Week 4 - Quality Management

Question 1

Describe the relaionship between GMP, quality assurance and quality control

Wtih regards pharmaceuticals how is QA divided and what does it ensure?

Answer 1

• The concepts of GMP, Quality Assurance (QA) and Uality COntrol (QC) are interrelated
• QA is divided into the following: quality control, development, production, distribution and inspections
• QA ensures that products are consistently produced and controlled to quality standards appropritate to their intended usem, therefore GMP is an integral part of QA

Question 2

In the pharmaceutical industry, what is quality management commonly referred to as?

Answer 2

• Referred ti as tge asoect if the management department that determines and implements the quality policy

Question 3

regarding the pharmaceutical industry what does “quality” mean?

Answer 3

• Refers to all characteristics of the pharmaceutical product or service that affect its ability to satisfy the intended use.

Question 4

Regarding the pharmaceutical industry what are the fundamental points of quality management?

Answer 4

Fundamental points are:

• A suitable quality system that includes the organisational procedures and processes;
• Methodical implementation to ensure that a given product (or service) will gratify the specific requirement for quality. The entirety of these activities is referred to as quality assurance.

Question 5

What does quality assurance do?

What does pharmaceutical quality arise from and how is it assessed?

Answer 5

• Quality assurance functions as a management tool within an organisation.
• The quality of pharmaceutical/medicinal products arises from the sum of many activities.
• Testing the end product alone is not sufficient to assess the product quality. Overall quality system is required, which ensures that the integrity of the product is upheld during the entire manufacturing process.

Question 6

What are the integrated aspects of quality management in the pharmaceutical industry?

Answer 6

• The notions of quality assurance, quality control and GMP are integrated aspects of quality management within the pharmaceutical industry.

Question 7

What does the term ‘quality assurance’ mean in regards to the pharmaceutical industry?

Answer 7

• Quality assurance is a notion that includes subjects that influence the quality of a product.
• It’s the entirety of the arrangements, with the common aim of ensuring that pharmaceutical products are of a high quality, in relation to their intended use.
• Includes factors such as GMP

Question 8

What should quality assurance systems suitable to the manufacture of pharmaceutical products confirm?

(Compliance & specification)

Answer 8

• The designs of pharmaceutical products are compliant with the requirements set by GLP, GCP and GMP.
• Production and control operations are specified.
• Managerial duties are specified.

Question 9

What should quality assurance systems suitable to the manufacture of pharmaceutical products confirm?

(prepartations, final product, release onto the market)

Answer 9

• Preparations are in place to ensure that the manufacture use appropriate starting and packaging materials.
• The final product is accurately processed and checked in compliance with the relevant procedures.
• Pharmaceutical products are not released on the market before authorised personnel, in compliance with the requirements of the marketing authorisation, have certified each production batch.

Question 10

What should quality assurance systems suitable to the manufacture of pharmaceutical products confirm?

(agreements, self-inspection/quality audit reports, consistency of process)

Answer 10

• Suitable agreements to ensure that the pharmaceutical products are stored, distributed, and handled, by the manufacturer, in an satisfactory manner so that the quality is upheld throughout the specified shelf-life.
• There is a system for self-inspection and/or quality audit reports, which regularly assess the effectiveness and applicability of the quality assurance system.
• Regular assessments of the quality of pharmaceutical products to verify their consistency of the process and ensuring its continuous improvement.

Question 11

What is Quality Control concerned with?

Answer 11

• Concerned with sampling and testing of the pharmaceutical product and the documentation and release procedures, ensuring that the quality of the product has been certified as satisfactory for intended use.
• Quality control must be included in all decisions regarding the quality of the product.

Question 12

Describe pharmaceutical quality control function

Answer 12

• Pharmaceutical manufacturers should have a quality control function, independent of other departments.
• Sufficient resources must be available to ensure that the quality control preparations can be carried out effectively.

Question 13

What are the main points for quality control?

Answer 13

• Satisfactory facilities and procedures (in additional to qualified personnel) must be available for inspecting and testing manufacturing materials.
• Sampling inspection and testing procedure must be reported to ensure that they have been performed accurately.
• finished product must contain all specified ingredients, in compliance with the quantitative and qualitative constituents of the product specified in the marketing authorisation documentation.
• The inspection and testing results must be recorded and validated against specifications.
• The product must not be released for sale until the appropriate authorised personnel have certified the product, in accordance with the requirements issued by the marketing authorisation.
• Samples of pharmaceutical product, in addition to starting and packaging materials must be retained for future examination if required.

Question 14

What are Quality Control systems responsible for?

Answer 14

• Quality control systems are also responsible for ensuring that the pharmaceutical ingredients are stable and that the final product is safe and effective.

Question 15

Who is responsible for Quality Control and what are their responsabilities?

Answer 15

• approve/ reject starting materials, packaging materials and finished products;
• assess batch records;
• ensure that the required testing protocols are carried out effectively;
• ensure that analytical procedures and calibrations of equipment is carried out effectively.
• assess the maintenance of the premises and equipment;
• ensure that adequate training is given to all quality control personnel.

Question 16

What is the main aim of self-inspection, what is self-inspection for and what should their frequency be?

Answer 16

• Principle aim of self-inspection is to assess the manufacturer’s compliance with GMP in all areas of production.
• The self-inspection programme should be created to detect errors in compliance to GMP and to suggest the necessary corrective procedures.
• The frequency that self-inspections are performed, depends on the requirements issued by the company.

Question 17

Who is responsible for self-inspection and what much they do?

Answer 17

• The team responsible for self-inspection must be able to assess the manufacturer’s compliance with GMP impartially

Question 18

What should the self-inspection report include?

Why should regular audits be performed?

Answer 18

• Self-inspection results
• Conclusions
• Corrective actions
• To evaluate the effectiveness of the quality system, and to ensure that the production of the pharmaceutical product meets the requirements of GMP, regular audits must be performed.

Question 19

Define the term “audit”

Answer 19

systematic, independent and documented examination

Question 20

State the EU GMP Directive statement for self-inspection

Answer 20

• The manufacturer shall conduct repeated self-inspections as part of the quality assurance system in order to monitor the implementation and respect of good manufacturing practice and to propose any necessary corrective measures.
• Records of such self-inspections and any subsequent correct action shall be maintained

Question 21

What main points are applicable to all audits?

Answer 21

• Repeated audits are necessary.
• Audits have a dual purpose: (1) To assess the current situation and (2) recommend corrective measures.
• A formally written document of the findings should be prepared, which should also include information of any succeeding activities. This suggests that effective actions are implemented specifically to the findings documented in the audit report.

Question 22

According to the WHO what does a Quality Audit consist of?

Answer 22

• a quality audit comprises of an assessment, of all aspects of a quality control system with the overall purpose of improving it.

Question 23

What is the purpose of auditing?

What are the regulatory requirements?

Answer 23

• EU GMP Directive only addresses the requirement for self-inspection not quality audits
• To be compliant with other requirements, quality audits are required
• EU GMP Guide states:
  • “The Contract Giver is responsible for assessing the competence of the Contract Acceptor to carry out successfully the work required and for ensuring… that the principles and guidelines of GMP … are followed”

Question 24

What is the purpose of auditing?

What is the most suitable way to gain knowledge required for the assessment and approval of vendors and contractors?

How is this recognised by the WHO

Answer 24

• auditing is the most suitable way
• WHO GMP Guide states that “Before suppliers are approved… they should be evaluated. The evaluation should take into account a supplier’s history and the nature of materials to be supplied. If an audit is required, it should determine the supplier’s ability to conform with GMP standards

Question 25

What is the purpose of auditing?

What are the expectations of the world-wide regulatory authorities regarding auditing?

Answer 25

• clear expectation that audits will be performed, both internally and externally, of contractors and vendors.

Question 26

What is the purpose of auditing?

How can auditing lead to business benefits?

Answer 26

• ‘good’ audit is an evaluation of the current quality system against current and future requirements, correctly establishing the current status and the required changes that need to be made.

Question 27

What is the purpose of auditing?

How can detecting deficiencies in an audit lead to business benefits?

Answer 27

• deficiencies are detected in the audit report, root causes of the initial problem must be determined and addressed, in order for the quality system to receive continuous improvement.

Question 28

What is the purpose of auditing?

How can audits be viewed in a negative and positive light?

Answer 28

• Remember that audits are not solely a regulatory requirement, otherwise they can be negatively viewed.
• Instead, audits also highlight positive aspects of the existing system, in hope to promote good practices.

Question 29

What is the purpose of auditing?

What can audits that are effectively performed help to do?

Answer 29

• Ensure customer requirements are comprehended and addressed
• Improve processes
• Reduce control testing

Question 30

What are the main types of audit?

Answer 30

Three main types of pharmaceutical audits, which include:

• internal audits
• external audits
• regulatory audits

Question 31

Describe the internal audit type

Answer 31

• A requirement issued by GMP legislation, which is performed by a particular organisation on its own systems, procedures and facilities.
• The manner in which internal audits are performed will depend on the size of the organisation.
• A system should be in place to ensure that internal audits occur and are effectively pursued

Question 32

With regards internal audits, what is the three-tier approach?

Answer 32

• Ensures that internal audits occur and are effectively pursued.

1. Tier 1: Audits performed internally within a department, by a departmental staff member.
2. Tier 2: A local quality assurance group commonly leads audits of this nature, involving independent staff, impartial of the department being audited.
3. Tier 3: Audits performed by a corporate compliance group.

Question 33

What is an external audit?

Answer 33

• External audits are performed by a company on its vendors/ subcontractors.
• The extent of the audit will depend on the association between the interested parties. In most cases, there will be an initial assessment audit to evaluate the overall suitability of the vendor or contractor.
• Consequently, there will be routine audits to evaluate compliance with contractual regulations. Typically, the regularity of the subsequent audits will rely on the initial report and the involved of the vendor/contractor.

Question 34

What does the extent of the external audit depend on?

Answer 34

• The extent of the audit will depend on the association between the interested parties.
• In most cases, there will be an initial assessment audit to evaluate the overall suitability of the vendor or contractor.
• Consequently, there will be routine audits to evaluate compliance with contractual regulations.

Question 35

How is the regularity of external audits decided?

Answer 35

• Regularity of the subsequent audits will rely on the initial report and the involved of the vendor/contractor.

Question 36

Describe the person in charge of managing external audits

Who else might manage external audits?

Answer 36

• The person in control of managing external audits will have expertise in GMP legislation and quality system auditing.
  
  • Audit reports of this nature, may be circulated within the company.
• In some cases, external audits may be performed by external consultants, which are commonly referred to as third-party audits.

Question 37

Who is responsible for carrying out regulatory audits?

Give some examples of these organisations

Answer 37

• Regulatory bodies are responsible for carrying out regulatory audits, in relation to the applicable regulations for the manufacture and supply of pharmaceutical products.
• These regulatory bodies differ in respect to the country:
  
  • Medicines Control Agency in the UK
  • Food and Drug Administration in the USA
  • Health Protection Branch in Canada

Question 38

Ouline the mutual recognition of audit finding between different regulatory bodies

Answer 38

• Pharmaceutical Inspection Convention (PIC):
  
  • available to any United Nations member.
• European Agency for the Evaluation of Medicinal Products (EMEA):
  
  • Has a role in sharing inspection reports between EU member states.

Question 39

Describe when and from whom pharmaceutical companies recieve regulatory audits from

Answer 39

• All authorised pharmaceutical manufactures will routinely receive regulatory audits.
• Pharmaceutical manufacturers may also receive audits from regulatory bodies, in other countries where the products are sold

Question 40

Describe the process of regulatory audits

Answer 40

• Similarly to other audits, regulatory audits begin with an initial meeting to discuss the scope of the audit and intermittent assessments that may follow.
• However, regulatory audits differ in their depth, frequency and duration.

Question 41

What is the significance of failing a regulatory audit?

Answer 41

• Failure to pass a regulatory audit may result in restrictions or withdrawal of a manufacturing license.
• This is an example of how important it is for companies to have an effective process for addressing these audits.

Question 42

With regarding auditors and auditees, what points should be considered?

Answer 42

• Both auditors and auditees should have satisfactory knowledge of GMP standards and quality systems appropriate to the area being audited.
• Both parties are required to undergo regular training to ensure continuous professional development.
• Both parties should appreciate that auditing is not solely a theoretical approach, but is also a practical activity.

Question 43

Give a brief overview of the categories considered when preparing an audit?

Answer 43

• Personnel
• Standards
• Depth of the audit
• Agreements
• Information
• Audit plans and checklists

Question 44

Points to consider when preparing an audit:

Personnel

Answer 44

• The selection of auditors for a specific audit should take into account the general audit skills needed for the process to be performed effectively and accurately.

Question 45

Points to consider when preparing an audit:

Standards

Answer 45

• The auditor should be competent, and should ensure that the auditee is informed, of the different standards and regulations that are being used to in the assessment e.g. EU GMP or FDA.

Question 46

Points to consider when preparing an audit:

Depth of audit

Answer 46

• The scope of the audit must be clearly defined for both the auditor and auditee.

Question 47

Points to consider when preparing an audit:

Agreements

Answer 47

• The audit of vendors/contractors will involve a series of transactions between the participating organisations.
• These transactions may refer to confidentiality, supply and technical issues.
• The auditor needs to determine if there is any restrictions within the agreement that may compromise the main objectives of the audit e.g. limited access to particular facilities.

Question 48

Points to consider when preparing an audit:

Information - what is a useful tool for obtaining information?

Answer 48

• Generic audit questionnaire templates can be used as a helpful tool for obtaining information, however the template should be customised to ensure the appropriate information is obtained.
• In some cases, questionnaires may be used instead of auditing.

Question 49

Points to consider when preparing an audit:

Information - when may a questionnaire be used instead of auditing?

Answer 49

• Questionnaires may be more efficiently used to approve a supplier of a material with a ‘low criticality score’.
• In these situations, additional documentation is also required.
  
  • May include copies of quality manuals, SOPs or other reports.

Question 50

Points to consider when preparing an audit:

Audit plans and checklists

Answer 50

• Auditor is recommended to issue an audit plan, which consist of the estimated time required to assess the areas of interest.
• The auditor takes into consideration: the location, the time needed for each assessment and when the inspection will occur.
• Some auditors use checklists to conduct an audit.
• Similar to questionnaires, customisation of a generic checklist is recommended for each audit.

Question 51

When conducting an audit, what influences the outcome?

Answer 51

• The manner in which an audit is conducted and received by the auditee will influence the outcome

Question 52

Briefly outline the key stages that occur when conducting an audit

Answer 52

• Pre-audit
• Opening Meeting
• Audit Technique
• Closing meeting

Question 53

Conducting an audit

Pre-audit

Answer 53

• Between the notification and the beginning of the audit, the auditee performs internal audits of the possible areas of inspection, systems and documents.
• Help ensure that there routine practices are compliant with GMP standards.
• If poor practices are detected, corrective actions should be initiated to rectify these issues before the external audit starts.

Question 54

Conducting an audit

Opening meeting

Answer 54

• Very important stage of the audit.
• The auditor uses this opportunity to reiterate the audit purpose, the technique that will be observed in the audit, the standards against which the audit will be performed and the acceptance criteria, so that all parties comprehend the scope of the audit.

Question 55

Conducting an audit

Audit technique

Answer 55

• The audit method used will influence the course of the audit.
• Irrespective of the audit method adopted, the auditor will verify that documented procedures are in practice and that these procedures comply with the regulations or guidelines application to the audit scope.

Question 56

Conducting an audit

Audit technique - what may happen during an audit?

Answer 56

• When the audit is being conducted, it is recommended that the auditor informs the auditee of any deficiencies and to ensure that the observations have been agreed upon.
• In some cases, it may become apparent to the auditor that the auditee will not meet the necessary standards and it is to their discretion whether to continue with the audit.

Question 57

Conducting an audit

Closing meeting

Answer 57

• The auditor presents a balanced argument of the findings detected in the audit, in a structure and productive manner.
• Auditor is precise with their findings, provide examples where applicable, and outline the regulatory requirements.

Question 58

Conducting an audit

Closing meeting - depending on the findings of the audit what may happen?

Answer 58

• Providing that active co-operation between both parties were performed during the audit, there should be no surprises at this stage.
• A future audit might be arranged once the auditee has implemented the appropriate corrective actions.
• The auditor should also inform the auditee when the final audit report will be issued.