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Pharmaceutical principles of QA, GMP and QC
- 1. Chapter 6 Pharmaceutical principles of QA, GMP and QC Title slide
- 2. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 2 Main concerns over medicines • Traditional stance the pharmaceutical industry has taken – Quality – Quality Assurance – Good Manufacturing Practice – Quality Control
- 3. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 3 Main concerns over medicines Safety Quality Efficacy
- 4. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 4 Safety and efficacy • Research and Development – Safety and efficacy – Effective – Safe • Risks versus benefits
- 5. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 5 Quality Manufacturing facility Made to the required quality then it should be safe and effective
- 6. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 6 Quality and medicines • Risks: – The wrong medicine – The correct medicine, but a higher than expected strength – The correct medicine, but a lower than expected strength – Contaminated or degraded in some way – Incorrectly labelled – Delivery system associated with the medicine fails Fatal to the end user
- 7. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 7 Quality of medicines in Manufacturing • Need to ensure: – Right product – Right strength – Free from contamination – Not deteriorated – Right container – Correctly labelled – Sealed and protected against damage • Frequency – All of the time – Every unit Every batch Every product – Shelf-life
- 8. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 8 Quality Control • Check your raw materials – Less problems in production • Check your finished product – Less problems from the market • Quality Control – Part of GMP • QC sampling certainly has its limitations
- 9. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 9 Limitations of QC sampling • Testing samples – Destructive testing – Small sample – Chances of detecting the problem are very low • A small amount of defects in a batch can have very serious problems • Extremely unlikely that the recipient will spot that something is wrong It by no means guarantees that the product is OK
- 10. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 10 Good Manufacturing Practice • Concerns of product not being of the right quality • Coupled with the weakness of QC sampling • The principles of GMP were developed • EU GMP Chapter 1 – Quality Management – Pharmaceutical Quality System
- 11. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 11 EU GMP Chapter 1 EU GMP Chapter 1 - Quality Management 1.2 Quality Assurance 1.3 Good Manufacturing Practice 1.4 Quality Control
- 12. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 12 Quality Assurance (1.2) “Quality Assurance is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product” “Is the total sum of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use” “Quality Assurance therefore incorporates Good Manufacturing Practice ... factors outside the scope of this Guide”
- 13. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 13 Good Manufacturing Practice (1.3) “Good Manufacturing Practice is that part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use” “Good Manufacturing Practice is concerned with both production and quality control”
- 14. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 14 Quality Control (1.4) “Quality Control is that part of Good Manufacturing Practice” “Is concerned with sampling, specifications and testing, and with the organisation, documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory” • Sample • Inspect / Test / Check • Pass or reject
- 15. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 15 QC, GMP and QA interrelationship QC GMP QA GMP includes QC and QA includes GMP plus factors outside the scope of GMP QA = GMP + X
- 16. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 16 GMPs thinking of both QC and QA • Quality Control – Samples – Inspects / Tests / Checks – Passes or rejects • Quality Assurance – Product of the right quality – Compliance with requirements – The patient
- 17. Inspired Pharma Training Ltd 10/06/13 Quality Management Systems 17 In Summary • Safety, efficacy and quality • GMP – Product Quality Standard – Safe medicines – Compliance with requirements – The patient – Production and QC • Quality Control • Quality Assurance
Editor's Notes
- COMMENTARY: In earlier chapters we looked at the evolution of both contemporary quality and Quality Management System thinking. In the previous chapter we began to place this in the context of the pharmaceutical industry with our look at the structure and update of EU GMP. We will now continue this positioning and look more deeply at EU GMP and so, welcome to this chapter on “Pharmaceutical principles of QA, GMP and QC”. YOUR NOTES:
- COMMENTARY: In this chapter we have a look at the traditional stance the pharmaceutical industry has taken and in particular determine how it has both viewed quality and defined Quality Assurance, Good Manufacturing Practice and Quality Control, the very bedrocks of pharmaceutical quality thinking. YOUR NOTES:
- COMMENTARY: When we talk about what is important when it comes to pharmaceuticals three words always get mentioned, these are the safety, efficacy and quality of medicines. In other words medicines must be safe to use, they must be effective (they must work) and they must be of the quality required. YOUR NOTES:
- COMMENTARY: The terms safety, efficacy and quality are all interlinked, but generally you can say that the main focus of the Research and Development (R&D) function is safety and efficacy. This is not to say that “quality” is not important to them but one of the pivotal roles of the people who are developing new drugs of the future is to prove that they work (that they are effective) and that as far as possible they are safe to use. This is demonstrated via tissue studies, animal studies and clinical trials. Of note is that the safety and effectiveness of a medicine is always a balance of risks versus benefits of taking the medicine. YOUR NOTES:
- COMMENTARY: Once a medicine has been approved by the Regulatory Authority is it then usually transferred from an R&D facility to a manufacturing facility. This may involve the building of new facilities and the purchasing of new manufacturing and testing equipment all of which will require validation to demonstrate that they work to the required standard consistently. Once a product is manufactured commercially then quality becomes the most significant term. Again it is not to say that safety and efficacy are not important in manufacturing but when you are producing a product and it is made to the required quality (in other words it meets its specifications) then it should be safe and effective. YOUR NOTES:
- COMMENTARY: So when it comes to quality and medicines what do we mean? One way of looking at this is from the view point of the end user, the patient or recipient of the medicine. There are some very significant and serious concerns here and the following risks to the end-user are evident; They receive the wrong medicine. They receive the correct medicine, but a higher than expected strength. They receive the correct medicine, but a lower than expected strength. The medicine is contaminated or degraded in some way. The medicine is incorrectly labelled. The delivery system associated with the medicine fails. All of these could be fatal to the end user. YOUR NOTES:
- COMMENTARY: The repercussions of identifying these risks and placing this in a manufacturing context are, again, significant. We need to ensure that: We have the right product, of the right strength. The product is free from contamination and has not deteriorated. The product is put in the right container, is correctly labelled and is sealed and protected against damage. In order to make this even more complicated we must also remember the frequency in which we have to do this. Not some of the time, not most of the time – but all of the time. This is a big “ask” for any manufacturing organisation. Achieving all of this for every unit, of every batch, of every product throughout its shelf-life. But how do we achieve this? YOUR NOTES:
- COMMENTARY: Well in the 1960’s & 1970’s all leading industries (including the pharmaceutical industry) were introducing Quality Control for incoming materials and finished product. Put simply the idea of Quality Control (or QC) is this. Check your raw materials before you use them and you should have less problems in production. Check your finished product before you release it and you should have less problems from the market. Whilst the pharmaceutical industry has embraced the principles of Quality Control, principles that are still a very important part of Good Manufacturing Practice (GMP) today, it recognised that QC was not perfect for medicinal product manufacturing. Relying on QC sampling certainly has its limitations within pharmaceuticals. YOUR NOTES:
- COMMENTARY: Whilst QC is a very important part of GMP it has three main limitations when it comes to sampling. Firstly, the majority of pharmaceutical testing involves testing samples rather than testing the entire batch. The testing performed is then usually destructive testing. You destroy what you sample when performing the test. When it comes to making cars for example you could 100% inspect every car that comes off a production line, even drive them around town and then still be able to sell them afterwards. In the pharmaceutical world all you are generally doing when you are Quality Controlling is testing a sample, often a small sample of the material in question. If there is a problem with the material being tested, especially if it is contaminated, then the chances of detecting the problem are very low. Secondly, a small amount of defects in a batch can have very serious problems. You only have to have a few non-sterile injection products on the market to kill a number of people. And thirdly, we can’t even rely on the one thing that many other manufacturing industries can fall back on. This is the fact that the consumer will notice that something is wrong and return or dispose of the item. With pharmaceuticals it is extremely unlikely that the recipient will spot that something is wrong before they take it. Once they take the medicine they may (or may not) notice that something is wrong but now the consequences can be very serious and you can’t get the medicine back out of the body. Put simply if a pharmaceutical product has passed its QC testing it by no means guarantees that the product is OK. YOUR NOTES:
- COMMENTARY: Due to the concerns of product not being of the right quality, coupled with the weakness of QC sampling, and to compensate for this, the principles of GMP were developed. In GMP there are definitions of three key quality terms when it comes to Pharmaceutical Quality Management. These are Quality Control (QC), Good Manufacturing Practice (GMP) and Quality Assurance (QA). In EU GMP these are detailed in Chapter 1 a chapter that has, historically, always been entitled “Quality Management”. With recent developments in Pharmaceutical Quality Management System thinking it has been updated (early 2013) to a newly named chapter entitled “Pharmaceutical Quality System”. These changes will be discussed later, but for now we are going to focus on the traditional viewpoints associated with QC, GMP and QA. YOUR NOTES:
- COMMENTARY: In the ATTACHMENTS part of this presentation you will see a PDF copy of EU GMP Chapter 1 – Quality Management. This has now been superseded, but we would like you to look at it to show you the traditional stance of Quality Management historically taken by GMP. Open it up and/ or print it off now. It will be best to PAUSE the presentation whilst you do this. Within the chapter there are some statements that define what GMP’s “traditional” opinion of QC, GMP and QA is. These can be seen at clauses: 1.2 – Quality Assurance, 1.3 – Good Manufacturing Practice and 1.4 – Quality Control Have a quick read of these sections of Chapter 1 as well as the accompanying bullet points to get an understanding of what GMP’s “traditional” opinion of these concepts is. It will be best to PAUSE the presentation whilst you do this. YOUR NOTES:
- COMMENTARY: Firstly, Quality Assurance. At Clause 1.2 it states that “Quality Assurance is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product”. Of note that there is the vague statement on “wide-ranging concept”! Also of note is the focus on quality of the product. GMP is a standard that has always focused exclusively on product quality. It continues; Quality Assurance “is the total sum of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use”. It concludes with the statement that “Quality Assurance therefore incorporates Good Manufacturing Practice”. A reminder that GMP, whilst an important part of a Quality Management System is, on its own, not a Quality Management System. Importantly it also states that it incorporates “factors outside the scope of this Guide”! We are not told what these factors are, simply that Quality Assurance should include other factors! What about GMP itself? YOUR NOTES:
- COMMENTARY: At clause 1.3 we are told that “Good Manufacturing Practice is that part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use”. Of note here is that GMP is part of Quality Assurance. In other words, and again, GMP on its own is not a Quality Management System. It also goes on to say that “Good Manufacturing Practice is concerned with both production and quality control”. Here then we establish the main focus areas of GMP – namely production and quality control. These areas are at the heart of GMP and subject to chapters of GMP in their own right (Chapters 5 and 6 respectively). Finally Quality Control … YOUR NOTES:
- COMMENTARY: Clause 1.4 states that “Quality Control is that part of Good Manufacturing Practice” – and so QC is seen as part of GMP - and “is concerned with sampling, specifications and testing, and with the organisation, documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory”. In other words what should QC do? Well they should sample, then inspect/ test and/ or check and then either pass or reject. YOUR NOTES:
- COMMENTARY: Consequently, through our analysis of these traditional quality-related definitions, we can define the inter-relationship of QC, GMP and QA thus. GMP includes QC and QA includes GMP plus factors outside the scope of GMP. In other words QA = GMP + X. YOUR NOTES:
- COMMENTARY: In this chapter we have looked at the conceptual thinking behind the need for Good Manufacturing Practice and, through our analysis of associated definitions, looked at the inter-relationship of its essential elements – QA, QC and GMP itself. To re-cap this relationship; the Quality Control requirements (set down at EU GMP Chapter 6) are detailed and precise and in the eyes of GMP are this - QC samples, then inspects/ tests and/ or checks and then either passes or rejects. Perhaps, in terms of contemporary QC thinking, a little narrow – an element taken forward in the next chapter of this unit. Similarly, in looking at Quality Assurance. GMP’s thinking of QA appears a little outdated. The traditional focus of QA has been on getting product of the right quality, compliance with requirements and thinking about the single customer of GMP, the patient. Whilst there is no argument that these still remain a vitally important part of pharmaceutical production, it should be noted that Quality Assurance in other leading industries and contemporary Quality Management System thinking looks at much more than this, again an element taken forward in our next chapter. YOUR NOTES:
- COMMENTARY: In this chapter we have looked at the notions of safety, efficacy and quality. In order to ensure product of the right quality we engage GMP, a product quality standard focused on providing safe medicines, focused on compliance with requirements and focused on the patient. It sees its domain as that associated with Production and QC and it has an excellent track record. We have looked at how, traditionally, the pharmaceutical industry has viewed Quality Control and Quality Assurance and have perhaps hinted that how we actually view these elements falls a little short of how these may be viewed in other industries and in the light of our thoughts on contemporary quality and Quality Management System thinking. Having established a “GMP base-line” we will now move our thought process forward and more formally compare this traditional pharmaceutical thinking with that of contemporary quality and Quality Management System thinking. YOUR NOTES: