Quality Management system, QC vs QA, Pharmacopoeia.pdf
- 2. Table of Contents Topics no. Head of Topics Page no. 01 1. Quality Management system in Pharmaceutical Industry 1-2 1.1 Pharmaceutical Development 1.2 Analytical method development 1.3 Objectives 1.4 Elements of Pharmaceutical Quality System 02 2. Quality Assurance and Quality Control in Pharmaceutical Industry 3 2.1 Quality Assurance 2.2 Quality Control 2.3 QA/QC in the pharmaceutical industry 03 3. Difference between Quality Assurance and Quality Control 4 3.1 Q/A vs Q/C 04 4. Briefly describe Pharmacopoeia, Drug Formulary, Drug compendia, Pharmaceutical codex 5-6 4.1 Pharmacopoeia 4.2 Drug Formulary 4.3 Drug Compendia 4.4 Pharmaceutical codex 05 5. Short notes on British Pharmacopoeia, US Pharmacopoeia, European Pharmacopoeia, Japanese Pharmacopoeia, British Pharmaceutical Codex 6-14 5.1 British Pharmacopoeia 5.2 US Pharmacopoeia 5.3 European Pharmacopoeia 5.4 Japanese Pharmacopoeia 5.5 British Pharmaceutical Codex 06 6. What is monograph in Pharmacopoeia? What does it contain? 14 6.1 What is monograph in Pharmacopoeia? 6.2 What does it contain?
- 3. A quality management systems definition would necessarily cover the concept of a quality control unit, which is responsible for overall quality management systems. The quality control unit is primarily responsible for documentation (procedures, sops, policies, etc.) and control of all documents that impact product quality and safety. Pharmaceutical quality management system It is applicable to drug products, including biotechnology and biological products, throughout the product lifecycle, the systems supporting the development and manufacture of pharmaceutical drug substances. It includes: 1. Pharmaceutical Development ▪ Manufacturing and development of APIs. ▪ Manufacture of medical kits and devices for investigation. ▪ Development of medical delivery systems. ▪ Pilot plant scale-up activities ▪ The manufacturing process of formulation ▪ Development of medical devices for accurate dosing 2. Analytical method development i. During the manufacturing process ▪ Acquisition and control of materials ▪ Provision of facilities, utilities, and equipment ▪ Production (including packaging and labeling) ▪ Quality control and assurance ▪ Release ▪ Storage 1.Quality Management system in Pharmaceutical Industry 1
- 4. ii. During product technology transfer. iii. During product discontinuation ▪ Retention of sample and related documentation ▪ Continued product assessment and reporting Objectives: Three main objectives are as follows: 1. Achieve Product Realization 2. Effective control over variables 3. Continuous Improvement Elements of Pharmaceutical Quality System Fundamental elements for effective pharmaceutical quality systems are as follows: ➢ Managerial review of process performance and product quality ➢ Process performance and product quality monitoring system ➢ Corrective action and preventive action (CAPA) system ➢ Change control management system The objective is to establish, implement, and maintain a system that allows the delivery of products with the desired quality attributes. Quality risk management also helps in developing effective monitoring and control systems for specified process performance that in turn establishes the capability of processes. It is useful for identifying and prioritizing areas for continual improvement in terms of quality attributes, process technology and other technical aspects. These objectives ultimately contribute to the betterment of end-product quality and better process understanding. The design, organization, and documentation of the pharmaceutical quality system should be appropriate and exhaustive enough to facilitate shared understanding. The quality manuals should be prepared in line with the quality policy of the organization. 2
- 5. • Quality Assurance Quality Assurance is known as QA and focuses on preventing defects. Quality Assurance ensures that the approaches, techniques, methods and processes are designed for the projects are implemented correctly. Quality assurance activities monitor and verify that the processes used to manage and create the deliverables have been followed and are operative. Quality Assurance is a proactive process and is Prevention in nature. It recognizes flaws in the process. Quality Assurance has to complete before Quality Control. • Quality Control Quality Control is known as QC and focuses on identifying a defect. QC ensures that the approaches, techniques, methods and processes are designed in the project are following correctly. QC activities monitor and verify that the project deliverables meet the defined quality standards. Quality Control is a reactive process and is detection in nature. It recognizes the defects. Quality Control has to complete after Quality Assurance. QA/QC in the pharmaceutical industry A quality assurance audit at a pharmaceutical firm would focus on the process elements of a project. More specifically, a QA professional would determine if the requirements determined and defined during QA have the proper level of detail. QA individuals process the documentation, establish standards, and conduct internal audits to ensure continued compliance. A QC professional, on the other hand, focuses on product elements. The individual would determine whether the requirements highlighted during QA implementation are executed adequately during regular production of the product. It is a QC professional’s job to perform inspections on products and conduct tests. Their information contributes to the quality assurance process. However, in many cases, the job title is something like QA/QC Manager, so there is a bit of both involved. 2. Quality Assurance and Quality Control in Pharmaceutical Industry 3
- 6. 3. Difference between Quality Assurance and Quality Control Quality Assurance Quality Control It is a process which deliberates on providing assurance that quality request will be achieved. QC is a process which deliberates on fulfilling the quality request. A QA aim is to prevent the defect. A QC aim is to identify and improve the defects. QA is the technique of managing quality. QC is a method to verify quality. QA does not involve executing the program QC always involves executing the program. All team members are responsible for QA. Testing team is responsible for QC. QA Example: Verification QC Example: Validation. QA means Planning for doing a process. QC Means Action for executing the planned process. Statistical Technique used on QA is known as Statistical Process Control (SPC.) Statistical Technique used on QC is known as Statistical Quality Control (SQC.) QA makes sure you are doing the right things. QC makes sure the results of what you've done are what you expected. QA Defines standards and methodologies to followed in order to meet the customer requirements. QC ensures that the standards are followed while working on the product. QA is the process to create the deliverables. QC is the process to verify that deliverables. QA is responsible for full software development life cycle. QC is responsible for software testing life cycle. QA is a managerial tool. QC is a corrective tool. QA is process oriented. QC is product oriented. QA company based. QC lab based. Document review, inspection, test cases review etc. are used. Functional testing, automation testing etc. are used. QA vs QC 4
- 7. 4. Briefly describe Pharmacopoeia, Drug Formulary, Drug compendia, Pharmaceutical codex. Pharmacopoeia This word derived from Greek word ‘Pharmakon’ means drug and ‘Poiea’ means to make. A book containing a selected list of medicinal substances and their dosage forms, providing also a description and the standards for purity and strength for each. It is a legal and official book issued by recognized authorities usually appointed by the government of each country. It comprises a list of pharmaceutical substances, formulae along with their description and standards. Drug Formulary A list of approved prescription medications that the plan will cover and that will be distributed from affiliated pharmacies. Or, The most basic way to define a drug formulary is "a list of prescription drugs that are paid for by a health plan." It could be the government's drug plan or a private plan that we have purchased through an insurance company. A formulary is the product of an evaluative process, the formulary system, conducted by a proficient panel that both sanctions and guides the selection, prescription, administration, and monitoring of pharmaceuticals and related items for a given environment. An expert panel often called the Pharmacy and Therapeutics Committee (P&T), is a group of pharmacists, physicians, nurses, and administrators assembled to provide guidance and validation for pharmaceutical utilization in a given organization. Drug Compendia Drug compendia are defined as summaries of drug information that are compiled by experts who have reviewed clinical data on drugs. Drug compendia are extensive collections of the drugs that are revised by physicians, pharmacists and medical scientists. In these compendia can you find information about drug dosage, usage, mechanism of action, counterindications, risks, side effects and more. Each country has their own drug compendia. 5
- 8. Pharmaceutical codex The Pharmaceutical Codex means the book of that name published by direction of the Council of the Pharmaceutical Society of Great Britain. The regulations may, in making provision for or concerning the determination of any standards, adopt by reference the whole or any part of any monograph or other material contained in a prescribed publication or any such monograph as modified under subsection. Short notes on British Pharmacopoeia, US Pharmacopoeia, European Pharmacopoeia, Japanese Pharmacopoeia, British Pharmaceutical Codex British Pharmacopoeia The BP makes an important contribution to the role of the Medicines and Healthcare products Regulatory Agency (MHRA) in protecting public health by providing quality standards for UK pharmaceutical substances and medicinal products. The BP has a wide international reach and: • It is used in over 100 countries • It forms an inherent part of established medicines legislation in Commonwealth countries • provides expert advice to the European Pharmacopoeia and plays a significant role in the standard-setting process in Europe • provides expert advice to the World Health Organization • has strong links with leading world pharmacopoeias, ensuring the quality of medicines is always at the forefront of international discussions The BP has been providing official standards for medicines since 1864. The legal status of the British Pharmacopoeia Commission and of the British Pharmacopoeia was established under the 1968 Medicines Act. This Act has been superseded by the Human Medicines Regulations 2012. 5. Short notes on British Pharmacopoeia, US Pharmacopoeia, European Pharmacopoeia, Japanese Pharmacopoeia, British Pharmaceutical Codex 6
- 9. The British Pharmacopoeia and coronavirus (COVID-19 Last updated: 1 July 2020 During the COVID-19 outbreak the BP is committed to keeping our users updated and supporting the wider healthcare response. We will be making regular updates to this page. Products and services All our products and services are currently available, including the BP publications and the BPCRS. Whilst our staff based in central London are now working remotely, our laboratories remain open. Shipment of BPCRS products are currently not significantly impacted. We are prioritizing work to ensure that our website and processing orders of the BPCRS can continue uninterrupted. International Collaboration The BP works with pharmacopoeias globally through the World Health Organization’s (WHO) International Meeting of World Pharmacopoeias (IMWP). Following the initiation of a global pharmacopeial alert, pharmacopoeias have worked together to support the public health response. This has included identifying existing pharmacopeial monographs for medicinal substances and products under investigation for the treatment of COVID-19. The WHO update and list of standards can be found on the IMWP website. Meetings and advisory groups All our meetings, including the British Pharmacopoeia Commission, Expert Advisory Groups, Expert Panels and Working Parties are now being held remotely. If you are involved in our work, you will be contacted by the BP Secretariat directly with further instructions. Important changes to ordering BPCRS We want to make sure that existing BPCRS customers with an active account on pharmacopoeia.com can order the products they need. As such, we have put the following changes in place to ensure the quick, reliable and fair supply of the chemical reference standards listed in the tables below. • A limit of 5 or less vials per customer, per order for the products listed below. • The time allowed between maximum (repeated) orders is 30 days (e.g. 5 or 2 vials in a 30- day period). • Distributors will be asked to demonstrate that orders exceeding the maximum amount are on behalf of individual customers. 7
- 10. • The list below is subject to change. We appreciate your continued cooperation during this period and should you need to contact us further about these changes please email bpcrs@mhra.gov.uk. The chemical reference substances listed below have been restricted to 5 vials per customer to ensure supply of these standards. The list below is subject to change. Catalogue Number Name Update 19 AMOXICILLIN TRIHYDRATE 41 BETAMETHASONE SODIUM PHOSPHATE 63 CEFRADINE 89 CLOXACILLIN SODIUM 90 CODEINE PHOSPHATE 284 PHENYLEPHRINE HYDROCHLORIDE 24th June 2020 302 SALBUTAMOL SULFATE 407 HALOPERIDOL 431 DIHYDROCODEINE TARTRATE 576 HYDROCORTISONE 578 DEXAMETHASONE 17th June 2020 627 3-FORMYLRIFAMYCIN SV 698 PROPOFOL DIMER 1st July 2020 730 N-DESALKYLFLURAZEPAM 765 OMEPRAZOLE 852 SALBUTAMOL IMPURITY B 880 IBUPROFEN IMPURITY B 8
- 11. US Pharmacopoeia The united states pharmacopoeia (USP): - USP stands for “The united states pharmacopoeia”. The USP is recognized as official compendia & is used as reference book for determining the strength quality purity packaging & labeling of medicine & other related articles the USP was originally published in 1920 under the authority of the united states pharmacopoeia convention. Then the new edition of this book ravished. So long it is continued in our present age. • About USP At USP, everything they do is in service of their mission to help protect and improve the health of people around the world. From the standards they create to the partnerships they foster; they continually work to build and reinforce a foundation that draws them closer to a world where everyone can be confident of quality in health and healthcare. • Mission To improve global health through public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods. • Vision USP envisions a world in which all have access to high quality, safe, and beneficial medicines and foods. USP approaches this vision with a sense of urgency and purpose, strengthened by its cadre of dedicated volunteers, members, and staff, and by working collaboratively with key stakeholders across the globe. • Impact As the world gets smaller and more connected, quality issues affect everyone. Diseases travel. Drug resistance grows. Fake medicines kill. The foundation of quality they are building helps address these and other global health issues. Whether decreasing the prevalence of substandard and poor-quality medicines or helping to curb antimicrobial resistance, they are there working to protect the health of people all over the world. 9
- 12. European Pharmacopoeia • Content of the European Pharmacopoeia The European Pharmacopoeia contains a series of general monographs for the manufacturing of medicines, general methods of analysis of substances and medicines, and some general requirements for dosage forms (tablets, capsules, injections, etc.). The methods of analysis may also be used by the pharmaceutical industry for substances and medicines not described in the pharmacopoeia. The bulk of the Ph. Eur. is made up of quality standards, which are noted both in the monographs and general methods sections. Quality standards contain analytical methods to identify the substance and evaluate its quality and quantitative strength. Perhaps the essential part of a quality standard of an active substance is the section on impurities. Active substances of medicines are pharmacologically active due to the structure of the chemical molecule. No substance can be 100% pure, and impurities may come from: o The manufacturing method – how a substance is produced or synthesized o Degradation of the active substance – in other words, if it breaks down • Why we need the European Pharmacopoeia The European Pharmacopoeia (Ph. Eur.) is a single reference work for the quality control of medicines. The official standards it contains provide a scientific basis for quality control during the entire life cycle of a product. These standards are legally binding – as laid down in the Council of Europe Convention on the Elaboration of a European Pharmacopoeia and in EU and national pharmaceutical legislation. Ph. Eur. quality standards become mandatory on the same date in all States Parties to the convention. • Quality standards of the European Pharmacopoeia Ethnopharmacological relevance: The European Pharmacopoeia (Ph. Eur.) provides a legal and scientific reference for the quality control of medicines. It is legally binding in the 38 signatory parties of the Convention on the elaboration of a European Pharmacopoeia (37 member states and the European Union). 10
- 13. Materials and methods: The requirements for a specific herbal drug are prescribed in the corresponding individual monograph and the relevant general monographs. Criteria for pesticides and heavy metals for example are defined in the general monograph on Herbal drugs. The Ph. Eur. also provides general methods including methods for determination of aflatoxins B1 and ochratoxin A. Screening methods for aristolochic acids are applied for herbal drugs that may be subject to adulteration or substitution with plant material containing aristolochic acids. Conclusion: The Ph. Eur. collaborate in many areas with the European Medicines Agency (EMA) to ensure close collaboration as regards the respective work programmers and approach. Japanese Pharmacopoeia • History and Legal Status of JP ▪ JP was first published on June 25, 1886 and implemented on July 1, 1887. ▪ JP has the history of 129 years. ▪ JP is published by the Japanese Government as a Ministerial Notification by the Ministry of Health, Labour and Welfare. ▪ JP is published in accordance with the Pharmaceutical & Medical Devices (PMD) Act which is the most fundamental law for pharmaceutical regulation in Japan. 11
- 14. British Pharmaceutical Codex The BPC - a book of reference, published by the Pharmaceutical Society of Great Britain, intended to aid those engaged in the prescribing and dispensing of medicines. It had a companion volume, the British Pharmacopoeia. • A SURVEY OF MATERIA MEDICA We welcome the publication today of the fourth edition of the British Pharmaceutical Codex. This is one of the most useful reference books available to the medical profession, and our gratitude is due to the Codex Committee of the Pharmaceutical Society for providing an authoritative account of the majority of the drugs used in medicine. Eleven years have passed since the last edition appeared, and the dates of the three previous issues are 1907, 1911, and 1923. Inspection of the volume will explain these relatively long intervals: it is a work whose revision must entail an enormous amount of labor. A comparison of the new edition with that of 1923 shows that the size, form, and general arrangement of the book have not changed greatly, but on closer examination, it is evident that the material has been almost wholly rewritten. A large amount of 12
- 15. new information has been introduced, and the size has been kept constant by careful editing of the old material. The scope of the revision can be indicated by the analysis of a typical section- namely, the monographs on sodium salts: in the last edition, there were forty-three of these monographs and they occupied forty-four pages, while in the new edition there are thirty-six monographs, which occupy forty-one pages. These figures do not, however, indicate the amount of change, since thirteen of the old monographs have been discarded and six new ones introduced. Moreover, the monographs retained have been rewritten. The first essential for a work of reference is that it should be up to date, and the new B.P.C. is completely satisfactory in this respect. For example, monographs on the following subjects are included: solution of vitamin A, vitamin B concentrates, vitamin C concentrates, cortin, corpus luteum, oestrin, parathyroid extract, and extract of the anterior lobe of the pituitary. • PHARMACOLOGICAL AND THERAPEUTIC ACTIONS Another important difference between the Pharmacopoeia and the Codex is that the former confines itself to laying down standards for drugs, whereas the Codex in addition gives information about their pharmacological and therapeutic actions. This feature makes the Codex very valuable to medical practitioners, but it has involved the editors in the difficult task of reconciling therapeutic customs with known scientific facts. The compromise adopted has been to list the preparations actually in frequent use, and at the same time to indicate their probable value. For example, eight preparations of dilute hypophosphorous acid are described, whilst under the heading " Actions and Uses " is the simple statement: " There is no pharmacological evidence that they (hypophosphites) behave differently from other inorganic salts, and any benefit derived is ascribed to the iron or calcium with which the acid may be combined." Similarly, two varieties of parathyroid tablets are described, but the reader is warned that this preparation is of little value when taken by mouth. There are also monographs on eight lithium salts, but in each case, it is pointed out that the action is essentially the same as that of sodium or potassium salts. The attitude adopted seems a reasonable corniromise, but it is important to realize that the Codex simply describes what the medical profession prescribes, and does not reject any substance in common use merely because there is no rational foundation for such usage. • A THOUSAND STANDARD PRESCRIPTIONS The monographs on drugs and on dressings occupy two thirds of the volume, while the formulary occupies more than half of the remainder. This formulary contains about 1,000 standard prescriptions. Not only is the prescription given, but, where necessary, notes on dispensing are added, and in all cases standards for the resulting mixture are given. In this section regard is paid to elegance rather than to economy. Prescriptions with more than twelve ingredients are not uncommon, and a link with the past is preserved by the inclusion of the antiperiodic tincture, which, with its nineteen ingredients, is a lineal descendant of the theriac’s or treacle’s of the Middle Ages. The insurance practitioner who followed these models would, however, probably 13
- 16. get into difficulties with the local Panel Committee, and it seems a pity that simpler if less interesting prescriptions have not been included. For example, a formula that will provide a satisfactory emulsion of liquid paraffin and agar is often required, but the one included in the Codex contains nine ingredients, and it seems probable that a simpler formula could be devised. The Codex would certainly perform a useful service if, in addition to the elegant formulae set out, which often contain half a dozen different flavoring agents, the editors would also give a parallel series of utilitarian formulae. 6. What is monograph in Pharmacopoeia? What does it contain? • What is a Pharmacopeial Monograph? A pharmacopeial monograph contains typically necessary chemical information for the ingredient, as well as its description and function (for food ingredients). Furthermore, a monograph contains detailed instructions for identification, purity tests and other specific tests to limit the number of undesirable impurities, all of which may be used to verify standard requirements by manufacturers and formulators concerned with the quality of their ingredients and products. • What does it contain? A monograph is an expert work of writing (in contrast to reference works) or exhibition on a single subject or an aspect of a subject, often by a single author or artist, and usually on a scholarly subject. In this context only, books such as novels are monographs. A monograph is a written document that reflects the quality characteristics of medicines approved by the U.S. Food and Drug Administration (US FDA). Some of these attributes include Identity - Tests to identify that a particular substance is a medicine that it claims to be. 14