INTRODUCTION - Product Catalog - Parenteral Drug … · . ... Introduction 5 Batch documentation...
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INTRODUCTION The drug manufacturer needs to ensure that all methods of production, as far as they are part of a registered procedure, are carried out in agreement with the specifications of a product licence approved by the licensing authorities. The manufacturer must carry out regular checks of the manufacturing process, considering research and technical progress. Should changes occur in the registered procedures, these changes are to be presented to the appropriate authorities. For this reason it is important that an efficient and well-functioning Quality Assurance (QA) system is introduced and operated. QA covers all the points that could influence the quality of a product. Consequently, measures must be met and defined to enable the required drug quality to be achieved. Because of the existing connections between QA, Quality Control (QC) and Good Manufacturing Practice (GMP), QA begins in pharmaceutical research and accompanies the process through development, retailing and use of the final product; therefore, also including Good Development Practice (GDP), Good Clinical Practice (GCP), GMP, Good Storage Practice (GSP), Good Distribution Practice (GDP) and further components. Apart from other factors, QA ensures that the range of responsibility on management level is clearly fixed, and that employees are regularly trained to be kept up-to-date. Training should include theory and employ QA and GMP. Hygiene programmes must be set-up and followed. Premises and equipment used must be carefully examined and approved. QA demands set standards for the practical execution of qualification and documentation. QA makes regular checks to ensure it is possible to trace back every batch by documentation, that production and Quality Control procedures are specified and that production processes (after foregoing authorised instructions and process descriptions) are carried out in agreement with GMP, and that every manufacturing procedure and every fundamental change in process is validated. Self Inspections are carried out as part ofthe QA system, whereby suggestions can lead to necessary revisions. Storage and terms of distribution for products should be suitable and followed as well as supervised in accordance with GMP regulations. This guarantees that products are produced and examined in compliance with company Quality Standards (QS) and in accordance with the registered documents. www.pda.org/bookstore
Transcript of INTRODUCTION - Product Catalog - Parenteral Drug … · . ... Introduction 5 Batch documentation...
INTRODUCTION
The drug manufacturer needs to ensure that all methods of production, as far as theyare part of a registered procedure, are carried out in agreement with the specificationsof a product licence approved by the licensing authorities. The manufacturer mustcarry out regular checks of the manufacturing process, considering research andtechnical progress. Should changes occur in the registered procedures, these changesare to be presented to the appropriate authorities. For this reason it is important that anefficient and well-functioning Quality Assurance (QA) system is introduced andoperated. QA covers all the points that could influence the quality of a product.Consequently, measures must be met and defined to enable the required drug qualityto be achieved. Because of the existing connections between QA, Quality Control(QC) and Good Manufacturing Practice (GMP), QA begins in pharmaceutical researchand accompanies the process through development, retailing and use of the finalproduct; therefore, also including Good Development Practice (GDP), Good ClinicalPractice (GCP), GMP, Good Storage Practice (GSP), Good Distribution Practice(GDP) and further components.
Apart from other factors, QA ensures that the range of responsibility onmanagement level is clearly fixed, and that employees are regularly trained to be keptup-to-date. Training should include theory and employ QA and GMP. Hygieneprogrammes must be set-up and followed. Premises and equipment used must becarefully examined and approved. QA demands set standards for the practicalexecution of qualification and documentation. QA makes regular checks to ensure itis possible to trace back every batch by documentation, that production and QualityControl procedures are specified and that production processes (after foregoingauthorised instructions and process descriptions) are carried out in agreement withGMP, and that every manufacturing procedure and every fundamental change inprocess is validated. Self Inspections are carried out as part ofthe QA system, wherebysuggestions can lead to necessary revisions. Storage and terms of distribution forproducts should be suitable and followed as well as supervised in accordance withGMP regulations. This guarantees that products are produced and examined incompliance with company Quality Standards (QS) and in accordance with theregistered documents.
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2 Quality Assurance Workbook for Pharmaceutical Manufacturers
QA also works to establish a system for produced batches to be recalled fromdelivery or sales, when necessary, so that complaints can be checked and suitablemeasures taken to prevent re-occurrence. Figure I illustrates how closely QA is linkedwith GMP and, with that, QC and production.
Figure 1 Interrelationship between QA, QC and Pharmaceutical Production
QA covers a wide range of measures in which GMP specifically represents thesections that guarantee products are produced and examined within constant QS. GMPGuidelines clearly assign responsibilities to pharmaceutical production and QC.General measures are assigned to the responsibility of QA (Fig. I).
Pharmaceutical production guarantees that a stable and repetitive product qualityis maintained. QC is the part of GMP that deals with specimen tests, specification andexaminations as well as organisation, documentation and release procedures.
QA also includes all general measures necessary to enable suitable standards ofproduction to be maintained (suitable premises and installations, documentationsystems, pre- and post-audit preparations, self-inspections, etc.). QA is, therefore, theconnecting link between GMP (including Production and QC) and all generalmeasures.
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Introduction 3
Principles and Duties of Production
Production processes must follow clearly defined methods of procedure. Productionshould be implemented and supervised by competent and experienced personnel.These personnel are responsible for ensuring:
GMP regulations are followed
Cross-examination is avoided
Production and fitted equipment (including computer systems) are validated
Appropriate basic substances are used
Intermediate products and stock supply are correctly processed
Suitable packaging material is used
Appropriate packaging procedures are applied
Finished products are kept in quarantine until released
. Rejected, recycled and returned stock is identified
(
Principles and Duties of Quality Control
QC deals with independent Quality Assessments of materials and stock based on the(mainly analytical) judgement taken, and/or the examination of submitted documentsthat have been presented. QC is not limited to laboratory work, but is also involved inall decisions which influence product quality.
QC should be organised and established independently from production (SeeSection 1, Fig. 4). The principle duties of QC ensure that:
The requirements of Good Laboratory Practice (GLP) are followed
Every procedure is sufficiently recorded
Tests are set up and carried out
Suitable (analytical) methods for product examination are used
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4 Quality Assurance Workbook for Pharmaceutical Manufacturers
Moreover, the Quality Control Manager (Qualified Person [QP]) monitors therelease of stocks, intermediates, and final products throughout the process.
Principlesand Duties of Quality Assurance
Having defined the principles and duties of pharmaceutical production and QC inaccordance with the European Community (EC) Manual of Good ManufacturingPractice for Drugs, the following assignments ensure a thorough QA system incooperation with pharmaceutical production and QC management is achieved:
Personnel
Organisation schemesTrainingHygiene requirementsStaff in key positionsJob description
..Premises and Equipment
Definition of requirementsDefinition of production, warehouse and additional areasEquipment.
Quality Management system
. Definition of general requirementsSpecificationsDocumentationManufacturing and inspection protocolsStorage and retrievalOrganisation of the Quality Manual (QM)
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.Contract Manufacturing and Inspection
Drug contract manufacturing contracts to be defined, agreed upon andcontrolled
Confidentiality agreementsEstablishing responsibility between customer and contractorResponsibility and delimitation requirementsManufacturing requirements (Technology Transfer)Analytical requirements (Analytical Methods Transfer)
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Introduction 5
Batch documentation
Manufacturing according to registered procedures
Complaints and Product Returns
Dealing with, and settling complaints
Self- Inspections
Introduction, coordination and pursuit of steps for corrective actionsLooking after and dealing with internal and external audits
Quality Management, Quality Assurance and Quality Control
The following example shows how closely Quality Management (QM), QA and QCare associated (Fig. 2):
Figure 2 Model of a Quality Management System
Quality Assurance
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6 Quality Assurance Workbook for Pharmaceutical Manufacturers
The Production department (Production) is in the centre of the QualityManagement (QM) system. The quality of the production process is monitored byoperators and in-process control (IPe) environmental monitoring, and controlled byindependent persons (Quality Control) for final examination. The next operating stageis Quality Assurance. Using appropriate means and methods it is determined whether:
The Production and QC departments function according to GMP requirements
Ample measures have been taken and, in a suitable manner, applied
. Laws and International Agreements have been observed
An adequate document handling system exists
The safety of patients and personnel is guaranteed
Personnel involved are sufficiently trained, etc.
Finally, GMP checks and assures that the required product quality is achieved andthe safety of the patient is guaranteed.
Once the decision has been taken to incorporate a QM system, and implement anin-process control (IPe) and release, differences in viewpoints between the UnitedStates (US) and Europe are important points to consider. The Food and DrugAdministration (FDA) regards QA and QC as a single unit; the division of tasks andindependence from one another appears to be of little importance. In contrast to thisthe EMEA (European Agency for the Evaluation of Medicinal Products) understandsthat the QA unit is a staff position independent from QC and directly responsible tothe Management. This is layed down in Pharmaceutical Inspection Convention(Ple)-GMP Guidelines.
From the customers point of view a QM system should guarantee that the productrequirements are realised and that the product is manufactured and distributed so as tosatisfy the customer. Customer complaints should be incorporated in a continuousimprovement of the QM system thus enhancing product quality and resourcemanagement.
General Management is involved in a prominent position to support continuousimprovement ofQM system. The cycle of continuous improvement of the QM systemis depicted in Figure 3.
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Introduction 7
Figure 3 Process Oriented QuaLity Management System
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