Presentation on theme: "World Health Organization"— Presentation transcript:
1 World Health Organization 15 April, 2017Basic Principles of GMPPersonnelCompanies can make investments and buy facilities and equipment. However, the greatest resource that a company has is its personnel. But human resources also need a lot of attention. If a company does not have correctly educated, trained and motivated people working in its factory or laboratory, it is necessary to provide training in order to overcome any inherent weaknesses and to build upon existing strengths.This module will consist of:Presentation - general issues 30 minutesGroup session minutesPlenary feedback minutesPresentation - specific issues minutesPlenary feedback minutesTest minutesExact times will need to be worked out when details of participant numbers and experience are known. The module should be tailored to run between 1/2 and 1 day.9
2 World Health Organization PersonnelWorld Health Organization15 April, 2017ObjectivesTo review general issues related to personnelTo review requirements for key personnelTo review the training of personnelTo consider some specific issuesThere are four objectives for this session:1. We are going to start by looking at the principles and general issues around personnel such as the personnel policies and practices.2. We will look at the responsibilities of certain key personnel in the organization.3. We will review continuous training of personnel.4. We will look at the specific issues that are likely to arise during your inspection visits.
3 World Health Organization Personnel15 April, 2017PrincipleEstablishment and maintenance of satisfactory system of QA, manufacture and control of products and actives rely on people.Must be sufficient qualified personnel to carry out tasksIndividual responsibilities must be clearly defined and understood by individuals concernedWritten job descriptionsAll personnel should be aware of the principles of GMP that affect themThe principle that companies should apply to their people has a number of key features.The personnel is the most important asset of a company, and the easiest to neglect. The establishment and maintenance of a satisfactory system of quality assurance and GMP relies upon people who develop the system, the people who use the system and the people who examine the system to see if it has worked. People are involved, no matter how automated the process or how capital intensive the operation. The behaviour of the people is fundamental to any system of GMP. Personnel policies must reflect this. In our first group session we will be looking at those policies that encourage compliance with GMP.Sufficient number of staff must be available to carry out the work for which the manufacturer is responsible. These people must have the level of training and experience that will enable them to do their work.The staff must have written job descriptions to ensure that they understand clearly what it is that they have to do, and what they are responsible for.Finally these staff must have a knowledge and understanding of GMP to enable them to carry out their duties in accordance with GMP.Let us now look at these areas in more detail.9.1
4 World Health Organization Personnel15 April, 2017General (1)Personnel requirements:Adequate number of personsWith necessary qualificationsWith practical experienceAn individual’s responsibilities should not be so extensive as to present a risk to qualityFor successful and good quality pharmaceutical production, it is essential to have people with sufficient knowledge and experience to undertake the work. They must have the authority and the means to do that work, and there must be enough of them available to carry out tasks effectively.It is most important that the people that are recruited are selected from a group that can meet the requirements. It is not recommended to recruit people to work in manufacturing areas if they are unable to read the instructions for their safety and for product quality. A medical examination should be included during the recruitment processes. Operators working with cytotoxic products may need blood tests at the time of recruitment and at six monthly intervals thereafter. Operators who will work on visual inspection processes should also undertake an eye test at the time of recruitment with a regular check on a periodic basis afterwards.A major and most common problem is that of insufficient people available to do the work. It is of little value having just one person well qualified and experienced, with no backup staff. What then happens in the case of sickness or holiday? This can be a very difficult area, and one which is harder for smaller companies than a multinational company or similar.Another issue that often surfaces is the employment of a well qualified, but inexperienced, person to manage, for example, quality. An illustration of this is the recruitment by the owner of a small company of a relative -- niece or nephew for example -- who is newly qualified, but completely inexperienced to run a laboratory or manufacturing area.The duties incumbent upon any one individual should not be so extensive that he/she cannot cope, resulting in a risk to quality of the product.In our second group session we will be looking at the experiences of bad practice and examining strategies to overcome them.9.2
5 World Health Organization Personnel15 April, 2017General (2)All responsible staff should have specific duties recorded in individual written job descriptionsHave adequate authority to carry out responsibilitiesMay delegate to designated deputies with qualificationsNo gaps or unexplained overlapsOrganization chartStaff must have a clear job description which tells them and the rest of the company what their role is, what their responsibilities are and what authority they have to carry out their tasks. The company should also have a written organization chart. The combination of organization chart and written job descriptions enables the company to see quickly whether there are any gaps or whether there are any areas of overlap, owing to too many people being involved. The organisation chart should make clear and ensure the independence of QA/QC from production.Personnel involved in QA/QC must have the authority to carry out their responsibilities. This is very easy to say and sometimes not so easy to ensure. Problems can emerge in every size of company, from small private companies to very large multinational enterprises. They arise because of a combination of human interactions, and the pressures placed on people by the business considerations.9.3
6 Basic Principles of GMP Organization chartThis is NOT what it should look like
7 World Health Organization Personnel15 April, 2017General (3)All personnel should be aware of GMPMust receive training in GMP:initial trainingcontinuing trainingincluding hygiene standardsMotivated tosupport the establishmentmaintain high-quality standardsAll personnel involved with materials and products should receive GMP training. This training should commence upon recruitment and continue throughout employment. The training should be appropriate to their needs and position within the company, and should include training in hygiene standards.Personnel policies should be designed to encourage people to support the development and maintenance of high quality standards in all work performed.9.4
8 World Health Organization Personnel15 April, 2017General (4)Prevent unauthorized accessTo production areasStorage areasQuality controlStop personnel who do not work in these areas using them as passagewaysThe company should prevent people who have not been properly trained from entering any production, storage or quality control area without strict supervision. For example: it should not be the case that people from accounts are allowed to walk through the factory to get to the warehouse to pick up or deliver invoices. Access to all other areas of the company should be organized so that no entry to production, storage or laboratory areas is necessary (see Premises).9.5
9 Basic Principles of GMP World Health Organization15 April, 2017The trainer should explain ways of ensuring access control to areas. Some companies have electronic card systems that allow entry to authorized persons to specific areas, others have a code that has to be entered at the door, etc.Only people authorized to go to areas, should be allowed to enter, wearing appropriate garments. They should have the relevant training before entering the areas. IN some cases, to ensure also better control between different classes of areas, airlocks are used.
10 World Health Organization Personnel15 April, 2017Key Personnel (1)Key personnel (which normally should befull-time) positions include:Authorized personHead of ProductionHead of Quality ControlMay delegate functions – not responsibilityHeads of Production and Quality Control should be independent of each otherWe have dealt with the generalities of an organization so far. We shall now deal with the requirements for certain key people in the organization. Who are these key people?The heads of production, quality control, sales and distribution and the authorized person who releases product for sale are all key people. Normally they should all be full-time positions. The heads of production and quality control should not report to one another (although they may both report to a technical director) but may share certain responsibilities. In large organizations, it may be necessary to delegate some of the functions; however, the responsibility cannot be delegated.We will look in a minute at shared responsibilities. Different countries take a different view of reporting relationships. Legislation in each country differs slightly and, of course, local legislation must be followed. The principle is that there must be independence of quality control from production. These key personnel must have the education and experience which is appropriate to their positions. As we mentioned earlier, difficulties can arise when family members who are recruited and who are inexperienced.9.6
11 World Health Organization Personnel15 April, 2017Key Personnel (2)Should posses appropriate qualificationsScientific education such as:chemistry or biochemistrychemical engineeringmicrobiologypharmaceutical sciences and technologypharmacology and toxicologyphysiology; orother related science subjects relevant to the responsibilities to be undertakenThe WHO GMP text part one, section 9.7 refers to some of the acceptable qualifications of key personnel and it goes into a lot of detail. Key personnel should first of all have the educational background specified by local legislation and with the requirements set out in company policy. This will include a combination of chemistry, biochemistry, chemical engineering, microbiology, pharmaceutical sciences and technology, pharmacology and toxicology, physiology or other related science subjects relevant to the responsibilities to be undertaken.In particular, the GMP text talks about gaining experience not in a haphazard way, but under specific guidance of an expert. This is in order to equip personnel with an ability to take difficult decisions in a professional and scientific way, and to resolve the problems encountered in manufacturing and quality control.It is clear, therefore, that we are talking about professionals who have had a practical as well as an academic training. They should also continue to have training in their area of expertise.There are others who play an important role in the operation of the factory, for example, engineers. Engineers are crucial to the maintenance and operation of the facility and equipment, in particular, for the processes of planned preventative maintenance and validation.9.7
12 World Health Organization Personnel15 April, 2017Key Personnel (3)Should posses appropriate experiencePractical experienceManufacture and quality assurancePreparatory period under professional guidance sometimes neededEducation and experience should enable personnel to take difficult decisions in an independent, professional and scientific wayresolve the problems encountered in manufacturing and QCPersonnel should also posses appropriate experience including practical experience in the manufacture and quality assurance of pharmaceutical products. It is common and recommended, that there should be a preparatory period under professional guidance for new employees.Education and experience should enable personnel to take difficult decisions in an independent, professional and scientific way, and to resolve the problems encountered in manufacturing and QC.9.7
13 World Health Organization Personnel15 April, 2017Shared Responsibilities (1)Heads of Production and Quality Control may share/jointly exercise some responsibilities relating to quality:authorization of written procedures (SOPs) and other documents, including amendmentsmonitoring and control of manufacturing environmentplant hygieneprocess validation and calibrationtraining, including application and principles of QAapproval and monitoring of suppliers and contract acceptorsThe responsibilities shared by the heads of the production and quality control departments are described in the WHO GMP texts. Clear written job descriptions must be available for these positions, showing where the shared responsibilities are.It is sensible that all procedures and documents used in manufacturing are approved by both the production and quality control departments. It is most important that an effective system of change control is implemented. It is essential that as SOPs are changed, all those who use them are given the latest version.Monitoring of the manufacturing environment is a task to be shared between QA/QC and production. These departments should conduct the monitoring and testing as appropriate, with the results made available to all who need to know.Both production and quality control have a role to play in the development and maintenance of an appropriate factory sanitation and hygiene management system.Both have a major contribution to make in the validation of processes and the calibration of equipment.A comprehensive training programme is required for personnel. The production and quality control department have a role to play in the development of the training programme. The heads of these departments, therefore, have a shared responsibility for the implementation of that programme.Approval of all suppliers and contract manufacturers is also an area of shared responsibility, with each contributing his/her own particular expertise9.8
14 World Health Organization Personnel15 April, 2017Shared Responsibilities (2)Designation and monitoring of storage conditions for materials and productsPerforming and evaluating in-process controlsRetention of recordsMonitoring compliance with GMPInspection, investigation, and taking of samples to monitor factors which may affect qualityResponsibility for the designation and monitoring of storage conditions is also shared.Since both have responsibility for the generation of records relevant to batches, then the arrangements for the storage of those records may be a shared responsibility. Alternatively a separate department may be available that manages all aspects of documentation and batch records.Monitoring of compliance with GMP is also a shared responsibility. This has to be correct because the achievement of GMP is everyone's responsibility.Some aspects of inspection, investigation and sampling may be conducted by people other than QC to monitor factors that affect quality of the products. Sampling should only be done by persons trained in the methods to be used.9.8
15 World Health Organization Personnel15 April, 2017Head of Production: Responsibilities (1)Product production and storage according to appropriate documentationApproval and implementation of production instructions, in-process QC and ensure strict implementationEnsures that production records are evaluated and signed by designated personLet us now look at the responsibilities carried by individuals. The production manager will normally have at least the responsibilities listed here. Let us look at them individually:. He or she must ensure that products are produced and stored in accordance with appropriate documentation to meet the required quality standards. In some facilities, the production manager may not be responsible for the warehouse. The person who is responsible for the warehouse must store and handle the products in such a way that their quality is unaffected by storage. The production manager must have in place the systems to ensure that production follows the instructions that have been prepared for it.. The production manager is also responsible for the preparation and maintenance of the production instructions and their implementation. This will include not only the production documentation itself, but also all the other procedures and documentation that are essential for the good operation of production. He/she will prepare many of these documents in partnership with quality control and product development staff. The in-process testing requirement must be specified.. Having ensured that production takes place in accordance with the available documents, the production manager must ensure that these documents have been used correctly to record the progress of manufacture. To do this, he/she must evaluate or designate someone to evaluate every batch record in order to satisfy himself/herself that all has gone as it should. He/she will also need to ensure that the documents have been completed correctly.Continued on the next slide ….9.9
16 World Health Organization Personnel15 April, 2017Head of Production: Responsibilities (2)Checks maintenance of production department, premises and equipmentEnsures process validation and calibration performed, recorded, and reports are made availableEnsures initial and continuous training of production personnelHead of Production responsibilities - Continued …. For manufacture to proceed as planned, it is essential that all the plant, facilities and equipment are operating as they should. This means that maintenance must be planned and implemented. This is normally done within a planned preventative maintenance programme. The production manager is responsible for ensuring that all the facilities and equipment under his/her control are properly maintained in accordance with this programme.. It is essential to check regularly that the processes will routinely produce a product that meets the registered specifications. The production manager must therefore ensure that all processes are validated and all equipment is calibrated in accordance with the written procedures. We will be talking specifically about weigh scales in this respect when we get to the module on equipment. It is particularly important that the production manager takes responsibility for the conduct of the in-process testing routines agreed with QA/QC.. The production manager is responsible for ensuring that the people who carry out all this work are well trained and motivated at the commencement of their work, and that they receive regular refresher training.9.9
17 World Health Organization Personnel15 April, 2017Head of Quality Control: Responsibilities (1)Approval or rejection of materials, e.g. packing materials, intermediates, bulk and finished products, in accordance with specificationsEvaluation of batch recordsEnsures carrying out of necessary testingApproval of quality control procedures, e.g. sampling and testing; specificationsNow let us look in more detail at the responsibilities of a QC manager:. The first item on the list is the approval or rejection of all starting and packaging materials and all intermediate, bulk and finished products. This is a critical area and one in which interference can arise particularly when the value of the materials is extremely high, orders have to be met and the owner of the business is directly involved.. The QC manager is also responsible for the evaluation of batch records coming from production. This should be done as part of the product release process. The purpose is to be reassured that products have been produced in accordance with the agreed process, and meets specifications. If there have been any deviations from the agreed process, these need to have been authorized by responsible persons. Additional testing may be needed before the product is released for supply. This review process is vital. The QC manager may delegate this review to an authorized person but the responsibility remains his/hers. In some countries this review is done by an authorized person who is, in effect, independent of both production and quality control.. The QC manager is responsible for ensuring that all the required testing is completed in accordance with specifications.. The QC manager will approve all the instructions that are required for the organisation and implementation of testing. The development of all these instructions, policies and procedures may well be done in co-operation with production and development personnel.9.10
18 World Health Organization Personnel15 April, 2017Head of Quality Control: Responsibilities (2)Approval and monitoring of all contract analysisChecks maintenance of quality department, premises and equipmentEnsures validation (including analytical procedure validation) and calibration of control equipmentEnsures initial and continuous training of QC personnelQC responsibilities continued …. The QC manager is responsible for all testing carried out on contract. The QC manager must be assured that the contract accepter:- can conduct the testing to the required standard- has all the necessary personnel- has the necessary equipment to conduct the testing- has a written contract specifying the responsibilities of all parties to the agreement.. As with production, the QC manager is responsible for ensuring that all the facilities and equipment under his/her control are properly maintained in accordance with the planned maintenance programme.. The QC manager is responsible for the validation of analytical methods and the calibration of laboratory equipment to ensure that results achieved by following the validated processes can be relied upon. Some aspects of validation will almost inevitably be shared with production and engineering.. The QC manager is responsible for ensuring that the people who carry out all this work are well trained and motivated at the commencement of their work and that they receive regular training and retraining.The quality control function has other duties as well. These are described in the module on Quality Management.9.10
19 World Health Organization Personnel15 April, 2017Authorized person: Responsibilities (1)Compliance with technical and regulatory requirementsApproval of the release of finished product for saleEstablishment and implementation of quality systemDevelopment of quality manualSupervision of self-inspections and quality auditsAuthorized person: Responsibilities (1)The authorized person is responsible for compliance with technicalor regulatory requirements related to the quality of finishedproducts and the approval of the release of the finished product forsale.The authorized person will also be involved in other activities,including the following:(a) implementation (and, when needed, establishment) of the qualitysystem;(b) participation in the development of the company’s qualitymanual;(c) supervision of the regular internal audits or self-inspections;9.11
20 World Health Organization Personnel15 April, 2017Authorized person: Responsibilities (2)Oversight of the QC departmentParticipation in external audits and vendor auditsParticipation in validation programmesMay delegate approval of release of product through approved procedureNormally by QA by means of batch reviewThe authorized person will also be involved in other activities,including the following:(d) oversight of the quality control department;(e) participation in external audit (vendor audit);(f) participation in validation programmes.The function of the approval of the release of a finished batch ora product can be delegated to a designated person with appropriatequalifications and experience who will release the product in accordancewith an approved procedure. This is normally done by qualityassurance by means of batch review.9.12, 9.13
21 World Health Organization Personnel15 April, 2017Person releasing the batch should ensure: (1)Each batch meets manufacturing and marketing authorization requirementsPrinciples and requirements of GMP are metAll checks and tests have been performedProduction conditions and manufacturing recordsPlanned changes and deviations reported - including where necessary to drug regulatory authorityThe person responsible for approving a batch for release shouldalways ensure that the following requirements have been met:(a) the marketing authorization and the manufacturing authorizationrequirements for the product have been met for the batchconcerned;(b) the principles and guidelines of GMP, as laid down in the guidelinespublished by WHO, have been followed;(c) the principal manufacturing and testing processes have been validated,if different;(d) all the necessary checks and tests have been performed andaccount taken of the production conditions and manufacturingrecords;(e) any planned changes or deviations in manufacturing or qualitycontrol have been notified in accordance with a well definedreporting system before any product is released. Such changesmay need notification to, and approval by, the drug regulatoryauthority;9.14 a - e
22 World Health Organization Personnel15 April, 2017Person releasing the batch should ensure: (2)Additional sampling, inspection, checks and tests had been done when requiredAll production and control documents are completed and endorsedAudits, inspections and spot-checks were doneQC approval has been givenAll other relevant factors have been consideredThe person responsible for approving a batch for release shouldalways ensure that the following requirements have been met:(f) any additional sampling, inspection, tests and checks have beencarried out or initiated, as appropriate, to cover planned changesand deviations;(g) all necessary production and quality control documentation hasbeen completed and endorsed by supervisors trained in appropriatedisciplines;(h) appropriate audits, self-inspections and spot-checks are carriedout by experienced and trained staff;(i) approval has been given by the head of quality control;(j) all relevant factors have been considered, including any not specificallyassociated with the output batch directly under review(e.g. subdivision of output batches from a common input, factorsassociated with continuous production runs).9.14 f - j
23 World Health Organization Personnel15 April, 2017Training (1)Training, in accordance with a written, approved programmeall personnel whose duties take them into production areas; orinto control laboratories; andfor others whose activities could affect the quality of the product including technical, maintenance and cleaning personnelInduction and continuing trainingon theory and practice of GMP and their dutiestraining records should be keptpractical effectiveness checkedtraining before undertaking any new taskInspectors should check the company procedure, training materials and records on training provided.Training should be given in accordance with a written, approved programme to all personnel whose duties take them into production areas; orinto control laboratories; andfor others whose activities could affect the quality of the product including technical, maintenance and cleaning personnel)On induction and continuing;1. Each company should establish a written training programme. New employees understand what is expected of them and the risks to patients and consumers if the products they make do not conform to requirements. This initial training must be given to all employees who have a direct impact on product quality.The training programme may consist of at least two parts. The first will be a general programme that all employees should receive which explains GMP and the importance of GMP to the company. There may well be a second programme, explaining the specific issues about the individual’s department.2. There should be a written re-training programme for all employees to ensure that their skills are continually brought up to date and that they are introduced to changes in practice as these develop.3. As employees go through their training, records should be kept of the training received and performance against tests. People have to realise that good performance is required otherwise retraining will be required.4. All areas of GMP relevant to the individual must be covered.5. Training records must be kept to ensure that as employees move around the company, they are not required to carry out work for which they have not been trained.10.1, 10.2
24 World Health Organization Personnel15 April, 2017Training (2)Specific training for staff in special areas, e.g.Where contamination is a hazardIncluding clean areas; orAreas where highly active, toxic, infectious, sensitizing materials are handledThe concept of QA should be fully discussed during training to facilitate proper understanding to ensure its implementationInspectors should check records on training. Continued ...6. People who work in special areas should receive additional training in the special nature of their area of work. Those people who work in sterile areas, with highly active or toxic materials or sensitizing agents, should receive specific instruction in the special nature and hazards associated with this activity.7. During training, every encouragement should be given to employees to discuss fully all aspects of quality and GMP with their trainers and among themselves. Staff should be encouraged to contribute to increased quality and GMP. A few additional words about visitors are necessary. See the next slide.10.3, 10.4
25 World Health Organization Personnel15 April, 2017Visitors or Untrained PersonnelPreferable not to enter production and control areas. If this is unavoidable then:They must be given information in advance, particularly aboutpersonal hygieneprotective clothing requirementsMust be accompanied and closely supervised at all timesOne of the questions that you should raise in all companies is how they handle visitors. The answer should be that their presence should be treated as a potential risk to the product and, therefore, steps should be taken to ensure that they cannot cause any hazard to product quality. Ideally, the company will do this by factory design that ensures that visitors cannot gain access to areas in operation. This is usually difficult and so it is necessary to give visitors a full briefing and to provide them with full protective clothing and give them strict instructions about where they may stand.For visitors there can be no exceptions to the rule of the wearing of appropriate clothing to protect the product.A word at this stage about visits by the owners of the business. This may be a difficult area because owners may feel that if the company is theirs they may do what they want, when they want. Somehow they have to understand that their investment is at risk if they do not behave as necessary. (Use flipchart again to record comments from the audience).10.5
26 World Health Organization Personnel15 April, 2017Consultants and contract staffShould be qualified for the services providedTraining records maintainedRecords should prove qualificationsA manufacturer may use the services of a consultant and contract staff. The company has to ensure that these people are qualified for the services provided.It may be useful for you to review also the training records maintained for contract staff. Some companies use contract workers for some activities including packaging of products. They should have been properly trained in GMP, QA and the relevant procedures and processes that they are responsible for.Records should prove persons' qualifications10.6
27 World Health Organization PersonnelWorld Health Organization15 April, 2017Group SessionWhat do you think will be the key personnel issues to arise during an inspection?What sort of responses do you think you should give to these issues when they become apparent?Having heard the presentation on personnel, use what you know to develop thoughts on the likely issues regarding the organization of personnel that you will meet during inspections in your countries.More personal issues arising during an inspection are dealt with in the modules on GMP inspections.Once you have drawn up a list, develop the responses that you feel would be appropriate in those circumstances.
28 World Health Organization PersonnelWorld Health Organization15 April, 2017Possible Issues – ILimited number of staffInadequate qualificationsInadequate experienceOwner interferes in quality decisionsLack of means to develop training materialsIn a company the issues will be around a lack of skills and resources to comply with all the requirements of GMP:Limited staff numbers may mean that people are under pressure to perform. They may be trying to do too much. There may be a lack of deputies during times of illness or holidays.Recruited staff may have inadequate qualifications.Recruited staff may have inadequate experience or experience in an inappropriate area. Sometimes the owner recruits relatives who are inadequately qualified or experienced.The owner may interfere with quality decisions, particularly if orders are required urgently or are very valuable. Senior staff may have difficulty in combating this, since it may cost them their jobs.Smaller companies may have no means to develop training materials to educate their staff in the requirements of GMP. They do not become members of the local manufacturers’ association because of cost. They do not then have access to training programmes that are available through the association.
29 World Health Organization PersonnelWorld Health Organization15 April, 2017Possible Issues – IICompany procedures take precedence over local legislationUnclear organization diagramStaff movementInadequate training recordsIllnessSubsidiaries of multinational companies may claim that company procedures or standards take precedence over local legislation. If this is claimed, it will be most unusual since all multinationals require local companies to conform first to local legislation. It will be worth exploring with the company what benefits are obtained by not conforming to local legislation.Large organizations often move people around through promotion, training, recruitment or relocation. In so doing they can lose sight of the requirements of GMP. Managers can be promoted into positions for which they are not qualified or experienced.Companies may not keep adequate training records even though people are apparently undergoing training.As with small companies, large companies may have personnel policies that penalize people. The problem is that if people are not going to be paid when sick or injured, they may work on under circumstances that create a risk to the product. What happens when they have an open wound, for example?