suppliers.

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Validation Process

1) All production processes are validated with theappropriate and implemented correctlyaccording to procedures that have beendetermined and the result is stored.

2) Before a parent applied processing steps shouldbe done to prove the compatibility with theimplementation of the production.

3) Changes in equipment or material accompanied

by re-validation action.

4) Processes and procedures are critically re-evaluated regularly.

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Contamination Chemical or microbial contamination to a drug

that can harm health or reduce the therapeuticor affect the quality of a product, can not beaccepted.

Batch

and

lo

t numbering system1) The numbering system described in detail2) numbering system is intertwined with the

products made.

3) The numbering system used to ensure that thenumbers are not repeated and facilitate themarking of a product if anything happens.

4) Giving the number recorded in a diary.

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Weighing andDelivery

1) Method of handling, weighing, calculation anddelivery of materials and products covered by

written procedures.

2) All expenditures of materials and products aredocumented.

3) Materials and products that may be submitted

only that have been passed by the quality control.4) Prior to the weighing is carried out checks on the

marking.

5) capacity, accuracy, and precision scales

according to the amount of material.

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ContinuE

6) At each weighing, measurements weremade documenting the accuracy of the identity andamount of material.

7) Hygiene and weighing the delivery is maintained.

8) Penimbangan dan penyerahan menggunakanperalatan yang cocok dan bersih. Weighing and

delivery using appropriate equipment and clean.

9) Raw materials delivered product be re-examined tominimize the risk of misuse and errors of rawmaterials to be produced

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Return

All materials early, packaging materials,intermediate products and bulk products

are returned to the warehouse is a productthat meets predetermined specificationsand documented properly anddirekonsilasi.

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Processing

1) All materials used are checked first.

2) The condition is monitored and controlledprocessing area.

3) The equipment used is checked first.

4) All processing activities follow writtenprocedures that have been determined and

reported irregularities with the excuses andexplanations.

5) The container and cover materials and cleanproduct.

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ContinuE6) All containers and equipment containing

materials and products be labeled appropriately.

7) All products are labeled right and quarantined

until released by the quality control.

8) The whole monitoring process should berecorded and investigated.

9) The results are recorded and matched the realview of the theoretical results.

10) In all stages of processing, consider theproblem of cross contamination.

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Materials anddried products

1) Material and dry products, handling a problem ofdust, and therefore need to be mounted vacuumsystem to prevent the spread of dust.

2) The mixing and granulation. Mixing machine,sieving and stirrer equipped with a dust controlsystem. And operational parameters are listed in

the Master Production Documents..

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ContinuE

3) Printing tablets. Machines equipped withadequate facilities, conducted a physical control,procedural and tagging.

4) Coating. Using a spray device that worksautomatically and has validated the power spray.

5) Charging hard capsules, empty capsules as astarting material, kept in good condition.

6) Marking coated tablets and capsules should beclear and understandable.

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7. QUALITY CONTROL

Quality control is an essential part ofGMP that anyof the drugs are designed to meet the quality

requirements set. Main tasks include thepreparation of quality control procedures,preparation, instruction, sampling plan, passed orrejected materials and products, examined the

record before the product is distributed, settingexpiration date, re-evaluate the test, approve theappointment of suppliers, evaluate the complaint.

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In the quality control of the things that need to beconsidered include:

How to berlaboratorium good quality control Laboratory testing includes the buildings and

tools supporting full and adequate, trained andresponsible personnel, equipment instrumentsand procedures that are suitable for periodiccalibration, reagents and culture media inaccordance with the monograph in question,specifications and testing procedures are

validated with the facilities used , recordsconcerning all aspects of testing required andthe remaining stored samples used insubsequent testing.

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Monitoring of the starting materials,

intermediate products, bulk product, andfinished drug

That must be considered in this regard is thespecification, the way sampling, testing of raw

materials, packaging, intermediates, bulk andfinished drug products, sterilization tests forsterile products, test pirogenitas and periodicenvironmental monitoring of chemical and

microbiological quality of water and productionenvironment.

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Documentation

Important documentation relating to qualitycontrol, which contains: specification, samplingprocedures, recording procedures and testing(including analysis worksheet and / or

laboratory notebooks), reports and / orcertificate of analysis / environmentalmonitoring data (if necessary), record validationmethods of analysis (when necessary),

procedures and instrument calibration recordsand maintenance equipment.

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Sampling

Sampling is an important activity of the qualityassurance system. Personnel who take samplesmust obtain initial training and periodic training.

Sampling was carried out on starting materialsand packaging materials. The number of samplestaken should be determined statistically andspecified in the pattern of sampling. Samplingactivities conducted in such a way as to preventcontamination or other effects that affect quality.

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Testing requirements Tests carried out on starting materials,

packaging materials, intermediate products,bulk products and finished products inaccordance with established specifications.

Control over the environment should be made asfollows: monitoring of water for the process bedone periodically, microbiological monitoringperformed in a production environment on aregular basis, monitoring the environment

around the production area to detect otherproducts that may contaminate the productsmade at regular intervals, and control of aircontaminant.

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All process controls carried out according tomethods approved by the Quality Supervision andthe results recorded. After a storage time limit forstarting materials, intermediate products, bulk

products and finished products is carried outretesting.

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Conducted additional testing of materials infinished products of reprocessing. Qualitycontrol procedures to participate in making theprocessing stem and stem packing procedures.

Stability studies designed to determine thestability of the product, and the program isadhered to and including the number, storageconditions, and testing methods. Stability

studies conducted on new products, newpackaging, changes to the formula and the batchreleased.

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8. SELF INSPECTION AND AUDIT

QUALITY

The goal is self-inspections to assess whether allaspects of production and quality control always

meet GMP.The things to note are: Things that are inspected include employees,buildings, storage, starting materials andfinished drug medication, equipment,

production, quality control, documentation,maintenance of buildings and equipment.

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Audit quality is useful as a complement of self-

inspections, including examination andassessment of all or part of the qualitymanagement system with specific objectives toimprove the quality generally conducted by

outside or independent specialists or specialteams.

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9.Against Handling Products, Product

Recalls and Product Returns

Withdrawal of the drug to be drawing back one

or several batches. This is done when there areproducts that cause side effects or other medicalproblems related to physical, allergic reactions,toxic effects. Handling complaints and reports

should be recorded and immediately addressedlater conducted research and evaluation.

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Drugs change can be classified as follows: that stillmeets the specifications that can be used, whichcan be reprocessed and that can not be

reprocessed. The procedure returns include the number of drug

treatment, quarantine, research, treatment andrecovery, inspection and thorough quality control.

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10. DOCUMENTATION

Documentation is part of the drug manufacturing

and management information system that includesspecification of raw materials, packaging materials,intermediate products, bulk and finished drugproducts, document production, document quality

control, storage and distribution of documents,documents in the maintenance,

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11. Preparation and Analysis Based

on Contract

Done to avoid misunderstandings that can lead

or work with a quality product that is notsatisfactory.Written contract between the giverand the recipient of the contract must bemade clearly define the responsibilities andobligations of each party.

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12.QUALIFICATION AND VALIDATION

Planning validation

All validation activities should be planned inadvance and documented as a brief, precise andclear in VMP (Validation Master Plan). VMP atleast include: policy validation; organizational

structure validation activities; summary of facilities,systems, equipment and processes to be validated;

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Documentation

Written validation protocol was made to specifythe qualification and validation to be performed,as well as detailing the critical steps and

acceptance criteria.Protocols should be reviewedand approved by the Head of QA.

The report must be made referring to thequalification protocols and / or validation

protocols that include all the results obtained andthe deviations that occur and the improvementsmade and documented.

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Qualification

1) Design Qualification (DQ) Is the first element in validating the facilities,

systems or new equipment.

2) Installation Qualification (IQ)

Made to the facilities, systems and new ormodified equipment. Minimum requirements forIQ were: equipment installation, piping andsupport facilities and instruments according to

specifications and engineering drawings aredesigned;

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3) Qualification Oprasional (QO) QO can be performed after RIC. QO minimum include:

the testing of processes, systems and equipment, andtesting that includes one or several conditions that includeupper and lower limits oprasional.QO formal settlementinclude: calibration, procedures, pengoprasian andcleaning, the selection operator and preventivemaintenance.

4) Performance Qualification (PQ) PQ carried out after the QO finish, although in some cases

families are united by knockout.PQ minimum include:Tests using raw materials, substitute materials that meet

specifications or products conducted simulations based onknowledge about the processes, facilities, systems andequipment,

5) Qualifying facilities, equipment and systems thathave been installed oprasional

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Validation process

Thera are 3 ways to do validation process:

1) Validation prospektif

Validation prosecess before product are sell.

2) Validation konkuren

Validation process at process production.

3) Validation retrospektif

Validation are done at after process before (frondata before). This Validationcan not use ifchange formula, tools dan prosedure

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THANK YOU